GOOD LABORATORY PRACTICES

1. Analysis should be carried out according to the documented procedures/

specifications. Analysts should not change documented methods unless the
changes are duly authorized.
2. All observations and calculations should be recorded on the Analytical
Report on the reverse side and conclusions on the front. Calculation sheet
can be attached wherever possible. Reports can be generated with the use of
computers in similar manner.
3. Wrong entries should be scored with a single line and the new entry made
alongside with an initial of the person correcting the mistake. Pleases do not
overwrite.
4. Every analysis should carry the date on which it was carried out. Spectra
and other test records should be attached to the Analytical Report and filed
in the docket.
5. All reagent bottles/chemicals should be properly labeled and stored in the
identified areas or shelves.
6. Labels should indicate the date on which the reagents were opened/prepared
or standardized.
7. Spoiled and disfigured labels should be replaced.
8. Labels which are not current should be peeled, covered with the no. label or
crossed with ink, whenever a solution is changed or freshly standardized,
solvent bottle should be kept in respective shelves after use.
9. Laboratory should be maintained in a clean and orderly manner at all times.
10. Care should be taken that instruments should be switched off and covered at
the end of the day.

General Instructions:
1. Keep all gangways, exits and fire fighting equipment free from obstruction.
2. Do not smoke, eat or drink in the laboratory.
3. Ensure that all chemical waste is disposed off in a predetermined manner.
4. All injuries, no matter how slight, must be treated immediately.
5. Any accident, however slight, must be reported.

Volatile materials:
1. Volatile solvents and corrosive liquids should never be pipetted directly.
2. Do not pour out volatile solvent near a naked flame.
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Corrosive Chemicals:
1. These should be prevented from coming in contact with body surfaces,
including eliminatory and respiratory systems. While handling these, rubber
gloves, rubber aprons, safety goggles and other necessary safety apparel
must be worn.
2. Do not store large bottles of acids and other corrosive materials above waist
level.
3. While handling cyanides and other poisons, keep antidote nearby. Poison
materials/chemicals should be locked & key should be under authority of
QC head.
4. Do not leave apparatus containing corrosive materials at the sink to be
washed; always drain out the apparatus before leaving for washing.
5. Bottles containing strong acids should be supported on acid resistant trays.
Acid splashes should be washed with water, and then neutralized with
sodium bicarbonate solution.
Glassware:
1. Examine glassware for defects before any experiment. Do not use cracked,
chipped or otherwise damaged glassware.
2. Reagent bottles and other glassware should be labeled correctly and clearly.
3. Pour liquids in a direction away from label to avoid damaging the label. If
any liquid spills on outside of bottles, wash/ wipe the outside of bottle with
water before returning to shelf.
4. To remove tight stoppers, top alternatively on each side of stopper. If this
does not work and the contents of the bottle are not flammable or toxic,
gently warm the neck of the bottle.
5. When a glass tube or rod is it be cut, use gloves and eye protection.
Fire Hazards:
1. Gas cylinders should not be stored in the direct sun and kept at a reasonable
distance from any source of heat. Cylinders should be fastened so that they
cannot roll or fall. They should be preferably enclosed in a cage.
a) All laboratory staff must be familiar with the position and operation of all fire
fighting equipment in their vicinity; these should also be a ‘First Aid’ trained
officer in the laboratory.
Electrical Hazards:
Ensure that there are no open connections and bare wires in the department.

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Environmental Safety:
1. Waste inflammable solvents which are not miscible with should be poured
into bottles intended for this purpose and not into the sink.

2. Dilute solutions of poisons like cyanide, etc., before imputing into the sink
and this should be followed by sufficient flushing with tap water.
Concentrated solutions should be treated to render them innocuous before
pouring down the drain.

3. Reactive chemicals like sodium metal, phosphorous pentoxide, etc. should

be converted to non-reactive compounds before pouring them down the
drain or disposal.

Safety Aids:
1. Safety goggles/Face Shield
These are used to protect eyes where splashing may occur or breaking of
glass, eg. while working with apparatus under pressure.
2. Gas Masks
These should be used for protection against toxic gases and fumes and when
an operation cannot be carried out in a fuming hood. They are available in
the Production departments.
3. Gloves
Heavy gloves should be used for handling concentrated acid, alkali and other
corrosive materials. Where finger dexterity is essential, surgeon’s gloves
can be used.
4. Laboratory coats and aprons
These must be worn at all times for protection of body and clothes. Rubber
aprons can be worn while handling corrosive materials.
5. Fuming hood cupboard
Any work involving fumes and harmful gases should be carried out in a
fuming cupboard. Make sure the ventilation is in order before commencing
the operations.
6. First aid box
This is equipped with medicines like antiseptic lotions eye wash solution,
paracetamol tablets, bandages, pads, ointments for burns etc. and
scissors/blade

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Accident Report Procedures:
1. Minor Injuries:
Appropriate first aid should be given in case of burn. The person should
then be taken to a medical center for further treatment.
2. Major Injuries:
Arrange immediate medical aid. Do not move the person except to a
position of less danger. Keep the person warm and quiet to minimize the
effect of shock.
3. Poison:
Arrange for medical aid. In the meantime, render the following treatment.
a) Give large quantities of water, milk or barely water to drink
b) Where the poison is non-corrosive, an antidote should be given, but
not for corrosive poisons. Burning of mouth and lips evinces a
corrosive poison.

4. Electric shock:
Turn off the current at the main switch of the area concerned, to rescue a
person in contact with a live switch. If not possible, use rubber gloves or
dries woolen materials to protect your hands.
5. Fire:
Put off the fire with an extinguisher. Switch off electricity to the area
concerned. If clothing catches fire, smother the flames by wrapping the
person in a blanket or coat or any such material so that the burning area is
completely covered. Report immediately to the General Manager/Unit Head.
The laboratory should be kept clean and tidy at all times by scheduling
routine house-keeping procedures.

Glassware and sampling equipments:

1. Soak the empty, used glassware in the basins/tub containing a solution of a
detergent in water.
2. Brush each item thoroughly, taking care to remove any stains or grease.
3. Rinse thoroughly with tap water several times and then with distilled water.
4. Dry in an oven or overnight in air and store in the designated place.
5. For microbiological analysis, pipettes and glassware have to be sterilized by
heating for 2 hours at 160 C or autoclave at 15 Lbs pressure for 20 minutes.

Pipettes:
1. Soak pipettes after use in a tall jar containing detergent solution for several
hours.
2. Drain and rinse with tap water and finally with distilled water and dry.
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Burettes:
1. Wash the burettle and stop cock separately.
2. Keep the empty cleaned burettes in inverted position

New glassware:
1. After routine cleaning, treat with a 5 percent solution of sodium carbonate
followed by soaking in 1 percent Hydrochloric acid solution.
2. Wash with excess quantity of tap water and then rinse with distilled water.
Cylinders, optical cells and curettes should be washed by the analysts
themselves.
3. The analysts should wash cylinders, optical cells and curettes themselves.
4. If corrosive chemicals have been used, the analyst should empty the flask
himself and rinse it before keeping for washing in the tub.
A volumetric (standard) solution is one of an accurately known strength. Solutions
of substances which are not approximate to the one desired and then standardized
against a known pure standard. (Primary standard)
1. Prepare the volumetric solution according to the individual procedures as
given in General Analytical methods.
2. Store these in bottles with labels indicating the name of the solution, its
strength, date of preparing and the person who has prepared it.
3. Standardize these solutions after preparation on the predetermined schedule
whenever required; in duplicate. Record the value as an average of 2
observations, which are much closed values.
4. Record the calculations, weights and normalities in the standardization log
book.
5. Before use check visually that the contents of the bottle are clear.
6. Volumetric solutions should not differ from the prescribed strength by more
than the 10 percent. Where the strength falls below 10 per cent the solution
should be replaced.
1. Every sample analyzed in the laboratory has a unique analytical Reference
number.
( A. R. No. ) i.e. AOF/ATN/001
a) The last three digits in the Finished product represent the serial no. of the
batch.
b) The I st 3 alphabets represent the status of the material.
i.e. AOF - Finished Product
AOI - Ariane Orgachem Intermediate
AOR - Raw Material

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 c) The next three alphabets in the Finished Product A. R. No. represent the short
forms of the product.
i.e. ATN - Atenolol
FRU - Frusemide
CPM- Chlorpheniramine Maleate
INT - Intremediate product sent to outside parties.
d) The next alphabet of the AOR in the Intermediate A. R. No. represent the
initial of the intermediates. i.e.
L - Lasamide
E - Epoxide

And the last seven digits represent the year and serial No. of batch i.e. 2000
/028.

e) The next digits of the AOR in the Raw material represent the year and the
serial No. of receiving of the raw material. i.e. AOR / 2000 / 018

2. Analytical Reference Numbers are assigned in registers maintained

separately for samples of raw material, intermediates, packaging materials,
finished products and R & D samples. Following details are recorded:
i) Sr. No.
ii) Date of receipt of sampling Advice document
iii) Batch Number.
iv) GR No. (Goods Received Number) (Wherever Applicable) or Sample
Reference No. sent to other units on T.I. sheets.
v) Analytical Reference Number ( A.R. No. )
vi) Recd from ........ dept/unit/source
vii) Sampled by /Analysed by
viii) Status (Passed, Rejection or Reported) with date

Reference Substances or Reference Standards are authentic samples of highly

purified chemicals supplied by the official Pharmacopoeial Commissions. These
are used as a basis of comparison for determining the purity of the test specimen.
As these are available only in small quantities, Working Standards are prepared to
act as substitutes. These are prepared from in-house manufacture material and
standardized against authentic Reference Substances.

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Reference Substances:
1. After receiving the Reference Substance, enter the details of the substance in
the register meant for the purpose.
2. Store it in an air-conditioned room/refrigerator and use as directed on the
label.
3. Whenever official standards get changed by Pharmacopoeial Commissions,
replace the old Reference Substances with the current Reference Standards.
4. Each Reference Substances should have a Reference Number with suffix
RS.

Working Standards:
1. Choose and standardize the purest possible material matching with the
Reference Substance in purity and in other standards. Working Standard
should have minimum purity of 99.5 % in anhydrous basis and least
possible related impurities
2. After standardization against the Reference Substance, enter the details like
date of standardization, purity standards, directions for use and date till
which it is valid in the register and working standard protocol and also the
label.
3. Store in an air-conditioned room/refrigerator after labeling appropriately.
4. Re-standardize it at about once a year against the official Reference
Substance

Persons responsible:
Sampling should be carried out only by trained Q.C. Personnel and should be done
in accordance with instructions as per sampling and handling sheet of individual
specifications.

Examination of consignment before sampling:

1. Prior to sampling, check the consignment for its identity, quantity and
manufacturer’s batch number and proper storage as per specifications.
2. See that the containers are not damaged or externally spoiled or
contaminated in a way that could result in the contamination of contents.
3. Check that the containers are properly labeled and tagged with consignment
details cards.

Method of sampling:
1. Check the details on the GR Notes to be complete.
2. Before opening the container, check that the outsides are free from dust or
any material that could contaminate the contents.
3. Affix the Under Test labels on the containers.

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4. Choose containers at random (Damaged containers must be sample
individually)
5. Mix thoroughly any material liable to inhomogeniety
6. Withdraw the sample from different layers in the material to make the
sample as Representative as possible using the appropriate sampling
equipment.
7. Keep the samples from individuals
8. Indicate on the sample label the container number from which the sample
has been drawn.
9. Identify by means of ‘Sampled Pack’ sticker labels the containers from
which samples have been drawn
10. Ensure proper closer of the containers after sampling.
11. Take the samples to the Quality Control and store in the designated place.

EQUIPMENTS TO BE USED FOR SAMPLING

Sampling equipments and containers should be kept in the custody of the Quality
Control Department. These must be cleaned and dried prior to use. For sampling
of materials for microbial examination, they must be sterilized before use.

1. Sampling of powder:
Stainless steel sampling scoop (3 feet in length) to be used and the samples
to be stored in virgin food grade self sealing poly bags. 2 x — gms (for two
analysis) to be separately kept.

2. Sampling of liquids:
Glass sampling tube ( 3 - 4 ft. in length ) to be used for the liquid in 200
litters drums and 25/50 ml pipettes to be used for the liquid in 2.5/3.5 litters
bottles or tins. The samples to be collected in cleaned and dried bottles with
HDPE caps.

SAMPLING LEVEL
1. RAW MATERIALS
a. If containers are less than 3 in number, sample from every container
minimum 20 ml for liquids and 10 g for solids or a specified in the
individual specifications of the material.
b. For consignments having 4 to 100 containers, use the formula \/ n +
1 to determine the number of containers to be sampled ( where n =
total no. of units in the consignment ).
c. For consignments of over 100 containers sample 1 container from
every additional 100 containers.
For example:

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 No. of containers No of samples.
1-3 3
4 - 100 \/ n + 1
101 - 200 12
210 - 300 13
Please ensure that when the number of containers are more than 100 -
say 200; 12 randomly chosen containers are sampled and no 11
randomly chosen containers from first 100 and 1 from the second
100.

2. BULK DRUGS
Sample every container in the batch.

3. PACKING MATERIAL
Draw the number of samples mentioned in the individual packing material
specifications. In case of visual inspection larger population of sample is
taken for evaluation of defects as given in specification.

4. QUALITY CONTROL CHECK - LIST FOR SAMPLING

Follow the check - list for sampling of any item.

a. Quality Control check - list for sampling of raw material.
b. Quality Control check -list for sampling of packing materials.
c. Quality Control check - list for sampling of Bulk Finished Products.
d. Quality Control check - list for sampling of Packed Finished Products.

The following is the manner in which various departments send an intimation to

Q.C. when any analysis is required.
a) When a consignment of raw materials is received by Stores, intimation is
sent to Quality Control Department on a Goods Received (G.R.) Note
b) Whenever manufacture of any bulk drug or formulation is complete, ‘Test
Request’ (T.R.) Forms are sent by Production Departments to the Quality
Control Department as an intimation for sampling.
c) The Production Department for all intermediates and in-process samples
sends technical Information T.I. sheets Samples are sent by the Production
Department alongwith the T.I. sheets.
1. After receiving the G.R. notes/T.R. forms/T.I. sheets, make entries in the
relevant Analytical Reference Number register, assigning an A.R. Number
to each batch.
2. Collect samples of the material/product form the Production
Department/Stores, and keep these in the designated placed. Affix Under

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 Test labels on the containers. Refer to the sampling checklist for individual
items.
3. Check the individual samples for their physical uniformity, eg. Color,
nature, appearance, etc.
4. Refer to the General Analytical methods.
5. If they pass preliminary examination, pool these together to form a
composite sample.
6. Withdraw a quantity from the composite sample to keep as ‘Reserve
Sample’, equivalent to 2 analyses.
7. Carry out the analysis on the 3rd portion of composite sample.
8. Record all details of tests carried out (like weights, volumes, dimensions,
normality, absorbance and other readings) on the reverse side of the
Analytical Report/Q.C. copy of the T.I. sheet.
9. Record the results/conclusions on the front of the same sheet or generated on
a computer. Attach all spectra and other, printed data pertaining to the tests
to the Analytical Test Report.
10. Have all calculations checked by a second chemist.
11. Indicate on the Analytical Test Report and GR note copy whether the same
complies with its specification or not by stamping the words ‘Passed’ or
‘Rejected’ except in case of samples accompanying T.I. sheets where only
results are to be reported. Give reasons in case of rejections.
12. Enter the status of the material in the relevant Analytical Reference Number
Register (Passed, Rejected or Reported).
13. Prepare the ‘Passed’ or ‘Rejected’ labels and get these affixed under your
supervision, in such a manner that the yellow portion of the ‘Under Test’
label is completely covered. Passed/ Rejected labels should be put on every
container.
14. Retain the Analytical Report and one copy of the G.R. Notes and send the
remaining copies to the Stores.
15. When a material has to be retested for any reason, ‘Quarantine’ labels are
affixed by the Stores/Production over the ‘Passed’ labels and T.I. sheet is
sent to the Q.C. by the concerned department.
16. Re-analyse the material as above and insure fresh ‘Passed’ ‘Rejected labels.

Sometimes a material is tested at another Unit or an outside laboratory due to non-

availability of equipment, facility or for confirmation of results.

The following procedure is followed by the laboratory requesting technical

information:
1. Sample the material and abstract a part of the sample sufficient for about 2
analyses.

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2. Pack this quantity in polythene bags and label appropriately
3. Send this with a set of two copies of the Technical Information Sheet
indicating the tests to be performed, quantity of sample, batch number and
sample reference number ( A.R. number assigned in your laboratory will be
the sample reference number ).
In the case of an outside laboratory send a covering letter.

The following procedure is followed by the testing laboratory (in case of inter
laboratory testing):
1. Record the receipt of the sample in the Analytical Reference Number
register and assign an A.R. No. to it.
2. Perform the requisite test, recording all calculations and observations on the
reverse of both copies of the T.I. sheet and results/concussions on the front.
3. Send the yellow copy of the T.I. sheet, along with a photocopy of the
instrument recordings. (Eg. Spectra and other graphs/scans)
4. Retain the white copy of the T.I. sheet with instrument recordings.

Note: The laboratory requesting information should file the results of analyses
of the product from both laboratories in the docket (Attach the T.I. sheet
and instrument recordings to your Analytical Report)

Reserve samples are preserved for the purpose of re-analysis, Re-analysis may be
necessary for tracing back in case of complaints received. The procedure for the
handling of reserve samples is given below.

I. Raw Materials/Bulk Drugs:

1. Retain reserve samples of every batch of all raw materials, which are active
ingredients in formulations, and all bulk drugs. Certain non-active raw
materials may also be kept as reserve samples if indicated in their
specifications.
2. When the composite sample is prepared in the laboratory for analysis,
abstract a quantity sufficient for at least 2 analyses as the reserve sample.
3. Store these as far as possible in containers simulating the ones in which the
material is normally stored or marketed.
4. Affix a label on it.
5. Where the material has been re-tested, retain a sample of the retested
material.
6. Make entries in the Reserve Sample Register meant for the purpose.
7. Store these in an air-conditioned room (to maintain their integrity as far as
possible so that any re-analysis performed reflects the original analysis)

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8. Examine the reserve samples of few batches of active ingredients visually at
least once a year unless the examination would affect the integrity of the
sample and record the results of the examination.
9. Arrange for the destruction of reserve samples which are not required at
regular intervals.

Item Period of Keeping

Till the finished product batch is
Intermediates
released by Q.A.
Key raw materials used in bulk
Till the batch of Bulk Drug is released.
drugs and bulk drugs intermediates.

Note: Do not keep reserve samples of corrosive/hazardous chemicals or volatile

liquids.

Procedure for the destruction of time expired samples.

1) Identify the batches of products to be destroy by reviewing the Register
periodically
2) In the case of items coming under Central Excise, send a list of these in the
prescribed format for computation of duty and get their approval.
3) Destroy the samples according to the disposal procedure laid down for the
material/product

The procedure given below outlines the method to be followed to establish the
stability of products and hence determine their shelf life.

Tentative storage conditions and expire dates are fixed based on stability of new
products. These are normally accelerated studies.

The storage conditions and expire dates are monitored and suitably revised if
necessary by conducting studies carried out on the product in the pack in which it is
marketed under conditions close to market conditions.

Conduction of stability studies is the responsibility of the Quality Assurance

Manager/ Q.C. Head/ Manager QA will prepare a stability testing protocol.

Stability studies are carried out on the following batches:

1) Initial R & D or pilot batches (three) at accelerated temperature and
humidity
2) Initial production batches (three) at ambient temperature.
3) Regular production batches (one batch a year) at ambient temperature.
4) Batches in which processes and packing material which come in contact
with the product have been changed by accelerated temperature and
humidity.
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Batches to be examined: (Schedule for stability study)
The batches on which the stability studies are to be carried out should be identified
in the annual scheduled program of the laboratory.

Quantity of sample:
From the above identified batches withdraw a quantity sufficient for about 10 - 12
analyses. Pack quantities sufficient for each analysis separately in polythene bags
and seal the bags. These are enclosed in miniature fiber board drums.

Storage:
Store at room temperature for bulk drugs in case of marketed products at
temperature specified for that product or as close to market conditions as follows.
Keep samples for accelerated studies under the specified conditions of temperature
and humidity as given in the protocol.

Frequency of examination:
Examine the batch at intervals of 3, 6, 9, 12, 18, 36, 48, and 60 months for ambient
temperature and at intervals of 1,2,3,4 months at 37 ºC, 45ºC and 65 % ( + 5 % )
humidity.

Tests to be performed:
Perform the tests pertaining to characteristics likely to change on storage and
specially those which help in detecting and quantifying degradation products or
related impurities. The following tests should be included:
a) Appearance - characteristics
b) L.O.D. / K.F.
c) pH
d) Related substances by TLC or HPLC or GLC. HPLC is the preferred method
if applicable
e) IR pattern
f) UV Scan
g) Assay
h) Color Index

Stability testing Protocol:

Draw a protocol for each product on the Stability Testing Form.
New Products - from R & D
Existing product - Production Department

Recording of result:
Record all observations and calculations on Stability Test Report and the results on
the Stability Studies Forms.
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New Products - from R & D
Existing product - Production Department

Enter results of subsequent analyses of the same batches on the same form. File the
S.T. Reporting and the Stability Study Form for each batch at one place.
Present the stability data in graphical form

Assessment of results:
The Quality Assurance Manager and R & D Manager make recommendation of the
shelf life of the product depending on these studies.

Documentation is a prime necessity in Quality Assurance. It serves to define

systems of control, to reduce the risks of error inherent in oral communication and
to ensure that personnel are instructed in the details of and follow procedures. It
also helps in tracing the history of each batch of product from the stage of receipt of
materials to the release of the batch to the market.

In the analytical laboratory the important aspects of Quality Control

documentation are:
a) The drawing up of reference documents, which outline procedures, to be
followed in assuring the quality of materials, intermediates and finished
products.
b) The recording and reporting of results of tests carried out in the laboratory
and on the shop floors, and
c) The storage of all documents pertaining to Quality Control

General
1. See that all documents bear a date and number and indicate which
documents they supersede.
2. Keep documents up-to-date. Get authorization in advance for any
amendment, which is to be made.
3. Where the amendment is permanent, replace the amended document by a
newly prepared one at the earliest.
4. Remove the superseded document from active use, retaining a copy for
reference.

Specifications:
The Quality Control Head in consultation with the R & D Manager of the Company
will write for each material a specification which is relevant to its intended use.
1. Draw up the specification consisting of three parts as given below:
(Specimens of raw material specification, packaging material specification
and finished product specification)

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 (1) The first part of “Specifications” provides information on sampling
and handling of the material. It includes the following:
a) Name of the material with common synonyms. The name
given in the Computer Code Manual should be used.
b) Date of the document and the one it supersedes
c) The computer code number for the material.
d) Reference to the pharmacopoeial monograph, where
appropriate.
e) Standard packing indicating the pack and pack quantity.
f) Storage requirements
g) Sampling level giving the number of containers to be sampled
and the quantity from each container.
h) Quantity of composite samples for analysis
i) Quantity of reserve sample.
j) The period after which the material should not be used in
production without retesting indicated by the words ‘Retest
after’
k) Hazards and precautions (only for raw materials and bulk
drugs )
l) Signature of the person preparing the specification.
m) Signature of the person checking/approving the document
n) Signature of the person authorizing the specification.

(2) The second part of ‘Specifications” provide information on standards

and limits. It includes the following:
a) Name of the material.
b) Molecular formula of the material where appropriate.
c) Molecular weight where appropriate.
d) Description of the physical characteristics of the material
e) Solubility
f) Identification
g) List of detailed specifications in quantitative terms, wherever
possible.

(3) The third part of "Specifications" provides the experimental details of

all the test methods to be used to assess the identity and quality and of
the assay of the material. It includes the following:
a) Methods used for all tests to be performed.

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 b) Where common methods are used, do not give details, but
gives a reference to the General Analytical Methods (GAMS).

2. While writing the specifications and methods of analysis:

a) List the tests in the same order as they are listed in the relevant
pharmacopoeia.
b) Indicate the specifications, which are additional to the pharmacopoeia ones
by means of an asterisk (*)
c) Mark by means of a double asterisk (**) those tests are not performed on a
routine basis and indicate when these are performed.

3. Review specifications on a yearly basis.

RECORDS
1. Note key observations, readings, and calculations, directly on the reverse
side of the Analytical Reports.

2. Enter the name of the material under test, batch number, and date of analysis
before carrying out the analysis.
3. Where analysis of the sample is spread over a number of days, record the
date on which each test was carried out.
4. Record the results on the front side of the Analytical Report.

5. Enter the date of testing, A.R. Number, batch number and test details on all
spectra and other instrument records and attach these to the main report.
6. Calculate the results of assay to one decimal place more than that indicated
in the specification but round up and report only to same number of places
given in the specification.
7. Generate the report with the help of computer whenever possible

8. Get all calculations checked by a second chemist.

EQUIPMENT OPERATING PROCEDURES

Operating procedures are available for every instrument in each laboratory. These
are kept in the form of readily referable documents.
Keep these at a place for ready reference and operate the instrument only when you
have ready and understood the procedure. Specimen of a typical operating
procedure

CALIBRATION AND MAINTENANCE OF INSTRUMENTS

Procedures for maintenance and calibration of equipment and schedules for the
same are drawn up in the laboratory.
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Calibrate the instruments according to the procedure and schedule periodically and
enter the results in a record log kept for each instrument
The laboratory should be kept clean and tidy at all times by scheduling routine
house-keeping procedures.
The Q.C. head at every unit prepares and submits a monthly report to the General
Manager. A copy of this is also sent to the Q.A. Manager at the Corporate Office

In general it contains information under the following headings:

A. Statistics of Analytical work:
(No. of samples received, the number pending, rejections, etc,)
B. Reject Analysis:
(Follow-up on rejects in consultation with Production and Purchase to
review effect on Production Planning.)
C. Problems:
(Encountered or anticipated, and their solutions or proposed solutions).
D. Personnel:
(Their significant contributions, training imparted to them etc.)

E. Improvements:
(Made or proposed)
F. Product Quality:
(Stability reviews, complaints, review of specifications, etc.)

VALIDATION OF ANALYTICAL METHODS

The word validate means to confirm. In other words, validation involves
confirming whether the procedure, system or method actually achieves what it is
supposed to.

There are two major components of validation:

a) The procedure or method must give accurate results, and

b) It must give reproducible results.

Validation normally involves the comparison of the method to be validated with a

known and accurate method or by comparing the results obtained with the method
in question with the results obtained on a known sample. Known samples are
usually reference standards of high purity supplied by pharmacopoeial commission.
Analytical methods given in the pharmacopoeia, in general, need not be validated
because they are certified to be accurate and have been tested to give reproducible
result. However, if the method is not official in the pharmacopoeia, then it must be
validated.

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The following is the suggested methodology for carrying out validation on
analytical methods.
1. Designate a team which will do the validation. In general, it is desirable to
have on this team at least one member who is not involved in routine
analysis (say, a member assigned for R & D /Instrumental analysis).
2. Write a protocol which gives:
a) The name of the method to be validated.
b) The purpose of the experiment.
c) The method to be used giving details of all steps to be followed
Example:
i) Test a known standard for its purity by the method to be validated. See
whether the results are comparable with its known assay.
ii) Test a sample for its purity by the method to be validated as also by a known
pharmacopial method. See whether the results are comparable.
3. In order to remove variation due to ‘chance’, it is recommended that the
procedure be repeated in duplicate.
4. The method is accurate if the results obtained with the method being
validated do not differ from the known results by more than +/- 2 percent.
5. It is reproducible if the results obtained in the replicate analysis using the
method being validated do not differ by more than +/- 2 percent.
6. Before carrying out the Validation studies, ensure that all glassware,
instruments, etc., are calibrated to ensure.
HANDLING OF COMPLAINTS
A product complaint may be considered as formal expression of dissatisfaction
with any of the Company’s products. It serves as the primary means of obtaining
feed back about product quality.
A) Bulk Drugs and Intermediates
Intra-Unit Complaints
Complaints from one unit’s of the company to another are normally received
by the Head of the Manufacturing Unit. Depending upon the nature of the
complaint, a sample of the material is also sent along with the complaint.
The Q.A. of the manufacturing unit initiates the investigation of the
complaint with the head of the Q.C. where a complaint sample has been
sent, the Q.C. examines it along with its reserve sample.
In other cases, a reference is made to the original analytical report and the
reserve sample is reanalysed by the Unit Q.C. and a report of the findings on
a Technical Information sheet (TI Sheet) is sent to Q.A.
Q.A. discusses the report with the General Manager of the Unit. The likely
reason for the complaint is investigated by the General Manager. Depending

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 upon the results of the investigation, the General Manager communicates to
the Unit Head of the Company whether the material is to be recalled or
could be used after suitable reprocessing at the complaining unit. In the later
case, corrective action is suggested in consultation with R & D.
When reprocessing is done at the complaining unit, the reprocessed material is
analyzed and cleared by the QC of that unit. A copy of the analytical report is sent
to the Q.C. of the original manufacturing unit.

HANDLING OF PRODUCT COMPLAINTS

I & II Complaints on physical and packaging defects

1) The Marketing department records the details of the complaint, using a set
for each complaint.
2) The Marketing department also acknowledges receipt of the complaint to the
complainant
3) The Executive sends the sample and the set of Product Surveillance forms to
the Head of the Unit, which had manufactured the product.
4) The Head of the Unit refers the complaint to the QA. QA in consultation
with the QC Lab and the concerned manufacturing department, investigates
the complaint and reports the findings to the Unit Head
5) The Unit Head communicates his findings to the Executive at Bombay
Central.
6) On receipt of the Report, the Exec.

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