Good Practices in Quality

Controls for pharmaceutical

manufacturers

Solomon G. (B.Pharm, MSc)

Outline

 Definition
 Management and infrastructure
 Materials, equipment,
instruments and other devices
 Working procedures
 Safety
 Stability studies
 Summary
Definition

 QC is concerned with sampling, specifications

and testing as well as the organisation,
documentation and release procedures which
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.

 QC is not confined to laboratory operations, but

must be involved in all decisions which may
concern the quality of the product.
 Each manufacturer should have a QC
Department and/or contract laboratory
fulfilling the requirement
 Independence from production is

fundamental for satisfactory compliance with

GMP
 Under the authority of an appropriately

qualified and experienced person with one or

several control laboratories at his or her
disposal
 Management and infrastructure
Control of
Organization & QMS documentation &
management records

Premises,
Data
equipment,
processing
instruments &
equipment
other devices

Working
procedures, Safety Personnel
documents
Organization and Management
 Function to meet Regulatory requirements
 Operate in accordance with Good Practice &
standards
 Good Manufacturing Practices and Good Practices
in Quality control
 Personnel
◦ Adequately Qualified , experienced and competent
◦ Managerial and technical positions to ensure operation
in accordance with quality systems
◦ No conflict of interest
 Organizational chart and job descriptions
 Supervision and training
Organization and Management
 Adequate information flow
 Traceability of the samples (from receipt to test
report completion)
 Procedures (SOP), Work instruction & documents
 Current specifications & test method
 MSDS
 Safety procedures
Quality management system
 The laboratory or organization management should
establish, implement and maintain a QMS
appropriate to the scope of its activities, including
the type, range and volume of testing and/or
calibration, validation and verification activities
it undertakes.

 The laboratory management should ensure that its

policies, systems, programmes, procedures and
instructions are described to the extent necessary to
enable the laboratory to assure the quality of the
test results that it generates.
 QMS….
 The documentation used in this QMS should be
communicated, available to, and understood and
implemented by, the appropriate personnel.

 The activities of the laboratory should be

systematically and periodically audited.

 Management review of quality issues should be

regularly undertaken (at least annually)
 QMS….
 The laboratory should establish, implement and
maintain authorized written SOPs including, but not
limited to, administrative and technical operations,
such as:
personnel
matters, qualification validation of
including & calibration analytical
qualifications, of procedures
training, clothing equipment,
and hygiene procurement,
preparation &
dealing with control of
the change
complaints reference
control,
& CAPA substances
internal audit
& reference
materials
 Documents in QC
Procedures should ensure that:
 All specifications, sampling plans, and test
procedures should be scientifically sound
 Shall be current documents with Ref No. Version
and effective date
 Authorized SOPs are available near points of use
 Invalid documents are removed and replaced
 Revised documents refer to the previous document
 Documents are archived,
 Staff are trained for the new and revised SOPs
 Records
 Procedure for the identification, collection,
indexing, retrieval, storage, maintenance and
disposal of documents/records.
 All original observations, calculations and
derived data, calibration, validation and
verification records, etc. and final results must
be retained on record for an appropriate period
of time, e.g.
 Records to contain sufficient information to
permit repetition of tests and traceability
 Records ……
 Legible, readily retrievable, stored and retained

 In a suitable environment that will prevent

modification, damage or deterioration and/or loss

 Secure, confidential. Access restricted to

authorized personnel.

 Electronic storage and signatures allowed restricted

access and in conformance with requirements for
electronic records
 QC personal
 Organization chart
 Assess
and ensure QC has sufficient people & shall have
appropriate Qualification /education, experience or trainings.
 Job description for each person
 Analyst qualification as per assigned work.
 Training
& retraining to analyst, reviewer, validation &
computer data evaluation
 Training on
◦Quality system procedures
◦Pharmacopeia General chapters
◦Test methods
◦Operation & calibration of Instruments
Basic Requirements
Resources
 Adequate facilities

(premises)
 Trained personnel

◦ Approved procedures
Analytical
◦ Equipment operation
◦ Logbook
◦ Forms/templates
◦ Formats
 Materials, equipment,
instruments and other devices
Reference
substances and
Reagents
reference
materials

Calibration,
verification of
performance Traceability
and qualification of
equipment,
Reagents
 All reagents and chemicals, including solvents and
materials used in tests and assays, should be of
appropriate quality.

 Reagents should be purchased from reputable,

approved suppliers and should be accompanied by
the COA, and the MSDS, if required.

 In the preparation of reagent solutions in the

laboratory: responsibility for this task should be
clearly specified in the job description
Reagents ….
 The labels of all reagents should clearly specify: (a)
content; (b) manufacturer; (c) date received and
date of opening of the container; (d) concentration,
if applicable; (e) storage conditions; and (f) expiry
date or retest date, as justified.

 The labels of reagent solutions prepared in the

laboratory should clearly specify: (a) name; (b) date
of preparation and initials of technician or analyst;
(c) expiry date or retest date, as justified; and (d)
concentration, if applicable
Reagents ….
Water
 Water should be considered as a reagent.
 The appropriate grade for a specific test should be used as
described in the pharmacopoeias or in an approved test
when available.
 Precautions should be taken to avoid contamination
 The quality of the water should be verified regularly to
ensure that the various grades of water meet the
appropriate specifications.
Reference substances & reference
materials
 Reference substances (primary reference substances or
secondary reference substances) are used for the
testing of a sample.
 Reference materials may be necessary for the
calibration and/or qualification of equipment,
instruments or other devices.
 All RSs prepared in the laboratory or supplied externally
should be retested at regular intervals to ensure that
deterioration has not occurred.
 The interval for retesting depends on a number of
factors, including stability of the substance, storage
conditions employed, type of container and extent of
use.
Calibration, verification of performance
and qualification of equipment,
 Each item of equipment, instrument or other device
used for testing, verification and/or calibration
should, when practicable, be uniquely identified.
 All equipment, instruments and other devices
requiring calibration should be labelled, coded or
otherwise identified to indicate the status of
calibration and the date when recalibration is due.
 Laboratory equipment should undergo DQ, IQ, OQ
and PQ.
Traceability
 The result of an analysis should be traceable,
when appropriate, ultimately to a primary
reference substance.

 All calibrations or qualification of instruments

should be traceable to certified reference
materials and to SI units (metrological
traceability).
 Working procedures
Testing &
Incoming Evaluation of test
samples results

Analytical
worksheet

Certificate of
Retained samples
analysis
Incoming samples

Starting Intermediates Packaging

materials Bulk products materials

Finished Environmental
Water
products conditions
Incoming samples …
 Sampling methods and personnel approved by QC/QA
department
 Sampling may not be necessarily done by QC/QA. Production

personnel may take sample depending on the situation.

 QC personnel should have access to all production area in any

case although they may not be responsible for sampling (e.g

aseptic processing area)
Adequate Sampling
◦ 100% sampling at least for ID test for API
◦ Composite sample for full analysis
◦ Root n + 1

Sampling under controlled area

◦ The same cleanness as for the next production processing
area
Incoming samples …

Test request Registration

& labeling

Visual
inspection

Forwarding to
testing Storage
Analytical worksheet
 The analytical worksheet is an internal document to
be used by the analyst for recording information
about the sample, the test procedure, calculations
and the results of testing.

 All values obtained from each test should

immediately be entered on the analytical worksheet.


 The completed analytical worksheet should be

signed by the responsible analyst(s), verified and
approved and signed by the supervisor.
Validation of analytical procedures
◦ All analytical procedures employed for
testing should be suitable for the intended
use.
◦ Analytical parameter subject to validation
Assay, related substance, residual solvent,
dissolution, CU where applicable.

◦ Validation parameter Accuracy, precision,

linearity, specificity, range, repeatability,
robustness, LOD and LOQ
Testing & Evaluation of test results
 The sample should be tested in accordance with
the work plan of the laboratory after completion
of the preliminary procedures.
 Test results should be reviewed and evaluated

statistically after completion of all the tests to

determine whether they are mutually consistent
and if they meet the specifications used.
 The evaluation should take into consideration the

results of all the tests.

 Whenever doubtful (atypical) results are obtained

they should be investigated.

Certifi cate of analysis
 usually contains the following information.
the name &
date of
Registration address
no of samples
receipt testing
laboratory

name, reference to
description the the results of
specification all tests
& batch
used for performed
number of testing
the sample

date on which the signature of

test(s) was
(were) the head of a conclusion
completed laboratory
Retained samples
 There should be a sufficient amount of
retained sample to allow at least two re-
analyses.

 The retained sample should be kept in its

final pack
 Stability studies

 Quality and stability of FPPs and, when necessary, of

starting materials and intermediate products
 Establish expiry dates and shelf-life specifications
on the basis of stability tests related to storage
conditions.
 Stability determined prior to marketing
 Significant changes in processes, equipment,
packaging materials, etc. – stability testing.
 Safety
 General and specific safety instructions
reflecting identified risk, should be made
available to each staff member
 General rules for safe working in accordance

with SOP
 SDS should be available to staff before testing is
carried out;
 smoking, eating and drinking in the laboratory should
be prohibited;
 staff should be familiar with the use of fire-fighting
equipment
 staff should wear laboratory coats or other protective
clothing, including eye protection
 Quality Control - summary

 QC is part of GMP –

 sampling  authorization
 specifications  definition of product
 testing quality
 release procedures  laboratory operations
 recalls and complaints  release decisions
 decision-making in all  investigation and
quality matters reporting
THANK YOU!!!