Posted on 04 Oct 2022

REGULATORY PUBLIC DISCLOSURE (RPD) - SEPTEMBER 2022

Medicines and Vaccines

ICH

  1. CIOMS compiled and published the “Glossary of ICH terms and definitions”, which combines terms and definitions included in the publicly available guidelines found on the ICH website.

CTR and CTIS

  1. On 14 July 2022, EMA hosted a dedicated workshop on the draft guidance on the protection of personal data and CCI in documents submitted or uploaded via CTIS - the Event Summary is presented on the EMA website.
  2. EU CTR: Get Ready to Adapt! The EU-CTR came into effect on January 31, 2022. From this date until January 30, 2023, sponsors can choose to submit CTA requests for new trials under the current EU Clinical Trials Directive 2001/20/EC (EU-CTD) or under the EU-CTR; however, after January 31, 2023, all new CTAs must follow EU-CTR processes. Sponsors must transition ongoing trials to EU-CTR by January 30, 2025. Preparing for the EU-CTR requires wide-ranging cross-company initiatives…are you ready?
  3. EMA is organising free, live bitesize talks for clinical trial sponsors focused on the functionalities of the CTIS on 28 September, 23 November, and 15 December 2022. Participants may submit questions in advance and vote for the questions they would like to see answered during the live event. 
  4. EMA has published the Clinical Trials Regulation (EU) No 536/2014 Questions & Answers Version 6.2.

EU Regulatory

The European Commission (EC), the Heads of Medicines Agencies (HMA) and the European Medicines Agency (EMA) have published a 2022-2026 workplan: “Accelerating Clinical Trials in the EU (ACT EU).” This workplan builds on the Clinical Trials Regulation (CTR), which became applicable in January 2022, and on the activities of the European regulatory network to support clinical trials. The focus of the 2022-2026 workplan is “innovation in clinical trials, robust methodologies and collaboration across stakeholders.” It outlines ten priority actions to transform clinical trials in Europe and lays out expected deliverables with their respective delivery timelines. A shortened summary is presented on the EMA website.

FDA Guidance and News

  1. The FDA released the final guidance “General Clinical Pharmacology Considerations for Neonatal Studies for Drugs and Biological Products Guidance for Industry” in July 2022.
  2. The FDA released final guidance titled ‘Submitting Documents Using Real-World Data and Real-World Evidence to FDA for Drug and Biological Products’ in Sept 2022. This guidance encourages sponsors and applicants to identify in their submission cover letters certain uses of RWD/RWE. and applies to submissions for investigational new drug applications (INDs), new drug applications (NDAs), and biologics license applications (BLAs) that contain RWD/RWE intended to support a regulatory decision regarding product safety and/or effectiveness.
  3. The FDA has published draft guidance (Sept 2022) entitled, “General Clinical Pharmacology Considerations for Pediatric Studies of Drugs, Including Biological Products Guidance for Industry.” The draft guidance presents considerations for PK/PD studies and ethical issues, discusses paediatric study plan designs and other considerations. Comments on the draft guidance are invited to be submitted to the FDA within 90 days of publication.
  4. The FDA released draft guidance titled ‘Ethical Considerations for Clinical Investigations of Medical Products Involving Children’ in Sept 2022 for comment purposes.  This guidance describes the FDA’s current thinking regarding ethical considerations for clinical investigations of medical products in children.
  5. The NIH has added a new Plain Language Checklist for Lay Brief Summaries to the Support Materials page on ClinicalTrials.gov. The checklist refers to plain language best practices to help investigators write brief summaries of clinical trials that can be easily understood by the general public.

EMA Guidance and News

  1. Data-sharing confirms reproducibility of trials submitted to the EMA: “For 10 trials [for which IPD were available], we identified 23 distinct primary outcomes for which the conclusions were reproduced in all re-analyses.” See the cross-sectional study on European Public Assessment Reports.
  2. A virtual webinar will be held jointly between EMA and  DIA on 16 Nov 2022. Entitled: Clinical Trials Information System (CTIS) Webinar - 9 months on and going forward, the agenda is available to download and you will need to register if you want to attend. Please note that a registration fee is payable. Participants can submit relevant questions to the panel by 17 October 2022.
  3. EU CTR new Statement of compliance template is available to indicate that for a specified clinical trial “The sponsor declares that data have been and will be collected and processed in accordance with the General Data Protection Regulation (EU) 2016/679 (GDPR)”.
  4. EMA has just published a good practice guide for the use of real-world metadata in identifying data sources for studies, released now for public consultation. As data needs become more complex and there is a lack of standardised information and statistics on real-world data sources, the identification of appropriate data sources becomes an increasing imperative for regulatory decision-making in the pharmaceutical field. All interested organisations, regulators and researchers are invited to send their comments by 16 November 2022.

Real-World Data

  1. The ICH Regulator, SwissMedic, issued a position paper in July 2022 to provide guidance regarding the legal basis, regulatory considerations and data requirements for marketing authorisation applications containing RWE.
  2. Wang et al have published a Nature Communications paper ‘Reproducibility of real-world evidence studies using clinical practice data to inform regulatory and coverage decisions’.
  3. Jonker et al. published a review article in August 2022 discussing the utility of patient registries across the different stages of development of orphan drugs to support regulatory decisions.
  4. Should the transparency of real word studies more closely match that expected of clinical trials? See What can be done to increase the transparency of real word studies? in The Publication Plan.

Transparency and Disclosure Resources and News

  1. Mantila et al.’s article in Clinical Pharmacology and Therapeutics in July 2022 titled “Medication Adherence Measurement Methods in Registration Trials Supporting the Approval of New Medicines: A Cross-Sectional Analysis of Centralized Procedures in the European Union 2010–2020” reports their findings on the varying methods used in measuring and presentation of  adherence rates between trials and therapeutic areas. Standardisation of adherence definitions and measurement methods in clinical registration trials is needed and they discuss how this may be achieved.
  2. Health Canada and CIHR (Canadian Institute of Health Research) have outlined plans to improve clinical trial reporting: clinical trials must be registered and results published within the mandated time frame in order to remain eligible for any new funding: CIHR Policy Guide - Requirements and Disclosure of Results from Clinical Trials.
  3. A report posted by Till Bruckner of TranspariMed outlines the six “Worst Violators of US Clinical Trial Disclosure Laws” and is based on data from the  FDAAA Trials Tracker, August 2022.
  4. The SPIRIT 2013 and CONSORT 2010 reporting guidelines are to be updated to enhance transparency in randomized trials. The two will be updated together “to align reporting in both checklists and to provide users with consistent guidance in the reporting of trial design, conduct and analysis, from trial protocol to final publication.” Stakeholders can take part in the Delphi survey process by registering their interest via the SPIRIT–CONSORT project website. Round 1 of the survey is due October 2022. Opinions are encouraged from “researchers with expertise in trial design and methodology; assessors/approvers of trials; commissioners of trial grants; users of SPIRIT and CONSORT guidelines; and consumers of trial results.” 
  5. The US Office of Inspector General (OIG) reported in August 2022 that half of the NIH-funded clinical trials did not comply with the federal reporting requirements in 2019 and 2020 in not posting their study results on ClinicalTrials.gov. The report also provided the reasons why NIH has failed to ensure compliance and recommendations to improve timely reporting.
  6. On September 12th the Clinical Research Data Sharing alliance (CRDSA) posted a white paper titled “A Review of BioPharma Sponsor Data Sharing Policies and Protection Methodologies”. The white paper examines clinical trial data contribution policies and the data protection methodologies applied to protect patient privacy.
  7. The reality of data sharing behaviour: do researchers share their data as promised? From The Publication Plan: “over 90% of authors who indicated willingness to share data did not do so when contacted”.

 Development Strategy News

  1. In June 2022, MRCT released ‘Incorporating Diversity and Inclusion into Clinical Research Protocol Templates: An Outline of Suggested Recommendations’. There do not appear to be any recommendations that are additional to those that protocol development teams are already including as best practice into protocols - but the MRCT summary can be used as a checklist or resource. The document uses the TransCelerate Common Protocol Template (CPT) as a source. 
  2. ‘The role of master protocols in pediatric drug development’ is described in a recent publication by Nelson et al, 2022. The authors describe possible benefits of master protocols in streamlining clinical development and creating efficiencies in clinical operations. However, as the authors point out, the amount of work needed to create this type of protocol “should not be underestimated.”
  3. TransCelerate and Association of Clinical Research Organizations (ACRO) Member Companies have jointly published points to consider when developing a CSR which has interruptions due to unforeseen circumstances e.g., war, a pandemic or other public health emergency, or any geospatial disruption. They propose that contract research organizations (CROs) and sponsors adjust how they develop CSRs for those clinical trials that have been impacted and provide some examples of how disruptions might be noted in the CSR. This publication notes that “…The CSR template developed by TransCelerate and the CORE Reference resources are also widely used. Our members generally have reported that most companies use these resources as a foundation and then tailor the structure of the CSR, creating their own individualized template.” The new 27-page resource (which is a forced download linked within the ‘points to consider’ document) builds on these formative resources and lists the considerations for CSRs using a proposed set of guiding principles along with two content-related sections.
  4. An update to the Good Publication Practice (GPP) guidelines for Company-sponsored biomedical research has been published, GPP 2022, which is the third update of the original GPP guidelines

 News from Asia Regulators

Three primary registries for clinical trials in Japan - JapicCTI, UMIN-CTR, and JMACCT-CTR - were unified into one centre, the Japan Registry of Clinical Trials (jRCT), from September 2020. All clinical trials are to be registered on jRCT and it is mandatory to register the protocol and post results in jRCT, except for bioequivalence studies. Information updates on JMACCT-CTR will be accepted only until 30 November 2022.

Medical Devices

Medical devices information is kindly compiled by Raquel Billiones.

Updates in the EU

  1. MDCG 2022-13 - Designation, re-assessment and notification of conformity assessment bodies and notified bodies. This document aims to provide guidance to the authorities responsible for assessment of Notified Bodies (NB) and other conformity assessments bodies (CABs) in the field of MDs and/or IVDs.
  2. MDCG 2022-14 - Transition to the MDR and IVDR - Notified body capacity and availability of MDs and IVDs. This document lists actions to enhance NB capacity, access to NB, and manufacturers’ preparedness in order to facilitate transition to the MDR and IVDR, hence avoiding shortages of MDs and IVDs.
  3. Borderline products are those where the regulatory pathway to follow is  unclear, ie. as a medicinal product, as an MD, or as an IVD. The Manual on Borderline and Classification for Medical Devices under the MDR and IVDR was recently released as a supportive tool for applications of such products.
  4. The European Commission released a clarification note on the relationship between MDCG 2020-6 Clinical evidence needed for medical devices previously CE marked under the Directives and the MEDDEV 2.7/1 rev. 4 on clinical evaluation (2016). The note specifies that Appendix I (Demonstration of equivalence) of MEDDEV 2.7/1 rev. 4 is still relevant under the MDR.
  5. EUDAMED Updates: The Technical documentation - UDI/Devices registration was updated in August 2022 (now Version 2.8).
  6. UK MHRA appoints first new UK Approved body to certify medical devices since Brexit: DEKRA Certification UK Ltd has now joined the three current UK Approved Bodies, increasing the UK’s capacity to process conformity assessments for medical devices to ensure safe and effective devices reach the UK public.
  7. The September 2022 issue of the Medical Devices News is out. 

UK Guidance on Software Updated

The MHRA updated its Guidance on medical devices: software applications including apps and IVDMDs. The guidance provides information on when software applications are considered to be a medical device and how they are regulated.

WHO Call for Public Comments on Digital Health Interventions

WHO is updating its Classification of Digital Health Interventions (CDHIs) v1.0 (2018). 

IMDRF Updates

The International Medical Device Regulators Forum (IMDRF) released its Standards Liaison Program Framework earlier this year. The IMDRF is a voluntary group of medical device regulators from around the world who have come together to build on the strong foundational work of the Global Harmonization Task Force on Medical Devices (GHTF) and aims to accelerate international medical device regulatory harmonization and convergence.

TGA Australia Updates

  1. The Australian regulatory guidelines for medical devices (ARGMD) is currently being updated; feedback can be provided on their website.
  2. Updates on the regulation of software based medical devices - Software based medical devices are medical devices that incorporate software or are software. This guidance is intended to provide information on the regulation in Australia for software and apps which meet the legislated definition of a medical device.
  3. Updates 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.