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Good
Manufacturing Practice (GMP) is an international set of regulations, codes,
and guidelines by which drugs (known as medicinal products in Europe),
medical devices, diagnostic products, foods and Active Pharmaceutical
Ingredients (APIs) are manufactured. The purpose of
GMP is to ensure quality product. Since sampling
products will statistically only ensure that the samples themselves (and
perhaps the areas adjacent to where the samples were taken) are suitable for
use, and end-point testing relies on sampling,
GMP takes the holistic approach of regulating the production and laboratory
testing environment itself. An extremely
important part of GMPs is documenting every aspect of the process,
activities, and of operations. If the
documentation is not correct and in order, showing how the product was made
and tested, that allows for traceability, and recall from the market in the
event of future problems, then the product is considered contaminated (in
the US considered adulterated). The World
Health Organization (WHO) version of GMPs is used by pharmaceutical
regulators and the pharmaceutical industry in over 100 countries worldwide,
primarily in the developing world. In the European
Union, the EU-GMPs, with more compliance requirements than those stated in
the WHO GMPs, are in force; while in the USA, FDA's version of GMPs,
including requirements over and above those stated in the WHO document, are
enforced. Similar forms
of GMP are used in other countries, with Australia, Canada, Japan, Singapore
and others having highy developed/sophisticated GMP requirements. Since the
publication in 1999 by the International Conference on Harmonization (ICH)
of "GMPs for Active Pharmaceutical Ingredients", GMPs also apply in those
countries and trade groupings that are signatories to ICH (the EU, Japan and
the USA) and other countries who adopt ICH Guidelines (e.g. Australia,
Canada, Singapore) to the manufacture and testing of active raw materials. Other 'Good
Practice' systems, along the same lines as GMP, exist. "Good
Laboratory Practices" (GLP) for laboratories conducting non-clinical studies
(toxicology and pharmacology studies in animals); "Good Clinical
Practices" for hospitals and clinicians conducting clinical studies on new
drugs in humans; "Good
Distribution Practices" (GDP) for wholesalers and distributors. Collectively
these 'Good Practice' requirements, and others not mentioned here, are
referred to as 'GxP' requirements, and all follow similar philosophies. In the United
States, the FDA or Food and Drug Administration sets GMP policy through the
mechanism of the Federal Register, and numerous guidelines it releases to
industry. The US GMPs are
a combination of the legislation (principally 21CFR part 210 and 211),
current industry best practice and the current FDA thinking, as expressed in
FDA's publications of Guides and Guidelines, and other internal FDA
documentation such as Compliance Policy Guides (CPGs) and sections of the
Inspector Operations Manual (IOM). Consequently
GMP is always moving ahead as each company improves. The scope of
the US GMPs are defined in FDA regulations (21CFR210.1) where it states that
the regulations presented in the chapter are "the minimum current GMPs". As such FDA
admitted in 1976 when the present set of GMPs were drafted, that the
regulations are considered to be 'dynamic' and constantly under change as
new technologies, concepts, or influences happen. Because of this
the US GMPs are referred to as 'current GMPs' (or cGMPs). Unlike European
or other GMP codes, that are typically updated and re-issued every 5-7
years, the US GMPs have basically remained unchanged in text for 30 years,
FDA feeling no pressing need to make revisions, as the "minimum current"
concept applies. Contrary to
many other countries, FDA's deliberations and publications, including
internal publications, are subject to the US Freedom of Information Act,
meaning that almost all the FDA documents refered to above are available for
downloading on the internet. A key GMP
resource for the pharmaceutical industry is FDA Pharmaceutical Industry Web
Portal In Europe GMP
is defined in [Commission Directive] 2003/94/EC.
Guidelines have
been produced to assist manufacturers in complying, these are included in a
collection called Eudralex, available for downloading from the EU GMP
webpage. Although each
GMP code world-wide states similar concepts, there are key differences. In the GMPs of
the European Union, and of those countries that are members of the
Pharmaceutical Inspection Cooperation Scheme (PIC/S), responsibility for
ensuring that drug products are manufactured in accordance with the
manufacturing and testing methods registered with the authorities and that
GMPs have been complied with, rests with the Qualified Person (the QP) or
the Responsible Person (RP), who takes personal, and legal, responsibility
certifying that each batch of product has been produced according to the
marketing authorization and GMPs. In the United
States the responsibilities of the QP are vested with the company's Quality
Assurance (QA) group. In Europe and
the member countries of the PIC/S, personal and legal responsibility for
non-compliance to the marketing authorization and to GMPs rests with the QP;
who potentially faces fines and jail sentences for non-compliance. In the United
States final responsibility, and potential fines and jail sentences, rests
with the Chief Executive Office (CEO) of the company. |
