If your company has ever received a warning letter from the U.S. Food and Drug Administration (FDA), you know how serious they can be. It’s a shot across the bow, serving as notice of problems but also providing an opportunity to improve before more serious issues occur.
With that in mind, let’s look at the top issues that lead to warning letters, and what companies can do to avoid finding themselves in the same boat.
A Fortune 500 pharmaceutical was recently fined more than $20 million dollars for failing to follow cGMP guidelines in the production of sterile solutions for IV use. The fine followed warning letters issued as early as 2011.
These fines were for adulteration of product, which is the most common violation cited in warning letters by the FDA. But what exactly is adulteration? Put simply, if the methods, facilities or controls used to make, package or store drugs do not conform to cGMP guidelines, the FDA considers the drug adulterated.
To make sure you adhere to cGMP guidelines, companies should have a system for tracking compliance obligations, linking controls to each requirement to ensure there aren’t any gaps.
Earlier this year, the FDA reported that data integrity made up more than a third of recent warning letters. Data integrity refers to the completeness, consistency and accuracy of data. Remember the acronym ALCOA, which stands for attributable, legible, contemporaneously recorded, original or a true copy and accurate (ALCOA).
What are the main requirements for data integrity? Steps to take include:
- Backing up data completely and in its original form.
- Storing data so that it can’t be erased, lost, degraded or changed in any way.
- Documenting activities at the time of performance.
- Using scientifically sound laboratory controls.
- Retaining original records or true copies of the originals.
- Including complete data derived from all tests.
Some of these are no-brainers, such as backup. Sometimes companies get tripped up with the completeness aspect of data integrity, however, running tests multiple times until they get a good value. Referred to as cherry-picking data or testing into compliance, this can get you in big trouble.
Other data violations to watch out for include recording data after you’ve performed activities. A technician who runs a test can’t write it on a slip of paper (or worse, a lab napkin) to record later. Companies need to ensure they record data in real-time as they happen, which is easier to do with automated GMP Regulatory Compliance Software.
Supplier and Contract Manufacturer Compliance
Supply chain problems are also one of the top issues that lead to FDA warning letters. The company producing the final product is responsible for ensuring cGMP compliance of pharmaceuticals and medical devices, but this can be a challenge when part of the manufacturing process occurs outside your own facility.
An integrated QMS with Supplier Management tools can significantly reduce risk in this area, allowing you to:
- Extend compliance responsibilities such as pre-shipping inspections and corrective action requests to suppliers and contract manufacturers.
- Use Supplier Ratings to benchmark top performers and identify those that need to improve performance.
- Collect quantitative data to better manage supplier quality agreements as well as future negotiations.
Looking at FDA warning letters, one thing you see the agency hammering companies for over and over again is inadequate use of audit trails. Audit trails create a formalized history, tracking the creation and any changes to electronic laboratory records.
What are some of the bigger mistakes with audit trails that can earn you a warning letter?
- Disabling audit trails on equipment.
- Audit trails that show deleted test results.
- Having software that doesn’t actually track audit trails.
- Not reviewing or retaining audit trails per FDA guidelines.
Again, automated GMP software can take the guesswork out of this common error.
Automation ensures your audit trails are secure, computer-generated and time-stamped, also incorporating any change management activities into electronic records.
At the end of the day, avoiding scrutiny (and potential fines) from the FDA is all about doing your due diligence to protect the safety of consumers. Having consistent systems in place, well-trained employees and comprehensive documentation of lab activities will help you avoid some of the most common issues that have tripped up others in the past.