FDA Guidance

Dissecting the FDA Guideline for Data Integrity – Article #4

Republished with permission from Roque A. Redondo



Dissecting the FDA Guideline for Data Integrity – Article #4


Author: Roque A. Redondo

VP Automation and Business Development USA Operations – mirus Consulting Group


So far, we are basically half-way on the discussion of the guideline. On this new Article #4, I expect to be able to discuss Question #9 through Question #14 of the new FDA Guideline on Data Integrity.


Question #9: – Can electronic copies be used as accurate reproductions of paper or electronic records?


The FDA answer related to this question can be summarized in the following bullets:


-Yes. Electronic copies can be used as true copies of paper or electronic records, provided the copies preserve the content and meaning of the original record, which includes all metadata required to reconstruct the CGMP activity and the static or dynamic nature of the original records. It is recommended that the copies be controlled to avoid having copies all over the site.


-True copies of dynamic electronic records may be made and maintained in the format of the original records or in a format that allows for the content and meaning of the original records to be preserved if a suitable reader and copying equipment (e.g., software and hardware, including media readers) are readily available.


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Question #10: Is it acceptable to retain paper printouts or static records instead of original electronic records from stand-alone computerized laboratory instruments, such as an FT-IR instrument?


The answer from the FDA establishes that:


-A paper printout or static record may satisfy retention requirements if it is the original record or a true copy of the original record.


-During data acquisition, for example, pH meters and balances may create a paper printout or static record as the original record. In this case, the paper printout or static record, or a true copy, must be retained.


-Electronic records from certain types of laboratory instruments are dynamic. In these cases, a printout or a static record does not preserve the dynamic record format that is part of the complete original record (e.g. the spectral file created by FT-IR is dynamic and can be reprocessed.


-Original laboratory records, including paper and electronic records, are subject to second-person review to make certain that all test results and associated information are appropriately reported.


-Similarly, in microbiology, a contemporaneous written record is maintained of the colony counts of a petri dish, and the record is then subject to second-person review


Question #11: Can electronic signatures be used instead of handwritten signatures for master production and control records?


The FDA answer was that:


-Yes, electronic signatures with the appropriate controls can be used instead of handwritten signatures or initials in any CGMP required record. We have to comply with the requirements of the 21 CFR Part 11 Guideline for Electronic Records and Signatures.


-The signature must securely link the signature to the record so it will be legally binding to the author.


-Firms using electronic signatures should document the controls used to ensure that they are able to identify the specific person who signed the records electronically.


Question #12: When does electronic data become a cGMP record?


Not all the records generated in a company are cGMP records. The FDA answer related to this question was that:


-When generated to satisfy a cGMP requirement, all data becomes a CGMP record.


-You must document, or save, the data at the time of performance to create a record in compliance with CGMP requirements.


-FDA expects processes to be designed so that data required to be created and maintained cannot be modified without a record of the modification (audit trails). For example, chromatographic data should be saved to durable media upon completion of each step or injection instead of at the end of an injection set, and changes to the chromatographic data or injection sequence should be documented in an audit trail. Aborted or incomplete injections should be captured in audit trails and should be investigated and justified. This statement applies to all cGMP data during the process (good data or data from incomplete steps).


-It is not acceptable to record data on pieces of paper that will be discarded after the data is transcribed to a permanent laboratory notebook.


-You may employ a combination of technical and procedural controls to meet CGMP documentation practices for electronic systems.


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Question #13: Why has FDA cited use of actual samples during “system suitability” or test, prep or equilibration runs in Warning Letters?


The FDA has been very clear with the practice of sampling and testing with the main idea of getting a “good” result or to overcome a “bad” one. In other words, “testing into compliance” is not acceptable.


-The FDA has cited this practice when they have found that companies have used this methodology as a way of testing into compliance.


-If an actual sample is to be used for system suitability testing, it should be a properly characterized secondary standard, written procedures should be established and followed, and the sample should be from a different batch than the sample being tested.


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Question #14: Is it acceptable to only save the final results from reprocessed laboratory chromatography?


The FDA has been very clear and consistent about this practice. The guideline establishes:


-No, no & no. Analytical methods should be accurate and precise. Additionally, for most lab analysis, reprocessing data should not be needed.

-If chromatography is reprocessed, written procedures must be established and followed and each result retained for review.


-FDA requires complete data in laboratory records, which includes but is not limited to notebooks, worksheets, graphs, charts, spectra, and other types of data from laboratory instruments.


On this article, I included the discussion of Question #9 up to Question #14. On Article #5,I will continue presenting the information included in the next set of questions presented in the guideline. I expect to discuss Question #15 up to Question #18. In addition, I will include few examples of Data Integrity findings from FDA Warning Letter or FDA 483.


With this guideline, the FDA has been clear and emphatical about practices that they do not expect to find in current laboratories and manufacturing areas. They have been very direct about the importance of Data Integrity and how it should be the day to day way of thinking in the regulated environment where most of us work daily.