Quality control laboratory.

PREPARED BY: HELI N KARNAVAT GUIDED BY:
M.PHARM SEM-1 Ms.KRUPA THULA
ROLL NO:3 Assistant Professor
PMRA M.Pharm
LJ INSTITUTE OF PHARMACY
AHMEDABAD
1

CONTENTS
 INTRODUCTION
 RESPONSIBILITIES OF PERSONNELS
 ROUTINE CONTROL INSTRUMENTS
 REAGENTS
 SAMPLING PLANS
 STANDARD TEST PROCEDURES
 PROTOCOL
 DATA GENERATION AND STORAGE
 QUALITY CONTROL DOCUMENTS
 RETENTION SAMPLE
 RECORDS
 AUDITS OF QUALITY CONTROL FACILITIES
2

HISTORY OF QC LAB:
 GLP is a formal regulation that was created by the FDA (United
states food and drug administration) in 1978.
 Although GLP originated in the United States , it had a world
wide impact.
 Non-US companies that wanted to do business with the United
states or register their pharmacies in the United States had to
comply with the United States GLP regulations.
 They eventually started making GLP regulations in their home
countries.
 In 1981 an organization named OECD (organization for
economic co-operation and development ) produced GLP
principles that are international standard.
3

Quality Control Area.-(as per
schedule M)
 Quality Control Laboratories shall be independent of the
production areas.
 Separate areas shall be provided each for physico-chemical,
biological, microbiological or radio-isotope analysis.
Separate instrument room with adequate area shall be
provided for sensitive and sophisticated instruments
employed for analysis.
 Quality Control Laboratories shall be designed
appropriately for the operations to be carried out in them.
Adequate space shall be provided to avoid mix-ups and
cross-contamination. Sufficient and suitable storage space
shall be provided for test samples, retained samples,
reference standards, reagents and records.
4

Continued…
 The design of the laboratory shall take into account the
suitability of construction materials and ventilation.
Separate air handling units and other requirements shall be
provided for biological, microbiological and radioisotopes
testing areas. The laboratory shall be provided with regular
supply of water of appropriate quality for cleaning and
testing purpose.
 Quality Control Laboratory shall be divided into separate
sections i.e. for chemical, microbiological and wherever
required, biological testing. These shall have adequate area
for basis installation and for ancillary purposes. The
microbiology section shall have arrangements such as
airlocks and laminar air flow work station, wherever
considered necessary.
5

INTRODUCTION
 QUALITY CONTROL:
Quality control deals with the system which accepts or rejects
any activities or
parameters which affects the quality of product and thus
prevent quality deficiency.
Q.C. is not confined to only laboratory operation but must be
involved in all decisions,
concerning with the quality of the product”
6

AS PER WHO
DEFINITION:
Q.C. is the part of GMP concerned with sampling,
specification, and testing and with the organization,
documentation and release procedure which ensure that the
necessary and relevant tests are actually carried out and those
materials are not released for use, nor product released for
sale or supply, until their quality has bee satisfactory.
7

WHO guidelines for Q.C laboratory:
 Should be separated from production areas.
 Areas where biological, microbiological or
radioisotope test methods are employed should be
separated from each other.
 Control laboratory should be designed to suite the
operations to be carried out in them.
 There should be adequate suitable storage space
for samples, reference standards and records.
8

QUALITY CONTROL
LABORATORY
ABOVE SHOWN IS THE
OVERVIEW OF A QUALITY
CONTROL LABORATORY OF A
REPUTED PHARMACEUTICAL
COMPANY.
9
Figure:1.1- Quality
Control Laboratory

RESPONSIBILITIES OF
PERSONNELS
10

LABORATORY DIRECTOR
 Responsible for overall operation and administration of the
laboratory, including employment of competent qualified
personnels.
 To ensure that laboratory develops and uses a quality
system approach to laboratory testing that provides
accurate and reliable patient test results.
 Ongoing monitoring of each testing process used in
laboratory to identify potential problems that could result
in errors.
11

Continued…
 Take corrective action.
 Evaluate the corrective actions taken, to make sure that
they were effective and will not occur again.
 To ensure that testing systems in laboratory provides
quality services in all aspects of test performance.
12

Lab technicians
 To operate laboratory equipment and computers and
performs other assigned work, in accordance to
documented laboratory procedures.
 To perform chemical analysis.
 Responsible for operation of GC, Spectrophotometers,
balances, computers, etc. Responsible to be cross trained to
perform special laboratory functions.
 Carry out sampling, testing, measuring, recording and
analysing .
 provide all the required technical support to enable the
laboratory to function effectively whilst adhering to correct
procedures and health and safety guidelines.
13

Continued…
 performing laboratory tests in order to produce
reliable and precise data to support scientific
investigations;
 carrying out routine tasks accurately and following
strict methodologies to carry out analyses;
 preparing specimens and samples;
 constructing, maintaining and operating standard
laboratory equipment, for example centrifuges,
titrators, pipetting machines and pH meters;
14

Continued…
 ensuring the laboratory is well-stocked and resourced;
 recording and sometimes interpreting results to
present to senior colleagues
 keeping up to date with technical developments,
especially those which can save time and improve
reliability.
 following and ensuring strict safety procedures and
safety checks.
15

ROUTINE
CONTROL
INSTRUMENTS
16

Normally practiced routine control includes:
 The lab and instruments should be cleaned daily.
 All the instruments should be validated and checked and the
results should be recorded.
 The samples arrived in the lab should be noted in incoming
register.
 Humidity and temperature of the lab should be recorded daily.
 Log books should be filled correctly for every instrument used.
 The results of the tests should be recorded appropriately.
 Any fault in the instruments should be immediately reported to
the Q.C manager.
17

INSTRUMENT RELATED TERMS
o VERIFICATION: a quality control process used to
evaluate whether a product, service or system complies
with the regulations, specifications or conditions implied
by the standard.
o VALIDATION: is a quality assurance process of
establishing evidence that provides high degree of
assurance that the product meets its intended standards.
18

Continued…
o CALIBRATION: the set of operations that establishes the
relationship between values indicated by an instrument or
system and the corresponding known values of reference
standard.
o EQUIPMENT QUALIFICATION: the action of proving
that any equipment works properly and actually gives
accurate and reliable results.
19

Reagents
 Reagent quality control records must be retained for 5
years.
 Reagents shall be used and controlled according to
manufacturer’s recommendations.
 All reagents and chemicals, including solvents and
materials used in tests and assays, should be of
appropriate quality.
 Reagent should be purchased from reputable,
approved suppliers and should be accompanied by the
certiﬁcate of analysis, and the material safety data
sheet.
20

Preparation of reagents in
laboratory
 responsibility for this task should be clearly speciﬁed
in the job description of the person assigned to carry it
out
 prescribed procedures should be used which are in
accordance with published pharmacopoeial or other
standards where available. Records should be kept of
the preparation and standardization of volumetric
solutions.
21

The labels of all reagents should
clearly specify:
 Name;
 content;
 manufacturer;
 date received and date of opening of container;
 concentration;
 storage condition;
 expiry date or retest date
22

The labels for volumetric solutions
prepared in the laboratory should
clearly specify:
 Name;
 Molarity(concentration);
 Date of preparation and initials of technician/analyst;
 Date of standardization and initials of
technician/analyst;
 Standardization factor.
24

Transportation and subdivision of
reagents:
 Whenever possible they should be transported in the
original containers;
 When subdivision is necessary, clean containers
should be used and appropriately labelled.
 All reagent containers should be visually inspected
to ensure that the seals are intact, both when they
are delivered to the store and when they are
distributed to the units.
25

Continued...
 Reagents that appear to have been tampered with should
be rejected; however, this requirement may exceptionally
be waived if the identity and purity of the reagent
concerned can be confirmed by testing.
 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 during
its supply, storage and distribution.
 The quality of the water should be verified regularly to
ensure that the various grades of water meet the
appropriate specifications.
26

Continued…
 Stocks of reagents should be maintained in a store under
the appropriate storage conditions (ambient temperature,
under refrigeration or frozen).
 The store should contain a supply of clean bottles, vials,
spoons, funnels and labels, as required, for dispensing
reagents from larger to smaller containers.
 Special equipment may be needed for the transfer of larger
volumes of corrosive liquids.
 The person in charge of the store is responsible for looking
after the storage facilities and their inventory and for
noting the expiry date of chemicals and reagents.
 Training may be needed in handling chemicals safely and
with the necessary care.
27

Sampling plan:
 Sampling is an activity which is of crucial significance to the
quality control in Pharmaceutical and Healthcare industry
where necessary to take the samples.
 Sampling at the end of a manufacturing process provides a
check on the adequacy of the quality control procedures of
the manufacturing department.
 Sampling plan is detailed outline of which measurement
will be taken at what times,on which material,in what
manner,and by whom.
 In quality control activity “sampling” is one of the major
activity
28

Continued…
 In QC laboratory;
 Procedure available for receiving, storage and handling of
samples for analysis.
 Sample receiving procedure should be documented and keep
it.
 Each sample having distinct identification number and
information for its storage with handling and labeling.
 Storage condition facilities in laboratory like refrigerator and
absence of light.
 Detailed description of sub sampling of samples for analysis.
 Reserve samples should be retained for additional testing if
quantity is adequate.
29

Continued…
 Sampling may be required for different purposes for example;
 Acceptance of batches
 Clearance of batches
 In process controls
 Stability studies
 Complaints
 The control that applied to the samples may be;
 Checking the identity of materials
 Performing complete Pharmacopoeia or testing
 Performing the special test
30

Sampling kit
 The QC person may require the tools and equipment for collecting the
samples (Sampling kit).
 The tools are knives, pliers, saws, hammers, wrenches etc. to open
packages, barrels and containers.
 Not used the complicated tools for sampling of samples.
 Pipette with suction bulb use for liquid of low viscosity.
 Glass rod can be used for highly viscous liquid
 Spatulas and scoops used for granules.
 When it is necessary to take sample of materials at three different
strata (Top, Middle, Bottom) sampling stick used.
31

Continued…
 All tools and implements should be kept
scrupulously clean before use, washed it
thoroughly with water or suitable solvents and
then dried.
 It will be better if more than one set of sampling
kits are available in clean and dry condition.
32

Types of sampling:
 Single sampling.
 Double sampling.
 Continuous Sampling.
 Sequential Sampling
33

Single sampling:
 A single sampling plan is defined by sample size, n, and the
acceptance number c. Say there are N total items in a lot. Choose
n of the items at random. If at least c of the items are
unacceptable, reject the lot.
 N=LOT NUMBER
 For a single sampling plan, one sample of items is selected at
random from a lot and the disposition of the lot is determined
from the resulting information. These plans are also denoted as
(n,c) plans since there are n observations and the lot is rejected if
there are more than c defectives.
 Single sample plans are the most common and easiest plans to
use. However, they are not the most efficient in terms of the
average number of samples needed.
34

35
Inspect n
pieces in a
sample
If the number defective found in sample
Accept the
lot
Equals or
exceeds r
Does not
exceed c
Do not
accept lot
n= sample size,
c= allowable no. of defect in the sample,
r= rejection no.
Fig:1.3 SINGLE SAMPLING CHART.

DOULE SAMPLING
 Double and multiple sampling plans were invented to give a
questionable lot another chance. For example, if in double sampling
the results of the first sample are not conclusive with regard to
accepting or rejecting, a second sample is taken. Application of double
sampling requires that a first sample of size n1 is taken at random from
the (large) lot. The number of defectives is then counted and compared
to the first sample's acceptance number a1 and rejection number r1.
 Denote the number of defectives in sample 1 by d1 and in sample 2 by
d2, then:
 If d1≤a1, the lot is accepted.
If d1≥r1, the lot is rejected.
If a1<d1<r1, a second sample is taken.
36

Continued…
 If a second sample of size n2 is taken, the number of
defectives, d2, is counted. The total number of
defectives is D2=d1+d2. Now this is compared to the
acceptance number a2 and the rejection number r2 of
sample 2. In double sampling, r2=a2+1 to ensure a
decision on the sample.
 If D2≤a2, the lot is accepted.
 If D2≥r2, the lot is rejected.
37

38
Inspect first sample,n1 pieces
Does not exceed , c1
Do not accept lot
Equals or
exceed r2
Does not
exceed c2Accept lot
Inspect asecond sample ,
n2 pieces
Equals or exceeds , r1
If the no. of defectives in the first sample
Exceeds c1 but does not exceed r1
If the no. of defectives in combined sample
Fig:1.4 DOUBLE SMAPLIN CHART

CONTINUOUS SAMPLING
 Continuous sampling is used where product flow is
continuous and not easily grouped in lots. Two
parameters exist for continuous sampling. One is the
frequency (f) and the second is the clearing number
(i).
39

Continued…
 Carrying out a continuous sampling plan is simple and
can be carried out in 3 steps.
 1. Inspect all i data.
 2. If no defects are found, randomly sample fraction f
of data and check again for defects.
 3. Whenever a defect is found, correct the flaw and
repeat step 1.
40

SEQUENTIAL SAMPLING
 Sequential sampling is different from single, double or
multiple sampling. Here one takes a sequence of
samples from a lot. How many total samples looked at
is a function of the results of the sampling process.
 The sequence can be one sample at a time, and then
the sampling process is usually called item-by-item
sequential sampling. One can also select sample sizes
greater than one, in which case the process is referred
to as group sequential sampling.
41

STANDARD TEST PROCEDURE
 An authorized written procedure giving instructions
for performing operations not necessarily specific to
a given product or material but of a more general
nature (e.g. equipment operation, maintenance and
cleaning; validation; cleaning of premises and
environmental control; sampling and inspection).
Certain SOPs may be used to supplement product-
specific master batch production documentation.
 Sampling: -
 There shall be written Standard Operating
Procedures for sampling which include the
person(s) authorized to take the samples.
42

Continued…
 The sampling instruction shall include:
(a) The method of sampling and the sampling plan,
(b) The equipment to be used,
(c) any precautions to be observed to avoid contamination
of the material or any deterioration in its quality,
(d) The quantity of samples to be taken,
(e) instructions for any required sub-division or poling of
the samples,
(f) The types of sample containers to be used,
(g) any specific precautions to be observed, especially in
regard to sampling of sterile and hazardous materials.
 Testing:
There shall be written procedures for testing materials
and products at different stages of manufacture,
describing the methods and equipment to be used. The
tests performed shall be recorded.
43

44
Physical
Analysis
:
Description :
Diameter :Measure the diameter of approximately 6 tablet using Vernier
calipers.
Thickness : Measure the diameter of approximately 6 tablet using Vernier
calipers.
Hardness :Check the hardness of approximately 6 tablet using hardness
tester .
Friability :Note the accurate weight of 20 tablet. Keep it into drum of
friability apparatus and allow to rotate for 100 revolution at 25
RPM.
Disintegration :Place one tablet in each tube of basket rack assembly of
disintegration apparatus and observe the time period for
complete disintegration.

 Identification
 : Identification Test by HPLC.
 The retention time of the major peak in the chromatogram
of sample preparation should correspond to that of in the
chromatogram of working std preparation in the assay.
 Assay:
 Mobile Phase: Take 45volume of water in 55 volume of
Acetonitrile and add 0.1 volume of triethylamine. Adjust
pH 3.5 using phosphoric acid and filter it.
 Standard Preparation :
 Dilute 69.3mg amlodipine besilate (50mg amlodipine)+
54.39 mg Lisinopril
 (equal to Lisinopril Anhydrous ) working standard in
mobile phase to obtain 50ml Further dilute 5 ml in 25 ml in
mobile phase to get final concentration amlodipine 200
ppm / ml and Lisinopril Anhydrous 200 ppm/ml
45

 Test Preparation :
 Accurately weight of fine tablet powder equvalent to 10 mg Amlodipine
 +10 mg Lisinopril Anhydrous and dissolve in 50 ml to mobile phase to
get final concentration amlodipine 200 ppm / ml and Lisinopril
Anhydrous 200 ppm/ml.
 Column: C18
 Flow rate: 1.0 ml / min.
 Wavelength : 215 nm
 Run Time : 15 min.
 Procedure:
 Inject 20 l of standard preparation and test preparation separately.
And calculate the %assay for each tablet individually.
 Calculation:
 % Assay = Area of Sample X Std. Dilution X Potency
 Area of Std Sample Dilution 100

 Limit : 90 % to 110 %
46

DEFINITION
 Protocol is a system of rule about the correct way to act
in formal situation .
 Each study shall have an approved written protocol
that clearly indicates the objective and all methods for
the conduct of study.
48

WHAT SHOULD A PROTOCOL
CONTAIN???
 Every protocol needs to focus specifically on one type of
experiment to be performed.
 Title and statement of the purpose of the study
 Identification of the test and control articles by names,
chemical number or code number.
 The name of the sponsor and the name and address of the
testing facility at which the study is being conducted.
 The procedure for identification of the system
49

Continued…
 Type and frequency of test, analysis and
measurements to be made.
 Records to be maintained.
 The date of approval of the protocol by the sponsor
and the dated signature of the study director.
50

Continued…
 Each study shall have an approved written
protocol that clearly indicates the objectives and all
methods for the conduct of the study. The protocol
shall contain, as applicable, the following
information:
 The requirement to indicate “all methods for the
conduct of the study” does not mean that all
laboratory SOPs must be reiterated in the protocol;
it is sufficient if the protocol indicates “what” will be
done and “when” it will be done. Laboratory SOPs
describe “how” each study activity is to be
performed.
51

Continued…
 The description shall include specifications for
acceptable levels of contaminants that are reasonably
expected to be present in the materials and are known
to be capable of interfering with the purpose or
conduct of the study if present at levels greater than
established by the specifications.
 Each dosage level, expressed in milligram per
kilogram of body weight or other appropriate units, of
the test or control article to be administered and the
method and frequency of administration.
 The type and frequency of tests, analyses, and
measurements to be made.
52

DATA GENERATION
AND
STORAGE RECORDS
53

Continued…
 Storage facility for records should reflect the need to
preserve confidentially, integrity and logical retrieval.
 Thought should be given to the susceptibility of the
records to damage from fire (heat), flood (humidity),
electric or magnetic fields, dust, solvents etc.
 It is the responsibility of laboratory staff to ensure all
relevant documentation is kept for the specified
timeframes and to archive large quantities of
documentation that is to be kept long term but not
necessarily looked at on a regular basis.
54

PURPOSE
 The purpose of this procedure is to describe the
requirements for the retention of laboratory
documentation under GMP and the disposal of such
documentation.
55

DEFINITION
 A sample from every batch of product made and the
chemicals and components that make up a finished
good are kept for a set period of time for use as
reference material should be a problem with a specific
product or batch.
57

CONDITIONS TO BE MET
 The sample shall consist of at least twice the quantity
necessary for all tests required to determine its compliance
with specification.
 The sample shall be stored in controlled room temperature
expect where the product labeling or specification states
otherwise.
 The sample shall be stored in the same primary container
enclosure system in which the product is marked or shipped,
or in one that has essentially the same characteristic.
 The sample shall be securely stored in accordance with their
labels requirements and segregated from other material.
 The conditions in the store area must be supervised and
recorded.
58

Continued…
 Documentation is an essential part of the quality
management System.
 The laboratory should establish and maintain
procedures to control and review all documents (both
internally generated and from external sources) that
form part of the quality documentation.
60

THE PROCEDURES SHOULD ENSURE
 Each document, whether a technical or a quality
document, has a unique identifier, version number
and date of implementation;
 Appropriate, authorized SOPs are available at the
relevant locations, e.g. near instruments;
 Documents are kept up to date and reviewed as
required;
 Any invalid document is removed and replaced with
the authorized, revised document with immediate
effect.
61

Continued…
 A revised document includes references to the
previous documents.
 Old, invalid documents are retained in the archives to
ensure traceability of the evolution of the procedures;
any copies are destroyed.
 All relevant staff are trained for the new and revised
SOPs
 Quality documentation, including records, is retained
for a minimum of five years.
62

DEFINITION
 Any production, control, or distribution record that is
required to be maintained in compliance with this part
and is specifically associated with a batch of a drug
product shall be retained for at least 1 year after the
expiration date of the batch.
 Quality management records should include reports
from internal (and external if performed) audits and
management reviews, as well as records of all
complaints and their investigations, including records
of possible corrective and preventive actions
64

CLOSURE AND LABELLING RECORDS
 The identity and quantity of each shipment of each lot
of components,
 Drug product containers, closures, and labeling;
 The name of the supplier;
 The supplier’s lot number(s) if known;
 The receiving code and the date of receipt.
 The name and location of the prime manufacturer, if
different from the supplier, shall be listed if known.
65

MASTER PRODUCTION AND CONTROL
RECORDS
 The master manufacturing records should clearly
identify:
 Name of product,
 Product type,
 Strength Ingredients to be added,
 Name, alphanumeric code,
 Amounts or dosage unit or percentage Amount of
each ingredient for a batch
 Sequence of adding ingredients
66

Continued…
 Equipment to be utilized designated by name and,
where appropriate, by number processing steps with
details of conditions such as time, temperature, speed
 Special precautions and hazardous conditions which
exist and the necessary safety equipment to be used
 Theoretical yields and actual yields (action levels)
 Space for signature and date of operator/supervisor
performing or checking each significant step.
67

Quality control laboratory.

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