Present status of Good Laboratory Practices

Dr. Subhash C. Mandal

Chairman, Regulatory Affairs Division (RAD)

Indian Pharmaceutical Association

E-mail: subhash.mandaldr@gmail.com

Preamble:

Good Laboratory Practice (Schedule-L1) is now a mandatory requirement in the

Pharmaceutical industry. It has already been implemented mostly in the
developed countries and even in some developing countries. GLP has been
made mandatory in India from 1 st November 2010 through inclusion of Schedule
L1 in the Drugs and Cosmetics Rules.

Good laboratory practice(GLP) generally refers to a system of management

controls for laboratories and research organizations to ensure the consistency
and reliability of results as outlined in the Organization for Economic Co-
operation and Development (OECD) principles of GLP and national regulations.
It applies to non-clinical studies conducted for the assessment of the safety of
chemicals to man, animals and the environment, but it does not include clinical
research. The internationally accepted definition of GLP is as follows:

“Good Laboratory Practice (GLP) embodies a set of principles that provides a

framework within which laboratory studies are planned, performed, monitored,
recorded, reported and archived. These studies are undertaken to generate data
by which the hazards and risks to users, consumers and third parties, including
the environment, can be assessed for pharmaceuticals, agrochemicals,
veterinary medicines, industrial chemicals, cosmetics, food and feed additives
and biocides. GLP helps assure regulatory authorities that the data submitted are
a true reflection of the results obtained during the study and can therefore be
relied upon when making risk/safety assessments”. 

Status:

GLP in OECD member countries:

OECD has about 34 full members round the globe, from North and South
America to Europe and Asia-Pacific. They include many of the world’s most
advanced countries but also emerging countries like Mexico, Chile and Turkey,
where GLP is compulsory. OECD also work closely with emerging economies like
the People's Republic of China, India and Brazil and developing economies in
Africa, Asia, Latin America and the Caribbean.
 2
Mutual Acceptance of Data (MAD):

The testing of chemicals is labour intensive and expensive. Often the same
chemicals are being tested and assessed in several countries. The OECD council
therefore adopted a council decision in the year of 1981- on Mutual Acceptance
of Data (MAD)- stating that test data generated in any member country in
accordance with OECD Test Guidelines and Principles of Good Laboratory
Practice (GLP) shall be accepted in other member countries for assessment
purposes and other uses relating to the protection of human health and the
environment.

In line with the internationalization of research, the scheme is expanding beyond

OECD countries. Today, India has become the third key emerging economy to
sign up to MAD, after Singapore and South Africa, while Argentina, Brazil,
Malaysia and Thailand are provisional adherents to the system.

GLP in the OECD non-member countries:

An inspection in non-member economies by OECD inspectors will not guarantee

that, if they are found to be in compliance, their data will be accepted in other
member countries than the one to which they are submitting data and which has
thus sent inspectors to verify the accuracy of their compliance statement.

GLP in European Union:

The European Council had adopted two basic directives and a decision relating
to the application of the GLP principles since 1987 which are-

Directive one: " Directive 2004/10/EC of the European Parliament and of the
Council of 11 February 2004 on the harmonization of laws, regulations and
administrative provisions relating to the application of the principles of good
laboratory practice and the verification of their applications for tests on chemical
substances."

This directive prescribes the obligation of the Member countries to designate the
authorities responsible for GLP inspections in their territory. It also comprises
reporting the internal market and regulatory requirements regarding mutual
acceptance of data.

Directive two: “Directive 2004/9/EC of the European Parliament and of the

Council of 11 February 2004 on the inspection and verification of good laboratory
practice (GLP)".

The Directive requires that the OECD revised guidelines for compliance
monitoring procedures for GLP and the OECD guidance for the conduct of test
 3
facility Inspections and study audits must be followed during laboratory
inspections and study audits.

European Economic Community (EEC) Council had taken a decision on

28.07.1989 on the acceptance by the EEC of an OECD decision /
recommendation on compliance with principles of good laboratory practice. Apart
from these directives there are also 'Product Oriented Directives' referring to GLP
obligations in EU.

GLP in USA:

USA has its own rules applicable for preclinical trials in US on animals prior to
Clinical research in humans is 21 CFR 58. Anybody interested to submit data in
support of a New Drug Application in the USA required to follow 21 CFR 58 if
research is conducted in USA or required to follow OECD guidelines or 21 CFR
58 if research conducted outside USA.

GLP in India:
India is full-member for Mutual Acceptance of Data (MAD) in the OECD's Working
Group on GLP w.e.f March 3, 2011. As a consequence, the data generated by
Indian GLP laboratories is acceptable in all the OECD member countries. This
facilitates export of chemicals, drugs, pesticides etc. to these countries.
National Good Laboratory Practice (GLP) Compliance Monitoring Authority
(NGCMA) under the Dept. of Science & Technology, Govt. of India is working to
approve the Industries/test facilities/laboratories engaged in manufacturing of
industrial chemicals, pharmaceuticals, veterinary drugs, pesticides, cosmetic
products, food products, feed additives, etc., since 2002. Though this approval is
voluntary some laboratories have already obtained GLP Certificate from this
authority. Data generated by these GLP certified laboratories are accepted by the
OECD countries.

GLP (Schedule-L 1) under Drugs and Cosmetics Rules:

Govt. of India has notified GLP as mandatory vide G.S.R.780 (E) dated 10 th
November 2008 under schedule “L-1” with effect from the 1 st November, 2010.
This includes requirements in details about General requirements, Premises,
Personnel, Equipments, Chemicals and reagents, Good house keeping and
safety, Maintenance, calibration, and validation of equipments, Reference
materials, Quality system, Internal quality system audits, Management review,
Standard Operating Procedures, Protocols and specifications archive, Raw data,
Storage and archival,
Most of the GMP complied companies have already improved their laboratories
during compliance of Schedule M. A major part of the GLP requirements have
 4
been covered by the revised schedule M especially under section 5 & 6 of the
same.
2007 edition of the Indian Pharmacopoeia (IP) has prescribed some stringent
requirements which need the service of some sophisticated and costly
instruments. Except big and medium scale companies most of them are yet to
provide costly instruments like- AAS, HSGC, IR etc. and are outsourcing it to
approved laboratories. Some of them are trying to procure the same.

Conclusion:
Manufacturers exporting their products in the OECD member countries have
already complied with OECD requirements of GLP in addition to the country
specific requirements. Some manufacturers have complied 21 CFR 58
requirements who are exporting in USA in addition to OECD requirements. There
are some manufacturers who have already complied with the requirements of
GLP voluntarily.
India is full-member for Mutual Acceptance of Data (MAD) in the OECD's Working
Group on GLP w.e.f March 3, 2011. As a consequence, the data generated by
Indian GLP laboratories is acceptable in all the OECD member countries. This
facilitates export of chemicals, drugs, pesticides etc. to these countries.
Manufacturers of Drugs and Pharmaceuticals may procure GLP Certificate from
National Good Laboratory Practice (GLP) Compliance Monitoring Authority under
the Department of Science & Technology, Government of India which may give
them edge over their competitors (http://www.indiaglp.gov.in/) as the data
generated by the GLP certified laboratories is accepted by the OECD countries.
Good Laboratory Practice has been made mandatory through inclusion of
Schedule L1 to the Drugs and Cosmetics Rules effective from 1 st November,
2010. This requirement is mandatory for manufacturing Drugs in India and is
different from OECD requirements.