Regulatory Newsletter

WuXi Biologics’ Regulatory Affairs team is honored to provide you with a summary of specific regulatory updates (i.e., typically product development and CMC-related) 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)

Remote Interactive Evaluations of Drug Manufacturing and Bioresearch Monitoring Facilities

Oct 25, 2023

This guidance describes how the FDA requests and conducts voluntary remote interactive evaluations (RIE) at facilities where drugs are manufactured, processed, packed, compounded, or held, and at drug facilities covered under the FDA’s bioresearch monitoring (BIMO) program. The policy mentioned in this guidance applies to all drug inspection programs including, but not limited to:

• Preapproval Inspections (PAIs) and Prelicense Inspections (PLIs)
• Postapproval Inspections (PoAIs)
• Surveillance Inspections
• Follow-Up and Compliance Inspections
• Bioresearch Monitoring (BIMO) Inspections

The FDA intends to apply risk management methods and tools to determine when to request a facility’s participation in a remote interactive evaluation. Once the facility confirms its willingness and ability to participate in a remote interactive evaluation, the FDA will schedule a brief virtual meeting to discuss logistics, responsibilities, and expectations. When facilities agree to participate in a remote interactive evaluation, the same level of transparency is expected as that  during an FDA inspection. Upon completion of a remote interactive evaluation, the FDA will have a closeout meeting with the facility’s management and present a written list of observations in most cases. A Form FDA 483, Inspectional Observations will not be issued by the FDA but establishments are encouraged to provide responses in writing to the observations made during the RIE within fifteen U.S. business days. Any responses or corrective actions submitted to the FDA during that timeframe in response to the issues identified during the RIE generally will be considered before further Agency action or decision. For preapproval and prelicense inspection programs, the FDA may defer consideration of responses or corrective actions in the current application review cycle if received after 15 U.S. business days.

The full document can be found at the following address:

Remote Interactive Evaluations of Drug Manufacturing and Bioresearch Monitoring Facilities

Development of Monoclonal Antibody Products Targeting SARS-CoV-2 for Emergency Use Authorization

Dec 21, 2023

The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled “Development of Monoclonal Antibody Products Targeting SARS-CoV-2 for Emergency Use Authorization”. This guidance supersedes the guidance entitled “Development of Monoclonal Antibody Products Targeting SARS-CoV-2, Including Addressing the Impact of Emerging Variants, During the COVID-19 Public Health Emergency” issued on February 22, 2021. This guidance provides details on criteria for the issuance of an EUA (including chemistry, manufacturing, and controls; pharmacology/toxicology, virology and clinical four parts).

The full document can be found at the following address:

Development of Monoclonal Antibody Products Targeting SARS-CoV-2 for Emergency Use Authorization

The final guidance document can be found at the following address:

Final Guidance Document

Verification Systems Under the Drug Supply Chain Security Act for Certain Prescription Drugs

Dec 07, 2023

The FDA announced the availability of a final guidance for industry entitled “Verification Systems Under the Drug Supply Chain Security Act for Certain Prescription Drugs.” The guidance addresses the verification systems that manufacturers, repackagers, wholesale distributors, and dispensers must have in place to comply with the Federal Food, Drug, and Cosmetic Act (FD&C Act), as amended by the Drug Supply Chain Security Act (DSCSA). Specifically, the guidance covers the statutory verification systems requirements that include the quarantine and investigation of a product determined to be suspect and the quarantine and disposition of a product determined to be illegitimate.

The guidance also addresses the statutory requirement for notification to the Agency of a product that has been cleared by a manufacturer, repackager, wholesale distributor, or dispenser (also referred to as “trading partners”) after a suspect product investigation because it is determined that the product is not an illegitimate product. Finally, the guidance addresses the statutory requirement for responding to requests for verification and processing saleable returns.

Manufacturers and repackagers must have systems in place to respond to requests for verification from trading partners within 24 hours of receipt of a request. These systems must be in place by November 27, 2017, for manufacturers, and by November 27, 2018, for repackagers. The systems must allow the manufacturer or repackager to notify the trading partner making the request whether the product identifier, including the standardized numerical identifier that is the subject of the request, corresponds to the product identifier affixed or imprinted by that manufacturer or repackager.

The guidance notes that manufacturer, repackager, wholesale distributor, or dispenser should have a system in place for creating and maintaining records related to suspect product investigations and disposition of illegitimate products for a minimum of 6 years as required by section 582 of the FD&C Act.

The full document can be found at the following address:

Federal Register : Verification Systems Under the Drug Supply Chain Security Act for Certain Prescription Drugs; Guidance for Industry; Availability

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

Regulatory expectations and GMP certificates following the-COVID-19 public health emergency

Dec 07, 2023

The EMA and the European Commission and Heads of Medicines Agencies (HMA) have phased out the extraordinary regulatory flexibilities for medicines put in place during the COVID-19 pandemic to help address regulatory and supply challenges arising from the pandemic. This follows the end of the COVID-19 public health emergency declared by WHO in May 2023. On-site GMP and GDP inspections have restarted after being postponed or carried out remotely during the pandemic. However, a considerable number of postponed inspections still need to be carried out.

The validity of GMP and GDP certificates was extended until the end of 2023. The GMP/GDP Inspectors Working Group has decided to continue the extension of the validity date until 2024 or the conclusion of the next on-site inspection, whichever comes first, except where clarifying remarks in the document state otherwise. Meanwhile, competent authorities will perform risk-based supervision of sites, either by on-site inspections or distant assessments, and based on the outcome may continue to issue, withdraw or restrict GMP and GDP certificates, as appropriate. The inspections will be prioritized based on risk, so that the highest priority manufacturers, such as manufacturers of sterile products and biological products, and wholesale distributors are inspected first. In addition, inspections will be prioritized depending on the date of the last inspection.

It is incumbent upon manufacturers, importers and distributors to continue complying with GMP and GDP as appropriate. Inspections (including distant assessments) may be carried out at any time. In case of serious non-compliance, appropriate regulatory actions will be triggered.

MHRA has also decided to continue the extension of the validity date until 2024 or until the conclusion of the next inspection, whichever comes first. Meanwhile, the agency still reserve the right to decide, continue, withdraw or restrict the certificates as appropriate.

The full document can be found at the following address:

Good manufacturing practice | European Medicines Agency (europa.eu)

GMP & GDP Certificates: Validity Period Extended – MHRA Inspectorate (blog.gov.uk)

TGA (Therapeutic Goods Administration)

No updates provided by WuXi Biologics for the time period. To see past updates for this agency, go to our regulatory newsletter archive.

Health Canada

No updates provided by WuXi Biologics for the time period. To see past updates for this agency, go to our regulatory newsletter archive.

WHO (World Health Organization)

Potential benefits and limitations of mRNA technology for vaccine research and development for infectious diseases and virus-induced cancers

Dec 13, 2023

Prompted by the successful use of messenger RNA (mRNA) technology for the development of COVID-19 vaccines, the World Health Organization’s (WHO) Science Council has released a report reviewing the potential benefits and limitations of mRNA vaccine technology.

The full document can be found at the following address:

Potential benefits and limitations of mRNA technology for vaccine research and development for infectious diseases and virus-induced cancers (who.int)

The news release can be found at the following link:

WHO’s Science Council issues report on mRNA vaccine technology

MHRA 

International Recognition Procedure

Nov 20, 2023

The MHRA updated the guidance International Recognition Procedure that was initially published on 30^th August, 2023. The latest update includes additional guidance on the eligibility checker (EC) and marketing authorization application instructions, IRP product lifecycle and eCTD guidance for Mas and lifecycle.

The updated eligibility checker and marketing authorization instructions, indicate that starting1 January 2024, applicants will be able to apply for a marketing authorization under IRP which will replace the EC decision reliance procedure (ECDRP). The mutual recognition/decentralized reliance procedure (MRDCRP) will be incorporated under the umbrella of IRP. A product license (PL) number is required before completion of the eligibility checker. The eligibility checker should complete the initial MAAs (including line extension) and suitability for recognition A or B will be determined 6 weeks before the planned date of MAA submission. Eligibility checker form submission instruction is also listed in the guidance. The full document can be found in the following address: Eligibility Checker and submitting your Marketing Authorisation application – GOV.UK (www.gov.uk).

Applications should be submitted through the Human Medicines Portal under MHRA Submission Platform/Hub. No other submission route is acceptable for IRP. The full document can be found in the following address: International Recognition Procedure for Product Lifecycle.

The full document can be found in the following address: International Recognition Procedure – GOV.UK (www.gov.uk)

PMDA (Pharmaceuticals and Medical Devices Agency)

No updates provided by WuXi Biologics for the time period. To see past updates for this agency, go to our regulatory newsletter archive.

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

No updates provided by WuXi Biologics for the time period. To see past updates for this agency, go to our regulatory newsletter archive.

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

No updates provided by WuXi Biologics for the time period. To see past updates for this agency, go to our regulatory newsletter archive.

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

No updates provided by WuXi Biologics for the time period. To see past updates for this agency, go to our regulatory newsletter archive.

Health Products Regulatory Authority (HPRA)

No updates provided by WuXi Biologics for the time period. To see past updates for this agency, go to our regulatory newsletter archive.

National Medical Products Administration (NMPA)

NMPA Announcement on Strengthening Supervision and Management of Drug MAH’s Commissioned Production (No. 132 of 2023)

2023-10-23

In order to further implement the primary responsibilities of MAH (hereinafter referred to as Holders) for quality and safety of commission produced drugs, and to ensure the quality and safety throughout the entire lifecycle of drugs, the NMPA issued and implemented the “Announcement on Strengthening Supervision and Management of Commissioned Production by Drug MAHs (No. 132 of 2023)” on October 23, 2023. This announcement sets forth explicit requirements concerning the permit management of commissioned production, quality management, supervisory management, and other related matters.

The full document can be found at the following address:

https://www.nmpa.gov.cn/xxgk/ggtg/ypggtg/ypqtggtg/20231023160426145.html

Notice from the Comprehensive Department of the NMPA on Issuing the Guideline for On-Site Inspections of Drug MAH’s Commissioned Production

2023-10-24

To reinforce the supervision and management of commissioned production by drug marketing authorization holders, the NMPA drafted “Guideline for On-Site Inspections of Drug MAH’s Commissioned Production,” which was implemented on October 24, 2023. The Guideline provides detailed provisions on four aspects: organization and personnel, quality management system, holder’s management of the commissioned production, and other related areas.

The full document can be found at the following address:

https://www.nmpa.gov.cn/xxgk/fgwj/gzwj/gzwjyp/20231024161543188.html

NMPA has become an official applicant of the Pharmaceutical Inspection Co-operation Scheme (PIC/S)

2023-11-09

In late September 2023, the NMPA submitted formal application documents to the Pharmaceutical Inspection Co-operation Scheme (PIC/S). On November 8, 2023, PIC/S sent a letter to the NMPA acknowledging its status as an official applicant.

The full document can be found at the following address:

https://www.nmpa.gov.cn/yaowen/ypjgyw/ypyw/20231109101918137.html 

Announcement of the NMPA on the Applicability of ICH Guideline “Q13: Continuous Manufacturing of Drug Substances and Drug Products” (No. 158 of 2023)

2023-12-14

To align drug registration technical standards with international norms, the NMPA has decided to adopt the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Guideline “Q13: Continuous Manufacturing of Drug Substances and Drug Products” (hereinafter referred to as “Q13 Guideline”). Applicants are required to conduct research in accordance with the requirements of the Q13 Guideline, based on the current technical requirements for pharmaceutical research. Research studies starting from June 13, 2024 (based on the date of the experimental record), will be subject to the Q13 Guideline.

The full document can be found at the following address:

https://www.nmpa.gov.cn/xxgk/ggtg/ypggtg/ypqtggtg/20231214112008103.html

Notice on Public Consultation for “Requirements for Submission of Application Dossiers for Marketing Registration for Drugs Produced Overseas and Transferred to Domestic Production (Therapeutic Biological Products) (Draft for Comment)”

2023-12-22

To guide and support the application for marketing registration of therapeutic biological products that have been manufactured overseas and are transferred to domestic production, and to further implement the requirements of the “Post-approval Changes Management Procedures (Trial)” document, as well as to carry out the requirements issued by the State Council in the “Opinions on Further Optimizing the Foreign Investment Environment and Increasing Efforts to Attract Foreign Investment,” the CDE has coordinated relevant policies and strengthened the entire management process. By combining related laws, regulations, and guiding principles, and through preliminary research, discussions with enterprise symposiums, and internal consultations, the CDE has drafted the “Requirements for Submission of Application Dossiers for Drug Marketing Registration for Drugs Produced Overseas and Transferred to Domestic Production (Therapeutic Biological Products) (Draft for Comment).” This document clarifies the general requirements for dossiers for the marketing application of therapeutic biological products transferred to domestic production, as well as the specific application dossier content that can be simplified.

The full document can be found at the following address:

https://www.cde.org.cn/main/news/viewInfoCommon/668e45c24c822b89f653176dd6b4e7f5