April 2022

Medicines and Vaccines

ICH Guidance

Draft version (endorsed 04 April 2022) of ICH Guideline E11A ‘Pediatric Extrapolation’ is currently at Step 2 and is under public consultation.

EMA Guidance and News

  1. EMA have released new ‘Guidance for applicants/MAHs involved in GMP and GCP inspections coordinated by EMA’ first published on 06 Apr 2022. A full list of documents for inspection provided under the GCP inspections section starting on page 4 is most helpful. This and other useful documents reside on the EMA Good clinical practice webpage.

2. On 30 March 2022, EMA made this statement “Sponsors can adjust the way they run clinical trials that have been affected by the war in Ukraine using the experience gained during the COVID-19 pandemic. They can also apply the approaches and flexibilities agreed in the context of the pandemic.” Read more here.

3. Draft ‘Guidance document on how to approach the protection of personal data and commercially confidential information in documents uploaded and published in the Clinical Trial Information System (CTIS)’ is open for consultation until Sept 2022.

I draw your attention to:

Section 4.4.2. Proactive redaction minimisation approaches (lines 894 to 910)
“Medical writing can play an important role in reducing the need for redactions. It is expected that embedding a CCI identification and tracing strategy during the writing of the CTIS related documentation would limit the unnecessary dissemination of commercially confidential information in documents where these pieces of information are not essential, required or relevant. Therefore, it is
suggested that the sponsors and marketing authorisation applicants/holders consider identifying early during the development plan those pieces of information which are considered CCI, track these as the product evolves and proactively minimise the distribution of these pieces of information across the
clinical trial documentation already when the documents are written. This strategy can be further complemented by employing document templates which specifically indicate which information is required to be included in the documents according to the clinical trial legislation, scientific guidelines and regulatory guidance. As a complementary approach, tagging those pieces of information which are considered CCI at the time the clinical trial documents are written would facilitate the preparation of the document versions meant to be published. It is envisaged that implementing such approaches would reduce the efforts entailed by preparing separate document versions for publication purposes and it would allow the CTIS users to publish in higher proportion the very same documents which were submitted for scientific evaluation.”

It is good to see formal recommendations, often already captured in processes followed by the MW community. This shows the criticality of the MW in the document development process.

4. CTR (EU) 536/2014 Q&A Version 06 April 2022 has been submitted for discussion to the Expert Group on Clinical Trials.

EU CTR/CTIS News

‘CTIS Highlights’ has been renamed ‘Clinical Trials Highlights’ and issue 08 (published 25 Mar 2022) is out now. The name change allows inclusion of topics like ‘Accelerating Clinical Trials in the European Union’ (ACT EU) as well as CTIS. Sign up to receive the ‘CTIS Newsflash’ and the ‘Clinical Trials Newsletter’ by e-mailing CT.NewsletterSubscriptions@ema.europa.eu. In this issue, there is a link to the 20 Jan 2022 video demo of CTIS (bookmark the demo page). The 10th CTIS Newsflash reports metrics including 305 draft applications; 26 submitted applications; and 1 authorised – see below.

On 31 March 22, the first clinical trial authorisation was issued through CTIS The trial was originally registered under the Clinical Trials Directive in EudraCT and was subsequently moved under the EU CTR and into CTIS. The Member State Concerned is Sweden. On 01 April, there were no publicly available documents related to trial information – it’s early days and that may change – keep looking.

FDA Guidance and News

1. A JAMA survey conducted in July 2021 and published in February 2022 shows that a representative cohort of US adults overwhelmingly support greater transparency at the FDA. It is suggested that the results may reflect the public’s improved understanding of the drug development process in the context of the COVID-19 health emergency.

2. FDA Guidance ‘Emergency Use Authorization for Vaccines to Prevent COVID-19’ was updated on 31 March 2022. This supersedes the Guidance last issued in May 2021.

3. Final FDA Guidance E8(R1) ‘General Considerations for Clinical Studies’ is now available (April 2022).

4. National Institutes of Health (NIH) have a new NIH Scientific Data Sharing Website. Resources include the ‘Data Management and Sharing Policy’ referenced in an earlier CORE Reference post.

5. Draft FDA Guidance titled: ‘Diversity Plans to Improve Enrollment of Participants from Underrepresented Racial and Ethnic Populations in Clinical Trials’ is open for comment. Per the Introduction: “Adequate representation of these populations in clinical trials and studies supporting regulatory submissions helps ensure that the data generated in the development program reflect the racial and ethnic diversity of the population expected to use the medical product if approved…”

6. FDA have released Final Guidance in April 2022 on Bioavailability Studies Submitted in NDAs or INDs – General Considerations.

Health Canada

The ‘Public release of clinical information for drugs and medical devices in COVID-19 interim orders applications: Guidance’ was modified Q1 2022. Access to data for COVID-19 therapeutics sold in Canada under two interim orders is available. 

Big Data

EMA are publishing a quarterly progress update on the work of the HMA-EMA Big Data Steering Group. Issue 1 of ‘Big Data Highlights’ is out now (published 15 Feb 2022). To subscribe contact bigdata@ema.europa.eu. The following excerpt titled ‘Regulatory capability to analyse data: pilot on raw data use’ is of particular relevance to the clinical trials industry and our own regulatory MW community: “EMA, in partnership with the Advisory Group on Raw Data comprising representatives of the Big Data Steering Group, NCAs, EMA committees and working parties and patients representatives, is preparing a pilot to clarify the benefits and practicalities of access to individual (raw) patient data from clinical trials in the assessment of medicines. The pilot, which is expected to start in the second quarter of 2022, will analyse raw data from selected marketing authorisation applications to support the CHMP assessment. The results of the pilot, expected in 2023, will help the EU medicines regulatory network to make an informed decision on the place of raw data in regulatory decision-making.”

Transparency and Disclosure Resources and News

1. This article in the Journal of Law, Medicine & Ethics titled ‘Transparency of Regulatory Data across the European Medicines Agency, Health Canada, and US Food and Drug Administration’ provides a snapshot of current clinical trial information sharing by RAs for a broader audience than clinical trials professionals. It is actually a really good introduction to the topic for newer members of our community too.

2. The PHUSE Data Transparency Summer Event will be free to attend and is planned for 28-30 June 2022. Registration is not yet open; save the date in your calendars for now. The Winter Event recording is now available at the PHUSE Engagement Hub and a summary is available here in the Summary Blog.

3. Bamford et al have a paper published (08 April 2022) in Applied Clinical Trials titled ‘Sharing Anonymized and Functionally Effective (SAFE) Data Standard for Safely Sharing Rich Clinical Trial Data’. This collaborative paper by Janssen’s Head of Clinical Data Standards & Transparency and experts in the field from Privacy Analytics makes interesting reading.

4. Christian De Mey’s letter published in Eur J Clin Pharmacol in Feb 2022 is titled ‘Phase I studies in EU: due change in compliance and transparency under the EU clinical trials regulation’. View the letter via this open access link..

5. UK Research and Innovation’s (UKRI) open access policy is in effect since 01 April 2022.

6. This 40 minute YouTube video is a roundtable where participants discuss transparently reporting preregistration changes to protocols.

7. The Real Life Sciences 2022 Webinar series is free to join – register here. The Webinar ‘Trial Disclosure – A focus on rare diseases’ will be held on 28 April 2022 at 10.00 am ET (US/Canada), and will focus on best practices to apply when working with rare disease trials and populations.

8. This CMRO paper titled ‘Building consensus on author selection practices for industry-sponsored research: recommendations from an expert task force of medical publication professionals’ recommends careful and consistent interpretation of ICMJE authorship criteria to support transparency.

MHRA News

1. This TranspariMED article shows that the ‘UK proposes global effort to strengthen clinical trial transparency'. The draft resolution requests that WHO develop a global action plan for implementing the suggested principles at the 76th World Health Assembly in 2023. This is one to keep an eye on.

2. The PDF on the MHRA page ‘Clinical trials for medicines: authorisation assessment performance’ has been updated.

3. Regulatory approval of the COVID-19 vaccine, Nuvaxovid, has been granted in the UK - with the publicly available documents on this page.

Plain Language Summary

1. This CMRO paper titled ‘Putting plain language summaries into perspective’ presents the perspectives of a variety of PLS end users.

2. This short CMRO paper by Karen Woolley and colleagues presents ‘Clarifications and corrections on PubMed’s plain language summary requirements’

3. This 25 Mar 2022 ‘Peek Behind the Research” interview series presents a poster presented at the January 2022 ISMPP meeting titled ‘Analysis of reach for different formats of plain language summaries’.

Development Strategy News

1. TransCelerate Biopharma have published a paper titled “US Regulatory Landscape: Diversity in Clinical Trials”. The paper categorises regulatory guidelines in four domains – Design, Data, Site, and Participant. From the Executive Summary: “This resource is meant to help inform decisions on the regulatory requirements and recommendations to ensure an adequate racially and ethnically representation in clinical trial participants”.

2. This LinkedIn article titled ‘A Spotlight on Self-assessed Competencies of Clinical Research Professionals and Recommendations for Further Training’ is of interest for those of us engaged in clinical study protocol development. It includes multiple links to other interesting articles.

3. The eSource-readiness assessment tool (eSRA) is provided by eClinical Forum. “The tool contains questions based on regulations and regulatory agency guidelines for clinical research data sources and should be used to evaluate the suitability of an Investigator Site computerized system to provide data for clinical trials”. It may be useful to raise awareness of this tool in disciplines within the clinical research community, but outside of medical writing. Data ends up eventually in our CSRs.

Transparency and Disclosure

1. This UK Government Press Release details recommendations to improve patient healthcare through the safer use of health data.

2. Paludan-Müller et al’s March 2022 article published in J Clin Epidemiology, titled ‘Substantial delays in clinical data published by the European Medicines Agency – a cross sectional study’ provides evidence of considerable delays by EMA in publication of CSRs under Policy 0070. The Agency performed better for clinical data packages published under COVID-19 transparency measures.

 

 

Medical Devices

Medical devices information is kindly compiled by Raquel Billiones.

MDR and IVDR Updates

The EUDAMED: Economic Operator User Guide was updated in April 2022. The guide describes how economic operators can use the actor registration module, including the concept, registration, management, access and mandates.

The EU Directorate-General for Health and Food Safety updated the IVDR Joint Implementation Plan in preparation of the In Vitro Diagnostic Regulation date of application in May 2022.

Check out this blog on the compliance navigator of the Notified Body BSI for quality management systems (QMS) and pre-market clinical investigations.

In April 2022, the European Commission released a report to the European Parliament on the exercise of the power to adopt delegated acts pursuant to the MDR and IVDR. Some of the topics covered are updates on products without an intended purpose, tasks of expert panels and expert laboratories, the UDI system, and minimum content of the EU declaration of conformity.

EUDAMED Updates

This month, there have been updates to the technical documentations for the EUDAMED Notified Bodies & Certificates module and the UDI/Devices module. In addition, two user guides have been updated, the economic operator user guide V2.7 and the UDI user guide v2.7. 

Draft FDA Guidance on Cybersecurity in Medical Devices

The US FDA Draft Guidance on Cybersecurity in Medical Devices: Quality System Considerations and Content of Premarket Submissions is now open for comments until 07 Jul 2022. The updated guidance highlights secure device design and recommendations to address cybersecurity in premarket submissions. When final, this guidance will supersede the cybersecurity guidance from Oct 2014.

TGA Australia 

The Australian Therapeutic Goods Administration released the latest guidance on the reclassification of active implantable medical devices (AIMD). This guidance aims to assist sponsors of active implantable medical devices (AIMD) with meeting their obligations and outlines transitional arrangements to help comply with new regulations.

ISO 14155 Work Group Updates

The ISO 14155 (Clinical investigation of medical devices for human subjects — Good clinical practice) Work Group has restarted discussions around this guideline which was updated in 2020. Topics under discussion are harmonization with the EU MDR, the clinical evaluation process, and the link between risk management and the clinical documents. Check out this video by work group member Danielle Giroud. Questions to the work group can be submitted here.

EC Releases Eudamed Timelines

The European Commission issued their targeted timelines for the Eudamed. Currently, 3 of the 6 modules are functional. It is expected that all modules will go live in Q4 2023, and the use of Eudamed will then become mandatory.

ISO Updates on Medical Devices - Needle-based Injections

The ISO series ISO 11608 Needle-based injection systems for medical use — Requirements and test methods have been updated, as listed below.

FDA on Augmented/Virtual Reality (AR/VR) Medical Devices

As technology advances, regulations on medical devices have to be constantly updated. The FDA Patient Engagement Advisory Committee will meet in July 2022 to discuss the benefits, risks, and uncertainty of AR/VR Medical Devices and come up with recommendations.

MDCG 2022-5

The MDCG released a very important guidance on borderline between medical devices and medicinal products under Regulation (EU) 2017/745 on medical devices. Medical devices are regulated under the MDR, medical product under the Medicinal Product Directive (MDP). Borderline products are those whose regulatory classification are not clear. This guidance document provides definitions and clarifications.

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