July 2021

Medicines and Vaccines

Clinical Trials Information System Update

New versions of the below documents were added in the CTIS training Module 07 (Management of registered users and role matrix) on 30 June 2021:

Additionally, the complete recorded webinar for Day 1 of SME and Academia Clinical Trials Information System (CTIS) two-part training webinar is also published on June 30. Day 1 of this webinar took place on 22 February 2021.

Check out the post-event recording of the CTIS Webinar of 29 July 2021 to show how Sponsors can prepare for CTIS. Here are a few ‘nuggets’ from that CTIS training which - although they cannot be validated - if taken in the spirit of intelligence sharing, are of great interest:

  • For the CTIS to be functional by January 2022, it should be published in the EU Journal 6 months prior – which means this week
  • Start of trial is not FPFV but ‘First Recruitment Activity’
  • The IB and parts of IMPD will be made public. There are options for deferrals but with limited timelines.
  • The DSUR seems to be called Annual Safety Report now in CTIS
  • The summary of clinical trial results will be submitted as document (not as structured data) and will need to be accompanied with a “Declaration of accuracy” from the Sponsor.

On 29 July, the following CTIS resources were released (each forces a download):

Note that deadlines will apply to ensure a smooth transition from the current processes into the CTIS/CTR 536/2014 – and that transition deadlines must take account of the Christmas 2021 and New Year 2022 holiday period.

Patient Centricity Initiatives by the Regulators

All such initiatives will eventually impact the protocols, CSRs, and submissions packages that we as MWs contribute to. Watch this developing space with interest...

  • ICH Advance Patient Focused Drug Development

This ICH Reflection Paper proposes ICH guideline work to advance patient focused drug development and shows us that this approach is almost inevitably ahead…

  • Patient Experience Data in FDA Regulatory Decision-Making

Patient-Focused Drug Development (PFDD) is “a systematic approach to help ensure that patients’ experiences, perspectives, needs, and priorities are captured and meaningfully incorporated into drug development and evaluation.” Eastern Research Group (ERG) have examined FDA review documents and product labelling for approved applications in a three-year cohort to determine what patient experience data applicants submitted and where and how FDA used the data. Read the ERG Report ‘Assessment of the Use of Patient Experience Data in Regulatory Decision-Making’ dated 18 June 2021. Section 4. ‘Findings and Recommendations’ makes interesting reading.

  • New FDA Guidance on PROs in Oncology Trials

The FDA has issued new draft guidance on core patient-reported outcomes (PROs) in cancer trials. The document was issued for consultation on 10 June 2021 and provides sponsors with recommendations on the collection of a core set of PROs in cancer clinical trials, and related considerations for instrument selection and trial design. It focuses on PRO measures and is specific to registration trials for anti-cancer therapies intended to demonstrate an effect on survival, tumour response or delay in disease progression. The draft guidance should facilitate the generation of high-quality data on a core set of patient-reported symptom and functional impacts that are important contributors to a patient’s health-related quality of life. The recommendations supplement previous guidance on the use of PROs in clinical trials by providing considerations that are specific to the cancer setting. Comments should be submitted by 9 August 2021. [Credit to www.brookwood-global.com for the excerpt].

  • Patient Engagement by EMA

On 01 July 2021, the first meeting was held of the CTTI/FDA Patient Engagement Collaborative (PEC) and EMA Patients and Consumers Working Party (PCWP). The agenda indicates that collaboration is ongoing and that next steps are pending.

  • Patient Engagement by UK’s MHRA and NHS

Read the MHRA’s Press Release about their 2021-2023 Delivery Plan. Despite the claim that MHRA are ‘putting patients at the heart’ of this Delivery Plan, it is noteworthy that there is no stated commitment to the transparency and disclosure of clinical trial data and documents. The Combined Review Service planned to start in Jan 2022, does demonstrate MHRA’s push towards speedier clinical trial review, with the aim to open trials sooner, for the benefit of all, and not least, patients.

The UK National Health Service (NHS) Health Research Authority (HRA) is hosting their first #MakeItPublic virtual conference on 03 and 04 November 2021. HRA will be showcasing best practice examples of transparent research and how individuals and organisations across the sector are working together to improve visibility of studies for the benefit of all. Read the HRA strategy here.

Further, MHRA and Health Canada are collaborating to improve patient safety in clinical trials by improving the quality of Development Safety Update Reports (DSURs).

FDA Guidances

The following recently released FDA guidance documents are of interest:

  • Sponsor Responsibilities— Safety Reporting Requirements and Safety Assessment for IND and Bioavailability/Bioequivalence Studies Guidance for Industry
  • Providing Regulatory Submissions In Electronic Format — Standardized Study Data Guidance for Industry
  • Providing Regulatory Submissions in Alternate Electronic Format - Guidance for Industry

Quantitative Risk Approaches for Data and Documents – Workshop Recording

d-wise have made available a recording of their 2020 PHUSE EU Connect Workshop on ‘Quantitative risk approaches for data and documents’. Watch it here. Cathal Gallagher's presentation includes a great demo of anonymisation on a dataset in xlsx.

Also note that a summary of what took place at ‘PHUSE US Connect 2021’ held 14-18 June 2021 is now available.

SAE Data Collection Standard – T/Cel and CDISC

Sponsors are required to follow SAE reporting regulations, but there is a lack of standardization across the data fields collected on SAE case report forms and SAE paper reporting forms. Developing and adopting an industry standard around SAE data collection is expected to add inherent value across patients, sites, sponsors, and health authorities. TransCelerate BioPharma & CDISC are in collaboration to attempt to do so. Of course, this will impact clinical study reporting of SAEs… eventually.

RPD SIG ‘Meet and Share’ 02 July 2021

Thanks to all those who attended the first EMWA RPD SIG ‘Meet and Share’ on 02 July 2021. There were 30+ attendees and the discussion around the Plain Language Summary (PLS) and clinical data and documents disclosure was dynamic.

Links of useful resources shared in the meeting ‘chat’ are below:

Additional useful resources to help with best practice for writing the PLS can be found here at the Publication Plan’s page for ‘Patient Centricity/Lay Summary’.


Update on Combination Products in the EU

Many healthcare products in the EU are combination products. On 23 June 2021, the EMA released an update to the guidance document Questions & Answers for Applicants, Marketing Authorisation Holders of Medicinal Products and Notified Bodies with Respect to The Implementation of the Medical Devices and In Vitro Diagnostic Medical Devices Regulations ((EU) 2017/745 and (EU) 2017/74 Rev 2. This is an update to original guidance (Rev 1) issued on 21 October 2019. This Q&A document provides practical considerations concerning the implementation of the medical devices and the in vitro diagnostic medical devices regulations (MDR and IVDR, respectively) in products that have device and medicinal product components.

Related to combination products, also check out the EMA draft guidance on the Quality Requirements for Drug-Device Combinations (dated 29 May 2019).

Update on the European Database for Medical Devices (EUDAMED)

The EUDAMED is key to transparency and public disclosure of devices. Also this month, the Medical Device Coordinating Group (MDCG) released the latest guidance document Questions & Answers on Obligations and Related Rules for the Registration in EUDAMED of actors other than manufacturers, authorised representatives and importers subject to the obligations of Article 31 MDR and Article 28 IVDR.

Clinical Investigation ID for Medical Device Clinical Studies

Clinical investigations (CIV) are clinical studies/trials for medical devices under the EU MDR 2017/745. Like any clinical trial, CIVs are also subject to T&D requirements, from registration to results posting.

Before the EUDAMED is fully functional, for the purpose of CIV registration in the EU, a CIV sponsor must apply for a CIV-ID (referred to as the EU-wide unique single identification number [SIN] in the MDR).

The EU Medical Device Coordination Group (MDCG) recently issued the MDCG 2021-20 Instructions for generating CIV-ID for MDR Clinical Investigations.

Summary of Safety and Clinical Performance (SSCP)

The SSCP is a document required for Class III and implantable medical devices. The document should be written in a way that is clear to the intended user and, if relevant, to the patient. It shall be made available to the public via EUDAMED. As EUDAMED is not yet operational, the SSCP shall be made available to the public upon request without undue delay or the manufacturer shall specify where it is publicly available. For more information, see the MDCG 2021-1 Rev.1 Guidance on harmonised administrative practices and alternative technical solutions until EUDAMED is fully functional.

Guidance Documents for In Vitro Diagnostic Devices (IVDs)

An in vitro diagnostic device (IVD) is “any medical device which is a reagent, reagent product, calibrator, control material, kit, instrument, apparatus, piece of equipment, software or system, whether used alone or in combination, intended by the manufacturer to be used in vitro for the examination of specimens, including blood and tissue donations, derived from the human body, solely or principally for the purpose of providing information on one or more of the following:

  • concerning a physiological or pathological process or state;
  • concerning congenital physical or mental impairments;
  • concerning the predisposition to a medical condition or a disease;
  • to determine the safety and compatibility with potential recipients;
  •  to predict treatment response or reactions;
  • to define or monitoring therapeutic measures.”

This definition is coming from the EU IVDR 2017/746, the regulation governing IVDs in the EU. Like medical devices, IVDs are also subject to T&D requirements.
The MDCG has issued a set of guidance documents for IVDs, including IVD classification rules and IVDR codes for Notified Bodies.

In addition, several guidance documents specific for COVID-19 IVDs have been released by the MDCG since the start of the pandemic. These documents are available under the COVID-19 section of the MDCG page.

Finally, the Official Journal of the European Union (OJEU) recently referenced harmonised standards in support of the IVDR 2017/746, including several ISO standards.

On Notified Bodies

Notified Bodies (NBs) are private/non-governmental bodies in the EU responsible for conformity assessment of medical devices. NBs also have T&D requirements to comply with under the MDR and the IVDR within the EUDAMED Certificates Module.

The MDG recently released several guidance documents (MDCG 2021-15, 16, 17, 18) for NBs for medical devices and IVDs. Check out the documents under the Notified Bodies section of the MDCG page.

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