GLPs and the Importance of Standard Operating Procedures

Aug 01, 2003
Volume 16, Issue 8

Good laboratory practice (GLP) is a standard by which laboratory studies are designed, implemented, and reported to assure the public that the results are correct and the experiment can be reproduced exactly, at any time in the future. In less technical terms, GLP is the cornerstone of all laboratory-based activities in any organization that prides itself on the quality of the work it performs. And, despite its immediate association with the pharmaceutical sector (Figure 1), GLPs can (and should) be applied to virtually all industries in which laboratory work is performed, including companies involved in drug manufacturing, food and drink production, and engineering. In addition, commercial testing laboratories (for toxicology, metabolism, materials and safety, for example), research establishments, and universities - in fact, all laboratories engaged in product or safety testing or research and development - should adopt and apply the doctrines of GLP.

GLP is not a luxury. It is a necessity for any professional laboratory wishing to gain and retain the respect of its employees, clients, regulators and perhaps most importantly, its competitors. If a company is seen to be applying and adhering to the highest standards of laboratory practice, it will gain significant competitive advantage and will compete successfully for business and recognition within its operational environment. Conversely, without rigidly enforced GLPs - and good manufacturing practices (GMPs) - a scientific organization will not achieve the commercial success and respect that its products and personnel deserve.

Figure 1. The ubiquitous nature of GLPs in the pharmaceutical industry (adapted from Edwards and Murji, 2001, see reading list).
A Brief History of GLP Up until the early 1970s, many private and public laboratories applied GLP-type principles in one form or another. Repeat-dose safety studies involving a variety of techniques concerned with animal handling, dosing, and observation were regularly conducted. In 1972, New Zealand formally introduced GLP as the Testing Laboratory Registration Act, which covered staff records, procedures, equipment, and facilities. The act prompted the establishment of a related council "to promote the development and maintenance of GLP in testing." In the same year, Denmark also introduced a law to promote GLP.

Significant events took place in 1975 when Senator Edward Kennedy (Dem-MA) and members of FDA made allegations against research laboratories in the USA (Searle and Hazelton) related to preclinical research studies. Both sites were subsequently investigated, which revealed serious problems with the conduct of safety studies submitted to the agency. Violations included poor record keeping and data storage, inadequate personnel training, poor test facility management, and even fraud.

Our Laboratories, Inc.
By January 1986, scientists at Searle had developed a document, Good Laboratory Practice, which was designed to be used as guidance to evaluate research activities, and submitted it to both FDA and the Pharmaceutical Research and Manufacturers Association of America (PhRMA). In August of the same year, FDA released a draft GLP document based on the Searle paper and published GLP regulations in the Federal Register. At the same time, the agency was creating 606 new positions to monitor biological research, and it also began a pilot inspection program to establish baseline levels of competence. Items listed as "major failings" included failure to have a quality assurance (QA) department, failure to test every batch of manufactured product, and failure to maintain standard operating procedures (SOPs).

In December 1978, FDA published final GLP regulations and made compliance with them the law in the United States in June 1979. These regulations were collected in Title 21: "Food and Drugs" of the Code of Federal Regulations (CFR) as Part 58: "Good Laboratory Practice for Nonclinical Laboratory Studies," and they applied to all nonclinical safety studies intended to support research permits or marketing authorizations of products regulated by FDA. Subsequently, FDA's Office of Regulatory Affairs (ORA) released two Guidance for Industry documents to ensure the proper and consistent interpretation of the directives by industry and by FDA's field investigators. Further changes to the GLP rules were proposed in 1984, and in September 1987, FDA published its "Final Rule" - Compliance Program Bioresearch Monitoring: Good Laboratory Practices, which was expanded to incorporate the following:

  • the requirement for a QA department
  • the requirement for protocol preparation (study plan)
  • the characterization of test and control materials
  • the requirement to retain specimens and samples.

Since then, the requirement for laboratories to apply and comply with GLP principles has extended from pharmaceutical companies to many other types of research and testing establishments throughout the developed world. In Europe, adherence to the principles of GLP is governed by European Union (EU) law and, in compliance with EU Directives, an inspection program confirms that "toxicological studies for the regulatory assessment of industrial chemicals, medicines, veterinary medicines, food and animal feed additives, cosmetics, and pesticides must be conducted in accordance with GLP."

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