Foolproof Batch Records – the Process Approach

Properly designed batch records

In my experience, many companies don’t realize that to develop a batch record properly; the underlying manufacturing process should be thoroughly engineered and organized.

We all know that batch records should be designed to fulfill many requirements. Our previous post detailed these requirements from a regulatory point of view. Just to recap, your batch records must be;

• Compliant with the dossier and GMP,
• Easy to fill in,
• Easy to review by the QP,
• Promote Data Integrity principles.

Many GMP companies don’t realize that to develop a batch record properly; the underlying manufacturing process should be thoroughly engineered and organized.

Everyone is talking about Quality by Design, but do we get the right results during the technical transfer? When the design phase is concluded, I would expect to find a well-organized process with properly defined inputs (materials), parameters and sampling plan. After all, this is the basis for a decent batch record.

Examples of an unorganized manufacturing process

What I observe in many cases are organized manufacturing processes which aren’t properly organized, I have listed a few examples;

• Production steps are not (or wrongly) numbered (might be a result of one or more of the following points),
• Summarizing diagrams are not included, these are intended to explain how the process is organized,
• Multiple production steps are combined into one step (e.g., harvest from the fermenter followed by centrifugation),
• It’s unclear exactly WHERE and WHEN raw materials are needed in a production step,
• Parameters are not properly specified as critical or key (and why),
• No ranges are provided for process parameters, and what will happen with the process or the product if the process operates outside of those ranges,
• No insight is provided into why parameters are chosen, or exactly when and how to take a sample,
• No intermediates and/or maximum Holding Times for those intermediates.

The result of these factors will usually be a poor batch record, simply because the background (Design of the Process) is poor, which is caused by the issue that proper process design is usually not considered to be critical to success.

If the process is not well engineered in itself, it will be difficult to design a unidirectional GMP Batch Record. This will negatively influence adherence to Data Integrity Principles at the very least. If a process is well designed, it allows you to have a separate batch record for each major processing step/activity.

Benefits of unidirectional GMP batch records

The benefit of this approach is that while the process is progressing, the finished records can be sent to QA for review much quicker. As a result, if QA observes issues, the repair of the issues can be done much earlier during the process of reviewing and approval of the records.

Common mistakes

Just as a side-step: I have seen companies using batch records requiring Quality Control results to be written down in the batch record. Besides the fact that this is already violating the principles of Data Integrity in itself, it forces the records to be held in inside the manufacturing area for prolonged periods of time without purpose. It’s better to have separate records for those exercises (or automated systems).

Another thing I often observe is batch records which require more than one parameter to be filled in in a single table cell, without having lines or other separators indicating where to fill in the outcome exactly. This is not supporting the requirement; easy to fill in, nor is it easy to review.

Other batch records contain a lot of check-lists, which makes the records rather bulky. Many of those checks are not critical to quality while filling the shelves for a minimum of 5 years. Many companies have special vaults for these records, meaning it’s expensive, crucial storage space being wasted on paper which doesn’t contain crucial data.

Only include critical GMP elements

In my opinion, it’s better to have only the critical elements of a process in your batch records. All other operational required checks etc. should be recorded using separate systems.

This saves QA (and QP’s in Europe and China) a lot of review time as well.What you should avoid in your batch records are standard sentences or complete Bills of Equipment and other lists of materials which aren’t essential.

Many companies have (physically) fixed equipment in many rooms, in other words: operators don’t have a choice other than using the equipment fixed in that room. Yes, they need to record using it, but to provide lengthy Bills of Equipment for each record on a separate page is not useful.

The outcome of a properly designed batch record

To summarize, the design of proper Batch Records has many angles of approach. But, if done properly, efficient usage is promoted. Finally, I am convinced that if the design of the batch records is done properly, the produced batches will be more proper.