Good manufacturing practice

Good manufacturing practices (GMP) are the practices required in order to conform to the guidelines recommended by agencies that control authorization and licensing for manufacture and sale of food, drug products, and active pharmaceutical products. These guidelines provide minimum requirements that a pharmaceutical or a food product manufacturer must meet to assure that the products are of high quality and do not pose any risk to the consumer or public.

Good manufacturing practices, along with good agricultural practices, good laboratory practices and good clinical practices, are overseen by regulatory agencies in the United States, Canada, Europe, China, and other countries.

High-level details

Good manufacturing practice guidelines provide guidance for manufacturing, testing, and quality assurance in order to ensure that a food or drug product is safe for human consumption. Many countries have legislated that food and pharmaceutical and medical device manufacturers follow GMP procedures and create their own GMP guidelines that correspond with their legislation.

All guidelines follow a few basic principles:

• Manufacturing facilities must maintain a clean and hygienic manufacturing area.
• Controlled environmental conditions in order to prevent cross contamination of food or drug product from adulterants that may render the product unsafe for human consumption.
• Manufacturing processes are clearly defined and controlled. All critical processes are validated to ensure consistency and compliance with specifications.
• Manufacturing processes are controlled, and any changes to the process are evaluated. Changes that affect the quality of the drug are validated as necessary.
• Instructions and procedures are written in clear and unambiguous language. (Good Documentation Practices)
• Operators are trained to carry out and document procedures.
• Cross contamination with unlabelled major allergens is prevented.
• Records are made, manually or by instruments, during manufacture that demonstrate that all the steps required by the defined procedures and instructions were in fact taken and that the quantity and quality of the food or drug was as expected. Deviations are investigated and documented.
• Records of manufacture (including distribution) that enable the complete history of a batch to be traced are retained in a comprehensible and accessible form.
• The distribution of the food or drugs minimizes any risk to their quality.
• A system is available for recalling any batch from sale or supply.
• Complaints about marketed products are examined, the causes of quality defects are investigated, and appropriate measures are taken with respect to the defective products and to prevent recurrence.

Practices are recommended with the goal of safeguarding the health of consumers and patients as well as producing good quality food, medicine, medical devices, or active pharmaceutical products. In the United States, a food or drug may be deemed "adulterated" if it has passed all of the specifications tests, but is found to be manufactured in a facility or condition which violates or does not comply with current good manufacturing guideline. Therefore, complying with GMP is mandatory in all pharmaceutical manufacturing, and most food processing.

GMP guidelines are not prescriptive instructions on how to manufacture products. They are a series of general principles that must be observed during manufacturing. When a company is setting up its quality program and manufacturing process, there may be many ways it can fulfil GMP requirements. It is the company's responsibility to determine the most effective and efficient quality process.

The quality is built into the product and GMP is the most essential part of ensuring this product quality.

Guideline versions

GMPs are enforced in the United States by the U.S. Food and Drug Administration (FDA), under Title 21 CFR. The regulations use the phrase "current good manufacturing practices" (cGMP) to describe these guidelines. Courts may theoretically hold that a product is adulterated even if there is no specific regulatory requirement that was violated as long as the process was not performed according to industry standards. Since June 2010, a different set of cGMP requirements have applied to all manufacturers of dietary supplements.^[1]

The World Health Organization (WHO) version of GMP is used by pharmaceutical regulators and the pharmaceutical industry in over one hundred countries worldwide, primarily in the developing world. The European Union's GMP (EU-GMP) enforces similar requirements to WHO GMP, as does the FDA's version in the US. Similar GMPs are used in other countries, with Australia, Canada, Japan, Saudi Arabia, Singapore, Philippines, Vietnam and others having highly developed/sophisticated GMP requirements. In the United Kingdom, the Medicines Act (1968) covers most aspects of GMP in what is commonly referred to as "The Orange Guide", which is named so because of the color of its cover; it is officially known as Rules and Guidance for Pharmaceutical Manufacturers and Distributors.^[2]

Since the 1999 publication of GMPs for Active Pharmaceutical Ingredients, by the International Conference on Harmonization (ICH), GMPs now apply in those countries and trade groupings that are signatories to ICH (the EU, Japan and the U.S.), and applies in other countries (e.g., Australia, Canada, Singapore) which adopt ICH guidelines for the manufacture and testing of active raw materials.

GMC is part of quality assurance which ensures that products are consistently produced and controlled to the quality standards appropriate to their intended use and as required by marketing authorization or product specification.

Enforcement

Within the European Union, GMP inspections are performed by National Regulatory Agencies (e.g., GMP inspections are performed in the United Kingdom by the Medicines and Healthcare Products Regulatory Agency (MHRA)); in the Republic of Korea (South Korea) by the Ministry of Food and Drug Safety (KFDA); in Australia by the Therapeutic Goods Administration (TGA); in Bangladesh by the Directorate General of Drug Administration (DGDA); in South Africa by the Medicines Control Council (MCC); in Brazil by the National Health Surveillance Agency (ANVISA); in India GMP inspections are carried out by state Food and Drugs Administrations (FDA) and these FDA report to the Central Drugs Standard Control Organization; in Pakistan by the Drug Regulatory Authority of Pakistan; in Nigeria by NAFDAC; and by similar national organisations worldwide. Each of the inspectorates carry out routine GMP inspections to ensure that drug products are produced safely and correctly; additionally, many countries perform pre-approval inspections (PAI) for GMP compliance prior to the approval of a new drug for marketing.

cGMP Software solution providers

Regulatory agencies (including the FDA in the U.S. and regulatory agencies in many European nations) are authorized to conduct unannounced inspections, though some are scheduled. FDA routine domestic inspections are usually unannounced, but must be conducted according to 704(a) of the FD&C Act (21 USCS § 374), which requires that they are performed at a "reasonable time". Courts have held that any time the firm is open for business is a reasonable time for an inspection.

Other good practices

Other good-practice systems, along the same lines as GMP, exist:

• Good agricultural practice (GAP), for farming and ranching
• Good laboratory practice (GLP), for laboratories conducting non-clinical studies (toxicology and pharmacology studies in animals)
• Good clinical practice (GCP), for hospitals and clinicians conducting clinical studies on new drugs in humans
• Good regulatory practice (GRP), for the management of regulatory commitments, procedures and documentation
• Good distribution practice (GDP) deals with the guidelines for the proper distribution of medicinal products for human use
• Good transportation practice (GTP) deals with the guidelines for the proper domestic and international transportation of medicinal products for human use
• Good pharmacovigilance practice (GVP) deals with the safety of produced drugs.

Collectively, these and other good-practice requirements are referred to as "GxP" requirements, all of which follow similar philosophies. (Other examples include good agriculture practices, good guidance practices, and good tissue practices.) In the U.S., medical device manufacturers must follow what are called "quality system regulations" which are deliberately harmonized with ISO requirements, not cGMPs.

See also

• Best practice
• Corrective and preventive action (CAPA)
• EudraLex
• Food safety
• Good Automated Manufacturing Practice (GAMP)
• Site master file (pharmaceuticals)

References

Sources

• 21 CFR Parts 210/211 Drug GMPs
• Pharma GMP Guidelines
• GMP Audit Checklist

External links

• FDA: Good Manufacturing Practices - United States
• Health Canada: Good Manufacturing Practices - Canada
• Pharmaceutical Inspection Cooperation Scheme: GMP Guides - 46 participating members
• MHRA Good Manufacturing Guide - United Kingdom
• Therapeutic Goods Association: Good Manufacturing Practices - Australia
• WHO: GMP Guidelines - World Health Organization
• EU: GMP Guidelines - European Union