MHRA produced FAQs for Trial Master Files (TMF) and Archiving

[MHRA Super Moderator]

15. Can the sponsor retain (archive) the investigator’s TMF?

The investigator should retain control of the documentation contained in the investigator site file. The investigator site file should never be sent to the sponsor organisation except in sponsor-investigator situations. This requirement does not mean that an external sponsor cannot arrange the archiving on behalf of the investigator, which is acceptable, subject to the following being implemented:

• The archive arrangements are formally agreed and documented between the sponsor and investigator or host institution
• A formal procedure is in place such that the documents are only released from the external archive with the approval of the investigator or host institution. It is recommended that this is tested for robustness. Permission from the investigator or host organisation should also be required to permit access to the contents of investigator site archived materials at the archive facility
• The records go directly between the investigator site and an archive facility independent of the sponsor, thereby ensuring that the Sponsor does not have uncontrolled access to the investigator files.

Version 1: 17th December 2012

[MHRA Super Moderator]

16. Are there any requirements for the archive storage conditions?

The storage area for the TMF records must be appropriate to maintain the documents such that they remain complete and legible throughout the required period of retention and can be made available to the competent authorities upon request. This should be assessed on a risk based approach. Where a sponsor is conducting many trials in support of a marketing authorisation, the requirement for long term storage in appropriate conditions will be higher than for a sponsor-investigator undertaking one small Type A category trial where its publication is not likely to affect prescribing practice. Adequate and suitable space should be provided for the secure storage of all essential records from completed trials. Thus, for an investigator storing a TMF or investigator site file the sponsor may consider that the office filing cabinet may provide a suitably secure environment for a 5 year retention period, whereas a large sponsor that is required to retain documents in excess of 15 years, may need more specialist facilities with sufficient level of controls. The areas to be considered when performing such a risk assessment include:

• Security – how accessible are the documents, are there locks in place on doors/cupboards, what is the risk of unauthorised access, are there windows on the ground floor etc?
• Location - what risks are there from water (burst pipes, flood), fire (what activities take place in the room next door/above/below), what runs in the ceiling/floor void etc?
• Size – is the archive facility large enough and have the appropriate off floor shelving to accommodate the expected documentation?
• Environmental – are there risks from excessive temperature, humidity, sunlight, contamination (dust, fumes, smoke etc)?
• Pests – are there risks from rodents, insects etc?

The British Standard BS 5454:2000 “Recommendations for the storage and exhibition of archival documents” is a standard for commercial archive facilities and sponsors may refer to this for consideration in maintaining purpose built archive facilities as well as taking it into account when assessing potential contract archiving companies.

It is essential that sponsors make a documented assessment of the storage conditions at the investigator site for the investigator site file and that the investigator provides this information. The importance is illustrated by a UK investigator site where the archive facility was inspected and found to contain an automatic water pump to extract flood water, together with numerous decorating products stored above the investigator site files. The inspector outlined the risks to the documentation, but this was not acted upon as a subsequent serious breach report was received of water damage to the investigator files when the pump failed to operate during a river flood.

Version 1: 17th December 2012

[MHRA Super Moderator]

17. How should electronic documents/data be archived?

The use of electronic systems for such activities as data management, statistical analysis, reporting, trial management systems and eTMFs means that electronic documentation and data is likely to need to be retained. The data may be on a server or on transportable media, e.g. USB drives, CDs, tapes etc. It is recommended that more than one copy of the data is retained, for example where the data is archived in a specific server, this should be subject to back up, with the back up media stored in a separate location. Consideration may be given to storing the data in differing formats on different types of media or even on the same media from different manufacturers.

Access to archived data must be suitably restricted, either by user access levels to the archive area of a server or by controls to access the storage area where the media are retained (as for paper). Additionally, the electronic documents or data that have been archived must be protected from unauthorised changes to maintain authenticity.

It is important that future access to records and data is maintained. This could include maintaining the system (hardware and software) to access the data in its original format or the use of a new system to emulate the old software or migration of the data into a new format to ensure continual access with new software. This issue should be addressed by the organisation via formal procedures.

Media used to store the data may potentially deteriorate or become obsolete, for example, during a recent inspection a paper file contained a 3.5” floppy diskette containing the randomisation schedule. At the current time, PCs with ability to use such media are rare and future potential access would not be guaranteed, thus transfer to an alternative would need to be considered. The media should be stored under appropriate conditions. The transfer of data to new media as technology advances would need to be considered by the organisation. It is also recommended that periodic test retrieval or restores are undertaken to confirm that ongoing availability to the data is being maintained.

Where data is required to be migrated to new media or a new format, then the transfer should be validated and fully documented, so that it can be subject to audit, to ensure and demonstrate that there has been no loss, changes or corruption to the data or meta data and that authenticity is maintained.

Version 1: 17th December 2012

[MHRA Super Moderator]

18. Is there a need for an Archivist?

It is a legal requirement that the sponsor appoints a named individual within the organisation to be responsible for archiving the documents which are, or have been, contained in the TMF and that access to these documents shall be restricted to those appointed individuals and auditors or inspectors (SI 2004/1031 [as amended] 31A, (9)). There can be more than one such person named and the requirement can be met by either having specific archivist role(s) or person(s) in another role may also have the specific archiving duties, but either way there should be clear documentation to support the appointment(s) and appropriate training provided. The named individual responsible must have a clear legal link to the sponsor, in that they are the sponsor/co-sponsor themselves or employed or contracted by the sponsor/co-sponsor (SI 2004/1031 [as amended] 31A, (11)). Whilst an investigator site institution is not required to have a named individual (unless they are a sponsor in their own right), where the organisation has many trials, a person responsible for this activity would be recommended.

Version 1: 17th December 2012