1. GMP history and sources
Shutdown event
In the late 1950s, the German company Grunenthal began to study the sedative hypnotic effect of thalidomide and found that it could effectively inhibit morning sickness in pregnant women。1957年，Granta Group under the banner of "non-toxic side effects" will "reaction stop" (generic name thalidomide，The chemical peptide amiperidone was first introduced to the European market，The drug has received a huge response on the market，In less than a year，"Reaction Stop" is popular in Japan, Australia, New Zealand, Canada, as well as 46 countries in Africa and Latin America，Countless pregnant women use the drug to ease pregnancy reactions。However, who would have guessed that the nightmare was creeping up。
In the six years since the drug was sold, more than 12,000 cases of deformed fetuses have been found in 28 countries in the former Federal Republic of Germany, Australia, Canada, Japan, and Latin America and Africa。The child had congenital abnormalities such as absence of limbs, short limbs, webbing between limbs, heart malformations, etc., showing seal malformation。Thousands of people are still alive, placing a huge burden on society。Another side effect of thalidomide is multiple neuritis, which occurs in about 1300 cases。The reasons for this drug disaster, one is that "thalidomide" has not undergone rigorous preclinical pharmacological experiments, and the other is that the manufacturer of the drug, Glennan Su Pharmaceutical, has received more than 100 reports of toxic reactions to thalidomide, but they have been concealed。The US avoided the disaster by failing to approve the import of "thalidomide" after learning the lessons of the 1938 sulfanilamide 醑剂 case, when FDA officials reviewing the drug found insufficient clinical trial data and refused to import it。But the serious consequences of the incident caused unease in the United States, stoking public interest in drug oversight and drug regulations in general, and ultimately leading to major congressional changes to the Food, Drug, and Cosmetic Act。
The 1962 amendment significantly strengthened the role of the Drug Act in the following three areas:
(1) Require pharmaceutical companies to prove not only that the drug is effective, but also that the drug is safe。
(2) Require pharmaceutical companies to report adverse drug reactions to the FDA。
(3) Require pharmaceutical enterprises to implement drug production and quality management practices。
In accordance with the requirements of the amendment, the United States Congress promulgated the world's first GMP in 1963, which was written by six professors at Temple University in the United States, and was discussed and revised by FDA officials for many times, and implemented for several years。
2. GMP content
GMP is an abbreviation of the English name Good Manufacturing Practices for Drugs or Good Practice in the Manufacturing and Quality Control of Drugs。GMP can be literally translated as "good production practice";Here, of course, we refer primarily to the production of pharmaceuticals。
Food, cosmetics, etc., should also be produced according to GMP。
The content can be summarized as wet parts, hardware and software。
(1) Wetware refers to personnel, there must be a certain number of professional and technical personnel, all staff need to carry out professional knowledge training and GMP knowledge training。
(2) Hardware refers to plant, facility and equipment，Plant facilities shall comply with GMP clean level requirements，Drugs must be produced in clean areas，The production equipment used requires a combination of advanced nature and applicability，Equipment easy to clean，No change with drugs (generally made of stainless steel)。
(3) Software refers to the organization, system, process, operation, health standards, records, education and other management provisions, it is necessary to formulate perfect technical standards, management standards, working standards and record documents。It includes production, technology, quality, equipment, materials, verification, sales, plant, purification system, health, training and other aspects。
3. New GMP features
The 2010 version of GMP consists of 14 chapters with 413 articles, which came into effect on March 1, 2011。The basic requirements for the quality management of drug production are described in detail, and most of the chapters and main contents of GMP version 98 are retained, covering the basic requirements of GMP of the EU and WHO, and applicable to the production of all drugs。
(1) Build a quality management system for drug production and comprehensively promote the improvement of the quality management level of enterprises。
(2) It emphasizes that the basis of GMP implementation is honesty and trustworthiness。
(3) The introduction of quality objectives, to systematically implement all requirements of drug registration into the whole process of drug production, control and product release, storage and shipping。
(4) Clarify the responsibility requirements of key personnel, and comprehensively strengthen the quality requirements of practitioners。
(5) Refine the software requirements, increase the difficulty of enterprise violations, and make the management program more instructive and operable。
(6) Improved drug safety and security measures, introduced the concept of quality risk management, and added new systems and measures such as supplier audit, change control, CAPA, and product quality review。
(7) It highlights the basic principles of GMP grasp and pays attention to scientific assessment of various complex and changeable situations。
(8) Absorb foreign advanced standards, while taking into account the national conditions of software and hardware, registration and production supervision will be linked。
(9) Put forward the concept of continuous stability and continuous improvement
(10) The production requirements of sterile drugs are more stringent, and dynamic detection in clean areas。
4. GMP requirement
Ensure continuous production and control of products in accordance with quality standards and marketing authorization requirements suitable for the intended purpose。The main purpose of GMP is to manage and reduce the internal risks of contamination, cross-contamination, confusion, error, etc., to ensure the quality, safety and effectiveness of products, and to ensure the continuous and stable production of drugs that meet the intended use and registration requirements。GMP requirements:
(1) All manufacturing processes shall clearly, systematically review risks based on manufacturing experience, and demonstrate the ability to continuously produce pharmaceutical products of the quality required by product standards。
(2) Confirmation and verification shall be carried out。
(3) Having sufficient suitably qualified and trained personnel。
(4) Sufficient workshop and space 。
(5) Suitable equipment and maintenance services 。
(6) Suitable materials, packaging containers and labels 。
(7) Approved procedures and instructions 。
(8) Suitable storage and transportation。
(9) Train the operator to implement the operation correctly according to the rules。
(10) During the production process, records (handwritten and/or instrumental records) should be filled in to show that all production steps in the established procedures and instructions have been carried out and that the quality and quantity of the product is as expected。All significant deviations should be fully documented and investigated to determine the root cause and take appropriate corrective and preventive actions。
(11) Records of the production and sale of products shall be kept in a form that is easily understood and accessible so that the complete history of each batch of products can be traced。
