In addition, we remain concerned that your (b)(4) adverse drug experience reporting system has not been fully validated, and may have resulted in inaccurate assessment and untimely submission of 15-day alerts. The current application was released into production on November 9, 2009 using an Interim Validation report (IVR) that is still not final.

Critical issues (deviations) identified in your interim validation report during the inspection included the following, but is not limited to: lack of training for your (b)(4)support team, incomplete SOPs and Work Instructions, and inaccurate data migration of legacy adverse experience cases from your previous adverse drug experience database, (b)(4). Currently, your (b)(4) system does not display accurate clock dates on MedWatch forms for cases which were initially entered in (b)(4) and later entered into (b)(4) due to the receipt of additional information (follow-up) for the same cases.

MedWatch forms printed out from (b)(4) for these migrated cases are documented as initial 15-day reports, instead of follow-up reports. Also, the report date in Block B5 of the MedWatch form is the print date, not the actual date of submission. Shortcomings such as these affect the accuracy, reliability, consistency of the system and your firm’s ability to discern invalid or altered electronic records or make timely submissions to FDA as required.

Comment

This audit observation (FDA 483) was made during an inspection of a pharmaceutical facility by the FDA focusing on the compliance with Postmarketing Adverse Drug Experience (PADE) reporting requirements. These are critical electronic records for any pharmaceutical company.

This observation relates to 21 CFR Part 11 and the integrity of electronic records. There are three interesting parts to this observation.

Validation

The validation of the system was criticised for not being complete and that critical issues (deviations) had not been closed. We have all been involved in projects where the system must go live due to project constraints and yet the system is either not finished or has not successfully completed the validation. Understanding the issues, documenting within a risk assessment with respects to patient safety and record (data) integrity to make an informed decision as to whether the system can be released to production.

If the system fails to meet the acceptance criteria, where significant risks to patient safety or record integrity cannot be controlled (technically or procedurally) then the quality unit must ensure that the system does not go in to production.

Clock

Within the FDA 483 it was observed that

Currently, your (b)(4) system does not display accurate clock dates on MedWatch forms for cases which were initially entered in (b)(4) and later entered into (b)(4) due to the receipt of additional information (follow-up) for the same cases.

The accuracy of clocks used within electronic record systems is imperative to ensuring accurate records. Within 21 CFR Part 11 the inclusion of date and time is quoted, including for creation, modification and deletion of records, audit trails and electronic signatures.

To ensure the accuracy of the time source for meeting electronic record requirements the computer time must be synchronised with a master clock. Where multiple countries are involve the time should also include the time zone.

Record Integrity

Although not citing against 21 CFR Part 11 directly this observation brings in to question the integrity of the record. The quote your firm’s ability to discern invalid or altered electronic records or make timely submissions to FDA as required is a direct quote from 21 CFR Part 11 (validation).

Care must be taken with electronic record systems to ensure that the integrity of the record is not compromised. The clock issue is one that should be simple to fix, synchronising PC clocks across the IT network.

The reporting of the migrated data should have been picked up during the testing prior to the system going live either with controls put in place to ensure that the records were accurate or the system not released for use until the issue was resolved.