By Danielle DeLucy, ASA Training & Quality Consulting, LLC
In today’s fast-paced environment, everything needs to be done right the first time. This is especially important when releasing pharmaceutical and biological products to the market. To accomplish this, firms employ a special group of quality professionals, called the batch review/release group, to review executed batch records and be that all-important final sign-off for release to market. This is no easy task. Much of the time, these executed batch records are many pages long with complex information and data to review for accuracy. Effective and efficient management of this review process is the key to a successful process.
According to the many global regulations on the topic, production and control records should be reviewed and any failure of a batch to meet specifications should be thoroughly investigated. The investigation should, if necessary, extend to other batches of the same product and other products that may have been associated with the specific failure. Most importantly, a written record of the investigation should include the conclusion and follow-up action. This is what usually slows down the batch record review process. Waiting for the investigation to be completed, reviewed, and approved and a product impact statement developed can take many days. During this time, the batch record sits in limbo awaiting its fate. Prior to these activities, however, reviewers can use the time to make sure the record is in compliance with good documentation practices (GDPs) and local and government regulations.
Batch Record Review — What To Look For
Along with reviewing the records for compliance to GDPs, there are certain critical process parameters (CPPs) and critical quality attributes (CQAs) each product is assigned when being manufactured. CPPs and CQAs need to meet the expected results. If at any time they do not, an investigation is necessary. Downtime logs, clearance logs, and cleaning logs all need to be reviewed for any discrepancies or mistakes. Samples are usually taken during the manufacturing process. The number of samples, the correct aliquot, and which test it is being taken for should be confirmed by the reviewer. In addition, all environmental monitoring (EM) should be documented and reviewed for compliance to the EM program. Being that these samples are incubated over a number of days, results will be confirmed/reviewed upon batch release of the product.
Along with reviewing all of the scientific and technical data of the record, the reviewer must also ensure anyone who has executed a task has not reviewed their own work or reviewed that section of the batch record; all rooms used in the production of the batch should be clearly listed and their status documented, e.g., “room cleared, cleaned, and ready for use.” Any equipment calibrations need to be listed and dated. Review all comments listed by the operators in the record. If any require further investigation, notify QA or operations management.
All of these parameters are required to be reviewed, but not only by the quality group. Operations and quality should look for the same parameters and ensure the record adheres to the same level of compliance. When reviewing a batch record, it is imperative that the production reviewers and quality reviewers review to the same standard. In many firms, one general “batch record review” SOP is created where both groups get trained on the same procedure to ensure consistency. Also, it is helpful to have the QA group assist with the training of any production reviewers.
How To Handle Corrections To The Batch Record
The ultimate goal of batch record review is not merely to identify exceptions (e.g., mistakes, oversights, illegible entries), but to have the record corrected in a timely manner so it provides accurate documentation of the steps that comprise the manufacturing or packaging of the cited batch. Batch records may be reviewed for information again in weeks, months, or years after a subject batch has been manufactured or packaged or may be identified for review as part of a regulatory inspection. They need to be corrected before being stored. Ideally, all entry mistakes should be identified in the departmental review before the record is returned to QA for the quality review. If such a review is conducted, the instructions must clearly state the review is to identify any missing information and that entries are correct and within established parameters.
Assuming, however, there is a question or required correction at the QA review level, the person who made the original entry (or failed to make the entry) on the batch record meets with the reviewer who identified the exception. This question or required correction is noted on the “corrections sheet” in sufficient detail to allow any subsequent person to understand the concern. After discussion, if needed for clarification, the batch record corrections are made by the operations person and verified by the reviewer. When an immediate correction is not possible due to shifts, someone on vacation, etc., the reviewer must inform the person who needs to review the batch record to specify a time this will be done. Corrections to records compete for the time of operating personnel, so it is helpful to be very specific on what the question or needed correction is. Partially completed records pose a logistical and document control challenge. A procedure is needed to describe how and where such records are to be stored and who is responsible for completion if the reviewer who started the review is not available for completion in a timely manner.
Why Training Is So Important
One key to a successful batch record review is proper training. In many firms, the reviewers are just given a record to review with a trainer and then given authority to review a record independently. For a firm to be successful, all reviewers need to be aware of what they are reviewing. A new reviewer should first be given a tour of all operations areas and a chance to observe all parts of the manufacturing process. This allows the reviewer to become very familiar with the processes they will read about later upon batch record review. Once the reviewer has observed these operations, she should be given a blank batch record for that process to review. Upon becoming familiar with the record, she should sit and observe a trained reviewer review the batch record. Once a few observations of the trained reviewer are completed, she is now ready for a review. In many firms, a “mock” batch record is made, complete with purposeful mistakes, for the trainee to review. A certain number of mistakes cannot be missed, and the trainee receives a grade on her performance. If a passing score is achieved, the trainee is considered trained to review that batch record. These training plans can be applied to both the operations and QA departments.
Reviewing a record is one of the most important jobs in a pharmaceutical firm. These reviewers are responsible for making sure the batch was made properly, according to procedure and regulatory requirements. Reviewers should have great attention to detail, be able to work independently, and have a thorough knowledge of the manufacturing process they are reviewing. Reviewers should be aware of the criticality of their review as well.
By reviewing the batch record, QA and operations have the opportunity to catch errors before the product is released to the public. These reviews can save the company thousands of dollars in fines and ensure they are maintaining compliance with regulatory regulations.
About The Author:
Danielle DeLucy is owner of ASA Training & Quality Consulting, LLC, which provides pharmaceutical- and biologics-based companies with training and quality systems assistance in order to meet regulatory compliance. Prior to this role, she spent 15 years in the industry serving in numerous quality management roles. She has helped lead many regulatory health inspections and was instrumental in the coaching process of her peers prior to any inspection. Currently, DeLucy assists companies that are faced with warning letters or consent decrees and those wishing to improve compliance and establish more robust quality systems.