Within certain industries, manufacturers are subject to strict production standards. This is the case in the (human and veterinary) pharmaceutical industry, the cosmetics industry and the food industry. Good Manufacturing Practice (GMP) is a well-known term in these industries. GMP is a quality assurance system which ensures that the production process is properly registered and therefore quality is guaranteed. Due to the major role in the pharmaceutical and cosmetics industry, only the GMP within these sectors will be discussed below.
History
Since the beginning of civilization, people have been concerned about the quality and safety of food and medicine. In 1202 the first English food law was created. It was much later, in 1902, that the Organic Control Act followed. This was introduced in the United States to regulate organic products. These products were legally tested on purity. The original Food and Drug Act, launched in 1906 and made it illegal to sell contaminated (falsified) food and demanded truthful labelling. After that, a number of other laws came into force. In 1938, the Food, Drug and Cosmetic Act was introduced. The Act required companies to provide proof that their products were safe and pure before they were put on the market. The FDA carried out investigations of contaminated tablets and revealed that serious irregularities in production were found at the factory and that it was no longer possible to trace how many other tablets were still contaminated. This incident forced the FDA to act on the situation and prevent recurrence by introducing invoicing and quality controls based on auditing standards for all pharmaceutical products. This led to what was later referred to as GMP. The expression ”Good manufacturing practice” appeared in the 1962s as an amendment to the American Food, Drug and Cosmetic Act.
The current European GMP regulations were developed in Europe and the United States.
Eventually the European countries also began to work together and drew up common GMP guidelines which were accepted by the European Union.
In addition, there are currently many other international laws and regulations in which GMP regulations have been included.
What is GMP?
GMP means ”a good way of producing”. GMP rules are included in all kinds of laws, but in essence these rules have the same purpose. GMP is especially applied in the pharmaceutical industry and it is intended for guaranteeing the quality of the production process. The quality of a product can never be completely determined by testing its composition. Not all impurities can be detected and not every product can be analysed. Quality can therefore only be guaranteed if the entire production process is carried out in a precisely prescribed and controlled manner. Only this way the production process ensures the quality of a medicine. This method of production, called Good Manufacturing Practice, is therefore a requirement for the production of medicines.
GMP is also of significant importance for international partnerships. Most countries only accept the import and sale of medicines produced in accordance with internationally recognised GMP. Governments that want to promote the export of medicines can do this by making GMP mandatory for all pharmaceutical production and by training their inspectors in the GMP guidelines.
GMP specifies how and under which conditions a medicine is manufactured. During production all materials, ingredients, intermediate products and the end product are checked and the process is precisely registered on the so-called preparation protocol. If afterwards something turns out to be wrong with a certain batch of products, it is always possible to find out how it was made, who tested it and where and which materials were used. It is possible to track down exactly where it went wrong.
While good control is necessary to guarantee the quality of pharmaceutical products, it has to be realized that the ultimate goal of quality control is to achieve perfection in the production process. Quality control was created to assure the consumer that a product meets the quality standards, correct labeling and all legal requirements. However, quality control alone is not enough to achieve all goals. There must be a commitment to achieving quality and reliability in every product, every batch. This commitment can best be described as GMP.
Laws and regulations
The GMP guidelines are laid down in various laws and regulations for the various industries. There are international laws and regulations, but there are also regulations at European and national level.
International
For the exporting companies to the United States, the GMP regulations by the United States Food and Drug Administration (FDA) are applicable. They enforce the rules under Title 21 of the Code of Federal Regulations. The guidelines are known there under the term ”Current Good Manufacturing Practice (cGMP)”.
Europe
The GMP guidelines which apply within the EU are laid down in European regulations. These regulations apply to all products which are traded within the European Union regardless of the manufacturer is based outside the EU.
For medicinal products intended for human use, the most important rules are regulation 1252/2014 and Directive 2003/94/EC. For medicinal products intended for veterinary use is Directive 91/412/EC applicable. There are more related laws and regulations that govern the medicinal market. The GMP requirements are the same for the human as for the veterinary medicines industry.For the interpretation of the standards laid down in this legislation, the EudraLex provides guidance. EudraLex is a collection of rules that apply to medicines within the EU. Volume 4 of the EudraLex contains the GMP rules. It is in fact a manual for applying the GMP guidelines and principles. These rules apply to both human and animal medicine.
National
The Ministry of Health, Welfare and Sport decides on a national level which pharmaceutical care can be imported under which conditions and for which medical indications. The Medicines Act describes the conditions for the manufacture of the medicine, its marketing and distribution up to the patient. For example The Opium Act prohibits the possession of certain drugs listed in lists l and ll of the Opium Act. There is also a regulation on precursors. According to these regulations, pharmacists may only stock and/or trade chemicals that can be used to make drugs or explosives (precursors) under certain conditions. There are also rules and guidelines such as the FMD regulation (measure against forgery of serial numbers) and the KNMP guidelines for pharmaceutical care and the Dutch Pharmacy Standard.
The European Medicines Agency (EMA) is responsible for the scientific evaluation, supervision and safety control of medicines in the EU. The Cosmetic Products Act Decree sets requirements for the production of cosmetics.
GMP requirements
GMP is part of quality assurance . In general, this assurance, besides the GMP, also includes areas such as product design and product development. Quality assurance is the totality of activities which must ensure that a product or service complies with the quality requirements. Quality assurance is one of the basic elements of quality management. The importance of quality management is crucial. If you only imagine for a moment what would happen if mistakes were made in the production of medicines and were discovered too late. Besides the human suffering , it would be a disaster for the reputation of the pharmaceutical company. Good manufacturing practice focuses on risks inherent in drug production, such as cross-contamination (contamination of one drug with components of another drug) and mix-ups (errors) caused by mislabelling.
The requirements which GMP sets for the manufacture of products are internationally agreed. This blog outlines the requirements resulting from the regulations relating to the pharmaceutical industry. In general, the same basic principles apply to every industry. These basic principles are internationally quit the same.
European legislation requires medicinal products to be manufactured in accordance with the principles and guidelines of good practice. The aspects covered by the guidelines are quality control, personnel, premises and equipment, documentation, production, quality control, subcontracting, complaints and product recall and self-inspection. The legislation obliges the manufacturer to establish and implement a pharmaceutical quality assurance system. These rules also apply to medicinal products intended for export.
The following GMP guidelines should be considered:
- Well trained, qualified staff,
- Hygiene is strictly maintained. If someone, for example due to a contagious disease or open wound, there is a notification obligation and follow-up protocol.
- Regular medical examinations of employees
- For employees who carry out visual inspections, there is also an additional visual inspection,
- Suitable equipment,
- Good materials, containers and labels,
- Approved work instructions,
- Suitable storage and transport,
- Adequate staff, laboratories and instruments for internal quality control,
- Work instructions (Standard Operating Procedures); work instructions are written in clear language and focused on the local situation,
- Training; operating personnel is trained to carry out the work instructions,
- Documentation; everything must be clearly on paper and the suitability of the staff
- Information on labels and method of labelling of raw materials, intermediate and finished products,
- There are clearly described, proven, reliable manufacturing processes in place,
- Inspections and validations are carried out,
- During manufacturing (manual or automated) it is recorded whether all steps have been carried out correctly,
- Deviations from the instructions are recorded and investigated in detail,
- The complete history of each batch (from raw material to customer) is stored in such a way that it can easily be traced,
- The products are stored and transported correctly,
- There is a method to remove batches from sales if necessary,
- Complaints about quality problems are dealt with and investigated adequately. If necessary, measures are taken to prevent recurrence.
Responsibilities
GMP assigns a series of responsibilities to key personnel, such as head of production and/or quality control and the authorized person. The authorised person is responsible for ensuring that all procedures and medicinal products are manufactured and handled in accordance in accordance with the guidelines. He or she signs (literally) for each batch of medicines coming from the factory. There is also a chief manager, who is responsible for ensuring that the products meet the legal requirements of the national authority for medicinal products, without putting patients at risk due to lack of safety, quality or efficacy. It should be obvious, but it is also the requirement that the medicines are suitable for the purpose for which they are intended.
Supervision and GMP certificate
At both European and national level, there are operators in charge of the supervisory task. These are the European Medicines Agency (EMA) and the Health Care and Youth Inspectorate (IGJ). In the Netherlands, the IGJ gives a GMP certificate to the manufacturer of medicines if he complies with the GMP guidelines. To make this possible, the IGJ carries out periodic inspections of manufacturers in the Netherlands to investigate whether they comply with the rules for GMP. If the GMP regulations are not met, the manufacturer will not only be withheld from a GMP certificate, but also from a production permit. The IGJ also inspects manufacturers in countries outside the European Union. This is done by order of the EMA and the Medicines Evaluation Board (CBG).
Also at the request of the Medicines Evaluation Board, the IGJ advises the manufacturers in the marketing authorisation dossier (site clearance). If a manufacturer does not work in accordance with GMP quality requirements, the Board may decide to have this manufacturer removed from the dossier of the marketing authorisation. The Board does this in consultation with the IGJ and other European inspection authorities and European bodies such as the Coordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh) and EMA. If this can lead to a shortage of a medicine for the Netherlands, the marketing authorisation holder must report this to the Medicines Deficiencies and Defects Disclosure Office (Meldpunt geneesmiddelen tekort en -defecten).
Cosmetics and GMP
For cosmetics, there are separate regulations to guarantee their quality. On a European level there is the Cosmetics Regulation 1223/2009/EC. This also determines that cosmetics must comply with GMP. The guideline used for this is the ISO 22916:2007 standard. This standard contains the basic principles of GMP which are focused on companies which produce finished cosmetics. This is an international standard and it has also been approved by the European Committee for Standardization (CEN). This is a European standardization body who creates standards that are in high demand. The application of these standards is not mandatory, but does show to the outside world that the products or services meet quality standards. The standardisation body also develop ‘harmonised standards’ at the request of the European Union.
These GMP regulations which are specified in the standard basically have the same goal as those for the pharmaceutical industry: to guarantee the quality and safety of the product. This standard only focuses on the cosmetics industry. It includes and covers :
- production,
- storage,
- packaging,
- testing and transport processes
- research and development
- distribution of finished cosmetics
- safety of production workers
- protection of the environment.
The standard not only ensures the application of product criteria and requirements for the production of goods. Applying the standard allows the manufacturer to manage the quality and safety requirements of the supply chain and to monitor the hazards and risks of cosmetics. The GMP Regulations correspond to the rules which were previously mentioned in detail in the section ”GMP requirements”.
Do you need advice or support on pharmaceutical law or cosmetics legislation? Or do you have any questions about this blog? Please contact lawyers at Law & More. We will answer your questions and provide legal assistance where necessary.