New FDA Guidance on Data Integrity, Classifying Co-Crystals

There are two items I would like to discuss today. The first is the increased attention that the FDA is paying to data integrity issues and the second is the new FDA guideline on Co-Crystals. Both of these topics are more completely covered in my courses on cGMPs and Process Validation, which are sponsored by the Center for Professional Innovation and Education (CfPIE).

To begin, data integrity has been a concern of the FDA for many years. In fact, the first Warning Letter issued (according to the current FDA warning letter database of 2005 to date) was in 2005, eleven years ago. According to the current website information, there are over 200 data integrity issues cited in the warning letters. Companies of all sizes and types are included.

According to their April 2016 draft Guideline, the FDA defines Data Integrity as follows:

"For the purposes of this guidance, data integrity 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)."

Thus, it covers ALL data recorded, transferred, or used in any manner for the production or development of a drug product. We will talk more about ALCOA in another discussion.

I would like to turn now to a discussion of the new FDA draft Guideline on Co-Crystals (August 2016). Co-Crystals are usually crystals made up of an API and an excipient. Up until now, these have been considered intermediate products formed during production. However, companies often wish to “tweak” the levels of the components in order to more effectively produce the final product. Thus—if classified as an intermediate—changes are difficult to make and justify. This leaves the manufacturer little or no chance to improve the product. Reclassifying the Co-Crystals as solvates allows the necessary changes to be made. Next time, I will do a more complete review of the new draft guideline.

My name is Steven A. Ostrove, Ph.D. As a course instructor at CfPIE since 2008, I have over 35 years of experience in the validation of regulatory affairs and research from the manufacturing side of the Pharmaceutical industry.

Both FDA data integrity and co-crystal guidance are covered more completely in two of my training classes sponsored by CfPIE, which are: Good Manufacturing Practices (cGMP) and Process Validation for Drugs and Biologics.

I also wrote a book in June 2016 entitled “How to Validate a Pharmaceutical Process, 1st Edition.” I will share additional insights that support the strategies and implementations of these topics.