May 2023

Medicines and Vaccines

ICH

  1. The final version of ICH S12 guideline on Nonclinical Biodistribution Considerations for Gene Therapy Products was released on 14 March 2023 and implemented in the US in May 2023. The guideline provides recommendations for the conduct of nonclinical biodistribution studies in the development of gene therapy products.
  1. Clinical Trials Transformation Initiative (CTTI) published a report on the ICH M11 webinar from Jan 2023. The succinct 4-page report includes ‘Key themes from the Q&A’ which are useful. 
  1. ICH GCP E6(R3) Endorsement by the Members of the ICH Assembly under Step 2 on 19 May 2023 is released and open for public consultation (links to provide comments are apparently ‘coming soon’ according to CDER). CDER’s Director in the Office of Medical Policy says: “We anticipate a very large number of comments. We strongly encourage you to consider prioritising key comments, correlating your comment with the corresponding line number of the draft guideline, providing justification and any relevant examples to support suggested changes, and consolidating comments from the same organisation, if appropriate.”

This version of E6 includes an updated version of the already-released GCP principles and the protocol content has moved from Section 6 in E6(R2) to Appendix B in E6(R3). This UK MHRA blog provides a somewhat wordy description of the changes, and the table therein provides a comprehensive comparison of level 1 and 2 headings in E6(R2) versus E6(R3). A more succinct summary of changes between R2 and R3 is provided here.

 4. On 24 May 2023, EMA published overview comments on the ICH M11 Guideline, Clinical Study Protocol Template.

CTR and CTIS

  1. EMA has opened a public consultation (news announcement) to review the transparency rules for the publication of information on clinical trials submitted through CTIS. Send your comments via an online form until midnight on 28 June 2023.
  2. Krystelis presented a webinar “One year of CTIS: Experience, learning, and perspectives of sponsors and service providers” on 3 May 2023, a recording of which can be found here

  3. EMA released an Interim guidance document on how to approach the protection of personal data and commercially confidential information while using CTIS, dated 3 May 2023. This replaces the draft guidance released in April 2022. However, only Sections 1 to 3 are reflected in the new ‘interim’ guidance, with Section 4 and 5 (focusing on CCI) to be released later, after an additional consultation period has concluded.

    The Annex to the Interim Guidance is a stand-alone document and replaces the Annex in the draft guidance released in April 2022. It includes a list of all documents required to be submitted, and describes the approach to publication of personal information within each document.

  4. EMA also released the latest Q&A on the protection of CCI and personal data while using CTIS dated 16 May 2023 (v1.2). The Q&A intends to provide more clarity on main aspects that have been discussed with the Clinical Trials Coordination Group (CTCG) and it should be read in conjunction with the Interim guidance document on how to approach PPD and CCI  while using the CTIS and its Annex - see point 3 above.

  5. The CTIS release deployed on 11 May 2023 implemented several improvements to enhance user experience. Information on the CTIS latest system improvements is available in the published release notes as well as in the Lists of known issues and proposed workarounds.

  6. Please note that the Clinical Trial Highlights Newsletter is moving to a new platform, Newsroom, used by European institutions and agencies to create and disseminate information online. Sign up here to receive future issues. The next issue of the Newsletter, due in July 2023, will only be sent via email to readers who signed up.

  7. EMA will host a bitesize talk on transitional trials in CTIS on 21 June 2023. This bitesize talk on CTIS provides an opportunity for sponsors to learn how to create and submit transitional trials in CTIS. Sponsors will also have the opportunity to ask questions on this CTIS topic before and during the event and are encouraged to consult the CTIS training and support materials prior to the event.

  8. EMA will host a Webinar titled ‘Clinical Trials Information System Webinar: Second Year of Transition’ on 14 July 2023, 13:00 - 17.30 CET. 

  9. EMA has a new webpage: Clinical Trials Regulation: progress on implementation.

  10.  CTIS is now a registered data provider for the World Health Organization (WHO). Data from authorised trials published on the CTIS website - excluding those with category 1 deferrals of the main characteristics - is now included in the search portal of WHO’s International Clinical Trials Registry Platform (ICTRP). This applies to relevant clinical trial data, as required by WHO, which has been published on CTIS since the launch of the system on 31 January 2022.

    Publicly accessible registries that are data providers to WHO’s ICTRP are accepted by the International Committee of Medical Journal Editors (ICMJE), according to its recommendations. Sponsors are reminded that clinical trials with any type of deferrals and a decision issued after mid-August 2022 are currently not published on the CTIS website. Therefore, these trials will not be included in WHO’s ICTRP.

  11. Clinical Trials Highlights Newsletter: Resubscribe here to receive future issues.

UK and MHRA News

The 02 May 2023 MHRA Inspectorate Blog post titled ‘ICH E6(R3) Good Clinical Practice guidance - Step 2 Public Consultation’ states ‘...MHRA wishes to consult directly with UK stakeholders to compile and coordinate their comments to the Expert Working Group (EWG)’. 

FDA Guidance and News

  1. FDA released a draft guidance to support the use of decentralised clinical trials (DCTs) for drugs, biologics and devices. It provides recommendations for sponsors, investigators and other stakeholders regarding the implementation of DCTs. DCTs will allow some or all trial-related activities to take place at trial participants’ homes or other convenient locations, instead of having them visit study sites, for examples, obtaining laboratory tests at a local facility rather than a research medical centre or conducting a clinical follow-up visit in the trial participant’s home using telemedicine. Leonard Sacks, MD, associate director for clinical methodology in CDER’s Office of Medical Policy, discusses the benefits as well as implementation challenges in this CDER Conversation.

As part of the FDA’s efforts to be responsive to the rapidly evolving clinical trial landscape and clarify the Agency’s recommendations on the conduct of DCTs, the FDA will provide an overview of the draft guidance titled Decentralized Clinical Trials for Drugs, Biological Products, and Devices on June 20, 2023; 3:00 PM - 4:00 PM ET. Register here.

  1. Updates to PRS Beta, including the protocol registration modules, have been released to the PRS. To learn more, read about the new features in the NLM Technical Bulletin. Note that data entered in the PRS Beta will be saved on both the classic and beta sites.

The latest release notes can be found here and the recordings and transcripts from the virtual public meeting held in April 2023 are now available on the ClinicalTrials.gov Modernization webpage.

  1. FDA is holding its ‘Regulatory Education for Industry (REdI) Annual Conference’. This is a free conference held on 5-9 June 2023. Agenda here. Register for free here. 
  1. On 7 and 8 June 2023, the FDA’s CDER, CBER, and the Duke-Margolis Center for Health Policy will host a jointly sponsored virtual public workshop on the Rare Disease Endpoint Advancement (RDEA) Pilot Program and novel endpoint development for rare disease drug development. The purpose of this public workshop is to discuss topics relevant to the development of endpoints for rare diseases.
  1. The FDA guidance of 25 May 2023 Adjusting for Covariates in Randomized Clinical Trials for Drugs and Biological Products describes FDA’s current recommendations regarding adjusting for covariates in the statistical analysis of randomized clinical trials in drug development programs. This guidance provides recommendations for the use of covariates in the analysis of randomized, parallel group clinical trials that are applicable to both superiority trials and noninferiority trials. Comments are open.

EMA Guidance and News

  1. EMA has published a points to consider document on managing ongoing clinical trials affected by political conflicts, natural disasters or other major disruptions. The advice draws from the experience of past major disruptions in society, including the Covid-19 pandemic and the most recent developments of the Russo-Ukrainian War.” Topics include “Risk assessment ”, “General principles/ Potential measures to be implemented”, “Transfer of trial participants to another trial site in the same clinical trial within the country of origin”, “Transfer of trial participants to an EU/EEA country where the clinical trial is also authorised”, “Transfer of trial participants to an EU/EEA country where the clinical trial is not authorised”, and “Use of data from trial participants transferred to another trial site and/or country”.
  1. The EMA 2022 Annual report is out now. The report draws attention to some major achievements of the Agency, high-impact activities and challenges in 2022. These include the implementation of the Clinical Trials Regulation and the successful launches of the Clinical Trials Information System (CTIS) and the Accelerating Clinical Trials in the EU (ACT EU) initiative - as well as presenting EMA’s initiatives aimed at driving transformation in regulatory decision-making by building capability and capacity in the analysis and use of data and real-world evidence.
  1. The presentations from EMA’s webinar on Clinical Data Publication (Policy 0070) re-launch can be found on the webinar page under “Documents”.

Transparency and Disclosure Resources and News

  1.  Registration for the PHUSE Data Transparency Summer Event (20–22 June 2023) is open. Virtual sessions run from 15:00 to 17:30 (BST). The agenda for the 3 days can be accessed here and includes an update on EMA Policy 0070 Data Transparency by Karen Quigley, EMA on Day 2 . To catch up on past events, see content available on demand from the PHUSE Engagement Hub, or read the high-level summaries for each event on the Working Groups Events Archive page.

  2. Canada’s Drug and Health Technology Agency (CADTH), the UK’s National Institute for Health and Care Excellence (NICE) and The US Institute for Clinical and Economic Review (ICER) have issued a joint position statement on redating clinical data awaiting publication. They “will not routinely redact clinical data that are awaiting publication when they publish their respective recommendations, guidance, or decisions.” NICE and CADTH will apply this for evaluations starting after April 2023 and ICER will allow redaction of data that is formally planned for public release for 12 months, as academic-in-confidence. Appendix A of the position statement provides a list of categories of clinical data that can/cannot be redacted. This update is to align with the May 2022 statement from International Committee of Medical Journal Editors (ICMJE) which does not consider “results or data contained in assessment reports published by health technology assessment agencies, medical regulators, medical device regulators, or other regulatory agencies to be duplicate publication.”

  3. Khaled El Emam, spoke at the IAPP Canada Privacy Symposium (25 and 26 May 2023) on future uses of data. 

    Khaled El Emam has also posted about the 7th June AccessPrivacy annual conference by Osler being sold out. There will be a panel on de-identification / anonymization practices, incorporating diverse perspectives from industry, academia, and regulators, which is very timely given the on-going legislative reform activity. 

    If you know anyone attending who is willing and able to share relevant outputs,   e.g. slide decks/recordings, from these conferences, please let the CORE Reference Team know (contact@core-reference.org) .

  4. TransCelerate’s Clinical Content and Reuse team has launched an eTemplate Implementation Survey open to ALL involved in the drafting of clinical research protocols. The survey is aimed to gain insight into asset use by stakeholders across the clinical research landscape in order to establish a long-term sustainability plan for the Clinical Template Suite (CTS). The survey will be active through the end of June 2023. 

  5. The updated version of the Proposed amendments to de-identification and anonymization provisions in the Digital Charter Implementation Act, 2022 (Bill C-27) from the Canadian Anonymization Network has been posted.

  6.  Private AI and Replica Analytics announce partnership to tackle data privacy.

Development Strategy News

On 7 and 8 June 2023, the FDA’s CDER, CBER, and the Duke-Margolis Center for Health Policy will host a jointly sponsored virtual public workshop on the Rare Disease Endpoint Advancement (RDEA) Pilot Program and novel endpoint development for rare disease drug development. The purpose of this public workshop is to discuss topics relevant to the development of endpoints for rare diseases.For more information and to register for this workshop, visit the Duke-Margolis Center for Health Policy RDEA public workshop webpage.

News from Asia Regulators

  1. In conjunction with the release of the ICH S12 guideline, China CDE drafted recommendations of implementation and translated a draft Mandarin version of ICH S12 guideline, both of which are open for public consultation until the end of May 2023. (Page in Mandarin)

  2.  China adopted the ICH E19 guideline on “A Selective Approach to Safety Data Collection in Specific Late-stage Pre-approval or Post-approval Clinical Trials” in April 2023 and will fully implement the guideline in China from 21 October 2023. (Page in Mandarin)

Artificial Intelligence (AI)/Machine Learning (ML) 

We introduce this new subsection to include AI/ML where they impact the regulatory MW arena - for example - clinical trial reporting, public disclosure of clinical documents and, more widely, strategic clinical drug development.  

  1. FDA has issued a discussion paper on Artificial Intelligence (AI) and Machine Learning (ML) in drug development - Drug Information Update. This paper aims to communicate with a range of stakeholders and to explore relevant considerations for the use of AI/ML in the development of drugs and biological products.
  1. FDA has also released two discussion papers to spur conversation about AI and ML in drug development and manufacturing.

Declaration of Helsinki (DoH) - next revision

The World Medical Association is committed to reviewing the DoH every 10 years and 2023 is the 10th year since the previous update (2013, Brazil). “The DoH is a set of requirements addressed by physicians to physicians. However, in order to facilitate collaboration with non-physician professionals and research participants, all these stakeholders need to have a sufficient common understanding of the updated, latest ethical principles.” Discussions are ongoing with the aim to adopt the revised version at the General Assembly in Helsinki, Finland in October 2024. You can read more in the 34th issue of the IFAPP Newsletter starting on page 8.

Medical Devices 

Medical devices information is kindly compiled by Raquel Billiones.

Updates from the European Commission

  1. The EC just released this guidance document on the content of the Summary of the Clinical Investigation Report (a requirement under the MDR and IVDR). “This guidance aims to ensure that the summary of the clinical investigation report presents information about the design, conduct, analysis, and results of the clinical investigation in terms and in a format that are easily understandable to the intended user of the medical device.” There is an equivalent requirement under the EU CTR – the Lay Summary of Clinical Study Results.
  2. The EC also updated information on the applications for designation as a notified body - Overview of CAB/NBs at each stage of the designation process (18 April 2023).

Updates from the MDCG

  • Revised: MDCG 2020-3 Rev. 1 Guidance on significant changes regarding the transitional provision under Article 120 of the MDR with regard to devices covered by certificates according to MDD or AIMDD.

Updates from the Notified Bodies

  1. Team NB released version 2.0 of Best Practice Guidance for the Submission of Technical Documentation under Annex II and III of Medical Device Regulation (EU) 2017/745.

  2. The NB BSI has a dedicated page on Notified Body and UK Approved Body, whose role is to conduct a Conformity Assessment.

Updates from the UK MHRA

  1. Update regarding the implementation of the future medical device regulations in GB and Northern Ireland markets.

  2. Update to Medical devices: Guidance for manufacturers on vigilance, which provides information for manufacturers of medical devices about reporting adverse incidents and field safety corrective actions to the MHRA.

  3. Update to the Guidance on  how to register medical devices with MHRA for the markets in GB and Northern Ireland (May 2023)

Updates from Switzerland

New releases from Swissmedic on clinical studies for medical devices and IVDs:

  1. Information Sheet Clinical Investigations with Medical Devices

  2. Information Sheet on Performance Studies with IVD 

Updates from the US FDA

Updates from Australia

TGA Australia releases and updates

  1. Updated Medical Devices Essential Principles Checklist that includes clauses relating to personalised medical devices and improved usability.
  2. Guidance on Progress of Regulatory Refinements to Personalised Medical Devices.

  3. Update to the Regulation of Software Based Medical Devices. 

  4. Update to the TGA Guidance on Reclassification of Active Implantable Medical Devices (AIMD) to assist sponsors of AIMD with meeting their obligations and outlines transitional arrangements (May 2023).

Updates from CORE-MD

  1. Check out this blogpost by Coordinating Research and Evidence for Medical Devices (CORE-MD) on Medical Devices for children.

  2. CORE-MD publication on “Artificial intelligence in medical device software and high-risk medical devices – a review of definitions, expert recommendations and regulatory” by Fraser et al.

Other resources

Policy Research Working Paper from the World Bank: A Framework for the Economic Evaluation of Digital Health Interventions.



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