Quality Assurance & Quality Control

Lecture - 11

Dr Shaouki Munir
MBBS (DU), MGMP (UTS), MPH (UNSW)
 Module Contents

This module covers the following topics:

a) Electronic Batch Records
b) Checklist for BMR & BPR
c) Annual Product Quality Review
d) Quality Audit
e) Complaint investigation & product recalls
f) Stability Protocol – Preparation & Maintenance
Electronic Batch Record

• Software applications that store and manage data electronically for each batch produced
in addition to the entire manufacturing process on a step-by-step basis

• EBR software typically relies on another system, such as a manufacturing execution

system or enterprise resource planning system, to systematically generate a formal master
batch record or EBR. This master record stores all the materials, processes and activities
which were required for the production of a given product

• Electronic batch records provide the structure and means for automatically compiling
batch production data into a formatted electronic document, reducing paper and manual
records for more accurate record keeping

• Data is recorded and stored in encrypted form, guaranteeing data privacy and security
What Does EBR Software Do?

• Manages process execution

• Captures event execution and data records automatically
• Enforces manual data entry
• Reduces manual activities associated with capturing batch data
• Generates electronic reports & production documents
• Maintains equipment histories and material genealogies
• Ensures compliance with FDA 21 CFR Part 11 CGMP
• Can be integrated into other systems such as manufacturing automation
equipment such as programmable logic controllers and distributed control
systems, business systems and more
Additional Functionality of Electronic Batch Record
Software

• Calculations
• May be able to perform simple to complex arithmetic operations
• Documents: Batch dates
• Batch weights
• Components in each batch
• Workers involved in handling & processing each batch
• Performs routine integrity checks of data Software tracks every piece of data
inserted into electronic forms
• This makes it easy for batch coordinators to follow up on the processing of every
batch
Which Industries Utilize Electronic Batch Records Software?
 BMR Checklist

• Quality Assurance person shall ensure the following Checklist For BMR Release

• The header section of the checklist must contain the Product brand name, Product
Generic name, Batch Number, Batch size, BMR number, and QA release number
A Checklist for BMR

1.1 All the materials taken for production are approved

1.2 All the quality raw materials used for Blending/Sieving/Milling are weighed and recorded correctly
1.3 All the materials have been taken as per the standard quantity

1.4 Is the quality of active ingredients taken for batch calculated correctly

1.5 Line clearance was taken before dispensing and counter-checked by IPQA properly

1.6 Temperature is within the limit in the dispensing room

1.7 Are correct sieves used for sieving the materials as per the batch record

1.8 The Blending duration and blending quantities are recorded as per the BR

1.9 All signatures and dates are filled properly in all columns
A Checklist for BMR (contd.)
2.0 Does the compression/filling start after the approval of the blend by QC
2.1 Blend report is approved and attached in BMR
2.2 Is line clearance taken before compression/filling
2.3 Compression/filling parameters are set as per the limits specified in BMR
2.4 Are the in-process checks performed at the frequency and recorded properly, and counter-checked by IPQA
2.5 In-process parameters are within limits
2.6 Temperature and Humidity in the compression/filling area are as per the limits
2.7 The QC report after compression/filling is attached to BMR
2.8 Is the coating started after the QC approval of compression
2.9 Machine setting parameters for coating are as per the limits specified in BMR
2.10 Are the visual checking parameters recorded properly
2.11 Overall signatures are filled correctly in the specified columns
2.12 The yield at all stages is within the limits as specified in BMR
2.13 QC report after the coating is approved and attached to BMR

In case of any discrepancy in the above points, fill BPRR/BPAR deviations /deficiencies form and verify the corrections made. The
Footer section for the Checklist for BMR must be checked by and approved with the sign and current date.
BMR (Batch Manufacturing Record)
QA Release Checklist for
BPR
MFR Sample
 Annual Product Quality Review

• Product quality review (APQR) shall be carried out for each product
manufactured in the year

• Products manufactured in the previous twelve (12) months shall be taken for
Product Quality Review (APQR) on a staggered basis covering all the batches
manufactured

• All products can be divided into three groups i.e. Group A (Tablets) – January
to December, Group B (Oral Liquids) – April to March, and Group C (Capsules)
– June to May and list them as per Annexure-I

• Priority in scheduling can be given on a risk-based approach (i.e. Market

complaint, Product Recall, Stability, or any other product issue) if required
 Annual Product Quality Review (contd.)

• Product quality review (APQR) shall be completed within 90 days; for example,
Product Quality Review (APQR) for products manufactured from January to
December 2018 shall be completed by March 2019

• The Product Quality Review (APQR) calendar shall be prepared by the quality
assurance officer and approved by the Head QA before execution

• Product Quality Review (APQR) shall be prepared product-wise and shall include all
batch sizes, different API vendors, and different codes in a single Product Quality
Review (APQR)

• If the same product is transferred/converted to other similar products, Product

Quality Review (APQR) shall be prepared as one and all market details like pack
style, Finish Pharmaceutical product testing (any additionally) shall be captured
 Quality Audit

A quality Audit is defined as a systematic and independent examination

to determine whether quality activities and related results comply with
planned arrangements and whether these arrangements are
implemented effectively and are suitable for achieving objectives.

Example Video:
https://www.youtube.com/watch?v=-p8Ms1iTEd0
https://www.youtube.com/watch?v=2iEcF9GBNOE
Types of Quality Audit

The quality audit system is mainly classified into the following different categories:-

1. Internal Audit: Done by auditors who work for the company

2. External Audit: Auditors may be hired by a supplier or customer to ensure that

the audited company meets their quality standards

3. Second-Party Audits: They may be hired by a supplier or customer to ensure that

the audited company meets their quality standards

4. Third-Party Audits: External quality audits done by an organisation that has no

contract with the company it is auditing is called a third party audit
Types of Quality Audit (contd.)

5. Process Audits: A process audit verifies that a documented process meets

quality standards

6. Product Audits: A product quality audit verifies that a physical product meets
design specifications and other quality measurements

7. System Audits: These review how the company measures and meets quality
standards. It verifies the procedures used to measure the quality of the product,
how defects are recorded, and how the company ensures that failed product is not
passed
Types of Quality Audit (contd.)

8. GMP Compliance Audit: this is an audit or an inspection conducted by someone

external to your organisation to discover GMP deficiencies.
A GMP Compliance Audit will allow you to avoid delays in bringing the product to
market due to not passing a GMP audit.
Preparation of Audit

• Should start from the beginning of the study

• Ensure that we have the documents to prove that the study
has been conducted properly
• According to ICH-GCP, Local regulation, Institution SOP
• All parties understand the protocol and procedure; any
concern raised by any party should be documented
• Aware of the chronology of the event, version of documents
Audit Process
Self-Inspection Program
Flow Chart
 MARKET COMPLAINTS

• A complaint is an objection to something unfair, unacceptable, or

otherwise not up to normal standards

• Complaint is any communication, written or verbal, received directly

from any customer, retailer, distributor, or representative of the
contract giver regarding the quality attributes, labelling defects or any
other matter; such complaints shall be considered as market
complaints
Why do customers complain?
Classification of Complaints

• A-Type Complaints: Adverse Drug Reaction, Major health hazard

causing permanent deficiency or death, Purity & Safety, Potency,
Product Stability

• B-Type Complaints: Problem with primary packaging of the product,

Chemical / Physical attributes of the product, Extraneous
contamination, mix-ups

• C-Type Complaints: Problem-related to labelling/coding of batch

details, Shortages, Secondary packaging material problem
Complaints Handling Steps

STEPS INVOLVED IN HANDLING OF COMPLAINTS

•Step I: Receiving
•Step II: Investigation
•Step III: Corrective Actions
•Step IV: Feedback to Customers
PRODUCT RECALL

Recalls are actions to remove a product from the market and

restrict further distribution and sale.

There should be a system to recall from the market, promptly and

effectively, products known or suspected to be defective. –WHO

To protect public health… necessary to implement urgent

measures such as the recall of one or more defective batches (es)
of a medicinal product from the market. – European Medicines
Agency (EMA)
RECALL CLASSIFICATION
Class 1 Recall
Situation in which there is a reasonable probability that the use or
exposure to the product will cause serious adverse health
consequences or death.
Class 2 Recall
Situation in which use or exposure to the product may cause temporary
or medically reversible adverse health consequences or where the
probability of serious adverse health consequences is remote.
Class 3 Recall
Situation in which use or exposure to the product is not likely to cause
adverse health consequences.
DURATION OF RECALL OPERATION

• Class 1 Recall – Within 24hr to Maximum 72 hr

• Class 2 Recall – Within 10 days

• Class 3 Recall – Within 30 days

TYPES OF RECALL

1. VOLUNTARY RECALL:
This is a product recall from the market or distribution network of the
entire available quantity at the time of recall initiation, based on a
decision by Recall Management Committee. This could be because of
the following:

• quality complaints from market

• discovery of some deficiency
• stability problem after dispatch
• unsold stocks (short expiry)
TYPES OF RECALL (contd.)

2. FORCED RECALL:
This is a recall forced by a regulatory agency upon
discovery/reporting of a violation or deficiency in the product.
Who will initiate the recall ?

▪ Head QA shall decide on recall in consultation with the management of the

firm, including crucial personnel involved in the handling of the recall,
based on the category of defects identified in the product/batch(es)
▪ In Case of filed products, the Head – QA shall consult Head-Regulatory
Affairs on the recall strategy, which shall include:
✓Decision to recall
✓Need to inform Marketing, Regulatory bodies and Customers,
✓Extent of effectiveness checks for recall (whether all consignees are to be
notified)
▪ In case of a domestic product recall, the local FDA shall be informed
depending on the class of recall
References

• Bhakar, N., 2021. [online] Available at: <https://pharmaguddu.com/quality-assurance-checklist-

bmr-release/> [Accessed 24 December 2021].

• Singh, J., 2020. APQR - Annual Product Quality Review in Pharma - Guidelines - SOPs. [online]
Guidelines - SOPs. Available at: <https://guideline-sop.com/apqr-annual-product-quality-
review/amp/> [Accessed 24 December 2021].

• Wilhite, T., 2017. Quality Audit Types. [online] Bizfluent. Available at: <https://bizfluent.com/list-
6833307-quality-audit-types.html> [Accessed 24 December 2021].

• Braga, G., 2007. [online] Available at: <https://onlinelibrary.wiley.com/doi/pdf/10.1002/qaj.398>

[Accessed 25 December 2021].