Posted on 25 Feb 2023

REGULATORY PUBLIC DISCLOSURE (RPD) - February 2023

Medicines and Vaccines

CTR and CTIS

  1. CTIS released a Q&A document to guide its users on how to protect personal data and commercially confidential information (CCI) in CTIS.

  2. The resource titled ‘Clinical Trials Regulation (EU) No 536/2014 in practice’ is a quick guide on the rules and procedures of the EU Clinical Trials Regulation drawn up by the Clinical Trials Coordination and Advisory Group (CTAG) as its members are the National Contact Points defined for the Regulation. At just 26 pages in length including Annexes, this could be a very useful resource. More detailed documents are published in full under Eudralex Volume 10.

  3. Sixty-two sponsors and other stakeholders provided their views on the new regulatory environment provided by the CTR and their experience with CTIS in the following report: EU Survey. Targeted consultation on the implementation of the Clinical Trials Regulation (EU) No 536/2014. Factual summary report. The report authors state that “The reported experience does not necessarily reflect the current status of CTIS user experience and the CTR implementation. Many of the issues reported have been addressed in the meantime via resolution of the encountered defects and new functionalities in CTIS, alignment of national legislation, additional guidance material for sponsors, as well as targeted modification of the rules of the CTR”.

  4. EMA has released an update of the EudraCT & EU Clinical Trial Register Frequently Asked Questions, v2.2 dated 31 January 2023.

  5. EMA have released a CTIS Risk Mitigation Plan to strengthen planning for the functioning of the CTIS in order to ensure that business-as-usual activities can be performed.

  6. EMA have released a document to provide answers to questions regarding CTIS and the CTR that were raised by representatives of sponsor associations, including the Association of Clinical Research Organisations (ACRO), the European Federation of Pharmaceutical Industries and Associations (EFPIA), the European Confederation of Pharmaceutical Entrepreneurs (EUCOPE) and the European Clinical Research Organisation Federation (EUCROF): Q&A - CTIS and CTR.

  7. The CTIS Newsflash dated 24 Feb 2023 is out now. Besides revisions to the EudraLex Q&A, and the usual list of upcoming CTIS trainings and resources, we learn that EMA has initiated the process to register CTIS as a WHO data provider. Once the registration process is completed, CTIS data will be included in WHO’s International Clinical Trials Registry Platform (ICTRP) Search Portal.

FDA Guidance and News

  1. FDA draft guidance titled, “Considerations for the Design and Conduct of Externally Controlled Trials for Drug and Biological Products” makes recommendations on the use of externally controlled clinical trials to show evidence of the safety and effectiveness of a drug.   Comments are open until 02 May 2023.
  2. Considerations are presented for designing and conducting externally controlled trials that use patient-level data (i.e., information on individual people, such as medical and treatment history) to study the effectiveness and safety of drugs, including threats to the validity of trial results from sources of potential bias. This draft guidance is part of a series under FDA’s RWE Program.
  3. The Good Cause Extension Request Process and Criteria explains the process for responsible parties to submit a good cause extension request, the information to include in such requests, and the criteria NIH use to evaluate such requests as of 15 February 2023. This document also provides a list of reasons generally considered "good cause" and "not good cause" for granting extensions. As described in this document, even if a request describes one of only a few situations that would constitute "good cause," all extension requests will be evaluated by NIH on a case by-case basis.
  4. Related to the previous topic, new and updated FAQs are available as follows:

EMA Guidance and News

  1. On 3 February 2023, EMA launched a public consultation on the establishment of a multi-stakeholder platform to improve clinical trials in the EU. The multi-stakeholder platform is a deliverable of the joint initiative Accelerating Clinical Trials in the EU (ACT EU) and was included in the ACT EU workplan for 2022-2026. As part of the consultation process comments on the ACT EU multi-stakeholder platform (ACT EU MSP) concept paper are welcomed.  The scope of the platform will encompass all aspects of clinical trials including design, conduct, statistical analysis, proposal of revision of regulation(s), transparency of data and patient engagement. Stakeholders can advise on the key priorities for discussion and express their interest to join the platform via the online form until 3 March 2023 at midnight CET.
  2. CTTI's webinar on New ICH M11 Harmonised Guideline, Protocol Template, and Technical Specification (slides) provides an overview of the draft M11 guideline and background/orientation on how the new template came to be.
  3. EMA Guidance for Stepwise PIP (sPIP) Pilot - the sPIP concepts will be piloted starting the first quarter of 2023 with 8 sPIP adopted initial opinions in order to gather experience to shape the process accordingly and to inform decision making on its use in the future.

Transparency and Disclosure Resources and News

EFPIA conducted a survey of compliance during July-September 2020 to assess the status of the implementation of the “Principles for Responsible Clinical Trial Data Sharing” among its member companies. The results are promising and show good commitment of the member companies in upholding the Principles. Read the full report here.

Development Strategy News

TransCelerate’s Whitepaper published in December 2022 is their ICH E8 Landscape Assessment that summarises results from member companies. The results show that two-thirds are still exploring E8(R1) and over half are still missing key definitions. Encouragingly, the most frequently cited starting point for Critical to Quality (CtQ) factor identification was during the clinical development plan, study outline, or draft protocol. About half were then reassessing CtQ factors at the time of final protocol. Other interesting insights include that ‘Medical Writing’ appears as a key stakeholder for protocol development with two thirds indicating MW involvement from the study design through to final protocol.

TransCelerate are hosting a webinar on What You Need to Know about ICH E8 (R1): Using TransCelerate’s Tools to Help Interpret and Implement ICH E8 (R1) on 02 March 2023 16:00-17:00 CET. The webinar will focus on: what’s new in ICH E8 (R1), the work of ICH E8 (R1) and how TransCelerate's focus topics were chosen, a run through of TransCelerate's published tools.

Here’s a reminder to sign up for Jonathan McKinnon’s regular and excellent ‘Protocol Development Newsletter’ on LinkedIn. We often present relevant material from this resource here - as above - but if you are involved in protocol development, you may wish to subscribe to receive the full summary.

Articles of Interest

This JAMA article titled “Frequency and Characteristics of Trials Using Medical Writer Support in High-Impact Oncology Journals” was published in Feb 2023.

Press release ‘EFPIA update on the readiness for mandatory use of the Clinical Trials Regulation’.

News from Asia Regulators

  1. At the end of January 2023, China NMPA fully enforced the implementation of ICH Q3D (R2) and M10 guidelines into drug research in the country. 
  2. In February 2023, China NMPA released 2 final guidelines on the use of real-world evidence in clinical trials: “Guidelines on Design and Protocol of Drug Real-world Evidence Study” and “Guidelines on Communication About Drug Registration Application Supported by Real-world Evidence”.

Medical Devices

Medical devices information is kindly compiled by Raquel Billiones.

EU Updates

NEW: MDCG 2023-1. Guidance on the health institution exemption under Article 5(5) of MDR and IVDR. The provisions in Article 5(5) are the basis for the regulatory control and oversight of in-house devices. This document provides guidance on the application of some of these rules and is written for healthcare professionals and researchers of health institutions aiming to design, manufacture, modify and use in-house devices.

NEW: MDCG 2023-2. This guidance document provides forms for Notified Bodies Medical Devices a List of Standard Fees for Conformity Assessment Activities under the MDR and IVDR.

NEW: In February 2023, EMA is launching a pilot to provide expert panels’ scientific advice to manufacturers of certain high-risk (Class III and Class IIb) medical devices.

UPDATED: MDCG 2020-16 rev.2. Guidance on Classification Rules for in vitro Diagnostic Medical Devices under IVDR.

UPDATED: The Coverage of Designation Codes by MDR/IVDR notified bodies was updated in January 2023.

Commission Document: Annual overview of devices subject to the clinical evaluation consultation procedure (CECP) pursuant to Article 54(4) of Regulation (EU) 2017/745 on medical devices (April 2021 - June 2022). This first overview covers activities of the expert panels from their start in April 2021 until 30 June 2022.

UPDATED: Notified Bodies list. TEAM-NB (European Association of Notified Bodies for Medical Devices) now has 34 member organisations from 17 member states.

Directive (EU) 2022/2555 of the European Parliament and of the Council of 14 December 2022 on measures for a high common level of cybersecurity across the Union is published and in force.

Updates from Switzerland

Swissmedic updated in January an information sheet with answers to FAQs about notifications to Swiss health authorities regarding medical devices.

Updates from the UK

The UK released in February the policy paper on medical technology strategy.

ISO Updates

The International Standards Organisation released in February the ISO/IEC 23894:2023 Information technology — Artificial intelligence — Guidance on risk management