Beyond GMPs: The Latest Approaches to Good Manufacturing Practices

Nov 15, 2004

GMP is the acronym for Good Manufacturing Practice. The GMPs represent a set of regulations that were promulgated as a final rule by FDA in 1978 and intended to ensure the safety and efficacy of the nation's drug products. The GMPs, as we know them today, are the result of over a century of actions by industry and reactions by government and consumer groups to bring guidance and controls to the food and drug industry, resulting in a safe supply of food and medicines. GMP compliance is the foundation of the pharmaceutical industry and has become the benchmark for success of any enterprise involved in the development, manufacture or testing of human and animal drug products. Often, the prefix c is used to indicate cGMPs. The c stands for current and raises regulatory expectations beyond the stated regulations to include current, state-of-the-industry standards.

Without robust quality systems supporting the manufacture, testing, and distribution of pharmaceuticals, our society, as we know it could not survive. When patients use medicines, they do so with the implicit knowledge that entire organizations went to painstaking efforts and extremes to ensure that the drugs are of the utmost quality. The GMP regulations far surpass the Hippocratic oath's requirement to "First Do No Harm," by requiring process and laboratory controls, verification and approvals, quality controls, structure and organization, material management, validation, and accurate documentation of these and other requirements. These controls are intended to ensure safe, pure and efficacious medicines are produced and available to patients in need.

Besides patients, hundreds of thousands of government and private sector employees depend on the pharmaceutical manufacturing industry for their jobs and careers. Shareholders expect regulatory compliance to protect their investment. Countries depend upon the industry for the health of their citizens. Companies that cannot meet GMP requirements routinely suffer severe financial penalties in fines, lost revenue, and damage to their reputations.

Requirements Industry personnel and government regulators involved in the research, production, and regulation of pharmaceutical products constitute society's most talented, dedicated workforce, devoted to their cause of helping mankind through the discovery and manufacture of medicines that cure and mitigate disease. The pharmaceutical industry is an intense, stringent, and competitive industry by nature. It is currently under extreme social and political pressure to deliver new medicines faster and cheaper. Existing regulations are being interpreted more conservatively and penalties for noncompliance — even for small errors — are at their highest in history.

People are not perfect, including the people who conduct the clinical studies, write the dossiers for submission and approval, obtain materials, and manufacture and package the medicines we consume. Good intentions can succumb to honest error, speed-to-market can lead to taking risky short cuts, and ambiguous data can be interpreted as acceptable. Regulations are necessary to provide a minimal guideline for ethics and acceptability. Without the GMPs, we would have chaos, and there would be no system to assess medicines.

Enforcement Enforcement of the GMPs is essential. FDA currently assesses acceptability of a drug product through its application review and facility inspection process. Reviewers at various centers evaluate scientific merit and supporting evidence, and field investigators perform onsite investigations to assure the information submitted in the application is authentic. Field investigators also perform an evaluation of the manufacturing environment, equipment, controls, procedures, and personnel. All of this is accomplished, in large part, by reviewing required documentation.

The number of domestic establishments FDA is required to regulate exceeds 120,000. Annual imports to the US number nearly 8 million shipments of FDA-regulated products from about 500,000 foreign manufacturers. Many of these foreign facilities have never received an FDA inspection.1 The agency is also being ordered by Congress to address even more complex issues, including bioterrorism, mad cow disease, foreign pharmacy imports, counterfeiting, and product diversion and tampering. Domestic and international regulatory agencies and customer expectations continue to demand increased compliance and consistent quality.