Good Laboratory Practice for Non-Clinical Laboratory Studies – Advanced Notice of Proposed

Rulemaking. (29) Nonclinical studies have changed markedly since issuance of the good
laboratory practices (GLP) regulation (21 CFR 58) in 1978. In recognition of this change, FDA
is seeking comment on whether to amend the regulation. Based on the agency’s review of the
1978 rule and preliminary stakeholder input, FDA believes that requiring nonclinical
facilities/laboratories to follow a risk-based GLP quality system will help ensure the integrity of
data in nonclinical studies.

In the experimental (non-clinical) research arena, good laboratory practice or GLP is a quality
system of management controls for research laboratories and organizations to ensure the
uniformity, consistency, reliability, reproducibility, quality, and integrity of chemical (including
pharmaceuticals) non-clinical safety tests; from physio-chemical properties through acute to
chronic toxicity tests.

Good laboratory practice or GLP is a set of principles intended to assure the quality and integrity
of non-clinical laboratory studies that are intended to support research or marketing permits for
products regulated by government agencies. The term GLP is most commonly associated with
the pharmaceutical industry and the required non-clinical animal testing that must be performed
prior to approval of new drug products. However, GLP applies to many other non-
pharmaceutical agents such as color additives, food additives, food contamination limits, food
packaging, and medical devices.

FDA requires researchers to use good laboratory practices (GLP), defined in medical product
development regulations, for preclinical laboratory studies. The GLP regulations are found in 21
CFR Part 58.1: Good Laboratory Practice for Nonclinical Laboratory Studies. These regulations
set the minimum basic requirements for:

An essential nonclinical laboratory study described in the PMA was not conducted in compliance
with the good laboratory practice (GLP) regulations in 21 CFR 58 and no reason for the
noncompliance is provided, or, if it is, the differences between the practices used in conducting
the study and the good laboratory practice regulations do not support the validity of the study.

The Good Laboratory Practice (GLP) regulations were put into place in 1978. They establish a
standard of practice to ensure that results from the nonclinical laboratory study reported to the
U.S. Food and Drug Administration (FDA) are valid and that the study report accurately reflects
the conduct of the study. While the GLP regulations promulgate…

Compliance with Good Laboratory Practice (GLP) is generally expected for pivotal in vitro and
in vivo studies submitted in support of an IND application. For each non-clinical laboratory
study subject to the GLP regulations, investigators are expected to state in the study report that
the study was conducted in compliance with the GLP regulations. If the study was not conducted
in compliance with the GLP regulations, investigators should submit a brief statement of the
reason for noncompliance.

Introduction Testing of FDA-regulated products may be performed under different regulations,

including Good Laboratory Practices (GLP) and Good Manufacturing Practices (GMP). This
white paper outlines the differences between GLP and GMP regulations that are significant to
testing, and provides guidance on when these regulations are applicable.

These steps are now necessary to adhere to good laboratory practice (GLP), good manufacturing
practice (GMP), and to ensure the use of accurate and credible data and standards to guarantee
patient safety. All these practices together guarantee that drugs are developed in accordance with
good clinical practice (GCP), and are both effective and safe to use.

The archiving of records and materials generated during the course of a non-clinical health or
environmental safety study is an impor- tant aspect of compliance with the Principles of Good
Laboratory Practice (GLP). The maintenance of the raw data associated with a specific study and
the specimens generated from that study are the only means that can be used to reconstruct the
study, enabling the information produced in the final report to be verified and the compliance
with GLP of a specific study to be confirmed.

Good Laboratory Practice (GLP) principles were established in 1981 by the OECD. GLP
examines how laboratory studies are planned, performed, monitored, recorded, reported and
archived, and so ensures that results are a true reflection of the study. GLP is implemented by
laboratory inspections and study audits.

Non-clinical studies to demonstrate the health or environmental safety of new chemical or

biological substances must be conducted in compliance with the principles of good laboratory
practice (GLP).11 The principles of GLP provide a framework within which laboratory studies,
both in vitro and in vivo, are planned, performed, monitored, recorded, reported and archived.
Directive 2001/83/EC expressly provides that certain non-clinical (pharmaco-toxicological)
studies of medicines must be carried out in conformity with GLP.

• archival of paper records by independent, designated personnel in secure and controlled paper
archives (archivist is the term used for these personnel in quality control, good laboratory
practices (GLP) and good clinical practices (GCP) settings. In good manufacturing practices
(GMP) settings this role is normally designated to specific individual(s) in the quality assurance
unit);

The Good Laboratory Practice (GLP) Training Manual set comprises of two manuals; one for the
trainer (red), one for the trainee (green). These have been designed for use as an introductory
course to GLP. They are accompanied by a WHO/TDR Handbook on GLP (blue) which includes
an introduction to GLP, texts concerning the salient points of the GLP Principles and suggestions
on how to implement GLP in laboratories. The handbook also includes all 15 of the OECD
guidance documents on GLP. WHO/TDR is particularly grateful to the OECD for permission to
reproduce these documents in extenso.

This is the second editon of the WHO/TDR GLP Training Manual for Trainers. It is a support
document for the WHO Good Laboratory Practice (GLP) Training Programme. The training is
based on the Organization for Economic Cooperation and Development (OECD) GLP Principles
which are recognized as the international standard for GLP. The training is designed to be
conducted over a three-day period.
To facilitate the mutual acceptance of test data generated for submission to Regulatory
Authorities of OECD Member coun- tries, harmonization of the procedures adopted to monitor
good laboratory practice compliance, as well as comparability of their quality and rigour, are
essential. The aim of this docu- ment is to provide detailed practical guidance to OECD Member
countries on the structure, mechanisms and proce- dures they should adopt when establishing
national Good Lab- oratory Practice compliance monitoring programmes so that these
programmes may be internationally acceptable.

• The OECD has a definition for test facility management: “..the person(s) who has the authority
and formal responsibility for the organization and functioning of the test facility according to
these Principles of Good Laboratory Practice.” In fine, the test facility management is, therefore,
responsible for the implementation and the main- tenance of GLP within the laboratory for which
he/she is responsible.

Standards for good laboratory practices overlap with standards for good laboratory network
operations. Good laboratory practice principles are simply applied to laboratory facilities that
meet proper standards for testing, safety, and security; employ a trained and proficiency-tested
staff; have standardized operating procedures, validated test protocols, and properly functioning
equipment; and use a communication system that relies on common platforms and accurately and
reliably reports test results in a timely manner. Communication lines and logistics need to be
established before an event occurs.