Quality control (QC)

The part of GMP which is concerned with

• sampling,
• specification and testing and organization,
• documentation and
• release of procedure to ensure the quality of the drug.

Involve
• in-process control,
• post-process control and
• finished goods control including stability testing

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Quality can be achieved by three managerial process include;

A. Quality planning:
• The initial activity of the plan is to identify the
customers and their need
• Then develop product and process design to respond
the need of the customers
B. Quality control:
• A regulatory process which measures the quality
performance of the products
• The activities of QC involve laboratory procedures
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 C. Quality improvement:
• Facilitates in improving deficiencies through the
feedback from customers or regulatory bodies
• The only way to achieve quality is to manufacture the
product correctly
• Quality can not be achieved merely by checking,
examination and testing.

• “There should not be any compromise for quality”

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• Quality control is a concept, which strive
– to produce a perfect product by series of measures designed to
prevent and eliminate errors at different stages of production.
• In popular practice, the quality of medicines or
pharmaceutical products is assured through quality control.

• Quality assurance department must adopt “good laboratory

practice”
– to ensure reliability and accuracy of results given out by
them.

• Consequently the manufacture and the control of drugs are

very responsible task and they need substantial knowledge of
the science.
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 Quality Control (QC)

• Each holder of a manufacturing authorization should have a

quality control department
– QC department should be independent from other department.

• The QC department must have adequate resource.

– That means:
• Adequate laboratory facilities or access to them.

e.g government or contract laboratories

• Appropriately qualified, trained and experienced personnel
• Approved written procedures
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The operational task of the quality control
department:

– Sampling
– Inspecting
– Analytical testing
– Monitoring of all materials and environmental conditions
in the factory
– Releasing or rejecting material for production use and
finished products

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 The target of these activities are:

– Starting materials
– Packaging materials
– Intermediates
– Bulk products
– Finished products
– Environmental conditions

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 Basic requirements for quality control:

1. Sampling should be under taken by methods and personnel

approved by the QC department
– It must be carried out in such a way that it is representative of
the batch and in accordance with an SOP
– QC personnel must have access to the production area to
undertake sampling when necessary.

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 Basic requirements for quality control …

2. Validated test methods should be applied.

– The validation of test methods include verification:
• Accuracy

• Precision

• Linearity

• Repeatability

• Robustness
• Specificity

– Test methods should be challenged to be able to demonstrate that the

tests are able to give an accurate result on repeatable bases.
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 Basic requirements for quality control …
– The method must be capable of being applied with precision

– The results obtained must be linear over a range of acceptable

response
– Finally the result must be repeatable over a number of identical
tests.

3. Records for sampling, inspecting, testing of materials,

intermediates and bulk and finished products need to be kept
– This means that there will be traceability on what happened.

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 Basic requirements for quality control …
4. The QC department should review and evaluate relevant production
documentation
– This review need to cover all quality aspects
– Ensures manufacturing documentations and the QA documentation
are in harmony.
5. The QC department should generate or review records for deviations and
failure investigations
– it is important that all deviation from the normal manufacturing
procedure are recorded or documented.
– Any impact on product quality must be assessed.
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 Basic requirements for quality control …

6. QC ensures that ingredients used comply with the qualitative and

quantitative composition of the finished product as approved in
market authorization.
7. QC ensure that proper containers are used

8. QC ensures correct labeling of finished products

9. QC ensures batches are released by appropriate authorization.

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 Basic requirements for quality control …

10. Sample of starting materials products are retained.

– Sufficient retention samples of the starting materials and the
finished products in its final pack should be kept for one year
past the expire date.
– This is to allow for an evaluation of the product after it has been
distributed should there be a need.
– It will also allow ongoing stability trial to be done

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 QC department has other duties to carry out,
including:
1. Establishing, validating and implementing all QC procedures
2. Evaluating, maintaining & storing reference standards
– RS are among the most critical materials that QC has to handle
– The result of much testing rely up on comparison with analytical RS.
– If RS has not been looked after properly then all the test results may
be incorrect.

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 QC department has other duties …

3. Ensuring correct labeling of containers of materials and

products.
– It is nearly impossible for operator to see that an error
has occurred.
– System must be in operation as the main safeguard.

– If equipment such as bar code readers are in operation

it must be regularly checked for effectiveness.

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 QC department has other duties …

4. Stability tasting of active ingredients and finished products

– A stability testing program should be developed for all products,
described in the form of an SOP.
– Stability of active pharmaceutical ingredients should be monitored

– Active ingredients should be regularly tested with in their shelf life

to confirm suitability for continued use.
– QC should ensure that samples are taken for stability testing
program and that analysis is under taken at the right time

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 QC department has other duties….

5. Participating in complaint investigation.

– Complaints offer an opportunity for the company to learn from
mistakes or product design failures.
– In this way actions can be taken to prevent re-occurance.

6. Participating in environmental monitoring.

– With regard to products, the environment refers to that which can
immediately affected product quality.
– E.g. swab testing and settle plates in a sterile area, testing of
temperature and humidity control.

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 Assessment of finished products should
embrace all relevant factors.

– Including the production condition

– The results of in-process testing
– The manufacturing (including packaging) documentation
– Compliance with the specification for the finished product,
and
– An examination of the finished pack

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 QC personnel must have access to production
areas
• For example sampling and inspection
• This must be balanced because it may not be appropriate
– QC staff enter aseptic filling suites, or
– Areas where there is high potent dangerous material such
as oncology (or cytotoxic materials) .

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 Head of QC responsibilities
• Approve or rejection of materials:
– Packaging material, intermediate, bulk and finished products
• Evaluation of batch records
• Carrying out necessary testing
• Approval of necessary QC procedures:
– Sampling instruction, Specifications, Test methods and other QC
procedures.
• Maintenance of quality department, premises and equipment
• Validation (including analytical procedure and calibration of
equipments)
• Initial and continuous training of QC personnel

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 Testing references: Pharmacopoeial standards
(USP, EP, BP, etc)

• Specification consists of test methods and their associated

acceptance criteria.
• Criteria applicable to all drug products:
– Identity

– Strength

– Purity

– Testing methods
• Physico-chemical analysis

• Microbiological analysis
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 Additional specifications

– Tablet & capsules • Suspension and solutions

– Disintegration – pH of solution

– Dissolution – Particle size of suspending drug

– Stereoisomeric purity – Clarity of solution (turbidity)

– Moisture (water) – Color of solution

– Residual solvents – Viscosity

– Volume of fill

– Preservative testing

– Microbial limits

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 How Is Medicine Quality Assured? (1)

 Product selection
 Long shelf-life
 Acceptable stability
 Acceptable bioavailability
 Selection of appropriate suppliers
 Supplier pre-qualification
 Request samples from new suppliers
 Request specific reports and data for certain medicines (e.g.,
bioavailability and stability studies)
 Collect and maintain information on supplier performance
 Product certification
 GMP certificate of manufacturer
 Product/batch certification (COA)
 Random local testing
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 How Is Medicine Quality Assured? (2)

 Contract and procurement specifications

 Pharmacopeia reference standard
 Local language for product label
 Standards for packaging to meet specific storage
and transport conditions

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 General tests for Dosage forms
 The main criteria for quality of any drug in solid dosage
forms (tablets and capsules) are its:
 safety, potency, efficacy and stability
patient acceptability and regulatory compliance.
 The purposes of IPQC are to produce a perfect finished
product by preventing or eliminating errors at every
stage in production
 Quality is not an accident this is the result of intelligent
effort
 The quality in the pharmaceutical industry has become
a very important and sensitive issue.
 UNIVERSAL TESTS
 For PHARMACEUTICAL TABLETS
 Universal Tests
 The tablet dosage form accounts for approximately 50% of all
dosage forms on the market
 There are four tests that are generally applicable to
pharmaceutical tablets and other drug products:
1. Description
 This test is often called appearance on a specification and is a
qualitative description of the pharmaceutical tablet.
 For example, the description of a tablet on a specification may
read: white, round, biconvex, film-coated tablet, imprinted
with ‘‘Rx’’ on one side
 Cont…
2. Identification
The purpose of this test is to verify the identity of
the API in the pharmaceutical tablet.
3. Assay
This test determines the strength or content of the
API in the pharmaceutical tablet and is sometimes
called a content test
4. Impurities
This test determines the presence of any
component that is not the API or an excipient of
pharmaceutical tablet.
 IPQC and FPQC Tests
 Physical parameters of pharmaceutical tablets that are
controlled by IPQC tests are temperature, pressure,
moisture content, time, weight, particle size,
hardness, loss on drying, disintegration time, color,
compactness, integrity etc.

 FPQC test for pharmaceutical tablets are assay,

uniformity of content, uniformity of mass, weight
variation, friability test, content of active ingredients,
hardness test, disintegration test, dissolution test etc.
 Cont…
1. Size and Shape
 The size and shape of the tablet can be dimensionally
described monitored and controlled.
 It is determined by the tooling during the compression process

2. Color and Odor

 Many pharmaceutical tablets use color as a vital means of
rapid identification and consumer acceptance. But it must be
uniform within a single tablet, from tablet to tablet and from
lot to lot.
 The presence of an odor in a batch of tablets could indicate a
stability problem
 Taste is important in consumer acceptance of chewable tablets
 Cont…
3. Moisture Content of Granules
 Granules should possess sufficient strength to
withstand normal handling and mixing processes
without breaking down and producing large amounts
of fine powder.
 On the other hand, some size reduction during
compaction into tablets is desirable to expose the
areas of clean surface necessary for optimum bonding
to take place so moisture content is the very
important factor for producing good pharmaceutical
product
 Cont…
4. Weight Variation
 Test According to the USP weight variation test is run by
weighting 20 tablets individually calculating the average
weights and comparing the individual tablet weights to the
average.
 The value of weight variation test is expressed in percentage.
 The following formula is used:
Weight Variation = (Iw - Aw)/Aw X 100% Where,
Iw = Individual weight of tablet;
Aw = Average weight of tablet.
 As per USP the tablet complies with the test if not more than 2
of the individual masses deviate from the average mass by
more than the percentage deviation
 Cont…
6. Thickness
 The thickness of a tablet is the only dimensional variable related
to the process.
 Thickness of individual tablets may be measured by a
micrometer.
 Other techniques involve placing 5 or 10 tablets in a holding
tray, where their total thickness may be measured by a sliding
caliper scale.
 Tablet thickness should be controlled within a ± 5 % variation of
a standard.
 Thickness must be controlled to facilitate packaging. It is
expressed in mm.
 Cont…

7. Hardness
 Test For this test one of the earliest testers was Ketan tablet
hardness tester, to evaluate tablet hardness tester.
 The tester consists of a barrel containing a compressible spring held
between two plungers.
 As the spring is compressed, a pointer rides along a gauge in the
barrel to indicate the force.
 The force of fracture is recorded in kilogram
 Ten tablets are crushed and measure their hardness and the
allowable range is between 4 - 6 kg (40 - 60 N) unless otherwise
specified.
 Cont…
8. Friability Test
 Friability of a tablet can determine in laboratory by Roche
friabilator.
 For this test twenty tablets are weighed and placed in the
friabilator and then operated at 25 rpm for 4 minutes.
 The tablets are then dedusted and weighed.
 The difference in the two weights is used to calculate friability
and the value of friability is expressed in percentage.
 It is determined by the following formula:
Friability = (Iw - Fw)/Iw x 100% Where,
Iw = Total Initial weight of tablets;
Fw = Total final weight of tablets.
 As stated by USP if conventional compressed tablets that loss
less than 0.5 % to 1 % (after 100 revolutions) of their weight
are generally considered acceptable
 Cont…
9. Disintegration Test:
 The USP disintegration apparatus consist of 6 glass tubes that
are 3 inches long, open at the top, and held against a 10-mesh
screen at the bottom end of the basket rack assembly
 The tablet complies with the test, if the tablets disintegrate,
and all particles pass through the 10-mesh screen in the time
specified. If any residue remains, it must have a soft mass with
no palpably firm core.
 The tablet complies with the test according to USP, if all of the
tablets have disintegrated completely.
 If 1 or 2 tablets fail to disintegrate completely, repeat the test
on 12 additional tablets.
 The requirement is met if not less than 16 of the total of 18
tablets tested are disintegrated
 Cont…
10. Dissolution Test
 The BP or USP dissolution apparatus (Basket apparatus) consist of
a cylindrical vessel with a hemispherical bottom, which may be
covered, made of glass or other inert, transparent material; a motor;
a metallic drive shaft; and a cylindrical basket
 Dissolution testing is a requirement for all solid oral dosage forms
and is used in all phases of development for product release and
stability testing.
 It is a key analytical test used for detecting physical changes in an
active pharmaceutical ingredient (API) and in the formulated
product.
 Repeat the test 3 times (1st with 6 tablets, if 1tab failed take 6 tabs
if failed acceptance limit take24 tabs) if failed acceptance limit
Reject the product for this test.
THANK YOU!!!