As per the New Drugs and Clinical Trial Rules (2019) and Good Clinical Practice Guidelines by CDSCO, all essential documents pertaining to a clinical trial must be archived. It is the responsibility of the sponsor to ensure that the documents and trial supplies are archived for at least three years after the completion of the trial, or submission to the regulatory agency; whichever is later. In addition to essential documents, and trial supplies, the sponsor may have specific policies pertaining to archiving for a clinical trial. The archival plan must incorporate these specifications as well. For instance, the sponsor may retain the documents for a longer duration. Archiving is a key requisite to ensure post-trial monitoring, evaluation and to facilitate further research.

In certain instances, the regulatory authority and/or the ethics committee may recommend a timeframe for archiving of documents for a clinical trial, at the time of granting an approval.

Archival Strategy

Prior to initiation of a trial, an archival strategy must be developed, which addresses the regulatory requirements.It should include the following elements:

Personnel responsible for implementing the archival plan.

• Documents to be archived

The plan must identify the documents, data, supplies, specimens, etc. that are to be archived. Some examples are: source documents, case record forms, informed consent documents, investigator site file, biological samples (if applicable), trial supplies (if applicable), etc.

• Period of archiving

The plan must indicate for how long the documents will be archived in compliance with the regulatory guidelines.

• Location

As per the requirements of the sponsor, the archival can be either at the sponsor’s or CRO’s office or at each participating site or at an off-site archival facility (third party archival facility). Regardless of the location, it should be ensured that the confidentiality and integrity of the documents is adequately maintained. The facility should be reviewed by the sponsor or its designated personnel before the process of archival commences. Some key requirements that must be fulfilled by a potential facility are:

• Provision of adequate space, staff and equipment
• Provision of stable environmental conditions to ensure that the documents, and other material are not affected (controlled temperature and humidity). Care must be taken when magnetic media or images are archived.
• Security of the premises: it must be ensured that the facility has provisions for restricted access, locked cabinets and intruder alarms.
• Hazard management

• Retrieval or Access of archived documents

The plan must specify that the documents will have a restricted access. It is advisable to identify the details of personnel that can access the archival facility. However, it should be clarified that the regulatory authority or ethics committees may request access to these documents.

• Disaster Recovery

The archival plan should include a disaster management plan, to recover the documents in case of an emergency. For example, electronic copies can be made of all documents and data that are archived. However, these electronic copies must be stored at a location other than the archival facility, and comply with confidentiality requirements.

• Procedure

It should be specified that the process of archival should only be commenced after:

• The final visit has been completed by the last trial participant.
• Trial Master File and Investigator Site File, are complete
• The data has been verified for accuracy
• All queries pertaining to data have been resolved, database is locked, and the data has been analysed.
• Final report has been submitted
• Any other pre-requisite specified by the sponsor, regulatory authority, ethics committee, etc.

An archival checklist may be helpful, in ensuring that all essential documents and supplies (if applicable) are archived. This document may be used as a template for developing an archival checklist.

Clinical Data Archiving

To successfully reconstruct a trial, one must be able to view the clinical data accompanied with the manner in which it was obtainedand managed. The following list summarises the type of data that should be archived:

• Clinical data: includes all the data collected during the trial, i.e. data from the CRFs, electronically submitted laboratory reports, imaging, etc.
• External data: if a Clinical Data Management System (CDMS) is used for a trial, then, the archive must include all files loaded in the CDMS including quality control documents.
• Laboratory reference ranges
• Lists of edit checks, derived data and change controls
• Data handling guidelines and discrepancy management logs
• Data Management Plan

Some of the most common formats that are used for clinical trial archives are: Comma Separated Values (CSV), Extensible Markup Language (XML), SAS transport files, Adobe PDF, etc. However, in most trails the sponsor will specify the format for archiving clinical data, and in multiple formats.

Archiving by the Ethics Committee(s)

Documents submitted to an Ethics Committee (EC) for approval, must be kept confidential, and stored as per their written SOPs. The EC(s) must archive all documents and records for a period of at least five years after the completion or termination of a clinical trial. The sponsor and/or the regulatory body may also request for the records to be retained for longer than five years. Records and documents retained by an EC must be accessible for an inspection by the regulatory body.

Documents that are retained by an EC, related to a proposal are:

• One hard copy and a soft copy of the initial review proposal, and all related documents – protocol, data collection format, Case Record Form, Investigator’s Brochure, and all other documents that were submitted for review
• Copies of decision letter(s)
• Any amendments submitted for review and approval
• Regulatory approvals
• SAE, AE reports
• Protocol deviations / violations
• Progress reports, continuing review activities, site monitoring reports
• All correspondence between the EC and the investigator(s), regarding the application, decision and follow-up, etc.
• Agenda and minutes of all meetings held by the EC pertaining to the trial. These must be signed by the Chairperson of the EC.
• Record of notification(s) or order(s) issued for premature termination of a study with a summary of the reasons
• Final report of the trial, with all microfilms, CDs, video recording, etc. (if applicable)
• Recommendations given by the EC for determining the compensation (if applicable)
• Records pertaining to SAE(s), medical management of the trial participant(s) and compensation paid (if applicable).
• Publications, if any

In addition to the above, the following EC-related documents must also be archived.

• Constitution and composition of the EC
• CV of all EC members
• SOPs followed by the EC
• National and international guidelines followed by the EC

Documents that have been archived by the EC, must have restricted access, with stable environmental conditions to preserve the integrity of the documents.

Archiving by the Investigator

The investigator must maintain and archive essential documents pertaining to a clinical trial. These documents should be archived for:

• for a period of at least two years, after the last approval of a marketing application
• or, for a period of two years until there are no pending or contemplated applications
• or,for at least two years after the formal discontinuation of clinical development of the investigational product.

The regulatory agency and/or the sponsor may request the investigator to archive these documents for longer than two years. The sponsor should notify the investigator / institution in writing, when the trial related documents are no longer required. The investigator should ensure that these archived documents have restricted access and are secured in a location that maintains their integrity.

References and Further Reading

• Good Clinical Practices for Clinical Research in India, Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, 2001, available online (last accessed on 26.02.2019).
• New Drugs and Clinical Trial Rules, 2019, G.S.R. 227(E), Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, available online (last accessed on 01.04.2019).
• National Ethical Guidelines for Biomedical and Health Research involving Human Participants, Indian Council of Medical Research, 2017, available online (last accessed on 26.02.2019).
• ICH Harmonised Guideline, Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6(R2), current step 4 version, dated 9^th November 2016, available online (last accessed on 26.02.2019).
• Clinical Development Services Agency SOP for Archiving of Study Documents, Version 1.0, dated 15^th February 2016.
• Good Clinical Data Management Practices, Society for Clinical Data Management, October 2013 edition, available online (last accessed on 26.02.2019).