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The use of drug product is widespread and touches all aspects of our daily lives without our knowing it. From aspirin to cardiac medicine and from hormones in animal feed to over-the-counter dietary supplements, these products are used every day. What they all have in common are specific government regulations known as Good Manufacturing Practices established to ensure that the drug product is safe, pure, and effective. They intend to ensure that all aspects of manufacturing use proper science to ensure the integrity and validity of all information and data used. These regulations can all be found under their respective sections of the Code of Federal Regulations.
Routine medical laboratories involved in patient care are covered by well-defined international quality standards (ISO 15189) and national laws (42 CFR 493). In pharmaceutical research and development, only the nonclinical (not involving humans) laboratory safety studies are governed by the Good Laboratory Practices (GLP) regulations (21 CFR 58). No other well-defined quality standards exist for other so-called non-GLP laboratory research. This leads to the absurd situation that in a research laboratory, for example, a blood sample from a rabbit is theoretically subject to a stricter quality standard than a human sample. The FDA expects that “sound quality principles” are applied to the processing of human samples, but these principles are nowhere defined.
Because of the rapid progress of biological sciences, non-GLP laboratory research (e.g., biomarker development, exploratory, mechanistic studies, etc.) has become increasingly critical for modern drug development. Many research institutions are recognizing the need to establish solid quality standards to ensure the integrity and validity of the data they generate. But which standards to follow, and how to introduce them, is the big question.
Non-GLP biomedical research has traditionally been considered to be off-limits for formal quality systems or management. Scientists in general regard their work as a highly intellectual activity where quality is knowledge and experience is an integral part of the scientific rigor that they apply. A longstanding tradition of quality control in science has been peer review of the results, but modern pharmaceutical research has become so complex that peer review has a limited value today.
The scope and sheer dimension of modern research is moving science out of the individual scientist’s domain and into a globalized team space where standards, transparency, and reproducibility have become key requirements. Scientific work that cannot be reproduced by others is a waste of valuable, limited resources. Also, biomedical research generates intellectual property, which in the pharmaceutical industry accounts for a large share of the overall company value. Biomedical research has become increasingly subject to internal and external scrutiny and is often challenged as potential litigations. The authenticity and integrity of scientific data is therefore of utmost importance. To prove the authenticity and integrity of scientific data, studies and experiments must be conducted under controlled and verifiable conditions.
In the face of serious global health challenges in developed as well as developing countries, the World Health Organization (WHO) has become increasingly concerned that time and resources in biomedical research are often wasted because of insufficient quality practices. Currently only binding quality regulations for nonclinical laboratory safety studies (GLP) and clinical trials (good clinical practices, or GCP) exist. The WHO concluded that there is a pressing global need to provide minimum quality guidance for basic biomedical research not covered by GLP or GCP regulations.
In 2000, a scientific working group composed of independent scientific experts convened by the WHO drafted a guide outlining quality standards for biomedical research. The draft was reviewed by a group of experts from a wide range of scientific disciplines and finally published in 2005 under the title “Handbook: Quality Practices in Basic Biomedical Research.” The handbook describes basic quality requirements ranging from personnel and training to study plans, resources, documentation, and reporting. The overall objective is to ensure the validity and credibility of the scientific data obtained.
Driven by similar concerns as the WHO, the British Association of Research Quality Assurance (BARQA) convened a Working Party on Quality in Non-Regulated Research and published specific quality guidelines in 2006 for biomedical research laboratories that do not fall under GLP. The group recognized that the entire landscape of drug research and development is changing rapidly and that research not (yet) governed by GLP or GCP has become increasingly vital for the success of a pharmaceutical company. Low quality in this area can have disastrous consequences ranging from loss of intellectual property rights to costly repetition of work already performed.
There are many different organizations that interface with and provide quality input to various regulatory bodies. We proposed that the American Society for Quality (ASQ), as one of the largest quality organizations in the world, take up the initiative and develop a national quality standard for biomedical laboratory research in the United States. The success of this standard could potentially lead to an international ISO standard.
The proposal for the new quality standard is based on:
A quality standard based on statistical models and scientific design is important for the future of drug research worldwide. Implementation of a national quality standard for biomedical research would not only serve as a strong base for the entire drug development process, but reduce the waste of valuable resources and increase business productivity.
The United States is still the world’s center for biomedical research. The potential for ASQ to contribute to that legacy is exciting, as is the opportunity to further strengthen its role as a lead quality organization.
About the authors
Rick Calabrese is corporate North American quality assurance manager for Sartorius Group North America Corp. He has been involved with quality in the pharmaceutical industry for more than 20 years. Calabrese holds a bachelor’s degree in Geology and a master’s degree in industrial management, both from SUNY Stony Brook in New York. Calabrese started his career in the laboratory working as a quality control analyst. He also worked briefly in manufacturing and regulatory affairs before spending the past 10 years in quality assurance. He has more 12 years of experience in performing internal and external audits. At a position just prior to working at Sartorius, Calabrese was the quality assurance lead on the facility and equipment qualification of a 103,000-square foot clinical manufacturing facility located on Long Island, New York. He is an active member of the American Society for Quality and is currently chairman of the regional councilor program for the FD&C division for ASQ, as well as the chairman for the Long Island section.
Ăślo Palm, M.D., Ph.D., MBA, ASQ-CMQ/OE, is currently global head laboratory and preclinical quality assurance for Novartis Pharmaceuticals Corp. He's responsible for developing and maintaining a quality strategy for all Novartis exploratory development and preclinical laboratories worldwide. He joined Novartis in 2002 as the global head clinical operations oncology business unit, where he was in charge of multiple global line functions including trial allocation and monitoring, data management, biostatistics, and operations. Before joining Novartis, Dr. Palm worked with Schering-Plough and Bayer in different operational and medical drug development functions. He has a total of 18 years of experience in the pharmaceutical industry. Dr. Palm earned his M.D. (clinical training in internal medicine, neurology, surgery) in 1986 from the University of Berlin, where he also received postgraduate research training as a medical scientist, which he completed with a Ph.D. in medical research in 1990. In 1995, he earned an MBA degree with a major in information technology/computer science from the AKAD University for Applied Science in Rendsburg, Germany. In 2008, he got certified as a manager of quality and organizational excellence by ASQ.
Dr. Palm’s vision is to expedite drug development by linking top medical science to operational excellence and 21st century technology.  He is author and co-author of a number of scientific articles in international journals and holder of two medical patents.