REGULATORY PUBLIC DISCLOSURE (RPD) - AUGUST 2022

Medicines and Vaccines

Good Publication Practice 2022

‘Good Publication Practice (GPP) Guidelines for Company-Sponsored Biomedical Research: 2022 Update’ or ‘GPP 2022’ was published in Annals of Internal Medicine on 30 Aug 2022. Read the highlights in the MAP Newsletter.

CTR and CTIS

Implementation of EU CTR continues to bring challenges. For instance, by 30 April this year 18% of Clinical Trial Applications (CTAs) submitted under EU CTR had either been withdrawn by the sponsor or had lapsed at the time of validation. In a Krystelis white paper “EU CTR 536/2014: A guide to support implementation”, Krystelis shares further ideas and insights on transitioning to EU CTR. Download the Whitepaper for details.

As of 31 July 2022, a total of 195 CTAs had been submitted under EU CTR 536/2014 through CTIS with volumes increasing steadily each month (According to EMA’s KPI report, 23 Aug 2022). Of these, 188 are initial CTAs, 4 are substantial modifications, and 3 are subsequent additions of a member state.

On Thursday 22 September 2022, EMA will organise an event to support CTIS users with organisation management system i.e., OMS-related questions.

EU Regulatory

The EMA’s ACT EU published its workplan for the next 4 years in ‘Accelerating Clinical Trials in the EU: publication of 2022-2026 workplan’. Plans for 2023 include:

• Large, multinational clinical trials: establishing a support process specifically aimed at academic sponsors in order to make the EU a more attractive region to conduct clinical research
• Implementation of the CTR: a particular focus on Clinical Trial Information System (CTIS) and CTR training activities and trouble-shooting any issues encountered by clinical trial sponsors
• Multi-stakeholder platform: will be established in 2023 to facilitate the evolution of the clinical trials environment through regular dialogue between all stakeholders, including patients, healthcare professionals and academia, to find practical solutions to enable and drive change
  Modernisation of good clinical practice: ACT EU will support not only the adoption but also the implementation of revised EU guidelines in technology and clinical trial design
• Facilitation of innovative clinical trial methods: the initiative will issue guidance on decentralised clinical trials by the end of 2022 and publish a methodology roadmap to identify and prioritise key advances in clinical trial methods.

FDA Guidance and News

1.Examples of standard tables and figures and standard adverse event groupings and queries for evaluation of Biologic/New Drug Applications are to be released for public view by the Office of New Drugs (OND) in the FDA Center for Drug Evaluation and Research (CDER). Further details will be shared at an FDA Public Workshop on 14 September. Details on how to attend this virtual workshop are here.

Additionally, Vaishali Popat MD, MPH, Associate Director of Biomedical Informatics and Regulatory Review Science, OND, CDER, FDA, will speak on this topic at the regulatory plenary session at PHUSE/FDA CSS 2022 in September 2022. Feedback on the documents will be discussed at breakout sessions, and it is planned that the PHUSE Safety Analytics Working Group will form a project to consolidate feedback; contact workinggroups@phuse.global for further information.

2.On 09 Aug 2022, the FDA’s Office of Global Policy and Strategy published “How a European Data Law is Impacting FDA,” which looks at how the European Union’s General Data Protection Regulation (GDPR) may be impacting the FDA’s public health activities. So far, the FDA’s bioresearch monitoring program, which oversees the conduct and reporting of FDA-regulated research, has been most affected by the law.

3. The Center for Information and Study on Clinical Research Participation (CISCRP) recently undertook a study of ClinicalTrials.gov listings to assess their readability for the average person. Examining the Current Value of ClinicalTrials.gov Listings for Patients and the Public was published August 12th in Applied Clinical Trials. The authors found listing trial details on ClinicalTrials.gov may meet regulatory requirements, but entries must be written in plain language understandable to the layperson to serve the registry’s purpose of making trials more accessible to the public.

4. Updates to CT.gov Beta are now available. New features include an improved search experience, along with a table view for search results. Other changes include improved accessibility and navigation. To learn more about these updates, please read the Release Notes found on ClinicalTrials.gov Beta under "About."

5. The FDA addresses inquiries from stakeholders related to good clinical practice and human subject protection policies on an ongoing basis. The agency published responses to inquiries from 2017 to 2021 to make this information available to stakeholders in a searchable format. Enquiries prior to 2017 are available in the FDA archive (which does not appear to be online as far as the CORE Reference Team can see). Please contact gcpquestions@fda.hhs.gov with questions.

Transparency and Disclosure Resources and News

1. An 18 Aug 2022 article in The Scientist titled ‘NIH Fails to Enforce Rules for Reporting Clinical Trial Results’ indicates that “A review by the US Office of Inspector General found that only about half of the scientists running clinical trials funded by the NIH in 2019 and 2020 appropriately recorded their findings in a federal database, as is legally required.”

2. Razack et al’s paper published in Science and Public Policy titled ‘Clinical trial transparency regulations: Implications to various scholarly publishing stakeholders’ is sadly not available open-access, but is worth a read if you are able; the message about the role of the professional medical writers (PMWs) is clear, as can be seen in excerpts, which include: "Assistance from PMWs is another important but ignored area for effective reporting. The crucial role of PMWs is associated with an overall improvement in the quality of CT reporting, as evident from a 2019 systematic review. The use of PMWs had shown improved reporting compliance using CONSORT. With the in-depth training, professionalism, and integrity that are usually driven from the professional writing or editing associations that they belong, PMWs respect ethical principles, help fulfil the reporting obligations of CTs, and are instrumental in the increasing trend of CT publications over the years."

3. Sharing Anonymized and Functionally Effective (SAFE) Data Standard for Safely Sharing Rich Clinical Trial Data - open-access paper on the SAFE Data Standard (a standard for Sharing Anonymous and Functionally Effective data) which focuses on protecting privacy to share non-identifiable clinical trial data for ethical secondary uses and disclosures.

4. No More Paywalls on Federally Funded Research: Biden Administration requires all publicly funded work to be freely available and publicly accessible by default at the time of publication by 2026 #openaccess.

5. The article ‘Long-term availability of data associated with articles in PLOS ONE’ by Lisa Federer explores the true availability of data associated with research articles. The suggestion is that “...URLs and DOIs may be an effective means for accessing data over time”.

6. Campbell et al’s article in Trials titled ‘Access to unpublished protocols and statistical analysis plans of randomised trials’ seeks to determine “...how often study investigators would share unavailable documents upon request”. The authors conclude that “Most study investigators did not share their unpublished protocols or SAPs upon direct request. Alternative strategies are needed to increase transparency of randomised trials and ensure access to protocols and SAPs.”

7. The Harvard Data Science Review article titled ‘Why It Takes a Village to Manage and Share Data’ looks ahead to the NIH policy for data management and sharing which will take effect in 2023.

 Development Strategy News

1. Data Analysis: A current hot topic is the potential for use of “R” in the processing of data in regulatory submissions. R is a programming language developed for statistical analysis and data visualizations, used widely by analysts and scientists. The advantages and disadvantages of using this open-source software compared to conventional packages are discussed in a Blog on the PHUSE website.

 News from Asia Regulators

1.The Taiwan FDA released the first draft guidance on “COVID-19 Biological Products: CMC and Development Strategy” (in Mandarin) in August 2022. The guidance references the US FDA Guidance for Industry: ‘Development of Monoclonal Antibody Products Targeting SARS-CoV-2, Including Addressing the Impact of Emerging Variants, During the COVID-19 Public Health Emergency’ and relevant global standards/experiences, providing recommendations to sponsors on developing monoclonal antibody products targeting SARS-CoV-2 in Taiwan.

Medical Devices

Medical devices information is kindly compiled by Raquel Billiones.

UPDATES FROM THE EUROPEAN MEDICAL TECHNOLOGY INDUSTRY (MEDTECH EUROPE)

On the EU Data Act
Following the publication of the new EU Data Act earlier this year, MedTech Europe called on EU legislators “to foster a data-sharing ecosystem that supports data-driven innovation whilst ensuring citizens’ rights.” Check out the press release here.

2022 Code of Ethical Business Practice
Also earlier this year, MedTech Europe adopted a revised Code of Ethical Business Practice, “a self-regulatory instrument developed by the medical technology industry which regulates all aspects of the industry’s relationship with Healthcare Professionals (HCPs) and Healthcare Organisations (HCOs).”

Position Paper on Guidance Documents for the MDR and IVDR
MedTech Europe released a position paper with Recommendations on the use of Guidance Documents Related to the Medical Device Regulation (MDR) and In vitro Diagnostics Regulation (IVDR). With this paper, the industry expresses its view on how MDCG guidance documents should be used in a prudent way without distruption to manufacturers’ efforts to transition to the new rules of the MDR and IVDR.

MedTech Europe Survey Report on availability of MDs under the MDR
MedTech Europe conducted a survey in April 2022 to assess the state of implementation of several key aspects of MDR. The results are presented in this report.

OTHER UPDATES
Open Medical Device Webinar by EUPATI
The European Patients’ Academy on Therapeutic Innovation (EUPATI) is organising an Open Webinar on Medical Devices on 13 Sep 2022.

Update from BSI
The Notified Body BSI recently released an updated brochure on Active Implantable Medical Devices (AIMD).

1. From early 2022, Taiwan FDA has implemented a new online Medical Device Electronic Pre-market Application Platform for Class II and III medical devices. Through the e-Submission system, medical device manufacturers could apply for Class II and III medical device registration, update the registration, or extend licensing. 
2. EUDAMED Delay
   The European Commission issued a new update on the European Database for Medical Devices (EUDAMED) timelines in June, indicating a delay of approximately a year. The EUDAMED is now expected to be fully functional in Q2 2024 and will be mandatory in Q2 2026 following a 2-year transition period.
3. MDCG-2022-12 on IVD in EUDAMED
   In July, the MDCG released a guidance on harmonised administrative practices and alternative technical solutions until Eudamed is fully functional in relation to the EU Regulation 2017/746 on in vitro diagnostic medical devices (IVDR).
4. MHRA Updates
   Last year, MHRA consulted on the new UK regulatory framework for medical devices post-Brexit. The full outcome of the consultation has been released.
5. Updates from China
   The NMPA released the “Guideline for Fundamental Principles Compliance of Medical Device Safety and Performance” which describes the general requirements for all medical devices and its risk-based approach for registration review.
6. An article on “China’s NMPA: The evolution of medical device regulation” was published in the June 2022 issue of RAPS RF Quarterly (RAPS membership is needed to access the article).