Schedule L1

GLPs in Drugs &

Cosmetics Rules
Kapil Bhargava
Dy. Drugs Controller (I) retired

Introduction
For GLPs a newly introduced Schedule in
Drugs and Cosmetics Rules
It

is applicable since 01.11.2010

Till

this introduction, GLPs were not

addressed as a legal requirement (Except
few of the conditions were mentioned for
PTLs in part XV (A) of D & C Rules)

Introduction
WHO GLP is in draft form
Another WHO draft only on
microbiology labs
Both above are guidelines and not
legal requirement
Not conforming to GLP may attract
administrative or legal penalty

Presentation shall cover

Salient features of this schedule
The different provisions those have
been added now
Difficult to understand requirements
Their logic

Clarifications required by / from

regulatory bodies for implementation
of requirements

Personnel
Technical manager or Quality Manager
Current mfg. lic. mention expert
technical staff for testing
Responsible for all technical activities
Implementation of documented quality
systems
Responsible for technical audit of the
laboratory for GLP compliance by an
expert appointed by the top-management

2. Premises
(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..

HVAC
(iv) air ventilation system shall ensure
dust free environment
Installation of HVAC is essential now
Design of the lab need modification and
the project in-charge or site engineer
must very clearly understand pressure
balancing (more so when fume hood is in
operation)
Humidity control is also necessary
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Premises / Work Area

(d) Tabletops shall be constructed with
acid, alkali, and solvent resistant
material and shall be smooth and free
from crevices as far as possible
In case this is not existing, the table
tops are to be replaced

Premises
e) All bio-medical laboratory waste
shall be destroyed as per the
provisions of the Bio-Medical waste
(Management and Handling) Rules,
1996.

Premises
Sterility Test Area
(g) The air circulation is maintained in
the area where sterility test is carried
out as per Schedule M
Schedule M does not prescribe air
circulation for testing laboratory,
requirement is for mfg. areas

Premises
(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
It is to be controlled

Animal House: (i) Animal House shall have the

approval of the Committee for the
Purpose of Control and Supervision on
Experiments on Animals (CPCSEA).

Animal House
(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

Personnel
(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!!

Personnel
(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 !!

Equipment
(f) A progress register for nonfunctional equipments and action for
procurement of spares and
accessories, monitoring thereof, shall
be maintained.

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Equipment
(g) A Standard Operating Procedure
for preventive maintenance of machine
or equipment or apparatus shall be
prepared by the laboratory
A matrix and compliance to this schedule
Demonstration to this compliance

Equipment
(h) Other equipment such as burettes,
pipettes, volumetric flasks, weight
boxes, thermometers, etc., shall be
thoroughly checked for calibration
before acceptance for use
Laboratory Glassware are termed as
equipment
It is to be decided if suppliers certificate
will be accepted or not

Equipment
(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

Equipment
(l) Autoclaves must meet the
requirements described for
operations, safety and validation
procedures, and the validation carried
out by the laboratory shall be recorded

Reagents
(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 !

Good house keeping and

safety
(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

Reference Materials
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!

RS/WRS & Secondary

Std.
Standard Operating Procedure (SOP)
for the maintenance of reference
standards and evaluation of Working
and Secondary standards

Ref. Subs. (Official)

Ref. Subs.
Secondary Ref. Substances
Working Standards

Working Standards
(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!

Reference Material
(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.
purpose of this requirement is unclear

Working Standards
(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

Microbiology Cultures
(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

Microbiology Cultures
(d) The laboratories shall perform
standard biochemical tests on the subculture as given in literature to ensure
their viability.
Biochemical tests are time consuming and
rather tough to be performed on each
subculture

Microbiology Culture
Practically it is not feasible to perform the
biochemical tests prior to use of every culture
Alternatively whenever a new vial of Working Seed
is used to prepare fresh slants for routine use, the
purity and characteristics of the microbial culture
shall be confirmed by microscopical and
biochemical examination
These slants thereafter can be used for routine
tests for a period of 1 month restricting the passage
up-to not more than five

Microbiology Work
(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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Microbiology Work
(d) The laboratories shall perform
standard biochemical tests on the subculture as given in literature to ensure
their viability
Each sub culturing 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

Quality system
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

Internal quality system

audits
(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

SOPs for:
(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;

SOPs for:
(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

SOPs for:
(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

SOPs for:
(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.

Protocols Archives
(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:-

Protocols Archives
(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.

Storage and archival

(a) The residual sample shall be
retained in proper storage condition
for a period of one year after the finial
report.

Storage and archival

(b) The laboratory must establish and
maintain procedures for the
identification collection, indexing,
retrieval, storage, maintenance, and
disposal of all quality documents.

Storage and archival

c. The archive shall provide a suitable
environment that will prevent
modification, damage, or deterioration
and/ or loss

Storage and archival

(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

Storage and archival

(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.

Summarizing
Provisions in Schedule L1 are legal
requirement and are to be complied with
strictly
Clarifications for provisions which are
rather ambiguous may be sought for from
regulatory authorities
Few actions for compliance are also
expected from regulatory authorities.

My references were
Schedule L1, Schedule M, WHO TRS and other WHO
documents
Acknowledgements
Support from Mr. R Raghunandanan, my colleagues,
ex colleagues and professional in the industry

26th Feb. 11

kplbhargava@yahoo.co.in

47

26th Feb. 11

kplbhargava@yahoo.co.in

48