During a clinical lab audit, you come across an instrument that doesn’t have access controls or an audit trail. You raise the problem as a finding during the audit, and the auditee objects:

“Where is THAT written?”
“It’s an approved device.” or “It has a CE mark.”
“Our raw data are paper.”

In this 2-post series, we’ll cover:

Counters to these 3 objections
A resource on data integrity from the MHRA

Objection 1: “Where is THAT written?”

Truth? It’s not spelled out in any regulation. You must understand the records and associated predicate rules, apply logic, and step into the digital age. 21 CFR Part 312.62 requires investigators to:

“Prepare and maintain adequate and accurate case histories that record all observations and other data pertinent to the investigation on each individual administered the investigational drug or employed as a control in the investigation. Case histories include the case report forms and supporting data including, for example, signed and dated consent forms and medical records including, for example, progress notes of the physician, the individual’s hospital chart(s), and the nurses’ notes.”

In addition, FDA reminds us in the Guidance for Industry Electronic Source Data in Clinical Investigations: “Source data should be attributable, legible, contemporaneous, original, and accurate (ALCOA) and must meet the regulatory requirements for record keeping.”

“But we’re a clinical lab, not an investigator!”

Also true. What else is certainly true? The chemistry analyzer that’s missing audit trails is creating, maintaining, and transmitting source data for clinical trial subjects.

Without an audit trail, you cannot demonstrate the source is adequate and accurate. The investigator’s only visibility into those data is the lab report, the central lab emails, or the faxes to them. The investigator is completely reliant on the central lab to maintain data integrity.

“That FDA guidance is about putting data in eCRFs. We don’t do that!”

Then where are the data stored? As Excel spreadsheets, CSV files, and SAS data sets on file shares at the lab and the sponsor. This kind of system presents additional data integrity issues.

“We’re a clinical lab, not a CRO!”

Again, a true statement. A bit legalistic, but true. But source data in a clinical trial should have the ALCOA attributes. Period.

You don’t even need 21 CFR Part 11! Make the discussion about the records and the need for data integrity. And if your contract with the clinical lab does not require them to create, modify, maintain, archive, retrieve, and transmit records with the ALCOA attributes, then work with your legal and contracting teams to improve your contracts.

Follow here for the remaining 2 objections + a helpful MHRA resource…

About the Author

Jamie Colgin is Govzilla’s GCP Product Manager and is the recipient of the prestigious Charles H. Butler Excellence in Teaching Award. She joins Govzilla from Colgin Consulting, Inc.