FDA’s published draft guidance on data integrity, to clarify the role of data integrity in current good manufacturing practice (cGMPs) with both electronic and paper based records.

Data integrity is defined as “refers to the completeness, consistency, and accuracy of data. Complete, consistent, and accurate data should be attributable, legible, contemporaneously recorded, original or a true copy, and accurate (ALCOA).”

Of particular interest is the parallel between electronic and paper based records, as specifically stated in the guidance “The requirements for record retention and review do not differ depending on the data format; paper-based and electronic data record-keeping systems are subject to the same requirements.”

Do 503B Outsourcing Facilities have to comply with Data Integrity issues – YES!

A recent 503B Outsouring Facility inspection identified issues with paper based records as identified on the firm’s 483 Observation 2, the FDA identified documents in a shredding bin where the firm discarded original documentation, including incidences, deviations, and manufacturing occurrences not elswhere offically documented.  Example:

“The production schedule for 05/11/2017 with a written instruction stating “date w/ date we are
compounding – not date making the record.”

“Numerous original documentation, including “Non-Controlled Concentrate Container
Accountability Form”, “Labeling and Bagging Form Area”, [redacted] Differential Pressure
Readings”, “Filling Check Weights”.

In part 2 of this observation – the FDA identified that the firm apprently has a practice of altering the manufacturing records based on the appending of notes to modify their contents.  Example:

“Batch Record for Neostigmine Methylsulfate 1 mg/ml lot 10355 had four (4) yellow sticky flags
instructing an operator to “rewrite”, ”writeover” and “Done By” (initial the document in the done by

“Batch Record for Rocuronium Bromide lot 10382 was observed to contain sticky flags throughout instructing to “For when you verified lot#” (in “Check By:” Section) and to indicate lot numbers.”

Per the background section of the FDA data integrity guidance:

In recent years, FDA has increasingly observed CGMP violations involving data integrity during
CGMP inspections. This is troubling because ensuring data integrity is an important component
of industry’s responsibility to ensure the safety, efficacy, and quality of drugs, and of FDA’s
ability to protect the public health. These data integrity-related CGMP violations have led to
numerous regulatory actions, including warning letters, import alerts, and consent decrees. The
underlying premise in §§ 210.1 and 212.2 is that CGMP sets forth minimum requirements to
assure that drugs meet the standards of the Federal Food, Drug, and Cosmetic Act (FD&C Act)
regarding safety, identity, strength, quality, and purity.

There is an assumption and level of trust that life science firms regulated by FDA follow the cGMPs, record data as required and perform investigations when required based on deviations, or manufacturing upsets.  The firms are expected to understand the rules of cGMPs and comply with them.  Once a firms integrity is in question it can be very difficult, challenging, and expensive to demonstrate to the agency that the firm is in compliance and to regain that level of trust with the agency.

Have a question on data integrity of either electronic or paper based records – contact Kevin Marcial or use our contact us form.

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