19 April 2022

A look at batch record review

The review of batch (manufacturing) records creates a story of the materials, manufacturing, and packaging involved in the production of medicinal products.

In EU Good Manufacturing Practice (GMP) guidelines three key personnel are named. The Head of Production, the Head of Quality Control (QC) and the Qualified Person (QP).  The duties and responsibilities of these three are also described in Chapter 2 Personnel  and Annex 16 Certification by a qualified person and batch release.

EU GMP (Chapter 2 Personnel, 2.6) states that a QP “must ensure that each batch has been manufactured and checked in compliance with the laws … and in accordance with the requirements of the marketing authorisation.” (2.6) and in Chapter 4 (Documentation) adds that “all records should be available to the Qualified Person” (4.27).

The QP is responsible for ensuring that each individual batch has been manufactured and checked in compliance with laws in force in the country where certification takes place. But is the QP also obliged and required to perform the review of the batch documentation personally prior to certification of a batch. The answer is no because this is not a requirement. EU GMP requires that a batch records are approved “by the person responsible for the processing operations” and that the QP ensures that the batch records have been reviewed appropriately – but they do not have to do this review themselves.

Each QP has a personal and professional responsibility for being certain that the various checks and tests have been carried out, however, the detail of this work can be the responsibility of others. Ultimately, the QP must be satisfied either directly or, more usually, by the proper operation of the Pharmaceutical Quality System, that manufacturing, packaging, and quality control testing comply with the relevant requirements and that any deviations are controlled and managed effectively. These requirements apply whether the work is carried out on site or at a different site.

So who should do the review?

The Head of the Production department needs “to ensure that the production records are evaluated and signed by an authorised person” (2.7iii). So, the first review has to be done by production personnel, a second one might be done by a quality function that has the competence and is authorised to do so. A short review by assistants to the QP based on a checklist could be an option. Annex 16 to the EU-GMP Guidelines states that the QP is responsible for ensuring that “all records are complete and endorsed by appropriate personnel” (1.7.11).  However, a “system should be in place to indicate special observations and any changes to critical data” (4.27). So the QP should easily see if there have been any non-conformances or changes in the manufacturing process before certifying a batch. The QP should also be able to rely on the systems and know what is going on in production and quality control.

The U.S. Food and Drug Administration (US FDA) sees the Quality Control Unit (QC) as being responsible to “review records to assure that no errors have occurred” (CFR 211.22). The QC also has the “responsibility for approving or rejecting all procedures or specifications.” CFR 211.192 requires that all drug product production and control records are reviewed and approved by the QC to determine compliance with written procedures before a batch is released or distributed.