FDA suggests that adherence to the data integrity is must to ensure the cGMP compliance. GMP is a system for ensuring that products are consistently produced and controlled according to quality standards.
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The data integrity issues have been frontrunners for the USFDA to hammer pharma companies. The data integrity-related CGMP violations have led to several regulatory actions, including warning letters, import alerts, and consent decrees. A few years ago, Ranbaxy signed a consent decree with USFDA and also paid $500mn in civil and criminal fines.
Plants of Wockhardt, IPCA laboratories remain under the warning letter/import alerts for long now. Dr. Reddy had received a warning letter in 2015 over data integrity issues, along with others. Over the last two years, Indian companies like USV, Hetero and Sri Krishna Pharmaceuticals (all unlisted), Agila Specialties (Mylan’s subsidiary), etc. have received warning letters over data integrity, which USFDA gives a very high importance.
Recently, Sun Pharma, Aurobindo, Biocon, etc. received form 483 observations, but there was no data integrity related observations, hence stocks did not tank heavily. In case of Sun Pharma, the stock moved up. This makes it interesting to understand data integrity, from the eyes of USFDA.
USFDA suggests that data integrity refers to the completeness, consistency, and accuracy of data, which should be attributable, legible, contemporaneously recorded, original or a true copy, and accurate. USFDA suggests that adherence to the data integrity is must to ensure the cGMP compliance. GMP is a system for ensuring that products are consistently produced and controlled according to quality standards.
FDA’s minimum data integrity requirements are:
Data should be secure from alteration, inadvertent erasures, or loss. Backup data should be exact and complete.
Data should be stored to prevent deterioration or loss.
Certain activities should be documented at the time of performance and that laboratory controls should be scientifically sound.
The records should be retained as original records, true copies, or other accurate reproductions of the original records.
FDA requires data to record complete information, a complete record of all data from all the tests performed, and no test or data should be failed to record.
FDA also requires metadata to be stored throughout the record’s retention period.
Other guidance that USFDA suggests when it comes to data integrity includes:
The data to be auditable for reconstruction of the past events relating to the creation, modification, or deletion of the records.
The manufacturing companies should enable appropriate controls over the data/records so that change in the records can only be made only by authorized personnel restricting of the alteration of the records.
The system administrator role for computers (having rights to alter files and settings) be assigned to personnel independent from those who are responsible for recording the content.
The systems controls, including documentation controls, should be designed to follow CGMP to assure product quality.
Companies must keep the incomplete or the erroneous forms as part of the permanent record along with written justification for their replacement.
All changes in the critical data to be audit trailed.
The processes should be designed so that quality data to be created and maintained cannot be modified.
USFDA prohibits followings:
Recording of the data on pieces of paper that can be discarded.
Storing of the data in temporary memory.
Sampling and testing with the goal of achieving a specific result or to overcome an unacceptable result as this is not as per the CGMP standards.
Use of actual samples to perform system suitability (system suitability tests should be done by using written procedures and data should be recorded for scientific justification for exclusion).
USFDA suggests that drug shall be deemed adulterated if the methods or facilities or controls used to manufacture, process, pack, or hold the drug does not conform to adherence to the current good manufacturing practice. The adherence to the cGMP is required to assure that the drug has safety, identity and strength that meets the on the quality and purity characteristics.
(Source for this is USFDA website: Data Integrity and Compliance With CGMP Guidance for Industry)