The document is a presentation on batch review and release within the context of quality management systems in the pharmaceutical industry, focusing on regulatory requirements and best practices according to 21 CFR standards. It covers the responsibilities of quality control units, importance of thorough documentation, in-process quality control, and case studies highlighting efficiency improvements. The use of technology, such as Aspen’s production execution manager, is emphasized for enhancing batch processing efficiency and reducing manual data entry efforts.

1. M.Pharm Sem 1 Presentation
Batch Review And Batch Release
SUBJECT-Quality Management System
Bubal Knowledge City,
MET’s Institute of
Pharmacy,
Adgaon, Nashik, 422003.
Maharashtra, India
Presented By-
Mr.Abhishek R. Jadhav
(QAT)
SEM I
ROLL NO. 06
Guided By-
Dr.S.P.Ahirrao
Academic Year-2021-22

2. Content
• Batch review and Batch release
• Concept of IPQC
• Line clearance
• Case Study

3. • Acc. to 21 CFR Part 211.188;
• For each batch of drug product produced, Batch Production and
Control Records must be kept, and they must contain all important
information on the batch's production and control. These records
must include the following items: -
Batch review and Batch release

4. Requirement
• The following items must be included in these records:
• Dates.
• The names of the principal pieces of equipment and lines that were
employed.
• Each batch of a component or in-process material used must be identified
specifically.
• Component weights and measurements used during processing.
• Results of in-process and laboratory controls.
• Before and after use, inspect the packing and labeling area.
• At the relevant stages of processing, a statement of the actual yield and a
statement of the percentage of the theoretical yield.
• Labeling control records in their entirety, including specimens or copies of
all labeling utilised.
• Containers and closures for pharmaceutical products.

5. Objective
• To ensure that there is enough evidence to show that the batch is of
acceptable quality and was produced in a controlled environment.
• Significance
• To ensure that there is enough evidence to show that the batch is of
acceptable quality and was produced in a controlled environment.

6. GMP requirement
• ICH Q7
Responsibilities of the Quality Unit-
• All quality-related papers should be reviewed and approved by the
quality unit.
The main responsibilities of the independent quality unit are;
• All APIs are either released or rejected. Release or rejection of
intermediates for usage outside the manufacturing company's control
• Putting in place a mechanism for releasing or rejecting raw materials,
intermediates, packing, and labeling materials.

7. • Approval of all specifications and production master instructions
• Making sure that audits are performed.
• Responsibility for Production Activities-
• Reviewing and verifying that all production batch records are
completed and signed.

8. .
• Assuring that all production variations are reported and analyzed, as
well as that important deviation are examined and the results
documented.
• Assuring that production facilities are clean and disinfected as
needed.
• Assuring that the buildings, equipment, and records are preserved in
good working order.

9. As per ICH Batch Review
• Before a batch is released or distributed, written procedures should
be established and followed for the evaluation and approval of batch
production and laboratory control records, including packaging and
labeling, to determine conformity of the intermediate or API with
defined requirements.
• Before an API batch is produced or distributed, the quality unit should
evaluate and approve the batch production and laboratory control
records of important process steps. Noncritical process step
production and laboratory control records can be checked by certified
production people or other units following procedures established by
the quality unit.
• As part of the batch record review, all deviations, investigations, and
OOS reports should be checked before releasing a batch. The quality
unit may delegate quality assurance to the production unit.

10. Production record review
• Before a batch is issued or distributed, the quality control unit must
evaluate and approve all drug product production and control
records, including those for packaging and labeling, to ensure
compliance with all established, approved written procedures.
• Any unexplained discrepancy or failure of a batch or any of its
components to satisfy any of its specifications, whether or not the
batch has been dispersed, must be properly scrutinized.
• Other batches of the same prescription product, as well as other drug
products that may have been linked to the specific failure or
discrepancy, will be investigated.

11. Responsibility Of QC Unit
as per 21 CFR 211.22
• Section 211.22: Quality Control Unit Responsibilities
• All components, drug product containers, closures, in-process
materials, packaging material, labeling, and drug products must be
approved or rejected by a quality control unit with the responsibility
and authority to do so.
• The quality control unit is in charge of approving or rejecting drug
items that have been manufactured, processed, packed, or held
under contract by a third party.
• The quality control unit's responsibilities and processes must be
written down, and these written procedures must be followed.

12. • Authority to conduct a review of production records to ensure that no
mistakes have happened.
• If mistakes have occurred, they have been thoroughly examined.

13. Effective batch review and batch release
• For an effective, consistent, and systematic review, the following
documents are required:
• Production, packaging, labelling, laboratory testing, and other aspects
of batch record review should be covered by the SOP.
• BPR Review Checklist - to guarantee that the BPR review is
comprehensive and documented.
• Also we can use Corrections Sheet

14. SOP for batch record review
• Describes the purpose/scope of the BPR Review
• Describes the BPR Review’s aim and scope. It’s not just about
identifying exceptions (mistakes, oversights, illegible input, and so
on) and taking action. Release authority/responsibility:
• QA head, Authorised person, or any other appropriately qualified
person Authorised Describes the importance of a thorough and
correct review of BPR.
• Its purpose is to ensure that the records are clear and correct, as well
as to provide evidence that the batch was created and regulated
according to internal processes and cGMPs.

15. SOP for Batch Record Review
• The following should be included in the batch record review SOP:
• Production and Quality Control Specifications Recommendations and
corrections from the reviewers. During the evaluation, the reviewer looks
for typos, missing entries, or failures to follow GDP.
• Describe the components of a “Corrections Sheet,” which a QA reviewer
can use to record corrections discovered during a review.
• Verification of source data, where possible, to ensure that the Record’s
contents are correct. – For instance, a material weighing print, a
temperature record, a dispensing record, and so on. If critical information
is missing, the SOP must specify how and when a QA reviewer should be
notified to begin and investigate deviations.

16. SOP for Batch Record Review
• To ensure that the product is of high quality and consistent, review and
verify the following.
• Controlling essential stages and other variables that affect quality ensures
this. Temperature, time, flow rates, pressures, and other discrete input
settings or output measurements on the process equipment are all
measured using a process meter (PP).
• Critical Process Parameters (CPPs)
• Critical Quality Attributes (CQAs) are process parameters that have an
impact on quality attributes.
• In terms of quality standards and process control- The findings of physical,
chemical, or microbiological tests are within the acceptable range.

17. SOP for Batch Record Review
• Investigating critical deviations or a batch of intermediate or API that
failed to satisfy specifications.
• Other batches that may have been linked to the specific failure or
deviation should be investigated as well.
• Before the batch is issued, all deviation, investigation, and OOS report
should be examined as part of the batch record review.

18. IN PROCESS QUALITY CONTROL
Definition
• IPQC is Concerned with providing a detailed and precise explanation of the
procedure to be followed from the receiving of raw materials through the
release of the finished product.
• During production, checks are carried out to monitor and, if necessary,
change the process to guarantee that the product meets its criteria.
Environmental or equipment control can also be considered a part of
process control.
• In most cases, in-process controls are carried out in the manufacturing
area.
• The implementation of such in-process controls should not have a
detrimental impact on the product's or another product's quality.

19. Objective
1. To reduce the number of human errors.
2. Describe the technique to be used in a precise, exact, and defined
manner.
3. To detect faults if and when they happen.
4. Human-initiated corrective action.
5. Assign responsibilities to the employees who are involved in the
process's functioning.
6. To ensure that manufacturing and packing operations are carried out by
specified routes and procedures.
7. Strictly adhered to.
8. Any irregularity should be detected immediately, and the type of action
required to fix the problem should be indicated.

20. Line clearance
• Definition- Line clearance is a structured procedure for ensuring that
equipment and work area are free from products, documents, and
material from the previous process that is not required for the next
schedule, and equipment is clean and ready for the next schedule
process.
• Filling/packing areas are immediately closed and free from all
previous filled/packed products.
• Rejected packing material should also be removed.
Procedure for line clearance-

21. • If the filling/packing area equipment has been idle for an extended
period then it should be re-inspected.
• After completion of all procedures, this will be checked and signed by
the supervisor.
• Line clearance will be recorded in a suitable format (attached with
sop)and this will form a part of the production record.

22. CASE STUDY
Introduction
GlaxoSmithKline (GSK) is a global healthcare company based on
science that develops and researches a wide range of innovative
medicines and brands. GSK's goal is to consistently deliver
outstanding quality, service, and value to patients and consumers
with zero defects, with manufacturing facilities in over 70 locations
around the world.
Several packaging lines process upwards of 10,000 batches per
year, with each batch record including over 1,000 manual record
entries, totaling more than 10 million manual record entries each
year. The preparation and evaluation period for each batch was
ten days.

23. Challenges
• As part of a continuous improvement approach, GSK sought to examine the
structure of its batch production record and associated workflows.
Reduced batch review time usually means faster batch cycle time, which
means increased throughput at the manufacturing facility and a shorter
cash-to-cash cycle time.
• Because of its interaction with other technologies, such as Aspen
InfoPlus.21, part of the Aspen AIoT Hub, and GSK's existing plant
automation software, AspenTech was chosen for this process (DCS). The
pilot project was a huge success, cutting order preparation time by 95%
and record review time by more than 50%.
• As the batch travels through the manufacturing process, Aspen Production
Execution Manager creates and maintains electronic records automatically,
eliminating manual effort while keeping the SOP visible.

24. Manual Process Slows Batch Release Time
• GSK is no exception to the pharmaceutical industry's inherent
complexity. Many of the company's procedures necessitate operators
performing several manual data entries regularly, in addition to other
production activities. For example, the Multi-Dose Powder Inhaler
(MDPI) Assembly & Pack at Ware processes 10 million manual data
inputs per year, requiring 3,000 man-hours per year to capture
Process Equipment Logbook (PEL) events.
• Over time, the batch record has required more and more information.
• This vital but bloated documentation hindered manual manufacturing
operations, and the paper trail caused quality investigations to take
longer than they should have.

25. Conquering the Complexity
• GSK began with a three-site pilot project: device assembly and packing at
two sites in two countries, as well as solid dosage manufacture at a third
site. GSK developed a core committee to communicate with the three sites,
set expectations, and monitor outcomes. The outcomes have been
spectacular. As the batch travels through the manufacturing process, Aspen
Production Execution Manager creates and maintains electronic records
automatically, eliminating manual effort while keeping the SOP visible. A
detailed examination of the audit process also revealed that GSK could
drastically reduce the amount of data needed to support a batch.
• Order preparation cycle time has been decreased by 95%, and record
review time has been reduced by 50%, allowing operators to work
significantly faster than before.

26. Reference
• https://www.aspentech.com/-
/media/aspentech/home/resources/case-study/pdfs/at-07380-
gsk_case-study_updates-0916.pdf
• https://www.ich.org/page/quality-guidelines
• https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.
cfm?fr=211.188
• https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.c
fm?fr=211.22

27. THANK YOU