Good manufacturing practice

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Good manufacturing practices (GMP) are the practices required in order to conform to the guidelines recommended by agencies that control the authorization and licensing of the manufacture and sale of food and beverages, [1] cosmetics, [2] pharmaceutical products, [3] dietary supplements, [4] and medical devices. [5] These guidelines provide minimum requirements that a manufacturer must meet to assure that their products are consistently high in quality, from batch to batch, for their intended use. The rules that govern each industry may differ significantly; however, the main purpose of GMP is always to prevent harm from occurring to the end user. [2] Additional tenets include ensuring the end product is free from contamination, that it is consistent in its manufacture, that its manufacture has been well documented, that personnel are well trained, and the product has been checked for quality more than just at the end phase. [2] GMP is typically ensured through the effective use of a quality management system (QMS). [1] [2]

Food industry collective of diverse businesses that supplies much of the worlds food

The food industry is a complex, global collective of diverse businesses that supplies most of the food consumed by the world's population. Only subsistence farmers, those who survive on what they grow, and hunter-gatherers can be considered outside the scope of the modern food industry.

Cosmetics substances used to enhance the appearance or odor of the human body

Cosmetics are substances or products used to enhance or alter the appearance of the face or fragrance and texture of the body. Many cosmetics are designed for use of applying to the face and body. They are generally mixtures of chemical compounds derived from natural sources, or may be synthetic or artificial. Cosmetics that are applied to the face to enhance one's appearance may be called makeup which include lipstick, mascara, eye shadow, foundation, blush, and bronzer, among other products.

Medication substance used to diagnose, cure, treat, or prevent disease

A medication is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy (pharmacotherapy) is an important part of the medical field and relies on the science of pharmacology for continual advancement and on pharmacy for appropriate management.

Contents

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

Good agricultural practice (GAP) are specific methods which, when applied to agriculture, create food for consumers or further processing that is safe and wholesome. While there are numerous competing definitions of what methods constitute good agricultural practice there are several broadly accepted schemes that producers can adhere to.

In the experimental (non-clinical) research arena, good laboratory practice or GLP is a quality system of management controls for research laboratories and organizations to ensure the uniformity, consistency, reliability, reproducibility, quality, and integrity of chemical non-clinical safety tests; from physio-chemical properties through acute to chronic toxicity tests.

Good clinical practice (GCP) is an international quality standard for conducting clinical trials that in some countries is provided by ICH, an international body that defines a set of standards, which governments can then transpose into regulations for clinical trials involving human subjects. In the European Union, Good Clinical Practice is backed and regulated by formal legislation contained in the Clinical Trial Directive. A similar guideline for clinical trials of medical devices is the international standard ISO 14155, which is valid in the European Union as a harmonized standard. These standards for clinical trials are sometimes referred to as ICH-GCP or ISO-GCP to differentiate between the two and the lowest grade of recommendation in clinical guidelines.

High-level details

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

All guideline follows a few basic principles [2] [6] :

Contamination is the presence of a constituent, impurity, or some other undesirable element that soils, corrupts, infects, makes unfit, or makes inferior a material, physical body, natural environment, workplace, etc.

Validation is the process of establishing documentary evidence demonstrating that a procedure, process, or activity carried out in testing and then production maintains the desired level of compliance at all stages. In the pharmaceutical industry, it is very important that in addition to final testing and compliance of products, it is also assured that the process will consistently produce the expected results. The desired results are established in terms of specifications for outcome of the process. Qualification of systems and equipment is therefore a part of the process of validation. Validation is a requirement of food, drug and pharmaceutical regulating agencies such as the US FDA and their good manufacturing practices guidelines. Since a wide variety of procedures, processes, and activities need to be validated, the field of validation is divided into a number of subsections including the following:

Good documentation practice is a term in the pharmaceutical and medical device industries to describe standards by which documents are created and maintained. While some GDP / GDocP standards are codified by various competent authorities, others are not but are considered cGMP. Some competent authorities release or adopt guidelines, and they may include non-codified GDP / GDocP expectations. While not law, authorities will inspect against these guidelines and cGMP expectations in addition to the legal requirements and make comments or observations if departures are seen. In the past years, the application of GDocP is also expanding to cosmetic industry, excipient and ingredient manufacturers.

Good manufacturing practices are recommended with the goal of safeguarding the health of consumers and patients as well as producing quality 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.

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 that both meets business and regulatory needs. [1] [2]

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. [7] [8] [9] [10] 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. [11] However, since June 2007, a different set of CGMP requirements have applied to all manufacturers of dietary supplements, with additional supporting guidance issued in 2010. [4] Additionally, in the U.S., medical device manufacturers must follow what are called "quality system regulations" which are deliberately harmonized with ISO requirements, not necessarily CGMPs. [9]

Food and Drug Administration agency of the United States Department of Health and Human Services

The Food and Drug Administration is a federal agency of the United States Department of Health and Human Services, one of the United States federal executive departments. The FDA is responsible for protecting and promoting public health through the control and supervision of food safety, tobacco products, dietary supplements, prescription and over-the-counter pharmaceutical drugs (medications), vaccines, biopharmaceuticals, blood transfusions, medical devices, electromagnetic radiation emitting devices (ERED), cosmetics, animal foods & feed and veterinary products.

Dietary supplement product that provides additional source of nutrients

A dietary supplement is a manufactured product intended to supplement the diet when taken by mouth as a pill, capsule, tablet, or liquid. A supplement can provide nutrients either extracted from food sources or synthetic, individually or in combination, in order to increase the quantity of their consumption. The class of nutrient compounds includes vitamins, minerals, fiber, fatty acids and amino acids. Dietary supplements can also contain substances that have not been confirmed as being essential to life, but are marketed as having a beneficial biological effect, such as plant pigments or polyphenols. Animals can also be a source of supplement ingredients, as for example collagen from chickens or fish. These are also sold individually and in combination, and may be combined with nutrient ingredients. In the United States and Canada, dietary supplements are considered a subset of foods, and are regulated accordingly. The European Commission has also established harmonized rules to help insure that food supplements are safe and properly labeled.

International Organization for Standardization An international standard-setting body composed of representatives from national organizations for standards

The International Organization for Standardization is an international standard-setting body composed of representatives from various national standards organizations.

The World Health Organization (WHO) version of GMP is used by pharmaceutical regulators and the pharmaceutical industry in over 100 countries worldwide, primarily in the developing world. [3] 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. [12] 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. [13]

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. [12]

Enforcement

Within the European Union GMP inspections are performed by National Regulatory Agencies. GMP inspections are performed in Canada by the Health Products and Food Branch Inspectorate; [14] the United Kingdom by the Medicines and Healthcare Products Regulatory Agency (MHRA); [15] in the Republic of Korea (South Korea) by the Ministry of Food and Drug Safety (MFDS); [16] in Australia by the Therapeutic Goods Administration (TGA); [17] in Bangladesh by the Directorate General of Drug Administration (DGDA); [18] ; in South Africa by the Medicines Control Council (MCC); [19] in Brazil by the National Health Surveillance Agency (ANVISA); [20] in India by state Food and Drugs Administrations (FDA), reporting to the Central Drugs Standard Control Organization; [21] in Pakistan by the Drug Regulatory Authority of Pakistan; [22] in Nigeria by NAFDAC; [23] and by similar national organizations worldwide. Each of the inspectorates carries 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 inspections

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. [7] [13] [16] [17] [18] [19] [21] [22] [23] FDA routine domestic inspections are usually unannounced, but must be conducted according to 704(a) of the Food, Drug and Cosmetic 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. [24]

Other good practices

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

Collectively, these and other good-practice requirements are referred to as "GxP" requirements, all of which follow similar philosophies. Other examples include good guidance practices, and good tissue practices.

See also

Related Research Articles

Ranbaxy Laboratories Limited was an Indian pharmaceutical company that was incorporated in India in 1961 and remained an entity until 2014. The company went public in 1973. Ownership of Ranbaxy changed twice over the course of its history. In 2008, Japanese pharmaceutical company Daiichi Sankyo acquired a controlling share in Ranbaxy and in 2014, Sun Pharma acquired 100% of Ranbaxy in an all-stock deal. The Sun Pharma acquisition brought all new management to Ranbaxy, which had been laden with controversy. Sun is the world's fifth largest specialty generic pharmaceutical company.

GxP is a general abbreviation for the "good practice" quality guidelines and regulations. The "x" stands for the various fields, including the pharmaceutical and food industries, for example good agricultural practice, or GAP.

Regulation of therapeutic goods

The regulation of therapeutic goods, defined as drugs and therapeutic devices, varies by jurisdiction. In some countries, such as the United States, they are regulated at the national level by a single agency. In other jurisdictions they are regulated at the state level, or at both state and national levels by various bodies, as in Australia.

Title 21 is the portion of the Code of Federal Regulations that governs food and drugs within the United States for the Food and Drug Administration (FDA), the Drug Enforcement Administration (DEA), and the Office of National Drug Control Policy (ONDCP).

"Good engineering practice" or "GEP" is engineering and technical activities that ensure that a company manufactures products of the required quality as expected. Good engineering practices are to ensure that the development and/or manufacturing effort consistently generates deliverables that support the requirements for qualification or validation. Good engineering practices are applied to all industries that require engineering.

Good automated manufacturing practice (GAMP) is both a technical subcommittee of the International Society for Pharmaceutical Engineering (ISPE) and a set of guidelines for manufacturers and users of automated systems in the pharmaceutical industry. More specifically, the ISPE's guide The Good Automated Manufacturing Practice (GAMP) Guide for Validation of Automated Systems in Pharmaceutical Manufacture describes a set of principles and procedures that help ensure that pharmaceutical products have the required quality. One of the core principles of GAMP is that quality cannot be tested into a batch of product but must be built into each stage of the manufacturing process. As a result, GAMP covers all aspects of production; from the raw materials, facility and equipment to the training and hygiene of staff. Standard operating procedures (SOPs) are essential for processes that can affect the quality of the finished product.

Clinical quality management systems (CQMS) are systems used in the life sciences sector designed to manage quality management best practices throughout clinical research and clinical study management. A CQMS system is designed to manage all of the documents, activities, tasks, processes, quality events, relationships, audits and training that must be administered and controlled throughout the life of a clinical trial. The premise of a CQMS is to bring together the activities led by two sectors of clinical research, Clinical Quality and Clinical Operations, to facilitate cross-functional activities to improve efficiencies and transparency and to encourage the use of risk mitigation and risk management practices at the clinical study level.

Quality by Design (QbD) is a concept first outlined by quality expert Joseph M. Juran in publications, most notably Juran on Quality by Design. Designing for quality and innovation is one of the three universal processes of the Juran Trilogy, in which Juran describes what is required to achieve breakthroughs in new products, services, and processes. Juran believed that quality could be planned, and that most quality crises and problems relate to the way in which quality was planned.

The U.S. Food and Drug Administration (FDA) is authorized to perform inspections under the Federal Food, Drug, and Cosmetic Act, Sec. 704 "Factory Inspection". Form FDA 483, "Inspectional Observations," is a form used by the FDA to document and communicate concerns discovered during these inspections. Also referred to as "Form 483" or merely "483", it states thereon that it

... lists observations made by the FDA representative(s) during the inspection of your facility. They are inspectional observations, and do not represent a final Agency determination regarding your compliance

An FDA warning letter is an official message from the United States Food and Drug Administration (FDA) to a manufacturer or other organization that has violated some rule in a federally regulated activity.

Pharmaceutical fraud involves activities that result in false claims to insurers or programs such as Medicare in the United States or equivalent state programs for financial gain to a pharmaceutical company. There are several different schemes used to defraud the health care system which are particular to the pharmaceutical industry. These include: Good Manufacturing Practice (GMP) Violations, Off Label Marketing, Best Price Fraud, CME Fraud, Medicaid Price Reporting, and Manufactured Compound Drugs. Examples of fraud cases include the GlaxoSmithKline $3 billion settlement, Pfizer $2.3 billion settlement, and Merck $650 million settlement. Damages from fraud can be recovered by use of the False Claims Act, most commonly under the qui tam provisions which rewards an individual for being a "whistleblower", or relator (law).

Pharmaceuticals and Medical Devices Agency administrative agency in Japan

The Pharmaceuticals and Medical Devices Agency is a Japanese governmental organization, similar in function to the Food and Drug Administration (FDA) in the United States or the Medicines and Healthcare products Regulatory Agency in the United Kingdom or the Central Drugs Standard Control Organization (CDSCO) in India or the European Medicines Agency in Europe.

Process validation is the analysis of data gathered throughout the design and manufacturing of a product in order to confirm that the process can reliably output products of a determined standard. Regulatory authorities like EMA and FDA have published guidelines relating to process validation. The purpose of process validation is to ensure varied inputs lead to consistent and high quality outputs. Process validation is an ongoing process that must be frequently adapted as manufacturing feedback is gathered. End-to-end validation of production processes is essential in determining product quality because quality cannot always be determined by finished-product inspection. Process validation can be broken down into 3 steps: process design, process qualification, and continued process verification.

Guidances for statistics in regulatory affairs are applicable to the pharmaceutical industry and medical devices industry. These Guidances represent the current thinking of regulatory agencies on a particular subject. It is to be noted that the term “Guidances” is used in the USA, whereas the term “Guidelines” is used in Europe.

Drug distribution is the process by means of which people get access to medication.

References

  1. 1 2 3 Institute of Food Science & Technology (2012). Food and Drink - Good Manufacturing Practice - A Guide to its responsible management. Wiley-Blackwell. p. 280. ISBN   9781118318232.
  2. 1 2 3 4 5 6 Moore, I. (2009). "Chapter 5: Manufacturing Cosmetic Ingredients According to Good Manufacturing Principles". In Lintner, K. (ed.). Global Regulatory Issues for the Cosmetic Industry. Elsevier. pp. 79–92. ISBN   9780815519645.
  3. 1 2 Nally, J.D., ed. (2007). Good Manufacturing Practices for Pharmaceuticals (6th ed.). CRC Press. p. 424. ISBN   9781420020939.
  4. 1 2 "Guidance for Industry: Current Good Manufacturing Practice in Manufacturing, Packaging, Labeling, or Holding Operations for Dietary Supplements; Small Entity Compliance Guide". U.S. Food and Drug and Administration. 12 November 2017. Retrieved 2 February 2018.
  5. Ramakrishna, S.; Tian, L.; Wang, C.; et al., eds. (2015). "Chapter 3.: Quality management systems for medical device manufacture". Medical Devices: Regulations, Standards and Practices. Woodhead Publishing Series in Biomaterials. 103. Elsevier. pp. 49–64. ISBN   9780081002919.
  6. World Health Organization (2007). "Chapter 1: WHO good manufacturing practices: Main principles for pharmaceutical products". Quality Assurance of Pharmaceuticals: A compendium of guidelines and related materials - Good manufacturing practices and inspection. 2 (2nd updated ed.). WHO Press. pp. 17–18. ISBN   9789241547086.
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  14. "Good Manufacturing Practices". Health Canada. Government of Canada. 27 February 2015. Retrieved 2 February 2018.
  15. Medicines and Healthcare Products Regulatory Agency (20 October 2017). "Good manufacturing practice and good distribution practice". Gov.uk. Retrieved 2 February 2018.
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  19. 1 2 Medicines Control Council (August 2010). "Guide to Good Manufacturing Practice for Medicines in South Africa" (PDF). Medicines Control Council. Retrieved 2 February 2018.
  20. World Trade Organization (13 May 2015). "Draft Technical Resolution nº 42, May 13th 2015" (PDF). Retrieved 2 February 2018.
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