How should QA review a batch record before release, and who has to do it?

1Who has to review the record.

In the US, the quality control unit has “the authority to review production records to assure that no errors have occurred or, if errors have occurred, that they have been fully investigated”.¹ Section 211.192 makes that review a condition of release: all drug product production and control records, “including those for packaging and labeling”, are reviewed and approved by the quality control unit “before a batch is released or distributed”.² Review also happens during the batch. The record identifies the people performing and directly supervising or checking each significant step, and laboratory records carry a second person’s review for accuracy, completeness and compliance with established standards.³

EU GMP spreads the same work across named roles. The head of Production ensures that production records “are evaluated and signed by an authorised person”, and the head of Quality Control that testing is done and its records evaluated.⁴ Each Batch Processing Record and Batch Packaging Record ends with approval by the person responsible for the operation.⁵ A Qualified Person then certifies each batch before sale, supply or export. Annex 16 lists what the QP must have secured, including that “all records are complete and endorsed by appropriate personnel”. Those checks may be delegated to trained staff; the QP relies on the quality system and should have ongoing assurance that the reliance is well founded.⁶ Where certification is recorded in a computerised system, only Qualified Persons should be able to certify, by electronic signature.⁷

For active pharmaceutical ingredients, ICH Q7 makes reviewing the completed batch production and laboratory control records of critical process steps a responsibility of the independent quality unit that should not be delegated. Records of non-critical steps “can be reviewed by qualified production personnel or other units following procedures approved by the quality unit(s)”, and production reviews all its batch records and ensures they are completed and signed.⁸

PIC/S summarises the sequence for critical steps: reviewed or witnessed at the time by independent, designated staff, reviewed by an approved person in production, then reviewed and approved by the quality unit before release or distribution.⁹

2What the reviewer checks.

The test in 211.192 is compliance “with all established, approved written procedures”.² In practice the reviewer checks the record against what the regulations require it to contain and the limits its master record sets.

• The record is an accurate, checked reproduction of the master, and every significant step is documented: dates, equipment, component lots and weights, in-process and laboratory results, line inspections, labelling and the people involved.³
• Actual yields fall within the maximum and minimum percentages in the master record; a yield outside them is investigated.²
• Labelling issued, used and returned is reconciled, and any discrepancy outside narrow preset limits is evaluated and investigated.³
• Laboratory results show conformance to final specifications, including the identity and strength of each active ingredient, before release.³
• Every deviation is recorded and justified, and every deviation, investigation and out-of-specification report is reviewed as part of the batch record review.³⁸
• Audit trails that capture changes to the data are reviewed along with the rest of the record.¹⁰
• Fields are completed on the current approved template, data are critically compared with acceptance criteria, and calculations are verified against the original data.⁹

In the EU, the QP’s list reaches beyond the record: the supply chain and audits, consistency with the marketing authorisation, the validated state, training, changes, stability data, investigations, complaints and technical agreements all have to support certification.⁶

3When the review finds a problem.

Under 211.192, an unexplained discrepancy, or the failure of a batch or any of its components to meet a specification, is “thoroughly investigated, whether or not the batch has already been distributed”. The investigation extends to other batches of the product and other products that may be associated with the failure, and its written record includes the conclusions and follow-up.² Batches that fail their specifications are rejected, though they may be reprocessed if the reprocessed material then meets them.³

A result invalidated by a scientifically sound investigation stays in the batch record given to the quality unit, with the investigation report that justifies invalidating it.¹⁰ Under Annex 16, all investigations pertaining to the batch, including out-of-specification and out-of-trend investigations, must be completed to a level that supports certification.⁶

4Paper and electronic records.

The requirements are the same for both: FDA says paper-based and electronic record-keeping systems “are subject to the same requirements” for retention and review.¹⁰ What changes is how the review can be done. EMA accepts a risk-based review of electronic data, and review by exception, when it is scientifically justified and the system and its exception report are validated.¹¹ On paper, PIC/S expects the reviewer to check that corrections leave the original readable and that changes to critical data carry a valid reason.⁹

5How it runs in Seal.

In Seal, batch release runs as a release case. The executed batch record, material genealogy, laboratory evidence and quality reviews come together, and each requirement has an owner, a source and a recorded outcome. Manufacturing, QC and QA can review completed evidence while later work continues, and QA’s disposition records the batch population, the evidence reviewed, the rationale and the meaning of the signature. In the EU the QP then certifies.

Neil, Seal’s AI agent, can prepare a batch for review: it checks execution, laboratory and quality evidence against your batch-review requirements and drafts a source-linked brief with missing evidence requested. In electronic batch records, completeness and exceptions are evaluated while the batch runs. Neil does not release a batch or replace a signature.