Regulatory Round-up - September 2023

UNITED KINGDOM

Medicines and Healthcare products Regulatory Agency (MHRA)

UK patients set to have faster access to innovative medical technologies via new pathway

The Innovative Devices Access Pathway (IDAP) pilot was launched on the 19^th of September 2023 by the Department of Health and Social Care (DHSC), Health Technology Wales (HTW), the Medicines and Healthcare products Regulatory Agency (MHRA), the National Health Service England (NHSE), the National Institute for Health and Care Excellence (NICE), the Office for Life Sciences (OLS), and the Scottish Health Technologies Group (SHTG). The aim of this new pathway is to support the rapid development of innovative technologies that can be introduced into the National Health Service (NHS) to address unmet clinical needs for patients and healthcare professionals at the earliest opportunity, without compromising on standards of safety, quality, and effectiveness. Please find further information here.

Guidance published on the new international regulatory recognition routes for medicines approvals

The MHRA has issued a detailed guidance on the new International Recognition Procedure (IRP) for medicines manufacturers, including how to use the scheme to apply for a medicine licence in the UK, following approval by trusted regulatory partners in Australia, Canada, the European Union, Japan, Switzerland, Singapore, and the United States.

As the UK exited the EU, the MHRA introduced a mechanism that allowed the agency to rely on European Commission (EC) decisions when considering application for a UK marketing authorisation to authorise medicinal products. This procedure, known as the European Commission Decision Reliance Procedure (ECDRP), is due to come to an end December 31, and the IRP will come into effect on 1 January 2024.

Transparency data: MHRA performance data for assessment of clinical trials and established medicines

The MHRA publishes routine updates to performance data for the assessment of clinical trials and established medicines to help improve the predictability of decision making in applications for clinical trials, marketing authorisations and variations to existing approvals. Please find the latest performance update here.

Three new UK Approved Bodies to certify medical devices announced by the MHRA

The MHRA has designated three new UK Approved Bodies, which significantly increases the UK’s capacity to certify medical devices, supporting faster certification of safe and effective medical devices for healthcare professionals and the public.

TÜV SÜD, Intertek, and TÜV Rheinland UK join the four current UK Approved Bodies, almost doubling current capacity for the certification of medical devices in the UK. Please find further information here.

EUROPE

European Commission (EC)

New ZLG Document on Transport Verification Published

The German Central Authority of the Länder for Health Protection with regard to Medicinal Products and Medical Devices (Zentralstelle der Länder für Gesundheitsschutz bei Arzneimitteln und Medizinprodukten, ZLG) has published a newly prepared document (in german only) entitled "Inspektion der Eignung von Transportprozessen" (Inspection of the Suitability of Transport Processes). The document, which is applicable to GMP and GDP areas, consists of a catalogue of standards, questions and recommendations, which serves to harmonise the preparation, execution and follow-up of an inspection.

As the transport of medicinal products, veterinary medicinal products and active pharmaceutical ingredients (APIs) are considered, the contents are of interest not only to inspectors but to pharmaceutical manufacturers and wholesalers as well.

European Directorate for the Quality of Medicines (EDQM)

Ph. Eur. allows the use of recombinant factor C for control of bacterial endotoxins in water monographs

Revised versions of the monographs, Water for injections (0169) and Purified water (0008), will be published in Supplement 11.4 of the European Pharmacopoeia (Ph. Eur.) in October 2023 with the implementation date of 1 April 2024. Adopted by the Ph. Eur. Commission at its 175^th session in March 2023, these two texts now allow the use of recombinant factor C (rFC) to test for bacterial endotoxins in pharmaceutical waters. The revision was carried out following the issuing of a new general chapter, Test for bacterial endotoxins using recombinant factor C (2.6.32), describing a bacterial endotoxin test (BET) that can be used as an alternative to the classic limulus amoebocyte lysate (LAL)-based methods. The use of rFC is a step towards alleviating the need for animal resources as it is a synthetic reagent which does not rely on lysate derived from species of horseshoe crab. Please find further information here.

European Pharmacopoeia Workshop in New Jersey (USA), 24-25 October 2023

EDQM is holding a two-day European Pharmacopoeia Workshop which will take place in Iselin, New Jersey (USA) on 24 and 25 October 2023. The following topics will be discussed:

• Flexibility in the Ph. Eur.: concepts related to analytical procedures
• Control of impurities in APIs and excipients: challenges and strategies
• Genotoxic impurities, nitrosamines and individual monographs
• mRNA vaccines, ATMPs, mAb performance standards, new technologies
• Phasing out the rabbit pyrogen test: vision on potential global strategy
• Continuous manufacturing
• Analytical Quality by Design (AQbD) in the Ph. Eur.
• Communication channels: identify ways to improve and address unmet needs
• Programme and registration

Please find further information on this event including how to register here.

European Medicines Agency (EMA)

Towards a permanent collaboration framework for EMA and Health Technology Assessment bodies

Since 2021, EMA and the European Network for Health Technology Assessment (EUnetHTA 21) consortium have delivered a number of milestones to prepare the EU for the application of the Regulation on Health Technology Assessment (EU) 2021/228 which entered into force in January 2022 and applies as of January 2025. It will govern the European cooperation between medicine regulators and HTA bodies. Under the new framework, EMA and HTA bodies will collaborate in the context of joint clinical assessments, joint scientific consultations, and the identification of emerging health technologies. EUnetHTA 21 ceased to operate on 16 September 2023, and preparations will now continue for the implementation of the Regulation, under the direction of the HTA Coordination Group. Please find further details here.

USA

Food and Drug Administration (FDA)

Considerations for the Use of Real-World Data and Real-World Evidence To Support Regulatory Decision-Making for Drug and Biological Products

The 21st Century Cures Act (2016) is intended to accelerate medical product development and bring innovations faster and more efficiently to patients. Cures Act added section 505F to the Federal Food, Drug, and Cosmetic Act (FD&C Act). In accordance with this section, FDA has created a framework for a Real-World Evidence (RWE) Program to evaluate the potential use of RWE in regulatory decision-making for drugs. As part of its RWE Program, the FDA has issued a final guidance document on the use of RWE to help support approval of a new indication for a drug already approved under section 505(c) of the FD&C Act (21 U.S.C. 355(c)) or to help support post approval study requirements. Please find information on how to submit comments here.

Use of International Standard ISO 10993-1, "Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process"

FDA has issued a final guidance document to assist industry in preparing Premarket Applications (PMAs), Humanitarian Device Exceptions (HDEs), Investigational Device Applications (IDEs), Premarket Notifications, and De Novo requests for medical devices that come into direct or indirect contact with the human body in order to determine the potential for an unacceptable adverse biological response resulting from contact of the component materials of the device with the body. It is intended to provide further clarification and information on the use of International Standard ISO 10993-1, "Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process" to support applications to FDA.

FDA issues draft guidance regarding confirmatory evidence of clinical trials

FDA has issued a draft guidance Demonstrating Substantial Evidence of Effectiveness Based on One Adequate and Well-Controlled Clinical Investigation and Confirmatory Evidence that supplements and expands the recommendations in the 2019 Substantial Evidence of Effectiveness draft guidance by providing further detail on the use of data drawn from one or more sources (e.g., clinical data, mechanistic data, animal data) to support the results of one adequate and well-controlled clinical investigation. It also provides examples of types of data that could be considered confirmatory evidence. Importantly, this guidance emphasizes the need for early engagement with the agency for sponsors that intend to establish substantial evidence of effectiveness with one adequate and well-controlled clinical investigation and confirmatory evidence. Details on how to submit comments can be found here.

Annual Status Report Information and Other Submissions for Postmarketing Requirements and Commitments: Using Forms FDA 3988 and FDA 3989 Guidance for Industry

The FDA has announced the availability of a final guidance entitled “Annual Status Report Information and Other Submissions for Postmarketing Requirements and Commitments: Using Forms FDA 3988 and FDA 3989” which is intended for applicants that are required to report annually on the status of postmarketing studies and clinical trials for human drug and biological products under section 506B of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 356b) and its implementing regulations at 21 CFR 314.81(b)(2)(vii) and 601.70. This guidance describes the purpose and content of Form FDA 3988, Transmittal of PMR/PMC Submissions for Drugs and Biologics

Formal Meetings Between the FDA and Sponsors or Applicants of PDUFA Products

The FDA has issued a draft guidance to provide recommendations to industry on formal meetings between the Food and Drug Administration (FDA) and sponsors or applicants relating to the development and review of drug or biological drug products regulated by the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research 20 (CBER). This guidance discusses the principles of good meeting management practices as well as the standardized procedures for requesting, preparing, scheduling, conducting, and documenting such formal meetings.

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

This guidance provides information by the FDA and industry in a question and answer format and clarifies how the unique aspects of a combination product influence the considerations within the human factors engineering (HFE) process.

Alternative Tools: Assessing Drug Manufacturing Facilities Identified in Pending Applications Guidance for Industry

This draft guidance, within the context of FDA approval and license decisions, describes the use of alternative tools to assess manufacturing facilities identified in an NDA, an ANDA, or a BLA to establish that these facilities meet the applicable requirements, including under section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 351(a)(2)(B). The use of alternative tools will help FDA fulfill its commitments to meet user fee goal dates and to make timely application decisions. Please find information on how to submit comments here.

Considerations for the Conduct of Clinical Trials of Medical Products During Major Disruptions Due to Disasters and Public Health Emergencies

Guidance for Industry, Investigators, and Institutional Review Boards

The FDA recognizes that disasters and public health emergencies can cause major disruptions to the conduct of clinical trials of medical products which can create difficulties in complying with protocol-specified procedures. As a result, the FDA has issued a final guidance which recommends approaches that sponsors of clinical trials of medical products can consider when there is a major disruption to clinical trial conduct and operations due to disasters or public health emergencies.

Public consultations

Medicines and Healthcare products Regulatory Agency (MHRA)

EUROPEAN MEDICINES AGENCY (EMA)

Food and Drug Administration (FDA)

International Conference on Harmonisation (ICH)

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