Introduction
As more pharmaceutical and medical device manufacturers move to electronic and paperless systems, the FDA has begun to pay special attention to manufacturer adherence to the 9 data integrity principles.
The FDA issued a draft guidance [https://www.fda.gov/regulatory-information/search-fda-guidance-documents/data-integrity-and-compliance-drug-cgmp-questions-and-answers-guidance-industry] on data integrity for pharmaceutical manufacturers required to adhere to 21 CFR Parts 210-212. The guidance states that all data within the scope of Parts 210-212 must adhere to data integrity principles throughout the cGMP lifecycle, including in creation, modification, processing, maintenance, archival, retrieval, transmission, and disposition when the retention period ends.
What is Data Integrity?
Data integrity is the completeness, consistency, and accuracy of data. There are 9 principles of data integrity that, when followed, can ensure the integrity of cGMP data in pharmaceutical and medical device manufacturing.
The 9 ALCOA+ Principles
1. Attributable
Data that can be traced to the unique user who generated the record. Every user who generates cGMP electronic records must have a unique user account, and no account sharing is allowed.
2. Legible
Data that can be easily read and understood. It is fully legible and unobscured.
3. Contemporaneous
Contemporaneous data is recorded at the time of data generation. Backdating and/or “pencil whipping” data is strictly forbidden. Late data entries must be clearly marked as late entries, and any values entered as late entries must have a verifiable source (i.e., they cannot be guessed).
4. Original
The original data record must be stored in its original (or compatible with the original) format. True copies are acceptable. A true copy has been reviewed and verified to be a complete and accurate copy of the original data.
5. Accurate
Accurate data is free from errors and is gathered according to protocol. It must be reviewed and verified by someone other than the tester. Data restored from an archive must be the same as the data originally collected and include all original metadata. All edited data must have a documented reason why, and all edits must be visible (with legible original data).
The original five ALCOA principles have been updated to include the following principles (the + in ALCOA +):
6. Complete
Complete data has an associated audit trail record. Audit trails include the records that track creation, modification, or deletion of data (parameters, results, and other cGMP data). They should include:
- Who is responsible for the data (creation or modification)
- What data was created or changed
- When the record was created
- Where the data was generated (system, unit op, etc.)
- Why the record was created, including any justification for change
7. Consistent
Consistent data is recorded in chronological order. The date and time stamps in the audit trail are recorded in the expected sequence, with the expected time consistent with the system clock.
8. Enduring
Enduring data can be read, retrieved, restored, and reviewed for the entirety of the data’s prescribed lifecycle.
9. Available
Available dataexists in a complete form and is accessible for audit, review, etc. throughout the data lifecycle.
Conclusion
Ensuring that data used in cGMP decisions is uncompromised can be one of the most important steps of process design and maintenance. Adhering to the 9 ALCOA+ principles can help ensure data integrity, and Skellig’s SMEs are ready to help every step of the way. No matter where you are in the process lifecycle, we can help bring your facility up to standard.