FDA Data Integrity Guidance Analyzed

Attorneys Frederick Ball and Carolyn Alenci (Duane Morris) say that a recent FDA draft guidance on data integrity and subsequent Warning Letter to Sri Krishna Pharmaceuticals indicate that “FDA is anticipating long-term measures to be part of a corrective action plan that includes enhancing procedures, systems, and ‘human resources.’” They add that noncompliance with data integrity current good manufacturing practice (CGMP) may result in significant sanctions, including consent decrees, import alerts, or the like.

Writing in an online blog post, the attorneys analyze the draft guidance, noting the agency’s assertion in the document that the only time CGMP data may be excluded from decision-making is when there is a “valid documented, scientific justification for its exclusion.” In other situations, the guidance says, any data created as part of a CGMP record must be evaluated by the quality unit as part of release criteria.

FDA says in the draft that every workflow, including creation of an electronic master production and control record, must be checked through validation for its intended purpose, and appropriate controls must be used to assure that changes to computerized master production and control records or other records or input of laboratory data into computerized records can be made only by authorized personnel.

Any data generated to satisfy a CGMP requirement is considered to be a “CGMP record” and thus the agency requires the data to be documented or saved at the time of performance. The post says it is important to recognize that FDA finds it unacceptable to record data on paper that will be thrown out after it is incorporated into a permanent notebook. It is likewise unacceptable to store data in temporary memory or in a manner that allows for it to be manipulated before being permanently recorded.

If there is any indication of a quality issue, such as suspected or known falsification or alteration of a record, the draft guidance says that it must be formally and fully investigated under the CGMP quality system to determine: (1) the effect of the event on patient safety, product quality and data reliability; and (2) the root cause. The purpose of the investigation, the post says, is to ensure that necessary corrective actions are taken.