Data Integrity Trends in 483s and Warning Letters: Part 1

Why do we care about data integrity?

Data Integrity (DI) is, perhaps, the most important concept in Drug Manufacturing.  Drug Manufacturing is an incredibly complex process, requiring sophisticated science and instrumentation at every step of production and storage. If you cannot trust the data of the process and its results, then can you really trust anything?

Accordingly, DI is amongst the top items cited on Warning Letters.  In fact, the FDA cited DI on 79% of the Drug Warning Letters over the last 5 years, and they have increased the number of Warning Letters citing DI by over four times (Figure 1).


In this three-part series, we’re going to examine what exactly data integrity means to the FDA and why it matters. We looked at 483s and warning letters with data integrity citations issued over the last five years and will show you:

  • How often data integrity is cited
  • How citation rates change by region
  • Distinct keywords and phrases
  • Differences between keywords used in 483s and warning letters

(NOTE: Looking for an easier way to research observations by specific keyword?  Get your FREE 483 Observation Report and you can quickly determine who has been hit with the same observations. Learn more here!)


Why is the concept of Data Integrity so elusive?

DI is one of the more elusive concepts in Drug manufacturing.  I don’t think it is hard to understand per se, but it is very hard to find. Allow me to explain.

We had to implement over 200 unique keywords and keyword strings to identify DI in FDA enforcement documents.  200! In fact, the FDA has over 20 ways of stating “original data” (original HPLC, original results, original document etc).

DI is so elusive that the words “data integrity” ranks 33 out of 200 for the most mentioned keywords.  Yes, you read that correctly. It’s so elusive that if you searched for the words “data integrity”, you would find less than 5% of the 483s that cite DI!

Who gets hit harder, smaller companies or Big Pharma?

Now that we know how elusive the concept is, let’s look at whether Big Pharma is any better at DI versus the rest of the industry.  Turns out that they aren’t any better!

We discovered that DI citation rates are roughly the same for Big Pharma as CDER as a whole when it comes to 483s (Figure 2).

One item to note, however, is that while roughly half of Big Pharma’s 483s cite DI, ~86% of their warning letters cite data integrity. We’ll look at more differences between 483 and warning letter data integrity citations later in this series.


How do data integrity citation rates change by region?

As we’ve discovered in other CDER enforcement trend reports, Asia consistently receives more citations for data integrity than any other region (Figure 3).  This could be a result of the increasing inspection in Asia by the FDA after the United States Government Accountability Office report on international inspections not keeping up with the increasing number of drugs and active ingredients coming from Asia.

Europe, on the other hand, ranks as the region with the fewest citations.

(RELATED: Learn more about drug GMP warning letter trends for countries outside the U.S. here.)


Next Steps

In subsequent posts, we will walk through additional DI trends, align the FDA’s citations to the concept of ALCOA plus, and walk through our methodology.  Continue reading to part two here.

What else would you like to see? Please leave us a comment below.

(NOTE: Did you know you can easily search observations by keywords such as data integrity, process validation, complaints and more?  Get your FREE 483 Observation Report and you can quickly determine who has been hit with the same observations. Learn more here!)



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