Comparison of QMS ministerial ordinance and enforcement notice

Ministerial Ordinance on Manufacturing Control and Quality Control Standards for Medical Devices and In-Vitro Diagnostic Reagents (QMS Ministerial Ordinance)

Regarding the revision of the Ministerial Ordinance on Standards for Manufacturing Control and Quality Control of Medical Devices and In-Vitro Diagnostic Reagents in accordance with the enforcement of the Act to Partially Amend the Pharmaceutical Affairs Law, etc. (Pharmacy, Food and Drug Administration Notice No. 26 dated August 8, 27) Notification No. 0827)

limited edition

Three types*

Chapter I General Provisions

Effect

Article 1 This Ministerial Ordinance is pursuant to the 23rd Act on Ensuring the Quality, Efficacy, and Safety of Pharmaceuticals, Medical Devices, etc. (Article 145 of the 1960 Act; hereinafter referred to as the "Act"). Article 2-5, paragraph 2, item 4 (including cases where it is applied mutatis mutandis in Article 23-2-17, paragraph 5; the same shall apply hereinafter) and the Ordinance of the Ministry of Health, Labor and Welfare prescribed in Article 80, paragraph 2. The standards set forth in the following shall be established.

1. About Article 1 (Purpose)

(1) The QMS Ministerial Ordinance is stipulated in Article 23-2-5, Paragraph 2, Item 4 of the Act (including cases where it is applied mutatis mutandis pursuant to Article 23-2-17, Paragraph 5) and Article 80, Paragraph 2 of the Act. It must be clearly stated that the standards have been established as standards for manufacturing control or quality control methods for medical devices, etc.

Definition

Article 2 In this Ministerial Ordinance, the term "manufacturer, etc." refers to a manufacturer of medical devices or in vitro diagnostic reagents (hereinafter referred to as "medical devices, etc.") (Article 23-2-17 of the Act) Designated foreign-manufactured medical device manufacturers, etc. (hereinafter referred to as "designated foreign-manufactured medical devices, etc. manufacturers") as prescribed in paragraph 1 and designated altitudes appointed pursuant to the provisions of Article 23-3, Paragraph 1 of the Act. Manufacturers of controlled medical devices, etc. (hereinafter referred to as "appointed foreign designated highly controlled medical devices, etc. manufacturers") are excluded), foreign manufacturing as stipulated in Article 23-2-17, Paragraph 4 of the Act. Persons with special approval for medical devices, etc. (hereinafter referred to as "persons with special approval for foreign-manufactured medical devices, etc.") or foreign-designated highly controlled medical device manufacturers, etc. as prescribed in Article 23-2-23, Paragraph 1 of the Act A business operator (hereinafter referred to as a "foreign designated highly controlled medical device manufacturing business operator").

(1) "Manufacturer, etc." refers to a manufacturer of medical devices, etc. (a designated foreign-manufactured medical device, etc. manufacturer, as defined in Article 23-2-17, Paragraph 4 of the Act, and Article 23-3 of the Act) Excluding designated foreign-designated highly controlled medical device manufacturers and distributors appointed pursuant to the provisions of Paragraph 1), persons with special approval for foreign-manufactured medical devices, etc. as prescribed in Article 23-2-17, Paragraph 4 of the Law; Must be a foreign designated highly controlled medical device manufacturing business, etc. as prescribed in Article 23-2-23, Paragraph 1. In this definition, "designated foreign-manufactured medical devices, etc. manufacturers" and "designated foreign-designated highly controlled medical devices, etc. manufacturers," which are not included in the marketing authorization holders, etc., are responsible for the operations performed in accordance with the provisions of this Ministerial Ordinance. At least the work specified in Article 72-3 shall be carried out.

2 In this Ministerial Ordinance, the term "product" refers to a product that consists of component parts, etc., and that has gone through the manufacturing process at a manufacturing facility (a product that is made in an intermediate process of manufacturing and becomes a product through subsequent manufacturing processes). (hereinafter referred to as "intermediate products").

(2) "Product" refers to a product consisting of component parts, etc., which has gone through the manufacturing process at a manufacturing facility (a product made in an intermediate process of manufacturing and which becomes a product through subsequent manufacturing processes) (hereinafter referred to as "intermediate products").

3 In this Ministerial Ordinance, "component parts, etc." refers to parts used in the manufacturing process, assemblies (limited to those used in products), raw materials, materials, containers, packaging, and labeling (including attached documents). (hereinafter the same shall apply), etc., which are part of the product and product software (excluding medical device programs prescribed in Article 2, Paragraph 13 of the Act).

(3) "Components, etc." refers to parts used in the manufacturing process, assemblies (limited to those used in products), raw materials, materials, containers, packaging, and display items (including attached documents). ), etc., which are part of the product and product software (excluding cases where the product is a medical device program as stipulated in Article 2, Paragraph 13 of the Act). In this definition, "displayed material" refers to labels stating the matters stipulated in Article 50 of the Act, Article 63 of the Act, Article 52 of the Act, or Article 63-2 of the Act, and Article 52 or Article 63-2 of the Act. Refers to the attached document, etc. that describes the matters stipulated in .

4. In this Ministerial Ordinance, "manufacturing substances" refer to substances used in intermediate products in the manufacturing process (excluding those that become part of the product).

(4) "Manufacturing materials" refer to materials used in intermediate products in the manufacturing process (excluding materials that become part of the product). Specifically, this applies to substances that are volatilized or removed during the process, such as cleaning water, solvents, mold release agents, ethylene oxide gas for sterilization, etc.

5 In this Ministerial Ordinance, a "lot" refers to a group of products, manufacturing materials, component parts, etc. (hereinafter referred to as "products, etc.") that are manufactured to have homogeneity through a series of manufacturing processes within one manufacturing period. means.

(5) "Lot" refers to a group of products, manufacturing materials, components, etc. that are manufactured with uniformity through a series of manufacturing processes within one manufacturing period. Specifically, it refers to products manufactured to have uniform characteristics and quality within predetermined limits under essentially the same conditions. It is also possible that one product or component may be considered one lot. A lot is sometimes called a "batch."

6. In this Ministerial Ordinance, "sterilized products" refer to medical devices, etc. that are sterilized during the manufacturing process.

(6) “Sterilized products” refer to medical devices, etc. that are sterilized during the manufacturing process and must meet sterilization requirements.

7. In this Ministerial Ordinance, the term "facility" refers to a facility (including manufacturing site) related to product realization included in the quality control supervision system.

(7) "Facilities" shall mean facilities (including manufacturing sites) related to product realization included in the quality control supervision system. Specifically, it refers to facilities that conduct operations such as designing, purchasing, manufacturing, providing services, installing, ancillary services, packaging, and storing medical devices, etc., which are managed and supervised by the quality control supervision system of a manufacturer, etc. and shall not be limited to manufacturing facilities that require registration as provided in Article 23-2-3 or Article 23-2-4 of the Act. However, this does not include establishments that outsource processes pursuant to the provisions of Article 5, Paragraph 4, or establishments that purchase goods as prescribed in Article 38, Paragraph 1, Item 1.

8 In this Ministerial Ordinance, "validation" refers to verifying that structures, equipment, procedures, processes, and other manufacturing control and quality control methods (hereinafter referred to as "manufacturing procedures, etc.") give the expected results, and documenting this. means to do so.

(8) "Validation" means verifying that the facility's structures, equipment, procedures, processes, and other manufacturing control and quality control methods give the expected results, and documenting this. . For example, design and development validation in Article 35, Paragraph 1 means confirming that a product with the expected quality, safety, performance, etc. has been designed and developed, and documenting this. thing.

9 In this Ministerial Ordinance, "clean area" refers to a place where manufacturing work is performed (hereinafter referred to as a "work place") where components are weighed and prepared, and where containers after cleaning come into contact with the air in the work place. Refers to a place.

(9) “Clean area” refers to a workplace that has a predetermined cleanliness level regarding particulates and microorganisms, where components are weighed and prepared, and where containers after cleaning are kept within the workplace. A place that comes into contact with air.

10 In this Ministerial Ordinance, "sterile area" refers to a workplace where sterilized products or components or sterilized containers come into contact with the air within the workplace, a place where containers are closed, and sterility testing, etc. A place where sterile procedures are performed.

(10) "Sterile area" refers to a place in a workplace where sterilized products or components or sterilized containers come into contact with the air within the workplace, a place where containers are closed, and a place where sterilization tests, etc. A place where sterile procedures are performed.

11. In this Ministerial Ordinance, the term "cell tissue medical device" refers to a medical device composed of human or animal cells or tissues.

(11) "Cell tissue medical device" refers to a medical device composed of human or animal cells or tissues, and excludes "regenerative medicine products" under Article 2, Paragraph 9 of the Act. thing.

12 In the Ministerial Ordinance, the term "donor" refers to a person who donates cells or tissue that will become the material for cell tissue medical devices (brain-dead person as defined in Article 6, Paragraph 2 of the Act on Organ Transplantation (Act No. 104 of 1997)). (excluding those related to the person's body).

(12) “Donor” means a person who donates cells or tissues that will be the materials for cell tissue medical devices (brain-dead as defined in Article 6, Paragraph 2 of the Act on Organ Transplantation (Act No. 104 of 1997)). (excluding those related to the person's body).

13. In this Ministerial Ordinance, the term "donor animal" refers to an animal that donates cells or tissues that serve as materials for cell-tissue medical devices.

(13) "Donor animal" refers to an animal that provides cells or tissues that will be used as materials for cell-tissue medical devices.

14. In this Ministerial Ordinance, "process input information" refers to information necessary for manufacturing control and quality control that is provided when implementing a certain process.

(13485) "Process input information" corresponds to "input" in ISO2003:XNUMX, and refers to information necessary for manufacturing management and quality control that is provided when implementing a certain process. To be.

15 In this Ministerial Ordinance, "process output information" refers to information etc. obtained as a result of implementing a certain process.

(13485) "Process output information" corresponds to "output" in ISO2003:XNUMX, and refers to information etc. obtained as a result of implementing a certain process.

16. In this Ministerial Ordinance, the term "management supervisor" refers to an officer, etc. who supervises at the highest level the operations related to the quality control supervision system of a marketing authorization holder, etc. However, in Chapters 2 to 5, which are applied mutatis mutandis by replacing the terms in Articles 82 and 83, this term refers to officers, etc. who manage and supervise operations related to the manufacturer's quality control and supervision system at the highest level. .

(13485) “Management supervisor” corresponds to “top management” in ISO2003:XNUMX, and is an officer who manages and supervises operations related to the quality control supervision system at the highest level, such as a representative of a manufacturer, etc. In addition to specific individuals, such as specific individuals, it is also possible for specific organizations (e.g., conference bodies, etc.) to be given the responsibility and authority as supervisors as stipulated in this Ministerial Ordinance. In this case, a specific individual within the organization must be identified as the person responsible for managing and supervising the organization. However, in Chapters XNUMX to XNUMX, which are applied mutatis mutandis by replacing the terms in Articles XNUMX and XNUMX, this term refers to officers, etc. who manage and supervise operations related to the manufacturer's quality control and supervision system at the highest level. To be something.

17. In this Ministerial Ordinance, the term "product recipient" refers to any person who handles the product after it is released on the market. However, in Chapters 2 through 5, which are applied mutatis mutandis in Article 82 and Article 83, this refers to all persons who handle the product after it has been shipped from the manufacturer.

(17) "Product recipient" shall mean any person who handles the product after it is released on the market. However, in Chapters 2 to 5, which are applied mutatis mutandis in Articles 82 and 83, they refer to all persons who handle the product after it is shipped from the manufacturer. Product recipients may include, for example, end users such as medical professionals, distributors, and patients.

18. In this Ministerial Ordinance, the term "quality policy" refers to the basic policy established and announced by managers and supervisors to ensure product quality.

(13485) "Quality policy" corresponds to "quality policy" in ISO2003:XNUMX, and refers to the basic policy established and expressed by management supervisors to ensure product quality. thing.

19 In this Ministerial Ordinance, the term "quality control and supervision system" refers to a system for manufacturers, etc. to manage and supervise quality. However, in Chapters XNUMX to XNUMX, which are read and applied mutatis mutandis in Article XNUMX, the system for manufacturers to manage and supervise manufacturing facilities regarding quality shall be read and applied mutatis mutandis in Article XNUMX. Chapters XNUMX to XNUMX refer to the system by which manufacturers manage and supervise quality.

(13485) "Quality management supervision system" corresponds to the "quality management system" in 2003:XNUMX, and refers to a system established by manufacturers, etc. to supervise and manage quality. thing. However, in Chapters XNUMX to XNUMX, which shall be read and applied mutatis mutandis pursuant to the provisions of Article XNUMX, the system for the manufacturer to manage and supervise the manufacturing facility regarding quality shall be read and applied mutatis mutandis pursuant to the provisions of Article XNUMX. Chapters XNUMX to XNUMX refer to the system by which manufacturers manage and supervise quality.

20 In this Ministerial Ordinance, "verification" refers to determining the appropriateness and effectiveness in achieving the set goals.

(13485) "Verification" is equivalent to "review" in ISO2003:XNUMX, and refers to determining the appropriateness and effectiveness in achieving the set goals.

21. In this Ministerial Ordinance, "resources" refers to the knowledge and skills possessed by individuals, as well as technology, equipment, and other resources utilized in the work of facilities.

(13485) "Resource" corresponds to "resource" in ISO 2003:XNUMX, and refers to the knowledge and skills possessed by individuals, as well as technology, equipment, and other resources utilized in operations at facilities.

22. In this Ministerial Ordinance, "business operation infrastructure" refers to the system of facilities, equipment, and services necessary for operations at a facility.

(13485) "Business operation infrastructure" corresponds to "infrastructure" in ISO2003:XNUMX, and refers to the system of facilities, equipment, and services necessary for operations at a facility.

23. In this Ministerial Ordinance, "product realization" refers to a series of operations performed from the development stage to product shipment and provision of incidental services.

(23) "Product realization" refers to a series of operations performed from the design and development stage to shipping the product and providing associated services.

24 In this Ministerial Ordinance, "traceability" refers to being able to trace the history, application, or location.

(13485) "Traceability" corresponds to "traceability" in ISO2003:XNUMX, and means that the history, application, or location can be traced.

25 In the Ministerial Ordinance, the term "notification" refers to a document issued after delivery of a product to supplement the information provided at the time of delivery or to advise on measures to be taken in the use, modification, return, and destruction of the product. means.

(13485) "Notices" are equivalent to "advisory notices" in ISO2003:XNUMX, and supplement the information provided at the time of delivery of the product, or indicate measures to be taken when using, modifying, returning, and disposing of the product. A document issued after delivery of the product to advise on the

26 In this Ministerial Ordinance, "Special Adoption" refers to products that do not comply with product-related requirements, if there is no hindrance to the manufacturing control and quality control of the product, and if there is no hindrance to the manufacturing control and quality control of the product, and there are laws and regulations related to pharmaceutical affairs or orders or dispositions based thereon (hereinafter referred to as "Special Adoption"). Permission to use or operate the product, permission to proceed to the next stage of the process, or decision to ship the product is given after appropriately confirming that the product complies with legal regulations.

(26) “Special adoption” refers to products that do not comply with product-related requirements, after appropriate confirmation that there is no problem with manufacturing control and quality control of the product, and that it complies with the provisions of laws and regulations. This means giving permission for its use or operation, permission to proceed to the next step in the process, or decision to ship.

Scope of application

Article 3 A marketing authorization holder, etc. shall conduct manufacturing control and quality control of products based on the provisions of Chapters II and III.

3. Regarding Article 3 (Scope of Application)

(13485) Chapter 2003 of this Ministerial Ordinance is in harmony with ISOXNUMX:XNUMX and is positioned as a basic requirement. It shall be an additional requirement.

(2) Manufacturing and sales businesses, etc. must carry out manufacturing control and quality control of products based on Chapters 2 and 3.

(3) In addition to the provisions of Chapters 2 and 3, manufacturers, etc. must conduct manufacturing control and quality control of products related to biological medical devices, etc. based on the provisions of Chapter 4.

(4) Manufacturers, etc. must conduct manufacturing control and quality control of products related to radioactive in vitro diagnostic reagents based on the provisions of Chapter 5, in addition to the provisions of Chapters 2 and 3.

(5) Some provisions will not apply to products related to limited general medical devices and limited third-class medical device manufacturers, as shown in the attached document.

2. A marketing authorization holder, etc. is responsible for medical devices that are biological products (hereinafter referred to as "biological medical devices"), medical devices designated by the Minister of Health, Labor and Welfare under Article 43, Paragraph 2 of the Act, and cell tissue medical devices (hereinafter referred to as "biological medical devices"). Manufacturing control and quality control of products related to "biological medical devices, etc." shall be conducted in accordance with the provisions of Chapter 4 in addition to the provisions of Chapters 2 and 3.

3. A marketing authorization holder, etc. shall purchase in vitro diagnostic pharmaceuticals (radiopharmaceuticals prescribed in Article 1, Item 1 of the Radiopharmaceutical Manufacturing and Handling Regulations (Ministry of Health and Welfare Ordinance No. 4 of 1960)). Manufacturing control and quality control of products related to (hereinafter referred to as "radioactive in vitro diagnostic drugs") shall be conducted in accordance with the provisions of Chapter 5 in addition to the provisions of Chapters 2 and 3.

Chapter 2 Basic requirements related to manufacturing control and quality control of medical devices, etc.

Section 1 General rules

Be applicable

Article 4 Medical devices and in vitro diagnostic drugs prescribed in Article 23-2-5, paragraph 1 of the Act, and designated highly controlled medical devices prescribed in Article 23-2-23, paragraph 1 of the Act The provisions of Articles 30 to 36 do not apply to products related to medical devices, etc. other than the above.

4. Article 4 (Application)

(1) Products related to medical devices that do not require approval or certification under the law (medical devices that require design and development management under the old law (designated in the Design and Development Notification (Ministry of Health, Labor and Welfare Notification No. 84 of 2005)) The provisions of Articles 30 to 36 shall not apply to medical devices (excluding medical devices). If this is not applicable, it shall be stated in the quality control supervision system standards that the product is not a medical device, etc. that requires design and development control.

(2) If any of the provisions of Chapter 2, Section 5 (Product Realization) cannot be applied due to the characteristics of a medical device, such provisions may not be applied to its quality control supervision system. To be. In cases where it is not actually applied, the provisions that are not applicable and the reasons for their non-applicability shall be clearly stated in the quality control and supervision system standards, based on the provisions of Article 7, Paragraph 1.

2. If a marketing authorization holder, etc. cannot apply any of the provisions of Section 5 of this chapter due to the characteristics of the medical device, etc. related to the product, the marketing authorization holder, etc. shall not apply such provisions to its quality control supervision system. Can be done.

3. If any of the provisions of the preceding two paragraphs apply, the marketing authorization holder, etc. shall include a statement to that effect in the document that stipulates the quality control and supervision system for the product (hereinafter referred to as the "Quality Control and Supervision System Standards"). must be stated.

Section 2 Quality Control Supervision System

Requirements related to quality control supervision system

Article 5 A marketing authorization holder, etc. must establish, document, and implement a quality control and supervision system in accordance with the provisions of this chapter, and maintain its effectiveness.

(13485) This article corresponds to "2003 General requirements" of ISO4.1:XNUMX.

(13485) "Process" shall correspond to "process" in ISO2003:XNUMX.

(3) When manufacturing medical devices, etc., manufacturers, etc., must establish a quality control and supervision system necessary for product realization. In addition, the application of the system to each facility should be clarified, such as by identifying the relevant processes for each facility.

(4) In cases where the quality control supervision system is integrated including facilities located in foreign countries, the management supervisor under Article 10 and the manager under Article 16 shall be The person may be a member of the

(5) Members shall mean all persons engaged in work that affects product quality.

(6) If the business outsourced pursuant to paragraph 4 is a registered manufacturing facility, the manufacturer that manages and supervises the registered manufacturing facility shall comply with the law regarding the quality control and supervision system of the manufacturer involved in the manufacture of the product concerned. We can respond to investigations pursuant to the provisions of Article 23-2-5, Paragraph 6 or Paragraph 11, and investigations pursuant to the provisions of Article 23-2-23, Paragraph 3 or 6 of the Act (hereinafter referred to as "QMS investigation"). Please prepare accordingly.

(7) The “necessary measures” in Paragraph 2, Item 6 may include the following measures:

a. Clarify the definition of the process.

stomach. Properly monitor and measure according to the provisions of Article 57, Paragraphs 1 and 2, using a method appropriate to the process, and demonstrate that the process can achieve the results specified in the plan under Article 14, Paragraph 1. to do.

cormorant. When making changes to the quality control supervision system based on the provisions of Article 14, Paragraph 2, do so appropriately.

workman. Utilize the results of the internal audit under Article 56, the results of the management supervisor review under Article 18, etc.

(8) "Processes that affect compliance with product requirements (including legal provisions, etc.; hereinafter referred to as "product requirements")" in Paragraph 4 refer to processes performed at registered manufacturing facilities. In addition, for example, processes related to external testing and inspection institutions, processes related to external design development management institutions, etc. may be included.

2. A marketing authorization holder, etc. must conduct the following operations:

(1) Clarify the contents (including the results achieved by the process) of the processes necessary for the quality control supervision system (hereinafter simply referred to as "processes" in this chapter), and inform each facility about each of the processes. Clarify the mode of involvement.

2. Clarify the order of processes and their mutual relationships.

3. Clarify the criteria and methods necessary to ensure the effectiveness of process implementation and management.

4. Ensure that the resources and information necessary to implement, monitor and measure the process are available.

(v) Monitoring, measuring, and analyzing processes.

(vi) To take necessary measures regarding the process in order to obtain the results set forth in item (i) and to maintain effectiveness.

3. A marketing authorization holder, etc. must manage and supervise the process in accordance with the provisions of this chapter.

4. When a marketing authorization holder, etc. decides to outsource a process that affects compliance with product-related requirements (including legal provisions, etc.; hereinafter referred to as "product requirements"), the manufacturer, etc. must be managed.

5. Marketing authorization holders, etc. must clearly stipulate the method of process control mentioned in the preceding paragraph in their quality control supervision system.

Documentation of quality control supervision system

Article 1 A marketing authorization holder, etc. shall include the following matters (limited class XNUMX medical device marketing authorization holder (general medical device manufacturing management or quality control (hereinafter referred to as "Limited General Medical Devices") other than medical devices designated by the Minister of Health, Labor and Welfare as requiring special care. (excluding item XNUMX) must be entered.

13485. Related to Article 2003 (Documentation of Quality Control Supervision System) (4.2.1) This article corresponds to “XNUMX Documentation requirements – General” of ISOXNUMX:XNUMX.

(2) Among the documents and records specified in this article, those necessary for the management of processes in which each facility is involved shall be kept up-to-date by providing copies or using information and communication technology. Make sure that information is shared.

(3) Documented procedures (hereinafter referred to as "procedure manuals") are documents that clarify established procedures to ensure smooth and appropriate execution of operations. It must be prepared taking into account the method of work carried out by members and the level of skills and education and training required for that work.

(13485) "Documentation" in Paragraph 2003, Item 4.2.1 corresponds to "documented" in XNUMX of ISOXNUMX:XNUMX, and refers to documentation of requirements, procedures, activities, or special arrangements. It must be implemented and maintained at the appropriate time.

(5) "Product standards" in paragraph 2 refers to documents that contain the documents related to the design, development, manufacturing, etc. of individual products, or documents that contain the location of these documents, and may include the following items: To be something. Furthermore, documents related to manufacturing, etc. should only contain the information necessary to appropriately manage the processes, etc. that are carried out or outsourced by the marketing authorization holder, etc., as well as the goods, etc. that are purchased.

a. Product group, general name, and brand name of medical devices related to the product (including the model number if it has a model number)

stomach. The manufacturing and marketing approval (certification) date and manufacturing and marketing approval (certification) number of the medical device, etc. related to the product (in the case of products that do not require manufacturing and marketing approval and manufacturing and marketing certification, the year of manufacturing and sales notification) time

cormorant. Item specifications

workman. How to operate or use

O. Product design, drawings and specifications or ingredients and quantities

mosquito. Manufacturing methods and manufacturing procedures (including matters related to equipment, instruments and devices used in manufacturing, and the working environment)

tree. If importing, the name of the country of import, the main country of sale of the imported medical devices, etc., and the name of the product.

nine. Matters regarding labeling and packaging

K. Testing and inspection methods for products, manufacturing substances, component parts, etc. specified in the manufacturing and marketing approval (certificate)

Ko. In cases where stricter standards and more accurate test and inspection methods are used than those in

sa. Standards and tests and inspections that are voluntarily established as necessary for quality control among products, manufacturing substances, components, etc. that are not specified in the manufacturing and sales approval (certification) document.

C. When testing and inspecting products, manufacturing substances, component parts, etc. using external testing and inspection institutions, etc., the test and inspection items performed using these institutions, their standards, and testing and inspection methods.

vinegar. Storage methods, storage conditions, and shelf life or expiry date of products, manufacturing substances, component parts, etc. (including the results of stability tests that are the basis for the shelf life or expiration date)

C. Procedures for determining whether or not it can be shipped from the facility and whether it can be shipped to the market

So. Methods and procedures for transporting products

Ta. Product repair procedures and components used for repair

Storage method and storage period

blood. Matters related to installation work and ancillary service work

tsu. For sterilized products, matters related to sterilization (must be described based on the results of process validation)

Te. Documents showing the details of the agreement between the marketing authorization holder and the facility or office (including the agreement prescribed in Article 72-2, Paragraph 1) (e.g., a copy of the contract signed for the agreement)

to. Interrelationships between manufacturers, related facilities, and registered manufacturing sites in terms of quality control supervision system

(6) In response to requests from overseas regulations, etc., if a "document that stipulates or clarifies the specifications and requirements related to the quality control and supervision system" has been created, such document shall be included in the product standard. It may be used as a book or part of it.

(7) Based on the provisions of Article 8, the product standard document shall state the person who approved its creation and the date of creation, and if revised, the person who approved the revision, date, content, and reason.

(1) Quality policy and quality objectives

(ii) Standards for quality control supervision system

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(iii) Necessary matters to ensure effective and systematic implementation and management of processes at each facility.

(iv) Procedures and records prescribed in this chapter

(v) Other matters that are required to be documented pursuant to the provisions of laws and regulations regarding pharmaceutical affairs.

2. For each product, a marketing authorization holder, etc. shall prepare a document (hereinafter referred to as "product standard document") that stipulates the specifications and requirements for the quality control and supervision system, or clarifies the contents thereof, and shall comply with this document. must be kept.

3. A marketing authorization holder, etc. shall specify all manufacturing processes related to the product at each facility in the product standard document, and shall carry out the establishment of Article 42, Paragraph 1 and the operations prescribed in Article 43, Paragraph 1. In such cases, the content of the business shall be determined.

Quality control supervision system standards

Article 7 A marketing authorization holder, etc. must prepare and maintain a quality control and supervision system standards document that includes the following matters:

7. Regarding Article 7 (Quality Control Supervision System Standards)

(13485) This article corresponds to "2003 Quality manual" of ISO4.2.2:XNUMX.

(2) Within the scope (processes, etc.) to which the quality control and supervision system is applied, details of the items to be excluded or non-applicable and the reasons justifying the exclusion must be clearly stated.

(3) The outline of the system of documents used in the quality control supervision system in paragraph 2 refers to a description showing the hierarchical structure of the documents used and a description showing the relationship between the list of documents and the process to which the documents are applied. etc. may be included.

(i) Scope of the quality control supervision system (if there are any items that are excluded or non-applicable, including the details and the reasons justifying the exclusion)

(ii) The contents of a procedure manual (meaning a document that describes established procedures; the same shall apply hereinafter) prepared for the quality control supervision system, or the document number and other reference information of the procedure manual.

3. Mutual relationship between each process

2. A marketing authorization holder, etc. (excluding a limited type 3 medical device marketing authorization holder) must provide an overview of the document system related to the quality management supervision system in the quality management supervision system standards.

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Management of quality control supervision documents

Article 8 A marketing authorization holder, etc. shall manage the documents stipulated in the preceding two articles and other provisions of this chapter, as well as other documents necessary to implement the quality control supervision system (excluding records; hereinafter referred to as "quality control supervision documents"). There must be.

8. Article 8 (Document management)

(13485) This article corresponds to "2003 Control of documents" of ISO4.2.3:XNUMX.

(2) In addition to the procedure manuals listed in (3), the "documents specified in this chapter" in Paragraph 1 may include the following (*1): (*1) The following items are listed on a separate sheet.

(3) Chapter 2 of this Ministerial Ordinance requires the following (*1) procedures to be established and documented, and all of these fall under the quality control supervisory documents in paragraph 1. It must be managed appropriately in accordance with the provisions of Paragraphs 2 to 4. (*1) The next steps are listed on a separate sheet.

(4) Quality control supervision documents should be managed appropriately and separated from documents that are not subject to management. (5) Regarding the procedures related to product realization (procedures from E to G in (3)), the following points should also be noted.

a. In order to prevent confusion, mistakes, etc. during each task, a method must be established to clearly distinguish the work implementation status, etc.

stomach. Appropriate equipment should be used during manufacturing. If such documents are retained, regardless of their purpose, they must be properly identified as obsolete.

cormorant. Monitor appropriate process variables and product characteristics.

(6) The "necessary review" of quality control supervisory documents in Paragraph 2, Item 2 may be performed as a result of, for example, changes in the organization or members, the results of internal audits, or the addition of new products, etc. To be something.

2. A marketing authorization holder, etc. must establish procedures for the management methods necessary for the following operations and document them.

(1) When issuing a quality control supervisory document, verify the validity of the quality control supervisory document and approve its issuance.

(ii) Perform the necessary checks on the quality control supervisory documents and approve the updates when they are updated.

(iii) It shall be possible to identify the content of changes to quality control supervision documents and the latest revision status.

(4) If the quality control supervisory document is revised, the revised version of the quality control supervisory document shall be made available.

(5) Ensure that quality control supervision documents are easy to read and the contents can be easily understood.

6. Identify quality control supervision documents prepared externally and manage their distribution.

(vii) To prevent the abolished quality control supervisory documents from being used against the intended purpose. If such documents are retained, regardless of their purpose, they must be properly identified as obsolete.

3. When making changes to quality control supervisory documents, have the department that originally approved the change or another pre-designated department, which is in a position to obtain the information that serves as the basis for the change, review the change and obtain approval from that department. You have to get it.

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4. A marketing authorization holder, etc. must retain at least a portion of the quality control supervision document or a copy thereof for the period specified in Article 67.

Control of records

Article 9 In order to demonstrate compliance with the requirements stipulated in this chapter and the effective implementation of a quality control and supervision system, a marketing authorization holder shall provide information that is easy to read and understand, and that is searchable. Records must be created and kept to ensure that the

9. Article 9 (Record Management)

(13485) This article corresponds to "2003 Control of records" of ISO4.2.4:XNUMX.

(2) The records required to be created and kept under paragraph 1 may include the following (*2): (*2) is written on a separate sheet

(3) "Protection" in Paragraph 2 includes, for example, recording the date on which the record was actually made, assigning page numbers to the format of the record, and managing identification so that the consistency of the record can be seen. to do. If there is an error, it may be corrected in a way that allows the original entry to be seen.

2. A marketing authorization holder, etc. must establish and document procedures regarding the necessary management methods for identification, storage, protection, retrieval, storage period, and disposal of the records set forth in the preceding paragraph.

3. A marketing authorization holder, etc. must retain the records set forth in paragraph 1 for the period specified in Article 68.

Section 3 Responsibilities of management supervisors

Supervisor involvement

Article 10 The management supervisor shall be responsible for the establishment and implementation of the quality control supervision system and the maintenance of its effectiveness. (limited to the operations listed in items 4 and 5).

10. Article 10 (Involvement of management and supervisors)

(13485) This article corresponds to "2003 Management commitment" of ISO5.1:XNUMX.

(13485) Item 2003, “responsibly involved”, corresponds to “commitment” in ISOXNUMX:XNUMX.

(1) Establishing a quality policy.

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2. Ensure that quality objectives are established.

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(iii) To conduct the inspection prescribed in Article 18, paragraph 1.

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4. Securing a system that allows resources to be used.

(v) Matters required by product recipients among the provisions of laws and regulations and product requirements (hereinafter referred to as "product recipient requirements") (for supervisors of limited type 3 medical device manufacturers, laws and regulations Disseminate to all facilities the importance of complying with the regulations, etc.).

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Product recipient focus

Article 11 Management supervisors (excluding management supervisors of limited type 3 medical device manufacturers; the same applies in the following Article to Article 14, Article 16, and Article 18) shall be responsible for receiving products. It must be ensured that the requirements of the recipient of the product are clear and that the product complies with the requirements of the recipient of the product.

11. Regarding Article 11 (emphasis on product recipient)

(13485) This article corresponds to "2003 Customer focus" of ISO5.2:XNUMX.

(2) "Requirements for product recipients have been clarified" means that requirements for product recipients have been clarified based on the provisions of Article 27.

(3) Ensure that the provisions of Article 55 are properly implemented and that product recipients comply with the requirements.

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Quality Policy

Article 12 The manager must ensure that the quality policy conforms to the following conditions:

1 2. Regarding Article 12 (Quality Policy)

(13485) This article corresponds to "2003 Quality policy" of ISO5.3:XNUMX.

(2) The quality policy shall be stated in the quality control supervision document based on the provisions of Article 6, Paragraph 1, Item 1.

(3) Item 5, “Being reviewed to maintain validity” refers to the periodic evaluation of room for improvement and necessity of changes in management/supervisor reviews stipulated in Article 18. It must be ensured by doing it properly.

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(i) It shall be appropriate in light of the intentions of the marketing authorization holder, etc. regarding the quality of the product.

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(ii) It stipulates that the management supervisor will be responsible for ensuring compliance with requirements and maintaining the effectiveness of the quality control and supervision system.

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(iii) It shall serve as a framework for formulating and reviewing quality objectives.

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(4) Be known and understood by all facilities.

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(v) It has been checked to maintain validity.

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Quality goal

Article 13 The management supervisor must ensure that quality goals (including goals necessary for compliance with product requirements) are established for each department and each level in each facility. .

13. Regarding Article 13 (Quality Objectives)

(13485) This article corresponds to "2003 Quality objectives" of ISO5.4.1:XNUMX.

(2) Managers do not necessarily need to be directly involved in establishing quality goals for each department and each level at each facility related to the quality control supervision system, such as a manufacturing/distributor. No, but they are responsible.

(3) The quality objectives mentioned here include not only quality objectives related to the quality control and supervision system, but also objectives necessary for compliance with product requirements, and regarding the latter, Article 26, Paragraph 1. Appropriate clarification is required when formulating a product realization plan based on the regulations.

(4) "According to each department and each level in each facility" means that each facility is required to set quality goals at an appropriate level or organizational unit, but It is also possible that quality targets may be set for each appropriate department.

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2. The quality objectives set forth in the preceding paragraph must be such that their achievement status can be evaluated, and must be consistent with the quality policy.

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Developing a quality control supervision system plan

Article 14 The manager must ensure that a plan is formulated for the implementation of the quality control and supervision system so that it complies with the provisions of Article 5 and quality objectives.

14. Regarding Article 14 (Formulation of plan for quality control supervision system)

(13485) This article corresponds to "2003 Quality management system planning" of ISO5.4.2:XNUMX.

(2) The quality control supervisory system plan can be planned and implemented continuously, and even if there are changes to the quality control supervisory system as a result of management review, corrective measures, or preventive measures, the relevant The quality control and supervision system shall be maintained to ensure that there are no deficiencies.

(3) When formulating a plan for the quality control supervision system, regulatory requirements, quality policies, quality objectives, results of management and supervisor reviews, and necessary changes as corrective and preventive measures are considered as process input information. Process output information may include the creation and revision of quality control supervision documents.

(4) Plans regarding product realization shall be formulated based on the provisions of Article 26.

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2. When planning and implementing changes to the quality control supervision system, managers and supervisors must maintain the quality control supervision system to be free from deficiencies.

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Responsibility and authority

Article 15 The management supervisor must ensure that the responsibilities and authorities of each department and the members of that department are defined, documented, and widely known in all facilities.

15. Article 15 (Responsibility and Authority)

(13485) This article corresponds to "2003 Responsibility and authority" of ISO5.5.1:XNUMX.

(2) Under this section, the responsibilities and authority of the supervisor himself shall also be specified.

(3) In Paragraph 1, "The responsibilities and authorities for each department and the members of the department are defined, documented, and made known" means, for example, that an organizational chart, division of duties table, etc. This can be achieved by disseminating the information to all concerned parties and implementing it in practice.

(4) Examples of the "necessary independence" in Paragraph 1 include eliminating as much as possible the impact of work that affects quality from a sales perspective, such as profitability, and asking internal auditors to avoid work that is subject to internal audits. (Article 56, Paragraph 5), etc.

2. Supervisors shall determine the mutual relationships of all those who manage, supervise, implement, or verify work that affects quality, ensure the independence necessary for performing the relevant duties, and ensure that the necessary shall be given appropriate responsibility and authority.

Chief administrator

Article 16 The supervisor shall be the person responsible for implementing and maintaining the quality control and supervision system of the marketing authorization holder (hereinafter referred to as " A person responsible for management shall be appointed.

16. Article 16 (Management Responsible Person)

(13485) This article corresponds to a part of "2003 Management representative" of ISO5.5.2:XNUMX.

(2) In Paragraph 1, "officers of marketing authorization holders, persons in managerial positions, and other equivalent persons" may appropriately carry out the duties prescribed in this article on behalf of management supervisors. If the supervisor determines that the person has the ability, the person responsible for management may be selected and appointed, for example, from the management level, rather than necessarily from among the executives of the manufacturer, etc. (3) The management supervisor shall appropriately grant responsibility and authority for the duties stipulated in this article to the administrator, and ensure that the duties of the administrator are carried out without omission in all facilities. .

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2. The management supervisor must give the management supervisor the responsibility and authority for the following tasks:

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(1) Ensuring that processes are established and implemented, and that their effectiveness is maintained.

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(ii) Reporting to the management supervisor regarding the implementation status of the quality control supervision system and the need for improvement thereof.

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(iii) To ensure that all facilities have increased awareness of legal provisions, etc. and product recipient requirements.

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Internal information communication

Article 17 The management supervisor shall establish a mechanism for appropriately communicating information within each facility and between facilities, and ensure that information regarding the effectiveness of the quality control and supervision system is reliably exchanged. Must.

17. Regarding Article 17 (Internal Information Communication)

(13485) This article corresponds to "2003 Internal communication" of ISO5.5.3:XNUMX.

(2) In order for the quality control and supervision system to function effectively, the management supervisor shall establish a mechanism within the organization to appropriately communicate information based on this article, and provide information regarding the effectiveness of the quality control and supervision system. To ensure that the exchange takes place reliably.

(3) In Chapter 2, the provisions requiring appropriate communication and exchange of information include the following:

a. Awareness of the importance of conforming to product recipient requirements, etc.

(Article 10, item 5)

stomach. Dissemination of quality policy (Article 12, Item 4)

Management supervisor review

Article 18 The management supervisor shall conduct a review of the quality control supervision system to confirm its validity and maintenance of effectiveness (necessity of improvement or change of the quality control supervision system (including quality policy and quality objectives)) (hereinafter referred to as "supervisor review") shall be conducted at predetermined intervals.

18. Regarding Article 18 (Management Supervisor Review)

(13485) This article corresponds to “2003 Management review – General” of ISO5.6.1:XNUMX.

(2) Management and supervisor reviews must be conducted periodically. If there are no particular problems, checking once a year is fine, but when changes are planned or have been made, timely and appropriate checks should be carried out to ensure the effectiveness of the quality control supervision system. Strive to maintain sexual health (including improvements necessary for maintenance).

(3) Management and supervisor reviews must be carefully planned and conducted to ensure that the scope and participants are appropriate.

(4) The results of management and supervisory inspections can serve as important evidence of compliance with Articles 19 and 20, so records should be appropriately created and kept.

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2. A marketing authorization holder, etc. must create and retain records of the results of supervisory inspections.

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Process input information related to management supervisor review

Article 19 Management and supervisor reviews must be conducted based on the following process input information:

19. Regarding Article 19 (Process input information related to management supervisor review)

(13485) This article corresponds to "200 Review input" of ISO5.6.2:XNUMX.

(2) The process input information includes at least No. 1 to No. 8, but is not limited to these.

(3) The "audit results" in Item 1 shall include not only the results of internal audits but also the results of external audits.

(4) Item 2, "Opinions from product recipients," shall include complaints from product recipients.

(5) The information obtained through the analysis of the data set forth in Article 61, Paragraph 1 shall also be appropriately utilized as information to be input into the management/supervisor review.

(ii) the results of the audit;

(ii) Opinions from product recipients.

(3) Conformity to process implementation status and product requirements (for products related to limited general medical devices, limited to process implementation status)

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(4) Corrective measures (referring to measures to eliminate the cause of nonconformity to prevent recurrence of nonconformity (referring to failure to comply with the requirements stipulated in this Ministerial Ordinance; the same shall apply hereinafter; the same shall apply hereinafter)) and preventive measures (the same shall apply hereinafter). Refers to measures to eliminate the causes of potential nonconformities. (The same applies hereinafter).

(v) Measures taken in response to the results of previous management/supervisor reviews.

(6) Changes that may affect the quality control supervision system.

7. Suggestions for improvement from departments, members, etc.

(viii) Provisions of laws and regulations related to pharmaceutical affairs that were newly enacted or revised after the previous management/supervisor review.

Process output information related to management supervisor review

Article 20 A marketing authorization holder, etc. (excluding a limited type 3 medical device marketing authorization holder) shall comply with the following matters (for products related to a limited general medical device, item 2) based on the management supervisor's review. (excluding the matters listed above) shall be obtained and the necessary measures shall be taken.

20. Regarding Article 20 (Process output information related to management supervisor review)

(13485) This article corresponds to “2003 Review output” of ISO5.6.3:XNUMX.

(2) When it is decided to take necessary measures such as corrective measures and preventive measures based on the results of the supervisory review, when creating the record of the supervisory review prescribed in Article 18, Paragraph 2, Clarify the content, responsibilities for implementing the measures, necessary resources, deadline for completing the measures, etc.

(3) Item 3 shall also include the results of examining the necessity of resources necessary for improvements in Items 1 and 2.

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(1) Improvements necessary to maintain the effectiveness of the quality control supervision system and process.

×

(ii) Product improvements related to product recipient requirements;

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(iii) Resources prescribed in the next article.

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Section 4 Resource Management and Supervision

Securing resources

Article 21 A marketing authorization holder, etc. must clarify and secure the resources necessary for the following operations:

21. Article 21 (Securing resources)

(13485) This article corresponds to "2003 Provision of resources" of ISO6.1:XNUMX.

(2) "Resources" here may include organizations and personnel, budgets, information, business management infrastructure, suppliers of purchased goods, etc.

(3) The necessity of resources stipulated in Article 21 is obtained as process output information for management/supervisor review, but the responsibility for securing it lies with the marketing authorization holder, etc.

(1) Implement a quality control and supervision system and maintain its effectiveness.

(ii) Comply with the provisions of laws and regulations and the requirements of product recipients (limited to the provisions of laws and regulations, etc. for limited type 3 medical device manufacturers and distributors);

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Competencies of quality workers

Article 22 A marketing authorization holder, etc. must ensure that all persons engaged in work that affects the quality of products have the necessary abilities for the work based on relevant education, training, skills, and experience. Must be.

22. Regarding Article 22 (Competence of Quality Work Personnel)

(13485) This article corresponds to "2003 Human resources-General" of ISO6.2.1:XNUMX.

Ability, awareness and training, etc.

Article 23 A marketing authorization holder, etc. must perform the following operations (excluding the operations listed in item 3 in the case of a limited type 3 medical device marketing authorization holder):

23. Related to Article 23 (Competence, Awareness and Education and Training)

(13485) This article corresponds to “2003 Competence, awareness and training” of ISO6.2.2:XNUMX.

(2) For example, the abilities required of members based on internal audits (Article 56) and management/supervisor reviews (Article 18) are included in those that should be clarified pursuant to the provisions of Item 1.

(3) “Other measures” in item 2 may include, for example, assigning or hiring new members with the necessary skills.

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(1) Clarify what kind of abilities are required of those engaged in work that affects product quality.

(ii) Implementing education and training and taking other measures in order to have the person acquire the abilities set forth in the preceding item.

(iii) Evaluate the effectiveness of the measures set forth in the preceding item.

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4. To ensure that all members are aware of the meaning and importance of their own work and how they can contribute to achieving quality goals.

(v) Create and maintain appropriate records regarding the education, training, skills, and experience of its members.

Business operation infrastructure

Article 24 The marketing authorization holder, etc. shall support the manufacturing of products, including the buildings, work rooms, water supply and other equipment attached to these facilities, process-related equipment (including software), transportation, and communication of information. The business operations infrastructure necessary to achieve compliance with service and other product requirements shall be defined, provided, and maintained.

24. Regarding Article 24 (Business operation infrastructure)

(13485) This article corresponds to "2003 Infrastructure" of ISO6.3:XNUMX.

(13485) “Water supply and other facilities attached to these” in paragraph 2003 corresponds to “associated utilities” in ISOXNUMX:XNUMX.

2. In cases where maintenance work, or the lack thereof, for business operation infrastructure may affect the quality of the product, the marketing authorization holder, etc. shall comply with the requirements related to the maintenance work (including requirements regarding the frequency of maintenance work). ), establish appropriate operation of the requirements, and document this. However, for a Type 3 Limited Medical Device Manufacturer, it is sufficient to establish appropriate operations for the maintenance work and document it.

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3. A marketing authorization holder, etc. (excluding a third-class limited medical device marketing authorization holder) must create and keep records related to maintenance work for business operation infrastructure.

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Work environment

Article 25 A marketing authorization holder, etc. (excluding a Type 3 limited medical device manufacturer; the same shall apply hereinafter from this article to Article 36) shall be a product (excluding a product pertaining to a limited general medical device). The same shall apply hereinafter from this article to Article 36.) The working environment necessary to conform to product requirements shall be clarified and managed and supervised.

25. Regarding Article 25 (Working Environment)

(13485) This article corresponds to "2003 Work environment" of ISO6.4:XNUMX.

(2) “Working environment” may include the following:

a. temperature, humidity and pressure

stomach. air cleanliness

cormorant. illumination

workman. sound and vibration

O. Cleanliness of work room

mosquito. water quality

tree. Number of people in the relevant work environment

(3) Regarding the requirements related to the health condition of the members in Paragraph 2 and the requirements related to the conditions of the working environment in Paragraph 3, this does not necessarily mean that a separate document must be created; Therefore, it is acceptable to specify and describe the necessary requirements in product standards documents, etc. as appropriate. Specific requirements regarding hygiene management for members include matters related to changing clothes of members, matters related to understanding the health status of members, matters related to hand washing methods, etc. Specific requirements regarding working environment conditions include matters regarding structures and equipment that must be kept clean, matters regarding intervals between cleaning of structures and equipment, matters regarding procedures for cleaning structures and equipment, and confirmation of cleanliness of structures and equipment. Matters related to the above should be mentioned.

(4) Products whose quality may be adversely affected by working environment conditions include, for example, products that are susceptible to electrostatic discharge such as electronic circuits, and products that are shipped without sterilization and are sterilized before use. What you can do.

(5) The documented "work instruction system" in paragraph 3 defines detailed procedures for appropriately implementing manufacturing activities or processes required by this Ministerial Ordinance. . The document shall be written in consideration of the method of work carried out by the members, as well as the level of skills and education and training required for the work, and shall ensure that operations are carried out in accordance with this.

(6) "Special working environments" in paragraph 4 include, for example, clean rooms, rooms whose temperature is controlled to be dangerous if exposed for a long period of time, and places where there is a possibility of exposure to harmful gases. To hear.

(7) "Contaminated or potentially contaminated products, etc." in paragraph 5 may include, for example, products returned for repair requests.

(8) The implementation guidelines in paragraph 5 include, for example, special identification of returned products, special handling of products that may be used in contact with the body, special repairs and rework, etc. It must be something that can be used.

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2. For processes where contact between members and the product, etc. or the working environment may have an adverse effect on the quality of the product, manufacturers, etc. must comply with requirements regarding the health status of members, degree of cleanliness, and work clothing, etc. The requirements shall be clarified, appropriate operations related to the requirements shall be established, and this shall be documented. However, if the product is cleaned pursuant to the provisions of Article 41, Paragraph 1, Item 1 or 2, this shall not apply to the steps prior to the cleaning step.

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3. Marketing authorization holders, etc. shall clarify the requirements related to the working environment conditions for processes where the working environment conditions may have an adverse effect on the quality of the product, and establish appropriate operations related to the requirements. At the same time, a system of procedures or work instructions for monitoring and controlling the conditions of the work environment must be established, and these must be documented. However, if the product is cleaned pursuant to the provisions of Article 41, Paragraph 1, Item 1 or 2, this shall not apply to the steps prior to the cleaning step.

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4. A marketing authorization holder, etc. shall have all members who are required to work temporarily under special working environment conditions undergo the education and training prescribed in Article 23, item 2, or They must be supervised by members who have received the education and training specified in .

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5. Unless a marketing authorization holder, etc. can demonstrate in writing that other methods are appropriate, a marketing authorization holder, etc. shall take measures to prevent contaminated or Establish implementation guidelines for the management of products, etc. that may be contaminated (including identification pursuant to the provisions of Article 47, Paragraph 3), establish appropriate operations based on the implementation guidelines, and implement them. Must be documented.

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Section 5 Product Realization

Product realization plan

Article 26 A marketing authorization holder, etc. must formulate and establish a plan for the processes necessary to realize the product.

26. Regarding Article 26 (Product Realization Plan)

(13485) This article corresponds to "2003 Planning of product realization" of ISO7.1:XNUMX.

(2) The product realization plan shall be formulated for each individual product and the processes related to product realization without contradicting the plan for the quality control and supervision system set forth in Article 14, Paragraph 1.

(3) "Other processes related to the quality control and supervision system" in paragraph 2 refers to processes that are included in the quality control and supervision system but not included in the product realization plan, such as: This may include management supervision, corrective measures, preventive measures, etc.

(4) "Format suitable for implementing the product realization plan" in paragraph 4 means that the plan may be created by the manufacturer, etc. without being restricted to a specific format, but be created in a format suitable for execution.

(5) "In all processes related to product realization" in Section 5 means that after looking over all the steps related to product realization in Section 5, those that should be subject to risk management and the results are applied. The purpose should be about what should be done.

(6) In creating the "Requirements for risk management" in Section 5, we first created the general risk management requirements for products, and then, when formulating the product realization plan for each product, It is desirable to create a specific product, taking into consideration the characteristics of the product in question.

(7) Clarification of requirements related to risk management based on the provisions of Paragraphs 5 and 6, establishment of operations, documentation, and creation and storage of records shall be designed and developed based on the provisions of Article 4, Paragraph 1. This is also required for medical devices, etc. to which the provisions related to (Articles 30 to 36) do not apply.

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2. Marketing authorization holders, etc. must ensure consistency between the plan set forth in the preceding paragraph (hereinafter referred to as the "product realization plan") and requirements related to other processes related to the quality control and supervision system.

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(iii) Work related to necessary verification, validation, monitoring, measurement, and testing that is unique to the product in question, as well as standards for determining whether or not the product can be shipped (hereinafter referred to as "shipmentability determination criteria").

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(1) Quality objectives and product requirements related to the product;

×

(ii) The process specific to the product, the need to formulate documents related to the process, and secure the necessary resources.

×

(iii) Work related to necessary verification, validation, monitoring, measurement, and testing that is specific to the product in question, as well as standards for determining whether or not the product can be shipped (hereinafter referred to as "shipmentability determination criteria").

×

(iv) Records necessary to demonstrate that the process involved in realizing the product and the resulting product conform to product requirements.

×

4. The product realization plan must be prepared in a format suitable for the marketing authorization holder, etc. to implement the product realization plan.

×

5. A marketing authorization holder, etc. must clarify the requirements related to product risk management in all processes related to product realization, establish appropriate operation of the requirements, and document this.

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6. Marketing authorization holders, etc. must create and retain records related to risk management.

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Clarification of product requirements

Article 27 A marketing authorization holder, etc. must clarify the following matters as product requirements:

27. Article 27 (clarification of product requirements)

(13485) This article corresponds to "2003 Determination of requirements related to the product" of ISO7.2.1:XNUMX.

(2) This article can be applied to both products to be designed and developed as well as existing products.

(3) Item 1 is a requirement specified by the product recipient for the product in question; item 2 is a requirement that is not specified as a requirement by the product recipient but is clearly required for the product in general. Item No. 3 indicates the requirements required by the provisions of laws and regulations.

(4) Item 1, “Delivery of the product to the product recipient and operations after the product recipient receives the product” refers to, for example, delivery to the product recipient, after-sales service, supply of maintenance parts, etc. The work must be performed after the product is shipped.

(5) Item 2, "requirements known to the manufacturer," refers to, for example, requirements that are necessary to meet the use or intended use specified in advance by the product recipient. , refers to requirements that do not need to be specified by the product recipient, or requirements that are not specified by the product recipient but are publicly known from information on existing products.

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(1) Requirements of the product recipient regarding the product (including requirements regarding delivery of the product to the product recipient and operations after the product recipient receives the product)

×

(ii) Necessary requirements for uses that are not explicitly specified by the product recipient but are previously specified or intended for the product by the product recipient and are known to the marketing authorization holder, etc.

×

(iii) Among the provisions of laws and regulations, those related to the product in question.

×

(iv) Other requirements regarding the product that the marketing authorization holder, etc. deems necessary.

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Verification of product requirements

Article 28 A marketing authorization holder, etc. must conduct a review of product requirements before engaging in the supply of products.

28. Regarding Article 28 (Verification of product requirements)

(13485) This article corresponds to “2003 Review of requirements related to the product” of ISO7.2.2:XNUMX.

(2) "When involved in the supply of products" in paragraph 1 refers to, for example, when documenting product requirements (e.g., product specifications) is exchanged with the product recipient, or when the product is being supplied for the first time. This may include when changing product requirements and when changing product requirements.

(3) "Records related to the results of the verification under paragraph 1" in paragraph 3 may include the signature and date of the person who conducted the verification, but the main details of the measures taken based on the verification shall be sufficient. Records should be made in more detail, including the item that caused the action.

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2. When conducting the inspection set forth in the preceding paragraph, the marketing authorization holder, etc. must confirm the following matters:

(1) Product requirements for the product concerned are defined and documented.

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(ii) If the requirements in the agreement with the product recipient or the requirements in the instructions from the product recipient differ from those previously presented, such differences must be agreed upon with the product recipient.

×

(iii) Each facility has the ability to comply with the specified requirements.

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3. A marketing authorization holder, etc. must prepare and maintain records regarding the results of the review set forth in paragraph 1 and the measures taken based on the results of the review.

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4. If the product recipient does not indicate the requirements in writing, the marketing authorization holder, etc. must confirm the content of the product recipient's requirements before accepting the requirements.

×

5. When product requirements are changed, the marketing authorization holder, etc. shall ensure that related documents are revised, and that relevant members are thoroughly informed of the changed product requirements and that they understand them. I have to let it happen.

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Exchange of information, etc. with product recipients

Article 29 A marketing authorization holder, etc. must clarify and implement effective methods for mutual exchange of information or opinions with product recipients regarding the following matters:

29. Article 29 (Exchange of information, etc. with product recipient)

(13485) This article corresponds to "2003 Customer communication" of ISO7.2.3:XNUMX.

(2) In addition to the provisions of this Ministerial Ordinance, the necessary information communication with product recipients based on the GVP Ministerial Ordinance, etc. shall also be covered.

×

1. Product information

×

(ii) Handling of inquiries, contracts, and orders (including changes thereto)

×

(iii) Opinions from product recipients (including complaints)

×

(iv) Written notification prescribed in Article 62, paragraph (2)

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design development plan

Article 30 A marketing authorization holder, etc. must establish procedures for product design and development and document them.

30. Regarding Article 30 (Design and Development Plan)

(13485) This article corresponds to “2003 Design and development planning” of ISO7.3.1:XNUMX.

(2) Based on the provisions of paragraph 2, create a design and development plan and manage the progress of work related to design and development based on the plan.

(3) Based on the provisions of Paragraph 3, Item 3 and Paragraph 4, the manufacturer, etc. shall clarify the organizational and technical relationships among the parties involved in design and development, and provide necessary information and information. Establish and manage and supervise a system for effective exchange of opinions.

×

2. A marketing authorization holder, etc. must formulate a design and development plan (hereinafter referred to as a "design and development plan") and manage the design and development.

×

3. A marketing authorization holder, etc. must clarify the following matters when formulating a design and development plan.

×

1. Design and development stage

×

(ii) Appropriate verification, verification, validation, and design transfer operations at each stage of design and development (process output information from design and development is verified in advance to see if it is suitable for actual manufacturing, and then )

×

(iii) Responsibility and authority of departments or members related to design and development.

×

4. A marketing authorization holder, etc. must manage and supervise communications between parties involved in design and development to ensure effective exchange of information and opinions and clear assignment of responsibility and authority. .

×

5. The marketing authorization holder, etc. must document the design and development plan and update it appropriately as the design and development progresses.

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Process input information for design and development

Article 31 When conducting design and development, a marketing authorization holder, etc. shall clarify the following process input information for design and development related to product requirements, and maintain records related to the process input information. must be created and stored.

31. Article 31 (Process input information for design and development)

(13485) This article corresponds to "2003 Design and development inputs" of ISO7.3.2:XNUMX.

(2) Process input information for design and development should be of an appropriate scope and level in order to make work related to design and development, such as verification and validation of design and development, effective and efficient. thing.

(3) Regarding item 3, “Make sure that there are no omissions, no ambiguity, and no mutually contradictory information,” process input information for design and development should be written down in as much detail as possible. It is also a good idea to take into account information obtained through the design and development of other products.

×

(1) Product requirements related to function, performance and safety according to the intended use;

×

(ii) Requirements that are information obtained from previous similar design and development that can be applied as process input information to the relevant design and development.

×

(iii) Requirements for process output information related to risk management prescribed in Article 26, paragraph 5.

×

(iv) Requirements based on legal provisions, etc.

×

(v) Other essential requirements for design and development.

×

2. A marketing authorization holder, etc. must check the validity of the process input information for design and development prescribed in the preceding paragraph and approve it.

×

3. A marketing authorization holder, etc. must ensure that the requirements stipulated in each item of paragraph 1 are complete, unambiguous, and mutually exclusive.

×

Process output information from design and development

Article 32 A marketing authorization holder, etc. must format the process output information from design and development in a format that enables verification in comparison with process input information for design and development.

32. Article 32 (Process output information from design and development)

(13485) This article corresponds to "2003 Design and development outputs" of ISO7.3.3:XNUMX.

(2) Process output information from design and development may include the following:

a. Specifications related to products, etc. (specifications, drawings, etc.)

stomach. Criteria for determining whether or not to ship

C. Requirements regarding procedures and work environment in manufacturing and service provision

workman. Packaging and labeling requirements

O. Identification requirements

mosquito. Traceability requirements

tree. Requirements related to ancillary services

nine. Requirements regarding package inserts

(3) “Record of process output information from design and development” in Paragraph 4 includes records that demonstrate that process output information from design and development has been obtained in accordance with the design and development plan in Article 30, Paragraph 2. It must be something that can be used.

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2. Before allowing a product to proceed from design and development to the next stage of the process, the marketing authorization holder, etc. must approve the process output information from the design and development in advance.

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3. A marketing authorization holder, etc. must ensure that process output information from design and development conforms to the following conditions:

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(1) It shall conform to the requirements for process input information for design and development as stipulated in the preceding article.

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(ii) Appropriate information shall be provided for purchasing, manufacturing and provision of services.

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(iii) Contains criteria for determining whether or not to ship, or can refer to the criteria for determining whether or not to ship.

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(iv) It stipulates the characteristics of the product that are essential for the safe and proper use or operation of the product.

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4. A marketing authorization holder, etc. must create and store records of process output information from design and development.

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Design development review

Article 33 Regarding design and development, a marketing authorization holder, etc. shall, at an appropriate stage, carry out a systematic review of the following matters (hereinafter referred to as "design and development review") in accordance with the design and development plan. must be carried out.

33. Related to Article 33 (Design and Development Review)

(13485) This article corresponds to "2003 Design and development review" of ISO7.3.4:XNUMX.

(2) The timing of design and development review should be determined in advance in the design and development plan set forth in Article 30, Paragraph 2.

(3) Matters to be considered in design and development reviews may include the following:

a. Is the process input information for the relevant design and development sufficient?

stomach. Is the process capacity of each facility sufficient to realize the manufacturing of the product related to the design and development?

cormorant. Has safety been considered?

(4) "Experts related to the relevant design and development" in Paragraph 2 should include not only experts who can understand the relevant design and development information, but also those who are not directly responsible for the design and development stage.

(5) The "Record of the results of design and development review" in Paragraph 3 may include the date of the review, names of attendees, names of affiliations, job titles, etc.

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(1) Evaluate whether the design and development results can comply with all requirements.

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(ii) If there is a problem with design and development, make sure to identify the nature of the problem and propose necessary measures.

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2. A marketing authorization holder, etc. must have representatives of departments related to the design and development stage that is the subject of the design and development review and experts related to the design and development concerned participate in the design and development review.

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3. A marketing authorization holder, etc. must create and keep records of the results of design and development reviews (including records of any necessary measures taken based on the results).

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Verification of design development

Article 34 In order to ensure that the process output information from design and development complies with the conditions listed in Article 32, Paragraph 3, Item 1, manufacturers, etc. shall, in accordance with the design and development plan, Verification shall be carried out.

34. Regarding Article 34 (Verification of Design and Development)

(13485) This article corresponds to "2003 Design and development verification" of ISO7.3.5:XNUMX.

(2) Verification may include comparison with proven designs and testing and inspection of prototypes if they are created.

(3) The safety and performance of a product should be verified under conditions that are most representative of the conditions in which it will actually be used.

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2. A marketing authorization holder, etc. must create and maintain records of the results of the verification set forth in the preceding paragraph (including records of any necessary measures taken based on the results of such verification).

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Design development validation

Article 35 In order to ensure that the designed and developed product conforms to the requirements related to the pre-specified function or performance or intended use, the marketing authorization holder, etc. shall, in accordance with the design and development plan for the product, Validation of the relevant design and development (hereinafter referred to as "design and development validation" in this article) must be conducted.

35. Related to Article 35 (Design Development Validation)

(13485) This article corresponds to "2003 Design and development validation" of ISO7.3.6:XNUMX.

(2) The design and development validation prescribed in paragraph 1 shall be carried out after the design and development verification has been passed, and the final product manufactured in the actual manufacturing process or a process equivalent to the actual manufacturing process or the final product in its form shall be tested. The work must be performed under actual or simulated conditions of use.

(3) As stipulated in Paragraph 2, it should be noted that, in principle, the product in question must not be shipped unless design and development validation has been completed in advance.

(4) Design and development validation includes analysis of scientific materials related to the product, analysis of appropriate related academic literature, preclinical evaluation of biological safety data, etc., and similar and valid products already on the market. It should also include clinical evaluation based on clinical evaluation and performance evaluation of in vitro diagnostic reagents in the actual testing environment.

(5) Paragraph 4 stipulates that for medical devices, etc. that are subject to clinical trials and usage results evaluation, the collection and creation of materials related to the clinical trials and usage results evaluation is part of the ongoing design, development, and validation process. That you are requesting feedback as a.

(6) For products other than those related to medical devices for which clinical trials and usage results evaluations are required, the collection and creation of materials related to clinical trials and usage results evaluations is part of the ongoing design and development validation. This shall not prevent you from giving feedback as such.

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2. A manufacturer, etc. must complete design and development validation before shipping a product. However, in cases where validation cannot be performed until after the product is assembled or installed during use of the medical device, etc., design and development validation must be performed before the medical device, etc. is delivered to the user. It won't happen.

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3. A marketing authorization holder, etc. must create and maintain records of the results of design and development validation (including records of any necessary measures taken based on the results of such validation).

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4. If the medical device, etc. for which the design and development is concerned is a medical device, etc. specified by the Ordinance of the Ministry of Health, Labor and Welfare as provided for in Article 23-2-5, Paragraph 3 of the Act, or the manufacturer, etc. In the case of medical devices, etc. specified by Ordinance of the Ministry of Health, Labor and Welfare as prescribed in Paragraph 2-9, Paragraph 4, the collection and preparation of materials based on these provisions must be carried out as part of design and development validation. .

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Manage design and development changes

Article 36 When a marketing authorization holder, etc. makes a change in the design and development, it must make the details of the change identifiable, and create and keep a record of the change. .

36. Regarding Article 36 (Management of changes in design and development)

(13485) This article corresponds to "2003 Control of design and development changes" of ISO7.3.7:XNUMX.

(2) Changes in design and development may include the following:

a. Changes requested by product recipient

stomach. Changes required by design and development review, design and development verification, or design and development validation.

cormorant. Changes required by corrective or preventive actions

(3) When making changes, consider that there will be no unintended adverse effects on other product characteristics.

(4) Based on the provisions of paragraph 4, when creating records related to the results of checking, verification, and validation of changes in design and development pursuant to the provisions of paragraph 2, the details of the changes in design and development shall also be recorded. thing.

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2. Before implementing changes in design and development, the marketing authorization holder, etc. must conduct appropriate checks, verification, and validation and approve them in advance.

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3. The marketing authorization holder, etc. shall ensure that the scope of review of changes in design and development pursuant to the provisions of the preceding paragraph includes evaluation of the impact of such changes on component parts, etc. and products that have already been shipped.

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4. The marketing authorization holder, etc. shall prepare records regarding the results of the review of changes pursuant to the provisions of paragraph 2 (including records if necessary measures have been taken based on the results of the review), and Must be kept.

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Purchasing process

Article 37 Manufacturers, etc. shall establish procedures to ensure that purchased products comply with the requirements for purchased products that they have specified (hereinafter referred to as "purchased product requirements"), and shall follow these procedures. Must be documented.

37. Regarding Article 37 (Purchasing process)

(13485) This article corresponds to "2003 Purchasing process" of ISO7.4.1:XNUMX.

(2) The "purchased goods" in paragraph 1 may include purchased components, manufacturing materials, equipment and instruments, outsourcing of processes, services, etc.

(3) For items that particularly affect the quality of purchased goods, it may not be possible to sufficiently ensure the quality through inspections performed by manufacturers, etc. at the time of purchase, so the supplier's quality control and supervision system should be adapted. Purchasing management should be carried out, including evaluation of the situation, and it should be confirmed that appropriate management is being carried out to ensure quality.

(4) “Management methods applied to purchased goods” in Paragraph 2 shall include the following items:

a. Matters regarding transportation of purchased goods

stomach. Matters regarding testing and inspection of purchased goods at the time of delivery

cormorant. stomach. Matters regarding the handling of purchased goods that do not meet the tests and inspections in

(5) Based on the provisions of paragraph 2, regarding component parts, etc. and manufacturing substances that have been determined to have a large impact on the subsequent process of product realization or on the final product, the applicable items shall be listed for each individual product. In addition to stipulating in the product standard document, traceability shall be ensured based on the provisions of Articles 48 and 49. In addition, the criteria for determining the degree of impact on the subsequent manufacturing process of purchased items or on the final product shall be clarified in the procedures described in Paragraph 1.

(6) Methods for "evaluating the supplier of purchased goods" in paragraph 3 range from auditing the supplier's quality control and supervision system by the manufacturer, etc. to certification of the supplier's quality control and supervision system. This may include evaluation of the product's history, and manufacturers, etc., should select an appropriate method by taking into consideration the impact on the product.

(7) Paragraph 4, “Criteria for selection, evaluation, and re-evaluation of suppliers of purchased goods” should be appropriate, taking into account the impact on the product, etc.

2. A marketing authorization holder, etc. shall specify the supplier of the purchased goods and the method and degree of control applied to the purchased goods, as well as the process or final product (referring to products other than intermediate products) related to the subsequent product realization of the purchased goods. shall be determined according to the impact it has on

3. A marketing authorization holder, etc. must evaluate and select a supplier of purchased goods based on their ability to supply the purchased goods in accordance with the requirements for purchased goods. However, it is sufficient to evaluate the supplier of purchased goods for products related to limited general medical devices.

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4. Marketing authorization holders, etc. shall establish criteria for selection, evaluation, and re-evaluation of suppliers of purchased goods (evaluation and re-evaluation for suppliers of purchased goods of products related to limited general medical devices). There must be.

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5. A marketing authorization holder, etc. must create and keep records regarding the results of the evaluation set forth in paragraph 3 (including records if necessary measures have been taken based on the results of the evaluation). .

Purchasing information

Article 38 A marketing authorization holder, etc. shall clarify information regarding purchased goods (hereinafter referred to as "purchase information"), unless it can be shown in writing that other methods are appropriate, and , purchasing information must include the following purchasing item requirements:

38. Regarding Article 38 (Purchasing Information)

(13485) This article corresponds to "2003 Purchasing information" of ISO7.4.2:XNUMX.

(2) "Other methods" in Paragraph 1 refer to, for example, agreements made between manufacturers, etc. and suppliers.

(3) “Purchase information” in Paragraph 1 may include the following:

a. Technical information and specifications of purchased goods

stomach. Requirements regarding test inspection methods and pass/fail criteria

cormorant. Requirements regarding the quality of purchased goods

workman. Working environment requirements

O. Requirements based on legal provisions, etc.

mosquito. Special equipment requirements or special instructions

tree. Matters related to evaluation conditions and agreement renewal

nine. Requirements regarding the qualifications and competence of the supplier's members

K. Compliance status of supplier with QMS ministerial ordinance or related standards, etc.

(4) In determining the necessary traceability based on the provisions of Article 48, Paragraph 2, taking into consideration the provisions of Paragraph 3, how should documents and records containing purchasing information that should be created and stored be prepared? It is necessary to determine what is desired.

(5) For example, when purchasing a certain component, if information regarding revisions to the specifications of the component (for example, version number, etc.) is important for ensuring traceability of the product, such information should be It should be kept as part of a document or record containing purchasing information.

(i) Requirements regarding procedures, processes, and equipment and utensils at the purchased goods and the business premises of the supplier of the purchased goods;

(ii) Requirements for confirming the qualifications of members of suppliers of purchased goods;

(iii) Requirements regarding the quality control and supervision system of suppliers of purchased goods;

2. Before presenting the requirements for purchased goods to the supplier of the purchased goods, the manufacturer, etc. must confirm the validity of the relevant purchased goods requirements in advance.

3. A marketing authorization holder, etc. (excluding a limited type 3 medical device marketing authorization holder) shall collect related purchasing information after ensuring traceability as specified in the procedure manual pursuant to the provisions of Article 48, Paragraph 2. Documents and records containing the information shall be created and retained. However, this does not apply to products related to limited general medical devices.

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Verification of purchased items

Article 39 In order to ensure that purchased goods comply with the requirements for purchased goods, a marketing authorization holder, etc. must establish and implement the necessary operations for testing, inspection, and other verification.

39. Regarding Article 39 (Verification of purchased goods)

(13485) This article corresponds to "2003 Verification of purchased product" of ISO7.4.3:XNUMX.

(2) The method and frequency of testing and inspection of purchased items shall be clarified, and the matters stipulated in Article 6, Paragraph 3 shall be stipulated in the product standard document.

(3) This article applies to all purchased goods received from outside the quality control supervision system, such as a marketing authorization holder, regardless of whether or not money is paid upon receipt of the purchased goods. Something.

2. When a marketing authorization holder, etc. decides to carry out verification of purchased goods by themselves or a related product recipient at the business office of the supplier of purchased goods, the manufacturer, etc. shall comply with the implementation guidelines and instructions from the supplier of the purchased goods. The method for determining whether or not to ship products must be made clear in the purchasing information.

3. A marketing authorization holder, etc. must create and keep records of the verification set forth in the preceding two paragraphs.

Manufacture and service provision management

Article 40 A marketing authorization holder, etc. (excluding a third-class limited medical device manufacturer; the same shall apply in Paragraph 3) shall be responsible for the sale of products (excluding products pertaining to limited general medical devices; the same shall apply in Paragraph 3). Plans for manufacturing and provision of services must be established and implemented under the following management conditions (limited to those applicable to the product in question):

13485. Article 2003 (Control of production and service provision) (7.5.1) This article corresponds to "XNUMX Control of production and service provision" of ISOXNUMX:XNUMX.

(2) The records referred to in paragraph 2 refer to so-called manufacturing records, and may include the titles and locations of records related to the following information or related documents. a. Product name and lot number or manufacturing number

stomach. Manufacturing process and work date

cormorant. Name, lot number or manufacturing number of component parts, etc., and usage amount

workman. Material name, control number and usage amount

O. Planned production quantity and actual production quantity in each manufacturing process

mosquito. Test and inspection results and measures taken when the results are inappropriate

tree. Recorder name and recording date

nine. Shipping determination quantity

K. Other items necessary for records related to product manufacturing

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(1) Information describing the characteristics of the product is available.

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2. Procedure manuals, documents containing requirements, and work instructions are available. Also, if necessary, be able to use the reference sample and confirm the reference measurement method.

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(iii) Equipment and tools suitable for the relevant manufacturing are used.

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(iv) Equipment and instruments for monitoring and measurement are available and are being used.

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(v) Monitoring and measurement shall be carried out in accordance with the provisions of Articles 57 to 59.

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(6) Based on the provisions of this Ministerial Ordinance, permission to proceed to the next stage of the process, decision on release to the market, delivery of the product to the product recipient, and operations after the product is received by the product recipient are performed. thing.

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(vii) Carrying out the work related to packaging and labeling specified in the procedure manual, etc.

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2. The marketing authorization holder, etc. must make it possible to trace each lot of the product to the extent specified in the procedure manual pursuant to the provisions of Article 48, Paragraph 2, and make it possible to identify the manufacturing quantity and the quantity decided for shipment. Records must be created and kept. However, for products related to limited general medical devices, it is sufficient to create and store records that allow identification of the manufacturing quantity and shipment quantity for each lot of the product.

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3. A marketing authorization holder, etc. must verify and approve the records for each lot of products prepared pursuant to the provisions of the preceding paragraph.

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Product cleanliness management

Article 41 Marketing Authorizers, etc. (excluding Class 3 Limited Medical Device Manufacturers; hereinafter the same shall apply in this Article to Article 51 and Article 53) shall refer to their products (Limited General Medical Devices). (hereinafter the same shall apply in this Article to Article 51 and Article 53) falls under any of the following items, the requirements regarding the cleanliness of the product. The requirements shall be clarified, appropriate operations related to the requirements shall be established, and this shall be documented.

41. Regarding Article 41 (Product cleanliness management)

(13485) This article corresponds to "2003 Cleanliness of product and contamination control" of ISO7.5.1.2.1:XNUMX.

(2) The provisions of item 1 apply to the manufacturer, etc. when implementing the cleaning process, and the provisions of items 2 and 3 apply to the manufacturer, etc. when supplying the product. The provisions of item 4 require the relevant marketing authorization holder to establish and document requirements regarding the cleanliness of the product when removing manufacturing substances.

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(i) Products that are sterilized or used or operated after the relevant marketing authorization holder, etc. (including facilities; hereinafter the same shall apply in this article) performs cleaning;

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(ii) Products that are supplied unsterilized by the relevant marketing authorization holder (including shipping; the same shall apply in the next item) and are then sterilized or used or manipulated after undergoing a cleaning process.

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(iii) Items that are supplied by the relevant marketing authorization holder, etc. as being used or operated unsterilized, and for which cleanliness during use or operation is important.

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(iv) Products for which the relevant marketing authorization holder, etc. removes the manufacturing substance during manufacturing.

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Installation work

Article 42 A marketing authorization holder, etc. shall comply with the Enforcement Regulations of the Act on Ensuring the Quality, Efficacy, and Safety of Pharmaceuticals, Medical Devices, etc. (Ministry of Health and Welfare Ordinance No. 1 of 1960; hereinafter referred to as the "Enforcement Regulations"). ) When handling the manufacture of products related to installation controlled medical devices prescribed in Article 114-55, Paragraph 1, cases where it can be shown in writing that other methods are appropriate. In addition to clarifying the requirements for the installation of medical devices and the verification of such installations, including criteria for deciding whether or not to proceed, the appropriate operation of these requirements must be established and documented.

42. Regarding Article 42 (Installation work)

(13485) This article corresponds to "2003 Installation activities" of ISO7.5.1.2.2:XNUMX.

(2) The requirements provided to persons who install medical devices and verify said installation pursuant to the provisions of paragraph 2 shall be provided to manufacturers, distributors, etc. based on the provisions of Article 114-55, paragraph 1 of the Enforcement Regulations. The information shall serve as the basic material for creating the installation management standards.

(3) Requirements are created from the perspective of correctly installing medical devices in medical care facilities, etc., and special attention should be paid to the installation of safety control mechanisms such as interlocks and safety control circuits. When creating a document, methods must be established to prevent human errors such as confusion and mistakes during work.

(4) Specific items to be included in the requirements may include the following.

a. Measures to ensure worker safety

stomach. Space required for use (length, width and height)

cormorant. Space required for ventilation

workman. Strength of building required for installation

O. Capacity of power supply equipment used

mosquito. Types and construction methods of protective earthing, additional protective earthing, functional earthing, and potential equalization equipment to be used

tree. Impact on the work site and surrounding environment during installation (ionizing radiation, electromagnetic interference, etc.)

nine. Management conditions and methods for the work site and surrounding environment during installation

K. How to handle parts, units, tools, etc. used for installation

Ko. Installation method (including assembly method if assembly work is required)

sa. How to check the quality, performance and safety of installed medical devices

C. Checklist to be used at the work site during installation

vinegar. Data related to the calibration of equipment and instruments used for monitoring and measurement used during installation

C. Other necessary matters

(5) In addition, the following guidelines should be followed when shipping products such as large medical devices that require a decision on whether or not to ship them during actual installation work.

a. Manufacturers, etc. bring manufactured or imported products to the delivery destination (installation location).

stomach. Upon installation, the relevant manufacturer, etc. shall conduct tests and inspections necessary to determine whether or not to ship, such as visual inspection, in accordance with the provisions of the QMS Ministerial Ordinance, and complete the manufacturing activities as the relevant manufacturer, etc. In addition, the procedures, etc. in this case should be stipulated in the procedure manual, etc. prepared by the manufacturer, etc. based on the QMS Ministerial Ordinance.

cormorant. The manufacturer, etc. completes all tests and inspections necessary to complete the manufacturing process, including visual inspection, and then decides whether or not to ship the product to the market.

workman. If the product is approved for shipment, ownership will be transferred from the manufacturer to the distributor, etc., and the manufacturer, etc. will issue the installation management standards document to the distributor, etc. (or a person entrusted by the manufacturer).

O. The relevant distributor, etc. (or a person entrusted by them) will manage the installation.

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2. In cases falling under the preceding paragraph, a person other than the marketing authorization holder, etc. or a person designated in advance by the marketing authorization holder, etc. may install the medical device and verify the installation, according to the product recipient requirements. In such cases, the requirements for the installation and verification shall be provided to the person performing the installation and verification.

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3. The marketing authorization holder, etc. shall prepare records of the installation of the medical device set forth in paragraph 1 and the verification of said installation (limited to those performed by the marketing authorization holder, etc. or a person designated in advance by the marketing authorization holder, etc.). and must store it.

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Ancillary service operations

Article 43 A marketing authorization holder, etc. shall, in cases where the implementation of operations related to services incidental to the supply of products (hereinafter referred to as "auxiliary service operations") are predetermined requirements, carry out such operations. A system of procedures and work instructions for verifying compliance with the relevant requirements shall be established, and these shall be documented. In addition, if necessary, reference samples and measurement procedures must also be established and documented.

43. Regarding Article 43 (Ancillary service operations)

(13485) This article corresponds to "2003 Servicing activities" of ISO7.5.1.2.3:XNUMX. (XNUMX) "Ancillary services" as used herein refers to services incidental to manufacturing and supplying products, including repair work, maintenance work, and, for example, provision of technical advice and user education. , supply of spare parts, etc.

(3) Pursuant to the provisions of Article 40-2 of the Act, no person may repair medical devices as a business unless he or she has received a license for medical device repair business (manufacturer (design Please note that manufacturers other than those who only store the final product (Article 196 of the Enforcement Regulations) are required to repair medical devices that they themselves manufacture.

(4) If a non-conforming product is discovered when repairing the product using the method stipulated in the procedure manual, appropriate management shall be carried out as necessary in accordance with the provisions of Article 60.

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2. A marketing authorization holder, etc. must create and retain records of the incidental service operations performed.

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Special requirements for manufacturing control of sterile products

Article 44 A manufacturer, etc. that handles sterilized products must prepare and maintain records of process index values ​​for the sterilization process for each sterilized lot.

44. Related to Article 44 (Special requirements regarding manufacturing control of sterile products)

(13485) This article corresponds to “2003 Particular requirements for sterile medical devices” of ISO7.5.1.3:XNUMX.

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2. A marketing authorization holder, etc. that handles sterilized products must keep the records set forth in the preceding paragraph in a way that can be traced back to each manufacturing lot of the product.

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Validation of manufacturing processes, etc.

Article 45 A marketing authorization holder, etc. shall not be able to verify the process output information as a result of the process through subsequent monitoring or measurement of the process involved in the production of a product or the provision of a service (if the product is (including cases where defects become apparent only after use, operation, or service provision), the relevant process must be validated.

13485. Article 2003 (Validation of manufacturing processes, etc.) (7.5.2.1) This article corresponds to “XNUMX Validation of processes for production and service provision – General requirements” of ISOXNUMX:XNUMX.

(2) If a sterilization process is implemented in the manufacturing of a product, validation of that process should be performed based on the provisions of Articles 45 and 46. In addition to the sterilization process, processes that should be subject to validation pursuant to the provisions of paragraph 1 may include maintenance of control conditions in environmental control areas, aseptic processing, sealing of sterile packaging, freeze-drying, heat treatment, etc. To be.

(3) "Validation related to the use of software" in paragraph 4 is to confirm whether the software is applied as intended.

(4) Based on the provisions of Paragraph 4, by appropriately implementing validation of changes related to software or changes related to its usage, this applies to manufacturing and service provision that affect compliance with product requirements. Appropriate management must be in place to prevent inappropriate changes to the software being used.

(5) The provisions of paragraph 5 do not apply to software that was already in use when the QMS Ministerial Ordinance came into effect and whose use is considered appropriate.

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2. A marketing authorization holder, etc. must demonstrate through validation that the process targeted for validation pursuant to the provisions of the preceding paragraph can obtain the results specified in the product realization plan.

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3. A marketing authorization holder, etc. shall formulate implementation guidelines regarding the following matters (excluding matters that are deemed not to apply based on the content of the process, etc.) for the process that is subject to validation pursuant to the provisions of paragraph 1. , and proper operation based on the implementation guidelines must be established.

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(i) Judgment criteria for inspection and approval of the relevant process;

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(ii) Approval of equipment and equipment and confirmation of suitability of members;

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(iii) methods and procedures;

×

(iv) Requirements regarding records prescribed in Article 9

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5. Revalidation (revalidation is performed when the manufacturing procedure is changed, etc.)

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4. If a manufacturer, etc. uses software for manufacturing or providing services that affects the conformity of a product to product requirements, the manufacturer, etc. shall not use the software (changes in the software or its usage). Procedures for validation shall be established and documented.

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5. When using the software set forth in the preceding paragraph for the first time, a marketing authorization holder, etc. must perform validation in advance.

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6. A marketing authorization holder, etc. must prepare and keep records of the validation prescribed in paragraphs 1 through the preceding paragraph.

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Sterilization process validation

Article 46 A manufacturer, etc. that handles sterilized products must establish procedures for validation of sterilization processes and document them.

13485. Article 2003 (Validation of sterile process) (7.5.2.2) This article corresponds to "XNUMX Particular requirements for sterile medical devices" of ISOXNUMX:XNUMX.

(2) When creating procedures for validation of sterilization processes pursuant to the provisions of paragraph 1, please refer to the "Sterilization Validation Standards" (dated March 30, 2005, Pharmaceutical Food and Drug Administration No. 0330001, Chapter 4, Section 4). Care should be taken to ensure that sterilization validation is performed appropriately based on the Pharmaceutical, Food and Drug Administration Notification No. 0330 No. 5 dated March 30, 2011).

(3) "When implementing a sterilization process for the first time" in paragraph 2 includes cases where a sterilized product is manufactured for the first time at the facility, as well as cases where a new sterilization process is added.

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2. Manufacturers, etc. who handle sterilized products must conduct validation before implementing the sterilization process for the first time.

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3. Manufacturers, etc. who handle sterilized products must create and maintain records of the results of sterilization process validation.

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Identify

Article 47 A marketing authorization holder, etc. must identify the product by appropriate means in all processes related to product realization.

47. Article 47 (Identification)

(13485) This article corresponds to "2003 Identification" of ISO7.5.3.1:XNUMX.

(2) Identification is important for managing component parts, etc. during manufacturing, verifying the origin and condition of the product, ensuring traceability, and investigating the cause in the event of a quality problem. thing.

(3) Items that should be identified pursuant to the provisions of paragraph 1 shall include not only products but also component parts, manufacturing substances, etc. as necessary.

(4) "Appropriate means" in Paragraph 1 may include, for example, labeling on products and categorizing physical locations.

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2. A marketing authorization holder, etc. must establish procedures related to the identification set forth in the preceding paragraph and document them.

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3. A marketing authorization holder, etc. shall establish procedures to ensure that products returned to the marketing authorization holder, etc. are clearly distinguished from conforming products (meaning products that comply with product requirements). This must be documented.

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Ensuring traceability

Article 48 A marketing authorization holder, etc. must establish procedures for ensuring product traceability and document them.

48. Article 48 (Ensuring traceability)

(13485) This article corresponds to “2003 Traceability–General” of ISO7.5.3.2.1:XNUMX.

(2) "Traceability" as defined in paragraph 1 refers to traceability in both the so-called upstream direction, such as the purchase of component parts and manufacturing materials, and the so-called downstream direction, up to shipment from the manufacturer, etc. It must be possible to trace the history, application, or location of the product.

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2. A marketing authorization holder, etc. must specify the extent to which traceability is to be ensured and the requirements for records necessary for that purpose for each product in a written procedure that describes the procedures set forth in the preceding paragraph.

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3. If ensuring traceability of a product is a product requirement, a marketing authorization holder, etc. must manage the product with a unique label for identification and record this.

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Ensuring traceability of products related to specified medical devices

Article 49 If there is a risk that a product related to a specified medical device will not comply with the product requirements due to the conditions of the component parts, etc. or the working environment, the marketing authorization holder, etc. shall traceability of all records shall be ensured.

49. Regarding Article 49 (Ensuring traceability of products related to specified medical devices)

(13485) This article corresponds to “2003 Particular requirements for active implantable medical devices and implantable medical devices” of ISO7.5.3.2.2:XNUMX.

(13485) The requirements of ISO2003:66 apply to so-called active implanted medical devices and implanted medical devices in general, but since Japan already has a specified medical device system, this ministerial ordinance applies to Article 66 of the Act. It shall be applied to products related to specified medical devices stipulated in Paragraph XNUMX of XNUMX. The purpose of this article is to ensure that persons who have obtained approval for specified medical devices based on the provisions of Article XNUMX-XNUMX of the Act prepare and keep records of the names, addresses, etc. of specified medical device users, and that doctors who handle specified medical devices This should be achieved in conjunction with the provision of information by other medical professionals to those who have obtained approval for specific medical devices.

(3) This does not preclude the management of products other than those related to specified medical devices to ensure traceability.

(66) "Records related to distribution" prescribed in paragraph XNUMX shall be created and kept in accordance with the matters prescribed in Article XNUMX-XNUMX of the Act. In addition, all or part of the work related to the creation and storage of such records can be outsourced to distributors, etc.

(5) When manufacturing and selling specified medical devices, manufacturers, etc., must provide records related to the distribution of the product to the distributors, etc. that handle the product in order to ensure traceability after the product is shipped. to create and store it. Furthermore, in cooperation with distributors, etc., a system must be established to ensure that such records can be presented without delay in the event of a request for investigation or audit of marketing authorization holders, etc.

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2 In order to ensure the traceability of products related to specified medical devices after shipment, marketing authorization holders, etc. shall The same shall apply in the following paragraph) to create and maintain records regarding the distribution of the product.

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3. The records set forth in the preceding paragraph shall be recorded by a marketing authorization holder, etc. regarding the product pursuant to the provisions of Article 23-2-5, paragraph 6 or 8 of the Act, or by Article 23-2-2-3, Article 23-2-3, or 5, or an on-site inspection pursuant to the provisions of Article 69, paragraph 1 or 4 of the Act, or by the Minister of Health, Labor and Welfare, the prefectural governor, or the quality of pharmaceuticals, medical devices, etc. When there is a request from a person conducting a medical device compatibility investigation as stipulated in Article 37-23 of the Enforcement Order of the Act on Ensuring Efficacy and Safety (Cabinet Order No. 11 of 1960) It must be kept in such a way that it can be presented to distributors, etc.

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Product condition identification

Article 50 A marketing authorization holder, etc. shall identify the condition of the product in light of the requirements regarding monitoring and measurement.

50. Article 50 (Identification of product condition)

(13485) This article corresponds to "2003 Status identification" of ISO7.5.3.3:XNUMX. (XNUMX) Apart from the provisions of Article XNUMX, this article stipulates requirements related to identification with the main purpose of ensuring that only conforming products are shipped.

(3) The "state" in Paragraph 1 includes a state where the product is determined to fully meet the product requirements, a state where a decision has been made to ship under special adoption, and a test/inspection to determine whether or not the product can be shipped. This may include a waiting state, a state in which the product is determined to be non-conforming as a result of a shipping decision, etc.

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2. A marketing authorization holder, etc. shall ensure that only products that have passed testing and inspection (including products for which a decision has been made to ship under approved special adoption) are shipped, used, operated, or installed. Therefore, the condition of the product must be identified and maintained during all processes related to product manufacturing, storage, installation, and ancillary service operations.

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Product recipient goods, etc.

Article 51 A marketing authorization holder, etc. shall identify the product recipient's goods, etc. (including intellectual property and information owned by the product recipient) provided for use in or incorporation into the product, etc. At the same time, it must be verified and protected.

51. Regarding Article 51 (Goods, etc. of product recipient)

(13485) This article corresponds to "2003 Customer property" of ISO7.5.4:XNUMX.

(2) "Goods, etc. of the product recipient" in paragraph 1 includes, for example, component parts supplied by the product recipient, as well as equipment and appliances, intellectual property, and information that the product recipient owns. must include.

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2. If the product, etc. mentioned in the preceding paragraph is lost or damaged, or if it is found to be unsuitable for use, the marketing authorization holder, etc. shall report the contents to the product recipient, create a record, and keep the same. must be kept.

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3. A marketing authorization holder, etc. must handle the articles, etc. set forth in paragraph 1 with due care while they are being managed or used by the marketing authorization holder, etc.

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product retention

Article 52 A marketing authorization holder, etc. shall maintain product compatibility (identification, handling, A system of procedures or work instructions (including packaging, storage, and protection) shall be established and documented. However, for products related to limited general medical devices, this is limited to the period of work that the manufacturer, etc. is responsible for with respect to the product.

52. Article 52 (Product Retention)

(13485) This article corresponds to "2003 Preservation of product" of ISO7.5.5:XNUMX. (XNUMX) In order to maintain product compatibility, special considerations include protection from damage, deterioration, contamination, etc. caused by impact, corrosion, temperature changes, and static electricity discharge during transportation, etc. .

(3) For products with a limited use period under paragraph 2, ensure that those whose use period has expired are properly managed as nonconforming products in accordance with the provisions of Article 60.

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2. A marketing authorization holder, etc. (excluding a limited type 3 medical device marketing authorization holder; the same shall apply in the next section) shall follow procedures or work instructions regarding the management of products with a limited shelf life or products that require special storage conditions. Such systems must be established and documented. However, this does not apply to products related to limited general medical devices.

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3. A marketing authorization holder, etc. must manage and record the special storage conditions set forth in the preceding paragraph. However, this does not apply to products related to limited general medical devices.

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Management of equipment and equipment

Article 53 A marketing authorization holder, etc. must specify the monitoring and measurement necessary to demonstrate the conformity of a product to product requirements, as well as the equipment and instruments for such monitoring and measurement.

53. Article 53 (Management of equipment and appliances)

(13485) This article corresponds to "2003 Control of monitoring and measuring devices" of ISO7.6:XNUMX.

(2) When performing calibration or verification as specified in paragraph 3 (hereinafter referred to as "calibration, etc."), the required accuracy must be taken into consideration. In addition, in consideration of the impact on quality of equipment and instruments for monitoring and measurement, the range of instruments subject to calibration, etc., the frequency of calibration, etc., and the method of calibration, etc. shall be determined, and this shall be specified in product standards or procedure manuals. be stipulated.

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2. A marketing authorization holder, etc. shall establish procedures to ensure that the monitoring and measurement set forth in the preceding paragraph is carried out in a method that is both practicable and consistent with the requirements for said monitoring and measurement, and shall follow these procedures. shall be documented.

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3. A marketing authorization holder, etc. must, when necessary to ensure the validity of monitoring and measurement results, ensure that equipment and instruments for monitoring and measurement comply with the following conditions.

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(1) Calibration or verification shall be carried out at predetermined intervals or prior to use by a method that can be traced back to the metrological standard (or, if such standards do not exist, the basis for the calibration or verification shall be recorded). what is being done.

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(ii) Necessary adjustments or readjustments have been made.

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(3) The calibration status shall be clearly identifiable.

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(4) Be protected from manipulation that would invalidate the results of monitoring and measurement.

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(v) be protected from damage and deterioration during handling, maintenance and storage;

4. If nonconformity of monitoring and measurement equipment and instruments with monitoring and measurement requirements is found, the marketing authorization holder, etc. shall evaluate the validity of the previous monitoring and measurement results and record them. Must.

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5. In the case referred to in the preceding paragraph, the marketing authorization holder, etc. shall take appropriate measures regarding the monitoring and measurement equipment and instruments and the products affected by the nonconformity referred to in the preceding paragraph.

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6. A marketing authorization holder, etc. must create and maintain records of the results of calibration and verification of equipment and instruments for monitoring and measurement.

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7. When a marketing authorization holder, etc. decides to use software for monitoring and measuring product requirements, when using it for the first time, the manufacturer, etc. must confirm in advance that the software is applied to the monitoring and measurement as intended. It must be acknowledged that there are

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Section 6 Measurement, Analysis and Improvement Analysis and Improvement

Measure, analyze and improve

Article 54 A marketing authorization holder, etc. (excluding a limited type 3 medical device marketing authorization holder; the same shall apply in the following paragraph and the following article) shall monitor, measure, analyze and improve necessary for the following operations (in the following paragraph: A plan must be formulated and implemented for the process related to "monitoring, etc."

54. Article 54 (Measurement, analysis and improvement)

(13485) This article corresponds to “2003 Measurement, analysis and improvement–General” of ISO8.1:XNUMX.

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(i) To demonstrate the suitability of products (excluding products related to limited general medical devices);

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(ii) Ensure the suitability of the quality control and supervision system and maintain its effectiveness.

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2 In the plan set forth in the preceding paragraph, the marketing authorization holder, etc. must specify the monitoring methods (including statistical methods) applicable to the process stipulated in the preceding paragraph and the scope of application of such methods.

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Product recipient opinions

Article 55 As part of the measurement of the implementation status of the quality control supervision system, the marketing authorization holder, etc. shall monitor information regarding whether all facilities, including the marketing authorization holder, etc., comply with product recipient requirements. Must.

55. Regarding Article 55 (Opinions of Product Recipients)

(13485) This article corresponds to "2003 Feedback" of ISO8.2:XNUMX.

(2) "Problems related to product quality" in paragraph 3 refers to problems related to product quality, the product's direct container and packaging, external containers and packaging, labeling, etc. .

(3) "Issuing an early warning" in paragraph 3 means that measures are taken promptly within the manufacturer, etc. after receiving information.

(4) "Opinions from product recipients" in paragraph 3 may include the following, in addition to complaints from manufacturers, medical providers, etc. who receive the product.

a. Survey conducted on product recipients

stomach. Product recipient requirements

cormorant. Points out from regulatory authorities

workman. Data related to service provision

(5) Paragraph 3, “Mechanism for collecting opinions,” includes the contents of the opinions (name, model, packaging form, test and inspection unit number of the target product, date of occurrence, place of occurrence, applicant's address, name, details, etc.) Investigation of the cause (investigation of the target product (investigated market name, distribution status, usage status, status of manufacturing control and quality control at each facility, etc.), investigation of test and inspection records, investigation of manufacturing records) This may include conducting a determination based on the results of investigating the cause.

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2. A marketing authorization holder, etc. must clarify the method for obtaining and utilizing the information set forth in the preceding paragraph.

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3. Marketing authorization holders, etc. shall implement procedures related to the system for collecting opinions from product recipients in order to issue early warnings regarding problems related to product quality, and to use them as process input information related to corrective and preventive measures. shall be established and documented.

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4. The marketing authorization holder, etc. shall make the review of information obtained after the product is shipped, such as information collected pursuant to the provisions of Article 68-2, Paragraph 1 of the Act, as part of the opinion gathering mechanism set forth in the preceding paragraph. It won't happen.

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Internal audit

Article 56 A marketing authorization holder, etc. shall conduct internal audits at predetermined intervals in order to clarify whether the quality control and supervision system complies with the following requirements:

56. Related to Article 56 (Internal Audit)

(13485) This article corresponds to "2003 Internal audit" of ISO8.2.2:XNUMX.

(2) Internal audits must be conducted regularly and effectively, including their effectiveness, in order to evaluate whether the manufacturing and quality control of products is being carried out appropriately at the relevant marketing authorization holder, etc. To be something. Additionally, in the following cases, special internal audits should be conducted as necessary.

a. When significant changes are made, such as organizational changes or revisions to procedures.

stomach. When it is recognized that the product may be non-conforming

cormorant. When corrective measures have been taken and there is a need to verify whether they were effective.

(3) The “Report of Internal Audit Results” in Section 6 shall be a document pointing out the nonconformities discovered and the necessary corrective measures for them. In addition, as a general rule, appropriate deadlines should be set for responding to or responding to matters pointed out by internal audits.

(4) The results of internal audits shall be appropriately communicated, and any necessary items shall be appropriately reviewed by management and supervisors.

(i) Conforms to the requirements related to the product realization plan, the provisions of this Ministerial Ordinance, and the relevant quality control and supervision system (excluding the product realization plan for products related to limited general medical devices).

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(ii) It is effectively implemented and maintained.

2. A marketing authorization holder, etc. must formulate an internal audit implementation plan, taking into consideration the status and importance of the processes and areas subject to internal audits, as well as the results of previous audits.

3. A marketing authorization holder, etc. must determine the criteria, scope, frequency, and method of internal audits.

4. A marketing authorization holder, etc. must ensure objectivity and fairness when selecting members to conduct internal audits (hereinafter referred to as "internal auditors") and implementing internal audits.

5. A marketing authorization holder, etc. (excluding a limited type 3 medical device marketing authorization holder) shall not have an internal auditor conduct an internal audit of its own operations.

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6. A marketing authorization holder, etc. must establish and document procedures that specify the responsibilities and requirements for formulating and implementing an internal audit implementation plan, reporting internal audit results, and storing records.

7. The marketing authorization holder, etc. shall have the responsible person responsible for the area that has been internally audited take measures to eliminate the discovered nonconformity and the cause of the nonconformity without delay, and have the person in charge of the area that has been internally audited take measures to eliminate the cause of the nonconformity, as well as have the person verify the measures. The results must be reported.

Process monitoring and measurement

Article 57 A marketing authorization holder, etc. must monitor each process related to the quality control and supervision system in an appropriate manner, and, if measurement is possible, also take measurements.

57. Article 57 (Process monitoring and measurement)

(13485) This article corresponds to “2003 Monitoring and measurement of processes” of ISO8.2.3:XNUMX.

(2) This article shall ensure that the quality control and supervision system constituted by the process specified in Article 5, paragraph 2, item 1 is capable of obtaining the results specified in the plan in Article 14, paragraph 1. It stipulates that the process in question shall be monitored and measured using the criteria and methods set forth in Article 5, Paragraph 2, Item 3 in order to verify the results.

2. A marketing authorization holder, etc. (excluding a limited type 3 medical device marketing authorization holder; the same shall apply in the next paragraph) shall ensure that the process obtains the results specified in the plan set forth in Article 14, paragraph 1 regarding the monitoring method set forth in the preceding paragraph. It must be possible to demonstrate that it is possible.

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3. If the marketing authorization holder, etc. is unable to obtain the results specified in the plan set forth in Article 14, Paragraph 1, the marketing authorization holder, etc. shall take measures to ensure the suitability of the product (excluding products related to limited general medical devices). , corrective and corrective measures shall be taken as appropriate.

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Product monitoring and measurement

Article 58 A marketing authorization holder, etc. shall monitor and measure the characteristics of a product in order to verify that the product conforms to product requirements.

58. Article 58 (Monitoring and measurement of products)

(13485) This article corresponds to “2003 Monitoring and measurement of product” of ISO8.2.4:XNUMX.

(2) The purpose of this article is that products, etc. that do not conform to standards, etc. must not be allowed to proceed to the next stage of the process or be allowed to be shipped. From this perspective, product standards and procedure manuals should be created. In addition, products must not be shipped unless a decision has been made as to whether or not they can be shipped.

(3) In carrying out the provisions of this article, the member may have the member conduct a test or inspection using an external test or inspection agency, or may request an external test or inspection agency to conduct a test or inspection at his or her own responsibility. When determining the results, the necessary technical conditions for commissioning the test, the method of quality control during transport of the specimen, the method of communication including the test and inspection results, etc. should be determined.

(4) "Permission to proceed to the next step in the process" in Paragraph 4 means that the manufacturer, etc., determines at what stage the product should be confirmed based on information such as design development and risk management, and It shall be indicated that it will be confirmed before proceeding to the next stage that monitoring and measurement based on the implementation guidelines specified in the implementation plan have been completed without any problems.

2. A marketing authorization holder, etc. (excluding a Type 3 limited medical device marketing authorization holder) shall carry out the monitoring and measurement set forth in the preceding paragraph in accordance with the product realization plan and the It must be carried out at an appropriate stage of the process related to product realization in accordance with the procedure manual prescribed in Article 10, Paragraph 1, Item 2.

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3. A marketing authorization holder, etc. must create and retain records that provide evidence of compliance with the criteria for determining whether or not a product can be shipped.

4. A marketing authorization holder, etc. must create and maintain a record identifying the person who gave permission to proceed to the next stage of the process and made the decision to ship the product.

5. The marketing authorization holder, etc. shall complete all necessary matters specified in the product realization plan (for products related to limited general medical devices, monitoring, measurement of product characteristics, and other necessary matters in paragraph 1) without any hindrance. Until such time, permission to proceed to the next stage of the process, determination of whether or not to ship, and provision of services shall not be made.

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Requirements specific to specific medical devices

Article 59 A marketing authorization holder, etc. (excluding a limited type 3 medical device marketing authorization holder; the same shall apply in the following article and Article 61) shall be responsible for products pertaining to specified medical devices (products pertaining to limited general medical devices). The same shall apply in the following article), records shall be created to identify the members who conducted all testing or inspection work related to the product.

13485. Article 2003 (Requirements specific to specific medical devices) (8.2.4.2) This article corresponds to "XNUMX Particular requirements for active implantable medical devices and implantable medical devices" of ISOXNUMX:XNUMX.

(2) This does not preclude the management of products other than those related to specified medical devices to ensure traceability.

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Management of nonconforming products

Article 60 A marketing authorization holder, etc. shall identify products that do not comply with product requirements (hereinafter referred to as "nonconforming products") in order to ensure that they are prevented from being used, operated, or shipped contrary to the intended purpose. , must be managed.

60. Regarding Article 60 (Management of nonconforming products)

(13485) This article corresponds to “2003 Control of nonconforming product” of ISO8.3:XNUMX.

(2) “Nonconforming products” are products, manufacturing materials, and component parts that are determined to be nonconforming to the standards specified in product standards, for example, due to test and inspection results or deviations from manufacturing conditions. etc.

(3) When a nonconforming product is recalled, unintended use or operation or shipment from the facility is prevented in accordance with the provisions of paragraph 1 until necessary measures are taken to investigate the cause of the recall. Appropriate management shall be carried out to ensure that.

(4) In order to ensure that the special recruitment procedures based on the provisions of paragraphs 3 and 4 are appropriate, when creating the procedure manual under paragraph 2, for example, it is necessary to Ensure that there are no omissions, such as by stipulating compliance procedures.

(5) Regarding the provisions of Paragraph 9, when remanufacturing is required, a procedure manual must be prepared in which the effects of remanufacturing are considered in advance. Records of remanufacturing shall be created and kept in accordance with paragraph 6.

(6) Regarding the provisions of Paragraph 10, even if remanufacturing has no adverse effect on the product, it is required to clearly document this fact.

(7) Regarding the documentation in Paragraph 10, it is not necessarily required to create an independent document for that purpose; for example, it is sufficient to appropriately describe it in a newly created work instruction. .

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2. A marketing authorization holder, etc. must establish and document procedures for the management of nonconforming products and related responsibilities and authorities.

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3. A marketing authorization holder, etc. must dispose of nonconforming products by one of the following methods:

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(1) To take measures to eliminate discovered nonconformities.

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(2) Under special adoption, permission to use or operate, permission to proceed to the next step in the process, or decision to ship.

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(iii) Taking measures to prevent the originally intended use, operation, or application.

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4. A marketing authorization holder, etc. shall not dispose of a nonconforming product through special adoption if it does not comply with the provisions of laws and regulations.

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5. When a nonconforming product is specially adopted, a marketing authorization holder, etc. must create and keep a record identifying the member who gave permission for the special adoption.

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6. A marketing authorization holder, etc. must create and maintain a record of the details of nonconformity and the measures taken in response to the nonconformity (including special adoption).

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7. When a manufacturer, etc. makes corrections to a nonconforming product, he or she must re-verify the corrected product to demonstrate its conformity to the product requirements.

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8. If a nonconforming product is discovered after delivery of the product to the product recipient or after the product has been used or operated, the marketing authorization holder, etc. shall take appropriate measures to address the effects or potential effects of the nonconformity. must be taken.

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9. If it is necessary to remanufacture the product, the marketing authorization holder, etc. must document the new procedures for the relevant process. In this case, the marketing authorization holder, etc. must go through the same approval procedures as the original procedure manual when issuing a manual that describes the procedure.

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10. Before carrying out the approval procedures set forth in the preceding paragraph, the marketing authorization holder, etc. must clarify and document any adverse effects that remanufacturing may have on the product in advance.

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Analyzing the data

Article 61 A marketing authorization holder, etc. shall take measures in order to demonstrate that the quality control supervision system is appropriate and effective, and if such measures are taken to improve the quality control supervision system. To identify, collect and analyze appropriate data (including data from monitoring and measurement results as well as data from other relevant sources) in order to assess the effectiveness of improvements in procedures shall be established and documented.

61. Article 61 (Data analysis)

(13485) This article corresponds to "2003 Analysis of data" of ISO8.4:XNUMX.

(2) The results of data analysis pursuant to this article shall be appropriately organized in order to guide appropriate judgment and action when submitted to management/supervisor review.

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2. A marketing authorization holder, etc. must obtain information regarding the following matters (for products related to limited general medical devices, limited to the matters listed in item 1) by analyzing the data set forth in the preceding paragraph.

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(1) Opinions from product recipients collected based on the procedure manual prepared pursuant to the provisions of Article 55, paragraph 3.

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(ii) Conformity to product requirements

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3. Characteristics and trends of processes and products (including those that may lead to taking preventive measures)

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(iv) Supplier of purchased goods, etc.

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3. A marketing authorization holder, etc. must create and retain records regarding the results of the data analysis set forth in the preceding two paragraphs. However, this does not apply to products related to limited general medical devices.

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improvement

Article 62 A marketing authorization holder, etc. (excluding a limited type 3 medical device marketing authorization holder) shall be subject to its quality policy, quality objectives, audit results, data analysis, corrective measures, preventive measures, and management/supervisor review. In order to maintain the validity and effectiveness of the quality control supervision system on an ongoing basis, all matters that need to be changed shall be clarified and such changes shall be implemented.

62. Article 62 (improvement)

(13485) This article corresponds to “2003 Improvement–General” of ISO8.5.1:XNUMX.

(2) The "notification" in Paragraph 2 is as defined in Article 2, Paragraph 25, and may include, for example, a document to notify related parties when conducting a collection. In addition, the "procedure manual for issuing and implementing notifications" should include the following procedures:

a. A management system that allows the procedure to be carried out even if the person in charge of the process is absent.

stomach. Level of management who decides to initiate corrective action and how affected products are identified

cormorant. Disposal of returned goods. For example, mechanisms for determining rework, repackaging, and disposal.

workman. Contact mechanism

(3) The matters to be stated in the notification shall include the following matters:

a. Name of medical device, etc. related to the product

stomach. Lot number or manufacturing number of the medical device, etc. related to the product

cormorant. Reason for issuing notice

workman. expected harm

O. Actions to be taken

(4) Investigations into complaints from product recipients under paragraph 3 should be conducted in a timely and appropriate manner, taking into account the provisions of Article 55.

(5) Based on the provisions of paragraph 6, manufacturers, etc. are required to prepare and properly implement procedures for notifying the Minister of Health, Labor and Welfare when they become aware of matters related to defects. That's what I'm doing. Also, consider the necessity of collection and take necessary measures. Furthermore, when conducting work related to post-marketing safety control, the provisions of Article 69 should be kept in mind.

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2. A marketing authorization holder, etc. must establish procedures for issuing and implementing notifications, document them, and be able to implement these procedures at any time.

3. A marketing authorization holder, etc. must prepare and retain records of all investigations conducted regarding complaints from product recipients.

4. As a result of the investigation set forth in the preceding paragraph, the marketing authorization holder, etc. has determined that work performed by persons other than all those involved in the processes necessary for the quality control supervision system, including the marketing authorization holder, etc., is a contributing factor to the product recipient's complaints. If this becomes clear, relevant information must be communicated to the relevant parties.

5. When a marketing authorization holder, etc. decides not to take corrective or preventive measures (limited to corrective measures in the case of a limited type 3 medical device marketing authorization holder) based on a complaint from a certain product recipient. shall approve and record the reasons.

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6. Marketing authorization holders, etc. (excluding Type 3 limited medical device manufacturing authorization holders) shall comply with Article 228-20, Article 2 of the Enforcement Regulations regarding products (excluding products related to limited general medical devices). When a person becomes aware of any of the matters listed in each item of the same paragraph, a procedure must be established for reporting to the Minister of Health, Labor and Welfare based on the provisions of the same paragraph, and this must be documented.

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Corrective action

Article 63 A marketing authorization holder, etc. must take appropriate corrective measures in accordance with the impact of the discovered nonconformity to prevent the recurrence of said nonconformity.

63. Regarding Article 63 (Corrective Measures)

(13485) This article corresponds to "2003 Corrective action" of ISO8.5.2:XNUMX.

(2) The "required corrective measures" in Paragraph 2, Item 4 may include the identification of the person responsible for implementing the corrective measures, the timing and method of implementing the corrective measures, and the method for verifying effectiveness. .

(3) The review of the effectiveness of the corrective measures set forth in Paragraph 2, Item 6 may include verification as to whether the corrective measures taken do not introduce new risks.

(4) When implementing corrective measures, in order to be as effective as possible, identify the recipient of the product in question, investigate other products, processes, etc. that may be affected; Efforts should be made to understand the root cause of nonconformity.

2. A marketing authorization holder, etc. must establish procedures for corrective measures that specify the necessary requirements regarding the following items and document them:

(i) Review of nonconformities (including complaints from product recipients);

(ii) Identification of the cause of nonconformity

(iii) Evaluation of the necessity of measures to ensure that nonconformities do not recur.

(4) Determination and implementation of necessary corrective measures (including updating of documents)

(v) If an investigation has been conducted regarding corrective measures, a record of the results and the results of the corrective measures taken based on the results;

(vi) Review of the corrective measures taken and their effectiveness;

precautionary measures

Article 64 A marketing authorization holder, etc. (excluding a limited type 3 medical device marketing authorization holder; hereinafter the same shall apply in this article and the following article) shall take measures to prevent the occurrence of a problem in light of the impact of the problem that may arise. Appropriate precautions must be identified and taken.

64. Related to Article 64 (Preventive Measures)

(13485) This article corresponds to "2003 Preventive action" of ISO8.5.3:XNUMX.

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2. Marketing authorization holders, etc. must establish procedures for preventive measures that specify the necessary requirements regarding the following items and document them:

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(i) Possible nonconformities and their causes;

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(ii) Evaluation of the necessity of preventive measures.

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(iii) Necessary preventive measures and implementation records.

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(iv) If an investigation has been conducted regarding preventive measures, records of the results and the results of preventive measures taken based on the results;

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(v) Review of the preventive measures taken and their effectiveness.

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Chapter 3 Additional requirements related to manufacturing control and quality control of medical devices, etc.

Establishment of a new quality control supervision system for registered manufacturing facilities

Article 65 A marketing authorization holder, etc. shall have a business office that outsources its processes pursuant to the provisions of Article 5, paragraph (4) or a business office of a supplier of purchased goods pursuant to Article 23-2-3 of the Act. If the manufacturing facility is registered pursuant to the provisions of Paragraph 1 or Article 23-2-4 Paragraph 1 of the Act (hereinafter referred to as a "registered manufacturing facility"), the manufacturing facility related to the registered manufacturing facility Necessary information regarding whether a foreign manufacturer of medical devices, etc. prescribed in the same paragraph (hereinafter referred to as a "manufacturer, etc. related to a registered manufacturing facility") is conducting manufacturing control and quality control based on an appropriate quality control supervision system. confirmation must be made.

65. Regarding Article 65 (Quality control supervision system for registered manufacturing facilities)

(1) This Article applies to Article 5 or 37 if the establishment that outsources the process that affects the realization of the product or the establishment of the supplier of purchased goods is a registered manufacturing establishment as defined by the Act. In addition to the management based on the provisions of Article 1, the marketing authorization holder, etc. shall conduct necessary confirmation that the manufacturer, etc. associated with the registered manufacturing facility is conducting manufacturing control and quality control based on an appropriate quality control supervision system. shall be stipulated.

(2) If, as a result of confirmation by the manufacturer, etc., there is a risk that the quality of the product will be seriously affected, ensure that necessary and appropriate measures are taken.

(3) The necessary confirmations stipulated in this article may be conducted before the start of manufacturing or periodically.

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Newly established additional requirements related to quality control supervision system

Article 66 In addition to the provisions of Chapter 2, a marketing authorization holder, etc. shall comply with the provisions of Chapters 3 to 5 (limited to the provisions that are applicable pursuant to the provisions of Article 3; hereinafter in this Article) ), a quality control oversight system must be established, documented, and implemented, and its effectiveness must be maintained.

66. Regarding Article 66 (Additional requirements related to quality control supervision system)

(1) This article applies to documents related to the quality control supervision system prescribed in Article 5, the processes prescribed in Article 5, paragraph 3, and the quality control supervision system prescribed in Article 6, paragraph 1, as well as It stipulates additional requirements for marketing authorization holders, etc., which should be implemented in accordance with the provisions of Chapters 3 to 5 based on the scope of application stipulated in Article 1.

(2) Manufacturers, etc. of medical devices and in vitro diagnostic reagents (excluding manufacturers, etc. of biological medical devices, etc. and radioactive in vitro diagnostic reagents) shall comply with the provisions of Chapters 2 and 3. Manufacture and quality control of products must be conducted in accordance with regulations.

(3) Manufacturers, etc. of biological medical devices, etc. must conduct manufacturing control and quality control of their products based on the provisions of Chapter 4 in addition to Chapters 2 and 3.

(4) Manufacturers, etc. of radioactive in vitro diagnostic reagents must conduct product manufacturing and quality control based on the provisions of Chapter 5 in addition to Chapters 2 and 3.

2. A marketing authorization holder, etc. must manage and supervise the process based on the provisions of Chapters 3 to 5 in addition to the provisions of Chapter 2.

3. A marketing authorization holder, etc. shall include in the documents related to the quality control and supervision system prescribed in Article 6, Paragraph 1, the matters listed in each item of the same paragraph, as well as the procedures and records prescribed in Chapters 3 to 5. Must be recorded.

New storage period for quality control supervision documents

Article 67 Pursuant to the provisions of Article 8, Paragraph 4, the period during which a marketing authorization holder, etc. retains a quality control supervision document or a copy thereof shall be the period listed in each of the following items from the date of abolition of said quality control supervision document ( (For those related to education and training, the period is five years). However, with regard to quality control supervision documents used in product manufacturing or testing and inspection, it is sufficient to keep them available for the period specified in the following article.

67. Regarding Article 67 (Document storage period)

(1) This article stipulates the "period specified in Article 67" prescribed in Article 8, Paragraph 4.

(2) “Documents specified in this chapter” may include the following:

・Documented quality control supervision system (Article 66)

・For all facilities and related registered manufacturing facilities to notify the marketing authorization holder, etc. of the matters listed in each item of Article 228-20, Paragraph 2 of the Enforcement Regulations when the facilities, etc. become aware of the matters listed in each item of Article 228-20, Paragraph 2 of the Enforcement Regulations regarding the product. Procedures for (Article 69)

・Document that stipulates the duties of the domestic quality operations manager (Article 72, Paragraph 2)

・Arrangements between manufacturers and related facilities and registered manufacturing sites (Article 72-2)

・Procedures for processing notifications from repair companies (Article 72-2, Paragraph 2, Item 1)

・Procedures for ensuring quality at distributors or lenders (Article 72-2, Paragraph 2, Item 2)

・Procedures for processing notifications from second-hand sellers or lenders (Article 72-2, Paragraph 2, Item 3)

(66) The "validity period or expiry date" prescribed in Articles XNUMX and XNUMX includes, in addition to the expiry date of medical devices that is required to be stated based on the provisions of Article XNUMX, Item XNUMX of the Act, The validity period set by the applicant during design activities, etc. must be included.

(4) With regard to documents used in the manufacturing or testing and inspection of products, it is sufficient to store them so that they can be used at least during the storage of records related to the products as stipulated in Article 9.

(5) This article does not preclude storage beyond the storage period stipulated in Article 67 (for example, during the product life specified by the manufacturer, etc.).

2. A marketing authorization holder, etc. must manage and supervise the process based on the provisions of Chapters 3 to 5 in addition to the provisions of Chapter 2.

3. A marketing authorization holder, etc. shall include in the documents related to the quality control and supervision system prescribed in Article 6, Paragraph 1, the matters listed in each item of the same paragraph, as well as the procedures and records prescribed in Chapters 3 to 5. Must be recorded.

New record retention period

Article 68 A marketing authorization holder, etc. shall keep the records prescribed in Article 9, paragraph 1 or this chapter for the period listed in the following items from the date of creation (five years in the case of records related to education and training). Must be kept.

68. Regarding Article 68 (Record retention period)

(66) This article stipulates the "period specified in Article XNUMX" stipulated in Article XNUMX, Paragraph XNUMX regarding the storage of records.

(2) “Records specified in this chapter” may include the following:

a. A copy of a document stating the necessary opinion to the marketing authorization holder, supervisor, or other person responsible for the relevant business (Article 71, Paragraph 1, Item 2)

stomach. Records of the results of the decision to ship products distributed domestically to the market for each lot and the shipping destination etc. to the market (Article 72, Paragraph 2, Item 3)

cormorant. For products distributed in Japan, a document reporting to the management supervisor and the general marketing and sales manager for medical devices (Article 72 Paragraph 2 No. 4)

workman. When obtaining information regarding the quality of a product distributed domestically (including information regarding quality defects or the risk of quality defects), report to the management supervisor and the general marketing and marketing manager for medical devices, etc. (Article 72, Paragraph 2, Item 5)

O. Records describing the details of the recall of domestically distributed products and records of reports of such records to the management supervisor and the general marketing and marketing manager for medical devices (Article 72, Paragraph 2, Item 6-B)

mosquito. In addition to what is listed in Article 72, Paragraph 2, Items 3 to 6, reporting to the Manager and the General Marketing and Marketing Manager for Medical Devices, etc. when deemed necessary for the performance of domestic quality control operations. documents (Article 72, Paragraph 2, Item 7)

tree. In carrying out domestic quality control operations, as necessary, to manufacturers of related registered manufacturing facilities, foreign manufacturers of medical devices, distributors, pharmacy establishments, hospital and clinic establishments, and other related parties. Documents of communications or instructions carried out (Article 72, Paragraph 2, Item 8)

nine. Document reporting information regarding safety measures stipulated in Article 2, Paragraph 2 of the GVP Ministerial Ordinance to the safety management department (department related to the supervision of safety assurance operations) (Article 72, Paragraph 2, Item 9)

K. Records regarding the decision on whether or not to ship to the market made by a person designated in advance by the person in charge of domestic quality operations, and a document reporting such records to the person in charge of domestic quality operations (Article 72, Paragraph 4)

(3) Records are broadly classified into those related to a specific product and those whose content is common to multiple products, but even records related to products related to medical devices other than specified maintenance management medical devices. If it is similarly related to products related to specified maintenance management medical devices (e.g. records related to shared business operation infrastructure, etc.), storage for 15 years or more is required based on the provisions of Paragraph 1, Item 1. To be something.

(1) For products related to specified maintenance management medical devices, 15 years (if the product's shelf life plus one year is longer than 15 years, the shelf life plus one year) )

(ii) For products related to medical devices, etc. other than specified maintenance management medical devices, five years (if the period of validity of the product plus one year is longer than five years, one year shall be added to the validity period of the product) (added period)

Reporting defects, etc. Newly established

Article 69 A marketing authorization holder, etc. shall notify all facilities and related registered manufacturing sites that the facilities and related registered manufacturing sites are responsible for the products in each item of Article 228-20, Paragraph 2 of the Enforcement Regulations. A procedure must be established for notifying the marketing authorization holder, etc. of the matters listed in (1) when the matter becomes known, and the procedure must be documented.

69. Regarding Article 69 (Fault Reporting)

(1) This article requires all facilities and related registered manufacturing facilities to report any defects related to the product in the event that they become aware of any defects related to each item of Article 228-20, Paragraph 2 of the Enforcement Regulations. Manufacturers, etc. are required to prepare procedures for notification and ensure that they are implemented appropriately.

(2) If a manufacturer, etc. receives a report based on the procedure from all facilities and related registered manufacturing sites, the manufacturer, etc. must properly implement the procedure in accordance with Article 62, Paragraph 6.

Relationship with post-marketing safety management standards New establishment

Article 70 When a marketing authorization holder, etc. conducts operations related to post-marketing safety management of products, in addition to the provisions of this Ministerial Ordinance, a marketing authorization holder, etc. This must be done in accordance with the provisions of the Ministerial Ordinance on Standards for Post-Marketing Safety Control (Ministry of Health, Labor and Welfare Ordinance No. 135 of 2004; hereinafter referred to as "Post-marketing Safety Control Standards").

70. Article 70 (Relationship with post-marketing safety management standards)

(1) If a marketing authorization holder conducts operations related to post-marketing safety management of products in accordance with this Ministerial Ordinance, such as reporting to the Minister of Health, Labor and Welfare pursuant to the provisions of Article 62, Paragraph 6, GVP Things that are required to be done based on ministerial ordinances.

Duties of general manufacturing and sales manager for medical devices, etc.) newly established

Article 71 A marketing authorization holder shall perform the duties listed in the following items as a general marketing manager for medical devices, etc. (hereinafter referred to as "medical devices, etc.") as prescribed in Article 23-2-14, paragraph 2 of the Act. (General manufacturing and sales manager).

71. Related to Article 71 (Duties of General Marketing and Marketing Manager for Medical Devices, etc.)

(1) In addition to what is stipulated by regulations and GVP ministerial ordinances, this article stipulates the operations related to manufacturing control and quality control that the general marketing and marketing manager for medical devices, etc. should perform.

(2) "Other manufacturing control and quality control operations" in Paragraph 1, Item 1 shall specify the operations necessary to unify the entire quality control supervision system. The general marketing and marketing manager for medical devices, etc. shall cooperate with the management supervisor and the manager, understand the quality control system of the marketing and marketing vendor, etc., and assume responsibility for each requirement stipulated by ministerial ordinance.

(3) The document referred to in Paragraph 1, Item 2 requires the general marketing and marketing manager for medical devices to keep a copy of the document. Furthermore, it is desirable to manage the original documents in such a way that the relationship between delivery and receipt of the document is known to "marketing authorization holders, managers and supervisors, and other persons responsible for the relevant operations."

(4) "Departments related to manufacturing control or quality control" in Paragraph 1, Item 5 refers to the quality assurance department prescribed in Article 72, Paragraph 1, Item 1, and other departments related to manufacturing control or quality control. to refer to.

(5) Paragraph 2 stipulates the persons in charge who can concurrently serve as the general marketing and marketing manager for medical devices. Furthermore, even if the person is concurrently serving as the person in charge as stipulated in paragraph 2, the general marketing and marketing manager for medical devices, etc. is required to work at the office that has the main function of the marketing and marketing business.

(6) The General Manufacturing and Sales Manager for Medical Devices, etc. shall concurrently hold two or more positions as a supervisor, manager, and domestic quality operations manager, as long as it does not interfere with business operations. What you can do. However, please note that this is limited to cases where the applicant satisfies the qualifications, etc. required for the position for which he/she wishes to concurrently hold the position.

(1) To supervise and be responsible for decisions regarding product shipment and other operations related to manufacturing control and quality control.

(ii) When it is deemed necessary for the fair and proper conduct of business, the necessary opinion shall be expressed in writing to the marketing authorization holder, manager and supervisor, or any other person responsible for the business, and a copy thereof shall be kept for five years. To be kept.

(3) Supervising the Domestic Quality Operations Manager prescribed in paragraph 1 of the following Article (excluding cases where the General Marketing and Marketing Manager for Medical Devices also serves as the Domestic Quality Operations Officer pursuant to the provisions of the following paragraph).

(4) Respect the opinions of the manager and the domestic quality operations manager prescribed in paragraph 1 of the following article (excluding the manager in the case of a third-class limited medical device marketing authorization holder).

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(5) Departments related to manufacturing control or quality control and the safety management department specified in Article 4, Paragraph 1 of the Post-Marketing Safety Management Standards (referred to as the "Safety Management Department" in Paragraph 2, Item 9 of the following Article). To ensure close cooperation between the two parties.

2. The general marketing and marketing manager for medical devices, etc. may also serve as a management supervisor, management manager, or domestic quality operations manager as prescribed in paragraph 1 of the following article.

Newly established domestic quality operations manager

Article 72 A marketing authorization holder shall, as the person responsible for the work to control the quality of products in Japan (hereinafter referred to as "quality control work") performed in accordance with the provisions of this Ministerial Ordinance, carry out the following at a facility located in Japan: A person in charge of domestic quality operations who meets the requirements must be appointed.

72. Related to Article 72 (Domestic Quality Operations Manager)

(1) "Facilities located in Japan" in paragraph 1 refers to, for example, the location of the office that has the main functions of the marketing authorization holder. In addition, if the person concurrently serves as the general marketing and marketing manager for medical devices as prescribed in Article 71, Paragraph 2, the person is required to work at the location of the office that has the main functions of the marketing authorization holder.

(2) “Quality Assurance Department” in Paragraph 1, Item 1 requires the establishment of a department that supervises quality control operations, and if the requirements of the ministerial ordinance are met, the name does not necessarily mean “Quality Assurance Department.” The name does not need to be "Assurance Department." Each company may decide on the name as it sees fit, but it must be clear which department is responsible for overseeing quality control operations.

(3) The provisions of Paragraph 1, Item 2 stipulate that the person responsible for domestic quality operations related to medical devices, etc. must be a person who takes product risks into consideration and has sufficient experience in quality control operations and is familiar with related operations. The regulations were established based on what should be done. "Persons who have been engaged in quality control work or similar work for three years or more" include the following persons in charge and those who have engaged in the work. Additionally, "3 years or more" may refer to the total number of years of relevant work, whether at the company or another company.

a. The person must be a person who is not likely to interfere with the proper and smooth performance of management and supervisory duties.

stomach. Chief administrator

cormorant. General manufacturing and sales manager for medical devices, etc.

workman. Quality assurance manager, manufacturing manager, and responsible engineer under the old law

O. Other marketing authorization holders or persons engaged in work related to manufacturing control or quality control in the manufacturing industry, etc.

(4) "Person who has the ability to appropriately perform quality control work" in Paragraph 1, Item 3 refers to the person who has the ability to appropriately perform quality control work, after comprehensively considering his or her work history, years of experience, education and training status, educational background, etc. Refers to a person to whom a distributor can entrust responsibility.

(5) The provisions of Paragraph 1, Item 4 were established in order to eliminate as much as possible the influence from a business standpoint, such as profitability, on the work carried out by the Domestic Quality Operations Manager. From this perspective, "other departments that affect the proper and smooth execution of quality control operations" can be considered to include, for example, departments that promote sales.

(6) "Related procedure manuals, etc. prepared in accordance with this Ministerial Ordinance" in paragraph 2 does not require the preparation of new procedure manuals for the operations carried out by the domestic quality operations manager. For example, it is possible to apply mutatis mutandis the procedures stipulated in Article 55, Paragraph 3 to the work prescribed in item 4, and Article 60, Paragraph 2 to the work prescribed in Item 6. thing.

(7) The "work related to domestic quality control" in Paragraph 2, Item 1 may include the work listed in Paragraph 2, Items 3 to 9 of this Article.

(8) The following may be considered as the contents to be recorded in Paragraph 2, Item 3. Furthermore, the records shall be based on Article 40, Paragraphs 2 and 3.

a. Record of receipt and delivery of medical devices, etc. (sales name, lot number)

number, delivery quantity, shipping destination, etc.)

stomach. Records related to evaluation of manufacturing control and quality control results

cormorant. Records related to the evaluation of information regarding quality, efficacy, and safety provided by the marketing authorization holder or manufacturer, etc. that may affect the decision on whether or not to release the product to the market.

workman. Records related to decisions on whether or not to ship to the market (sales name, lot number, decision maker, decision date, etc.)

(9) "Significant impact on quality" in Paragraph 2, Item 4 means that the manufacturer, who is responsible for the quality of the product, has determined, based on scientific evidence, that there is a possibility that the product's characteristics or changes may cause Appropriate judgment should be made based on such consideration. At least the changes to the content of the approval shall be included.

(10) Paragraph 2, Item 4 provides that when the domestic quality operations manager obtains information regarding changes in manufacturing methods or testing and inspection methods that may have a significant impact on the quality of domestically distributed products, the person responsible for domestic quality operations must promptly It stipulates that information should be provided to the person in charge of management and the general sales manager of medical devices, etc. of the relevant marketing authorization holder.

(11) Paragraph 2, Item 5 provides that if a quality defect or a risk of quality defects is found in the quality information, the person in charge of domestic quality operations promptly It stipulates that information be provided to the sales manager and appropriate measures be taken.

(12) "Quality, etc. of the product" in Paragraph 2, Item 5 includes the quality of containers, packaging, labeling, etc. In addition, the "necessary and appropriate measures" in the same item shall be appropriately reflected in manufacturing control and quality control operations, including the management of nonconforming products under Article 60 and consideration of recalls through corrective measures, etc. under Article 63. that it is necessary to

(13) The collection process referred to in Paragraph 2, Item 6 shall be carried out appropriately in cooperation with manufacturers, etc. of registered manufacturing facilities, distributors, pharmacy establishments, hospital and clinic establishments, and other related parties. thing.

(14) The "certain period" in Paragraph 2, Item 6, A. refers to the period until a decision is made on what to do with the recalled product.

(15) "When it is deemed necessary for the performance of domestic quality control operations" in Paragraph 2, Item 7 refers to, for example, operations related to shipping performed by a person designated in advance by the domestic quality operations manager. Include cases where improvements are required.

(16) The provisions of Paragraph 2, Item 8 require that information regarding recalls, suspension of manufacturing and sales, and other quality issues be provided to distributors, medical institutions, etc. as necessary.

(17) The provisions of Paragraph 2, Item 9 require that information regarding safety measures among quality information be provided in writing to the safety management department without delay. Furthermore, the safety management department shall provide information regarding quality in accordance with the provisions of Article 8, Paragraph 1, Item 2 of the GVP Ministerial Ordinance (including cases where it is applied mutatis mutandis in Articles 14 and 15 of the GVP Ministerial Ordinance). Please note that

(18) Based on the provisions of paragraph 3, the decision on whether or not to ship to the market shall be made by the person in charge of domestic quality operations, or by a person in the quality assurance department or a person in charge of domestic quality operations. It must be something that can be done by members of the registered manufacturing facility.

(19) The "person designated in advance" in paragraph 3 means a person who is familiar with the content of the business and has been designated in advance as the person in charge of the business.

(20) The "person who has the ability to properly and smoothly carry out the relevant work" in paragraph 3 is a person who meets the same requirements as the domestic quality business operations manager stipulated in Article 71, paragraph 1. thing.

(21) When a person other than the domestic quality operations manager makes a decision on whether or not to ship, the following matters should be considered in advance. (Or make it available.) Furthermore, the records must be based on Article 40, Paragraphs 2 and 3.

a. Instructions for managing shipments to market

stomach. Prompt reporting and instructions in the event of non-conformities, etc. found in the procedures stipulated in A.

cormorant. Periodic confirmation from manufacturers, etc.

workman. Information necessary for the person making the decision on whether or not to release the product to the market to appropriately and smoothly make the decision on whether or not to release the product to the market.

(22) The following items are considered to be included in the “Results and records regarding shipment to market such as shipping destination” in Paragraph 4.

a. Records of receipt and delivery of medical devices, etc. (sales name, lot number, quantity delivered, shipping destination, etc.)

stomach. Records related to evaluation of manufacturing control and quality control results

cormorant. Records related to the evaluation of information regarding quality, efficacy, and safety provided by the marketing authorization holder or manufacturer, etc. that may affect the decision on whether or not to release the product to the market.

workman. Records related to decisions on whether or not to ship to the market (sales name, lot number, decision maker, decision date, etc.)

(23) The purpose of the report in Paragraph 4 is to ensure that the person in charge of domestic quality operations compiles and manages information related to decisions on whether or not to ship to the market, and ensures that the operations are carried out appropriately. If it is implemented, it is understood that it is not necessarily necessary to report every time a decision is made on whether or not to release the product to the market.

(1) The person is the person in charge of the quality assurance department at the marketing authorization holder.

(ii) A person must have been engaged in quality control work or other similar work for three years or more.

(iii) Must have the ability to carry out domestic quality control operations appropriately and smoothly.

(iv) The person does not belong to a department related to the sale of medical devices, etc., and there is no other risk of interfering with the proper and smooth execution of domestic quality control operations.

2. A marketing authorization holder must have a domestic quality operations manager perform the following tasks based on the procedures, etc. prepared based on the provisions of this Ministerial Ordinance.

(1) To supervise domestic quality control operations.

(ii) Confirm that domestic quality control operations are being carried out properly and smoothly.

(3) For products to be distributed domestically, the decision to ship to the market is made for each lot (for medical devices, etc. that do not constitute a lot, for each manufacturing number or manufacturing code), and the results and destination etc. for shipping to the market are determined. Preparation of records (if a pre-designated person is required to make a decision on whether or not the product can be shipped to the market pursuant to the provisions of the next paragraph, appropriately understand the status of the decision on whether or not the product can be shipped to the market) thing.).

(iv) In the event that there is a change in the manufacturing method, testing or inspection method, etc. of a product distributed domestically that may affect the quality of the product, information regarding the change shall be collected from within and outside the country, and If the change is likely to have a significant impact on the quality of the product, the manager (in the case of the domestic quality operations manager of a Type 3 limited medical device manufacturer, the manager) The same shall apply in the following items to item 7) and the General Marketing and Marketing Manager for Medical Devices to ensure that necessary and appropriate measures are taken.

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(v) Information on the quality of products distributed domestically (including information on quality defects or the risk thereof) shall be collected from within and outside Japan, and when such information is obtained, it shall be immediately reported to the person in charge of management. and the General Marketing and Marketing Manager for Medical Devices, etc., shall report and record the information in writing, and ensure that necessary and appropriate measures are taken.

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(vi) To carry out the following operations when collecting domestically distributed products:

B. Collected medical devices, etc. should be separated and stored for a certain period of time, and then disposed of appropriately.

(b) A record describing the details of the recall shall be created and a written report shall be made to the person in charge of management and the general marketing and marketing manager for medical devices.

(vii) In addition to what is listed in items 4 through the preceding item, when it is deemed necessary for the performance of domestic quality control operations, the information shall be provided in writing to the management manager and the general marketing and marketing manager for medical devices, etc. Report.

(viii) In carrying out domestic quality control operations, as necessary, to manufacturers of related registered manufacturing facilities, foreign manufacturers of medical devices, etc., distributors, establishments of pharmacies, establishments of hospitals and clinics, and other related parties. , to communicate or give instructions in writing.

(9) When information regarding safety measures prescribed in Article 2, Paragraph 2 of the Post-Marketing Safety Management Standards becomes known, it shall be provided in writing to the safety management department without delay.

3. The decision to ship to the market as prescribed in item 3 of the preceding paragraph shall be made by a person designated in advance by the Domestic Quality Operations Manager (a person from the quality assurance department or a registered manufacturing facility (limited to those that ship to the market)). Only those who are members of the Board and have the ability to carry out the work properly and smoothly may be allowed to perform the work.

4. A person who has made a decision to ship to the market pursuant to the provisions of the preceding paragraph must prepare records regarding the results and shipping to the market, including the shipping destination, and must report in writing to the person in charge of domestic quality operations. .

5. The person responsible for domestic quality operations may also serve as the person responsible for management.

Other compliance matters

Article 72-2 A marketing authorization holder shall maintain the relationship with the business conducted pursuant to the provisions of Article 55 in order to ensure that the collection of information prescribed in Paragraph 2, Items 4 and 5 of the preceding Article is not hindered. In addition to developing the necessary systems based on the above, necessary and sufficient matters must be negotiated with related facilities and registered manufacturing sites, and these must be documented.

72-2. Regarding Article 72-2 (other matters to be observed)

(1) For products distributed domestically, manufacturers shall collect changes in manufacturing methods and testing methods listed in Article 72, Paragraph 2, Item 4, and quality information prescribed in Article 72, Paragraph 2, Item 5. There is a need to develop the necessary systems for this purpose. The agreement requires the marketing authorization holder to make appropriate information collection with the relevant facilities and registered manufacturing sites necessary for the marketing authorization holder to collect information related to the quality control supervision system. It does not require you to make arrangements with all facilities.

(2) Regarding the method of agreement, in addition to the format in which the details of the agreement are made clear in the contract itself, it may also be determined in a format that makes the details of the agreement clear to the outside.

(3) If the marketing authorization holder and the related facility or registered manufacturing site are the same corporation, the relationship between the marketing authorization holder and the related facility or registered manufacturing facility is appropriately regulated in the management regulations of the corporation. That's fine.

(4) Arrangements are basically made between the marketing authorization holder and the related facility or registered manufacturing facility, etc., but the details are agreed between the related facility and the registered manufacturing facility. It is also possible for three parties, including the manufacturer and distributor, to make an agreement. Furthermore, it does not necessarily require direct agreements with all facilities or registered manufacturing sites; for example, it may be necessary to conclude an agreement with a representative registered manufacturing facility that manages all processes, and This does not negate the use of other methods, such as stipulating management methods and communication methods for facilities, etc.

(5) "Necessary and sufficient matters between related facilities and registered manufacturing sites" in Paragraph 1 means, for example, in the case of nonconformity, changes that affect product quality, quality defects, etc. This refers to determining the method of prompt contact with the manufacturer and the person responsible for responding.

(6) Paragraph 2, Item 1 provides that if a notification is received from a repairer regarding the repair of a medical device that has been manufactured and sold, the repairer must be notified of the appropriate method of repairing the medical device and any other relevant information. It stipulates that written instructions must be provided regarding matters necessary to maintain the quality, effectiveness, and safety of medical devices.

(7) Paragraph 2, Item 2 stipulates that written instructions must be given to distributors or lenders of medical devices that intend to manufacture and sell them on how to ensure quality at predetermined business offices. What I did.

(8) Paragraph 2, Item 3 stipulates that if a notice is received from a used product seller or lender regarding the sale or loan of a used product, the seller, etc. should be informed of the quality of the medical device, It stipulates that written instructions must be given regarding matters necessary to maintain efficacy and safety.

2. A marketing authorization holder must establish procedures for the following matters and document them:

(i) Processing of notifications from medical device repair companies;

(ii) Ensuring quality at medical device distributors or lenders;

(iii) Processing notifications from second-hand product sellers or lenders.

Operations of a designated manufacturer and distributor of foreign-manufactured medical devices, etc.

Article 72-3 A person with special approval for foreign-manufactured medical devices, etc. must have a designated holder of marketing authorization for foreign-manufactured medical devices, etc. carry out the following operations among the operations performed pursuant to the provisions of this Ministerial Ordinance:

72-3. Article 72-3 (appointed foreign manufacturer of medical devices, etc.)

(66) Business related to document and record management prescribed in Paragraph XNUMX, Item XNUMX refers to document management prescribed in Article XNUMX, record management prescribed in Article XNUMX, and quality management prescribed in Article XNUMX. Requirement for storage of management and supervision documents, storage of records stipulated in Article XNUMX, etc.

(2) Paragraphs 1 and 3 stipulate the operations to be performed by a designated foreign-manufactured medical device manufacturer.

(3) Paragraphs 2 and 3 stipulate the operations to be performed by the designated foreign designated highly controlled medical device manufacturer.

(1) Among the operations carried out pursuant to the provisions of Article 17, those related to domestic operations.

(ii) Among the operations carried out pursuant to the provisions of Article 29, those related to domestic operations.

(iii) Among the operations carried out pursuant to the provisions of Article 43, those related to domestic operations.

(iv) Among the operations conducted pursuant to the provisions of Articles 48 and 49, those related to domestic operations.

(v) Among the operations carried out pursuant to the provisions of Article 55, those related to domestic operations.

(vi) Among the operations performed pursuant to the provisions of Article 60, those related to domestic operations.

(vii) Collection processing of domestic products

(viii) Operations related to post-marketing safety management of domestic products.

(ix) Perform necessary reports, exchange of information, and other relevant operations to the management supervisor, manager, and other related parties of the person who has obtained special approval for foreign-manufactured medical devices, etc., as a designated marketing authorization holder for foreign-manufactured medical devices, etc. Work to ensure necessary cooperation with persons who have obtained special approval for foreign-manufactured medical devices, etc. in order to carry out the work appropriately.

(x) Management of documents and records related to operations performed as a designated marketing authorization holder of foreign-manufactured medical devices, etc.

2. The provisions of the preceding paragraph shall apply mutatis mutandis to foreign designated highly controlled medical device manufacturers, etc. In this case, the term "designated foreign-manufactured medical device manufacturer" shall be read as "designated foreign designated manufacturer of highly controlled medical devices, etc.".

3. The provisions of Article 70 to the preceding Article (excluding Article 72, Paragraph 5) shall apply mutatis mutandis to the designated marketing authorization holder of foreign-manufactured medical devices, etc. or the designated foreign designated marketing authorization holder of highly controlled medical devices, etc. . In this case, "other" in Article 71, Paragraph 1, Item 1 refers to "other designated foreign-manufactured medical devices, etc. or designated foreign designated highly controlled medical devices, etc." ", and in item 2 of the same paragraph, ``manufacturer, supervisor, etc." means ``designated foreign-manufactured medical device manufacturer, or designated foreign-designated highly controlled medical device manufacturer, etc.'' In Item 4, "Manager and Paragraph 1 of the following Article" refers to "Paragraph 1 of the following Article" and "(For Limited Type 3 Medical Device Marketing Authorizers, excluding the Management Responsible Person. )'s opinion' means 'the opinion of',' and 'the manager or management supervisor or the following article, paragraph 1' in paragraph 2 of the same article means 'the following article, paragraph 1'. ``Accordingly'' in Article 72, Paragraph 1 means ``Therefore, as a designated foreign-manufactured medical device manufacturer or a designated foreign-designated highly controlled medical device, etc.'' ``Administrative supervisor (in the case of the domestic quality operations manager of a limited type 3 medical device manufacturer/distributor, the administrative supervisor. The same applies to the following item to item 7) and the general marketing and marketing manager of medical devices, etc. ” refers to “the general marketing and marketing manager for medical devices, etc.,” and in items 5, 6, b, and 7 of the same paragraph, the words “administrative officer and the general marketing and marketing manager for medical devices, etc.” refer to It shall be read as "General manufacturing and sales manager for medical devices, etc."