14. How long should the TMF be retained (archived) after the trial is completed?
Retention of the documents within the TMF (including the investigator site file) and the medical records of trial subjects is a legal requirement. The sponsor and the chief investigator must ensure that the documents contained, or which have been contained, in the TMF as well as the medical files of trial subjects are retained for at least 5 years after the conclusion of the trial (SI 2004/1031 [as amended] 31A, (7) and (8)). Trials where the data are used to support a marketing authorisation have further requirements as per Statutory Instrument 2004/3224 implementing Commission Directive 2003/63/EC. Here the documentation should be retained for at least 15 years after completion or discontinuation of the trial or for at least two years after the granting of the last marketing authorisation in the EC (when there are no pending or contemplated marketing applications in the EC) or for at least two years after formal discontinuation of clinical development of the investigational product. Additionally, the sponsor or other owner of the data must retain all other documentation pertaining to the trial as long as the product is authorised. This documentation shall include the trial protocol (which must include the rationale, objectives and statistical design and methodology of the trial, with conditions under which it is performed and managed, details of the investigational product, the reference medicinal product and/or the placebo used), any standard operating procedures used for conducting the trial, all written opinions on the protocol and procedures, the investigator’s brochure, case report forms on each trial subject, final report and audit certificate(s), if available, and staff training records. Additionally, the final report shall be retained by the sponsor or subsequent owner, for five years after the medicinal product is no longer authorised.
Trial subject’s medical files must be retained for at least 5 years in their original format and in accordance with the maximum period of time permitted by the hospital, institution or private practice. Scanning or microfiching of patient notes is acceptable provided the process is validated such that the institution can demonstrate that it is an authentic copy of the original and is kept in a format that means that the data can be retrieved in the future. It is recommended that the notes of patients that have been involved in clinical trials are clearly identified to prevent premature destruction. Many UK hospitals attach stickers to the notes with a “do not destroy” or “retain until” date clearly marked.
In addition to these retention times for the trial documentation, records relating to the full traceability of the IMP for Advanced Therapies have longer retention periods. These are 30 years after the expiry date of the product or longer if required by the clinical trial authorisation. This will include the relevant documentation contained in the sponsor and investigator files as well as the trial subjects’ medical records. Further information can be found in the EU detailed guidance on GCP for advanced therapy medicinal products, (2009).
It is the responsibility of the sponsor to inform the hospital, institution or practice as to when these documents no longer need to be retained. As such, the expectation would be that the retention requirements of the sponsor for the documentation and medical records held by the investigator should be agreed either in the protocol or a separate agreement. The sponsor would be expected to have systems in place to alert the investigator when the records are no longer required to be retained. The sponsor should notify investigators in writing when their trial records can be destroyed and up until that point the investigator or institution should take measures to prevent accidental or premature destruction of these documents. The ultimate responsibility for the documents to be retained by the investigator or institution resides with the investigator or institution. If the investigator becomes unable to be responsible for their essential documents (e.g. relocation, retirement etc) the sponsor should be notified in writing of this change and informed as to whom the responsibility has been transferred.
The EU Regulation on Medicinal Products for Paediatric Use 1901/2006, adopted in December 2006 and came into force in January 2007, enables the use of data from published literature for the application of Paediatric Use Marketing Authorisations (PUMAs). To this end, the archiving requirements should meet the requirement of Commission Directive 2003/63/EC. The data may not be used for a MAA when the TMF is only maintained for 5 years.
It is important that where an organisation has centralised records that may be relevant to a number of trials, for example, SOPs, staff training records or maintenance and calibration records for equipment used in the trial at a Phase 1 unit/NHS clinical research unit; that these are also considered in the arrangements for archiving and retention (including superseded versions or obsolete records for example training records of personnel who have left the organisation) as they may be required to be produced in addition to the TMF to demonstrate compliance.
The protocol or the formal procedures of the sponsor should contain details of the retention times for all the trial documentation as outlined above or the process used to determine how long particular documentation will be retained for and how this should be documented.
The requirements for the retention of sponsors’ records also apply to the records retained by CROs or other agents of the sponsor, unless arrangements have been made to transfer the documents to the sponsor. The details of the retention time of documents held by the CRO should be formalised in an agreement between the sponsor and the CRO or be clear within the CRO’s SOPs that will have been reviewed by the sponsor.
Investigators can retire, hospitals can close and CROs (some of which are also investigator sites, e.g. commercial phase 1 units) can go out of business or be acquired by other organisations. The sponsor should ensure that agreements cover such eventualities to ensure that the documentation remains available for inspection for the specified retention time. Sponsors outside of the UK should ensure that provision is made to make the archived documents for trials conducted in the UK available to the MHRA throughout the retention period, in particular for documentation held by CROs. This issue has occurred on several occasions in the UK when phase 1 units have closed and there has not been any contact with the trial sponsors to ensure the long term availability of their investigators files and data until the MHRA was informed.
Version 1: 17th December 2012
