January 2024

Medicines and Vaccines

CTR and CTIS

1. A list of the official public holidays in European countries for 2024, as recorded in CTIS has been published on the EMA website.

2. EMA is hosting a CTIS Walk-in Clinic on 24 January 2024 at 16:00-17:00 CET. Participants can submit their questions in advance until 15 January 2024 via Slido with the code #clinic241.

3. A recording of the CTIS bitesize talk 29 Nov 2023 entitled “Training materials, CTIS pre-requisites, and updates on transparency rules” has been published online and can be downloaded from here. 

4. A video recording of the EMA workshop on generating clinical evidence for treatment and prevention options for long-COVID/post-acute sequelae condition (PASC) is now available. Topics discussed include identifying appropriate patient population and efficacy endpoints in clinical trials.  

5. Clinical Trial Coordination and Advisory Group (CTAG) meeting minutes (held on 27 Nov 2023) and slides presenting the outcome of the second survey on CTR and CTIS  are now available to download. 

6. EMA has announced dates and information for the CTIS sponsor end user training programme planned for February, April and June 2024.

7. On 9 February 2024, EMA is hosting a training event to support non-commercial sponsors transition trials to CTIS. Participants can submit their questions in advance via slido with the code #Transitioningtrials. Agenda can be accessed here. During the event, representatives from the Member States and EMA will provide guidance and resources to support non-commercial sponsors in transitioning their trials to CTIS.

8. The December 2023 report on the implementation of the Clinical Trials Regulation (CTR) is now available to download and includes  an overview of  the cumulative numbers for initial clinical trial applications submitted since 31 January 2022. 
9. In CTIS Newsflash - 26 January 2024, EMA confirmed it is working on the technical implementation of the revised CTIS transparency rules, foreseen for Q2 2024. In the meantime, for initial clinical trials applications sponsors may follow the principles of the revised CTIS transparency rules. A sponsor may refrain from deferring publication of documents and provide a version ‘for publication’ and ‘not for publication’ only for those documents in scope of the revised rules (Annex I of the revised CTIS transparency rules). 

UK and MHRA News

1. The MHRA has developed a process to share operational information for new active substance MAAs or variation for indication extension applications to support timely patient access to medicine. The purpose of operational information sharing with health system partners, the nature of the information shared, and the consent, withdrawal of consent, and information management processes are detailed in the Operational Information Sharing Guidance.

2. The latest release of HRA Now clarifies the HRA policy on registration of Clinical Trials of Investigational Medicinal Products (CTIMPs) within the EU CTIS. CTIS does not allow users to submit information about UK CTIMPS conducted as part of a multinational trial. As such, research teams conducting a CTIMP in the UK as well in the EU or EEA (European Economic Area), need to register the trial with a registry such as ISRCTN and ClinicalTrials.gov.

FDA Guidance and News

1. FDA and Health Canada will be co-hosting a regional public meeting to provide information to stakeholders and solicit input prior to the next ICH Biannual Assembly meeting scheduled for June 4-5, 2024. register for the event here. Agenda can be downloaded here. 

2. ClinicalTrials.gov has updated “Notices of Noncompliance and Civil Money Penalty Actions.” The information is published as a table listing the responsible parties, NCT number, the Notices of Noncompliance sent by FDA and the amount (if any) of civil money penalties assessed.
3. The modernised ClinicalTrials.gov now includes a section called ‘Submit Studies’ where users can find PRS Help Resources, including How to Register Your Study and How to Submit Results. In addition, Policy Information can also be found in a new section called ‘Policy’, which also includes the FAQs and Date Element Definitions.

4. The Good Cause Extension (GCE) Request Process and Criteria document has been updated (January 2024) to include additional situations that would be considered “not good cause” for granting an extension request to extend the deadline for submitting clinical trial results information to ClinicalTrials.gov. A new FAQ was also added.

5. FDA released a draft guidance for industry entitled “Conducting Remote Regulatory Assessments--Question and Answers.” FDA has used remote regulatory assessments (RRAs) to conduct oversight, mitigate risk, meet critical public health needs and help maximise compliance of FDA-regulated products. This draft guidance provides Q&A regarding what RRAs are, when and why FDA may use them, and how FDA may conduct them, among others. It is open for comments until 27 March 2024.

6. The US FDA has published draft guidance document entitled “Collection of Race and Ethnicity Data in Clinical Trials and Clinical Studies for FDA-Regulated Medical Products” and presents a standardised approach to collecting and reporting race and ethnicity data in clinical trials. Public comment can be submitted until 29 April 2024 here.

EMA Guidance and News

1. EMA and the European Organisation for Research and Treatment of Cancer (EORTC) will jointly organise a workshop on 29 February 2024 on how patient-reported outcomes (PRO) and health-related quality of life (HRQoL) data can inform regulatory decisions.  Registration for online participation is open until 16 February 2024. Register here.

2. The EMA has released a major revision of its user guide for micro, small, and medium-sized enterprises (SMEs) in the pharmaceutical sector. It contains comprehensive information on the EU legislative framework for medicines, and provides requirements for the development and authorisation of medicines for human and veterinary use. The new release includes significant updates to veterinary regulation (fully revised to align with veterinary regulation); updated to to provide an overview of the CTR and CTIS (new section 4.4); and offering insights into the medical devices regulation for human medicines (new section 4.8)

3. EMA has added the section “Resumption of clinical data publication for all medicines” in the clinical data publication website. After a period of suspension, EMA has resumed clinical data publication for medicines with new active substances that received a CHMP opinion from September 2023 onwards. The clinical data packages for non-COVID-19 medicines published following the resumption are available in January 2024 via EMA's clinical data website.

Real-World Data

1. European Joint Programme on Rare Diseases (EJP RD) online training webinar on 26 January 2024: Real-World data, machine learning and deep analytics in rare diseases: Regulatory grade data collection for marketing authorization submissions – what is buzz, what is realistic? The workshop is free but you must  register in advance here. Registration deadline: 25 January 2024.

2. HMA/EMA joint Big Data Steering Group published the updated Big Data Workplan 2023-2025 (Version 1.2 – January 2024) and includes an overview of  timelines. The full presentation can be downloaded here.

Transparency and Disclosure Resources and News

1. Registration for PHUSE Data Transparency Winter Event to be held 6-8 Feb 2024 is now open. This is a virtual event with presentations delivered on each of the 3 days from 15:00-17:30 (GMT). There will also be a panel discussion and Q&A session each day. Speaker and abstract details together with registration info  can be found here.

2. The December 2023 Biotechnology issue of EMWA’s Medical Writing journal  features an article by Elliot Zimmerman entitled “Overcoming confidential information challenges faced by study sponsors.”  The full article can be downloaded here. 

3. The Clinical Trials Transformation Initiative (CTTI) investigated factors and barriers to registration and reporting summary results information.  Suggestions for improvement for applicable clinical trials (ACTs) are presented in their report entitled “Improving Timely, Accurate, and Complete Registration and Reporting of Summary Results Information on ClinicalTrials.gov”. An overview is available here. Following the release of the CTTI report, this blog post discussed further the main findings and take-home messages of the report.

4. The 2 first serious breaches in clinical trials were made public on EU CTIS. They can be viewed by searching  in the database under “Advanced Criteria”, then check the box “Serious Breach”. 

5. DeVito et al published a cross sectional audit study on the availability of results of clinical trials registered on EU Clinical Trials Register (EUCTR). Out of 500 trials, results of 53.2% trials are available on EUCTR, which exceeded the proportion of results available on other registries with matched records. The median time to results was fastest on EUCTR (1142 days), which exceeded ClinicalTrials.gov (3321 days). Read the full paper for more details.

6. Gattrell et al. published the first reporting guideline dedicated to all consensus-based biomedical research entitled “ACCORD (ACcurate COnsensus Reporting Document): A reporting guideline for consensus methods in biomedicine developed via a modified Delphi”. It aims to support authors in writing accurate, detailed manuscripts in a complete and transparent manner when reporting the methods used to reach agreement.

Development Strategy News

1. A recently published open access article by Hey et al. entitled “A Future European Scientific Dialogue Regulatory Framework: Connecting the Dots” provides an overview of challenges that the multiple options for accessing EMA Scientific Advice (SA) and reflects on the ways in which the present SA options could be consolidated and optimised to meets the scientific needs of medicine development. 

2. Master trial design is becoming common to address challenges in traditional trial design. An online article written by Laura C. Collada Ali explores the concept of master trials and summarises the critical contents when drafting a related clinical study protocol.

3. The last periodic review of the World Medical Association (WMA) Declaration of Helsinki was conducted by a new workgroup in 2023. To maximise input by all stakeholders and the public, the revision proposed by the workgroup is provided for public comments. Phase 1 of the public comment period is being held now. Follow the instructions in the WMA webpage to submit comments by 7 February 2024. A phase 2 comment period will follow in the spring when additional topics have been addressed.

Artificial Intelligence/Machine Learning

1. Further information on the European Joint Programme on Rare Diseases (EJP RD) online training webinar on 26 January 2024 is provided in the Real World Data section.

2. On 24 January 2024, the European Commission launched “a package of measures to support European startups and SMEs in the development of trustworthy Artificial Intelligence (AI) that respects EU values and rules.” This follows the political agreement reached in December 2023 on the EU AI Act which will support the development, deployment and take-up of trustworthy AI in the EU. Further information and the full press release can be accessed here.

News from Asia Regulators

1. Effective 1 January 2024, the Thai Clinical Trial Registry (TCTR) is transferred from the Medical Research Foundation to the Foundation for Human Research Promotion in Thailand. Additional details regarding the registration system's operation will be provided as soon as they are available. The TCTR gradually stopped its operation in November 2023 due to lack of financial support.

2. On 16 January 2024, the National Medical Research Register (NMRR), Malaysia, published an update to provide information on the latest developments, including the following updated documents:
   • Data Elements and Parameters for NMRR Submission (V2.1)
   • User Guideline for Investigator/CRA - New Research Registration & Other Submission Purposes, NMRR v2.0.

Medical Devices

Updates on Drug-Device Combination Products

1. A Regulatory Affairs Professionals Society open access article written by  Chin-Wei Soo and Niedre Heckman entitled “Drug-device combination products: Device regulatory submission content and considerations” is available to view. The article provides practical advice and guidance for the inclusion of medical devices in the electronic common technical document structure.

2. EMWA is offering a new workshop on “Introduction to Drug-Device Combination Products” this year. Watch this space for more information.

Updates from the MDCG and the European Commission

1. Language requirements for medical devices: With 27 EU member states and 24 EU official languages, health companies in the EU face challenges with respect to the languages of product documentations and labels. Hence the European Commission and Member States have created tables to help companies, especially SMEs, to understand the language requirements under the MDR and IVDR for the information and instructions that accompany a device in a specific country. The tables provide an overview of the language requirements for each Member State.

2. Online survey: The European Commission is conducting a survey (from 13 December 2023 - 31 January 2024) to identify the key benefits and challenges of the current EU medical device governance and regulations and their impact on innovation. The survey, in the form of an online questionnaire, targets all types of actors and stakeholders. This includes but is not limited to Competent Authorities, Notified Bodies, economic operators (especially SMEs) and their representatives, as well as patient and professional organisations, and other sectorial interested parties. So everyone working in the field of medicines is encouraged to participate.

3. The European Commission is proposing more time for companies to apply the In Vitro Diagnostic Medical Devices Regulation (IVDR), under certain conditions. The Commission is also proposing measures to enhance transparency in Medical Devices including speeding up the launch of some elements of the European Database on Medical Devices – EUDAMED. Read the full press release here.

4. The EMA has released a major revision of its user guide for micro, small, and medium-sized enterprises (SMEs) in the pharmaceutical sector including offering insights into the medical devices regulation for human medicines (new section 4.8). Details of other changes are provided under EMA Guidance and News above.

Updates from the Notified Bodies

What is the “lifetime” of a medical device and why is it important? There are certain regulatory requirements that apply throughout the whole lifetime of a medical device. Team NB released in December 2023 a position paper on Medical Device Lifetime. “As there is no specific definition for device lifetime within the regulatory text, this position paper is intended to promote consistency in approach, to provide an overview of existing  guidance and standards, to identify expectations and illustrate the matter for different device types.

Updates from the MHRA

In January 2024, the MHRA released a Roadmap Towards the Future Regulatory Framework for Medical Devices. The regulatory roadmap sets out plans for new measures to support safe access to medical technology including AI and diagnostics in the UK. The visual timeline of the MHRA roadmap can be found here.