Regulatory Newsletter

WuXi Biologics’ Regulatory Affairs team is honored to provide you with a summary of what we deem as the relevant (i.e., product development and CMC-related) regulatory updates from the last three months organized by agency and by topic. We have compiled these updates to support your efforts to stay current in the ever-changing regulatory environment for biological therapeutics and vaccines.

Purpose & Disclaimer: The intent of this update is to provide the global regulatory agencies’ updates and new or revised documents during the period stated here. The items listed should neither be considered comprehensive nor exhaustive of all updates from the regulatory agencies but as such, the list contains items that the WuXi Biologics’ Regulatory Affairs 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 foregoing, 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

Quick Links to Agency Sections: U.S. Food & Drug Administration (FDA) | European Medicines Agency (EMA) | Health Canada | World Health Organization (WHO) | Pharmaceutical Inspection Co-operation Scheme (PIC/S) | Pharmaceuticals and Medical Devices Agency (PMDA) | Australian Department of Health Therapeutic Goods Administration (TGA) | MHRA – Medicines and Healthcare Products Regulatory Agency | International Council for Harmonisation (ICH) | National Medical Products Administration (NMPA)

Special regulatory update:

Special Topic – COVID-19 Pandemic Outbreak

FDA

Good Manufacturing Practice Considerations for Responding to COVID-19 Infection in Employees in Drug and Biological Products Manufacturing (June 2020)

This guidance intends to provide GMP recommendations to drug and biological product manufacturers in order to prevent or mitigate potential adverse effects on the safety and quality of drugs from an infected or potentially infected employee engaged in drug manufacturing. This policy intends to remain in effect only for the duration of the public health emergency related to COVID-19 declared by the Secretary of Health and Human Services (HHS).

The following points should be taken into consideration by the manufacturers:

• Evaluate the CGMP controls regarding restriction of sick employees from production areas
• Review CGMP requirements and recommendations related to facility and equipment cleaning and sanitation and other controls that ensure materials, APIs, components, drug product containers and closures, in-process materials, and drug products are safe and meet their quality requirements
• Risk assessment of SARS-CoV-2 concerning drug safety or quality
• For biological products, the potential for the production cell line to replicate SARS-CoV-2, the capability to detect SARS-CoV-2 in current cell bank and harvest testing, the effectiveness of viral clearance and inactivation steps for SARS-CoV-2, as well as the controls in place for procedures taking place in open systems (e.g., buffer and media preparation areas) are recommended to be assessed by the manufacturers

COVID-19 Public Health Emergency: General Considerations for Pre-IND Meeting Requests for COVID-19 Related Drugs and Biological Products (May 2020)

This guidance provides general nonclinical, clinical, and product quality considerations to assist sponsors in preparing pre-IND meeting requests for COVID-19 related drugs. This policy is intended to remain in effect only for the duration of the public health emergency related to COVID-19 declared by the Secretary of HHS. For pre-IND requests for drugs that treat or prevent COVID-19, the content requests and processes described within this guidance substitute for those used in other settings described in the draft guidance for industry Formal Meetings Between the FDA and Sponsors or Applicants of PDUFA Products (December 2017).

Sponsors developing drugs for use in treatment or prevention of COVID-19 have three options for submitting their pre-IND meeting requests:

• Electronic Submissions Gateway (ESG, the preferred method)
• NextGen Portal (for CDER pre-IND meeting requests)
• Sending emails to CBERDCC_eMailSub@fda.hhs.gov (for CBER pre-IND meeting requests that cannot be sent through ESG).

Effects of the COVID-19 Public Health Emergency on Formal Meetings and User Fee Applications – Questions and Answers (May 2020)

This guidance provides answers to frequently asked questions about regulatory and policy issues related to drug development for the duration of the COVID-19 public health emergency declared by the HHS. The following are two examples of this important Q&A document:

Q: Will some PDUFA and BsUFA applications be delayed because of the COVID-19 public health emergency?

The FDA intends to focus resources on INDs, NDAs, and BLAs (both 351(a) and 351 (k) applications) for drugs or biologics related to COVID-19 or certain other life-threatening conditions. Exceptions include the initial IND 30-day safety review and other important safety issues that may emerge during IND development.

Q: Does FDA expect that PDUFA and BsUFA goal dates will be missed, or will the goal dates be extended because of the COVID-19 public health emergency?

Though the FDA is committed to working to meet the performance goals outlined in the PDUFA VI and BsUFA II goals letters, the FDA may anticipate missing a PDUFA or BsUFA goal date because of the current public health emergency. In such case, the FDA will communicate with the sponsor or applicant directly.

Coronavirus (COVID-19) Update: FDA Updates on Surveillance Inspections during COVID-19 (May 2020)

During COVID-19, the FDA will continue to utilize and implement additional alternative inspection tools and approaches while postponing domestic and foreign routine surveillance inspections. This will continue as local, national and international conditions warrant, with the exception of certain mission critical inspections identified on a case-by-case basis. The alternative approaches can include, among other things, evaluating records in lieu of conducting an onsite inspection on an interim basis when travel is not permissible.

Coronavirus Disease (COVID-19) Related News

COVID-19-Related Guidance Documents for Industry, FDA Staff, and Other Stakeholders (Updated: June 2020)

COVID-19 and Beyond: Oversight of the FDA’s Foreign Drug Manufacturing Inspection Process (June 2020)

Rare Disease Therapy Development and Access Remain Top FDA Priorities During COVID-19 (June 2020)

FDA Maintains the Pace of Meeting Its Goals on Applications for Medical Products During the Pandemic (June 2020)

Development and Licensure of Vaccines to Prevent COVID-19 (June 2020)

Coronavirus (COVID-19) Update: FDA Takes New Actions to Accelerate Development of Novel Prevention, Treatment Options for COVID-19 (May 2020)

Drug Development Inquiries for Drugs to Address the COVID-19 Public Health Emergency (May 2020)

Coronavirus Treatment Acceleration Program (CTAP) (April 2020)

Letter to Sponsors, Applicants and Regulated Entities on COVID-19 (April 2020)

Other News Updates

Master Files for CBER-Regulated Products (June 2020)

SOPP 8214 Rev.2 Interact Meetings with Sponsors for Drugs and Biological Products (June 2020)

Advancing FDA’s Public Health Mission in our International Affairs: FDA’s Office of Global Policy and Strategy Unveils Key Five-Year Strategic Plan to Strengthen its International Operations (June 2020)

Guidance Agenda: Guidance Documents CBER is Planning to Publish During Calendar Year 2020 (June 2020)

MAPP 5017.1 Rev. 1: Office of Biotechnology Products and Office of Pharmaceutical Manufacturing Assessment, Interactions on BLA Assessments (May 2020)

MAPP 5017.2 Rev.1: Establishing Impurity Acceptance Criteria As Part of Specifications for NDAs, ANDAs, and BLAs Based on Clinical Relevance (May 2020)

MAPP 5015.12: Process for Evaluating Emerging Technologies Related to Quality (May 2020)

MAPP 5022.0: CDER Liaisons to Official Compendia and Standards Development Organizations – Selection Process, Roles, and Responsibilities (May 2020)

FY 2019 PDUFA Performance Report (May 2020)

Q3C(R8) Recommendations for the Permitted Daily Exposures for Three Solvents—2-Methyltetrahydrofuran, Cyclopentyl Methyl Ether, and Tert-Butyl Alcohol—According to the Maintenance Procedures for the Guidance Q3C Impurities: Residual Solvents (May 2020)

SOPP 8426: Rev.3 Assignment of Biological and Drug Product Proper Names and Biological Suffixes (April 2020)

SOPP 8201: Administrative Processing of Clinical Holds for Investigational New Drug Applications (April 2020)

SOPP 8117 Rev.6 Issuing Tracking Numbers in Advance of Electronic Submissions in eCTD Format (April 2020)

FY 2019 BsUFA Performance Reports (April 2020)

EMA

Targeted Stakeholder Consultation on the Pilot Project ‘Market Launch Intentions of Centrally Authorised Products’ (June 2020)

Period of consultation: June 22 – July 22, 2020

The following is summary of this topic:

A centralized marketing authorization granted by the European Commission is valid throughout the EU, allowing the marketing of the medicinal product in all Member States. However, in practice, there are still important differences with regards to when a new centrally authorized medicinal product (CAP) is made available in each EU Member State. The lack of availability of medicinal products is a general concern. In order to increase availability of CAPs, an ad hoc working group was set-up under the Human Pharmaceutical Committee. One of the agreed actions is a ‘pilot project’ to raise awareness on this issue and engage with prospective marketing authorization holders (MAHs) through voluntary sharing of their marketing intentions for specific types of CAPs in the pre-authorization phase, and to improve regulators’ knowledge on the mechanism behind delayed market launch. Prospective MAHs participating in this pilot will be invited to share this information on a confidential basis.

• This pilot will be restricted to MAHs of orphan medicines and/or oncology medicines.
• This online consultation is seeking the stakeholders’ feedback on the proposed pilot project and its template for ‘Market Launch Intentions.’
• The implementation of this pilot project should start later this year.
• Feedback mechanism is provided.

COVID-19: How EMA Fast-Tracks Development Support and Approval of Medicines and Vaccines (May 2020)

This press release summarizes the rapid procedures the EMA implemented to accelerate medicines and vaccines against COVID-19 regulatory pathway while assuring robustness of scientific opinions. Key procedures are outlined below:

• Accelerated support during research and development, including 1) rapid scientific advice; 2) rapid agreement of paediatric investigation plans (PIPs) and rapid compliance check
• Accelerated evaluation in authorization and post-authorization procedures, including: 1) Rolling review; 2) Accelerated assessment; 3) EMA further flexibility
• For a complete list and details, please refer to the inventory.

Notice to Stakeholders: Questions and Answers on Regulatory Expectations for Medicinal Products for Human Use During the COVID-19 Pandemic (April 2020)

This document provides guidance on regulatory expectations and flexibility to marketing authorization holders (MAHs) of medicinal products for human use during the COVID-19 pandemic. The document is being updated continuously, and the current key topics include:

• Issues related to marketing authorizations, and marketing authorization procedures
• Manufacturing, importation of finished products and active pharmaceutical ingredients; GMP and GDP issues
• Quality variations
• Product information and labelling
• Additional temporary GMP and GDP flexibility

Coronavirus Disease (COVID-19) Related News

Guidance for Medicine Developers and Companies on COVID-19 (Updated: June 2020)

EDQM Provides COVID-19 Vaccine Developers with Free Access to Quality Standards Applicable in Europe (June 2020)

First COVID-19 Treatment Recommended for EU Authorisation (June 2020)

EMA and Korean Ministry of Food and Drug Safety to Share Confidential COVID-19 Information (June 2020)

EMA Establishes Task Force to Take Quick and Coordinated Regulatory Action Related to COVID-19 Medicines (April 2020)

Update to Guidance on Regulatory Expectations in the Context of COVID-19 Pandemic (April 2020)

Other News Updates

Guide to Information on Human Medicines Evaluated by European Medicines Agency: What the Agency Publishes and When (Updated: June 2020)

2019 Annual Report of the European Medicines Agency (June 2020)

Validation/Verification of Analytical Procedures (June 2020)

Procedural Advice for Orphan Medicinal Product Designation (June 2020)

Academia Developing Medicines for Rare Diseases to Receive Free EMA Scientific Advice (June 2020)

Second Targeted Stakeholders’ Consultation on the Revision of Annex 1, on Manufacturing of Sterile Medicinal Products, of Eudralex Volume 4 (May 2020)

• Due to the challenges posed by COVID-19, the timeline for the second targeted consultation has been extended until July 20, 2020.

European Pharmacopoeia: Adoption of a New General Chapter on Multivariate Statistical Process Control (May 2020)

Subscriptions Now Open for the European Pharmacopoeia 10th Edition, Supplements 10.3-10.5 (May 2020)

European Medicines Agency Pre-authorisation Procedural Advice for Users of the Centralised Procedure (May 2020)

European Medicines Agency Post-authorisation Procedural Advice for Users of the Centralised Procedure (May 2020)

Guidance for Applicants on a Pilot for Simultaneous National Scientific Advice (SNSA) (April 2020)

CHMP Rules of Procedure (Updated: April 2020)

Pharmeuropa 32.2 Just Released (April 2020)

Reflection paper on Good Manufacturing Practice and Marketing Authorisation Holders (Draft: April 2020)

• The deadline for comments is extended from April 17, 2020 to July 17, 2020

Cross Agency Collaboration

Coronavirus Disease (COVID-19) Related News

Global Regulators Work towards Alignment on Policy Approaches and Regulatory Flexibility during COVID-19 (June 2020)

Partnering with the European Union and Global Regulators on COVID-19 (June 2020)

FDA Holds Meetings with EC and EMA to Strengthen Medical Products Cooperation (June 2020)

Health Canada

Other News Updates

Release of Draft (Step 2) ICH Guidance: Q3C(R8): Impurities: Residual Solvents (June 2020)

Coronavirus Disease (COVID-19) Related News

Applications for Drug Clinical Trials under the Interim Order: Guidance Document (May 2020)

WHO

Points to Consider on the Different Approaches – including HBEL – to Establish Carryover Limits in Cleaning Validation for Identification of Contamination Risks when Manufacturing in Shared Facilities (Draft: May 2020)

This guidance provides considerations for the prevention of cross-contamination in production in shared facilities including HBEL (Health-Based Exposure Limits) assessment and it specifically outlines the possible approaches used to establish safe carryover limits in cleaning validation when manufacturing in shared facilities. Considerations for cleaning validation in multi-product facilities and approaches for HBEL setting in cleaning and cleaning validation are further clarified in this document. It also emphasizes the importance of identifying and implementing appropriate controls to mitigate all risks for contamination and cross-contamination in multi-product facilities.

Other News Updates

Good Reliance Practices in Regulatory Decision-Making: High-level Principles and Recommendations (Draft: June 2020)

FAQ: Variations to Prequalified Pharmaceutical Products (June 2020)

PIC/S

Questions and Answers on Implementation of Risk-based Prevention of Cross-contamination in Production and Guideline on Setting Health-based Exposure Limits for Use in Risk Identification in the Manufacture of Different Medicinal Products in Shared Facilities (June 2020)

Inspection of Health Based Exposure Limit Assessments and Use in Quality Risk Management (June 2020)

These two guidances provide general considerations for the prevention of cross-contamination in production in shared facilities including HBEL (Health-Based Exposure Limits) assessment. The EMA Q&As document has been adopted by PIC/S to support the PIC/S Guideline on Setting Health-based Exposure Limits (HBEL) for Use in Risk Identification in the Manufacture of Different Medicinal Products in Shared Facilities to clarify questions related to the implementation of risk-based prevention of cross-contamination in production and HBEL assessment.

The PIC/S inspection guide describes an approach that inspectors may consider when inspecting HBEL documents. An aide-memoire incorporating inspection of the HBEL assessment report as well as the Quality Risk Management (QRM) assessment for cross contamination control are listed in this document, which can be used as a supporting document for inspection of cross contamination risk in shared facilities.

Other News Updates

PIC/S Annual Report 2019 (May 2020)

PMDA

Other News Updates

PDG (Pharmacopoeial Discussion Group) Stage 2 Official Inquiry (June 2020)

JP Drafts for Public Comments (June 2020)

JP17 Updated Errata, JP17-1 Errata, and JP17-2 Errata Posted (May 2020)

Coronavirus Disease (COVID-19) Related News

PMDA pledge to tackle COVID-19 Pandemic (March 2020)

TGA

Transition to New GMP Requirements for Medicinal Products (June 2020)

This notice provides notification on adopting the current PIC/S Guide to Good Manufacturing Practice for Medicinal Products (PE009-14, 1 July 2018), excluding Annexes 4, 5, and 14, as the current Manufacturing Principle for medicines and active pharmaceutical ingredients.

The new Manufacturing Principle adoption is scheduled to commence on July 1, 2020, and the basic requirements of the guide will be expected as of this date. Full compliance will be expected after a 12-month graduated transition period. An incremental adoption plan “Transition to New GMP Requirements for Medicinal Products” was published by the TGA on June 22, 2020, to outline the new and amended GMP requirements and the incrementally increasing compliance expectations, throughout the 12 months transition period, for all manufacturers and to ensure pragmatic implementation of the new guide.

Other News Updates

Australian Regulatory Guidelines for Listed Medicines and Registered Complementary Medicines (May 2020)

Update to Manufacturing Principles for Medicines, APIs & Sunscreens (May 2020)

MHRA

Other News Updates

Medicines: Apply for a Parallel Import Licence (Updated: June 2020)

Medicines and Healthcare Products Regulatory Agency Business Plan 2020 to 2021 (June 2020)

Apply for the Early Access to Medicines Scheme (EAMS) (Updated: June 2020)

Good Manufacturing Practice and Good Distribution Practice (June 2020)

Medicines: Get Scientific Advice from MHRA (April 2020)

Decide if Your Product is a Medicine or a Medical Device (March 2020)

Coronavirus Disease (COVID-19) Related News

MHRA Regulatory Flexibilities Resulting from Coronavirus (COVID-19) (Updated: June 2020)

MHRA Guidance on Coronavirus (COVID-19) (Updated: June 2020)

Exceptional GMP Flexibilities for Medicines Manufacturers during the Coronavirus (COVID-19) Outbreak (Updated: May 2020)

Guidance for Manufacturers and Good Practice (GxP) Laboratories on Exceptional Flexibilities for Maintenance and Calibration during the Coronavirus COVID-19 Outbreak (April 2020)

Approval of GxP Documents when Working from Home during the Coronavirus (COVID-19) Outbreak (April 2020)

New Arrangements for MHRA Good Practice (GxP) Inspections due to Coronavirus (COVID-19) (March 2020)

Exceptional GMP Flexibilities for Medicines Imported from Third Countries during the Coronavirus (COVID-19) Outbreak (March 2020)

Guidance for Good Laboratory Practice (GLP) Facilities in Relation to Coronavirus (COVID-19) (March 2020)

ICH

Other News Updates

The eCTD v4.0 Q&A v1.3 Reaches Step 4 of the ICH Process (June 2020)

NMPA

The NMPA guidance documents and updates are written in Chinese, therefore, we have provided more detailed summaries in English for your benefit. The WuXi Biologics Regulatory Affairs team may be available for consultation should your organization be actively pursuing drug development or entering clinical trials in China.

China Pharmacopeia 2020 (July 2020)

The Chinese Pharmacopeia (ChP) 2020 edition, which is the 11th edition since it was first issued in 1953, will be put into implementation on December 30, 2020. This update includes an increased number of monographs, introduces product lifecycle management, upgrades the national standards for drugs, raises requirements on drug safety and efficacy, applies better analytical techniques, and adopts harmonized international standards.

Notice from CDE of Drug Registration Application Dossiers Format and Arrangement Standard (July 2020)

Notice from NMPA of Requirements for Registration Classification and Application Dossiers of Biological Products (June 2020)

Department of Comprehensive Affairs, Planning, and Finance Affairs of NMPA Solicited Public Opinions on the Basic Requirements for Drug Registration Application Dossiers (Draft for Comments) (April 2020)

To facilitate the implementation of Drug Registration Regulations, complementary/supporting regulations were published. In these updates, biological products are divided into three categories: preventive biological products (hereinafter referred to as vaccine), therapeutic biological products, and in vitro diagnostic reagents regulated as biological products. Cell therapy and gene therapy products are categorized as therapeutic biological products.

The requirements for vaccines and therapeutic biological products are addressed based on their respective characteristics. In addition, vaccines and therapeutic biological products are further divided into three sub-categories according to their stage of development – innovative, improved, and domestic- or overseas-marketed vaccines/biological products. In order to align with international standards, the application dossiers for both clinical trial application (i.e., IND or CTA) and marketing registration application (i.e., NDA) shall be prepared in the CTD format.

Notice on Soliciting Public Opinions on the Procedures and Technical Requirements for Drug Registration Testing (Trial Version) (July 2020)

Notice on Soliciting Public Opinions on the Implementation Principles and Procedures for Drug Registration Inspection (Draft for Comments) and Other Two Documents (May 2020)

Notice on Soliciting Public Opinions on the Provisions for the Initiation Principles and Procedures for Drug Registration Inspection and Testing (Trial Version) (Draft for Comments) (April 2020)

In comparison with the previous version of Drug Registration Regulations, significant changes were made in the new version on inspection and testing. First, instead of conducting an inspection for every clinical trial application and drug registration application, inspection will only be initiated based on the potential risks. Second, the working procedures for registration testing are optimized. In addition, the review, inspection, and testing are now conducted in parallel. In principle, the inspection and testing should be completed within the 200 days overall timeframe specified in Drug Registration Regulations to ensure the agency’s goal for review duration is met.

To implement the new Drug Registration Regulations, CDE, Center for Food and Drug Inspection (CFDI), and National Institutes for Food and Drug Control (NIFDC) later issued several supporting documents to clarify requirements for registrational inspection and registrational testing initiation and conduct.

Registrational Inspection

• CDE establishes a risk-based assessment mechanism. In consideration of the drug category and manufacturer’s compliance factors, the risks of an application are divided into three levels: high, medium, and lo The percentage of on-site inspections for each risk level will be adjusted with the constraint of the inspectorate’s resources to focus on the applications determined to be of high risk.
• The risk level of the registration application is determined by the drug category and manufacturer’s compliance factors, whichever is higher. The compliance factor shall be determined in combination with the recent inspection history, regulatory audit, relationship between the contracted entities and sponsor, as well as previous rectification results. Since biological products are deemed to be in the high-risk category, a registrational inspection shall be expected in principle.
• The development site inspection aims to verify the authenticity and consistency of application dossiers and original records through on-site auditing on the development condition of accepted drug registration applications. Manufacturing site inspection for drug registration aims to ensure the raw materials, excipients, formulation, test methods, quality standards, stability studies, and production processes are as declared in the application dossier and check the facility’s commercial production capability. During the manufacturing site inspection, it may be necessary to conduct dynamic production in part of or all of the production steps to ensure the quality of inspection. The inspection batch shall be the same scale as commercial production or the validation batches.
• Inspection is initiated by CDE and conducted by CFDI. Please refer to Key Points and Decision Principles for Drug Registration Inspection (CMC and Manufacturing Site) (Draft for Comments), attachment 2-4 of Notice on Soliciting Public Opinions on the Implementation Principles and Procedures for Drug Registration Inspection (Draft for Comments) and Other Two Documents, for detailed information.

Registrational Testing

Registrational testing is divided into four categories, which are pre-registration testing, testing at the time an NDA passes the formal review, testing during an NDA review, and testing for post-approval supplemental application.

According to the new Drug Registration Regulations, the applicant can apply for a registrational testing to the NIFDC or provincial medical products administration after completing the validation of the commercial-scale manufacturing and before submitting the NDA/MAA. Otherwise, CDE will initiate the registrational testing and notify the drug testing institution when the registration application is accepted.

The procedure for the testing is optimized. A new step is added to allow applicants to communicate with the NIFDC prior to the acceptance of a testing application. In addition, to increase efficiency, the applicant shall submit application documents for registrational testing for review first Samples for testing shall be sent to NIFDC after the acceptance of application documents.

CMC Guidance for Medicine Developers and Companies on COVID-19 Neutralizing Antibody Development (May 2020)

The CDE released a CMC guidance to accelerate neutralizing antibody development and approval for COVID-19.

COVID-19 neutralizing antibody development may be accelerated based on knowledge gained from similar products manufactured with the same mature platform manufacturing technology as used for COVID-19 neutralizing antibody. Similarly, with appropriate justification, some aspects of manufacture and control may be based on the platform knowledge, and the need for product-specific data may be reduced. CDE recommends that manufacturers engage in early communications with CDE to discuss the type and extent of CMC information needed for the development and licensure of their COVID-19 neutralizing antibodies.

NMPA Issues the Biological Products Appendix of 2010 GMP (April 2020)

The National Medical Products Administration (NMPA) issued the revised Biological Products Appendix of the 2010 Edition of the Good Manufacturing Practice of Pharmaceutical Products (2010 GMP) in accordance with the Drug Administration Law and Vaccine Administration Law of China.

The appendix became effective on July 1, 2020. In addition, as provided in Article 59 of the Appendix, vaccine manufacturers shall adopt IT systems with real-time data collection. Considering the system establishment requires a certain period, the establishment should be completed no later than July 1, 2022.

The revised Biological Products Appendix contains a total of 63 articles in eight chapters. Compared with the previous edition, 6 articles were added and 14 articles were revised. The revision aims at strengthening regulation and streamlining production and quality control.

NMPA Solicits Comments on Technical Guideline for Post-marketing Pharmaceutical Change of Biological Products (April 2020)

The document provides guidance to biological product marketing authorization hold (MAH) or manufacturers on recommended studies and data to support post-approval changes of commercial biological products. Common changes are listed in this guideline, including changes on sources, methods, and control conditions in manufacturing, quality control, and other established conditions of the products. The guideline also defines the reporting categories with the respective prerequisites and basic technical requirements for the changes discussed to provide a harmonized guideline, as much as possible, to be aligned with international standards.

According to the guideline, changes are categorized into three classes depending on the risk of potential impacts on quality, safety, and efficacy of products. Upon the completion of relevant studies, supplemental applications, record registration, or annual reports should be submitted as stipulated in Drug Registration Regulations and relevant requirements.

Minor changes (Type Ⅰ): changes that have minor or basically no impact on the quality, safety, and efficacy of biological products.

Moderate changes (Type Ⅱ): changes that have a moderate impact on the quality, safety, or efficacy of biological products and necessitate studies to demonstrate that the changes will not impact the quality, safety, and efficacy of the products.

Major changes (Type Ⅲ): changes that will potentially have a significant impact on the quality, safety, and efficacy of biological products. Extensive studies are required to demonstrate the changes have no negative influence on product quality, safety, and efficacy.

NMPA Solicits Comments on the Rules for Production and Distribution of Vaccines (Draft: April 2020)

To facilitate the implementation of the Drug Administration Law and the Vaccine Administration Law of China, the NMPA released Rules for Production and Distribution of Vaccines, Draft and is soliciting public comments.

NMPA and NHC Issued the 2020 GCP (April 2020)

The NMPA and NHC (National Health Commission) issued the 2020 Edition of the Good Clinical Practice of Drug Clinical Trials (2020 GCP). The regulation has a total of 83 articles in nine chapters, including General Principles, Terminologies and Definitions, Ethics Committee, Investigator, Sponsor, Clinical Trial Protocol, Investigator’s Brochure, Essential Documents Management, and Appendices. It is to become effective on July 1, 2020.

Notice of CDE on Relevant Matters Concerning the Confirmation of Marketing Authorization Holder of Drug Marketing Application (April 2020)

According to the Drug Administration Law (implemented on December 1, 2019), the Center for Drug Evaluation (CDE) specifies that the MAH shall be a single entity. For the NDAs submitted and accepted for review before implementation of the Drug Administration Law, all applicants shall sign and submit a Confirmation Letter of Marketing Registration Applicant prior to the completion of technical review. If two or more joint applicants are involved, one of the applicants shall be determined as the MAH. For the NDAs submitted after the implementation date of the Drug Administration Law, the NDAs applied jointly by two or more entities will no longer be accepted.

Drug R&D and Technical Evaluation Communications (April 2020)

The CDE released Rules for Drug R&D and Technical Evaluation Communications (The Rules), Draft.

The Rules stipulate communications during R&D process and registration application of

innovative drugs, modified new drugs (Me-Betters), biosimilars, and complex generics. For example, meetings to address major safety issues found during clinical trials, major technical issues in the development of the drugs for breakthrough therapy, and major technical issues before an initial clinical trial application (Pre-IND Meeting). The forms of consultation include face-to-face meeting, video conference, teleconference, and written correspondence. Applicants are encouraged to communicate with CDE through teleconference. The Rules also define the three types of consultation meetings, the application procedures, and relevant consultation requirements before, during, and after the meeting.

Guide for Formal Review of Biological Products Application (Part 2 Therapeutic Biological Products) (April 2020)

This guide applies to both IND and NDA of therapeutic biological products. Registration of therapeutic biological products shall follow the procedures stipulated in this guide. In an IND or NDA application, the applicant shall submit completed CMC, pharmacological and toxicological studies, and other related study data as per the requirements on application dossiers. The application shall be accepted when the application dossiers pass the formal review.