FDA warning letters-2015 on Data Integrity Issues

FDA issued two warning letters in January 2015 relating to Data Integrity

data_integrityData integrity is essential requirement in a pharmaceutical quality system, which ensures that medicines are of required quality.

If FDA finds that the data are not valid and reliable, it is the indication for FDA that the entire system is out of control and quality of medicine from that manufacturer cannot be assured.

In the last one year (2014) US Food and Drug Administration (FDA) issued eight warning letters to pharmaceutical manufacturers from India and china based on the findings related to the data integrity practices.

Further to year 2014, two more warning letters were issued recently in January 2015.

The common data integrity problems that have been observed by FDA inspectors in past:

Non contemporaneous Recording: Failure to record activities at the time when activity was performed. There is evidence that the records were signed by company personnel when the person was actually absent on that day.

Document back-dating: Backdating stability test results to meet the required commitments.

Copy of existing data as new information: Test results from previous batches were used to substitute testing for another batch or acceptable test results were created without performing the test.

Re-running samples to obtain better results: Multiple analyses of assay were done with the same sample without adequate justification and in some cases samples were tested unofficially or as a trial analysis until desired test results obtained.

Data fabrication and data discarding: Original raw data and records were altered for e.g., by using of correction fluid or Manipulation of a poorly defined analytical procedure and associated data analysis in order to obtain passing results.

FDA expects that pharmaceutical companies should retain complete and accurate records and all raw data and to make that available to FDA inspectors, as an evidence that manufacturing processes comply with cGMP regulations.

The integrity of data generated by a regulated pharmaceutical companies and laboratories matters most, because properly recorded information is the basis for manufacturers to assure product identity, strength, purity, and safety and non-compliances found in the integrity of data leads warning letters and a regulatory action from the U.S. Food and Drug Administration (USFDA).

What GMP regulations (21 CFR 211) say about data integrity:

  • All written procedures must be established, approved and followed; any deviation from these written procedures shall be recorded and justified [211.160(a)]
  • Instruments must be qualified, fit for purpose and perform a function satisfactorily and shall not be used if not meeting established specifications [211.68(a) and 211.160(b)]
  • Any calculations and formula used must be verified independently by second person to ensure accuracy, completeness and conformance with procedures [211.68(b), 211.103, 211.194(a)(8)]
  • Data generated in an analysis must be backed up and secure from alteration, unintentional erasures, or loss [211.68(b)]
  • Test data must be accurate and complete and in compliance with established specifications and standards [211.194(a)]
  • A complete record of all data for each testing including all graphs, charts, and spectra from laboratory instrumentation must be properly identified and secured [211.194(a) 4]
  • Any modification of an established method employed in testing must be documented and such records shall include the reason for the modification [211.194(b)]
  • Reagents and reference solutions should be prepared correctly with appropriate records [211.194(c)]


Due to increased fraud detected by the agency and in the changing regulatory scenario, inspectors are now trained to review electronic records with more focus on system and audit trails rather than reviewing the paper print outs.


Below is list of warning letters issued by FDA in year 2014-15 related to data integrity

Micro Labs Limited 1/9/15
Apotex Research Private Limited 1/30/15
Cadila Pharmaceuticals Limited 10/15/14
Apotex Pharmachem India Pvt Ltd. 6/16/14
Tianjin Zhongan Pharmaceutical Co., Ltd. 6/10/14
Sun Pharmaceutical Industries Limited – Karkhadi 5/7/14
Canton Laboratories Pvt. Ltd. 2/27/14
Usv Limited 2/6/14


Regulatory Agencies does not expect from pharmaceutical industries to review the data by applying Forensic approaches however it is expected that the industries should design the system in such a way that can assure the integrity of records and data with full evidence of supporting raw data that should be secure from alteration, unintentional erasures, or loss.

Recently MHRA released guidance on data integrity (Revision-1) in January 2015

This MHRA Guidance mentioned Regulatory expectations from pharmaceutical industries on GMP data integrity.

In brief, this guidance suggest about establishing data criticality and inherent integrity risk, designing systems to assure data quality and integrity, also tells about ALCOA approach for data.


A= Attributable to the person generating the data
L= Legible and permanent
C= Contemporaneous
O=Orignal (or ‘True copy”)
A= Accurate

1 responses on "FDA warning letters-2015 on Data Integrity Issues"

  1. You are doing good job. Some of the information are very useful

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