IPA Bangaluru Branch
4th September
Bangaluru
Kapil Bhargava
Dy. Drugs Controller (I) retired
Mumbai
For GLPs a newly introduced Schedule in
 Drugs
and Cosmetics Rules
 It is applicable from 01.11.2010
 WHO
has also introduced a new
Annexure and has been titled with
similar words – popularly known as
GLP and in in draft form
 Another WHO draft only on
microbiology Labs
kplbhargava@yahoo.co.in
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 Salient
features of this schedule
 How on existing laboratories it may
have effect
 The different provisions (already non
existing ones) to be added now
 Difficult to understand requirements
• Their logic
 Any
Correction are needed or
clarifications required by regulatory
bodies
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• a) The laboratory or the organization of which
it is a part must be an entity that is legally
authorized to function and can be held legally
responsible.
 Legal
Status of the laboratory attached
to a manufacturing unit
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• (c) Laboratory management shall have a
qualified individual to be known as quality
manager or technical manager for carrying
out all technical activities and for the
implementation of documented quality system
and shall report to the top management
directly.
 quality
manager or technical manager
for carrying out all technical activities!
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• (d) The quality manager shall prepare a
schedule for technical audit of the laboratory
for GLP compliance by an expert appointed by
the top-management other than the in charge
of the laboratory and shall ensure the
maintenance of documented quality system
as per quality, manual
 GLP
compliance by an expert
appointed by the top-management
other than the in charge of the
laboratory – An outside auditor is must!
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• (a) (i) the laboratories shall be designed,
constructed and maintained so as to prevent
entry of insects and rodents besides cross
contamination
 besides
cross contamination –
Cross contamination in the laboratory is to be
avoided
 Two different samples cannot be handled by an
analyst and so on..

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 (iv)
air ventilation system shall ensure
dust free environment
• Installation of HVAC is essential now
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 (b)
The laboratories shall be provided
with adequate lighting and ventilation
and if necessary air- conditioning to
maintain satisfactory temperature and
relative humidity that will not adversely
affect the testing and storage of drugs
or the accuracy of the functioning of
the laboratory equipments or
instruments.
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 (d)
Tabletops shall be constructed with
acid, alkali, and solvent resistant
material and shall be smooth and free
from crevices as far as possible • Permitting some crevices on table tops?
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 (e)
All bio-medical laboratory waste
shall be destroyed as per the
provisions of the Bio-Medical waste
(Management and Handling) Rules,
1996.
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 (f)
Adequate space with proper storage
conditions in the laboratory shall be
provided for keeping reference and
working standards and be maintained
by the quality control department.
 Standard Operating Procedure (SOP)
for the maintenance of reference
standards and evaluation of Working
and Secondary standards…
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 (g)
The air circulation is maintained in
the area where sterility test is carried
out as per Schedule ‘M’
• Schedule M does not prescribe fair circulation
for testing laboratory, it is there for mfg. areas
 (h)
Bio-burden shall be routinely
maintained in the controlled and
uncontrolled area. (e.g. air locks)
• It is not good to “maintain” bio-burden
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 (i)
Animal House shall have the
approval of the Committee for the
Purpose of Control and Supervision on
Experiments on Animals (CPCSEA).
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 (ii)
Designed in such a way that there is
an arrangement to quarantine the new
animals procured or purchased and
have a provision for clean corridor and
dirty corridor
• Clean and Dirty corridor -- Very difficult
provision for already existing animal houses
particularly those attached to small size mfg.
units
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 (c)
Head of the laboratory must be of
high professional standing with
experience in drug analysis and
laboratory managements who is
responsible for…. :
• high professional standing!!
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 (iv)
taking final responsibilities for
recommending any regulatory action in
the event of non-compliance of tested
samples
• Head of the laboratory is now expected to
recommend to management the regulatory
action to be taken for non compliances !!
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 (f)
A progress register for nonfunctional equipments and action for
procurement of spares and
accessories, monitoring thereof, shall
be maintained.
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 (g)
A Standard Operating Procedure for
preventive maintenance of machine or
equipment or apparatus shall be
prepared by the laboratory.
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 (h)
Other equipment such as burettes,
pipettes, volumetric flasks, weight
boxes, thermometers, etc., shall be
thoroughly checked for calibration
before acceptance for use.
• shall be thoroughly checked for calibration
before acceptance for use – This means that
supplier’s certificate is not acceptable and
pipettes and volumetric flasks are to be
calibrated in-house!
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 (i)
Maintenance procedure in the form
of Standard Operating Procedures
must be prepared and regular
servicing must be performed by the
maintenance engineer or specialist
• Requirement of a maintenance engineer is
now essential
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 (l)
Autoclaves must meet the
requirements described for operations,
safety and validation procedures, and
the validation carried out by the
laboratory shall be recorded
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(d) Containers of stock solutions and
of standard shall bear the following
details-
(i)
(ii)
(iii) “use before date” depending upon the
stability of the solution; and
(iv) standardization records - It is very
difficult to mention standardization records
on stock solution containers !
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 (iv)
the laboratories shall have
adequate first aid kit and fire fighting
equipments located at the right places
and the staff must be familiar and
trained with the use of fire fighting
equipment including fire extinguishers,
fire blankets and gas masks.
• fire blankets and gas masks are essential now
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8
(a) Reference materials are
necessary for the testing and, or
calibration, validation or verification of
a sample or of equipment, instruments
or other devices and all such materials
shall be traceable to agency authorized
by Government of India or any other
International body
• Difficult to comply!
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 (b)
The laboratory shall prepare
working standard by comparing with
the reference standards and shall be
routinely checked for their purity by
selecting parameters such as identity,
loss on drying or on water, impurity and
assay, etc.
• Difficult to comply!
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 (c)
Wherever, any new reference
material is received by the laboratory, a
code number shall be assigned and
this code number shall be quoted on
the laboratory note book and analytical
work sheet.
 The working standard shall also be
provided with identification code.
• I did not understand the purpose of this
requirement
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 (e)
All working standards shall be
checked at appropriate intervals or
before use to ensure that it has not
deteriorated or decomposed during
storage.
• Checking deterioration or decomposition
frequently or prior to use is very difficult and
also time consuming . It may not serve the
intended purpose . This may be OK for PTLs
or Government Laboratories
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 (b)
if the cultures have become nonviable or mutant, proper procedure
shall be followed to destroy these
cultures by autoclaving under an
authorized personnel for biological
testing. Preferably not more than five
passages may be prepared.
• This is to be more scientific – Checking
culture purity is to be emphasised – more for
Assay Cultures and less for limit test cultures
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 (c)
All activities be carried out in a
aseptic area by authorized person.
• Now aseptic area is needed for all
microbiological work – In existing laboratories
Aseptic area is difficult to create (or upgrade)
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 (d)
The laboratories shall perform
standard biochemical tests on the subculture as given in literature to ensure
their viability
• Each subculturing all biochemical tests are
expected to be carried out
• Viability can be tested by other means too
• This provision is more suited for preparative
work
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The quality system shall be designed
to ensure the following objectives: (a) the measurements and calibrations
shall fully conform to the compendial
requirements and methods
demonstrably based on validation
protocols are followed

• Method Validation for all the analytical
methods is compulsory now!!
• No references in IP or Drug Rules are
available
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
(a) Internal audits are done…. to
comply with requirements of
regulatory authorities.
•
Some Check-list from Govt. is needed
Internal audits shall be carried out by
trained and qualified personnel who
are independent of the activity to be
audited
In smaller labs this too is difficult for
compliance
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(i) sample handling and
accountability;
(ii) receipt identification, storage
mixing and method sampling of the
test and control articles;
(iii) record keeping, reporting, storage
and retrieval of data;
(iv) coding of different studies,
handling of data including use of
computerized data system;
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(v) operation of technical audit
personnel in performing and reporting
audits, inspections and final report
reviews;
(vi) routine inspection of cleaning,
maintenance, testing, calibration and
standardization of instruments;
(vii) action to be taken in respect of
equipments failure;
(viii) analytical data methods;
(ix) the raw data;
(x) data handling and storage retrieval
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(xi)
(xii)
(xiii)
(xiv)
(xv) maintenance of sterility room (i.e. constant
maintenance and monitoring of Aseptic condition of
sterility room)
(xvi)
(xvii)
(xviii) monitoring of testing of samples – I have not
understood this SOP
(xix) methods of retention of unexpended samples,
their location, maintenance and disposal – easy to
write SOP but difficult to comply
(xx) document control
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(xxi) redressal of technical
complaints;
(xxii) housing-keeping
(xiii) corrective and preventive action;
(xxiv) working procedure (test
methods);
(xxv) calibration Manual; and
(xxvi) training manual.
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 (b)
All updates and corrections must be
noted in the master volumes of
Pharmacopoeias to prevent the use of
obsolete sections; supplement and
addendum shall also be made available
in the laboratory.
 (c)
The specification archive shall
contain the following:kplbhargava@yahoo.co.in
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(i)
(ii) a file on patent and proprietary medicines
(non- pharmacopoeial) test methods to
specifications prepared and validated by the
manufacturer or by the laboratory itself.
The test methods shall be submitted to the
concerned Drugs Control Authority.
The validated test methods developed by the
manufacturer or the laboratory shall stand to the
requirements of compendial parameters in regards
to its precision, accuracy, reproducibility, specificity,
linearity, and ruggedness etc.
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The residual sample shall be
retained in proper storage condition for
a period of one year after the finial
report.
 (a)
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 (b)
The laboratory must establish and
maintain procedures for the
identification collection, indexing,
retrieval, storage, maintenance, and
disposal of all quality documents.
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 ©….
The archive shall provide a
suitable environment that will prevent
modification, damage, or deterioration
and/ or loss
 (d) The condition under which the
original documents are stored must
ensure their security and
confidentiality.
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 (e)
Paper documents shall not be kept
for long periods under high humidity
and raw data in the form to tape and
discs are to be preserved with care
 (f)
In case of storage of only optical
disc, the life of disc shall be longer
than the storage time.
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 (g)
Raw data on thermal paper might
fade away with time; therefore, a
photocopy of the thermal paper shall
also be retained in the archive.
 (h)
Time for which records are retained
shall be prescribed in the documents.”
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•
•
•
On reading the GLP Schedule one may get
impression that it has been designed with
PTLs and other such laboratories in mind
All provisions here may not be relevant to
laboratories attached to manufacturing units
Provisions in Schedule L1 are legal
requirement and are to be complied with
strictly therefore clarifications may be sought
for provisions which are either not clear or not
relevant
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My references were
•Schedule L1, Schedule M, WHO TRS and other
WHO documents
•Support from my colleagues, ex colleagues and
professional in the industry
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