18.2 Records Retention and Archiving

The Importance of Records Retention

In clinical research, the old adage "if it wasn't documented, it wasn't done" is only half the story. The full truth is: "if it wasn't documented, and the document isn't securely retained, it wasn't done." Records retention is the practice of maintaining trial-related documents for a specified period after the study has closed. These records are vital for regulatory inspections, verifying trial data integrity, and supporting future medical research.

Regulatory Frameworks for Retention

The Clinical Research Coordinator (CRC) must navigate a complex web of retention requirements dictated by federal regulations, international guidelines, institutional policies, and sponsor contracts.

FDA Regulations (21 CFR 312.62)

For studies conducted under an Investigational New Drug (IND) application, the US Food and Drug Administration (FDA) requires investigators to retain records for a period of 2 years following the date a marketing application is approved for the drug for the indication for which it is being investigated. If no application is to be filed or if the application is not approved, records must be kept for 2 years after the investigation is discontinued and the FDA is notified.

ICH GCP Guidelines (E6 R2)

The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Good Clinical Practice (GCP) guidelines are often more stringent. ICH GCP requires essential documents to be retained until at least 2 years after the last approval of a marketing application in an ICH region and until there are no pending or contemplated marketing applications in an ICH region, or at least 2 years have elapsed since the formal discontinuation of clinical development of the investigational product.

Sponsor and Institutional Policies

Because tracking international marketing approvals is practically impossible for an individual clinical site, sponsors take on the responsibility of notifying the site when records can finally be destroyed. Consequently, clinical trial agreements (CTAs) typically stipulate that sites cannot destroy any records without written permission from the sponsor. Many sponsors mandate retention periods of 15, 20, or even 25 years. Furthermore, a hospital or university's own institutional policies might require permanent retention of certain medical records. The golden rule is: always follow the longest mandated retention period.

Essential Documents to Retain

The Investigator Site File (ISF) or Regulatory Binder contains the "Essential Documents" that must be archived. Key documents include:

• Informed Consent Forms (ICFs): Original, signed, and dated ICFs for all subjects (including screen failures).
• Source Documents: Hospital records, clinical and office charts, laboratory notes, memoranda, subjects' diaries, and pharmacy dispensing records.
• Case Report Forms (CRFs): Copies of all completed CRFs submitted to the sponsor.
• Regulatory Documents: Form FDA 1572, IRB approval letters, investigator CVs, financial disclosure forms, and the Investigator's Brochure (IB).
• Drug Accountability Records: Logs detailing the receipt, dispensing, and return or destruction of the investigational product.
• Communication Logs: Correspondence with the sponsor, IRB, and monitors.

Best Practices for Archiving

When a trial is closed out, the active files are moved into long-term archiving. This transition must be handled meticulously by the CRC to ensure documents remain accessible and legible.

Environmental Controls

Whether archiving is managed on-site or at a third-party commercial storage facility, the environment must be controlled to prevent document degradation. This include:

• Climate Control: Regulating temperature and humidity to prevent mold and paper decay.
• Pest Control: Ensuring the facility is secure against rodents and insects.
• Disaster Prevention: Utilizing fire-resistant cabinets, sprinkler systems (preferably dry-pipe), and storing boxes off the floor to mitigate water damage.

Security and Access Control

Archived records contain Protected Health Information (PHI) and proprietary sponsor data. Access must be strictly restricted to authorized personnel. If a regulatory inspector requests a document from an archived study, the site must be able to retrieve it promptly. Therefore, a robust indexing and tracking system is essential. The index should list the box contents, study number, PI name, date of archiving, and the anticipated destruction date.

Electronic Archiving

The industry is rapidly shifting toward electronic Trial Master Files (eTMF) and electronic investigator site files (eISF). When archiving electronic records, CRCs must ensure the media used (e.g., hard drives, cloud servers) is durable and that the files will remain readable as software evolves (e.g., saving files in standard formats like PDF/A). Additionally, electronic archives must be backed up, and access must be governed by strict authentication protocols, complying with 21 CFR Part 11 requirements. Certified copies—exact replicas of the original records—can be used to replace paper documents, provided the certification process is validated.