CFDA document, adjuvant or elimination

Source: CFDA 2016-10-20 notice issued by the State Food and drug administration raised the quality supervision of biochemical drugs to GMP level On October 19, CFDA General Administration issued the appendix of GMP for biochemical drugs (Draft for comments) (hereinafter referred to as the appendix of GMP for biochemical drugs) This is after three flight inspections of biochemical drugs were reported in September, which is also eight years after the issuance of the notice on basic technical requirements for chemical injection and multi-component biochemical drug injection in 2008, CFDA finally put forward new requirements for the quality management of biochemical drugs Biochemical drugs are mostly "auxiliary drugs" or "key monitoring drugs" In the notice on Issuing basic technical requirements for chemical drug injection and multi-component biochemical drug injection 8 years ago, the definition of "multi-component biochemical drugs" is that raw materials come from human and animal tissues or body fluids, or non single component drugs come from fermentation In the GMP appendix of biochemical drugs, biochemical drugs refer to safe, effective and quality controlled drugs prepared from animal organs, tissues, body fluids and secretions through pretreatment, extraction, separation and purification; products from human tissues and urine also follow the appendix Once again, it emphasizes the attributes of drugs - "safety, effectiveness and quality control" According to the notice, biochemical drugs mainly include: proteins, polypeptides, amino acids and their derivatives, polysaccharides, nucleotides and their derivatives, lipids, enzymes and coenzymes (excluding the products listed in the appendix of biological products) Combined with the current market situation, it can be seen that the biochemical drugs with large sales volume in the hospital include thymopentin, deproteinized extract of calf blood, thymosin, cerebrosinylgosin and complex coenzyme, etc., which are mainly used clinically as neuroprotective agents and Immunoenhancers This kind of product is often defined as "auxiliary drug" because of its unclear composition structure and unclear curative effect, and it is listed in the "list of key monitored drugs" because of its large clinical use At present, the policy of adjusting the medical insurance catalogue has a negative attitude towards auxiliary drugs, and the policy of medical insurance payment tends to strictly control the use of such drugs As a whole, the sales growth of these varieties is under pressure Now CFDA issues GMP appendix of biochemical drugs under strict supervision, which will increase the cost of enterprises and accelerate the elimination of biochemical drugs enterprises In 2015, CFDA had carried out follow-up inspection on thymosin products enterprises The reasons are: the origin of thymus is not clear, the supplier management of thymus is insufficient, the validation of virus inactivation process of production system is not aimed at the key process parameters, and the internal control standard of quality control system is missing The GMP appendix of biochemical drugs, especially in the chapters of supply chain management, plant and equipment, virus removal / inactivation and validation, specifies the implementation regulations and requires enterprises to improve quality management In Article 27 "supplier management" of "supply chain management", it is clearly required that the quality management department shall establish supplier quality management files according to the characteristics of varieties, and regularly conduct on-site audit on raw material suppliers according to Article 28 "supplier audit" Article 15 "requirements for setting up production area" of "plant and equipment" has clear requirements for "pretreatment" The pretreatment of raw materials shall have a special area, and the preparation of raw materials (raw liquid) and preparation production area shall be strictly separated The air conditioning purification system for raw material (stock solution) preparation and preparation production shall be set independently The GMP appendix of biochemical drugs does not meet the GMP requirements of "Chinese patent medicine" for the time being For the GMP certificate of Chinese patent medicine containing "extraction of traditional Chinese medicine", the link of "pretreatment of biochemical drugs" will be indicated in brackets The "virus removal / inactivation and verification" link was earlier required in the notice on the issuance of basic technical requirements for chemical injection and multi-component biochemical injection The new regulation of GMP appendix of biochemical drugs specifies that the virus challenge test in the validation of virus removal / inactivation method shall not use production plant facilities and equipment, which means that enterprises need to use the simulated process conditions closest to the actual production process (appropriately reduced) to carry out process validation The process parameters (temperature, time, model and specification of membrane, type and concentration of inactivating agent, etc.) and other conditions (pH, ion concentration, protein concentration, type and concentration of protective agent, etc.) of the validated effective process steps shall not be changed in the actual production process, and must be maintained within the scope of permission determined during validation If it exceeds the original limit, it needs to be verified again Once the policy is approved, biochemical drug enterprises that have not established key process parameters of "virus removal / inactivation and validation" may have to stop production for some time to make adjustments The quality control must be carried out in accordance with the Pharmacopoeia of the people's Republic of China and the quality standards approved by the State Drug Administration to inspect the raw materials, auxiliary materials, intermediate products, raw materials (raw liquids) and finished products of biochemical drugs If it is impossible to set a standard, the enterprise shall establish an appropriate internal control quality standard according to the variety quality risk This rule is good for the enterprises whose products have been listed in the Pharmacopoeia, such as thymopentin and heparin sodium, or the biochemical medicine enterprises which have established strict internal control quality standard system The GMP appendix of biochemical drugs advocates the use of biological analysis technology for the quality control of biochemical drugs The author believes that the highest cost lies in the identification of animal species of raw materials (such as PCR method) For enterprises, the requirements for supporting instruments and quality analysts are relatively high Conclusion the publication of GMP appendix of biochemical drugs will standardize the production of biochemical drugs enterprises and benefit the public health However, for most biochemical drug manufacturers, the introduction of this rule will speed up the survival of the fittest in the industry Only those enterprises that pass both hardware and management software can get tickets to the future market.