White Paper: Effective Batch Record Review

Practices

Author: Danielle DeLucy

Owner, ASA Training & Quality Consulting, LLC

A strong batch record review system is essential in order to properly document all critical
processing parameters that go along with the production and manufacture of
pharmaceuticals, biologics, medical devices, etc.

Most Regulatory Agencies require firms to have written procedures in place to document
production and process controls, better known as batch records. Additionally, there must
be written procedures for a batch record review process that demonstrate compliance.
The WHO Guideline states that production and control records should be reviewed and any
failure of a batch to meet its 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. A written record of the
investigation should include the conclusion and follow up action. Likewise, FDA also has
specific requirements for Batch Records. Per CFR requirements (Section 211.192
Production Record Review), “All drug product production and control records…shall be
reviewed and approved by the quality unit to determine compliance with all established,
approved written procedures before a batch is released or distributed.”

It is important to know what to look for when reviewing a Batch Record. There are certain
Critical Processing Parameters and Critical Quality Attributes that each product is assigned
when being manufactured. These CPPs and CQAs are necessary for the proper
manufacture of the batch. In addition, Good Documentation Practices, (GDPs), need to be
followed when executing a batch record.

All entries to a cGMP document must be accompanied by the identity of the person (initials
or signature) and the date that the entry was made. This is required by the Code of Federal
Regulations (CFRs) and serves as a tracking method to determine that a task was indeed
performed and who did the work. Initials are the accepted standard method of
identification. However, some operations require a signature. For example, an “Approved
by” space must be filled with a signature, not initials. For larger companies with people
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Practices

that have the same initials you will need to make a standard. Examples of your signature
and initials will also be recorded by the various companies.

When remediating a correction there are a number of steps to follow to ensure it is done
the correct way. When making a correction to a manually recorded entry on a controlled
document performs the following steps:

 Place a single line through the incorrect entry

 Initial and date the adjacent to the cross-out
 Enter the correct data near the original entry
 The mistake must still be legible through the cross-out.
 Date of the correction is the date the correction was made, not the date the error
was made.

No handwritten changes or corrections will be made to the printed text of an approved

cGMP document. Consult with your supervisor if you discover an error. Any changes
required to an approved cGMP documents shall be implemented through the established
quality system.

If information is not entered at the time or completing the step, the blank entry shall be
marked by an asterisk or similar notation. The use of each notation is limited to one per
page. Comments explaining the reason information is missing, along with the proper
information (e.g., date event actually occurred), shall be documented on the same page of
the record. The explanation shall be initialed and dated at the time of recording.

Once a batch is selected to be manufactured, a record is printed out or in the cases where
electronic batch records are used, the proper recipe is selected. All ingredients that are
used are listed, all time ranges are documented along with the person performing the
activity. Once the batch is deemed completed, the operations group is ready to review the
batch record for any errors. Once they have performed their review, the record is sent to
the QA group for a final review.
 White Paper: Effective Batch Record Review
Practices

Operations and Quality should be looking for the same parameters and ensure that the
record adheres to the same level of compliance. All documents related to the manufacture
of a batch should be prepared according to written procedures. Each specification for any
ingredient used in a batch should controlled and maintained by the QC department. All
Batch Record (BR) reviewers should be aware of these specifications and notify a manager
or the QA department management when once of these specifications is not met.

The issuance, revision, superseding and withdrawal of batch records should be controlled.
These items should be reviewed at the time the executed batch record is completed. Chain
of custody of the records should have a procedure and all reviewers need to be trained on
this. Each record should consist of a signature page where anyone who has performed
work or review in/of the batch record needs to print/sign his/her name. All times need to
have consistent units associated with them, i.e., if military time is used, ensure that it is
used throughout the document.

Ensure that 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, i.e. “room cleared, cleaned and ready for use.”
All equipment calibrations need to be listed and in date. Review any/all comments listed
by the operators in the record. If any require further investigation, notify QA or operations
management.

CPPs and CQAs need to meet the expected results. If at any time, these do not, an
investigation is necessary. Downtime logs, clearance logs, cleaning logs all need to be
reviewed. Any/all samples needed to be taken during the manufacture of the batch should
be confirmed by the reviewer. All environmental monitoring should be documented and
reviewed for compliance to the EM program. Results will be confirmed / reviewed upon
batch release of the product.

Operator training needs to be confirmed. Any associated training modules needed to be

completed prior to working on a batch should be documented in the record and the
operator’s compliance to that module is necessary. The amount of time for review should
have some general guidelines around it. For example, once a batch is made, the firm should
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Practices

establish time limits around operations review of the record, how long it took to get the
record to QA and QA timeliness of review as well.

Reviewing a record is once of the most important jobs in the pharmaceutical firm. These
reviewers are responsible to make sure that the batch was made properly, according to
procedure and regulatory requirements. Reviewers should have a 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.

The ultimate goal of batch record review is not merely to identify exceptions (e.g., mistakes,
oversights, illegible entries, etc.), but to have the record corrected in a timely manner so
that 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.

Batch Record review is one of the most essential functions in the Pharmaceutical Firm.

By reviewing the batch record, QA and Operations have the opportunity to catch errors
before the product is released for public sale/use.

These reviews can save the company thousands of dollars in fines and ensures that they are
maintaining compliance with Regulatory Regulations.