Regulation EU 536/2014: A Records Manager and Archivist’s Perspective - Arkivum

eTMF & GCP Data / 24 Sep, 2021

Regulation EU 536/2014: A Records Manager and Archivist’s Perspective

In April 2021, the European Medicines Agency Management Board confirmed that the Clinical Trial EU Portal and Database (a key component of the Clinical Trial Information System (CTIS) on which Regulation (EU) No 536/2014 (“The Regulation”) was contingent) is now fully functional and due to “go live” by 31st January 2022. This new regulation will come into effect on the same day, introducing significant changes regarding the conduct of clinical trials.

In this article, we shall consider the impact this will have upon records management.

Simplifying retention requirements: 

For Records Managers and Archivists in the life sciences, perhaps the most welcomed change of all is that “The Regulation” simplifies retention requirements: A minimum retention period of “25 years after the end of the clinical trial”1 is mandated for the Trial Master File (TMF).

As much as this simplification is an eagerly awaited change, the extended retention period will have an impact on records storage requirements, particularly for electronic data and documents. Bearing in mind recent data integrity guidance published by regulators such as the MHRA, FDA, and WHO, integrity is best preserved through the use of enabling technologies (e.g. eTMF) for live documents and digital preservation technologies (e.g. Arkivum Trust) for archiving. Moreover, it will be necessary for Records Managers and Archivists to ensure that their organisations have robust preservation policies (with periodic checks for degradation or obsolescence, including records of these checks) if data and documents are to remain accessible, readable, and (where required) usable for the 25-year retention period. File storage applications such as network directories and file hosting services (e.g. OneDrive or DropBox) do not provide the requisite levels compliance in terms of integrity or preservation for either live or archived records.

What should be documented in the TMF? 

Records Managers and Archivists may already have identified that the regulation potentially requires a number of new TMF documents, among them:

  • Documentation that identifies the EU legal representative2
  • A “clinical trial application withdrawal” document3
  • Evidence (including tracking tools) of compliance with the dates of the start of a clinical trial and of the end of recruitment4
  • A record of Member State clinical trial authorisation decisions5 (possibly via a “print decision” option in the CTIS)
  • A Clinical Trial Summary Report6, which must be submitted within one year from the end of the clinical trial in all Member States
  • A version of the Clinical Trial Summary Report that is in plain language and understandable to “laypersons”6
  • Qualified Person Batch Certification7, which (it is now implied) should be retained in the TMF
  • A record of the decision that the Summary of Product Characteristics (SmPC) is deemed to be equivalent to an Investigator Brochure8, (including mechanism(s) to track the use of SmPC)
  • A simplified Investigational Medicinal Product Dossier (IMPD) or other record9, again including mechanism(s) to control and track that documentation
  • Possible additional pharmacovigilance records10 to cover “unexpected events which affect the benefit-risk balance of the clinical trial”10
  • Contracts, agreements, and task definitions in relation to co-sponsorship arrangements11 (especially in relation to which components of the TMF should be held by which co-sponsor).

Much of this documentation should already have a placeholder within most organisations current TMF architecture. Nonetheless, it is advisable to check whether new sub-artefacts or templates need to be added, or SOPs/working practices require updating.

Streamlining processes: 

New documentation requirements aside, 536/2014 also introduces changes to processes, such as:

  • It will harmonise and simplify the clinical trial application process but notifications regarding start, end, temporary halt, and early termination dates will now be made via the CTIS12. However, there is no clear guidance on how this information should be captured or by whom.
  • The new definition of clinical trial start13 (an event often used to help define which documents need to be retained if the trial ends prematurely) means that Records Managers and Archivists will need to reconsider retention requirements for early-terminated trials.
  • The regulation refers throughout to “the clinical trial master file” (emphasis mine), rather than the Investigator Site File (ISF) and Sponsor TMF. Currently the ISF and TMF are managed as distinctly separate records due to their differing content, purpose, and the divergent nature of the responsibilities of investigators and sponsors14. It is unclear whether a unified TMF will be required.
  • The requirement for sponsors and investigators to report on safety matters within agreed reporting timeframes10 increases the burden on sponsors to produce pharmacovigilance reports in more timely and contemporaneous manner.
  • The acknowledgment that informed consent may be obtained by using audio or video recorders15 means that Records Managers and Archivists will need to carefully consider how such records would be filed in the TMF and then preserved. The same is true for communications via social media channels, both of which are being used with increasing frequency in clinical trials.

Indicative, perhaps, that regulation 536/2014 is now somewhat aged, it reinforces some aspects of TMF management that are now (and in many instances have been for some time) considered best practice.

For example:

  • The TMF “shall at all times contain the essential documents relating to that clinical trial” and “shall be readily available and directly accessible upon request to the Members States”16;
  • There must be traceability of alterations to TMF content, although this is only referenced specifically in relation to archiving1 despite there being frequent emphasis on the importance of “data reliability and robustness” (it is worth noting that data integrity guidance22 requirements apply systems holding “live” content).
  • Sponsors must “apply appropriate technical and organisational measures to protect information and personal data against unauthorised or unlawful access, disclosure, dissemination, alteration, or destruction or accidental loss”17 which is (in any event) a GDPR requirement (it would, however, be prudent to consider the need for additional procedural controls should an eTMF not provide sufficient protection).
  • The responsibility of “the sponsor [to] appoint individuals within its organisation to be responsible for archives”14 …although no mention is made of the responsibility of the investigator or any other party to do so!

Although most organisations will already fulfil these requirements, the introduction of 536/2014 provides a timely reminder to revisit current practices to confirm appropriate levels of compliance are being applied.

This regulation is (to quote The European Federation of Pharmaceutical Industries and Associations) “an important step towards a much-needed simplification and standardisation of clinical trials administration” and aims to introduce clarity and improve upon existing practices in some elements of clinical trials, such as records retention.

However, there remains room for interpretation and Records Managers and Archivists will need to continue to engage with colleagues involved in the conduct of clinical trials to ensure that there is continued effective learning so that its overarching ambitions can be mutually understood, appropriately applied, and the intended improvements delivered.


1 Reg (EU) 536/2014 Article 58 10 Reg (EU) 536/2014 Article 53
2 Reg (EU) 536/2014 Article 74 11 Reg (EU) 536/2014 Preamble 59
3 Reg (EU) 536/2014 Preamble (21) 12 Reg (EU) 536/2014 Article 36
4 Reg (EU) 536/2014 Article 36 (1) 13 Reg (EU) 536/2014 Article 2 (25)
5 Reg (EU) 536/2014 Article 8 (1) 14 Reg (EU) 536/2014 Article 57
6 Reg (EU) 536/2014 Article 37 (4) 15 Reg (EU) 536/2014 Preamble 30
7 Reg (EU) 536/2014 Article 62 16 MHRA Data Integrity Guidance and Definitions 2018
8 Reg (EU) 536/2014 Annex 1 E28 17 Reg (EU) 536/2014 Article 56
9 Reg (EU) 536/2014 Annex 1 G37


Russell Joyce

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