Good Manufacturing Practice
Encyclopedia
"Good manufacturing practice" or "GMP" are practices and the systems required to be adapted in pharmaceutical manufacturing, quality control, quality system covering the manufacture and testing of pharmaceuticals or drugs including active pharmaceutical ingredients, diagnostics, foods, pharmaceutical products, and medical devices. GMPs are guidance that outline the aspects of production and testing that can impact the quality of a product. Many countries have legislated that pharmaceutical and medical device companies must follow GMP procedures, and have created their own GMP guidelines that correspond with their legislation. Basic concepts of all of these guidelines remain more or less similar to the ultimate goals of safeguarding the health of the patient as well as producing good quality medicine, medical devices or active pharmaceutical products. In the U.S. a drug may be deemed adulterated if it passes all of the specifications tests but is found to be manufactured in a condition which violates current good manufacturing guidelines. Therefore, complying with GMP is a mandatory aspect in pharmaceutical manufacturing.
Although there are a number of them, all guidelines follow a few basic principles.
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 fulfill GMP requirements. It is the company's responsibility to determine the most effective and efficient quality process.
351). The regulations use the phrase "current good manufacturing practices" (cGMP) to describe these guidelines. Courts may theoretically hold that a drug 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. As of June 2010, a different set of cGMP requirements apply to all manufacturers of dietary supplements.
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 Food and Drug Administration
's version in the US. Similar GMPs are used in other countries, with Australia
, Canada
, Japan
, Singapore
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.
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.
(MHRA)); in the Republic of Korea (South Korea) by the Korea Food & Drug Administration
(KFDA); in Australia by the Therapeutical Goods Administration (TGA); in South Africa by the Medicines Control Council (MCC); in Brazil by the Agência Nacional de Vigilância Sanitária
(National Health Surveillance Agency Brazil) (ANVISA); in Iran
, in India
gmp inspections are carried out by state FDA and these FDA report to Central Drugs Standard Control Organization and Pakistan
by the Ministry of Health;, Nigeri has NAFDAC and by similar national organisations worldwide. Each of the inspectorate
s 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.
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 (21USC374), 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.
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.
Although there are a number of them, all guidelines follow a few basic principles.
- 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 have an impact on the quality of the drug are validated as necessary.
- Instructions and procedures are written in clear and unambiguous language. (Good Documentation PracticeGood Documentation PracticeGood Documentation Practice is a term in the pharmaceutical industry to describe standards by which documents are created and maintained. While some GDP standards are codified by various competent authorities, others are not but are considered cGMP...
s) - Operators are trained to carry out and document procedures.
- 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 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 drugs minimizes any risk to their quality.
- A system is available for recalling any batch of drug from sale or supply.
- Complaints about marketed drugs are examined, the causes of quality defects are investigated, and appropriate measures are taken with respect to the defective drugs and to prevent recurrence.
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 fulfill GMP requirements. It is the company's responsibility to determine the most effective and efficient quality process.
Guideline versions
GMPs are enforced in the United States by the US FDA, under Section 501(B) of the 1938 Food, Drug, and Cosmetic Act (21USCUnited States Code
The Code of Laws of the United States of America is a compilation and codification of the general and permanent federal laws of the United States...
351). The regulations use the phrase "current good manufacturing practices" (cGMP) to describe these guidelines. Courts may theoretically hold that a drug 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. As of June 2010, a different set of cGMP requirements apply to all manufacturers of dietary supplements.
The World Health Organization
World Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...
(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
European Union
The European Union is an economic and political union of 27 independent member states which are located primarily in Europe. The EU traces its origins from the European Coal and Steel Community and the European Economic Community , formed by six countries in 1958...
's GMP (EU-GMP) enforces similar requirements to WHO GMP, as does the Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
's version in the US. Similar GMPs are used in other countries, with Australia
Australia
Australia , officially the Commonwealth of Australia, is a country in the Southern Hemisphere comprising the mainland of the Australian continent, the island of Tasmania, and numerous smaller islands in the Indian and Pacific Oceans. It is the world's sixth-largest country by total area...
, Canada
Canada
Canada is a North American country consisting of ten provinces and three territories. Located in the northern part of the continent, it extends from the Atlantic Ocean in the east to the Pacific Ocean in the west, and northward into the Arctic Ocean...
, Japan
Japan
Japan is an island nation in East Asia. Located in the Pacific Ocean, it lies to the east of the Sea of Japan, China, North Korea, South Korea and Russia, stretching from the Sea of Okhotsk in the north to the East China Sea and Taiwan in the south...
, Singapore
Singapore
Singapore , officially the Republic of Singapore, is a Southeast Asian city-state off the southern tip of the Malay Peninsula, north of the equator. An island country made up of 63 islands, it is separated from Malaysia by the Straits of Johor to its north and from Indonesia's Riau Islands by the...
and others having highly developed/sophisticated GMP requirements. In the United Kingdom
United Kingdom
The United Kingdom of Great Britain and Northern IrelandIn the United Kingdom and Dependencies, other languages have been officially recognised as legitimate autochthonous languages under the European Charter for Regional or Minority Languages...
, 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.
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
Japan
Japan is an island nation in East Asia. Located in the Pacific Ocean, it lies to the east of the Sea of Japan, China, North Korea, South Korea and Russia, stretching from the Sea of Okhotsk in the north to the East China Sea and Taiwan in the south...
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.
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 AgencyMedicines and Healthcare products Regulatory Agency
The Medicines and Healthcare products Regulatory Agency is the UK government agency which is responsible for ensuring that medicines and medical devices work and are acceptably safe....
(MHRA)); in the Republic of Korea (South Korea) by the Korea Food & Drug Administration
Korea Food & Drug Administration
The Korea Food & Drug Administration is a South Korea government agency responsible for promoting the public health by ensuring the safety and efficiency of foods, pharmaceuticals, medical devices and cosmetics as well as supporting the development of the food and pharmaceutical industries...
(KFDA); in Australia by the Therapeutical Goods Administration (TGA); in South Africa by the Medicines Control Council (MCC); in Brazil by the Agência Nacional de Vigilância Sanitária
National Health Surveillance Agency
The National Health Surveillance Agency is an autonomous organ of the government of Brazil. It is "an independently administered, financially-autonomous regulatory agency, with security of tenure for its directors during the period of their mandates...
(National Health Surveillance Agency Brazil) (ANVISA); in Iran
Iran
Iran , officially the Islamic Republic of Iran , is a country in Southern and Western Asia. The name "Iran" has been in use natively since the Sassanian era and came into use internationally in 1935, before which the country was known to the Western world as Persia...
, in India
India
India , officially the Republic of India , is a country in South Asia. It is the seventh-largest country by geographical area, the second-most populous country with over 1.2 billion people, and the most populous democracy in the world...
gmp inspections are carried out by state FDA and these FDA report to Central Drugs Standard Control Organization and Pakistan
Pakistan
Pakistan , officially the Islamic Republic of Pakistan is a sovereign state in South Asia. It has a coastline along the Arabian Sea and the Gulf of Oman in the south and is bordered by Afghanistan and Iran in the west, India in the east and China in the far northeast. In the north, Tajikistan...
by the Ministry of Health;, Nigeri has NAFDAC and by similar national organisations worldwide. Each of the inspectorate
Inspectorate
An Inspectorate or Inspectorate-General is a civil or military body charged with inspecting and reporting on some institution or institutions in its field of competence...
s 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.
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 (21USC374), 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 laboratory practiceGood Laboratory PracticeIn the experimental research arena, the phrase good laboratory practice or GLP specifically refers to a quality system of management controls for research laboratories and organizations to try to ensure the uniformity, consistency, reliability, reproducibility, quality, and integrity of chemical ...
(GLP), for laboratories conducting non-clinical studiesClinical trialClinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...
(toxicologyToxicologyToxicology is a branch of biology, chemistry, and medicine concerned with the study of the adverse effects of chemicals on living organisms...
and pharmacologyPharmacologyPharmacology is the branch of medicine and biology concerned with the study of drug action. More specifically, it is the study of the interactions that occur between a living organism and chemicals that affect normal or abnormal biochemical function...
studies in animals); - Good clinical practiceGood clinical practiceGood Clinical Practice is an international quality standard that is provided by International Conference on Harmonisation , an international body that defines standards, which governments can transpose into regulations for clinical trials involving human subjects.Good Clinical Practice guidelines...
(GCP), for hospitalHospitalA hospital is a health care institution providing patient treatment by specialized staff and equipment. Hospitals often, but not always, provide for inpatient care or longer-term patient stays....
s 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 PracticeGood distribution practiceGood Distribution Practice deals with the guidelines for the proper distribution of medicinal products for human use. GDP is a quality warranty system, which includes requirements for purchase, receiving, storage and export of drugs intended for human consumption.GDP regulates the division and...
(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
Collectively, these and other good-practice requirements are referred to as "GxP
GxP
GxP is a general term for Good Practice quality guidelines and regulations. These guidelines are used in many fields, including the pharmaceutical and food industries....
" 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
- Corrective and preventive actionCorrective and preventive actionCorrective action and preventive action are improvements to an organization's processes taken to eliminate causes of non-conformities or other undesirable situations. CAPA is a concept within good manufacturing practice...
(CAPA) - EudraLexEudraLexEudraLex is the collection of rules and regulations governing medicinal products in the European Union.-Volumes:EudraLex consists of 10 volumes:*Concerning Medicinal Products for Human use:**Volume 1 - Pharmaceutical Legislation....
- Food safetyFood safetyFood safety is a scientific discipline describing handling, preparation, and storage of food in ways that prevent foodborne illness. This includes a number of routines that should be followed to avoid potentially severe health hazards....
- Good Automated Manufacturing PracticeGood Automated Manufacturing PracticeGood Automated Manufacturing Practice is a trademark of the International Society for Pharmaceutical Engineering . The ISPE's guide The Good Automated Manufacturing Practice Guide for Validation of Automated Systems in Pharmaceutical Manufacture describes a set of principles and procedures that...
(GAMP) - Packaging
- Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation SchemePharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation SchemeThe Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation Scheme are two international instruments between countries and pharmaceutical inspection authorities...
- Validation (drug manufacture)Validation (drug manufacture)Validation in the pharmaceutical, medical device, food, blood establishments, tissue establishments, and clinical trials industries is defined as the documented act of demonstrating that a procedure, process, and activity will consistently lead to the expected results. It often includes the...
- Verification and validationVerification and ValidationIn software project management, software testing, and software engineering, verification and validation is the process of checking that a software system meets specifications and that it fulfills its intended purpose...