July 2023

Medicines and Vaccines

ICH

  1. The ICH Reflection Paper ‘International Harmonisation of Real-World Evidence Terminology and Convergence of General Principles Regarding Planning and Reporting of Studies Using Real-World Data’ is now available for public consultation until 30 September 2023. The paper presents opportunities for development of new ICH Guidelines and is anticipated for adoption in June 2024 further to the consideration of comments received. The paper outlines the need for harmonised RWD/RWE terminology, metadata and assessment principles, as well as standardized formats for protocol, reporting, and transparency

  2. The Assembly of the ICH in Vancouver in June 2023 adopted three new topics for harmonisation: an efficacy guideline “General Considerations for Patient Preference Studies”; a safety guideline “Nonclinical Safety Studies for Oligonucleotide-based Therapeutics”; and a multidisciplinary guideline “Bioequivalence for Modified-Release Products”. Other topics include a new ICH discussion group and the progress of ICH guideline development and important revisions

  3. ICH published an ICH E6(R3) 9-minute Explanatory Video that provides the rationale for the update of GCP, and the foundational elements that the update aims to achieve. The video also describes the feedback that the EWG are looking for.

  4. ICH published the latest glossary version 4, dated 20 July 2023. The 200-page glossary was compiled by CIOMS from the publicly available guidelines on the ICH website and includes the terms and definitions included in the guidelines of the ICH. Available for free download.

CTR and CTIS

  1.  Slide presentations from the EMA webinar “Clinical Trials Information System Webinar: Second Year of Transition” are available to view (held on 4 July 2023). The topics covered include Sponsor experiences and perspective on transitional trials.

  2. A further update to “Guidance document on how to approach the protection of personal data and commercially confidential information while using the Clinical Trials Information System (CTIS)” was published 10 July 2023 (Version 1.1).   The guidance now includes Chapter 4 on CCI (entitled “Management of commercially confidential information [CCI] in clinical trial information submitted to CTIS) and Chapter 5 on GCP Inspection Reports. Accompanying the guidance update there has been an update to Annex I of  the guideline (dated 10 July 2023).  Annex II to the guidance document (dated 10 July 2023) is a template that applies to Good Clinical Practice (GCP) inspections carried out on category 1 trials where the publication of clinical trial information is delayed by a deferral . 

  3. Directorate-General for Health and Food Safety published a new document entitled “Guidance for the transition of clinical trials from the Clinical Trials Directive to the Clinical Trials Regulation (v1.4)” dated 19 July 2023. The new Guidance reflects the agreement reached by CTAG Contact Points and supersedes chapter 11 of the Q&A on the application of the CTR (version 6.4). The guidance is a series of questions and answers aimed at providing information on the type of clinical trials that sponsors have to transfer to CTIS, the timeline, and the content of the application for mono- and multinational trials.

  4.  The European Commission has published the latest version (6.5) of the Q&A - Regulation (EU) 536/2014, which removes Chapter 11 on transition trials following the publication of the guidance mentioned above.

  5. The public consultation on the CTIS transparency rules, which was open from 3 May to 28 June 2023, is now concluded. EMA is currently reviewing the comments received, with the aim of publishing a concept paper with the proposed simplified transparency rules later this year

FDA Guidance and News

  1. The FDA’s CDER published two Guidance Snapshots that highlight its commitment to improving the diversity of participants in clinical trials. The first snapshot is aimed at patients - it explains what eligibility criteria are, what are diverse populations, how sponsors can improve enrollment and retention, and make clinical trials less burdensome for participants. The second snapshot is aimed at sponsors - it covers similar topics with additional detail on the recommendations in the FDA guidance. The Guidance Snapshots also provide links to two Guidance Recap Podcasts.

  2. In May 2023, FDA issued the draft guidance “Diabetes Mellitus: Efficacy Endpoints for Clinical Trials Investigating Antidiabetic Drugs and Biological Products” for adults and children with type 1 or type 2 diabetes mellitus. The guidance provides recommendations for demonstrating the efficacy of anti-diabetic drugs intended to reduce diabetes-related hyperglycaemia (anti-hyperglycaemic drugs) and to mitigate iatrogenic hypoglycemia associated with diabetes management. Comments should be submitted by 24 August 2023

EMA Guidance and News

  1. EMA’s new IT service management solution, ServiceNow, will replace the current tool ‘JIRA’ by 31 July 2023. Users must have completed their Multi-Factor Authentication to log in with their username followed by @id.ema.europa.eu. Data related to CTIS tickets that were opened prior to 31 July 2023 will continue to be accessible in JIRA until they are closed. In case of issues or difficulties logging in, users are recommended to visit EMA Account Management or contact ServiceNow@ema.europa.eu for support.

  2. EMA’s Clinical Trials Highlights Issue 15, July 2023 is out now. This issue marks the mid way of the CTR transition period, and is packed with information that we recommend you read in full yourselves. Many of the items covered have been brought to you by the CORE Reference Team through the CORE Reference News Summaries, so a lot of it should be familiar. Other noteworthy points in Issue 15 include a planned Sponsor survey on CTR implementation - due to open in September 2023; an update on the ICH E6 R3 Workshop on 13-14 July 2023; and Transitional Trials: 05 July 2023 dedicated workshop and updated CTCG guidance. Happy reading!

  3. EMA’s experience gained so far in conducting studies with real-world data to support EMA’s regulatory decision making is published in this infosheet and new report. The data indicate that RWE can complement other evidence and support assessments of EMA’s scientific committees, working parties and national competent authorities, but it remains necessary to better anticipate the need for these studies and speed up their launch to ensure regulators’ timely access to real-world evidence.

  4. Read the Artificial Intelligence/Machine Learning subsection below to read about EMA’s public consultation on a reflection paper - and see how you can contribute.

  5. EMA has published a workshop report with proposed actions to improve the way clinical trials are set up and conducted in the EU during public health emergencies. Read the News Announcement. The workshop discussions emphasised the need for larger studies across several European countries, speedier recruitment and delivery of conclusive results with accelerated timelines during a public health emergency. The report will be taken into account by the European Commission, EMA and the Member States in establishing a concrete roadmap for improved clinical trials during public health emergencies in the EU.

  6. The Heads of Medicines Agencies (HMA) Clinical Trial Coordination Group (CTCG) published the following documents:

Transparency and Disclosure Resources and News

  1. The first Plain Language Standard is now approved by the International Organization of Standardization (ISO), and can be purchased and used by organisations or individuals. The standard was developed by an international committee of experts and is based on empirical evidence. You can learn how this standard can help you here. There is also a FAQ page.

  2.  The British Heart Foundation (BHF) charity - the biggest independent funder of cardiovascular research in the UK - has reviewed compliance with BHF policies on clinical trial registration and reporting in a systematic way. BHF expects that the primary results of a BHF-funded clinical trial are published in a peer-reviewed journal or platform within 24 months of primary study completion. Of 14 trials that completed at least 24 months prior to 31/03/2023, 100% had results published in a peer-reviewed journal, with 86% (12/14) publishing within 24 months of study completion. 14% (2/14) published primary results >24 months after study completion. Read the Transparimed summary here and the full BHF report here.

Development Strategy News

  1. Cro et al’s paper in Trials, ‘Starting a conversation about estimands with public partners involved in clinical trials: a co-developed tool’ bridges the gap between designing estimands and patient engagement in study design. The challenge in explaining and designing estimands with a non-technical audience is considerable. The Patient and Public Involvement Tool received unanimous support from the cohort and could help study teams engage with patients during protocol development.

  2. Englert et al have published ‘Defining estimands for efficacy assessment in single arm phase 1b or phase 2 clinical trials in oncology early development’. The article provides an important case study and framework for defining phase 1b/2 estimands for oncology studies. With representation from multiple pharmaceutical and clinical trial organisations - the article breaks down the challenge by estimand attribute before addressing common oncology problems and then consolidates in the form of case studies.

  3. On 19 July 2023, an on open consultation was launched on the draft WHO guidance on best practices for clinical trials, following the resolution on ‘Strengthening clinical trials to provide high-quality evidence on health interventions and to improve research quality and coordination’ adopted by the 75th World Health Assembly. Stakeholders can provide their comments by 15 September 2023.
  4. The World Health Organization (WHO) has issued a draft guidance detailing important scientific and ethical considerations for well-designed clinical trials. The draft guidance is open for public consultation until 15 September 2023. The draft guidance document incorporates the draft ICH Harmonised E6(R3) Good Clinical Practice guideline and the ICH E8 General considerations for clinical studies as well as  the guidance of the Council for International Organizations of Medical Sciences (CIOMS) on clinical research in resource-limited settings and the Good Clinical Trials Collaborative for good randomised clinical trials. Relevant stakeholders should provide comments via the WHO online form.

Real-World Data 

  1. EFPIA published a position paper (21 June 2023): Randomised pragmatic trials (RPTs) to generate high-quality real-world evidence for regulatory decisions. The position paper reviews some of the important  guidances and initiatives and summarises key challenges and recommendations for next steps. The type of pragmatic trials with the highest potential to generate RWE to inform regulatory decision making are defined. Opportunities and advantages for patients, healthcare providers, regulators and drug developers are outlined. Considerations in designing RPTs and of potential challenges and recommendations for actions to enhance the utility of RPT in the European Union (EU) are discussed.

News from Asia Regulators

The Health Sciences Authority (HSA) of Singapore is planning to launch the eCTD to enable full e-submissions in Q4 2024 to minimise the use of storage media such as CD-ROMs/DVDs for submitting documents. The HSA will adopt a phased approach to the use of the eCTD. The use of eCTD for dossier submission will be on a voluntary basis. The initial launch will be open to new drug applications, generic drug applications and their corresponding Drug Master File (DMF) submissions.

Artificial Intelligence/Machine Learning

EMA has opened a public consultation on a reflection paper presenting views on artificial intelligence and machine learning at any step of the lifecycle of human and veterinary medicines, from drug discovery to the post-authorisation setting. Please provide feedback by 31 December 2023 using the dedicated form to help EMA identify opportunities and risks of AI in the field of medicines. The topic will be further discussed during a joint workshop organised with the Heads of Medicines Agencies (HMA) scheduled for 20-21 November 2023. Read  EMA’s News Announcement here.

Medical Devices

Medical devices information is kindly compiled by Raquel Billiones.

Updates from the European Commission

The EC published a list of harmonised standards for sterilisation of health care products and biological evaluation of medical devices under the MDR and the IVDR.

Updates from the MDCG

Revised: MDCG 2022-18 ADD.1 - MDCG Position Paper on the application of Article 97 MDR to legacy devices for which the MDD or AIMDD certificate expires before the issuance of a MDR certificate.

Updates from the UK MHRA

MHRA released the Guidance for Manufacturers on Reporting Adverse Incidents Involving Software as a Medical Device under the vigilance system.

Updates from Switzerland

  1. New communication from Swissmedic on medicinal products with a medical device component (combination products). 
  2. New update to the Guidance Document on Mobile Technologies for both human and veterinary medicinal products. The main objective is to enhance information accessibility for individuals with disabilities with respect to packaging and product information of health products.

Updates from Australia

TGA Australia has launched a consultation on the regulatory requirements for medical devices containing materials of animal, microbial or recombinant origin. TGA is inviting stakeholders, experts, and the public to participate in this important consultation process.

Other resources

The European Academy of Paediatrics (EAP) along with 22 clinical associations with an interest in child health wrote an open letter to the European Commissioner for Health to call for immediate action to address the availability of orphan and paediatric medical devices in Europe.

Updates from China

China NMPA issued “Guidance on Application Materials for Classification of Medical Devices” (page in Mandarin) in June 2023, which is applicable to both domestic and overseas manufacturers. A snapshot of the materials required is described in a third-party website here.

Updates from India

In May 2023, the Indian government proposed the new “National Medical Devices Policy, 2023” to put in place a patient-centric, comprehensive framework for ensuring sustained growth and development of the sector in a holistic and coordinated manner.

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