Regulatory Newsletter

Q1 2020 Regulatory Updates

Mar. 27, 2020

Q1 2020 Regulatory Updates

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: Australian Department of Health Therapeutic Goods Administration (TGA) | Cross – Agency Collaboration | European Medicines Agency (EMA) | Health Canada | International Council for Harmonisation (ICH) | National Medical Products Administration (NMPA) | Pharmaceuticals and Medical Devices Agency (PMDA) | U.S. Food & Drug Administration (FDA) | World Health Organization (WHO)

Special regulatory updates:

Brexit Special Topic: Pharmaceutical Regulatory Schemes of EMA and MHRA Post-Brexit
Special Topic – COVID-19 Pandemic Outbreak

FDA

Guidance Agenda: Guidances CDER is Planning to Develop During the Calendar Year 2020 (January 2020)

The categories covered in this Guidance Agenda include biostatistics, clinical, drug safety, electronic submissions, generics, labeling, CMC, procedures, amongst other. A selection of CMC-related guidances are listed below:

ICH Q12, General Considerations for FDA Implementation
Inspection of Injectable Products for Visible Particulates
Quality and Stability Testing of Drug Substances and Drug Products for NDAs, ANDAs, and BLAs and Associated Labeling Statements for Drug Products
Setting Endotoxin Limits During Development of Investigational Oncology Drugs and Biologics
Establishment Registration and Drug Listing

Coronavirus Disease 2019 (COVID-19) Update: Foreign Inspections (March 2020)

In this update, the FDA announced that it will postpone most foreign inspections through April 2020. Inspections outside the U.S. deemed mission-critical will still be considered on a case-by-case basis.

Additional tools are applied as an interim measure to ensure the safety of products imported to the U.S., including denying entry of unsafe products into the U.S., physical examinations and/or product sampling at the borders, reviewing a firm’s previous compliance history, using information sharing from foreign governments as part of mutual recognition and confidentiality agreements and requesting records in advance of or in lieu of on-site drug inspections.

Definition of the Term “Biological Product” (February 2020)

The FDA is issuing a final rule to amend its regulation that defines “biological product” to incorporate changes made by the Biologics Price Competition and Innovation (BPCI) Act of 2009 and the Further Consolidated Appropriations (FCA) Act of 2020, which removed the parenthetical “(except any chemically synthesized polypeptide)” from the statutory category of “protein,” and to provide its interpretation of the statutory term “protein.”

Under this final rule, the termproteinmeans any alpha amino acid polymer with a specific, defined sequence that is greater than 40 amino acids in size. This final rule is intended to clarify the statutory framework under which such products are regulated. This rule is effective on March 23rd, 2020. At the same time, the FDA also released the news about the agency’s work to ensure regulatory transition of insulin and other biological products.

Providing Regulatory Submissions in Electronic Format – Certain Human Pharmaceutical Product Applications and Related Submissions Using the eCTD Specifications Guidance for Industry(February 2020)

This guidance describes how sponsors and applicants must organize the content that they submit to the Agency electronically for all submission types under section 745A(a) of the FD&C Act. The revised standards are detailed here:

This revised guidance replaces the previous final guidance issued in January 2019 and modifies previous versions by including exemptions for Type III DMFs. In addition, this guidance includes updated criteria identifying types of submissions that may be qualified for long and short-term waivers, as well as instructions for how to submit a waiver request.
NDAs, ANDAs, and BLAs are mandatory for eCTD submissions from May 5th, 2017. Commercial INDs, DMFs (other than Type III) are mandatory for eCTD submissions from May 5th, 2018.
All submissions to noncommercial INDs (research and investigator-sponsored INDs) are exempt from the eCTD requirements.
For a complete listing of all documents and supportive files needed to submit electronically, please refer to the eCTD website.

Drug Development and Quality Guideline News Updates

Q3D(R1) Elemental Impurities –FDA Implementation(March 2020)

Regulatory Submission and Procedure News Updates

Assessing User Fees Under the Biosimilar User Fee Amendments of 2017 (January 2020)

Electronic Common Technical Document v4.0 Technical Conformance Guide; Food and Drug Administration Electronic Common Technical Document v4.0 Module 1 Implementation Package; Request for Comments (February 2020)

Providing Regulatory Submissions in Alternate Electronic Format Guidance for Industry (March 2020)

Vaccines, Gene Therapy, and Advanced Therapy Medicinal Products News Updates

SOPP 8504: Release of Establishment Inspection Reports to the Inspected Establishments Pursuant to Field Management Directive 145 (January 2020)

SOPP 8506: Management of Shortages of CBER-Regulated Products (January 2020)

Chemistry, Manufacturing, and Control (CMC) Information for Human Gene Therapy Investigational New Drug Applications (INDs) (January 2020)

Human Gene Therapy for Rare Diseases (January 2020)

Human Gene Therapy for Hemophilia (January 2020)

Human Gene Therapy for Retinal Disorders (January 2020)

Testing of Retroviral Vector-Based Human Gene Therapy Products for Replication Competent Retrovirus During Product Manufacture and Patient Follow-up (January 2020)

Interpreting Sameness of Gene Therapy Products Under the Orphan Drug Regulations (January 2020)

SOPP 8402: Designation of Amendments as Major (Updated: January 2020)

SOPP 8404: Refusal to File Procedures (Updated: January 2020)

SOPP 8401.4: Review Responsibilities for the CMC Section of Biologic License Applications, New Drug Applications and Supplements (Updated: January 2020)

SOPP 8405.1: Procedures for Resubmissions to an Application or Supplement (February 2020)

SOPP 8401: Administrative Processing of Original Biologics License Applications (BLA) and New Drug Applications (NDA) (February 2020)

SOPP 8119: Use of Email for Regulatory Communications (February 2020)

SOPP 8408.1: Development of Laboratory Quality Product Testing Plans and Release of Lots as Part of the BLA Approval Process (February 2020)

SOPP 8417: Implementation and Management of Risk Evaluation and Mitigation Strategies (REMS) (February 2020)

Updated Instructions for Submitting Lot Release Samples and Protocols for CBER-regulated Products During the COVID-19 Pandemic (March 2020)

Nonclinical Study Related News

Nonclinical Safety Evaluation of the Immunotoxic Potential of Drugs and Biologics (February 2020)

Coronavirus Disease (COVID-19) Related News

Emergency Investigational New Drug (EIND) Applications for Antiviral Products (January 2020)

FDA Announces Key Actions to Advance Development of Novel Coronavirus Medical Countermeasures (January 2020)

Novel Coronavirus (2019-nCoV) (Updated: February 2020)

Coronavirus Update: FDA Steps to Ensure Quality of Foreign Products (February 2020)

Coronavirus (COVID-19) Update: FDA Focuses on Safety of Regulated Products While Scaling Back Domestic Inspections (March 2020)

Coronavirus (COVID-19) Update: FDA Issues Guidance for Conducting Clinical Trials of Medical Products during COVID-19 Pandemic, Guidance for Industry, Investigators, and Institutional Review Boards (March 2020)

Notifying FDA of a Permanent Discontinuance or Interruption in Manufacturing Under Section 506C of the FD&C Act (March 2020)

Other News Updates

New Drug Therapy Approvals 2019 (January 2020)

Oncology Center of Excellence 2019 Annual Report (February 2020)

Office of Pharmaceutical Quality 2019 Annual Report (February 2020)

FDA In Brief: FDA Enhances Purple Book to Support Transparency in Biosimilars (February 2020)

Promotional Labeling and Advertising Considerations for Prescription Biological Reference and Biosimilar Products Questions and Answers (February 2020)

Biosimilars and Interchangeable Biosimilars: Licensure for Fewer Than All Conditions of Use for Which the Reference Product Has Been Licensed (Draft: February 2020)

The “Deemed to be a License” Provision of the BPCI Act: Questions and Answers (March 2020)

Purple Book Enhancement; Establishment of a Public Docket; Request for Comments (March 2020)

EMA

ICH Q12 Guideline on Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management – Step 5 Implementation (March 2020)

This guideline provides a framework to facilitate the management of post-approval CMC changes. Some of its principles have been inspired by the current EU legal framework on variations. Several of the tools and concepts foreseen in the ICH Q12 guideline are considered compatible with the EU legal framework on variations, and some even stem directly from this framework. These tools and concepts can already be applied, as such, by industry by following the current EU variations framework. In other words, no particular actions are required in the EU in order to implement these parts.

Key topics in this guidance include categorization of post-approval CMC changes, Established Conditions (ECs), Post-approval Change Management Protocol (PACMP), Product Lifecycle Management (PLCM) document, as well as Pharmaceutical Quality System (PQS) and change management, etc. An explanatory note was published in parallel with this guidance.

Scientific Guideline: Reflection Paper on Good Manufacturing Practice and Marketing Authorisation Holders (January 2020)

This paper provides clarity, by collating and discussing the requirements spread out in various EU guides, as to what the various GMP-related responsibilities are and what they mean for Marketing Authorization Holders (MAHs) at a practical level. This paper also addresses the various legislative provisions which relate to GMP and which concern MAHs. The summary includes:

Key topics in this Guideline include but are not limited to: outsourcing and technical agreements, audits and qualification activities, communication with manufacturing sites (e.g., marketing authorization dossier information, variations, and regulatory commitments, amongst others), product quality reviews, maintenance of supply of medicinal products, and continual improvement activities.

Ph. Eur. Supplement 10.2 Available Now (January 2020)

The 10.2 supplement of theEuropean Pharmacopoeiais now available and will be applicable in 38 European countries as of July 1st, 2020. Please refer to the Contents of Supplement 10.2 for details about the new, revised, and deleted texts.

The European Pharmacopoeia (Ph. Eur.) 9th Edition has been obsolete since January 1, 2020. Consequently, the online 9th Edition and all previous versions, including the Ph. Eur. archives for 9th Edition clients, have no longer been accessible since March 1, 2020. See Shutdown of European Pharmacopoeia 9th Edition.

European Pharmacopoeia Updates Testing for Particulate Contamination in Pharmaceutical Preparations(February 2020)

This update communicates that two chapters (listed below) will be published in European Pharmacopoeia (Ph. Eur.) Supplement 10.3 and will become effective on January 1, 2021. The summary is detailed below:

Revisions togeneral chapter 2.9.19. Particulate contamination: sub-visible particles, which supplement the Pharmacopoeial Discussion Group (PDG) harmonized text with alternative local requirements applicable to biological parenteral preparations.
New, non-mandatorygeneral chapter 5.17.2. Recommendations on testing of particulate contamination: visible particlesthat provides information on visual inspection and control of visible particles in liquid preparations for which testing according to thegeneral chapter 2.9.20. Particulate contamination: visible particles

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

The Simultaneous National Scientific Advice (SNSA) pilot program aims at providing coordinated national scientific advice particularly to developers of new medicines and therapies. The pilot adopts the “two in one” approach in which one single step national scientific and/or regulatory advice can be requested with two National Competent Authorities (NCAs) simultaneously. The target groups (applicants), initial participating NCAs, scope and procedure of the program are detailed in this guidance. The pilot project was implemented on February 1, 2020, and the first evaluation of the pilot is foreseen at the end of 2020.

Scientific advice is the provision of advice by the EMA (centrally coordinated by the agency) or NCA on the appropriate tests and studies required in the development of a medicine or on the quality of a medicine.

Targeted Stakeholders’ Consultation on Annex 21: Importation of Medicinal Products, of the Eudralex Volume 4 (Draft: March 2020)

This new Annex sets out the principles and guidelines of good practice requirements applicable to a Manufacturing and Importation Authorization (MIA) holder, which imports medicinal products through the EU/EEA borders. The importation of medicinal products is, in light of Article 40(3) of Directive 2001/83/EC, subject to GMP requirements.

GMP requirements and responsibilities for the MIA holder, the third country manufacturer, and the MAH related to the pharmaceutical quality system, premises and equipment, documentation, operations, complaints, quality defects and product recalls are specified in this Annex. The period of consultation is until June 20, 2020.

The sites which are considered to have specific importation responsibilities in relation to a medicinal product or imported dosage form include:

Site of physical importation
Site of QP certification of imported medicinal products or QP confirmation for intermediate products undergoing further processing, as appropriate

Drug Development and Quality Guideline News Updates

New Pharmeuropa Website Now Online (January 2020)

Pharmeuropa 32.1 Just Released (January 2020)

LC (Liquid Chromatography) and GC (Gas Chromatography) Columns in Monographs (January 2020)

World Pharmacopoeias Move Towards Increased Global Co-operation (February 2020)

Regulatory Submission and Procedure News Updates

Procedural Advice for Orphan Medicinal Product Designation (Updated: January 2020)

Procedural Advice for Post-orphan Medicinal Product Designation Activities (Updated:January 2020)

Type II Variation and Worksharing Assessment Timetables (January 2020)

Marketing Authorisation Application (MAA) – Pre-submission Meeting Request Form (Human) (Updated: January 2020)

Regulatory Information – Adjusted Fees for Applications to EMA from 1 April 2020 (March 2020)

Procedural Advice for Post-orphan Medicinal Product Designation Activities (March 2020)

Coronavirus Disease (COVID-19) Related News

Novel Coronavirus (Updated: February 2020)

The EU’s Response to COVID-19 (February 2020)

News and Press Releases: COVID-19: Developers of Medicines or Vaccines to Benefit from Free Scientific Advice (March 2020)

News and Press Releases: First Regulatory Workshop on COVID-19 Facilitates Global Collaboration on Vaccine Development (March 2020)

Coronavirus Disease (COVID-19) (Updated: March 2020)

Guidance on the Management of Clinical Trials during the COVID-19 (Coronavirus) pandemic (March 2020)

Other News Updates

Human Medicines Highlights 2019 (January 2020)

Newsletter: Human Medicines Highlights (February 2020)

Newsletter: Human Medicines Highlights (March 2020)

EMA Organisational Changes Come into Effect (March 2020)

EMA Management Board – Highlights of March 2020 Meeting (March 2020)

Cross Agency Collaboration

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

This revised Annex 1 for consultation is the result of collaborative efforts among EC, PIC/S, and WHO in order to maintain the global alignment of standards in the manufacture of sterile medicinal products. Some key points regarding this consultation is as follows:

This revision is intended to add clarity, introduce the principles of Quality Risk Management (QRM) to allow for the inclusion of new technologies and innovative processes, and to change the structure of the Annex to a more logical flow.
Key topics include: Pharmaceutical Quality System (PQS), premises, equipment, utilities, personnel, production and specific technologies, viable and non-viable environmental and process monitoring, and quality control. QRM applies to this document in its entirety, and specific limits or frequencies described in this Annex should be considered as a minimum requirement.
The period of consultation is until May 20, 2020.

Health Canada

Notice: Implementation of eCTD for Clinical Trial Regulatory Activities (February 2020)

Key topics in this Notice include:

Health Canada announced the success of the pilot for clinical trial regulatory activities in eCTD format. Therefore, implementation of Clinical Trials regulatory activities in eCTD format will begin immediately for Pre-Clinical Trial Application Consultation Meeting (PRE-CTA), Clinical Trial Applications (CTAs) and Clinical Trial Applications-Amendments (CTA-As), Clinical Trial Application-Notification (CTA-N), and all related responses and post-clearance data to these regulatory activities.
The use of the eCTD format for clinical trial regulatory activities is optional. However, once a sponsor files a regulatory activity in eCTD format, all additional information and subsequent regulatory transactions for the same dossier must also be filed in eCTD format.
The following regulatory activities and/or transactions are out-of-scope for filing in eCTD format:

Clinical Trial Site Information (CTSI)
Development Safety Update Report (DSUR)
Signal assessment related requests from the Therapeutic Products Directorate/Office of Clinical Trials – Adverse Drug Reaction division (OCT ADR)
Fax-Backs for the Biologics and Genetic Therapies Directorate

Regulatory Submission and Procedure News Updates

Guidance for Completing the Drug Submission Application Form (March 2020)

Coronavirus Disease (COVID-19) Related News

Coronavirus Disease (COVID-19): Canada’s Response (March 2020)

WHO

WHO Publishes Emergency Use Listing Procedure and Roadmap to Make New Medical Products More Readily Available during Health Emergencies (February 2020)

WHO published the Emergency Use Listing (EUL) procedure to streamline the process by which new or unlicensed products can be used during public health emergencies. The EUL concerns three product streams, including vaccines, therapeutics, and in vitro diagnostics, each of which has specific requirements for products to be eligible for evaluation under the EUL procedure.

PMDA

Drug Development and Quality Guideline News Updates

Supplement II to the JP 17th Edition (English Version) Posted (February 2020)

Coronavirus Disease (COVID-19) Related News

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

TGA

Drug Development and Quality Guideline News Updates

International Scientific Guidelines Adopted in Australia (March 2020)

Regulatory Submission and Procedure News Updates

Health Products Regulation Group: Regulatory Science Strategy, 2020-2025 (January 2020)

Reformatting Product Information: Frequently Asked Questions (March 2020)

Coronavirus Disease (COVID-19) Related News

TGA Response to Coronavirus (COVID-19) (March 2020)

TGA Suspends Overseas GMP Inspections and QMS Audits Until Further Notice (March 2020)

ICH

The ICH Q12 Introductory Training Presentation Available Now on the ICH Website (February 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.

Provisions for Registration of Drug Products

Provisions for Registration of Drug Products (2020 # No. 27) (March 30, 2020)
Policy Interpretation of Provisions for Registration of Drug Products (March 31, 2020)
Announcement of the National Medical Products (NMPA) Administration on Implementing the Registration of Drug Products (March 31, 2020)

The Provisions for Registration of Drug Products (NMPA Order #27, hereinafter referred to as “PRDP”) has been issued by the State Administration for Market Regulation (SAMR) and will come into effect on July 1, 2020. In order to implement the new PRDP and ensure a smooth transition to it, NMPA issued an announcement over related matters on March 31, 2020. The following is a summary of the information contained within the PRDP.

Full implementation of the MAH System

The new PRDP defines the responsibilities of manufacturers and drug R&D institutions. The responsibilities include establishing the drug quality system; facilitating full life cycle regulation of drug products; conducting post marketing research; and undertaking safety, efficacy and quality responsibilities of marketed products.

Optimization of drug evaluation and approval workflow

Clinical trial application

A clinical trial application will be considered approved after 60 working days if the applicant does not receive a rejection or an inquiry for clarification from the Center for Drug Evaluation (CDE).

Marketing authorization application

Drug approved for marketing shall be granted with a drug registration certificate and attachments. There are 3 approaches to apply for drug marketing authorization:

The drug marketing registration shall be submitted after completing CMC activities, pharmacology, toxicology, clinical trial studies, and determination of the quality standards and validation package/studies for the commercial-scale manufacturing process. The standard review time for a new drug application is 200 working days, while 130 working days will be granted for priority review and 70 working days for the priority review of overseas marketed drugs for rare diseases in urgent clinical need.
For generic drugs, in-vitro diagnostic reagents and other eligible circumstances, upon assessment, considering drug clinical trials are not needed, or cannot be carried out and conditions for waiving drug clinical trials are met, the applicant may directly apply for drug marketing authorization.
Non-prescription drugs can be directly submitted via the marketing authorization application route.

Four accelerated registration programs

To encourage the R&D and innovation of drugs, based on the actual needs for development by the pharmaceutical industry and for clinical treatment in China, the new PRDP introduced four programs with clear review timelines to make such drugs available as rapidly as possible. These programs are similar to those used by other international regulatory agencies. The four programs are as follows:

Breakthrough therapeutics
Conditional approval
Priority review
Special review

The PRDP outlines the scope, specific requirements, procedures, and support policies for each program. Drugs for urgent medical needs or that are in short supply, pediatric drugs, drugs for rare diseases, drugs for major infectious diseases, innovative vaccines and vaccines urgently needed for disease prevention and control shall be included in the scope of accelerated review.

Registration inspection and testing

Drug registration inspection refers to the development site inspection and manufacturing site inspection. The inspection shall be conducted based on risk instead of conducting inspections solely based on performing the inspections after a drug registration application is received.

The registration testing includes specification verification and sample testing. The testing request can be proposed to the National Institutes of Food and Drug Control (NIFDC) by the applicant after the related CMC studies, determination of product specifications, and commercial-scale manufacturing process validation has been completed. Otherwise, testing will be initiated by the CDE within 40 working days as of the drug registration application date of acceptance.

After the new PRDP comes into effect, dossier review, registration inspection and registration testing shall be carried out simultaneously within the 200-day registration review timeline instead of conducted in sequence.

Bundling review

The separate review of excipients and Container Closure Systems (CCS) will change to a bundling review process that is associated with the drug registration application. The new regulation emphasizes that it is the MAH who should take the main responsibility for management of excipients and CCS. In the interim, the MAH should ensure or define in the quality agreement that these excipients and CCS shall support a potentially extended inspection. Otherwise, the MAH may suffer from the risk of delay or failure of marketing authorization.

Changes during clinical trials and post-marketing

For changes to clinical protocols or drugs during the clinical trial period, where, upon assessment, the sponsor considers that subject safety is not affected, the changes may be directly implemented and reported in the Development Safety Update Report (DSUR). Where subject safety risks may be increased, a supplementary application shall be filed. Post-marketing changes to drugs shall be managed using a classification system based on risks to and extent of their impact on the safety, efficacy, and quality controllability of the drugs. Thus, post-marketing changes are classified into three categories and depending on priority of importance, changes can be implemented upon approval, after reporting to Provincial Medical Products Administration (PMPA) or as needed. The latter shall be reported in the Annual Report. Supporting regulations with further details will be released soon.

Provisions for the Control of Drug Manufacture

Provisions for Control of Drug Manufacture (2020 Order No. 28) (March 30, 2020)
Announcement of the National Medical Products Administration on Implementing the new Provisions for Control of Drug Manufacture (March 31, 2020)

The 2020 amendment of the “Provisions for Control of Drug Manufacture” (hereinafter referred to as “PCDM”) has been issued by the SAMR and will be implemented as of July 1, 2020. In order to further improve the supervision of drug production, the NMPA issued on March 31, 2020 an announcement on matters relating to the implementation of the PCDM. The following is a summary of the information contained within the PCDM.

Manufacture authorization

Where the pharmaceutical marketing authorization holder (hereinafter referred to as the “holder” or “MAH”) with the Pharmaceutical Manufacture License, contract manufactures drug formulations, it shall be handled in accordance with the provisions of Article 16. Where the holder contracts the production of drug formulation, it shall sign a contract manufacture agreement and quality agreement with a qualified pharmaceutical manufacturer, and the content of the contract manufacture agreement and quality agreement shall comply with the relevant laws and regulations. In addition, overseas applicants shall designate a domestic enterprise with a business entity within the territory of China who shall perform the responsibility of the MAH and establish a sound quality assurance team and drug quality system.

Production management

The new PCDM require that drugs should have a two-step release process before going on the market. The drug manufacturer shall ensure that the drug meets standards, and the required documents shall be signed by the Quality Person (QP) before release. Subsequently, the drug shall be released to the market after the MAH reviews the testing results and release documents of the drug, and the QP of the MAH signs the release documents.

Supervision and inspection

In the instance where the MAHs and contracted manufacturers are not in the same province, the contract manufacturer shall go through the on-site inspection of the drug production plant and production line by the PMPA and cooperate with the holder to provide relevant application materials. The PMPA, at the holder’s location, shall review the application materials submitted by the holder and, in conjunction with the contract manufacturer’s on-site inspection conclusions issued by the PMPA, to make a decision on the holder production address or production scope changes. Through the supervision and inspection information in the drug safety credit files (a database established by the state information center), the PMPAs may base their decisions of initiating inspections based on relevant inspection results and carry out joint inspections if necessary.

The new PCDM terminates the current requirement that drug administration authorities shall assess drug manufacture enterprises, and issue GMP certificates. Instead, the new regulation requires that drug manufacturing enterprises establish and improve the quality management systems of manufacture, and ensure that the process of manufacturing drugs always meets all legal requirements. In other words, a stricter form of supervision is implemented.

Legal Liability

Accountability will be strengthened with well-defined penalties. Cracking down on violations, including data violations, will be emphasized.

Inspection on Marketing Authorization Holder

The collection period for comments on these draft documents ended on March 18, 2020. These documents are applicable to both domestic and foreign MAHs for inspection of their non-clinical research, clinical research, production, distribution, post-marketing research of drug products, as well as their reporting, handling and surveillance of adverse drug reactions. Such inspections have two forms, field inspection and written inspection.

Both the MAH and the entrusted enterprise, as the main party and extended party of inspection, shall establish sound drug quality assurance systems, which can be effectively connected and managed by qualified personnel. For drug manufacturing, it is necessary to establish a classified management system in compliance with the regulatory requirements to comprehensively evaluate and verify the impact of changes and deviations on the safety, efficacy, and quality of the drug. Establishing drug manufacturing risk management procedures and implementing risk assessments on a regular basis is paramount to ensure product quality.

Quality Agreement

NMPA Solicited Public Opinions on the Guidelines for Quality Control Agreement on Drug Contract Manufacture and the Reference Template for Quality Agreement on Drug Contract Manufacture (Draft for Comments) (March 2, 2020)

The collection period for comments on this draft document ended on March 18, 2020. The guidelines are applicable to the MAH and the entrusted party. The guidelines outline the requirement for the MAH and entrusted party to sign a quality agreement for entrusted production, so as to clarify the quality responsibilities of the MAH and the entrusted party.

According to the NMPA, the documents are drawn to ensure MAHs are fulfilling their quality and safety assurance obligations through signing pharmaceutical production quality control agreements with their pharmaceutical contract manufacturers in accordance with all provisions of drug Good Manufacturing Practices (GMP) and relevant legal requirements for pharmaceutical manufacturing full process compliance. These documents are for reference by MAHs and their contract manufactures when they set up such agreements.

Polysorbate 80 (Chinese Pharmacopoeia, Edition 2020)

On March 4, 2020, the Chinese Pharmacopoeia Commission (ChPC) issued the Announcement on the Draft National Standard for Pharmaceutical Excipients of Polysorbate 80 (II) [formerly known as Polysorbate 80 (for Injection)]. Polysorbate 80 for injection is no longer specified. Each enterprise can choose to use Polysorbate 80 (II) or Polysorbate 80 based on production data.

Good Drug Record and Data Management Practices

The Comprehensive Affairs Department of NMPA Solicited Public Opinions on the Good Drug Record and Data Management Practice (Draft for Comments)(February 28, 2020)

On February 28, 2020, NMPA publicly solicited opinions from the Drug Record and Data Management Practice (Draft for Comments) (hereinafter referred to as the “Practice”). This Practice was created for the purpose of standardizing the management of records and data. It is applicable to the R & D, production, distribution, and use of drugs, and these records and data are legally required to be provided to drug administration.

ICH

These announcements serve to promote the NMPA’s decision to have technical standards for drug registration to be in alignment with international standards. NMPA has decided to apply 11 International Conference on Harmonization Technical Guidelines for Human Drug Registration (ICH), including Q2 (R1): Validation of Analytical Methods: Text and Methodology. In addition, it has been recommended to adopt 4 International Conference on Harmonization Technical Guidelines for Human Drug Registration (ICH), including Q8 (R2): Pharmaceutical Development. For the applicable guidelines, companies are required to conduct research in accordance with the ICH guidelines as soon as possible based on current pharmaceutical research technical requirements. These guidelines are still in the process of soliciting opinions. After these formal announcements, pharmaceutical research that begins 6 months after the date of publication of these announcements (subject to the time point of the trial record) should be conducted in accordance with the ICH guidelines.

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