Table of Contents

US Food and Drug Administration (FDA)

European Union (EU) and European Medicines Agency (EMA)

Therapeutic Goods Administration (TGA)

Health Canada.

World Health Organization.

Medicines and Healthcare products Regulatory Agency (MHRA)

Pharmaceuticals and Medical Devices Agency (PMDA)

International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH)

European Directorate for the Quality of Medicines & HealthCare (EDQM)

Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation Scheme (PIC/S)

Health Products Regulatory Agency (HPRA)

National Medical Products Administration (NMPA)

The WuXi Biologics regulatory affairs (RA) team is pleased to provide you with this biannual summary of regulatory updates (ie, typically product development and CMC-related) that are either in draft or final status by agency.

Purpose and Disclaimer

The intent of this newsletter is to provide global regulatory agencies with updates and new or revised documents during the indicated period. The items listed are neither comprehensive nor exhaustive of all updates from regulatory agencies. Rather, the newsletter lists items that the WuXi Biologics RA team deems relevant to our potential or existing clients and partners developing biological therapeutics and vaccines. Therefore, this update is for information purposes only and is provided “as is” without any warranty, expressed or implied, as to the completeness or accuracy of the contents or its use or fitness for a particular purpose.

Without limiting the generality of the preceding content, the document and information contained therein should not be construed as regulatory advice or representing, speaking, or acting for any regulatory agency. The information is provided to support your efforts to remain informed and should not be used as a substitute for your own regulatory due diligence or actions.

US Food and Drug Administration (FDA)

Key FDA Announcements

Control of Nitrosamine Impurities in Human Drugs

Link: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/control-nitrosamine-impurities-human-drugs

Date: September 4, 2024

FDA is announcing the availability of a final guidance for industry entitled “Control of Nitrosamine Impurities in Human Drugs.” This guidance recommends steps manufacturers of active pharmaceutical ingredients (APIs) and drug products should take to detect and prevent unacceptable levels of nitrosamine impurities in pharmaceutical products. This guidance revises the final guidance of the same name issued on February 24, 2021. The guidance describes two general structural classes of nitrosamine impurities: small-molecule nitrosamine impurities (ie, nitrosamine impurities that do not share structural similarity to the API), and nitrosamine drug substance-related impurities (NDSRIs), which share structural similarity to the API and are generally unique to each API. The guidance discusses the potential root causes of the presence of nitrosamine impurities, detection of nitrosamine impurities, and recommendations for risk assessments, testing, and implementation of controls and other appropriate strategies to prevent or reduce the presence of nitrosamine impurities in APIs and drug products. Recommendations for an alternative bioequivalence approach if manufacturers and applicants decide to reformulate their products to mitigate nitrosamine impurities are also provided in the guidance.

Revocation of Regulations Regarding the Mutual Recognition of Pharmaceutical Good Manufacturing Practice Reports, Medical Device Quality System Audit Reports, and Certain Medical Device Product Evaluation Reports: United States and The European Community

Link: https://www.federalregister.gov/documents/2024/09/20/2024-21559/revocation-of-regulations-regarding-the-mutual-recognition-of-pharmaceutical-good-manufacturing

Date: September 20, 2024

The proposed rule would revoke part 26—Mutual Recognition of Pharmaceutical Good Manufacturing Practice Reports, Medical Device Quality System Audit Reports, and Certain Medical Device Product Evaluation Reports: United States and The European Community. This part substantially reflects the 1998 MRA between the United States and the European Community that was created to better utilize the inspectional resources of each signatory by recognizing one another’s inspection reports. Part 26 consists of 3 subparts: Subpart A—Specific Sector Provisions for Pharmaceutical Good Manufacturing Practices (which substantially reflects the 1998 MRA’s “pharmaceutical sectoral annex”), Subpart B—Specific Sector Provisions for Medical Devices (which substantially reflects the 1998 MRA’s “medical device sectoral annex”), and Subpart C—“Framework” Provisions (which substantially reflects the 1998 MRA’s “umbrella” agreement that contained general provisions applicable to the operation of all of the sectoral annexes).FDA is collecting public comments on this regulation. Either electronic or written comments on the proposed rule must be submitted by November 19, 2024.

Food and Drug Administration Report and Plan on Best Practices for Guidance; Availability

Link: https://www.federalregister.gov/documents/2024/12/03/2024-28228/food-and-drug-administration-report-and-plan-on-best-practices-for-guidance-availability
Date: December 3, 2024

The Food and Drug Administration (FDA or Agency) is announcing the availability of a document entitled “Food and Drug Administration Report and Plan on Best Practices for Guidance” (Report and Plan).

Expedited Program for Serious Conditions—Accelerated Approval of Drugs and Biologics

Link: https://www.fda.gov/media/184120/download

Date: December 6, 2024

This guidance provides information on FDA’s policies and procedures for the accelerated approval program, including discussions of which products may be candidates for accelerated approval, the standards for granting accelerated approval, and the procedures for withdrawing accelerated approval.

MAPP 5019.2 Assessment of the Appropriate Net Container Content for Injectable Drug and Biological Products

Link: https://www.fda.gov/media/159219/download?attachment
Date: December 10, 2024

This MAPP establishes procedures for the assessment and documentation of the net container content(s) for injectable drug products filled into vials. This MAPP also establishes what information regarding the net container content(s) for injectable drug products filled into vials should be communicated to sponsors during product development. The policies and practices established by this document are intended to standardize the Office of Pharmaceutical Quality (OPQ) assessment of information contained in the electronic Common Technical Document (eCTD) section 3.2.P.2., Pharmaceutical Development.

Other FDA Announcements

European Union (EU) and European Medicines Agency (EMA)

Key EMA Announcements

The use of Artificial Intelligence (AI) in the Medicinal Product Lifecycle

Link: https://www.ema.europa.eu/en/use-artificial-intelligence-ai-medicinal-product-lifecycle

Date: September 30, 2024

The reflection paper on the use of artificial intelligence in the lifecycle of medicines outlines the current thinking on the use of artificial intelligence (AI) to support the safe and effective development, regulation and use of human and veterinary medicines. This paper reflects on principles relevant to the application of artificial intelligence (AI) and machine learning (ML) at any step of a medicines’ lifecycle, from drug discovery to the post-authorisation setting.

Co-ordinating GMP Inspections for Centrally Authorised Products

Link: https://www.ema.europa.eu/en/documents/regulatory-procedural-guideline/co-ordinating-good-manufacturing-practice-gmp-inspections-centrally-authorised-products_en.pdf

Date: December 17, 2024

The first version of coordinating GMP inspections for centrally authorized products was published in May 2023. Modifications were introduced as a result of the entry into application of the financial Regulation (EU) 2024/568 and associated working arrangements on fees and changes payable to the EMA applicable from Jan. 1, 2025.

Assessment templates and guidance (veterinary medicines)

Link: https://www.ema.europa.eu/en/veterinary-regulatory-overview/marketing-authorisation-veterinary-medicines/assessment-templates-guidance-veterinary-medicines

Date: December 18, 2024

EMA provides the templates and documents for rapporteurs of the committee for Veterinary Medicinal Products (CNMP) which should be used for the assessment of any new marketing authorization application for a veterinary medicine under centralized procedure. For initial marketing authorization application, EMA provides a version of the list of questions and the scientific overview.

Other EMA Announcements

Therapeutic Goods Administration (TGA)

Health Canada

World Health Organization

Medicines and Healthcare products Regulatory Agency (MHRA)

Key MHRA Announcement

Wholesalers & manufacturers guidance following agreement of the Windsor Framework

Link: https://www.gov.uk/government/publications/wholesalers-manufacturers-guidance-following-agreement-of-the-windsor-framework

Date: September 12, 2024

The document provides guidance for manufacturers and wholesale dealers authorized by the Medicines and Healthcare products Regulatory Agency (MHRA) in implementing the Windsor Framework for human medicines in the UK. It outlines the requirements for labeling and packaging, including the mandatory use of a ‘UK Only’ label starting from January 1, 2025, to ensure that medicines are correctly labeled for the UK market only and prevent their distribution within the EU. The guidance also covers the disapplication of the EU Falsified Medicines Directive in Northern Ireland, the responsibilities of Qualified Persons (QPs), and the conditions for exporting medicines. Additionally, it addresses the regulatory adjustments for Northern Ireland, ensuring continued access to necessary medicines through the Northern Ireland MHRA Approved Route (NIMAR). The document also includes specific instructions for handling medical devices and traditional herbal and homeopathic products.

Other MHRA Announcements

Pharmaceuticals and Medical Devices Agency (PMDA)

International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH)

Key ICH Announcements

ICH Q9(R1) IWG Updated Q9(R1) Annex 1- Q8/Q9/Q10 Questions & Answers

Link: https://www.ich.org/news/ich-q9r1-iwg-updated-q9r1-annex-1-q8q9q10-questions-answers

Date: December 6, 2024

The ICH Secretariat is pleased to announce the publication of the updated Q9(R1) Annex 1- Q8/Q9/Q10 Questions & Answers (R5) related to ICH Q9(R1) Quality Risk Management (QRM). The ICH Assembly approved this updated Q9(R1) Annex 1 on 30 October 2024.

The document is a comprehensive Questions and Answers guide related to the implementation of ICH Q8, Q9, and Q10 guidelines by the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH). It covers various topics including Quality by Design (QbD), Real Time Release Testing (RTRT), Control Strategy, Pharmaceutical Quality System, and the impact of these guidelines on GMP inspection practices. The document provides detailed explanations on how to implement these guidelines in pharmaceutical development and manufacturing, addressing common questions and providing clarifications on regulatory expectations, process validation, design space, and batch release among other topics. The guide emphasizes a science and risk-based approach to pharmaceutical quality to ensure product safety and efficacy.

ICH Q4B(R1) Guideline on Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions_Step 5

Link: https://www.ema.europa.eu/en/documents/scientific-guideline/ich-q4br1-guideline-evaluation-recommendation-pharmacopoeial-texts-use-ich-regions-step-5_en.pdf

Date: December 18, 2024

ICH Q4B(R1) guideline describes the process for the evaluation and recommendation of selected pharmacopoeial texts to facilitate their recognition by regulatory authorities for use as interchangeable by the ICH regulatory members, and the guideline is now moved to step 5.

Other ICH Announcements

European Directorate for the Quality of Medicines & HealthCare (EDQM)

Key EDQM Announcements

Ph. Eur. bids adieu to rabbit pyrogen test in its monographs

Link: https://www.edqm.eu/en/-/ph.-eur.-bids-adieu-to-rabbit-pyrogen-test-in-its-monographs

Date: July 5, 2024

The EP commission adopted 57 revised texts from which rabbit pyrogen test (RPT) has been deleted, together with a new general chapter on Pyrogenicity (5.1.13), making the end of the RPT ere in the EP. As a result, the use of the RPT will no longer be required in any text of the EP and it will be the responsibility of medicine developers to select a suitable in vitro test to control the pyrogenicity of their product, based on a risk assessment as described in the new general chapter. The revised tests omitting the RPT and Pyrogenicity (5.1.13) will be published in EP supplement 11.8, with an implementation date of 1 July, 2025.

General Chapter Elemental Impurities (G-07) Harmonised by the Pharmacopoeial Discussion Group

Link: https://www.edqm.eu/en/-/general-chapter-elemental-impurities-g-07-harmonised-by-the-pharmacopoeial-discussion-group

Date: November 25, 2024

The new harmonised general chapter “Elemental Impurities (G-07)” was signed-off by the Pharmacopoeial Discussion Group (PDG) on 19 June 2024. The PDG brings together the European Pharmacopoeia (Ph. Eur.), Indian Pharmacopoeia Commission (IPC), Japanese Pharmacopoeia (JP) and the United States Pharmacopeia (USP). The corresponding regional texts for the harmonised general chapter “Elemental Impurities” are scheduled for publication in July 2025 (Ph. Eur.), December 2025 (USP), April 2026 (JP) and July 2026 (Indian Pharmacopoeia Commission, IPC).

Other EDQM Announcements

Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation Scheme (PIC/S)

Key PIC/S Announcements

PIC/S Guidance on Remote Assessments (PI 056-1)

Link: https://picscheme.org/docview/9256

Date: December 13, 2024

The guidance is intended to provide guidance on the approach and use of remote assessments including a hybrid inspection as inspection tools to establish consistency amongst Inspectorates.

PIC/S Aide Memoire on Remote Assessment (PI 057-1)

Link: https://picscheme.org/docview/9257

Date: December 13, 2024

The purpose of this document is to assist GMP inspectors in the life cycle process of remote assessments. This Aide-Memoire should also contribute to a harmonised approach for remote assessments between the different PIC/S Members and foster reliance.

Other PIC/S Announcements

Health Products Regulatory Agency (HPRA)

National Medical Products Administration (NMPA)

Key NMPA Announcements

The National Medical Products Administration deploys pilot work on the reform of clinical trial review and approval for innovative drugs

Links:

• https://www.nmpa.gov.cn/yaowen/ypjgyw/hyxx/yphyxx/20240731090348182.html
• https://www.nmpa.gov.cn/xxgk/fgwj/gzwj/gzwjyp/20240731184417109.html
• https://www.nmpa.gov.cn/xxgk/fgwj/gzwj/gzwjyp/20240802085401168.html
• https://yjj.beijing.gov.cn/yjj/zwgk20/yjxw/543375588/index.html
• https://yjj.beijing.gov.cn/yjj/zwgk20/tz7/543375938/index.html
• https://yjj.sh.gov.cn/zx-yp/20240802/bef1aeb21f7344e7bde8b1d50819a0f4.html

On July 30, 2024, Li Li, the Party Secretary and Director of the National Medical Products Administration, chaired a meeting to study and deploy the reform work on the review and approval of clinical trials for innovative drugs, and reviewed and passed the “Pilot Work Plan for Optimizing the Review and Approval of Clinical Trials for Innovative Drugs.”

To implement the work deployment of the CPC Central Committee and the State Council on accelerating the development of new productive forces, continuously deepen the reform of the drug review and approval system, enhance the efficiency of drug review and approval, and support the R&D of innovative drugs, the National Medical Products Administration issued the “Pilot Work Plan for Optimizing the Review and Approval of Clinical Trials for Innovative Drugs” on July 31, 2024.

“Plan for Optimizing the Review and Approval of Clinical Trials for Innovative Drugs” on July 31, 2024:

1. 1. Work Objectives: To complete the review and approval of applications for clinical trials of innovative drugs within 30 working days, and shorten the time to start clinical trials.
2. 2. Requirements for inclusion in the pilot work, including requirements for pilot areas, pilot projects, and clinical trial institutions for pilot drugs.
3. 3. Implementation steps of the pilot work, including applications for pilot areas, pilot institutions, pilot projects, review and approval, and initiation of clinical trials.
4. 4. Timeline and Expected Outcomes: The pilot work will last for one year. During the pilot period, at least 10 varieties of clinical trial applications will be reviewed, approved, and initiated within the pilot areas.
5. 5. Safeguard Measures: Strictly implement the responsibilities of all parties, ensure fairness and justice, and strengthen technical training.

On August 2, 2024, the National Medical Products Administration issued a reply agreeing to carry out the pilot work for optimizing the review and approval of clinical trials for innovative drugs in Beijing and Shanghai. The Beijing Municipal Drug Administration and the Shanghai Municipal Drug Administration will strictly organize the pilot work in accordance with the requirements of the “Pilot Work Plan for Optimizing the Review and Approval of Clinical Trials for Innovative Drugs.”

On the same day, the Beijing Municipal Drug Administration issued a notice that Beijing was approved as a pilot area for optimizing the review and approval of clinical trials for innovative drugs, and released the requirements for organizing the implementation of the pilot application in Beijing, including determining clinical trial institutions for pilot drugs, determining clinical trial projects for pilot drugs, pilot implementation, and work requirements. The Shanghai Municipal Drug Administration released the “Work Plan for Carrying Out the Pilot of Optimizing the Review and Approval of Clinical Trials for Innovative Drugs by the Shanghai Municipal Drug Administration,” which includes work objectives, pilot scope, implementation steps, timeline, and safeguard measures.

Notification on Public Consultation for the “Guidelines for Clean Validation Technology (Draft for Comment)”

Link: https://www.cfdi.org.cn/resource/news/16001.html  

Date: July 7, 2024

This guideline provides an introduction and guidance on various aspects including the scope of application, full lifecycle management, and the basic principles of quality risk management, clean validation risk management (including validation master plan, worst-case scenario selection, sampling point determination, the impact of the surface of equipment to be cleaned on the cleaning process, hold time for equipment to be cleaned, hold time for cleaned equipment, periodic production equipment cleaning validation, etc), cleaning process design and development (including cleaning process design, cleaner selection, identification of critical quality attributes and critical process parameters, acceptable standards, cleaning development experiments, and the establishment of cleaning standard operating procedures and records), implementation of cleaning validation (including design and execution of the plan, validation report, sampling methods, and analytical methods), and continuous cleaning verification (including daily monitoring, change control and risk management, periodic re-validation or audit review). To better guide enterprises in implementing the provisions of this guideline, typical case analyses are provided in the appendix for reference. The deadline for feedback on the draft for comment is July 18, 2024.

Shanghai Municipal People’s Government Office on Supporting the Full Chain Innovation and Development of the Biomedical Industry Several Opinions

Link: https://www.shanghai.gov.cn/nw12344/20240730/0fe29fc2246e4b478757dee3a01ccd08.html

Date: July 30, 2024

To further establish a major strategic highland for the global biomedical industry in the new era and support the high-quality development of the city’s economy and society, the Office of the Shanghai Municipal People’s Government has proposed several opinions on supporting the full-chain innovation and development of the biomedical industry as follows: significantly enhance the capability for innovation at the source; promote better empowerment of industrial development by clinical resources; further accelerate the review and approval process, including seeking national registration review support, strengthening pre-registration review guidance services, speeding up the registration review of Class II medical devices, and enhancing the capabilities of drug and device registration inspection services; Accelerate the application and promotion of innovative products; Strengthen enterprise services and support for industrialization; Enhance investment and financing support; Unlock the value of data resources and promote the international development of the industry.

Notification on Conducting Self-Inspection and Self-Correction of Drug Production Quality and Safety for the Year 2024

Link: https://da.jiangsu.gov.cn/art/2024/8/2/art_84627_11316455.html

Date: August 2, 2024

To further promote the implementation of quality and safety responsibilities by the holders of drug marketing authorizations and pharmaceutical manufacturing enterprises across the province, and to standardize corporate production behaviors from the source to prevent risks and hidden dangers, The Jiangsu Provincial Drug Administration has issued a notification on matters related to the self-inspection and self-correction of drug production quality and safety for the year 2024. The notification includes three aspects: conduct thorough self-inspections and self-corrections, strengthen work inspection and guidance and enhance the use of effectiveness assessment.

The Department of Comprehensive Affairs of the National Medical Products Administration is publicly soliciting opinions on the “Regulations on the Supervision and Management of the Production of Exported Pharmaceuticals (Draft for Comment)”

Link: https://www.nmpa.gov.cn/xxgk/zhqyj/zhqyjyp/20240806165918189.html

Date: August 6, 2024

This document specifies the scope of application, related responsibilities, and service matters. It requires manufacturing enterprises to assume the primary responsibility for the quality and safety of exported drugs. Provincial drug regulatory authorities are responsible for inspecting production conditions, issuing export certification documents, and providing service facilitation. The document details the basic requirements for production sites, production compliance, co-line production, packaging labels, quality management in circulation, and archives of exported drugs. Additionally, it specifies the scope of application, issuing departments, templates, validity period of export certification documents, GMP compliance requirements, authenticity of application materials for export certification documents, and public disclosure of information. For the certification of drug export sales, the document specifies the application forms, required application materials for marketed and unmarketed drugs, and their numbering; it also sets out the requirements for the certification documents for exported APIs to the EU, including application forms, application materials (for cases with and without associated review and approval), and document numbering. For cases not managed according to export certification documents, the document proposes specific requirements and reporting content for self-manufactured exports and commissioned production by foreign pharmaceutical manufacturers, as well as additional considerations for reviewing the qualifications of the commissioning party, products, materials, and management issues regarding re-commissioning. Finally, the document provides detailed explanations for supervision and management.

The Jiangsu Provincial Drug Administration is publicly soliciting opinions on the “Jiangsu Province Drug Production Quality Management Standard Compliance Inspection Management Procedures (Trial) (Draft for Comment)”

Link: https://da.jiangsu.gov.cn/art/2024/8/19/art_84644_11328445.html

Date: August 19, 2024

To standardize the compliance inspection work for drug production quality management standards, Jiangsu Province has formulated the “Jiangsu Province Drug Production Quality Management Standard Compliance Inspection Management Procedures (Trial) (Draft for Comment).” The draft for comment includes six chapters: general provisions, drug GMP compliance inspection upon application, drug GMP compliance inspection according to responsibilities, handling of inspection results, optimization of inspection and others, and supplementary provisions. The annex includes a checklist of materials for drug GMP compliance inspection applications. The deadline for feedback on the draft for comment is September 18, 2024.

The Provincial Drug Inspection Center is exploring the implementation of off-site inspections for drug production

Link: https://mpa.zj.gov.cn/art/2024/8/22/art_1228989351_58937643.html

Date: August 22, 2024

To further advance the optimization of the business environment as part of the “Number One Reform Project,” alleviate the burden on enterprises, inject new vitality into drug production inspections, and aid in further optimizing the business environment, the Zhejiang Provincial Drug Inspection Center recently conducted its first off-site inspection for drug production enterprises following changes in the holder.

Notice on Public Consultation of the “Questions and Answers on Pharmaceutical Similarity Studies for Biosimilars (Draft for Comment)”

Link: https://www.shanghai.gov.cn/nw12344/20240730/0fe29fc2246e4b478757dee3a01ccd08.html

Date: September 9, 2024

To further advance the optimization of the business environment as part of the “Number One Reform Project,” alleviate the burden on enterprises, inject new vitality into drug production inspections, and aid in further optimizing the business environment, the Zhejiang Provincial Drug Inspection Center recently conducted its first off-site inspection for drug production enterprises following changes in the holder.

Announcement on the Additional Authorization Matters of the Wuxi Sub-center of the Jiangsu Provincial Drug Administration Review and Inspection

Link: https://da.jiangsu.gov.cn/art/2024/9/11/art_84622_11359228.html

Date: September 11, 2024

To implement the “Notice on the Action Plan for Optimizing Review and Approval Services to Promote the Use of Innovative Medical Devices and High-Quality Development of the Pharmaceutical Industry (2022-2024)” issued by the Office of the Provincial Government (Su Zheng Ban Fa [2022] No. 1), and in accordance with the “Jiangsu Provincial Drug Administration Review and Inspection Sub-center Assessment and Empowerment Implementation Measures (Trial)”, it has been decided that from September 11, 2024, twelve Type III review matters and twenty-eight Type III inspection matters will be authorized to the Wuxi Sub-center of the Jiangsu Provincial Drug Administration Review and Inspection.

Notice on Public Consultation of the “Technical Guidance for Pharmaceutical Research and Evaluation of Recombinant Glycoprotein Hormone Products (Draft for Comment)”

Link: https://www.cde.org.cn/main/news/viewInfoCommon/e4b98a4a5583d87c6195658264b183b8  

Date: September 12, 2024

This guidance primarily includes nine sections: foreword, scope of application, general principles, raw materials for production, production process, quality research and quality standards, stability studies, packaging materials and containers, and quality similarity studies.

The Beijing Municipal Drug Supervision Administration and other relevant departments have issued a notification regarding the publication of the “Detailed Rules for the Inspection of Drug Marketing Authorization Holders in Contract Manufacturing (2024 Edition).”

Link: https://yjj.beijing.gov.cn/yjj/zwgk20/tz7/543410686/index.html

Date: September 14, 2024

To further advance the optimization of the business environment as part of the “Number One Reform Project,” alleviate the burden on enterprises, inject new vitality into drug production inspections, and aid in further optimizing the business environment, the Zhejiang Provincial Drug Inspection Center recently conducted its first off-site inspection for drug production enterprises following changes in the holder.

The National Medical Products Administration has deployed a pilot reform for divided manufacturing of biological products

Links:

• https://www.nmpa.gov.cn/yaowen/ypjgyw/ypyw/20241018131800143.html
• https://www.nmpa.gov.cn/xxgk/fgwj/gzwj/gzwjyp/20241022112249149.html
• https://www.nmpa.gov.cn/xxgk/zhcjd/zhcjdyp/20241022112538156.html

Date: October 18, 2024

On October 18, 2024, the National Medical Products Administration held a meeting to study and deploy the pilot reform for divided manufacturing of biological products. The meeting reviewed and approved the “Pilot Work Plan for Divided Manufacturing of Biological Products”, which outlines the pilot scope, implementation steps, timeline, supervision and management requirements, and safeguard measures. On October 22, the “Pilot Work Plan for Divided Manufacturing of Biological Products” and its policy interpretation were released. The plan provides detailed information on the pilot regions, pilot enterprises, pilot varieties, pilot duration, and pilot work procedures.

The Center for Drug Evaluation of the National Medical Products Administration has released the “Requirements for the Application Dossier for Marketing Registration of Drugs Transferred from Overseas Production to Domestic Production (Prophylactic Biological Products)” (Announcement No. 43 of 2024)

Link: https://www.cde.org.cn/main/news/viewInfoCommon/bea94a23b9817235e0aeaa4ad08a2a67

Date: October 23, 2024

This document provides a detailed introduction from four aspects: overall requirements, general considerations, application dossier requirements, and other related requirements.

1. 1. Overall Requirements: Domestic applicants should submit marketing registration applications for prophylactic biological products under category 3.3.
2. 2. General Considerations: This includes principles for simplifying application dossiers, change risk assessment, related changes, and communication.
3. 3. Application Dossier Requirements: Detailed requirements and special considerations for Module 1, Module 2, Module 3, Module 4, and Module 5 are provided.
4. 4. Other Related Requirements: This includes requirements regarding the number of transfers and multiple specifications, inspection and testing, and GMP compliance inspection.

This document was issued and came into effect on October 23, 2024.

The General Office of the Shanghai Municipal People’s Government has issued the “Notice on Printing and Distributing the Action Plan for Enhancing the International Competitiveness of Biopharmaceutical Enterprises in Shanghai (2024-2027)”

Link: https://www.shanghai.gov.cn/nw12344/20241031/a0f2e023dbdc4f5fbdd7131fc079f721.html

Date: October 31, 2024

The plan aims to accelerate the expansion of innovative pharmaceutical and medical device products from Shanghai into international markets through the establishment or joint construction of international marketing networks, overseas rights licensing, procurement by international organizations, and aid and assistance. By 2027, the plan aims to further enhance the international development capabilities of Shanghai’s biopharmaceutical enterprises, with the export value of pharmaceutical and medical device products exceeding 50 billion Yuan, and 2-3 enterprises achieving overseas market sales of over 10 billion Yuan.

The plan includes five key tasks:

1. 1. Strengthening the research and development of innovative pharmaceutical and medical device products with international competitiveness.
2. 2. Accelerating the cultivation of local multinational enterprises.
3. 3. Promoting the international development of innovative small and medium-sized enterprises.
4. 4. Facilitating the entry of innovative pharmaceutical and medical device products into international markets.
5. 5. Optimizing the environment for the international development of enterprises.

These key tasks are further divided into 18 specific tasks.

Announcement on the Release of the “On-site Inspection Guidelines for Divided Manufacturing of Biological Products”

Link: https://www.cfdi.org.cn/resource/news/16139.html

Date: November 1, 2024

The guidelines aim to guide inspectors on how to focus on key inspection points for on-site inspections of divided manufacturing of biological products based on the principles of quality risk management, from the perspectives of the quality management system and divided manufacturing management. The inspection guidelines include key contents such as the purpose and scope of application of the inspection, regulatory basis, inspection strategies, quality management system inspection, and divided manufacturing management inspection.

The General Office of the National Medical Products Administration is publicly soliciting opinions on the “Announcement on Strengthening the Supervision and Management of Drug Contract Manufacturing (Draft for Comments)”

Link: https://www.nmpa.gov.cn/xxgk/zhqyj/zhqyjyp/20241105155114179.html

Date: November 5, 2024

The draft for comments consists of 28 articles and is mainly divided into three parts: strengthening the quality responsibility of contract manufacturing enterprises, enhancing the supervision and management of contract manufacturing, and other matters.

It also includes three attachments:

1. 1. List of application materials for the drug contract manufacturing opinion letter.
2. 2. Inspection requirements for issuing the “Consent for Contract Manufacturing Opinion Letter”.
3. 3. Template for the drug contract manufacturing opinion letter from the provincial (regional, municipal) drug supervision and administration bureau.

The deadline for submitting comments is December 10, 2024.

The Jiangsu Provincial Drug Administration has issued the “Notice on the Issuance of the Implementation Rules for Priority Acceptance and Review of Post-Marketing Production Site Changes of Drugs in Jiangsu Province (Trial)” (Effective)

Links:

• https://da.jiangsu.gov.cn/art/2024/11/6/art_84620_11413211.html
• https://da.jiangsu.gov.cn/art/2024/11/13/art_84602_11417750.html
• https://da.jiangsu.gov.cn/art/2024/11/28/art_84621_11430924.html

Date: November 6, 2024

On November 6, 2024, the Jiangsu Provincial Drug Administration issued the “Implementation Rules for Priority Acceptance and Review of Post-Marketing Production Site Changes of Drugs in Jiangsu Province (Trial).” The rules clarify five aspects: the scope of application, documentation requirements, work procedures, work timelines, and the implementation period.

Key points include:

• Work procedures and timelines: For eligible products, they will be marked and separately sorted in the system, with priority given to technical review, inspection, and approval. The stability test data of samples after site changes can be accepted with deficiencies and supplemented before the end of the technical review.
• The technical review timeline is reduced from 60 working days (excluding combined application items) and 80 working days (including combined application items) to 20 and 30 working days, respectively.

These implementation rules take effect from November 6, 2024, and are valid until November 5, 2026.

The Center for Drug Evaluation of the National Medical Products Administration has released the “Technical Requirements for Registration Application of Divided Manufacturing Pilot of Antibody-Drug Conjugates” (Announcement No. 47 of 2024)

Link: https://www.cde.org.cn/main/news/viewInfoCommon/612aa2c85a18c269b8d352202865b71e

Date: November 7, 2024

This document applies to marketing applications or post-marketing supplemental applications for ADC (Antibody-Drug Conjugates) products included in the divided manufacturing pilot. It provides guidance on the research and registration application work related to the divided manufacturing of small molecules, bulk drugs, or formulations. The general principles mention the need to conduct research and validation covering the entire production chain and lifecycle for the divided manufacturing of ADC products. Compared to non-divided manufacturing processes, the additional risks in the segmented production mode of ADC products mainly lie in the transportation and handover of intermediate products. Applicants/MAHs (Marketing Authorization Holders) should focus on quality control during transportation, the establishment of acceptance standards for outgoing and incoming intermediate products and change studies. Registration inspection and verification should be initiated based on risk.

The National Medical Products Administration (NMPA) has issued the “Announcement on the Issuance of the Interim Provisions on the Management of Designated Domestic Responsible Persons by Overseas Drug Marketing Authorization Holders” (2024 No. 137)

Link: https://www.nmpa.gov.cn/xxgk/ggtg/ypggtg/ypqtggtg/20241114172951120.html

Date: November 14, 2024

The National Medical Products Administration (NMPA) has formulated and issued the “Interim Provisions on the Management of Designated Domestic Responsible Persons by Overseas Drug Marketing Authorization Holders” (hereinafter referred to as the “Interim Provisions”), which will be implemented from July 1, 2025. To ensure the implementation of the “Interim Provisions,” the NMPA has developed relevant modules in the National Drug Business Application System, which were officially launched on November 14, 2024.

The “Interim Provisions” clarify the definitions and obligations of overseas holders and domestic responsible persons, the conditions and requirements for domestic responsible persons, the reporting methods and requirements for domestic responsible persons, the usage methods of the National Drug Business Application System, and the regulatory authorities’ supervision and inspection of domestic responsible persons fulfilling the obligations of overseas holders in drug-related activities.

Notice on Public Consultation for the “Guidelines for Process Validation Inspection (Draft for Comments)”

Link: https://www.cfdi.org.cn/cfdi/resource/news/16160.html

Date: November 15, 2024

To strengthen the quality management of commercial-scale process validation for drugs and guide inspectors in conducting on-site process validation inspections, the Center for Food and Drug Inspection of the National Medical Products Administration has organized the drafting of the “Guidelines for Process Validation Inspection (Draft for Comments).” The guidelines include the purpose, scope of application, basic principles of process validation, types of process validation, methods of process validation, implementation of commercial-scale production process validation, technical considerations for special situations, and key points for on-site process validation inspections. The consultation period ends on November 29, 2024.

Reply from the National Medical Products Administration on Approving Beijing and Nine Other Provinces (Cities) to Carry Out Pilot Reforms for Optimizing the Review and Approval Procedures of Drug Supplementary Applications

Links: https://www.nmpa.gov.cn/xxgk/fgwj/gzwj/gzwjyp/20241122180242111.html, https://www.cde.org.cn/main/news/viewInfoCommon/705545a2481fc16fdce1aa659fb08823
Date: November 22, 2024

On November 22, 2024, the National Medical Products Administration issued a reply approving Beijing, Tianjin, Hebei, Shanghai, Jiangsu, Zhejiang, Shandong, Guangdong, Chongqing, and Sichuan provinces (cities) to carry out pilot reforms for optimizing the review and approval procedures of drug supplementary applications. On November 25, the Center for Drug Evaluation announced the addition of a “Pilot Reform for Optimizing the Review and Approval Procedures of Drug Supplementary Applications” pre-service application function in the “Applicant’s Window.” Marketing authorization holders in the aforementioned ten pilot provinces (cities) can submit pre-service applications to their local provincial (city) bureaus as required. Subsequently, the provincial (city) bureaus of Jiangsu, Shandong, and Zhejiang have also successively issued announcements on the pilot reform work for optimizing the review and approval procedures of drug supplementary applications. Currently, the scope of pre-service provided by the provincial bureaus covers major post-approval changes in the chemistry of chemical drugs (including active pharmaceutical ingredients).

Notice on Public Consultation for the “Requirements for Writing Module 2.3 Pharmaceutical Documentation for Clinical Trial Applications of Therapeutic Biological Products (Draft for Comments)”

Links: https://www.cde.org.cn/main/news/viewInfoCommon/88fe69c55adc6d4b15152102fcfd003a
Date: December 16, 2024

In order to better serve applicants, guide the writing of pharmaceutical research-related content in clinical trial application documents, and improve the quality of application materials, the Center for Drug Evaluation (CDE) has drafted the “Requirements for Writing Module 2.3 Pharmaceutical Documentation for Clinical Trial Applications of Therapeutic Biological Products (Draft for Comments).” The consultation period is one month from the date of publication.

Other NMPA Announcements