WELCOME

TO THE TRAINING

Ataur Rahman
Deputy Manager, Quality Control
TODAY’S TOPIC
EU GMP_ Chapter 6: Quality Control

Effective from:
1 October 2014

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CONTENT OF PRESENTATION
 Introduction
 Objective
 Scope

 Quality Control Principle

 QC Overview
 General Principle

 Basic Requirement of Quality Control

 Quality control laboratory
 Responsibility

 Quality Control Documents

 Tasks of Quality Control
 End

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INTRODUCTION

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INTRODUCTION
 Good Manufacturing Practice (GMP) is the part of Quality
Assurance that ensures that products are produced and
controlled consistently and reliably. This consistency of
production and control is essential. It can only come about by
having clear descriptions of the way in which the work will be
done.

 GMP specifically addresses risks of cross-contamination. These

risks can best be controlled by having a managed system of
working that takes them into account. This means that the
quality checking system must be designed with these risks in
mind and set out to find whether any errors have occurred.
OBJECTIVES
 To understand key elements in quality
control.
 To understand specific requirements on
organization, procedures, processes and
resources.

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 SCOPE
 Quality control involved sampling, inspecting and testing of
starting materials, in process, intermediate, bulk and finished
products.
 It also includes where applicable, environment monitoring
program, review of batch documentation, sample retention
programs, stability studies and maintaining correct
specification of materials and products.

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QUALITY CONTROL PRINCIPLES

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 QUALITY CONTROL OVERVIEW

Assurance

Objective Product with consistent quality for its intended use

Established Quality System Requirements

How Product contain the correct materials of specified quality & quantity
Manufactured under proper conditions accordingly to SOPs

Sampling
Inspection & testing of: Starting Material, Bulk, Intermediate, Finished product
Key Environment monitoring program Batch record review/documentation
Focus
Area Sample retention program Stability study Calibration Reagent Handling
Release/Reject: Control for materials & product disposition

Reprocessing Specification Control Return

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GENERAL PRINCIPLES

 Each holder of a manufacturing authorization should

have a QC Department
 Independence from production and other departments
is considered to be fundamental
 Under the authority of an appropriately qualified and
experienced person.
 If do not have any facility, it can be managed by
appointed respective external laboratory institution(s).

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Principle

 Sampling, specifications and testing as well as the

organisation, documentation and release procedures.

 Ensure that the necessary and relevant tests are

carried out, and that materials are not released for
use, nor products released for sale or supply, until
their quality has been judged satisfactory.

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Principle

 Quality Control is not confined to laboratory

operations, but must be involved in all decisions
which may concern the quality of the product.

 The independence of Quality Control from Production

is considered fundamental to the satisfactory
operation of Quality Control.

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BASIC REQUIREMENTS OF
QUALITY CONTROL

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BASIC REQUIREMENTS
Quality Control department should have :
 Resources:
 adequate facilities
 qualified personnel
 approved written procedures
 Tasks :
 sampling, inspecting, testing,
 releasing or rejecting
 monitoring
 Objects :
 Starting materials, intermediates, bulk, and finished products
 Returned products
 Environmental conditions

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QC LABORATORY
 There shall be QC laboratory attached to each manufacturing unit.

 The laboratory shall be capable of performing all the test in

accordance to approve specification, or to perform part of test
while sub-contracting part of tests to approved contract laboratory.
 Where appropriate, QC laboratories shall be separated from
production areas especially for microbiology lab.
 The laboratories should be designed to suit the operations to be
carried out in them. Sufficient space should be given to avoid mix-
ups and cross-contamination. There should be adequate suitable
space for sample and records.
 Separate rooms may be necessary to protect sensitive instruments
from vibration, electrical interference, humidity, etc.

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Responsibilities
 Duties –
 To establish, validate and implement all quality
control procedures.

 Oversee the control of the reference and/or

retention samples of materials and products when
applicable.

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General

 Duties –
 Ensure the correct labelling of containers of
materials and products,

 Ensure the monitoring of the stability of the

products

 Participate in the investigation of complaints related

to the quality of the product, ……
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General

 All the operations should be carried out in accordance

with written procedures and, where necessary,
recorded.

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General
 Finished product assessment should embrace all
relevant factors –
 Production conditions,
 results of in-process testing,
 a review of manufacturing (including packaging)
documentation,
 compliance with Finished Product Specification and
examination of the final finished pack.
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General

 Quality Control personnel should have access to

production areas for sampling and investigation as
appropriate.

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Good Quality Control Laboratory Practice

 Quality Control laboratories should be separated from

production areas.

 Control laboratories should be designed to suit the

operations to be carried out in them.

 Sufficient space should be given to avoid mix-ups and

cross-contamination.

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Good Quality Control Laboratory Practice

 There should be adequate suitable storage space for

samples and records.

 Separate rooms may be necessary to protect sensitive

instruments from vibration, electrical interference,
humidity, etc.

 Special requirements are needed in laboratories

handling particular substances, such as biological or
radioactive samples 22
Good Quality Control Laboratory Practice

 Laboratory equipment should not be routinely moved

between high risk areas to avoid accidental cross-
contamination.

 The microbiological laboratory should be arranged so

as to minimize risk of cross-contamination.

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Good Quality Control Laboratory Practice

 The personnel, premises, and equipment in the

laboratories should be appropriate to the tasks
imposed by the nature and the scale of the
manufacturing operations.

 The use of outside laboratories, contract analysis can

be accepted for particular reasons, but this should be
stated in the Quality Control records.
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Documentation
Documentation
 Specifications should be readily available
.

 Procedures describing sampling, testing, records

(including test worksheets and/or laboratory
notebooks), recording and verifying;

 Procedures for and records of the

calibration/qualification of instruments and
maintenance of equipment;

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Documentation
 A procedure for the investigation of Out of
Specification and Out Of Trend results;

 Testing reports and/or certificates of analysis;

 Data from environmental (air, water and other utilities)

monitoring, where required;

 Validation records of test methods, where applicable.

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Documentation

 Any Quality Control documentation relating to a batch

record should be retained (up to shelf life plus one
year) on retention of batch documentation.

 Some kinds of data (e.g. tests results, yields,

environmental controls) should be recorded in a
manner permitting trend evaluation.

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Documentation

 Any out of trend or out of specification data should be

addressed and subject to investigation.

 In addition to the information which is part of the batch

documentation, other raw data such as laboratory
notebooks and/or records should be retained and
readily available.

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TASKS OF QUALITY CONTROL
QC WORK FLOW
Start
Quarantine
Quarantine • Intermediates
• Incoming materials
• Bulks
• Water
• Returned goods
2. Receiving • Finished goods
• Environment monitoring

3. Sampling
QC/QA Status
4. Test samples
Quarantine Lab
Quarantine Records
5. Review of batch record
Release
Release
NO 7. Non conformance or
Reject
Reject Meet specification out of specification
YES investigation
6. Goods release
Release
Release
8. Goods Reject Reject
Reject
End
End
Receipt
 There should be written procedure on the receiving, internal
labeling, quarantine and storage of starting materials,
packaging materials and other materials as appropriate
 Upon receiving of the supplied goods, its identity, legibility of
batch number, integrity of its primary packaging and seal
shall be verified prior to acceptance.
 Certificate of Analysis shall be provided by the supplier
accompanying the receiving of starting materials
 Quarantine goods shall be segregated from “Release” goods
 Reject goods shall be stored in a define area with
consideration of control access (eg. Locked area)
Sampling
The sample taking shall be done in accordance with written
procedure that describe:
 The method of sampling
 The sampling tools used
 The amount of samples to be taken
 The type and condition of the sample container to be
used (ie. amber glass bottle)
 The identification of the container sampled
 Special precaution for hazardous materials
 The storage condition (if any)
 Instruction for cleaning and storage of sampling
equipment
 Instruction for re-sealing the opened container.

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Sampling
 Sample containers should bear a label indicating the
contents, with the batch number, the date of sampling
and the containers from which samples have been
drawn.

 They should be managed in a manner to minimize the

risk of mix-up and to protect the samples from adverse
storage conditions.

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Sampling Tools

Scoop for solid

Dip tube Spears for bag

for liquid

Weighted container for large tank

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Testing
 Testing methods should be validated.

 A laboratory that is using a testing method and which

did not perform the original validation, should verify the
appropriateness of the testing method.

 All testing operations described in the marketing

authorisation or technical dossier should be carried out
according to the approved methods.

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Testing

 The results obtained should be recorded.

 Results of parameters identified as quality attribute or

as critical should be trended and checked to make
sure that they are consistent with each other.

 Any calculations should be critically examined.

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Testing
 The test record should include -

 Name of the material or product and, where

applicable, dosage form;
 Batch number and, where appropriate, the
manufacturer and/or supplier;
 References to the relevant specifications and
testing procedures;

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Testing
 The test record should include -
 Test results, including observations and
calculations, and reference to any certificates of
analysis;
 Dates of testing;
 Initials of the persons who performed the testing;
 Initials of the persons who verified the testing and
the calculations, where appropriate;
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Testing
 The test record should include -
 Initials of the persons who verified the testing and
the calculations, where appropriate;
 A clear statement of approval or rejection (or other
status decision) and the dated signature of the
designated responsible person;
 Reference to the equipment used.

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Testing
 In-process Control -
 All the in-process controls, including those made in
the production area by production personnel,
should be performed according to methods
approved by Quality Control and the results
recorded.

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Testing
 Special attention should be given to the quality of
laboratory reagents, solutions, glassware, reference
standards and culture media.

 They should be prepared and controlled in accordance

with written procedures.

 The level of controls should be commensurate to their

use and to the available stability data.

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Testing
 Reference Standard –
 Reference standards should be established as
suitable for their intended use.

 Their qualification and certification as such should

be clearly stated and documented.

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Testing
 Reference Standard –
 Whenever compendial reference standards from an
officially recognised source exist, these should
preferably be used as primary reference standards
unless fully justified (the use of secondary
standards is permitted once their traceability to
primary standards has been demonstrated and is
documented).
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Testing

 Reference Standard –
 These compendial materials should be used for the
purpose described in the appropiate monograph
unless otherwise authorised by the National
Competent Authority.

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LABORATORY REAGENT
 Reagent should be prepared in accordance with written procedures.
 Volumetric solution, the last date of standardization and the last current
factor should be indicated.
 Where necessary, the date of receipt of any reagents should be
indicated on the container. Instruction for use and storage should be
followed.
 Where necessary, the identification test and/or other testing of reagent
materials is required upon receipt or before use.
 Reagent to be certified by the original producer to the quality of reagent
grade purchased, typically a CoA shall be available for review and
verification on acceptance.
 Laboratory safety manual shall be available for safe operation of the
reagent and chemicals.

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LABORATORY REAGENT

All reagents should bear a label containing the

following information :
The name of the reagent
Its strength or concentration
Its expiration date
Date of preparation
Name of the individual who prepared it
Material Safety Data Sheet (MSDS)

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LABORATORY REAGENT

 Culture media should be prepared in accordance with

the media manufacturer’s requirements unless
scientifically justified.

 The performance of all culture media should be

verified prior to use.

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LABORATORY REAGENT

 Used microbiological media and strains should be

decontaminated according to a standard procedure
and disposed of in a manner to prevent the cross-
contamination and retention of residues.

 The in-use shelf life of microbiological media should be

established, documented and scientifically justified.

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STABILITY STUDY
 Stability test shall be carried out where applicable
 Real time stability shall extend to the end of shelf life
period for any new products and should include the
following parameters:-
Number of batch(es) for different batch size
Relevant physical, chemical, microbiological test
methods
Acceptance criteria
Description of the container closure system(s)
Testing intervals (time points)
Description of the condition of storage

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On-going stability programme
 After marketing, the stability of the medicinal product
should be monitored according to a continuous
appropriate programme that will permit the detection of
any stability issue (e.g. changes in levels of impurities
or dissolution profile) associated with the formulation in
the marketed package.

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On-going stability programme

 The purpose of the on-going stability programme is to

monitor the product over its shelf life and to determine
that the product remains, and can be expected to
remain, within specifications under the labelled storage
conditions.

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On-going stability programme

 This mainly applies to the medicinal product in the

package in which it is sold, but consideration should
also be given to the inclusion in the programme of bulk
product.

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On-going stability programme

 For example, when the bulk product is stored for a

long period before being packaged and/or shipped
from a manufacturing site to a packaging site, the
impact on the stability of the packaged product should
be evaluated and studied under ambient conditions.

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On-going stability programme

 The on-going stability programme should be described

in a written protocol and results formalised as a report.
 The equipment used for the ongoing stability
programme (stability chambers among others) should
be qualified and maintained as per GMP guidelines.
 The protocol for an on-going stability programme
should extend to the end of the shelf life period.

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On-going stability programme

 The protocol for the on-going stability programme

can be different from that of the initial long-term
stability study as submitted in the marketing
authorisation dossier provided that this is justified
and documented in the protocol (for example the
frequency of testing, or when updating to ICH/VICH
recommendations).

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On-going stability programme

 The number of batches and frequency of testing

should provide a sufficient amount of data to allow
for trend analysis.

 Unless otherwise justified, at least one batch per

year of product manufactured in every strength and
every primary packaging type, if relevant, should be
included in the stability programme (unless none
are produced during that year).
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On-going stability programme

 In certain situations, additional batches should be

included in the on-going stability programme.
 For example, an on-going stability study should be
conducted after any significant change or significant
deviation to the process or package. Any reworking,
reprocessing or recovery operation should also be
considered for inclusion.

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CALIBRATION
• To maintain the accuracy and precision of test equipment at all times.

• To ensure highest level of confidence in all measurement that affect

materials disposition decision, with unbroken chain of traceability to
national standard.
• To determine whether the equipment is still fit for its intended
purpose.
• It is based on the comparison of a primary standard or instrument of
known accuracy with another equipment (to be calibrated)
• It is used to detect, correlate, report or eliminate by adjustment of any
variation in the accuracy of the equipment being calibrated.

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CALIBRATION

CALIBRATION INTERVAL
Depending on:
 Classification of Critical or non-critical
 Usage (light or heavy usage)
 Handling (light or heavy handling)
 Manufacturer’s recommendation
 Reference to NIST or accreditation body
guideline for a specific measurement system

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CALIBRATION

CALIBRATION RECORDS
 Calibration Master Plan
Include the control of all critical measurement
equipment that contain the following details
 Name
 Identification by model # and serial #
 Location
 Owner/Responsible
 Calibration Frequency
 Calibration due date
 Calibration Certificate
 Calibration Procedure
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Technical transfer of testing methods

 Prior to transferring a test method, the transferring

site should verify that the test method(s) comply
with those as described in the Marketing
Authorisation or the relevant technical dossier.

 The original validation of the test method(s) should

be reviewed to ensure compliance with current
ICH/VICH requirements.
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Technical transfer of testing methods

The transfer of testing methods from one laboratory

(transferring laboratory) to another laboratory
(receiving laboratory) should be described in a
detailed protocol.

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Technical transfer of testing methods
 The transfer protocol should include, but not be
limited to, the following parameters:
 i. Identification of the testing to be performed
and the relevant test method(s) undergoing
transfer;
 ii. Identification of the additional training
requirements;

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Technical transfer of testing methods
 iii. Identification of standards and samples to be
tested;
 iv. Identification of any special transport and
storage conditions of test items;
 v. The acceptance criteria which should be
based upon the current validation study of the
methodology and with respect to ICH/VICH
requirements
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Technical transfer of testing methods
 Deviations from the protocol should be
investigated prior to closure of the technical
transfer process.
 The technical transfer report should document
the comparative outcome of the process and
should identify areas requiring further test
method revalidation, if applicable.

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REVIEW OF THE TRAINING PROGRAM

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