Sponsor, Pharmacy, Laboratory and Safety Records

Part of Clinical Research Associate (CRA) Training: Regulatory Documents and the Site File.

About 5 minutes. Free, in your language, no account needed.

Why this matters

Lesson 1 covered the people and the ethics committee. This lesson covers everything else the site must hold — and it is where records are most often incomplete, because no single person owns them.

Sponsor-provided documents

Protocol and amendments

The site keeps every version, with superseded versions clearly marked as such and removed from use.

What you check: the current version is in use; superseded versions are marked and not in circulation; and the site's training and implementation dates for each amendment are recorded.

Investigator's Brochure

Summarizes the clinical and non-clinical data on the investigational product, and contains the reference safety information used to judge whether an event is expected.

What you check: that each version was received, that ethics approval was obtained where required, and that site staff were trained on new versions. An investigator who has never read the current Investigator's Brochure cannot properly assess expectedness.

Study manuals

Laboratory manual, pharmacy manual, imaging manual, sample processing instructions, device manuals, the monitoring plan.

What you check: the correct versions are present, staff have access, and staff have been trained. Manuals are updated more often than protocols and are the most commonly outdated documents at a site.

Site-specific operational documents

The executed clinical trial agreement. Filed, and dated before activation.

Financial disclosure forms, as covered in Lesson 1.

Site standard operating procedures or written processes, where the site has them. Check that the SOP describes what the site actually does; a written procedure the site does not follow is worse than none.

Form FDA 1572 for sites under a United States investigational new drug application. Check that the information is complete and accurate, and that it is updated when sub-investigators or facilities change.

Clinical trial insurance documentation, where required, confirming that participants are covered.

Pharmacy and investigational product records

Accountability records covering receipt, storage, dispensing, return and destruction. Verified at every monitoring visit; Module 10 covers reconciliation in detail.

Temperature logs for product and any temperature-controlled supplies. Check for gaps as well as excursions. A gap in a log is a finding in its own right, because it means nobody can say what the temperature was.

Pharmacy manual and pharmacy staff training and delegation records. Confirm that whoever handles product is trained and delegated.

Laboratory records

Accreditation or certification — for example CLIA certification, CAP accreditation, or ISO certification at international sites. Check that it is current and that it covers the tests the protocol requires.

Normal reference ranges, current and dated, and matching the laboratory actually producing the results. Out-of-date ranges are a frequent finding and they matter, because they are what the investigator uses to judge clinical significance.

Laboratory staff training and delegation, where site laboratory personnel handle study samples.

Safety records

Safety letters and notifications of suspected unexpected serious adverse reactions. Check they are filed and that the investigator's review is evidenced with a date. Filing without evidence of review is the usual failure.

Periodic safety reports, such as development safety update reports, filed with evidence the investigator is aware.

Screening and enrollment records

Pre-screening logs, where the sponsor requires them, with de-identification standards followed.

Screening and enrollment logs, which must reconcile with the randomization system and with source documents. These are used to track accrual and are frequently the first thing an inspector asks for.

Recruitment materials, which must be ethics-approved before use, with versions matching the approvals.

Miscellaneous

Training records for new staff, reviewed at every visit. Device accountability records for device trials or device-supported endpoints.

In practice

Leah reviews the laboratory section of a VT-301 site file and finds normal reference ranges dated three years earlier.

The coordinator says the ranges have not changed. Leah asks the laboratory rather than accepting it. Two of the ranges have changed, including one used to judge a protocol-defined safety threshold.

She then works backwards. Three participants had results that fall between the old and the new ranges. Under the current ranges, two would have been flagged as clinically significant and reviewed.

Leah escalates this as a major finding, because it affects safety review rather than filing. The site obtains current ranges, the investigator re-reviews the affected results, and one adverse event is added retrospectively with a clear note explaining the discovery and its date.

Nothing was hidden and nothing was back-dated. The record shows exactly when the site learned it had been using stale ranges.

An out-of-date reference range is not an administrative finding. It is a safety finding wearing administrative clothes.

Key takeaways

• Study manuals are the most commonly outdated documents at a site, because they are revised more often than protocols.
• A gap in a temperature log is a finding in itself, because it means nobody can state what the temperature was.
• Laboratory reference ranges must be current and must match the laboratory producing the results, since the investigator uses them to judge clinical significance.
• Safety letters must be filed with dated evidence of investigator review, and filing without evidence of review is the usual failure.
• Screening and enrollment logs must reconcile with the randomization system and source documents, and are often the first record an inspector requests.