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Batch Records
SURVEY OF QUALITY REGULATIONS AND STANDARDS
CLASSROOM ACTIVITIES:
UNDERSTANDING BATCH RECORDS
Submitted by Madison Area Technical College
Contact Person: Diana Drier, Senior Research/Manufacturing Specialist
Waisman BioManufacturing
University of Wisconsin-Madison
Drier@waisman.wisc.edu
February, 2013
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PURPOSE
This exercise is intended to teach students about batch records in a cGMP facility. The following are
provided in this exercise:

Introductory information along with an example batch record to guide discussion in the
classroom. The example batch record is found in a separate file. It demonstrates the kinds of
information that should be captured in the document and the level of detail that is required for
cGMP compliance. While the format may vary from facility to facility the information captured
is generally the same.

A table with relevant terms for students to fill in (p. 5). Students are instructed to find
definitions for these terms and fill in the table.

Definitions of the relevant terms (“answer key” for the term table) (pp. 6-10).

Assignment in which students prepare a batch record of their own (p. 4).

Batch Record Assignment Checklist to guide students in setting up their batch record
and to guide evaluating student work (p. 11).
SUGGESTIONS TO THE INSTRUCTOR
1. Hand out to the class the Example Batch Record (from the separate file), Terminology Table
(p. 5), and Batch Record Assignment Checklist (p. 11).
2. Explain that this exercise has several parts. In the first part students will examine and discuss
an example batch record. They will also fill in a table with associated terminology. Filling in the
table can be assigned as homework or it can be done during class. After students have explored
the example batch record and completed the term table, they will create their own batch
record for a task of their choice.
3. Describe the scenario on p. 4 to create a context for the Example Batch Record. Observe that
this particular batch record is written within a contract cell manufacturing company, that is, a
company that grows cells on a contract basis for clients. Discuss the importance of only using
raw materials that have been approved by the company’s quality assurance/control team.
Discuss the importance of traceability, that is, being able to determine the origin of every
material that goes into manufacturing the cells. Discuss the importance of verification in
assuring that the manufacturing technician performs each step properly. Have students
evaluate the level of detail provided in the procedure.
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4. Following classroom discussion, assign the students to write their own batch record. The
example batch record defines what kinds of information should be captured in the
document and the level of detail that is required for cGMP compliance. While batch record
document format may vary among manufacturing facilities, the information captured
remains the same. The actual procedure in the students’ batch records should be written
with sufficient detail so that a person with a science background and relevant experience
would be able to follow the outline of steps to successful completion.
5. Explain that students will hand in the first draft of their batch records and fellow
classmates will do the initial document review, exchanging hard copies of batch records and
editing them with red pens. This will simulate the actual batch record review process that
occurs in the workplace and help students better understand what defines a well written
versus a poorly written document. Students will then return these edited documents to
the author for incorporating those changes that they see as valid improvements in the
document. Students will be graded on both their own batch records and the thoroughness
of their peer edits. Stress that these documents typically go through multiple edits and this
is how authors craft the strongest (most technically well defined) batch records.
The instructor can use the Batch Record Assignment Checklist for grading or can have
students use this checklist to “grade” one another.
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Scenario: A client has contacted the business manager of Cells R Us with an inquiry
about creating a Master Cell Bank. The client’s intention is to have Cells R Us culture
HEK293 cells to manufacture a single 300 vial lot of cGMP grade cells to serve as a
Master Cell Bank. The cells in the Master Cell Bank will be used in the future in the
manufacture of a viral vaccine for clinical trial therapies. Following this inquiry, the Cells
R Us business manager creates a proposal that details deliverables (300 vials at 1X106
cells/vial), costs, and projected time line. After negotiations, the contract is
approved/signed and a deposit is received by Cells R Us. A Cells R Us project leader is
assigned and following an internal meeting discussing contract details, a meeting with
the client is scheduled. During this meeting, more details regarding production and
testing of the final product are outlined. The project leader spends the next two weeks
putting together a first draft of the batch record.
Directions to students:
1. Review the example batch record and identify/highlight the terms listed in the terminology
table.
2. Find the definitions and acronym translation for each term and fill in the table. The links
below contain glossaries of cGMP terms but you may need to look for other sites on your own.
http://www.gmp-quality.com/GMP_Definitions_J.html
http://www.gmp-publishing.com/en/glossar.html#
3. Create your own cGMP batch record. Your batch record will detail a scientific protocol of
your own choice and can be taken from actual laboratory experience or a book/online source.
Batch record should be a minimum of 20 steps, demonstrate your understanding of the
intent of the document, and include items listed in Batch Record Assignment Checklist.
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Term
cGMP
Batch Records
Acronym translation and definition
GLP
Batch Record
SOP
QCP
Revision
Client Project Code
Lot/Batch Number
Document Approval
QA
QC
QA Issued
Pagination
Raw Material
Bill of Materials
C of A, C of C
Room Release
Verification- Operator, Verifier
Equipment Identification
Operator Comments
Deviation
QA Review
websites used:
_____________________________________________________________________________________
_____________________________________________________________________________________
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cGMP GLOSSARY
cGMP is an acronym for current Good Manufacturing Practices. These practices are defined by
US Food and Drug Administration in a unified federal code of regulations Title 21 CFR 210,211.
These documents outline expectations for the design, construction and operation of all facilities
that manufacture drugs/devices for human clinical applications. The intent of these regulations
is to assure the manufacture of a sterile, potent and uncontaminated product.
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?CFRPart=210
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?CFRPart=211
GLP is an acronym for Good Laboratory Practices and deals with the organization, process and
conditions under which laboratory studies are planned, performed, monitored, recorded and
reported. These practices are defined by US Food and Drug Administration in a unified federal
code of regulations Title 21 CFR 58. The intent of operating under GLP guidelines is to assure
the quality and validity of test data by mandating that laboratory research or testing is well
documented, that materials can be traced to their origin and that the research data gained can
be translated to clinical manufacture.
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=58
Quality Management System is the broad management oversight of a cGMP facility. It refers
to the system in place that ensures manufacture of a consistent and quality product and
encompasses Quality Assurance, Quality Control, Facility Operations and Manufacture. All
these facets of a cGMP facility must be strictly regulated in terms of documentation with the
goal of meeting government mandates intended to control safety and efficacy of manufactured
products as defined under cGMP guidelines.
Quality Control refers to the process of reviewing or testing a product. Within a cGMP facility
QC personnel are responsible for executing QCPs (Quality Control Procedures) that specifically
outline a test protocol. Typically the intent of testing is to confirm the identity of the product,
sterility, absence of contamination, concentration and activity or potency. A document called a
QCS (Quality Control Specifications) is always created for each product manufactured. The
QCS document dictates all the testing required and the specifications for passing those tests
prior to product release.
Quality Assurance refers to the process of controlling a facility with the intention of
maintaining it in accordance with cGMP guidelines with the ultimate goal of manufacturing a
reliably/consistently safe and effective product. QA personnel are responsible for overseeing
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documentation and maintaining records that demonstrate compliance with established
guidelines.
A batch record (BR) is a document written by a member of the manufacturing team that details
the complete step by step protocol for the manufacture of a batch/ lot of a particular product.
In the example provided the final product is an HEK293 Master Cell Bank. Note that the
example is incomplete in that it shows only the beginning of the MCB production, namely the
media preparation and initial thawing and seeding of cells. A batch record should be written
with explicit details, allowing that the manufacturing scientists have the required skill set (s), in
this case cell culture experience. The draft batch record is initially reviewed internally by
facility management (typically the managers of manufacturing, quality control and quality
assurance). After internal review and incorporation of identified edits, the batch record is given
to the client for review. A revised and final draft must then be approved by all parties involved
and officially issued prior to commencing manufacture.
A Standard Operation Procedure (SOP) is a document that details a procedure performed
repetitively within a cGMP facility. Unlike a batch record, an SOP is not client or product
specific and is often embedded within a batch record. In the example BR provided, the
procedures for release of clean room space based on proper preparation of the room for
manufacture, cleaning of the BSC and labeling of prepared medium and seeded flasks are three
examples that reference SOPs. SOPs can also be distinct from batch records; some examples
are sample shipping, maintenance and calibration of equipment, routine monitoring of air
quality in cleanroom space. SOPs are typically written by people most familiar with the
operation or procedure and are approved by manufacturing and quality assurance managers.
An essential step in the training of all cGMP employees is reading and comprehension of all
SOPs that pertain to their position. All employees have training folders that include a
comprehensive list of all SOPs read.
A Quality Control Procedure (QCP) is a document that details the protocol for a specific test
performed by members of the Quality Control (QC) team. These documents are typically
written by the member of the QC group that is most familiar with the protocol.
Verification is the initialing performed by the manufacturers after completion of a step that
confirms that each specific step was performed. In all cGMP manufacturing two people must
always be present in the cleanroom during production. One person is called the “operator” and
actually performs the operation as detailed in the batch record. The other person is the
“verifier” and confirms that the operator has performed the operation. Typically operations
that involve specified volumes or quantities, calculations, recording of RM/lot numbers, or
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labeling require confirmation by a “verifier”. Other steps may require only an “operator”
initial. This distinction is at the discretion of the client.
Revision Designation applies to all cGMP documentation and is used to identify documents
that have been changed after final approval. Typically the first version of a document will be
designated Rev. A. To initiate a change in most cGMP documents n additional document (called
a Document Control Change) must be completed. This describes the specific change(s) and an
explanation or justification for the change(s). As with all cGMP documentation, revisions must
route for review through Quality Management personnel. For example, a batch record might
be changed if a client returns with the intention of a repeat production run but wants to alter
some part of the process. An SOP might be changed to accommodate changes in catalog
numbers for required reagents. A QCP might be changed to provide a more clear explanation
of some step in the protocol. cGMP documentation should be viewed as dynamic in that
changes or improvements may be necessary.
Client Project Code (header) is a coded designation determined by QA that identifies the client,
the product, and in some cases the specific manufacturing process. In the example BR the
invented client is MATC and the product is an HEK293 master cell bank (MCB). The example BR
does not include a manufacturing process because it is a relatively simple protocol. A more
complicated protocol might be broken up into individual but related documents, for example,
manufacture of a cGMP protein might have separate documents for specific chromatography
steps, for buffer preparation, or for final formulation and packaging. All documents associated
with the production and testing and release of a product will reference this code.
Lot Number or Batch Number (header) is a code designation for the unique production of a
product following a single batch record. In the case of a repeat of the same process (returning
client) following the same batch record, a new lot number would be assigned to client project
code ie. MATC-HEK-MCB-001, MATC-HEK-MCB-002.
Document Approval Date is the date on which documents have routed through all necessary
participants and signatures have been recorded.
QA Issue Signature/Date (footer) is the signature/date of the QA personnel that issues the
document to the manufacture project lead prior. No steps in the production process can be
initiated without an issued/signed/dated BR.
QA Review is the process by which all cGMP documents are approved. Personnel trained in
this area are qualified to determine if a document passes cGMP regulations. In relation to
batch record review, QA carefully goes over the entire document looking for any missing
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information or inconsistencies in recorded information. A manufactured product cannot be
released without batch record review and approval by QA.
Pagination (footer) must be included in the BR and specified as Page # of Total Page #. This can
be included in the header or the footer of the BR.
Raw Materials (RMs) are reagents or supplies used in a cGMP manufacturing process. Some
clients specify that any item that comes in contact with the product be designated a raw
material. This is intended to ensure a product that is both sterile and free from contaminants.
Some items such as centrifuge tubes and pipets may not be classified as RMs. Unlike typical
lab reagents/supplies, RMs are received, stored and documented under strict FDA guidelines to
ensure product safety. They require a documented chain of traceability for ordering, receipt,
quarantined storage and release storage. RMs also require a Certificate of Analysis or
Compliance (C of A, C of C) from that manufacturer that lists material components,
manufacturing details, storage details, expiration date, and testing specifications and testing
results. Upon receipt, RMs are stored in a locked/quarantined area and designated
“quarantined”. QA is tasked with the review of all associated documentation prior to the
release labeling of RMs. “Released” RMs are stored in a separate locked storage area to
prevent use of those RMs not reviewed and officially “released”. No RM can be used in
manufacture until it is designated “released”.
The Bill of Materials is a list placed at the beginning of the BR that itemizes all the RMs to be
used in manufacture. The B of M should include the RM number (assigned by QA), it’s
associated lot number (assigned by QA), expiration date, vendor and catalog number. During
the manufacture process, the quantity of each RM used is captured in the batch record
document and tallies of each item is recorded in the B of M.
Equipment ID Numbers are numbers assigned by QA to each piece of equipment used within a
cGMP facility. These ID numbers are always recorded within batch records. The intent is to
capture information that will link manufacture with all equipment used and by association
confirm that equipment used has been appropriately maintained ie. routine
maintenance/calibration as specified in SOPs linked to specific pieces of equipment.
Deviations are any changes in the manufacture of a product that are not specifically outlined in
the batch record. While a well-crafted batch record should theoretically not require any
deviations to the process, there are very few that do not require deviations of any kind.
Common examples include simple typos in the document or wrong catalog numbers that are
not caught by reviewers. In the case of cell culture, sometimes cell viability can cause changes
in the culture strategy outlined in the batch record. In the case of protein manufacture,
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unforeseen problems in chromatography steps can result in the need for repurification. In the
best case scenarios, clients are willing to spend the time and money required to trouble shoot a
manufacturing process prior to cGMP manufacture but this is not always the case. Planned
deviations (those anticipated beforehand) require signature approval of the client and internal
approval by QA. Unplanned deviations that occur during the manufacture are more difficult in
terms of timing. If at all possible, it is always best to consult with the client and obtain approval
for any deviation that constitutes a significant change to the process.
Operator Comments is a section in the batch record that allows for space to record data that is
not specifically called for in the document. This is typically the area where unforeseen actions
are recorded by the operator and often times this area will make reference to deviations
associated with actions taken. Sometime this can serve as a space to record unexpected or
unusual observations that might not necessarily required action.
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Batch Record Assignment Checklist
Item
Document title
Revision designation
Company name
Client project code
Lot number
Document approval date
Bill of Materials
Non-RM Materials
Ancillary equipment
Manufacture room
Date/time of manufacture
Manufacture room release information
Detailed protocol steps
Raw data capture
Raw material identification
Equipment identification
SOP references
Signatures (operator/verifier),
Page numbers
Label information
Operator comments
QA review/approval notes
Check Mark
Deviation table
Headers/Footers
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