A Look at Batch Record Review

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The review of batch records creates a story of the materials, manufacturing, and packaging involved in the production of bio/pharmaceuticals, according to Susan Schniepp, distinguished fellow at Regulatory Compliance Associates.

Q: I have just been promoted to a new position in the quality organization at my company and will now be responsible for batch record release. I am a little nervous about this responsibility. Can you give me some tips for reviewing and releasing batch records? 

A: This is a great question. Batch record review and release is an important responsibility in any company and it should not be taken lightly. The best way to visualize a ‘batch’ record is to think of it as a series of photographs that, if put together in the proper sequence and with the correct background, tell a story about the quality and suitability of the product. 

The first picture in this story begins with the incoming raw materials that include the active ingredient(s), excipients, primary packaging, and labeling. Each one of these items should be properly received, sampled, and put into quarantine until the incoming quality group establishes their suitability for use. This includes testing of the water that might be used in manufacturing the product. The background of this picture would be making sure the laboratory equipment was properly calibrated, the methods validated, and the analysts properly trained. Once the materials are deemed suitable, they may be released to the manufacturing line for formulating and processing. The foreground in this picture should be the results from the laboratory testing, the inventory control procedures, and the certificate of analysis from the supplier(s). It is important to make sure that any deviations or errors associated with this activity have been properly investigated.

The next picture in the story is the actual manufacturing of the product. The picture here is a master batch record where the actual amounts of the actives and excipients are mixed together and formulated into the final product. In this particular photograph, it is important to notice the foreground as well as the background. The foreground should be the confirmation that all the materials used were appropriately discharged using calibrated equipment in a suitable environment. Also in the foreground should be some indication as to whether the manufacturing rooms were properly cleaned and cleared before the start of the next batch. The main focus of the picture should be the details of the batch manufacturing itself. Things to notice would be: 

  • Were the materials sequenced/combined in the proper order (if this matters)?

  • Were the materials mixed and stirred for the required length of time? 

  • Were the results of any in-process testing with in specification(s)? 

Attention needs to be paid to make sure that any deviations during this phase of production have been resolved.

Another focus of the picture should be the behavior of the operators, especially if your product is processed aseptically. It is also important to make sure that operators signed (this could be electronically) in the appropriate places indicating they performed the work. If required, there should also be an indication that another employee or a supervisor witnessed the work. This is particularly important when verifying the right ingredients were discharged to the line to make the right product with the right dosage amount. Attention should also be paid to making sure any deviations or investigation have been thoroughly investigated and closed before releasing the product. The background of this activity should focus on the training of the operators to perform their functions, robust process validation, the qualification of cleaning materials to prevent cross or microbial contamination, and other routine maintenance and monitoring procedures that maintain the manufacturing area and lines to an acceptable state of control. The background also should include results of environmental and personnel monitoring (if appropriate), media fills for aseptic processed product, particulate-matter monitoring, smoke study results, etc.

The next photograph in the batch record tale is the packaging of the final product into its primary container. The foreground in this photograph should be on the release of the labeling and confirmation that the lot number and the expiration date assigned are appropriate. The main picture should center on making sure there were no component mix-ups or line stoppages that would compromise the product during the packaging phase of the operation. Again, attention needs to be paid to make sure that any deviations during this phase of production have been resolved. Background for this photo includes container-closure integrity and stability.

There is actually no specific order in which the information/photo should be reviewed. Some reviewers like to wait until they have everything before they start their review so they can see the whole story upfront; others like to disposition or view the pictures as they come in and try to visualize the final picture. Either way is acceptable for batch record review. Many companies use a checklist to make sure all the elements of the master batch record are included in the product batch record. This is an acceptable practice and, when coupled with a thorough review of the contents of those elements, you should be able to rest assured that you will be able to have confidence in releasing product batches.