It’s well known that companies regulated by the FDA need to know what’s currently on the mind of the agency’s enforcement officials — so that the firms can know where to focus their compliance resources.

One way to do this is to make sure that the particular compliance issues that are currently important to the FDA get lots of attention.

Of course, an FDA inspection or a remote regulatory assessment can raise questions in investigators’ minds about any relevant compliance issue — so you can never predict with absolute certainty what agency enforcement officials will be interested in when they come knocking on your door or when they send you a request for documents.

The truth is, however, that neither the FDA nor the companies it regulates have infinite resources to devote to every possible compliance matter.

So, keeping up to date on what the FDA is concerned about may be one way to help you concentrate your compliance resources wisely.

Tracking Warning Letters

For anyone interested in following trends in FDA enforcement, one of the most useful things you can do is to follow the steady stream of Warning Letters that the agency releases.

Here at Thompson FDA, we constantly watch for new FDA Warning Letters, FDA Untitled Letters, and HHS Office for Human Research Protections (OHRP) Determination Letters. We report on the most important ones in our FDA Weekly News Roundup email newsletter.

And we make sure that new enforcement letters are quickly added to our searchable FDA Enforcement Letter Database — typically just a few days after the letters are posted.

What Summer Vacation?

One batch of Warning Letters that the FDA posted recently is a good case in point.

There seem to be no summer doldrums in the agency’s enforcement offices: 14 new Warning Letters were posted on Aug. 8.

More than half of the letters were issued to non-U.S. drug manufacturers by the same compliance office within the FDA.

And, lo and behold, half of the new letters covered the same topic: failing to test incoming drug product ingredients.

Specifically, the seven Warning Letters alleged that:

• the overseas pharmaceutical companies failed to conduct at least one test to verify the identity of each drug product component (21 C.F.R. §211.84(d)(1)); and
• the companies failed to establish adequate quality control units with the responsibility and authority to approve or reject drug product components (21 C.F.R. §211.22(a)).

Case in Point

For example, the FDA issued one of the Warning Letters to Istanbul, Turkey-based Tan Alize Kozmetik Ve Temizlik Urunleri, a manufacturer of sunscreens and other OTC drug products.

In the letter, CDER alleged that the company had not adequately tested each shipment of the incoming components that was at high risk of diethylene glycol (DEG) or ethylene glycol (EG) contamination.

Lots of Warning Letters lately — more than 25 so far this year — have shown the FDA’s concern with glycerin that may be contaminated with DEG or EG.

And for good reason. As the agency has told these companies, “The use of glycerin contaminated with DEG or EG has resulted in various lethal poisoning incidents in humans worldwide.”

But Wait …

And there are other patterns to spot in these seven Warning Letters.

Each of them was issued not following an inspection, but because of the results of a remote regulatory assessment.

Instead of conducting an on-site inspection, the FDA issued a Section 704(a)(4) request for records and other information in advance of or in lieu of an inspection. and the agency reviewed the records provided. (One company was cited for not responding to the Section 704(a)(4) request,)

These assessments were the go-to surveillance method for the FDA during the COVID-19 pandemic, when the ability to conduct an inspection was severely limited. Despite the easing of the pandemic, it looks like the assessments are here to stay.

Plus, each of the non-U.S. companies was placed on an Import Alert.

Lesson Learned

The takeaway: Watch for patterns in FDA Warning Letters.

Note the alleged violations that the agency cited, and take a close look at the FDA’s pronouncements on how the companies needed to come into compliance.

You might just end up being more prepared for the next round of FDA scrutiny that comes your way.