Biochemical drugs is derived from organisms and contains many active substances, such as peptides, polysaccharides and amino acids. In order to improve the quality control in biochemical drugs, it is the key to formulate quality standards that can distinguish authenticity, evaluate advantages and disadvantages, and monitor the stability and uniformity of quality. Methods: Fingerprint after scientific evaluation is an advanced means to effectively analyze complex biopharmaceuticals. Results: Through the basic research of fingerprint, the scientific detection method can comprehensively and systematically reflect the overall information of effective components. Conclusion: The fingerprint of biochemical drugs is a systematic study involving many subjects, which is original and novel, and is of great significance to improve the overall level of biochemical drugs in China. & ampmg； rare

Biochemical drugs is a basic substance with biochemical activity, which is separated and purified from organisms or their metabolic secretion products. It is used to prevent, treat and diagnose diseases, including such substances made by chemical synthesis or modern biotechnology. An important basic feature of biochemical drugs is that it comes from biology. Second, it is a basic biochemical component in living organisms. These basic biochemical substances mainly include amino acids, peptides, protein, enzymes and coenzymes, polysaccharides, lipids, nucleic acids and their degradation products all have various biological activities or physiological functions [1 ~ 2]. MAxU7~z5q/

The research and development of foreign biochemical drugs is relatively early. From 1930s to now, it has gradually developed in the direction of safety, standardized management, refining and purification, and the preparation of high activity and clear components by means of bioengineering. Although the research on biochemical drugs in China was carried out late, because China is a big country in animal husbandry and feeding, the raw materials in biochemical drugs are all slaughtered and processed as edible animals, and the comprehensive utilization cost is relatively low. In addition, biochemical drugs is easy to be absorbed and utilized by human body, with good safety and definite curative effect, which has been widely used in clinic, and the country attaches great importance to it. Therefore, a special authority has been set up for planning and management, and preferential policies have been given to support it, especially in the improvement of modern medicine, life sciences and biotechnology. It has promoted the rapid development of biochemical pharmaceutical industry. The level of scientific research and technology in biochemical drugs has improved and developed rapidly. There are many kinds of products developed. Just before 1998, there were hundreds in biochemical drugs. However, there are some serious quality problems such as repeated varieties, inconsistent standards of the same variety and uncertain curative effect, which have caused some confusion and accidents in drug use. The State Drug Administration attaches great importance to improving the quality of drugs, and from 1998, the quality standards of biochemical drugs were unified and standardized nationwide, which was completed in 2002. It has been greatly improved in ensuring safety, effectiveness and quality standards. Nearly 100 kinds of biochemical drugs, including thymosin for injection, cerebroprotein hydrolysate injection, cattle encephalon glycoside and ignotin injection and bone polypeptide injection, have been widely used in clinic, and the effect is generally good. Nevertheless, there are still many serious problems in production and quality management in biochemical drugs, mainly in the following aspects.

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1. 1 Materials are not strictly controlled. _xVV v4

At present, the sources of edible livestock and poultry organs in biochemical drugs are quite confusing. The market economy has diversified the aquaculture industry, and there are still many problems in the unified slaughter of meat and livestock. It is difficult to do a good job in routine quarantine of simple diseases and pathogens, and the accident is very noticeable. The problem of "reassuring meat" has attracted great attention from the state. There are serious hidden dangers in the quality and safety of organs and tissues obtained from this. In addition, bird flu, mad cow disease, SARS, foot-and-mouth disease and other diseases that have ravaged the world have also attracted great attention from the international community. (4) Because the state has not formulated inspection standards and items for medicinal animal organs, at present, all biochemical drug production enterprises directly process and produce the purchased animal organs, which can be said that there is no inspection and quarantine, and there is no health and quarantine certification for meat animals. In addition, it is common to use growth promoters and veterinary drugs to raise livestock and poultry, and it is also common to raise pigs in bulk and garbage. In this way, pollutants and pathogens (5) and (6) in animals, especially in organs, have caused serious pollution to biochemical drugs injected directly into the body, and the potential safety hazard is very serious. The state has instructed China Institute for the Control of Pharmaceutical and Biological Products to hold a special seminar and formulate corresponding measures to control such problems. $; . oyJ

1.2 The production process is not standardized. 2PtDVT

At present, biochemical drugs listed in the national drug standards, especially those extracted from organs, have no strict regulations on the selection of raw materials, processing and production technology of finished products for most varieties. Especially at present, the phenomenon of processing raw materials and outsourcing semi-finished products is very common, and it is difficult to guarantee the uniformity and controllability of the final quality of biochemical drugs products with complex components. In addition, there are problems in the monitoring of pollutants such as heavy metals and organic solvent residues in organ processing and production, as well as possible key production links such as pathogen inactivation. It also brings hidden dangers to the safe use of biochemical drugs (1). WixD & gtC

Controllability of 1 3 the standard is not strong. /B2#j"8x

Most of the quality standards of biochemical drugs that have been upgraded to national standards and are being implemented do not fully combine the complex components of biochemical drugs, and still follow the technical requirements of chemical drug quality standards. Although they draw lessons from the advantages of foreign quality standards ("cerebrolysin" and "Aiweizhi"), they only make a rough qualitative and quantitative analysis of the main effective components, mostly single components and single compounds in various components, such as protein, amino acids and polysaccharides. For example, protein or polypeptide is qualitatively identified by HPLC, SDS-PAGE, etc. It can only reflect the similarity of the main active ingredients and other ingredients. Although the activity index test items are added to further verify the biological activity, it is not specific enough to fully reflect the quantitative information of the efficacy characteristics of various active ingredients, and it is impossible to truly identify the true and false and evaluate the pros and cons. Dy & LT90%

Especially biochemical drugs from animal organs, such as thymosin injection, contains a variety of biochemical substances with activity and function. The composition of curative effect is not very clear, and it is often influenced by raw materials, auxiliary materials, reagents, technology and other factors, and the composition will change, which will directly affect the clinical curative effect and side effects. Only by strictly controlling the source and quality of raw materials, strictly standardizing the process of raw materials, strengthening the monitoring of production process, strictly inspecting semi-finished products, stipulating the quality standards of finished products, and having detailed, rapid, specific and accurate qualitative and quantitative inspection items, can the quality of biochemical drugs be ensured to be safe, effective and controllable (3). Hourcq rsen

2. The key to quality control in biochemical drugs is to formulate quality standards that can distinguish authenticity, evaluate advantages and disadvantages, and ensure quality stability and uniformity. DSmD/4D8

Fingerprint (or fingerprint) is a comprehensive and quantifiable identification method, which mainly uses modern analytical technology to obtain the characteristic spectra of detected multi-component substances by chromatography or spectrometry. It has been widely used in biochemistry, molecular biology, genomics and other research fields. In the standards of applying fingerprint to plant medicine abroad, Japan, the United States, France and Germany not only use it for plant medicine research, but also evaluate it as an important index for new drug research. China also attaches great importance to the study of fingerprint, which is an important work to promote the modernization of traditional Chinese medicine. In 2002, the US Food and Drug Administration clearly stipulated that all registered varieties of traditional Chinese medicine injections must be declared, and relevant fingerprint research data must be declared, including raw materials, extracts and products of traditional Chinese medicine. The correlation of fingerprints must be scientifically compared and analyzed, and the results are consistent before approval (7). It has played a great role in improving and standardizing the quality of traditional Chinese medicine and achieved remarkable results. Therefore, the state has given strong support to the fingerprint of traditional Chinese medicine from both policy and capital, and promoted it as an important work of the national industrial policy of modernization of traditional Chinese medicine. UNq(

Like traditional Chinese medicine from natural biological resources, biochemical drugs, especially biochemical drugs from animal organs, such as thymosin products, need to be frozen, extracted, hydrolyzed and purified. The composition of the final product is complex, and the pharmacological action is the result of the comprehensive action of all active ingredients. Therefore, it is more appropriate to use the fingerprint method which can compare the integrity and fuzziness to reflect the characteristics of the effective components of drugs, and at the same time meet the regulatory requirements of specificity, reproducibility and practicability of drug quality standard control. After strict quarantine of raw materials from animals is carried out in biochemical drugs and pathogen inspection to ensure the safety of organs taken, it is very suitable for confirming and monitoring the similarity of components of extracts, semi-finished products and finished products, especially for monitoring and evaluating the quality of the same variety from different batches and manufacturers, distinguishing authenticity and judging the quality of fingerprints. In addition, the production in biochemical drugs, mainly the production process of raw material extraction, has a great influence on the composition of active ingredients in the final product. By incorporating fingerprint into the inspection items of quality standards, the specificity and strictness of quality standards are strengthened, and the production process standardization of products is directly standardized. Can effectively ensure the stability of product quality. d @ V； XC

So far, in the production and quality control of biochemical drugs at home and abroad, there is no method that can fully reflect the complex quality differences in biochemical drugs. There are some studies on the fingerprints of physiological, pathological and animal organ extracts abroad (11) (12) (13). The Pharmacopoeia of developed countries has not stipulated the fingerprint in the quality inspection items of biochemical drugs, and the research on the fingerprint of biochemical drugs is still blank. Based on the research experience of traditional Chinese medicine, the fingerprint was applied to the quality research and quality standards in biochemical drugs, and the raw material extraction, intermediate processing, finished products and quality stability were strictly monitored to ensure the quality of biochemical drugs in an all-round way. It will have international innovation and independent intellectual property rights. It will also lay a theoretical foundation for the development of biochemical drugs in China. Therefore, the research and determination of biochemical drugs fingerprint is the key to improve the overall level of biochemical drugs in China, and it is also an important measure to raise the quality of biochemical drugs to the international level. ]TQ)3=

2. 1 biochemical drugs fingerprint basic research work sKnXo l

The research and analysis of biochemical drugs's fingerprint is a research subject involving the interdisciplinary and comprehensive application of analytical chemistry, biochemistry, biological separation technology, physiology, pharmacology, bioinformatics and so on. It involves a wide range of research disciplines and needs a lot of research work. It is a systematic project to apply fingerprint to the quality control of biochemical drug production, which involves many production quality management factors. Drawing lessons from the research experience of traditional Chinese medicine fingerprint, the fingerprint determination of biochemical drugs must be based on the biochemical and active characteristics of biochemical drugs, including the information of all effective components. It is the analysis of effective components and the study of quality characteristics under the guidance of biological activity and pharmacological action, not from the structure-activity relationship and molecular pharmacology of a chemical component, but from the comprehensive point of view of active component groups or groups, not limited to the study of surface physical and chemical properties of components, but scientific and reasonable. Perfecting the related basic research work is the key and prerequisite to develop the fingerprint of biochemical drugs. obm|！