监管机构资讯

WuXi Biologics Regulatory Updates

Quarter 3 – 2019

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.

U.S. FDA

Compliance Program Guidance Manual (CPGM) 7346.832 Pre-Approval Inspections/Investigations

The U.S. FDA’s Compliance Programs provide instructions to FDA personnel for conducting activities to evaluate industry compliance with the Federal Food, Drug and Cosmetic (FD&C) Act and other laws administered by the U.S. FDA. Compliance program 7346.832 (Pre-approval Inspections/Investigations) was revised to add instructions for potential official action indicated (pOAI) reporting responsibilities and to align with the Center for Drug Evaluation and Research (CDER) and the Office of Regulatory Affairs (ORA) agreement Integration of FDA Facility Evaluation and Inspection Program for Human Drugs: A Concept of Operations

Questions and Answers on Current Good Manufacturing Practices – Laboratory Controls (Updated: August 2019)

The Q&A section was updated. For the agency’s responses, click the link above to visit the FDA webpage.

Drugs Intended for Human Use That Are Improperly Listed Due to Lack of Annual Certification or Identification of a Manufacturing Establishment Not Duly Registered With the Food and Drug Administration; Action Dates (Posted: August 2019)

FDA will inactivate drug listing records that are improperly listed in accordance with FDA requirements, 21 CFR 207

Providing Regulatory Submissions in Electronic Format – Certain Human Pharmaceutical Product Applications and Related Submissions Using the eCTD Specifications Guidance for Industry (Draft) (Updated: July 2019)

This version of the draft guidance added the exemptions and waivers from complying with electronic Common Technical Document (eCTD) requirements. Other key points include:

• NDAs, ANDAs and BLAs are mandatory for eCTD submissions starting from May 5^th, 2017. Commercial INDs, DMFs (other than Type III) are mandatory for eCTD submissions starting from May 5^th, 2018.

• All type III DMF submissions are exempted, while the FDA still encourages applicants to submit in an alternative electronic format (e.g. PDF files following the CTD structure).

TRG Rapid Inquiry Program (TRIP) (June 2019)

Biological Product Deviations (July 2019)

Rare Pediatric Disease Pediatric Priority Review Vouchers; Draft Guidance for Industry (July 2019)

Pathology Peer Review in Nonclinical Toxicology Studies: Questions and Answers (July 2019)

Modernizing Pharmaceutical Quality Systems; Studying Quality Metrics and Quality Culture; Quality Metrics Feedback Program; Reopening of Submission Period (August 2019)

Requesting a Pre-Assigned Application Number (August 2019)

Prescription Drug User Fee Rates for Fiscal Year 2020 (August 2019)

Biosimilar User Fee Rates for Fiscal Year 2020 (August 2019)

Osteoporosis: Nonclinical Evaluation of Drugs Intended for Treatment Guidance for Industry (August 2019)

The Food and Drug Administration Report on the Performance of Drugs and Biologics Firms in Conducting Postmarketing Requirements and Commitments (Fiscal Year 2018 August 2019)

Oncology Therapeutic Radiopharmaceuticals: Nonclinical Studies and Labeling Recommendations Guidance for Industry (August 2019)

SOPP 8119: Use of Email for Regulatory Communications (August 2019)

SOPP 8401.2: Administrative Processing of BLA and NDA Supplements (August 2019)

SOPP 8415: Procedures for Developing Postmarketing Requirements and Commitments (August 2019)

SOPP 8408.3: Lot Release Activities for Licensed Biological Products (September 2019)

Interacting with the FDA on Complex Innovative Trial Designs for Drugs and Biological Products (Draft Guidance for Industry) (September 2019)

EMA

European Medicines Agency Procedural Advice for Users of the Centralised Procedure for Similar Biological Medicinal Product Applications (Updated: August 2019)

This guidance document addresses a number of questions that users of the centralised procedure may have. This revision removes guidelines referred that are related to the deletion of EudraLex – Volume 2A – Procedures for marketing authorisation, Chapter 4 – Centralised Procedure.

Volume 2A: Procedures for Marketing Authorisation – Chapter 1: Marketing Authorisation (Posted: July 2019)

This revised chapter provides general principles of the Union pharmaceutical legislation, including introduction and procedures of marketing authorization (MA), application types, data exclusivity and market protection, variations and extensions, amongst other topics.

Volume 2C: Guideline on the Categorisation of Extension Applications (EA) versus Variations Applications (V) (Posted: July 2019)

This revised guideline proposed a harmonized and agreed interpretation of extension applications (EA) versus variations regarding the Variation Regulation (EC) No 1234/2008. Other key points include:

• Relevant terms and principles, including pharmaceutical form and strength, are defined and agreed interpretations are established within this document.

• Examples are given to define an EA or variation in terms of changes on pharmaceutical form, strength, presentation, and route of administration.

Ph. Eur. 10th Edition – Now Available (Posted: September 2019)

The 10th Edition of the European Pharmacopoeia, which is applicable in 38 European countries from 1st January 2020 and is used worldwide, is now available in both print and electronic versions. The 10th Edition consists of three initial volumes (10.0), and will be updated with eight periodic supplements over the following three years (10.1 to 10.8).

Questions and Answers on the Exemption from Batch Controls Carried Out on ATMPs Imported into the European Union from a Third Country (July 2019)

Human Medicines Highlights (July 2019)

Detailed Guidance on the Electronic Submission of Information on Medicinal Products for Human Use by Marketing Authorisation Holders to the European Medicines Agency in Accordance with Article 57(2), Second Subparagraph of Regulation (EC) No 726/2004 (July 2019)

EMA Takes Note of the European Ombudsman’s Decision on Pre-submission Activities (July 2019)

Work Programme of the HMA/EMA Task Force on Availability of Authorised Medicines for Human and Veterinary Use (July 2019)

Safety Features for Medicinal Products for Human Use, Questions and Answers, Version 15 (July 2019)

Information on Batch Testing of Medicinal Products in the Context of Withdrawal of the United Kingdom from the Union (July 2019)

The Ph. Eur. Revises Its General Chapter on UV-Vis Absorption Spectrophotometry (July 2019)

Ph. Eur. Commission Consults Stakeholders on the General Chapter on Multivariate Statistical Process Control (MSPC) (5.28) (July 2019)

Dosage Form Monographs for Public Consultation (July 2019)

Human Medicines Highlights (August 2019)

SME Office Newsletter – Issue 47 (August 2019)

Human Medicines Highlights (September 2019)

Cross-Agency Collaboration

EMA & FDA

Questions and Answers on the Impact of Mutual Recognition Agreement between the European Union and the United States as of 11 July 2019 (Posted: July 2019)

Starting July 11^th 2019, the US and EU have fully implemented the mutual recognition agreement (MRA) for inspections of manufacturing sites for certain human medicines in their respective territories. The current operational scope of the agreement includes only human medicinal products, with the exclusion of vaccines and plasma-derived products.

Meeting Report: Workshop with Stakeholders on Support to Quality Development in Early Access Approaches (i.e. PRIME, Breakthrough Therapies) (Posted: July 2019)

• The EMA and the FDA launched the Priority Medicines (PRIME) and Breakthrough Therapy schemes, respectively, to strengthen their support for the development of medicines that address unmet medical needs.

• This report contains the discussion and opinions from EMA and FDA regulators on scope of early access approaches, process validation, control strategy, GMP-compliance, comparability, stability, regulatory tools, amongst other topics.

EMA/FDA Analysis Shows High Degree of Alignment in Marketing Application Decisions between EU and US (August 2019)

FDA, TGA and Health Canada

FDA Takes First Action under New International Collaboration with Australia and Canada Designed to Provide a Framework for Concurrent Review of Cancer Therapies, Approving Treatment for Patients with Endometrial Carcinoma (Posted: September 2019)

FDA is announcing Project Orbis, an initiative of the FDA Oncology Center of Excellence (OCE). It provides a framework for concurrent submission and review of oncology drugs among its international partners. Under this project, the FDA, the Australian Therapeutic Goods Administration (TGA) and Health Canada collaboratively reviewed applications for two oncology drugs, allowing for simultaneous decisions in all three countries.

TGA

GMP Clearance Applications Using Health Canada Evidence : Liaison Fee Required for All Compliance Verifications (CV) Using Inspection Exit Notice (Posted: August 2019)

Key points for this notice include:

• TGA and Health Canada (HC) have reached the current mutual recognition agreement (MRA), in which Australian sponsors who source medicines from a manufacturing site located in Canada, can use a HC issued ‘Inspection Exit Notice’ in lieu of a GMP Certificate to support the GMP Clearance application.

• However, when HC inspect outside their borders, the MRA no longer applies. TGA will liaise with HC to obtain further evidence related to the inspection as the evidence for GMP Clearance Compliance Verification (CV) pathway. The additional liaison fee will be applicable to all CV clearance applications submitted using HC ‘exit notices’, including all applications currently in progress.

Health Canada

Guidance Document: Management of Drug Submissions and Applications (Effective: July 2019)

This guidance was updated to reflect Health Canada’s current procedures of drug submissions and applications for Clinical Trial Application (CTA), Clinical Trial Application-Amendment (CTA-A), New Drug Submission (NDS), and Supplement to a New Drug Submission (SNDS), amongst other topics.

Notice – Mandatory Use of the Electronic Common Technical Document (eCTD) Format (Posted: September 2019)

The purpose of this updated notice is to communicate Health Canada’s intention to expand the scope of regulatory activity types where filing in eCTD format is a mandatory requirement. Regulatory activities, such as NDS and SNDS, are required in eCTD format. Regulatory activities such as Pre-CTA Consultation Meeting, CTA, and CTA-A, are recommended in eCTD format, but not mandatory.

Draft Guidance Document, Canadian Module 1 Technical Implementation Guide for the Electronic Common Technical Document (eCTD) v4.0 Format (July 2019)

Notice: Health Canada and United States Food and Drug Administration Joint Public Consultation on ICH Guidelines – Update (August 2019)

WHO

Quality Management System Requirements for National Inspectorates (Draft) (Posted: July 2019)

Key points for these draft documents include:

• This document, drafted for comments, describes the quality management system (QMS) requirements for the inspection within national regulatory authorities (NRA) or other state structures. WHO Guideline on the Implementation of Quality Management Systems for National Regulatory Authorities (draft) should be considered during the operation.

• This document also outlines the QMS requirements for inspectorates, competent for the oversight of GXP operations.

Policy on Remaining Shelf Life of Medical Products upon Delivery (Draft) (Posted: July 2019)

Key points for these draft documents include:

• This document, drafted for comments, presents policy on remaining shelf life of medical products upon delivery, and should be implemented by all stakeholders in supply chain of medical products.

• The principles include considerations on policy of national government, labeling, distribution, and risk assessment, which should be applied to all medical products, including finished pharmaceutical products, medical devices, vaccines and in vitro diagnostics.

Guideline for Assuring the Quality, Safety, and Efficacy of DNA Vaccines (July 2019)

PIC/S

Annex 2B Manufacture of Biological Medicinal Substances and Products for Human Use (Draft) (Posted: September 2019)

This annex provides guidance on the full range of medicinal products defined as biological with the exception of Advanced Therapy Medicinal Products (ATMPs). It is divided into two main parts:

• Part A contains supplementary guidance on the manufacture of biological active substances and medicinal products, from control over seed lots and cell banks through to finishing activities and testing.

• Part B contains further guidance on selected types of biological active substances and medicinal products (e.g. vaccines, recombinant products, monoclonal antibodies products, amongst other products.)

Annex 2A Manufacture of Advanced Therapy Medicinal Products for Human Use (Draft) (September 2019)

ICH

Final Minutes, ICH Assembly, 5 – 6 June 2019, Amsterdam, the Netherlands August 2019

PMDA

JP Drafts for Public Comments (September 2019)

• New General Test: 05 Size Exclusion Chromatography

• Revised General Test: 66 Elemental Impurities