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 that are either in draft or final status by agency. 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:

• FDA (U.S. Food & Drug Administration)
• EU (European Union) / EMA (European Medicines Agency) / EC (European Commission) 
• TGA (Therapeutic Goods Administration) 
• Health Canada 
• WHO (World Health Organization) 
• MHRA (Medicines and Healthcare products Regulatory Agency) 
• PMDA (Pharmaceuticals and Medical Devices Agency) 
• ICH (International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use)
• EDQM (European Directorate for the Quality of Medicines & HealthCare)
• PIC/S (Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation Scheme)
• Health Products Regulatory Authority (HPRA)
• National Medical Products Administration (NMPA)

FDA (U.S. Food and Drug Administration)

Manufacturing Changes and Comparability for Human Cellular and Gene Therapy Products

July 13, 2023

This draft guidance is being distributed for comment purposes only, comments should be submitted by September 12, 2023. This draft guidance reflects CBER’s thoughts on reporting and comparability studies of manufacturing changes for both investigational and licensed human cellular therapy or gene therapy (CGT) products.  

• The overall consideration for manufacturing changes management is described in this guidance including a systematic approach to risk management, the evaluation of necessity for stability and or/delivery device compatibility studies and the scenarios where additional non-clinical and clinical studies are required.
• The regulatory reporting pathway for manufacturing changes that happen during IND stage and BLA stage is introduced. It is recommended that the sponsor should submit the changes through an amendment. The changes that may lead to a new IND submission are also listed and examples are given in this guidance.
• Points to be considered/recommendations for comparability assessment and reporting are introduced. The sponsor is encouraged to conduct a detailed risk assessment per ICH Q9 Guidance for Industry: Q9 Quality Risk Management, June 2006 and seek FDA’s feedback prior to initiating the comparability study. Details of principles for the study design, results report, and how to submit in the filing can be found in this guidance.
• Special considerations for tissue-engineered medical products (TEMPs) are described.

The full document can be found at the following address:

Manufacturing Changes and Comparability for Human Cellular and Gene Therapy Products

E&C Republicans Press FDA Over Inadequate Inspection of Drug Manufacturing in India and China

July 18, 2023

To address shortages of critical drugs, the FDA allows the temporary import of unapproved drugs from India and China, which makes the effective foreign inspection programs in those countries critical. Given that approximately 32 percent of generic drugs and 45 percent of active pharmaceutical ingredients are from these two countries, the Republicans are worried that the United States is overly reliant on sourcing from foreign manufacturers with a demonstrated pattern of repeatedly violating FDA safety regulations. Three top Republicans on the House Energy and Commerce (E&C) Committee, sent a letter to Food and Drug Administration (FDA) Commissioner Robert Califf on July 18 raising questions regarding the FDA’s insufficient foreign drug inspections conducted in India and China. The letter raised 22 questions to the FDA, including general inspection questions, questions of inspections conducted in India, and inspection challenges in China posed by the China’s National Security Law.

As early as November 2022, the FDA was aware of significant, repeated quality control failures at Intas Pharmaceuticals’ Ahmedabad, India manufacturing facility. Intas voluntarily stopped manufacturing at its Ahmedabad plant in response to quality control failures on June 5, 2023 without the knowledge of the FDA which quickly led to a shortage of critical cancer drugs in the United States.

The letter says ”China presents a more dangerous situation than India”. Especially as the FDA conducted only 40 inspections in China between fiscal years (FY) 2020 and 2022 compared to 131 inspections in FY 2019 alone. The letter notes that the FDA didn’t restart the in-person inspections in China till April 2023.

Lastly, the letter raised concerns regarding how China’s National Security Law might impact FDA inspections in China. The FDA is asked to provide a plan to launch pre-announced inspections in China. In addition, for Chinese companies that have received warning letters in the past 10 years, the FDA is asked to respond with a list of which of these facilities have been inspected in-person, inspected remotely or not inspected at all since the Warning Letters were issued. In this letter, it also requested that the FDA provide copies of all communications with the government of China from January 2020 to the present regarding in-person inspections.

The full document can be found in the following address:

E&C Republicans Press FDA Over Inadequate Inspection of Drug Manufacturing in India and China

CDER Collaborates with Global Regulators on Pharmaceutical Quality Assessments and Inspections

July 28, 2023

The FDA and the European Medicines Agency (EMA) recently completed the first collaborative assessment of a proposed post-approval change for a critical oncology biologic with the Japanese Pharmaceuticals and Medical Devices Agency (PMDA) serving as an observer. The work, in which FDA and EMA reviewed and approved a proposal to add new manufacturing and quality control sites, can help assure the supply of the medicine.

This collaboration is the first achievement in an international pilot program conducted as part of the International Coalition of Medicines Regulatory Authorities (ICMRA) Pharmaceutical Quality Knowledge Management System (PQKMS) effort to bring regulators together to enable better industry quality management to reliably supply critical medicines for patients in need.

Further regulatory collaboration in ICMRA, coupled with CDER’s on-going standards efforts in other international regulatory harmonization and information-sharing bodies, such as the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), can drive toward a single assessment outcome across regions. The CDER will continue to work with our international counterparts in the ICMRA and other international venues, on these and other issues, to advance pharmaceutical quality to benefit patients and consumers in the U.S. and worldwide.

The full document can be found at the following address:

CDER collaborates with global regulators on pharmaceutical quality assessments and inspections | FDA

5016.8 Rev. 1 Using Four-Part Harmony in Quality-Related Assessment Communications

Aug 25, 2023

This MAPP (Manual of Policies and Procedures) mainly describes how the Office of Pharmaceutical Quality (OPQ) product quality assessors can follow the principles of Four-Part Harmony to enhance the clarity of quality-related communications. It applies to quality-related communications that are sent to applicants during assessments across the product life cycle.

Four-Part Harmony recommends that all quality-related communications address the following four essential components:

1. What was provided? Acknowledge the information submitted by the applicant and provide a reference to relevant modules, sections, page numbers, or tables unless the part of the application being referenced is obvious from the description (e.g., “your proposed drug product specification”).
2. What is the issue? Identify missing information or information that the FDA considers inadequate.
3. What is needed? Request additional information or recommend an alternative approach to address the issue.
4. Why is it needed? State the basis for the information request or deficiency, and include:
   • The impact of the issue on the overall regulatory decision.
   • References to all or part of applicable regulations, statutes, guidances, and/or FDA-recognized consensus standards, as appropriate.

The full document can be found at the following address:

5016.8 Rev. 1 Using Four-Part Harmony in Quality-Related Assessment Communications (fda.gov)

FDA: Application of Human Factors Engineering Principles for Combination Products: Questions and Answers

Sep 07 2023

This document contains questions and answers for industry and FDA staff on the application of human factors engineering (HFE) principles to the development of combination products as defined under 21 CFR part 3. This guidance finalizes the February 2016 draft version entitled Human Factors Studies and Related Clinical Study Considerations in Combination Product Design and Development. This guidance provides information in a question-and-answer format and clarifies how the unique aspects of a combination product influence the considerations within the HFE process.

HFE: The application of knowledge about human behavior, abilities, limitations, and other characteristics of medical device users to the design of medical devices including mechanical and software driven user interfaces, systems, tasks, user documentation, and user training to enhance and demonstrate safe and effective use. Human factors engineering and usability engineering can be considered to be synonymous terms.

The full document can be found at the following address:

Application of Human Factors Engineering Principles for Combination Products: Questions and Answers Guidance for Industry and FDA Staff

Other FDA Drug Development and Quality Guideline Updates

• General Instructions for Completing the Biological Product Deviation Report (BPDR) – Form FDA 3486 (Updated) 2023-07-13
• Formal Meetings Between the FDA and Sponsors or Applicants of BsUFA Products; Draft Guidance for Industry 2023-08-10
• Classification Categories for Certain Supplements Under BsUFA III; Draft Guidance for Industry 2023-08-10
• FDA Launches Pilot Program to Help Further Accelerate Development of Rare Disease Therapies | FDA 2023-09-29
• Instructions for Using the eBPDR System | FDA 2023-09-30
• General Instructions for Completing the Biological Product Deviation Report (BPDR) – Form FDA 3486 | FDA 2023-09-30
• Center for Drug Evaluation and Research’s Program for the Recognition of Voluntary Consensus Standards Related to Pharmaceutical Quality 2023-07-26
• Enhanced Drug Distribution Security Requirements Under Section 582(g)(1) of the Federal Food, Drug, and Cosmetic Act–Compliance Policies  2023-08-25
• Understanding FDA Inspections and Data 2023-08-10
• 2023 NanoDay Symposium: Continuous Manufacturing of Nanomaterials 2023-08-10
• Assessing User Fees Under the Biosimilar User Fee Amendments Guidance for Industry 2023-07-27
• Labeling for Biosimilar and Interchangeable Biosimilar Products 2023-09-15
• Biosimilarity and Interchangeability: Additional Draft Q&As on Biosimilar Development and the BPCI Act 2023-09-15
• Formal Meetings Between the FDA and Sponsors or Applicants of PDUFA Products 2023-09-21
• Alternative Tools: Assessing Drug Manufacturing Facilities Identified in Pending Applications (fda.gov) 2023-09-21

Federal Register Updates

• Chemistry, Manufacturing, and Controls Development and Readiness Pilot (CDRP) Program 2023-09-11
• Federal Register: New Animal Drugs; Approval of New Animal Drug Applications; Withdrawal of Approval of New Animal Drug Applications, Change of Sponsor, Change of Sponsor Address 2023-08-16
• Federal Register : Manufacturing Changes and Comparability for Human Cellular and Gene Therapy Products; Draft Guidance for Industry; Extension of the Comment Period 2023-08-24

USP Updates

• <660>Containers-Glass (posted 25-Aug-2023; official 01-Oct-2023) 2023-08-25
• <661.2>Plastic Packaging Systems for Pharmaceutical Use (posted 25-Aug-2023; official 01-Dec-2025) 2023-08-25
• <621> Chromatography 2023-08-25
• Nicardipine Hydrochloride Injection Notice and Monograph (uspnf.com) 2023-09-19
• <621> Chromatography Notice and Chapter (posted 29-Sep-2023; official 01-Oct-2023) 2023-09-29

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

Reflection paper on the use of Artificial Intelligence (AI) in the medicinal product lifecycle

July 19, 2023

The EMA has published a draft reflection paper outlining 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, which is now open for public consultation, reflects on principles relevant to the application of AI and machine learning (ML) at any step of a medicines’ lifecycle, from drug discovery to the post-authorization setting. EMA invites all interested partners and stakeholders to engage in a dialogue on AI in relation to medicines by providing their feedback by 31 December 2023.

The reflection paper is part of the joint HMA-EMA Big Data Steering Group (BDSG) initiatives to develop the European Medicines Regulatory Network’s capability in data-driven regulation. It has been developed in liaison between the BDSG, EMA’s Committee for Medicinal Products for Human Use (CHMP) and its Committee for Veterinary Medicinal Products (CVMP).

“The use of artificial intelligence is rapidly developing in society and as regulators we see more and more applications in the field of medicines. AI brings exciting opportunities to generate new insights and improve processes. To embrace them fully, we will need to be prepared for the regulatory challenges presented by this quickly evolving ecosystem” said Jesper Kjær, Director of the Data Analytics Centre at the Danish Medicines Agency and co-chair of the BDSG. “With this paper, we are opening a dialogue with developers, academics, and other regulators, to discuss ways forward, ensuring that the full potential of these innovations can be realized for the benefit of patient’ and animal health” said Peter Arlett, EMA’s Head of Data Analytics and Methods, co-chair of the BDSG.

The Draft Reflection Paper considers use of AI/ML at different stages along the product lifecycle and sets out principles and an indication of risk of applying AI/ML at each such stage:

• Drug discovery — the EMA acknowledges that the use of AI/ML in drug discovery may be low risk from a regulatory perspective, “as the risk of non-optimal performance often mainly affects the sponsor.”  However, if results contribute to the total body of evidence presented for regulatory review, then the regulatory risk increases.
• Non-clinical development — AI/ML (e.g, “AI/ML modelling approaches to replace, reduce, and refine the use of animals”) should follow Good Laboratory Practice (“GLP”), where applicable.  Applicants should consider Application of GLP Principles to Computerised Systems and GLP Data Integrity and their SOPs should cover AI/ML.
• Clinical trials— AI/ML models (for example, that support selection of patients based on disease characteristics or clinical parameters) must comply with ICH GCP.  The regulatory risk for use of AI/ML increases from early stage to pivotal clinical trials.  Where models are generated for clinical trials, it is likely they will be considered part of the clinical trial data or trial protocol dossier and the models must be made available for regulators to assess at the time of marketing authorisation or clinical trial application. Where data collected/generated with AI/ML may impact the regulatory assessment of a medicine, the EMA recommends early regulatory interaction.
• Precision medicine— the EMA considers the use of AI/ML in individualizing treatment (e.g., patient selection, dosing, de novo design of product variants) as high-risk from a medicines regulation perspective. The EMA recommends “special care in defining what constitutes a change in posology (requiring a regulatory evaluation before implementation), to provide guidance that the prescribers can critically apprehend, and include fall-back treatment strategies in cases of technical failure.”
• Product information— AI/ML might be used to draft, compile, translate or review information documents.  Recognizing the risk of hallucinations (which may be plausible but erroneous output) by generative language models, the EMA expects use of such technologies only under “close human supervision.”
• Manufacturing— use of AI/ML in drug manufacturing is expected to increase in the future and the EMA notes that this must comply with relevant quality management principles.
• Post-authorization phase— AI/ML is likely to have potential to support post-authorization safety and efficacy studies in human medicines, plus pharmacovigilance activities, such as adverse event report management and signal detection.  The MAH must “validate, monitor and document model performance and include AI/ML operations in the pharmacovigilance system, to mitigate risks related to all algorithms and models used.”

The reflection paper highlights that a human-centric approach should guide all development and deployment of AI and ML. The use of AI in the medicinal product lifecycle should always occur in compliance with the existing legal requirements, consider ethics and ensure due respect of fundamental rights.

If an AI/ML system is used in the context of medicines’ development, evaluation, or monitoring, and is expected to impact on the benefit-risk balance of a medicine, EMA advises developers to seek early regulatory support, e.g. through qualification of innovative development methods (for human medicines) or scientific advice.

All interested stakeholders are invited to comment on the draft reflection paper and to identify opportunities and risks of AI in the field of medicines. The public consultation is open until 31 December 2023 and the topic will be further discussed during a joint HMA/EMA workshop scheduled for 20-21 November 2023. The feedback from stakeholders will be analyzed and considered for the finalization of the reflection paper and future development of guidance as relevant.

The full document can be found at the following address:

Draft Reflection paper on the use of Artificial Intelligence (AI) in the medicinal product lifecycle

Other EMA Updates

• Guidance on Parallel EMA/HTA body (HTAb) Scientific Advice for the Interim Period 2023-07-03
• Questions and Answers on the ‘OPEN’ Framework 2023-07-03
• Questions and answers for marketing authorisation holders/applicants on the CHMP Opinion for the Article 5(3) of Regulation (EC) No 726/2004 referral on nitrosamine impurities in human medicinal products 2023-07-07
• Guidance on Good Manufacturing Practice and Good Distribution Practice: Questions and Answers (Updated) 2023-07-13
• Concept paper on the revision of the Guideline on Radiopharmaceuticals Based on Monoclonal Antibodies 2023-07-21
• Important update on N-nitrosamine impurities in substances covered by CEPs 2023-07-21
• N-nitrosamine Impurities in Ph. Eur. Monographs: Update on Approach 2023-07-24
• CEP 2.0: The CEP Letter of Access is Ready for Use! 2023-07-24
• Guidance on Good Manufacturing Practice and Good Distribution Practice: Questions and Answers (Updated) 2023-07-25
• Nitrosamines EMEA-H-A5(3)-1490 – Questions and Answers for Marketing Authorisation Holders/Applicants on the CHMP Opinion for the Article 5(3) of Regulation (EC) No 726/2004 Referral on Nitrosamine Impurities in Human Medicinal Products (Updated) 2023-07-28
• Webinar on Regulatory Procedure Management for Product Lifecycle Management 1st roll-out on IRIS | European Medicines Agency (europa.eu) 2023-08-16
• Frequently Asked Questions about Parallel Distribution (Updated) 2023-09-04
• Guideline on quality data requirements for applications for biological veterinary medicinal products intended for limited markets 2023-09-15
• Questions and Answers for Biological Medicinal Products 2023-09-18
• Vaccine Monitoring Platform | European Medicines Agency (europa.eu) 2023-09-26
• Pre-authorisation guidance | European Medicines Agency (europa.eu) 2023-09-29
• Validating Analytical Procedures for Determining Nitrosamines in Pharmaceuticals: European OMCLs Participate in Collaborative Study with International Regulatory Agencies 2023-09-08
• Ph. Eur. allows the use of recombinant factor C for control of bacterial endotoxins in water monographs 2023-09-13

TGA (Therapeutic Goods Administration)

TGA Updates

• New reporting requirements for medicine shortages | Therapeutic Goods Administration (TGA) 2023-08-17

Health Canada

Health Canada Updates

• Guidance on nitrosamine impurities in medications 2023-07-24
• Consultation: Draft guidance on the preparation of the product monograph in XML format – Canada.ca 2023-08-15

WHO (World Health Organization)

Impact of the WHO regulation and prequalification work; assessment outlines successes and opportunities for future work

Sep 28 2023

The WHO department of regulation and prequalification (RPQ) had built effective and efficient regulatory systems of WHO’s RPQ five-year plan (2019-2023) under the published independent impact assessment of WHO prequalification (PQ) in 2018.

After five years into the plan, an independent impact assessment of the RPQ department has been commissioned to inform future direction. The impact assessment has reflected four specific objectives which include 1) Generate qualitative and quantitative assessments of the value created by the RPQ department for its stakeholders with a focus on country impact in line with the RPQ’s four strategic priorities, 2) Create a 360-degree view of the value creation across all stakeholders, 3) Identify and analyze the main developments since the population of the previous assessment in 2018, 4) Develop insights and recommendations that enable both operational quick wins and long-term improvement.

The assessment addressed 4 key findings:

• The RPQ department has had significant impact in terms of enabling access to critical health products for the global population. Through the program and under the Emergency User Listing (EUL) and prequalification, 11 COVID-19 vaccines, 42 COVID-19 diagnostic products and 17 prequalified COVID-19 related medicines were approved to grant 170+ member states and territories with access to COVID-19 medical products.
• Investing in RPQ remains a sound investment since every $1 invested in running PQ contributes to savings of approximately $30-40 across medicines, vaccine, and diagnostics.
• The RPQ department has played a direct and significant role in strengthening global regulatory systems.
• The RPQ department has supported Member States in strengthening local production of medicines and other health technologies through the establishment of a number of supporting activities and the establishment of the “World Local Production Forum”.

The report also identified 3 key aspects of opportunities for improvement:

• Strengthen external and internal coordination & communication efforts
• Readjust strategic priorities or tracking metrics to drive more focused impact on areas of most need for the ecosystem
• Improve internal operational efficiency and team’s capacity

Specific recommendations are being addressed via immediate actions but also include a number of activities under debate with stakeholders in dedicated workshops and workplans to be implemented in 2024.

The full document can be found at the following address:

Impact of the WHO Regulation and Prequalification work; assessment outlines successes and opportunities for future work

MHRA 

International Recognition Procedure

Aug 30, 2023

From 1 January 2024, the EC Decision Reliance Procedure (ECDRP) will be replaced by the new International Recognition procedure (IRP). The Mutual Recognition/Decentralised Reliance Procedure (MRDCRP) will be incorporated under the umbrella of IRP.

ECDRP and MRDCRP submissions received before 1 January 2024 will be processed under the existing practices. For ECDRP applications, the Committee for Medicinal Products for Human Use (CHMP) positive opinion (but not necessarily the European Commission Decision) should be received before 31 December 2023.

IRP will be open to applicants that have already received an authorisation for the same product (having the same qualitative and quantitative composition, and the same pharmaceutical form, from applicants belonging to the same company or group of companies or which are ‘licensees’.) from one of MHRA’s specified Reference Regulators (includes TGA, Health Canada, SwissMedic, HAS, PMDA, FDA, EMA and Member State Competent Authorities).

IRP can be used for the following types of marketing authorisation applications (MAAs) (except for Traditional Herbal Registrations, Homoeopathic Registrations and Homeopathic National Rules Authorisations):

• Regulation 50: chemical and biological new active substances and known active substances.
• Regulation 51, 51A and 51B: generic applications
• Regulation 52, 52A and 52B: hybrid applications
• Regulation 53, 53A and 53B: biosimilar applications
• Regulation 55: new fixed combination product applications

IRP can also be used for post-authorisation procedures including line extensions, variations and renewals.

This guide also gives a specific introduction in Recognition A and B, Product lifecycle, How to apply, National requirements, Fees and Reference regulator documents.

The full document can be found at the following address:

International Recognition Procedure.

Other MHRA Updates

• Medicines: Marketing Authorisation Holders’ submission of Nitrosamine risk evaluation, risk assessment and confirmatory testing  2023-08-09
• Guidance Published on the New International Regulatory Recognition Routes for Medicines Approvals (Updated) 2023-09-04

PMDA (Pharmaceuticals and Medical Devices Agency)

GMP compliance inspection concerning drugs and quasi-drags of foreign manufacturers

Sep 26 2023

PMDA published a tentative translation of the GMP compliance inspection for the compliance of manufacturing control and quality control methods at the relevant manufacturing sites with Japanese GMP conducted by the PMDA.

The paper introduced the types of GMP compliance inspections that includes application-based inspections such as upon the application for new marketing approval or the application for partial changes of approval information, and inspections not based on applications such as normal inspections which are planned by the PMDA, based on the risk analysis.

Manufacturing sites subject to the inspection cover the following two cases:

1. “Inspections that are conducted upon the application for new marketing approval or the application for partial changes of approved information” and “inspections for confirmation of PACMP”.
2. “Periodic inspections that are conducted every five years following the obtainment of marketing approval”.

In addition, manufacturing sites for active substance of OTC drugs are not required to apply for GMP inspection.

Two examples of GMP inspection flow were addressed: onsite and desk-top. Relevant documents should be attached to the application for inspection.

The full document can be found at the following address:

GMP Compliance Inspection concerning Drugs and Quasi-drags of Foreign Manufacturers(Overview Guidance for Foreign Drugs Manufacturers) | Pharmaceuticals and Medical Devices Agency (pmda.go.jp)

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

No updates provided by WuXi Biologics for the time period

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

No updates provided by WuXi Biologics for the time period

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

Entry Into Force of Revised GMP Annex 1

Aug 25, 2023

The revised Annex 1 on “sterile manufacturing of the PIC/S GMP Guide entered into force on 25 August 2023 and has been published on https://picscheme.org/en/publications. Compared to Sep 2022 version of PIC/S, only Appendix 1 title capitals changed, 8.123 added a footnote, but the rest of content is not updated. The document map includes Scope, Principle, Pharmaceutical Quality System, Premises, Equipment, Utilities, Personnel, Production and specific technologies, Environmental and process monitoring, Quality control, amongst other topics. More information can be found at this link: PICS GMP Guide (Annexes) (picscheme.org)). This guideline entered into operation the same day as the revised Annex 1 of the EU GMP Guide, which is identical with PIC/S Annex 1 (with some minor differences). The revised Annex 1 is now applicable with the exception of paragraph 8.123. This paragraph has a later date of entry into force, which is on 25 August 2024. For the background to the revision of Annex 1, see https://picscheme.org/en/news?dateselect=2022.

The revised Annex 1 is an integral part of the PIC/S GMP Guide (PE 009-17), which has also been revised. The GMP Guide has 4 parts: Introduction, Part I, Part II, and Annexes. Annex 1 can be found under ‘PIC/S GMP Guide (PE 009-17) Annexes’.

The full document can be found at the following address:

Entry Into Force of Revised GMP Annex 1

Health Products Regulatory Authority (HPRA)

No updates provided by WuXi Biologics for the time period

National Medical Products Administration (NMPA)

Selected Regulatory Update Summaries

Guidelines for the Evaluation of Exterior Defects in Medicinal Glass Containers

Jul 13, 2023

The standard of the China Pharmaceutical Packaging Association, “Guidelines for the Evaluation of Exterior Defects of Pharmaceutical Glass Containers,” will be implemented from July 13, 2023.

The purpose of this guidance is to evaluate methods for assessing the visual defects of medicinal glass containers and their associated risks. It is intended to provide guidance for quality control in the production of medicinal glass containers and for incoming inspections at pharmaceutical plants. Medicinal glass container manufacturers and pharmaceutical plants should independently assess the relevant defects that may affect the quality of drug packaging and determine which defects need to be controlled.

This guidance categorizes the impact of cosmetic defects on medicinal glass containers into three types: critical defects, major defects, and minor defects. It also identifies and classifies common defects and special defects in terms of their causes and morphological characteristics. Several tables in this guide list the common defects of medicinal glass containers and provide specific information on the special cosmetic defects of various types of medicinal glass containers, including infusion bottles, molded injection vials, molded medicine bottles, controlled injection vials, controlled medicine bottles, glass ampoules, glass sleeves for pen-style injectors, and glass sleeves for prefilled syringes. Additionally, it provides a table of defect names in both Chinese and English, as well as illustrative diagrams of some defects to guide quality control in medicinal glass container manufacturing plants and incoming inspections at pharmaceutical factories.

The full document can be found at the following address:

https://www.cnppa.org/index.php/home/bz/show_2019/id/1707.html

Notice Regarding the Release of the Digital Factory Construction Plan

Jul 12, 2023

Summary: The notification includes two “digital factory construction plans” for chemical raw materials and injections, which can be used by pharmaceutical enterprises for digital transformation to identify and rectify deficiencies, serving as a systematic reference guide. The plans revolve around the key management aspects of chemical raw material and injection factories, proposing comprehensive solutions for constructing digital factories, aimed at assisting relevant enterprises in empowering their businesses through digitalization, optimizing operational management, improving quality control, and enhancing corporate performance. This plan represents the consensus of a group of industry experts, and enterprises still need to combine their own process foundation, management foundation, business characteristics, and various conditions in the construction of digital factories, adopt appropriate strategies and paths, and prioritize optimizing management processes.

Combining the characteristics of the injection production, the mainline of factory business management activities revolves around “production management, quality management, equipment/energy management, warehousing/supply chain management, and environmental/health/safety management (EHS).” According to the main components/functions at the equipment layer, control layer, business management layer, and operational management layer, the system architecture and management architecture of the injection digital factory are shown in the figure. The goal is to deeply integrate information technology with the entire process and all elements of injection production, implement lean management, and optimize and re-engineer business processes, achieve manufacturing system upgrades, and build a high-level, competitive injection digital factory.

The full document can be found at the following address:

http://www.cpema.org/index.php?m=content&c=index&a=show&catid=26&id=7717

Administrative Norms and Guidelines for the Implementation of Approval for High Pathogenic or Suspected High Pathogenic Microorganism Experimental Activities and Approval for the Transportation of High Pathogenic Microorganisms

Aug 31, 2023

Summary: The National Health Commission issued the “Administrative Measures and Guidelines for Approval of Experimental Activities with Highly Pathogenic or Suspected Highly Pathogenic Microorganisms and Approval of Transport of Highly Pathogenic Microorganisms” on August 31, 2023. The administrative measures include the “Administrative Measures for Approval of Experimental Activities with Highly Pathogenic or Suspected Highly Pathogenic Pathogenic Microorganisms” and the “Administrative Measures for Approval of Transport of Highly Pathogenic Pathogenic Microorganisms.” The guidelines include the “Guidelines for Approval of Experimental Activities with Highly Pathogenic or Suspected Highly Pathogenic Pathogenic Microorganisms conducted in Biosafety Level 4 laboratories or beyond the scope of laboratory authority,” the “Guidelines for Approval of Experimental Activities with Pathogenic Microorganisms not yet discovered or declared eradicated in China,” and the “Guidelines for Approval of Transport of Highly Pathogenic Pathogenic Microorganisms across provincial administrative regions or to foreign countries.”

The full document can be found at the following address:

https://zwfw.nhc.gov.cn/kzx/zcfg/gzbxbywswsyhdsp_242/202309/t20230901_2585.html

Technical Guide for Pollution Control Strategies in Aseptic Pharmaceutical Production (draft for soliciting opinions)

Sep 07, 2023

Summary: The Aseptic Drug Advanced Manufacturing Professional Committee of the China Association for Medical Equipment’s Engineering released the group standard “Control Strategy for Production Pollution of Aseptic Drugs (CCS) Technical Guidelines (Draft for Comments)” in Shanghai, seeking opinions from its member units and the industry. The deadline for comments is October 8, 2023. This guideline is applicable to the contamination control practices of microorganisms, pyrogens/endotoxins, and particles in the production of aseptic drugs, without involving the relevant requirements for cross-contamination. Non-aseptic drugs are not within the scope of this guideline, but they can serve as a reference for improving contamination control when necessary.

The guideline primarily introduces the formulation of pollution control strategies, clarifying that pollution control strategies are a set of planned control measures for microorganisms, heat origin/endotoxins, and particulates based on an understanding of products and processes. It comprehensively reflects the concepts and requirements of ICH Q8, Q9, and Q10. Whether for newly constructed plants or existing ones, their formulation depends on detailed technical and process knowledge, needs to be approached from a holistic perspective, integrated with a risk management awareness, and consider all aspects of pollution prevention and control, covering all elements closely related to the production process, including plant facilities, equipment, personnel, utility systems, materials, products and processes, environmental monitoring, and establishing internal connections within and among these elements to achieve comprehensive and proactive pollution control. It also lists typical steps for formulating and maintaining pollution control strategies and provides an illustrative example of a multi-product pollution control strategy framework, serving as guidance for enterprises in specifying pollution control strategies.

The guideline reflects the role of the quality system in pollution control strategies, illustrating that the entire lifecycle of the development, maintenance, and effectiveness evaluation of pollution control strategies needs robust support from a strong quality system. Quality systems such as quality risk management, change control, investigations, corrective and preventive actions, quality reviews and trend analysis, supplier management, and quality control provide an operational framework and feedback mechanism for pollution control. They drive the effective operation of various control elements, ensuring their continuous optimization and enhancement. Simultaneously, the guideline indicates that pollution control strategies are formulated based on the concept of quality risk management, utilizing scientific knowledge that includes production system knowledge, product and process knowledge, microbiology, thermal origins/endotoxins, and particle knowledge. These strategies are based on a continuously improving quality management system, quality culture, and personnel awareness.

Furthermore, the guideline introduces the control elements of pollution control strategies, encompassing plant facilities, equipment, utility systems, personnel, materials, products and processes, environmental monitoring, as well as the interconnections among these control elements of pollution control strategies, as shown in the diagram below. Finally, it emphasizes that the monitoring and effectiveness analysis of pollution control strategies should be regularly evaluated for the overall effectiveness of pollution control measures. This periodic assessment should be carried out by a cross-functional team to monitor the effectiveness of pollution control related to processes, products, personnel, facilities, and utility systems.

This guide provides relevant instructions for the industry on the design, implementation, evaluation, and management of pollution control strategies in the pharmaceutical production process. It assists businesses and personnel in understanding the concept of pollution control strategies and in establishing and implementing them more effectively. This guide serves as a technical reference for pharmaceutical production companies, factory facility design units, equipment manufacturers, and others, but it is not mandatory.

The full document can be found at the following address:

http://www.cpape.org.cn/index/article/index/aid/878.html

To view the guideline, click here

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• The Announcement from the National Medical Products Administration Regarding the Application of the “M10: Bioanalytical Method Validation and Sample Analysis” International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use Guidance Principles Q&A Document and Frequently Asked Questions Document. 2023-07-04
• Announcement by the National Medical Products Administration on the Issuance of the ‘Drug Reference Standards Management Measures’ 2023-07-05
• The Policy Interpretation of the “Drug Reference Standard Management Measures” 2023-07-05
• Publishing of Policy Poster: Drug Reference Standards Management Measures 2023-07-08
• The Notice Regarding the Revision of Partial Terms of “Provisional Measures for Drug Inspection Management” by the NMPA. 2023-07-21
• Storage time limit Validation 2023-08-02
• The National Medical Products Administration has approved the marketing of Toraysi monoclonal antibody injection 2023-08-16
• The Announcement of the NMPA on the Issuance of the “Standard System for Drug Regulation Informatization 2023-08-17
• The Announcement of the NMPA on the Application of the Guiding Principles of the ICH of Technical Requirements for Registration of Pharmaceuticals for Human Use – Q12: Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management. 2023-08-25
• Announcement of the NMPA on the Application of the ICH Guideline on Risk Management (Q9(R1)) in the Registration of Human Medicinal Products 2023-09-05
• (Q9(R1)) Guideline on Risk Management in the Registration of Human Medicinal Products 2023-09-11
• Title: Can Pharmaceuticals and Medical Devices Be Produced on the Same Production Line 2023-09-27

Centre for Drug Evaluation Regulatory Updates

• The notification regarding the use of the new office address by the Drug Evaluation Center of the National Medical Products Administration. 2023-08-10
• Li Qiang presided over the executive meeting of the State Council, and passed Action Plan for the High-Quality Development of the Pharmaceutical Industry (2023-2025); Action Plan for the High-Quality Development of the Medical Equipment Industry (2023-2025), and Guiding Opinions on the Planning and Construction of Affordable Housing 2023-08-28
• CDE: The Introduction of the Drug Clinical Trial Registration and Information Disclosure Platform 2023-09-20

National Health Commission Regulatory Updates

• The notification issued by the National Health Commission on the compilation of a catalog of human infectious pathogenic microorganisms 2023-08-28
• Interpretation of the Catalog of Pathogenic Microorganisms Transmitted Among Humans 2023-08-28

National Institute for Food and Drug Control Regulatory Updates

• The notification from the China National Institute of Inspection and Quarantine regarding the matters concerning the acceptance of inspection services at the Tiantan site after the closure of the Tiantan testing business processing center 2023-07-13
• Changes and Reissuance of Inspection Reports 2023-09-26

National Center for Drug Re-evaluation Regulatory Updates

• The notice regarding the relocation of the office address of the Drug Evaluation Center of the National Medical Products Administration 2023-07-13

PMPA Regulatory Updates

• The Notification on Issuing the Pilot Scheme for the Import of Research and Development Goods for Biopharmaceuticals in Shanghai, released by the Shanghai Municipal Commission of Commerce, Shanghai Customs, Shanghai Municipal Administration for Market Regulation, Shanghai Municipal Science and Technology Commission, and the Office for the Promotion of the Construction of Shanghai Science and Technology Innovation Center. 2023-07-31
• The notice issued by the Shanghai Municipal Food and Drug Administration, Shanghai Municipal Administration for Market Regulation, Shanghai High People’s Court, Shanghai People’s Procuratorate, and Shanghai Public Security Bureau on the implementation details of “Shanghai Municipal Administrative Enforcement of Drugs and Criminal Justice Integration Work Rules 2023-08-08
• Jiangsu Province, new QR Code Filing Requirements for Drug Package Insert 2023-08-14
• Notice on Soliciting Opinions for the ‘Work Procedures for Handling Pharmaceutical Business Supervision and Inspection by the Shandong Provincial Drug Administration 2023-08-18

Chinese Pharmacopoeia Regulatory Updates

• The Notice on Soliciting Samples for the Improvement of Drug Standards. 2023-08-11
• Notice on Soliciting Research Samples for Improving Standards of Medicinal Excipients (Third Batch of 2023) 2023-08-15