The document discusses the roles and responsibilities of chemistry, manufacturing, and controls (CMC) regulatory affairs professionals. CMC ensures that pharmaceutical products are manufactured according to good manufacturing practices and that facilities meet regulatory standards. CMC regulatory affairs professionals work with various teams to provide CMC strategy, submit required information to regulatory agencies for approvals, and make submissions for any post-approval changes or studies. They act as responsible agents and certify that submissions meet all requirements.
The Product Quality Review (PQR) is a regular review of all licensed medicinal products conducted to verify consistency of manufacturing processes and the appropriateness of specifications. The objectives of the PQR include determining the need for process, specification or validation changes; verifying compliance; identifying trends; and determining corrective actions. The EU requires annual PQRs that review areas like starting materials, process and product testing results, failed batches, deviations, changes made, and stability monitoring results. The PQR is intended to enhance quality and identify improvements.
Impact and Influence of Regulatory Changes to the Pharmaceutical Contract Man...PharmOut
How the adoption of the PIC/S GMP code by the Australian Therapeutic Goods Administration (TGA) will impact pharmaceutical companies who use contract manufacturers.
Presentation discusses the regulatory obligations and how quality risk management should be used.
Presentation: TGA manufacturing principles update - Adoption of PIC/S Guide t...TGA Australia
TGA is adopting updates to the PIC/S Guide to GMP including PE009-13 and future revisions such as PE009-14. Key points include:
- PE009-13 was adopted on January 1, 2018 with a 12 month transition period for industry to comply.
- Future revisions will address additional chapters and annexes to further clarify requirements.
- TGA plays an active role in updating PIC/S GMP guidance to ensure risks are addressed and GMP keeps pace with innovation.
- Adopting international standards supports TGA's mutual recognition agreements and provides assurance in international markets.
The document discusses the role of Chemistry, Manufacturing, and Controls (CMC) regulatory affairs in managing post-approval changes to drugs. It explains that CMC regulatory affairs professionals work to assure drug quality from clinical trials through marketing by determining the appropriate regulatory submissions for manufacturing changes. They assess proposed changes and provide initial and final responses on whether a prior approval supplement, changes-being-effected supplement, annual report, or no submission is required. This change control process involves interactions with manufacturing and consideration of regulations, guidance, and potential effects on drug quality and equivalence.
Regulatory aspect of pharmaceutical change control systemDeveshDRA
The document discusses the regulatory aspects of pharmaceutical change control systems. It outlines the benefits of a change control system, including ensuring changes are properly documented, validated, approved and traceable. It describes the different categories of changes (major, moderate, minor) and approval processes. A successful change control system requires identifying the need for a change, reviewing documentation, preparing a change proposal, classifying and approving the change, developing an implementation plan, verification and closure. Regulatory guidelines require formal change control systems to evaluate all changes that could affect product quality or manufacturing processes.
PET - Quality Assurance of PET Radiopharmaceutials@Saudi_nmc
Quality assurance of PET radiopharmaceuticals ensures patient safety and product efficacy through systematic activities implemented throughout the production process. This includes regulating raw materials, equipment, documentation, and product release. The batch record documents all production details for traceability. Products must meet criteria for purity, safety, and efficacy before release. Non-conforming products that fail quality control tests are removed and investigations are conducted to implement corrective actions. Quality is built into the production process through regulated procedures and cannot be tested in after the fact.
Regulatory affairs cmc , post approval regulatory affairsArjunDhawale
The document summarizes CMC (chemistry, manufacturing and controls) regulatory affairs for pharmaceutical products. It discusses the CMC section of regulatory filings which contains information on drug substance and product characteristics, manufacturing and quality. It describes the chemistry, manufacturing process, specifications and controls for ensuring consistent quality batches. It also covers CMC regulatory compliance after approval and post-approval regulatory requirements to ensure continued safety and effectiveness. The goal of CMC regulatory affairs is to provide the necessary CMC information and strategy to obtain and maintain regulatory approvals.
The document discusses the roles and responsibilities of chemistry, manufacturing, and controls (CMC) regulatory affairs professionals. CMC ensures that pharmaceutical products are manufactured according to good manufacturing practices and that facilities meet regulatory standards. CMC regulatory affairs professionals work with various teams to provide CMC strategy, submit required information to regulatory agencies for approvals, and make submissions for any post-approval changes or studies. They act as responsible agents and certify that submissions meet all requirements.
The Product Quality Review (PQR) is a regular review of all licensed medicinal products conducted to verify consistency of manufacturing processes and the appropriateness of specifications. The objectives of the PQR include determining the need for process, specification or validation changes; verifying compliance; identifying trends; and determining corrective actions. The EU requires annual PQRs that review areas like starting materials, process and product testing results, failed batches, deviations, changes made, and stability monitoring results. The PQR is intended to enhance quality and identify improvements.
Impact and Influence of Regulatory Changes to the Pharmaceutical Contract Man...PharmOut
How the adoption of the PIC/S GMP code by the Australian Therapeutic Goods Administration (TGA) will impact pharmaceutical companies who use contract manufacturers.
Presentation discusses the regulatory obligations and how quality risk management should be used.
Presentation: TGA manufacturing principles update - Adoption of PIC/S Guide t...TGA Australia
TGA is adopting updates to the PIC/S Guide to GMP including PE009-13 and future revisions such as PE009-14. Key points include:
- PE009-13 was adopted on January 1, 2018 with a 12 month transition period for industry to comply.
- Future revisions will address additional chapters and annexes to further clarify requirements.
- TGA plays an active role in updating PIC/S GMP guidance to ensure risks are addressed and GMP keeps pace with innovation.
- Adopting international standards supports TGA's mutual recognition agreements and provides assurance in international markets.
The document discusses the role of Chemistry, Manufacturing, and Controls (CMC) regulatory affairs in managing post-approval changes to drugs. It explains that CMC regulatory affairs professionals work to assure drug quality from clinical trials through marketing by determining the appropriate regulatory submissions for manufacturing changes. They assess proposed changes and provide initial and final responses on whether a prior approval supplement, changes-being-effected supplement, annual report, or no submission is required. This change control process involves interactions with manufacturing and consideration of regulations, guidance, and potential effects on drug quality and equivalence.
Regulatory aspect of pharmaceutical change control systemDeveshDRA
The document discusses the regulatory aspects of pharmaceutical change control systems. It outlines the benefits of a change control system, including ensuring changes are properly documented, validated, approved and traceable. It describes the different categories of changes (major, moderate, minor) and approval processes. A successful change control system requires identifying the need for a change, reviewing documentation, preparing a change proposal, classifying and approving the change, developing an implementation plan, verification and closure. Regulatory guidelines require formal change control systems to evaluate all changes that could affect product quality or manufacturing processes.
PET - Quality Assurance of PET Radiopharmaceutials@Saudi_nmc
Quality assurance of PET radiopharmaceuticals ensures patient safety and product efficacy through systematic activities implemented throughout the production process. This includes regulating raw materials, equipment, documentation, and product release. The batch record documents all production details for traceability. Products must meet criteria for purity, safety, and efficacy before release. Non-conforming products that fail quality control tests are removed and investigations are conducted to implement corrective actions. Quality is built into the production process through regulated procedures and cannot be tested in after the fact.
Regulatory affairs cmc , post approval regulatory affairsArjunDhawale
The document summarizes CMC (chemistry, manufacturing and controls) regulatory affairs for pharmaceutical products. It discusses the CMC section of regulatory filings which contains information on drug substance and product characteristics, manufacturing and quality. It describes the chemistry, manufacturing process, specifications and controls for ensuring consistent quality batches. It also covers CMC regulatory compliance after approval and post-approval regulatory requirements to ensure continued safety and effectiveness. The goal of CMC regulatory affairs is to provide the necessary CMC information and strategy to obtain and maintain regulatory approvals.
This document discusses regulations regarding the manufacture of pharmaceutical products and active ingredients, including requirements for qualifying vendors that supply materials. Strict good manufacturing practices (GMP) are required to ensure quality, safety and efficacy. Vendor qualification is important to provide assurance of drug product performance and avoid risks like contamination. The document refers to other guidance on topics like quality agreements, auditing, and assessing vendor performance on supply assurance, quality, costs, and responsiveness. Packaging component supplier audits are also discussed.
This document discusses regulatory and quality assurance considerations for drug product development. It outlines that CMC development should ensure patient safety and product quality through standards like GMP. Information provided to regulators should increase in detail as development progresses from Phase 1 to Phase 3. The quality assurance function is responsible for independent assessment and oversight of manufacturing to ensure standards are met.
This document discusses regulatory and quality assurance considerations for drug product development. It outlines that CMC development should ensure patient safety and proceed simultaneously with clinical trials. Information generated at each stage of development should build upon early work and support product approval. The roles of quality assurance, quality control, and regulatory affairs are described. Guidance is provided on the type of CMC information needed for original INDs and as development progresses towards an NDA.
Regulatory agencies like the FDA, WHO, EU, and PIC/S have established validation guidelines and requirements for the pharmaceutical industry. Process validation is required to provide documented evidence that manufacturing processes produce consistent and quality products meeting specifications. It involves qualification of facilities, equipment, utilities, and processes. Validation studies include design qualification, installation qualification, operational qualification, and performance qualification. Regulatory guidelines cover validation of automated processes, suppliers' test results, sterilization processes, and analytical methods. A validation master plan and validation reports are required documentation.
What Is An Assistant Drug Controller (Adc) Noc In India And Why Is It Importa...PranshuCorpseed
The pharmaceutical industry plays a pivotal role in public health by manufacturing and distributing drugs and medical products. To ensure the safety, quality, and efficacy of pharmaceuticals, governments around the world have established stringent regulatory frameworks. In India, the Assistant Drug Controller (ADC) assumes a crucial role in this regulatory process. This article delves into the significance of an Assistant Drug Controller (ADC) No Objection Certificate (NOC) in India and its pivotal role in the pharmaceutical sector.
CMC, post approval regulatory affairs, etcJayeshRajput7
this document covers points such as CMC, post approval regulatory affairs, regulation for combination products, and medical devices, common technical document (CTD) and electronic common technical document (eCTD) format, industry and FDA liasion, ICH guidelines of ICH Q,S,E,M, regulatory requirements of EU, MHRA, TGA and ROW countries.
This document is a presentation on Quality by Design (QbD) in the pharmaceutical industry. It begins with an introduction comparing the traditional Quality by Test (QbT) approach to QbD. The presentation defines QbD and discusses ICH guidelines on QbD. It identifies key elements of QbD including Quality Target Product Profile, Critical Quality Attributes, Critical Material Attributes, Critical Process Parameters. The presentation outlines the steps for QbD implementation and importance of QbD in ensuring product quality and facilitating innovation.
The document summarizes recent advancements in Indian drug regulations regarding amendments to Schedule M. It provides an overview of the Central Drugs Standard Control Organization (CDSCO) and its geographical locations across India. It then discusses the background and content of the existing Schedule M-2001 and the proposed Draft Schedule M-2018, highlighting new additions around pharmaceutical quality systems, quality risk management, and change control. Key features of the draft include expanded requirements for suppliers, stability studies, and continual improvement in quality systems.
The document summarizes recent advancements in Indian drug regulations regarding the draft amendment of Schedule M. It provides background on CDSCO and regulatory authorities in India. It discusses the content of the existing Schedule M-2001 and the draft Schedule M-2018, highlighting new sections on pharmaceutical quality systems, quality risk management, and change control. The document also outlines CDSCO initiatives like e-governance systems for drug applications and a portal for laboratory functions.
The document outlines the process of change control for pharmaceutical companies. It defines types of changes like temporary, permanent, major and minor changes. The change control procedure ensures that all changes to procedures, materials, methods, equipment and software are properly documented, approved, validated and traceable. Changes are classified based on their potential impact on product quality. The change control process aims to complete approval within 30 days and closure within 90 days, with provisions for extension. Trending of change controls is also carried out monthly.
The document discusses Chemistry, Manufacturing and Controls (CMC) and its role in pharmaceutical product development and regulatory approval. It provides details on:
- The key functions of CMC including process development, facility inspections, and ensuring compliance.
- CMC content requirements for different application types like NDAs, ANDAs, and INDs.
- How the CMC section evolves over clinical trial phases from laboratory to commercial scale.
- Procedures for developing and submitting post-approval study protocols to regulatory agencies.
The document discusses current and future regulation of biological products by the Korea Food and Drug Administration (KFDA). It provides an overview of the KFDA's functions in regulating biological product quality, registration processes, relevant laws and guidelines. It also discusses specific areas like viral product control and challenges in regulating this emerging field.
Product Quality Reviews (PQRs) are conducted annually to review manufacturing processes, specifications, trends, and identify improvements for pharmaceutical products. PQRs can be done on individual products, grouped products, or through exception reviews. The objective is to verify consistency, specifications, identify trends, and improvements. PQRs provide information on processes, quality requirements, and release decisions. Outcomes are used to identify continuous quality improvements through action plans. Manufacturers are responsible for preparing review data and lists, while reviews consider starting materials, specifications, failures, deviations, changes, variations, stability, complaints, and contractual arrangements.
This document provides an overview of Good Manufacturing Practices (GMP) guidelines from various regulatory authorities like WHO, US FDA, ICH, and MHRA. It discusses the objectives of GMPs, including ensuring product quality and compliance. The key GMP guidelines from WHO, US FDA, and ICH are summarized, covering topics like pharmaceutical quality systems, sanitation procedures, and guidelines for quality control. Validation is also discussed as important for quality assurance and reducing compliance issues.
Process validation is establishing documented evidence that a process will consistently produce a product meeting predetermined specifications. This presentation discusses process validation, including its definition, scope, objectives, types (prospective, retrospective, concurrent, revalidation), stages, responsibilities of different departments, protocols, sampling procedures, acceptance criteria, and reports. Key aspects of process validation include protocols, sampling plans, specifications, batch execution records, and data analysis to ensure a process is capable of reproducible commercial manufacturing of pharmaceutical products that meet quality standards.
This document discusses various post-approval requirements and processes for pharmaceutical drugs, including prior approval supplements, changes being effected in 30 days supplements, annual reports, labeling changes, recalls, FDA inspections, and ISO 31000 risk management standards. It provides details on submission requirements and timelines for different types of post-approval changes, as well as FDA enforcement actions like warning letters, seizures, and injunctions.
Complete discussion about the Pharmaceutical validation, its types, difference between calibration and validation, validation master & calibration master plan
This document discusses regulations regarding the manufacture of pharmaceutical products and active ingredients, including requirements for qualifying vendors that supply materials. Strict good manufacturing practices (GMP) are required to ensure quality, safety and efficacy. Vendor qualification is important to provide assurance of drug product performance and avoid risks like contamination. The document refers to other guidance on topics like quality agreements, auditing, and assessing vendor performance on supply assurance, quality, costs, and responsiveness. Packaging component supplier audits are also discussed.
This document discusses regulatory and quality assurance considerations for drug product development. It outlines that CMC development should ensure patient safety and product quality through standards like GMP. Information provided to regulators should increase in detail as development progresses from Phase 1 to Phase 3. The quality assurance function is responsible for independent assessment and oversight of manufacturing to ensure standards are met.
This document discusses regulatory and quality assurance considerations for drug product development. It outlines that CMC development should ensure patient safety and proceed simultaneously with clinical trials. Information generated at each stage of development should build upon early work and support product approval. The roles of quality assurance, quality control, and regulatory affairs are described. Guidance is provided on the type of CMC information needed for original INDs and as development progresses towards an NDA.
Regulatory agencies like the FDA, WHO, EU, and PIC/S have established validation guidelines and requirements for the pharmaceutical industry. Process validation is required to provide documented evidence that manufacturing processes produce consistent and quality products meeting specifications. It involves qualification of facilities, equipment, utilities, and processes. Validation studies include design qualification, installation qualification, operational qualification, and performance qualification. Regulatory guidelines cover validation of automated processes, suppliers' test results, sterilization processes, and analytical methods. A validation master plan and validation reports are required documentation.
What Is An Assistant Drug Controller (Adc) Noc In India And Why Is It Importa...PranshuCorpseed
The pharmaceutical industry plays a pivotal role in public health by manufacturing and distributing drugs and medical products. To ensure the safety, quality, and efficacy of pharmaceuticals, governments around the world have established stringent regulatory frameworks. In India, the Assistant Drug Controller (ADC) assumes a crucial role in this regulatory process. This article delves into the significance of an Assistant Drug Controller (ADC) No Objection Certificate (NOC) in India and its pivotal role in the pharmaceutical sector.
CMC, post approval regulatory affairs, etcJayeshRajput7
this document covers points such as CMC, post approval regulatory affairs, regulation for combination products, and medical devices, common technical document (CTD) and electronic common technical document (eCTD) format, industry and FDA liasion, ICH guidelines of ICH Q,S,E,M, regulatory requirements of EU, MHRA, TGA and ROW countries.
This document is a presentation on Quality by Design (QbD) in the pharmaceutical industry. It begins with an introduction comparing the traditional Quality by Test (QbT) approach to QbD. The presentation defines QbD and discusses ICH guidelines on QbD. It identifies key elements of QbD including Quality Target Product Profile, Critical Quality Attributes, Critical Material Attributes, Critical Process Parameters. The presentation outlines the steps for QbD implementation and importance of QbD in ensuring product quality and facilitating innovation.
The document summarizes recent advancements in Indian drug regulations regarding amendments to Schedule M. It provides an overview of the Central Drugs Standard Control Organization (CDSCO) and its geographical locations across India. It then discusses the background and content of the existing Schedule M-2001 and the proposed Draft Schedule M-2018, highlighting new additions around pharmaceutical quality systems, quality risk management, and change control. Key features of the draft include expanded requirements for suppliers, stability studies, and continual improvement in quality systems.
The document summarizes recent advancements in Indian drug regulations regarding the draft amendment of Schedule M. It provides background on CDSCO and regulatory authorities in India. It discusses the content of the existing Schedule M-2001 and the draft Schedule M-2018, highlighting new sections on pharmaceutical quality systems, quality risk management, and change control. The document also outlines CDSCO initiatives like e-governance systems for drug applications and a portal for laboratory functions.
The document outlines the process of change control for pharmaceutical companies. It defines types of changes like temporary, permanent, major and minor changes. The change control procedure ensures that all changes to procedures, materials, methods, equipment and software are properly documented, approved, validated and traceable. Changes are classified based on their potential impact on product quality. The change control process aims to complete approval within 30 days and closure within 90 days, with provisions for extension. Trending of change controls is also carried out monthly.
The document discusses Chemistry, Manufacturing and Controls (CMC) and its role in pharmaceutical product development and regulatory approval. It provides details on:
- The key functions of CMC including process development, facility inspections, and ensuring compliance.
- CMC content requirements for different application types like NDAs, ANDAs, and INDs.
- How the CMC section evolves over clinical trial phases from laboratory to commercial scale.
- Procedures for developing and submitting post-approval study protocols to regulatory agencies.
The document discusses current and future regulation of biological products by the Korea Food and Drug Administration (KFDA). It provides an overview of the KFDA's functions in regulating biological product quality, registration processes, relevant laws and guidelines. It also discusses specific areas like viral product control and challenges in regulating this emerging field.
Product Quality Reviews (PQRs) are conducted annually to review manufacturing processes, specifications, trends, and identify improvements for pharmaceutical products. PQRs can be done on individual products, grouped products, or through exception reviews. The objective is to verify consistency, specifications, identify trends, and improvements. PQRs provide information on processes, quality requirements, and release decisions. Outcomes are used to identify continuous quality improvements through action plans. Manufacturers are responsible for preparing review data and lists, while reviews consider starting materials, specifications, failures, deviations, changes, variations, stability, complaints, and contractual arrangements.
This document provides an overview of Good Manufacturing Practices (GMP) guidelines from various regulatory authorities like WHO, US FDA, ICH, and MHRA. It discusses the objectives of GMPs, including ensuring product quality and compliance. The key GMP guidelines from WHO, US FDA, and ICH are summarized, covering topics like pharmaceutical quality systems, sanitation procedures, and guidelines for quality control. Validation is also discussed as important for quality assurance and reducing compliance issues.
Process validation is establishing documented evidence that a process will consistently produce a product meeting predetermined specifications. This presentation discusses process validation, including its definition, scope, objectives, types (prospective, retrospective, concurrent, revalidation), stages, responsibilities of different departments, protocols, sampling procedures, acceptance criteria, and reports. Key aspects of process validation include protocols, sampling plans, specifications, batch execution records, and data analysis to ensure a process is capable of reproducible commercial manufacturing of pharmaceutical products that meet quality standards.
This document discusses various post-approval requirements and processes for pharmaceutical drugs, including prior approval supplements, changes being effected in 30 days supplements, annual reports, labeling changes, recalls, FDA inspections, and ISO 31000 risk management standards. It provides details on submission requirements and timelines for different types of post-approval changes, as well as FDA enforcement actions like warning letters, seizures, and injunctions.
Complete discussion about the Pharmaceutical validation, its types, difference between calibration and validation, validation master & calibration master plan
Similar to Hài hòa GMP toàn cầu - Góc nhìn từ Nhật Bản (20)
This document provides guidance on good manufacturing practices for medicinal products. It discusses the importance of a pharmaceutical quality system to ensure that manufactured medicines are fit for use and comply with regulatory standards. Key elements of the quality system include good manufacturing practices, quality control, product quality reviews, and quality risk management. The quality system requires participation across all departments and levels of the company to ensure product safety, quality and efficacy.
This document discusses key aspects of designing pharmaceutical manufacturing facilities according to current Good Manufacturing Practices (cGMP). It covers process design tools like block flow diagrams, process flow diagrams, and piping and instrumentation diagrams that are used to design the facility layout and process flows. The document also discusses various unit operations in solid dosage manufacturing like material handling, milling, blending, compression, and coating. Facility design must meet regulatory requirements to facilitate operations, control materials, and prevent contamination according to cGMP.
This document lists various prequalified active pharmaceutical ingredients from the WHO. It includes the product ID, INN, grade, therapeutic area, applicant, date of prequalification, and confirmation date. There are over 400 entries listed with information about different APIs that have been prequalified for treatments of conditions like HIV/AIDS, malaria, tuberculosis, hepatitis, and others.
Danh mục 37 thuốc sản xuất trong nước được cấp giấy phép lưu hành tại Việt Nam - Đợt 185.
Quyết định được Cục Quản lý Dược Việt Nam ban hành vào tháng 7 năm 2023.
Danh mục 259 thuốc sản xuất trong nước được cấp giấy đăng ký lưu hành tại Việt Nam - Đợt 185.
Danh mục được ban hành bới Cục Quản lý Dược Việt Nam tháng 7 năm 2023.
Ngày 21/06 vừa qua, cục Quản lý Dược vừa ban hành quyết định về việc công bố danh mục thuốc biệt dược gốc - đợt 2 năm 2023.
Ban hành kèm theo quyết định này bao gồm 83 thuốc biệt dược gốc.
Xem thêm các tài liệu khác trên trang của công ty cổ phần Tư vấn thiết kế GMP-EU.
Hướng dẫn thực hành này cung cấp thông tin cho các nhà sản xuất thức ăn có chất sát khuẩn không an toàn do thuốc chuyển sang thức ăn chăn nuôi không chứa thuốc hoặc một loại thức ăn khác. Mục đích của hướng dẫn này:
• “Sản xuất và phân phối thức ăn có chứa thuốc” đề cập đến việc sử dụng thiết bị để sản xuất, chế biến, đóng gói, giữ và phân phối thức ăn.
• “Thức ăn chăn nuôi” được sản xuất có thêm hóa chất bảo quản. Thức ăn cho động vật như vậy có thể được gọi trong hướng dẫn này là “thức ăn có tẩm thuốc” hoặc “thức ăn không có tẩm thuốc”, tùy thuộc vào việc thức ăn đó có được pha chế để chứa một loại thuốc mới dành cho động vật hay không. Để thuận tiện, chúng tôi gọi những loại thuốc mới dành cho động vật này đơn giản là “thuốc”.
• “Thuốc mang theo” đề cập đến sự hiện diện của thuốc trong lô thức ăn chăn nuôi tiếp theo.
• “Ô nhiễm không an toàn”: đề cập đến mức độ nhiễm bẩn, do một loại thuốc được phép sử dụng trong thức ăn chăn nuôi, gây ra rủi ro không thể chấp nhận được đối với sức khỏe con người hoặc động vật.
Nói chung, các tài liệu hướng dẫn của FDA không thiết lập các trách nhiệm có thể thực thi về mặt pháp lý. Thay vào đó nó mô tả Cơ quan về một chủ đề và chỉ nên được xem dưới dạng khuyến nghị, trừ khi các yêu cầu pháp lý hoặc quy định cụ thể được trích dẫn. Việc sử dụng từ nên trong hướng dẫn của Cơ quan có nghĩa là điều gì đó được gợi ý hoặc khuyến nghị, nhưng không bắt buộc.
Xem thêm các tài liệu khác trên trang của công ty cổ phần tư vấn thiết kể GMP EU.
Cục Quản lý Thực phẩm và Dược phẩm Hoa Kỳ đưa ra hướng dẫn cho các nhà sản xuất và phân phối sữa cho trẻ sơ sinh về các yêu cầu ghi nhãn nhất định đối với các sản phẩm này. Hướng dẫn này đặc biệt chú trọng đến số lượng các công thức sữa cho trẻ sơ sinh có bao bì tương tự nhưng khác nhau về thành phần hoặc mục đích sử dụng. Ngày càng nhiều các sản phẩm ghi sai nhãn về hàm lượng chất dinh dưỡng, do vậy hướng dẫn này cung cấp thông tin có thể giúp các nhà sản xuất hiểu và tuân thủ các yêu cầu ghi nhãn liên quan.
Hướng dẫn này không bao gồm đầy đủ tất cả các quy định liên quan đến việc ghi nhãn sữa công thức dành cho trẻ sơ sinh. Vì vậy bạn có thể xem thêm các hướng dẫn khác tại www.fda.gov/FoodGuidances hoặc các tài liệu trên kênh của công ty cổ phần tư vấn thiết kế GMP EU.
Ngày 25/05 vừa qua, Cục quản lý Dược vừa ban hành danh mục 69 thuốc sản xuất trong nước được cấp giấy đăng ký lưu hành tại Việt Nam - Đợt 184.
Theo đó, ban hành kèm theo Quyết định này danh mục 69 thuốc sản xuất trong nước được cấp giấy đăng ký lưu hành tại Việt Nam - Đợt 184, cụ thể:
1. Danh mục 64 thuốc sản xuất trong nước được cấp giấy đăng ký lưu hành tại Việt Nam hiệu lực 05 năm (Phụ lục I kèm theo).
2. Danh mục 05 thuốc sản xuất trong nước được cấp giấy đăng ký lưu hành tại Việt Nam hiệu lực 03 năm (Phụ lục II kèm theo).
Xem thêm các tài liệu khác trên trang của công tư cổ phần tư vấn thiết kế GMP EU.
Ngày 25/05 vừa qua, Cục quản lý Dược đã ban hành quyết định số 352/QĐ-QLD về việc ban hành danh mục 231 thuốc nước ngoài được cấp, gia hạn giấy đăng ký lưu hành tại Việt Nam - Đợt 184.
Theo đề nghị của Trưởng phòng Đăng ký thuốc, Cục Quản lý Dược quyết định:
Ban hành kèm theo Quyết định này danh mục 231 thuốc sản xuất trong nước được cấp giấy đăng ký lưu hành tại Việt Nam - Đợt 184, cụ thể:
1. Danh mục 172 thuốc sản xuất trong nước được gia hạn giấy đăng ký lưu hành hiệu lực 05 năm (Phụ lục I kèm theo).
2. Danh mục 52 thuốc sản xuất trong nước được gia hạn giấy đăng ký lưu hành hiệu lực 03 năm (Phụ lục II kèm theo).
3. Danh mục 07 thuốc sản xuất trong nước được gia hạn đăng ký lưu hành đến 31/12/2025 (Phụ lục III kèm theo).
Xem thêm các tài liệu khác trên trang của công ty cổ phần Tư vấn thiết kế GMP EU.
Ngày 26/05 vừa qua, Cục Quản lý Dược đã ban hành quyết định số 371/QĐ-QLD về việc công bố danh mục thuốc biệt dược gốc Đợt 1 - năm 2023.
Theo đề nghị của Trưởng phòng Đăng ký thuốc - Cục Quản lý Dược, quyết định:
Công bố Danh mục 56 thuốc Biệt dược gốc Đợt 1 - Năm 2023 tại Phụ lục kèm theo Quyết định này.
Xem thêm các tài liệu khác trên trang của công ty cổ phần Tư vấn thiết kế GMP EU.
Ngày 26/05 vừa qua, Cục Quản lý Dược vừa ra quyết định số 370/QĐ-QLD về việc ban hành danh mục 50 thuốc nước ngoài được cấp, gia hạn giấy đăng ký lưu hành tại Việt Nam - Đợt 111 bổ sung.
Theo đề nghị của Trưởng phòng Đăng ký thuốc - Cục Quản lý Dược quyết định:
Ban hành kèm theo Quyết định này danh mục 50 thuốc nước ngoài được cấp, gia hạn giấy đăng ký lưu hành tại Việt Nam - Đợt 111 bổ sung, bao gồm:
1. Danh mục 41 thuốc nước ngoài được cấp giấy đăng ký lưu hành hiệu lực 05 năm - Đợt 111 bổ sung (tại Phụ lục I kèm theo).
2. Danh mục 01 thuốc nước ngoài được cấp giấy đăng ký lưu hành hiệu lực 03 năm - Đợt 111 bổ sung (tại Phụ lục II kèm theo).
3. Danh mục 07 thuốc nước ngoài được gia hạn giấy đăng ký lưu hành hiệu lực 05 năm - Đợt 111 bổ sung (tại Phụ lục III kèm theo).
4. Danh mục 01 thuốc nước ngoài được gia hạn giấy đăng ký lưu hành đến 31/12/2025 - Đợt 111 bổ sung (tại Phụ lục IV kèm theo).
Ngày 24/05 vừa qua, Bộ Y tế vừa ban hành quyết định về việc công bố danh mục thuốc có chứng minh tương đương sinh học đợt 2 - năm 2023.
Theo đề nghị của Trưởng phòng Đăng ký thuốc - Cục quản lý Dược, quyết định:
Công bố Danh mục 28 thuốc có chứng minh tương đương sinh học Đợt 2 - Năm 2023 tại Phụ lục kèm theo Quyết định này.
Xem thêm các tài liệu khác của Công ty cổ phần Tư vấn thiết kế GMP EU.
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1. ISPE Prague September 19-21 2005 1
Global GMP Harmonisation –
A Japanese Perspective
Yukio Hiyama, Ph.D.
Chief, Third Section, Division of Drugs,National
Institute of Health Sciences,
The Ministry of Health Labour and Welfare,JAPAN
2. ISPE Prague September 19-21 2005 2
Presentation Key Points
Changes in Pharmaceutical Affairs Law
Quality Regulations under the Revised
Pharmaceutical Affairs Law
Commitment of Manufacturing Process as
Approval Matters
Role of ICH Pharmaceutical Development
Role of the Quality Overall Summary
GMP Regulations and related Guidelines
3. ISPE Prague September 19-21 2005 3
Revision of the Pharmaceutical
Affairs Regulation
(effective April 2005)
Revision of the Approval and Licensing System
= From Manufacturing (or Importation)
Approval/License to Marketing Authorization
Enhancement of Post-marketing Measures
= To clarify the Market Authorization Holder’s
(MAH) responsibility of the safety measures as well
as quality management (GVP, GQP)
4. ISPE Prague September 19-21 2005 4
Revision of the Quality Regulation
1. MAH’s* responsibility for the Quality
management *Marketing Authorization Holder
2. Requirement Changes in Approval Matters
3. Drug Master File system to support CTD based
application
4. Consolidation of the Legal Positioning of GMP
5. Revision and Consolidation of GMP standards
5. Revision of approval and license system for
pharmaceuticals and medical devices
Attention to
manufacturing
Prefecture
1. Companies are supposed to have their own
manufacturing establishment
2. “Approval” is for “manufacturing”, not for
“marketing” (Minister manufacturing approval)
3. Final manufacturing “license” is issued, based on
approval. (Mainly prefectural manufacturing
licensing)
Attention to whole process
( from manufacturing to
PMS)
1. Introduction of “Marketing Approval” for overall evaluating quality, safety & efficacy and
manufacturing for marketing
2. Manufacturing establishment license is separated from product authorisation process, which
allows companies to subcontract whole manufacturing process
3. Instead, company’s ability of pharmacovigilance is subject to review for Marketing Approval
Holder (MAH)
MHLW
Research & Development
From Development to Use
Evaluation of quality, effect & safety
(manufacturing approval for each product)
Manufacturing
(manufacturinglicense)
New System
Old system
Use
Sale
6. Manufacturing
Approval
Manufacturing
Application (MHLW)
Licensed
Establishment
1-Step process
Start production
Comparison Flowcharts of Approval and License
Product
OLD system
Product
REVISED system
Quality, Safety & Efficacy
Establishment
G
GM
MP
P
Requirement
Quality, Safety & Efficacy
• Companies’ PMS
compliance system
• Companies’ Quality
Assurance System
Self production
OR
Subcontracting
Establishment
• MHLW inspection :
New drug &
Partial
subcontracting
biologics
• Prefectural inspection: Others
: Recurred for each product
Start manufacturing
Points: (1) MAH’s requirements for PMS system, (2) Allow complete subcontract
manufacturing, (3) Introduce marketing approval system
Partial License
Establishment License
inspection
(5 yearly renewal) )
License application
(Prefecture)
Start marketing
Marketing Approval
inspection
( Renewal) Every 5 years
2-Step process
Marketing Application
(MHLW)
Licensed Marketing
Approval Holder
7. ISPE Prague September 19-21 2005
軽微変更届出
7
Framework for
Review and Inspection
Application of
partial change
Review
Application
form
Review
Approval
letter
Notification of
minor partial
change
G
GM
MP
P
i
in
ns
sp
pe
ec
ct
ti
io
on
n
Pilot scale data
New Drug
Application
Collection of
production
scale data
Re-submission
of application
form
Pre-approval
GMP Inspection
Commercial
Production
Minor
Change
Partial
Change
Minor
Change
Partial
Change
Validation Data etc.
8. ISPE Prague September 19-21 2005 8
From Multi sets to One set of
regulations
Previously: No inspections at foreign GMP
sites/Under GMPI →Foreign inspections by PMDA
Previously: Approvals given to API and Product.
Only specs are set for API of imported products
→Approvals only to products including API specs
and manufacturing process
Previously: Whole Manufacture contracts NOT
allowed for domestic industry→ Contracts allowed
everyone
9. ISPE Prague September 19-21 2005 9
Revision of the Quality Regulation
1. MAH’s* responsibility for quality management
*Marketing Authorization Holder
2. Requirement changes in Approval Matters
3. Drug Master File system to support CTD based
application
4. Consolidation of the Legal Positioning of GMP
5. Revision and Consolidation of GMP standards
10. ISPE Prague September 19-21 2005 10
1. MAH’s responsibility for quality
management (GQP)
Supervise and manage the manufacturer, and
ensure the compliance with GMP of all
manufacturing sites
Ensure proper product release to the market
Respond quickly with complaints and recall, etc.
Conduct quality management based on post-
marketing information, etc.
11. ISPE Prague September 19-21 2005 11
Revision of the Quality Regulation
1. MAH’s* responsibility for quality management
*Marketing Authorization Holder
2. Requirement changes in Approval Matters
3. Drug Master File system to support CTD based
application
4. Consolidation of the Legal Positioning of GMP
5. Revision and Consolidation of GMP standards
12. ISPE Prague September 19-21 2005 12
2. Application Form and
Approval Matters
Contents provided in the NDA
application form are dealt with as
“matters subject to approval.”
Contents described in approval letter are
“legal binding” approval matters.
13. ISPE Prague September 19-21 2005 13
Approval Matters
General name (for drug substance)
Brand name
Composition
Dosage and administration
Manufacturing process, including control
of materials
Indications
Storage condition and shelf-life
Specifications and analytical procedures
14. ISPE Prague September 19-21 2005 14
No change:
Approval Letter
• Approval letter system
Changes:
• From manufacturing approval to marketing approval
• Requirement of detailed description in application
form regarding manufacturing process and control
Encourage industry to better controlqualityof products
Link assessment and inspection
• Introduction of a notification system pertaining to
minor change
Effective regulatorysystem
15. Application Form after the Enforcement of
Revised Pharmaceutical Affairs Law
High
OLD APPLICATION
Manufacturing Application
CTD-BASED APPLICATION
Marketing Application
Specification+
Manufacturing
(Process Control)
Low QualityInformation Module 3
Quality Information
Application
form
GAIYO
Batch Data etc
Approval
Matter
(Specification)
Module 2
Minor change
(notification)
Partial Change
(application)
Batch Data etc
P
P
o
o
s
s
s
s
i
i
b
b
i
i
l
l
i
i
t
t
y
y
t
t
h
h
a
a
t
t
c
c
h
h
a
a
n
n
g
g
e
e
s
s
a
a
f
f
f
f
e
e
c
c
t
t
d
d
r
r
u
u
g
g
q
q
u
u
a
a
l
l
i
i
t
t
y
y
16. ISPE Prague September 19-21 2005 16
Approval Matters Policy
Notification from Director of Review Management,
0210001 February 10, 2005
Manufacturing Process: Principles and end points
of the critical manufacturing steps with key
operational parameters of commercial scale will
become approval matters. Principle and quality
end point for each manufacturing step will be
subject to pre-approval review.
In-process procedure is pre-approval matter if it
replaces final specification test.
17. ISPE Prague September 19-21 2005 17
Approval Matters Policy (continued)
A pilot scale manufacturing processes may be
submitted at Application.
The commercial scale processes will be subject to
Pre-approval GMP inspection and the commercial
scale must be described in the approval.
Pre-approval vs. notification classification may be
determined through the review process
18. Matter Subject to Approval under
Revised Pharmaceutical Affairs Law
(Chemical drug substance and drug product)
Manufacturing site
Manufacturing method
Detailed information about:
• Manufacturing process and process
control
• Control of material
• Container-closure system
19. Matter to Be Described in Application Form
-Drug Products-
All processes from raw material(s) to
packaging process
– A flow diagram of manufacturing process
including:
• Raw materials
• Charge-in amount
• Yield
• Solvent
• Intermediate materials
• Process parameter (e.g. Target Value and Set Value)
– A narrative description of manufacturing process
20. Narrative Description of
Manufacturing Process
– Matters needed for assuring the quality consistency
should be selected
Quantities of raw materials, critical processes,
process control, equipment, process parameter
(speed, time, temp., pressure, pH, etc)
Test and acceptance criteria of critical step and
intermediate
Identity and specification of primary packaging
material (or manufacturer and type number of the
packaging material)
21. Case1
Observed
Value A
Case 2
Observed
Value B
Target
Value/Set
Value
Target Value and Set Value
In cases where target value/set value are set:
– Permissible range of target value/set value must be
described on the master production documents or SOPs.
Case 2:
– The suitability of product should be judged based on GMP.
Temp
Permissible range
22. Hydroxypropylcellulose Process Control 1
Blending Kakikukekon
Calcium Carmellose
Lactose
Flow Diagram of Manufacturing process (Tablet)
Step Operation Raw Material In-process Test
1st Step Content Unifomity
particle size
Content Unifomity
Dissolution
2nd Step
Drying
Size Granulation
Screenφ1mm
Process Control 2
Temp. of exhaust air
Water act.
Stability of dissolution
Quality
endpoint
criteria
Granulation
Quality endpoint
criteria
23. ISPE Prague September 19-21 2005 23
Distinctions between Partial Change
Approval Application and Minor
Change Notification
Partial Change
Approval Application
Minor Partial Change
Notification
Change in the principle of
unit operation of critical
process
Process parameter to
control the quality
endpoint criteria
Change in process control
criteria as quality endpoint
criteria
24. ISPE Prague September 19-21 2005 24
Examples of Matter Subject to a
Partial Change Application
Change in principle of unit operation of critical
process: matter subject to approval
• In that case, the evaluation methods which was approved at
the time of previous submission might be invalidated.
Change in materials of primary packaging component
Change in matters for aseptic manufacturing
Change in specification of intermediate product in
case that the test is performed instead of release test of
final drug product
25. ISPE Prague September 19-21 2005 25
Some matters are subject to application of
partial change, based on the information
described in P2.
The Role of P2 Document in Reviewing
New Drug Application (NDA) under
Revised Pharmaceutical Affairs Law
(PAL)
26. Matters described
in Module3
P2
Matters subject
to approval
Matters not subject
to approval
The Role of P2 document in
reviewing NDA under revised PAL
P2
Partial change approval application
Minor partial change
notification
27. ISPE Prague September 19-21 2005 27
The new requirement regarding the approval
letter is applicable to:
1. market applications after April 2005
2. renewals of existing licenses, which may occur by
2010
for case 2, the manufacturing section of approval letter
may be rewritten without review/assessment.
For most of those approvals, CTD information was NOT
submitted (did not exist).
28. ISPE Prague September 19-21 2005 28
Opportunities by ICH CTD based application
Complete description of product specific quality
system
Better knowledge transfer tool within the sponsor
organization, between industry and regulator, and
within the regulator organizations---QoS:Module 2
plays important roles
ICH Pharmaceutical Development Q 8 (step 2 in
Yokohama)
29. ISPE Prague September 19-21 2005 29
Role of Module 2 in Japan
Module 2 bridges NDA Application Form
and Module 3
Module 2 is one of the key review
documents
• Reviewers evaluate Module 2 and then narrow
down into Module 3, 4, or 5 when they need
more detailed information.
• Module 1 and 2 together with reports written
by reviewers are evaluated in Pharmaceutical
Affairs and Food Sanitation Council.
30. Relationship between
Application Form and CTD format
Module 3
Module 2
• Tabulated summary of
specifications
• Analytical procedures
• Tabulated summary of
batch analyses
• Justification etc.
Raw data
3.2.S4.1Specification
3.2.S4.2Analytical Procedures(SOP)
3.2.S4.3Validation of Analytical
Procedures
3.2.S4.4Batch Analyses
3.2. S4.5 Justification of Specification
Application
form
Approval
Matters
31. 4. Legal position of GMP
Flowchart of Approval and License
Manufacturer Holder Company
Requirement:
Human Resource
Facility
Requirement:
Human resource
GVP/GQP compliance
(renewal/ X years)
Self production
or
Subcontracting
(renewal/ X years)
Product
Manufacturing Start
Pre-approval inspection
Post-approval inspection
Requirement:
Quality, Safety & Efficacy
GMP compliance
Product Marketing
Approval
(every 5 years)
ISPE Prague September 19-21 2005 31
Marketing Start
Product Marketing
Application
Manufacturing
License
MAH License
Manufacturing
License Application
MAH License
Application
33. ISPE Prague September 19-21 2005 33
Revision of the Quality Regulation
1. MAH’s* responsibility for the quality
management *Marketing Authorization Holder
2. Approval Matters Requirements Change
3. Drug Master File system to support CTD based
application
4. Consolidation of the Legal Positioning of GMP
5. Revision and Consolidation of GMP standards
34. ISPE Prague September 19-21 2005 34
4. Consolidation of the Legal
Positioning of GMP
Became a requirement for product approval
GMP inspection prior to approval, and
periodical GMP inspection in post-marketing
phase
GMP inspection at the time of application for
partial change of the approval matters
GMP inspection at foreign sites
35. ISPE Prague September 19-21 2005 35
Revision of the Quality Regulation
1. MAH’s* responsibility for the quality
management *Marketing Authorization Holder
2. Approval Matters Requirements Change
3. Drug Master File system to support CTD based
application
4. Consolidation of the Legal Positioning of GMP
5. Revision and Consolidation of GMP standards
36. ISPE Prague September 19-21 2005 36
5. Revision and Consolidation of GMP
Standards
Revised Pharmaceutical Affairs Law (passed July 2002,
Effective April 2005)
MHLW Ministerial Ordinance No. 179 on GMP (published
December 2004)
Notification on GMP (March 30, 2005) – “Instructions to
inspection body RE the Ministerial Ordinance, revision of
Validation standards”
Major Changes:
Content of Approval Letters (Manufacturing Processes, Container
Closure etc)-define where GMP applies “legally”
Change control and Deviation control
37. ISPE Prague September 19-21 2005 37
Perceived Problems
Superficial approaches to GMP -non validated
procedures, little connection with QC results,
procedures override science
Regulations might not encourage good practices
Poor communication between R&D and
Manufacturing Plant
Poor development and or change control of
manufacturing
Detail GMP related guidance and inspection
manuals are NOT readily available in Japan
38. ISPE Prague September 19-21 2005 38
GMP related guidelines
Product GMP Guideline: Level is similar to ICH
Q7A, with emphasis of Periodical Quality Review
Technology Transfer, Process Validation Strategy,
and Site Qualification of Pharmacopoeia Tests
Technology Transfer Guideline: R&D
responsibility and on Study Report ←ICH Q8
Laboratory Control Guideline
The guidelines are posted at NIHS web site.
39. ISPE Prague September 19-21 2005 39
Challenges
Training for reviewers and inspectors on
process/manufacturing sciences
Industry side
•Reluctant or unable to give a complete story
•Regulatory personnel training
•Superficial development (meeting specs is all)
40. ISPE Prague September 19-21 2005 40
Establishment of
Pharmaceuticals and Medical Devises
Agency (PMDA)
Integration of review division, safety information
management division, and GMP inspection division
Strengthening resources for review and inspection
Established in April 2004
Efficient review system
More emphasis on pharmaceuticals with high risks
41. ISPE Prague September 19-21 2005 41
PMDA
New Office:6th-10th
FLOOR
Introduction of PMDA
42. ISPE Prague September 19-21 2005 42
The Feature of PMDA
Effective operation under “Mid-term Plan” for 5
years’ activities
Subject to regular evaluation of performance by
Independent “ Administrative Agency Evaluation
Committee”
Financial resources are consist of
• User fee (Review and inspection)
• Contribution Funds (Post-marketing, Relief)
• National Budget
43. ISPE Prague September 19-21 2005 43
The Feature of PMDA
Effective operation under “Mid-term Plan” for 5
years’ activities
Subject to regular evaluation of performance by
Independent “ Administrative Agency Evaluation
Committee”
Financial resources are consist of
• User fee (Review and inspection)
• Contribution Funds (Post-marketing, Relief)
• National Budget
44. ISPE Prague September 19-21 2005 44
PMDA
GMP Inspection
OPSR/KIKO
Establishing the PMDA
Equivalency Review, Clinical trial
consultation, compliance audit, safety
information (Drug)
PMDEC
Substantial NDA review
(excluding the duties of OPSR/KIKO)
JAAME
Equivalency Review (Device)
Law for the incorporated Administrative
agency-Pharmaceuticals and Medical
Devices Agency
Regional Bureau of MHLW
PMDA
45. ISPE Prague September 19-21 2005 45
Office of Conformity
Audit
(GLP, GCP/ On-site Audit and
Document Audit)
(GMP & Standards/GL)
PMDA Organizational Structure(Outline)
Office of General Affairs/Office
of Planning and Coordination
Auditor
Auditor
Office of ReliefFunds
Review system
8 Office/ 1 Director
Senior
Executive
Director Office of Biologics
Office of OTC/GenericDrugs
Office of Medical Devices
Executive
Director
Executive
Director
Office of Safety
Office of Compliance
and Standards
Post-Marketing system
Director,
Center for
Product
Evaluation
Office of New Drug I - III
Office of Review Administration
C
h
i
e
f
E
x
e
c
u
t
i
v
e
46. ISPE Prague September 19-21 2005 46
Enforcement of New Regulations
2002 2003.4 2004.4 2005.4
PAL revision
Marketing Authorization
GMP Strengthening
New Biologics regulation
everything else
PMDA establishment ●
New GMP Standards ●
●: Publication
:Enforcement
●
●
●
●
47. Japanese CMC Review System with
the Quality overall Summary
Yukio Hiyama, Ph.D.
Section Chief, Division of Drugs, National Institute of
Health Sciences, Ministry of Health, Labour and
Welfare, JAPAN
9/6/2005 AAPS workshop on Pharm Quality 1
Assessment
48. experts
Review & Advisory
Approval letter
team
Advisory
experts
Flowchart of Reviewing Process
Meeting
Meetingon
key issues
Review
team
Consultation
Advice
NIHS scientists
Academia
* PAFSC: The Pharmaceutical
Affairs and Food Sanitation
Council
Committeeson New drugs, PAFSC*
9/6/2005 2
Applicant
Review report-2
Review report-1
Evaluation and Licensing Division in Pharmaceutical
and Food Safety Bureau, MHLW
Revised QOS
Application form
Module2 (QOS)
Module3 (4,5)
Pharmaceuticals andMedical
Devices Agency (PMDA)
Application form
Module2 (QOS)
Module3 (4.5)
49. 9/6/2005 AAPS workshop on Pharm Quality
Assessment
3
Ensure Product Quality and
Consistency
• Thorough product characterization during
development (*including manufacturing process)
• Appropriate specifications
• Adherence to GMP;
suitable facilities, a validated manufacturing
process, validated test procedure, raw material
testing, in-process testing, stability testing
FROM ICH Q6A &B
50. 9/6/2005 AAPS workshop on Pharm Quality
Assessment
4
Quality (CMC) Review Areas
Risk Evaluation Phase:Identify basis for Quality
• Design and establishment of product
• Design and establishment of process and quality
control of drug substance and products
Risk Control Phase:
• Commitment of control methods of process and
quality control of drug substance and products
(This phase was NOT well reviewed in Japan for system
reasons before April 2005)
51. 9/6/2005 AAPS workshop on Pharm Quality
Assessment
5
Basis for Quality(CMC) Review
ICH Guidelines are the basis for NDA review.
• PMDA has a CTD-based GRP(Good Review
Practices).
There are some domestic guides for those not covered
by ICH Guidelines.
The Japanese Pharmacopoeia (JP) is also the basis for
setting specifications and acceptance criteria of drug
substances and drug products.
• “General methods described in the JP, and
internationally harmonized methods are considered to
be validated.”
52. 9/6/2005 AAPS workshop on Pharm Quality
Assessment
6
Basis for Quality Review
ICH Q8 concept (minimum; identify risk,
additional; Design Space) may be used to
classify approval matters in the manufacturing
process.
53. Comparison of Application Forms
before and after the Revision
All matters were
for partial change
application
Former manufacturing
application
CTD-based marketing
application
9/6/2005
Quality information 7
GAIYO
Application
Form
Specification &
Manufacturing
(Process Control)
Matters for
partial change
application
Matters for
minor change
notification
Module 2
(QOS)
Quality information
Module 3
(Batch data
etc)
Batch data etc
Application
Form
Specification
54. Revised
Former Revised
Balance between “Specification” and
“Control of Manufacturing”
◼ Implementation of ICH-CTD (July, 2003)
◼ Revision of Pharmaceutical Affairs Law
(April, 2005)
Specifications Manufacturing
Manufacturing
55. Considered as a summary;
not reviewed; not used as the
basis for approval decision
•
• U
Us
se
ed
d a
as
s a
an
n i
in
nt
tr
ro
od
du
uc
ct
ti
io
on
n t
to
o
M
Mo
od
du
ul
le
e 3
3
•
• M
Mo
od
du
ul
le
e 3
3 i
is
s r
re
ev
vi
ie
ew
we
ed
d a
an
nd
d
s
se
er
rv
ve
es
s a
as
s t
th
he
e b
ba
as
si
is
s f
fo
or
r
a
as
ss
se
es
ss
sm
me
en
nt
t r
re
ep
po
or
rt
t .
.
•
• E
EU
U:
: c
ca
an
n b
be
e u
us
se
ed
d a
as
s a
a f
fr
ra
am
me
e
f
fo
or
r d
dr
ra
af
ft
ti
in
ng
g a
as
ss
se
es
ss
sm
me
en
nt
t
r
re
ep
po
or
rt
t.
.
QOS is main review document.
•
•
Applicants are expected to
summarizecritical data in
module 3 into QOS, along with a
sufficient discussion on every
critical point for ensuring the
quality, efficacy and safety of
the drug.
QOS makes it possible for
reviewers to understand the
characteristicsof the drug
within a short time, and to
review the NDA application
efficiently.
Comparison of Purposes of QOS
between EU/USA and Japan
EU/USA Japan
56. 9/6/2005 AAPS workshop on Pharm Quality
Assessment
10
Characteristics of Japanese QOS
• Within CTD guideline
• Include many figures and tables which
summarize critical data
• Include narrative summary and/or
discussion on data
• Should be written in Japanese :Tables &
Figures may be in English
57. 9/6/2005 AAPS workshop on Pharm Quality
Assessment
11
QOS is main Document for Reviewing
NDA in Japan
1. Expert team in PMDA reviews NDA application using
module 2 (QOS) as main review document and referring
to module 3, and prepares a review report.
2. (Final)QOS and review report are submitted to the
Committees on new drugs in the Pharmaceutical Affairs
and Food Sanitation Council (PAFSC).
3. The committee members discuss quality, efficacy and
safety of the drug based on the review report and QOS.
(Usually, the committee members do not review module
3.)
4. The opinion of the committee is sent to MHLW together
with the review report, then the Minister of Health,
Labor and Welfare grants the new drug approval to the
applicant.
58. 1) Determination of structure
2) Physicochemical properties
3) Manufacturing process (brief
outline)
4) Specifications and test methods
5) Stability: stress test, accelerated
test, long-term test
Requirements for Mockup of QOS
Preparation of
Mockup of
Module 2 (QOS)
What to describe?
How to describe?
Former NDA Dossier CTD-based NDA Dossier
3.2.S.2 (P.2) Manufacture
3.2.S.6 (P.7) Container closure
system
3.2.P.2 Pharmaceutical
development
3.2.P.4 Control of excipients
3.2.S.1 General information
3.2.S.3 Characterization
3.2.S.4 (P.5) Control of drug
substances (products)
3.2.S.5 (P.6) Reference standards or
materials
3.2.S.7 (P.8) Stability
59. Mockup of Japanese QOS
• Published by Pharmaceutical Manufacturers
Association of Tokyo, Osaka Pharmaceutical
Manufacturers Association and Japan Health Sciences
Foundation in July 2002
• Merely shows an example of description for each
module 2 section and just a reference for an applicant
to prepare QOS.
• Not covers all information required for each NDA,
nor shows acceptance criteria for each categories.
• NEED more description on pharmaceutical
development and on justification of manufacturing
process according to ICH Q8 and the revised PAL.
9/6/2005 AAPS workshop on Pharm Quality 13
Assessment
60. Applicationform
(in Japanese)
Analytical
procedures
(JP style) &
acceptance
criteria
Manufacturi
ng process
Relationship between Application Form and
CTD Documents
Module 2 (QOS)
(in Japanese)
Module 3 (in Japanese
or English)
•Specifications
• Analytical procedures
•Pharmaceutical
Development
•Manufacturing Process
• batch analyses
• Justification etc.
3.2.S4.1 Specification
3.2.S4.2 Analytical procedures
3.2.S4.3 Validation of analytical
procedures
3.2.S4.4 Batch analyses
3.2.S4.5 Justification of specification
Raw data
61. 9/6/2005 AAPS workshop on Pharm Quality
Assessment
軽微変更届出
15
Revised Framework for Review
and GMP Inspection
Application of
partial change
Review
Application
form
Review
Approval
letter
Notification of
minor partial
change
GMP
inspection
New drug
application
Collection of
commercial
scale data
Re-submission
of application
form
Pre-approval
inspection
Commercial
production
Minor
change
Partial
change
Minor
change
Partial
change
Validation data etc
Pilot scale data
62. Benefits from comprehensive QoS
• Writing Japanese style QoS takes
significant time and energy. BUT it helps
the applicant organizations to understand
own product and process consistently
• QoS can be a vehicle for knowledge
management in regulatory authorities and in
industry
9/6/2005 AAPS workshop on Pharm Quality 16
Assessment
63. AAPS Workshop on Pharmaceutical Quality Assessment -
A Science and Risk-Based CMC Approach in the 21st Century
Co-sponsored with ISPE & FDA
October 6, 2005
B
Br
re
ea
ak
ko
ou
ut
t S
Se
es
ss
si
io
on
n G
G:
: Q
QO
OS
S
C
Ca
an
n Q
QO
OS
S b
be
e u
us
se
ed
d a
as
s a
an
n e
ef
ff
fe
ec
ct
ti
iv
ve
e r
re
ev
vi
ie
ew
w t
to
oo
ol
l?
?
M
Mo
od
de
er
ra
at
to
or
rs
s:
:
G
Ga
ar
ry
y C
Co
on
nd
dr
ra
an
n,
, H
He
ea
al
lt
th
h C
Ca
an
na
ad
da
a
Y
Yu
uk
ki
io
o H
Hi
iy
ya
am
ma
a,
, M
MH
HL
LW
W,
, J
Ja
ap
pa
an
n
N
No
or
rm
ma
an
n S
Sc
ch
hm
mu
uf
ff
f,
, U
US
S F
FD
DA
A
R
Ri
ic
ch
ha
ar
rd
d P
Po
os
sk
ka
a,
, A
Ab
bb
bo
ot
tt
t
64. B
Br
re
ea
ak
ko
ou
ut
t S
Se
es
ss
si
io
on
n O
Ou
ut
tl
li
in
ne
e
I
Is
ss
su
ue
es
s D
Di
is
sc
cu
us
ss
se
ed
d
S
Sh
ha
ar
re
ed
d U
Un
nd
de
er
rs
st
ta
an
nd
di
in
ng
g &
& A
Ag
gr
re
ee
em
me
en
nt
ts
s
R
Re
em
ma
ai
in
ni
in
ng
g C
Ch
ha
al
ll
le
en
ng
ge
es
s
R
Re
ec
co
om
mm
me
en
nd
da
at
ti
io
on
ns
s
S
St
tr
ra
at
te
eg
gi
ie
es
s t
to
o i
im
mp
pl
le
em
me
en
nt
t a
ag
gr
re
ee
ed
d-
-u
up
po
on
n i
is
ss
su
ue
es
s
P
Pr
ro
op
po
os
sa
al
ls
s t
to
o r
re
es
so
ol
lv
ve
e r
re
em
ma
ai
in
ni
in
ng
g c
ch
ha
al
ll
le
en
ng
ge
es
s
65. I
Is
ss
su
ue
es
s D
Di
is
sc
cu
us
ss
se
ed
d
W
Wh
ha
at
t a
ar
re
e t
th
he
e p
pr
ro
os
s a
an
nd
d c
co
on
ns
s o
of
f t
th
he
e d
di
if
ff
fe
er
re
en
nt
t Q
QO
OS
S
m
mo
od
de
el
ls
s?
? S
Sh
ho
ou
ul
ld
d Q
QO
OS
S b
be
e r
re
e-
-e
ex
xa
am
mi
in
ne
ed
d?
?
•
• H
Ho
ow
w c
co
ou
ul
ld
d t
th
he
e Q
QO
OS
S b
be
e r
re
ep
pu
ur
rp
po
os
se
ed
d/
/r
re
ed
de
ef
fi
in
ne
ed
d t
to
o b
be
e
a
a m
mo
or
re
e u
us
se
ef
fu
ul
l d
do
oc
cu
um
me
en
nt
t f
fo
or
r i
in
nd
du
us
st
tr
ry
y a
an
nd
d r
re
eg
gu
ul
la
at
to
or
ry
y
a
ag
ge
en
nc
ci
ie
es
s?
?
•
• W
Wh
ha
at
t a
ar
re
e t
th
he
e c
cu
ur
rr
re
en
nt
t c
ch
ha
al
ll
le
en
ng
ge
es
s i
in
n p
pr
re
ep
pa
ar
ri
in
ng
g
Q
QO
OS
Ss
s f
fo
or
r g
gl
lo
ob
ba
al
l s
su
ub
bm
mi
is
ss
si
io
on
ns
s a
an
nd
d w
wh
ha
at
t c
ch
ha
al
ll
le
en
ng
ge
es
s
c
ca
an
n b
be
e a
an
nt
ti
ic
ci
ip
pa
at
te
ed
d i
in
n r
re
ev
vi
is
si
it
ti
in
ng
g t
th
he
e d
do
oc
cu
um
me
en
nt
t t
to
o
a
ac
ch
hi
ie
ev
ve
e a
a b
be
et
tt
te
er
r Q
QO
OS
S?
?
•
• S
Sh
ho
ou
ul
ld
d a
a h
ha
ar
rm
mo
on
ni
iz
ze
ed
d Q
QO
OS
S b
be
e a
an
n I
IC
CH
H t
to
op
pi
ic
c?
?
•
• C
Ca
an
n t
th
he
e Q
QO
OS
S b
be
e u
ut
ti
il
li
iz
ze
ed
d f
fo
or
r p
po
os
st
t-
-a
ap
pp
pr
ro
ov
va
al
l
c
ch
ha
an
ng
ge
es
s?
?
67. S
Sh
ha
ar
re
ed
d U
Un
nd
de
er
rs
st
ta
an
nd
di
in
ng
g
a
an
nd
d A
Ag
gr
re
ee
em
me
en
nt
ts
s
Q
QO
OS
S s
sh
ho
ou
ul
ld
d b
be
e r
re
e-
-e
ex
xa
am
mi
in
ne
ed
d
R
Re
eg
gi
io
on
na
al
l d
di
if
ff
fe
er
re
en
nc
ce
es
s i
in
n h
ho
ow
w Q
QO
OS
S i
is
s p
pr
re
ep
pa
ar
re
ed
d
N
Ne
ee
ed
d f
fo
or
r c
cl
la
ar
ri
if
fi
ic
ca
at
ti
io
on
n o
on
n h
ho
ow
w Q
QO
OS
S w
wi
il
ll
l b
be
e u
us
se
ed
d
P
Pr
ri
im
ma
ar
ry
y R
Re
ev
vi
ie
ew
w v
vs
s S
Su
um
mm
ma
ar
ry
y d
do
oc
cu
um
me
en
nt
t
C
Cu
ur
rr
re
en
nt
t U
US
S/
/E
EU
U a
ap
pp
pl
li
ic
ca
at
ti
io
on
n o
of
f Q
QO
OS
S l
la
ac
ck
ks
s s
su
uf
ff
fi
ic
ci
ie
en
nt
t d
de
et
ta
ai
il
l t
to
o
b
be
e p
pr
ri
im
ma
ar
ry
y r
re
ev
vi
ie
ew
w d
do
oc
cu
um
me
en
nt
t
I
In
nd
du
us
st
tr
ry
y w
wi
il
ll
li
in
ng
g t
to
o r
re
ev
vi
is
si
it
t Q
QO
OS
S
P
Po
ot
te
en
nt
ti
ia
al
l b
be
en
ne
ef
fi
it
t i
is
s i
im
mp
pr
ro
ov
ve
ed
d C
CM
MC
C r
re
ev
vi
ie
ew
w e
ef
ff
fi
ic
ci
ie
en
nc
cy
y
P
Pr
re
ef
fe
er
r s
si
in
ng
gl
le
e g
gl
lo
ob
ba
al
ll
ly
y a
ac
cc
ce
ep
pt
te
ed
d Q
QO
OS
S m
mo
od
de
el
l a
an
nd
d a
a
s
si
in
ng
gl
le
e p
pr
ri
im
ma
ar
ry
y r
re
ev
vi
ie
ew
w d
do
oc
cu
um
me
en
nt
t
68. R
Re
em
ma
ai
in
ni
in
ng
g C
Ch
ha
al
ll
le
en
ng
ge
es
s
a
an
nd
d O
Ou
ut
ts
st
ta
an
nd
di
in
ng
g I
Is
ss
su
ue
es
s
R
Re
eg
gi
io
on
na
al
l b
ba
ar
rr
ri
ie
er
rs
s t
to
o g
ge
en
ne
er
ra
al
l s
su
ub
bm
mi
is
ss
si
io
on
n
h
ha
ar
rm
mo
on
ni
iz
za
at
ti
io
on
n
E
E.
.g
g.
. C
Co
om
mp
pe
en
nd
di
ia
al
l s
st
ta
an
nd
da
ar
rd
ds
s,
, D
DM
MF
Fs
s,
, p
pa
ac
ck
ka
ag
ge
es
s
C
Cl
la
ar
ri
if
fi
ic
ca
at
ti
io
on
n o
of
f r
re
el
la
at
ti
io
on
ns
sh
hi
ip
p Q
QO
OS
S t
to
o M
Mo
od
du
ul
le
e 3
3
I
In
nc
cl
lu
ud
de
e P
P2
2 o
or
r n
no
ot
t o
or
r s
su
um
mm
ma
ar
ri
iz
ze
ed
d?
?
H
Ho
ow
w/
/w
wh
he
en
n/
/w
wh
he
er
re
e s
sh
ho
ou
ul
ld
d d
de
es
si
ig
gn
n s
sp
pa
ac
ce
e b
be
e
c
ca
ap
pt
tu
ur
re
ed
d?
?
Q
QO
OS
S s
sh
ho
ou
ul
ld
d n
no
ot
t b
be
e a
a d
da
at
ta
a d
du
um
mp
p f
fr
ro
om
m M
Mo
od
du
ul
le
e 3
3
S
Sh
ho
ou
ul
ld
d Q
QO
OS
S l
le
en
ng
gt
th
h b
be
e d
de
et
te
er
rm
mi
in
ne
ed
d b
by
y p
pr
ro
od
du
uc
ct
t
c
co
om
mp
pl
le
ex
xi
it
ty
y?
?
69. R
Re
em
ma
ai
in
ni
in
ng
g C
Ch
ha
al
ll
le
en
ng
ge
es
s
a
an
nd
d O
Ou
ut
ts
st
ta
an
nd
di
in
ng
g I
Is
ss
su
ue
es
s
W
Wh
ha
at
t c
co
on
ns
st
ti
it
tu
ut
te
es
s t
th
he
e r
re
eg
gu
ul
la
at
to
or
ry
y a
ag
gr
re
ee
em
me
en
nt
t
a
an
nd
d r
re
el
la
at
ti
io
on
ns
sh
hi
ip
p t
to
o Q
QO
OS
S?
?
I
Is
s t
th
he
er
re
e a
a p
po
ot
te
en
nt
ti
ia
al
l u
us
se
e o
of
f Q
QO
OS
S d
du
ur
ri
in
ng
g I
IN
ND
D
P
Ph
ha
as
se
es
s?
?
R
Ro
ol
le
e i
in
n p
po
os
st
t a
ap
pp
pr
ro
ov
va
al
l s
su
ub
bm
mi
is
ss
si
io
on
ns
s
P
Po
or
rt
ti
io
on
ns
s v
vs
s.
. n
no
o i
in
nv
vo
ol
lv
ve
em
me
en
nt
t
I
IC
CH
H Q
Q1
10
0
I
Is
s Q
QO
OS
S a
a l
li
iv
vi
in
ng
g v
vs
s.
. s
st
ta
at
ti
ic
c d
do
oc
cu
um
me
en
nt
t?
?
70. R
Re
ec
co
om
mm
me
en
nd
da
at
ti
io
on
ns
s
S
St
tr
ra
at
te
eg
gi
ie
es
s t
to
o i
im
mp
pl
le
em
me
en
nt
t a
ag
gr
re
ee
ed
d-
-u
up
po
on
n i
is
ss
su
ue
es
s
F
Fu
ur
rt
th
he
er
r d
di
is
sc
cu
us
ss
si
io
on
n
a
an
nd
d c
cl
la
ar
ri
if
fi
ic
ca
at
ti
io
on
n
r
re
eq
qu
ui
ir
re
ed
d f
fo
or
r a
a r
re
e-
-
w
wo
or
rk
ke
ed
d Q
QO
OS
S
I
If
f t
th
he
er
re
e i
is
s a
a d
de
ec
ci
is
si
io
on
n
t
to
o r
re
ev
vi
is
si
it
t Q
QO
OS
S,
, i
it
t
s
sh
ho
ou
ul
ld
d b
be
e g
gl
lo
ob
ba
al
ll
ly
y
h
ha
ar
rm
mo
on
ni
iz
ze
ed
d t
th
hr
ro
ou
ug
gh
h
t
th
he
e I
IC
CH
H p
pr
ro
oc
ce
es
ss
s