Vaccines can be divided into five stages from research and development to use: research and development, registration, production, circulation and use. Each of these big stages contains a number of small stages, so let’s break them out.
1,Vaccine development stage
The entire process from getting the virus and developing a vaccine to completing a Phase III clinical study is called the r&d phase. It mainly consists of the following parts: laboratory development, preclinical study, phase I, II and III clinical study.
The laboratory stage is one of the most unpredictable in terms of time, which is why it takes a long time to develop a vaccine from scratch. It takes repeated studies, repeated modification procedures, repeated test results to get the vaccine that the research is looking for. At present, the vaccine is only a preliminary product of research, which needs further verification of its safety, effectiveness and other effects before it can be put on the market.
This stage of research has been carried out mainly in animals, such as guinea pigs, rabbits and even our closest primate relatives. Preclinical studies refer to chemical synthesis or purification of natural products, drug analysis, pharmacodynamics, pharmacokinetic and toxicological studies, and pharmacy studies before drugs enter clinical studies.
Pre-clinical studies of drugs for drug registration, including drug synthesis process, extraction method, physical and chemical properties and purity, dosage form selection, prescription screening, preparation process, test method, quality indicators, stability, pharmacology, toxicology, animal pharmacokinetics, etc. Biological products also include the origin, quality standards, preservation conditions, biological characteristics, genetic stability and immunological studies of starting materials such as bacterial strains, cell lines and biological tissues.
After the completion of the preclinical study, the third stage of the development phase, the clinical study. It is mainly divided into stage I, II, III and III clinical trials. In terms of clinical vaccine, the main introduction of phase III clinical trial is as follows:
Phase I clinical
Assess safety (tolerability)
About 20 adult subjects
First adults, then children, then infants
Assess immune response
Phase II clinical
Evaluate immunogenicity, immunization program, and safety
300 healthy subjects
Determine dosage form dosage and formulation
Determine immunization procedures and routes
Confirm vaccine safety
Phase III clinical
Assess protection effectiveness/safety
500 to/more than 10,000 healthy subjects
Prove that vaccines prevent infection, disease
The relevance of immunology to protection
After the above development phase is completed, the drug registration phase needs to be started. Drug registration refers to the state food and drug administration according to the applications for drug registration, in accordance with legal procedures, sell drugs to be listed on the safety, efficacy and quality control, etc.
To review, and decide whether or not to approve the application approval process (drug registration noun explanation from the drug registration management measures (bureau to 28) “). Of course, there are overlaps between drug registration and clinical research in the research and development stage. Clinical research also needs to submit relevant materials and can enter the clinical research stage only after passing the examination.
Vaccines are prophylactic biological products and require information on about 20 categories and relevant supporting documents. For example, research results summary and evaluation data, production bacteria (virus) species research data, quality research data, pre-clinical effectiveness and safety research data, draft manufacturing and verification procedures, attached with drafting instructions and relevant literature, manufacturing verification records of clinical trial application samples, Preliminary stability test data, certification of experimental animals for production, research and verification. Only after passing a series of procedures, such as document review, production site inspection and rectification review, can the drug manufacturer get the drug registration approval.
After receiving the drug approval, the manufacturer should start to conduct GMP inspection on the manufacturing site (” GMP “refers to the” Good Manufacturing Practice “). The GMP certificate can be obtained only after the RELEVANT personnel are checked and qualified by CFDA. Only then can the manufacturer officially produce the product for the market.
3,Vaccine production stage
This stage is relatively easy to understand, is to follow the approved process of production, verification, filling, etc. After the product is produced, it needs to be sent to China National Institute for Food and Drug Control and National Institute for Drug Control for sampling identification. After the verification of qualified certificate, the product can be on the market for sale!
This stage is mainly the sales and product shipping process. Most vaccines need to be refrigerated at 2-8℃. Therefore, the cold chain transportation of drugs is also very important in the process of transportation. At the end of 2013, the country issued a new version of the GSP, also known as the Quality Management Standard for Drug Distribution, to regulate the temperature guarantee of cold chain products such as vaccines during shipment.
There’s really nothing to explain at this stage, but the main thing I want to mention is that there’s also a subset of clinical studies at this stage called Phase IV clinical studies. This stage refers to the application research stage after the new drug is put on the market. The main objective is to evaluate the effectiveness/safety of protection for large populations. Usually thousands to tens of thousands of people are observed, mainly for the protective efficacy/safety of post-marketing vaccines.
All of these steps are easy to say, but they take a lot of time and money to do. In recent years, the relevant laws and regulations of the state on vaccines have been constantly launched and updated, aiming to ensure that the listed vaccine products can effectively and safely protect the public.