The Importance of Batch Record Reviews During Audits

Q. We, a contract manufacturing organization (CMO), have a written rule that describes that we will not show batch records, which have not been completely reviewed and approved by the quality function, during a customer audit. We consider this an absolute necessity to avoid an auditor finding missing or incorrect entries in the batch record. Yet, we received a critical finding for that in a recent audit. We pointed out to the auditor that we are following our quality system, but the auditor would not change the criticality of the observation. Do you think this is fair?

A. Clearly, if this had been a regulatory inspection, refusal to present a batch record, whether reviewed by your quality unit or not, would be considered preventing an inspection, with all its consequences (1). However, this was an audit, so this is a different situation.

We must consider why a CMO may not wish to present a batch record during an audit. The one obvious and valid reason is client confidentiality. But even this can easily be overcome by asking the client to use an impartial auditor.

You cite a very different reason, namely the need to have the batch record first reviewed and approved by the quality unit in order to have a “perfect” batch record. The best way to demonstrate the error in this is by presenting real examples from various CMO audits.

The regulations specify that batch record entries must be made contemporaneously (2). That means as close to the event as is possible. During an audit of a filling line, it was found that the machine had broken down and two engineers were busy repairing the equipment. As this would take a while, the operators had left the line and went to have an unscheduled break. The review of the batch record revealed that there were no entries for the following:

• The equipment having broken down, or when
• The shift operators having left the room, or when they left
• The engineers being present in the room, or when
  they entered.

The site’s quality system explicitly required all these to be documented, yet it hadn’t happened. Only the possibility to review the batch record allowed the auditor to find and record this deviation. Even a later review by the quality unit could not have found these errors and omissions. Thus, only a review of the batch record at the time of the audit can uncover such non-compliances.

When the shift operators returned to the line, they were confronted with the missing entries. Thereupon, one of the operators started to enter the data from memory, in fact backdating the events. Again, something impossible to detect at a later date.

The regulations also specify that entries cannot be made before the actual activity has taken place (3). A good time to perform audits is during lunch breaks when staff are away from their workplaces. During an audit of a packaging line, a batch record was found that had signed entries for completed actions that would only take place after the lunch break. If the batch record had not been presented in that audit, it would not have been possible to find this serious deviation from the basic principles of good documentation practice.

Batch record reviews by the quality unit typically take 40 or more days at CMOs, by which time the audit report has long been written and issued. In most cases, auditors would thus be unable to even review the “sanitised” version of the batch record.

These few actual examples clearly demonstrate the absolute need for auditors to have access to the batch records of the activities they are reviewing. If this is prevented, they cannot verify the truthfulness (i.e., the integrity) of data in the batch record. And to most auditors, this is a critical observation.

References

1. FDA, Circumstances that Constitute Delaying, Denying, Limiting, or Refusing a Drug Inspection, Guidance for Industry (October 2014).

2. FDA, Data Integrity and Compliance With Drug CGMP, Questions and Answers, Guidance for Industry (December 2018),

3. PIC/S, PIC/S Guidance Good Practices for Data Management and Integrity in Regulated GMP/GDP Environments PI 041-1, (July 1, 2021).

About the author

Siegfried Schmitt is vice president, Technical at Parexel.

Article Details

BioPharm International
Vol. 35, No. 3
March 2022
Pages: 38

Citation

When referring to this article, please cite it as S. Schmitt, “The Importance of Batch Record Reviews During Audits,” BioPharm International, 35(3) 2022.