What problems should be paid attention to in the process of new drug research and development?

Market is the ultimate judge of product life. Therefore, to demonstrate a project, we must first demonstrate its market. This requires specialized market researchers to conduct actual analysis and data comparison. What we should also consider is the market change forecast within 3-5 years when new drugs are developed.

Epidemiological investigation-epidemiological investigation is a survey of market capacity, mainly to understand the incidence of indications for drugs. The higher the incidence, the greater the market capacity. Such as diabetes, cardiovascular and cerebrovascular diseases, Alzheimer's disease, senile osteoporosis, viral diseases, malignant tumors, senile urinary incontinence, etc., are all diseases with high incidence, and such drugs have a good market prospect. Of course, there is also a stable market for therapeutic drugs that have specific effects on some minor diseases (such as herpes zoster and pancreatitis).

Investigation of similar products-with the development of science and technology today, it can be said that no disease can be cured by only one medicine. Market competition requires that new products must be unique. The growth trend of sales data of similar varieties can generally judge whether the variety is in the development stage, such as growth stage, maturity stage or decline stage. Therefore, it is necessary to collect and compare the data of similar products as comprehensively as possible. When comparing the developed varieties with similar products on the market, we should pay attention to the following aspects: first, whether the curative effect is better; Second, whether the side effects are lower; Third, whether the dosage form and dosage are more convenient to use; Fourth, whether the packaging is convenient for patients to carry; 5. Whether the market price is cheap, etc.

Growth market: select drugs that can be used to prevent and treat new disease spectrum as the research topic. As a scarce or even blank drug in clinic, it must have a strong competitive advantage. For example, drugs used to treat depression, endocrine disorders, sexual dysfunction and other dysfunction caused by accelerated social rhythm have become research hotspots since the 1990s, and have been widely used in clinical practice, with promising market prospects; For example, some diseases, such as stroke and climacteric syndrome, tend to be younger, so the research and development of drugs to prevent and treat these diseases should have a good market prospect.

Mature market: taking new technology, new preparation, new route of administration, new quality control method and new mechanism of action as research topics, selecting and developing drugs. Even the products that tend to be saturated and excessively competitive in the market can regain their competitiveness as long as we can optimize their technology. For example, the "Banlangen Granule" flooding the market has improved its product competitiveness and market growth point by controlling its quality standards through fingerprint technology; After the dosage form of "Huoxiang Zhengqi Water" was reformed into "Huoxiang Zhengqi Soft Capsule", the number of users increased greatly and the market share increased. After the chiral structure of "(dextro) ofloxacin" was changed to "levofloxacin", the clinical efficacy was greatly enhanced and the side effects were significantly reduced, making it one of the fastest developing drugs on the market at that time.

Hidden market: choose to develop drugs with good social benefits as the research topic. Such projects can get more funds from government organizations, attract more public attention and promote economic benefits.

1. Develop drugs to prevent and treat social problems such as drug addiction, AIDS and infectious diseases.

2. Develop drugs to prevent and treat diseases of vulnerable groups such as the elderly, women and children;

3. Develop medicinal resources that can increase the local government's economic income, and conduct in-depth research and project transformation;

4. Develop substitutes for rare and precious medicinal materials.

Second, technical factors.

Technical feasibility determines the difficulty and investment of development, which is another important aspect to avoid risks. The technical demonstration of the project should include the following aspects:

(1) Source of raw materials-Chinese medicine should be understood as follows: ① There are nonstandard medicinal materials. If there are non-standard medicinal materials, it is necessary to establish the standard of medicinal materials first, which will be a great workload. ② Whether to use toxic medicinal materials involves quality standards and clinical difficulty. (3) Whether there are pangolin and other national protected varieties. This problem directly affects the supply of mass production. (4) The sufficiency of raw materials is related to the sustainable production of drugs, which should be paid enough attention, especially the use of wild plant drugs involves resource regeneration. Western medicine should know whether the raw material supply can be localized and the technological difficulty, otherwise the auxiliary materials will also affect the project progress.

(2) Pharmaceutical part-mainly including technology, quality standards and stability research. The first is the feasibility, practicability and advancement of the process. The improvement of technology must adhere to the principle of combining advanced, practical and feasible. The establishment of quality control indicators and methods should also be repeatedly demonstrated. Although some components are high in content, they are unstable and fluctuate too much to be used as index components; In addition, the requirements of test methods for test instruments are directly related to the investment in project development and the affordability of enterprises. The stability of dosage forms is also very important, which affects both the curative effect and the market. This point must be made clear so as not to bring unnecessary trouble to the later work. Details are as follows:

1. synthetic route

① Analyze the synthetic route: judge whether the synthetic route is difficult, easy or impossible;

(2) analyzing the source of synthetic raw materials: judging whether the starting raw materials or intermediates are difficult to obtain, easy to obtain or impossible to obtain; And contact with each raw material or intermediate;

③ Analysis of synthetic equipment: analyze the equipment needed in each step. If there is no such equipment, inquire about the manufacturers who produce this equipment and contact them;

④ Analysis of synthesis cost: judge whether it is worthwhile to synthesize the product.

Step 2 prepare

① Technical analysis of preparation prescription: judge the difficulty of prescription technology or whether it is possible to prepare;

(2) Analyze the raw materials of the preparation process: judge whether the raw materials are available or not, and contact the raw materials externally;

(3) Analysis of preparation equipment: analyze the equipment used in preparation, compare the existing equipment with the insufficient equipment, and make a decision after a detailed investigation of special equipment;

④ Preparation cost analysis: judge the cost of producing this product.

3. Quality research

① Analyze quality research data: judge the feasibility of this analysis method;

② Analysis and testing instruments: judge whether it is necessary to buy new instruments; And contact with the outside world;

③ Analyze the chemical reagents needed for quality research: judge whether the required chemical reagents can be obtained, and contact the reagent supplier;

④ Analysis of reference substance: It includes two aspects, namely, the reference substance formally needed and the reference substance required by Document No.6;

(3) Pharmacology and Toxicology-It is necessary to know whether there is a standardized animal model for pharmacodynamic research when demonstrating. New drug guidelines cannot include research models that provide all diseases. If the project to be developed does not have a known model, and it is very difficult to rebuild the model, then such a project had better be postponed. Are there any special requirements for animals in toxicology research? For example, drugs for the treatment of AIDS are promising projects, but the requirements for experimental animals are high, so the intervention units are small.

(4) The clinical part-the dosage, course of treatment and clinical cycle of drugs are directly related to the investment, so we should have a clear understanding of these issues. In addition, whether the clinical research scheme provided by the research unit is feasible and whether the guiding principles are ready-made, etc., must be demonstrated.

(5) When copying and developing this dosage form, we should also pay attention to inquiring about the original standard and its related registration and declaration. When designing a new dosage form, it is necessary to investigate the usage and dosage of the original dosage form to ensure that the developed dosage form is not only novel, but also safer and more effective.

Three. Efficacy and safety factors

Medicine is a special commodity, and its particularity lies in: specific people use it periodically at a specific time; It has the characteristics of treating diseases and saving lives; Improper use will cause physical injury; It must be purchased in a designated place, such as a drugstore or a hospital, and cannot be circulated through channels at will.

Therefore, the above characteristics define that drugs must be effective, and patients will not use or reuse ineffective drugs. Even if it is developed, there will be no market prospect.

Therefore, the approved new drug must be effective and superior to the main clinical products at present, including Chinese and western drugs in comparison.

The same is true of drug safety. Before the project is established, the adverse reactions of similar products should be tracked and investigated, and some adverse reactions are limited to the designed dosage forms. The design and research of pharmaceutical preparations have great influence on exerting the curative effect of drugs and reducing adverse reactions. For example, among fluoroquinolones, ofloxacin, the most toxic drug, is made into eye drops. It is reported that among 65,438+0,585 clinical trials of systemic drugs in the United States, 65,438+0.26 cases (7.9%) had phototoxic reactions, some of which could occur after one oral administration. To this end, the FDA has warned doctors and indicated in the instructions that the product is for use only. (2) acute attack of chronic bronchitis, and attention should be paid to avoid sunlight, sunlight and ultraviolet radiation during and 5 days after taking the medicine. Patients with phototoxicity should not be exposed to sunlight, sunlight and ultraviolet radiation within 5 days after the symptoms have not recovered and disappeared, so as to avoid phototoxicity recurrence. In view of the above reasons, the safety of this product as eye drops for local use cannot be guaranteed.

Fourth, intellectual property factors.

In the process of project demonstration, we should pay close attention to related patents and search for patent, administrative protection and confidential varieties through authoritative organizations to avoid infringement. Especially the patent of synthetic route and preparation technology. In addition to patent factors, we should also pay attention to the monitoring period of drugs and the protected varieties of traditional Chinese medicine. It can effectively avoid property rights disputes of developed varieties, and also apply for property rights protection in time when developing new products, so as to increase the competitiveness and exclusive property rights barriers of new products.

One possibility is that the relevant patents could not be found when the project was established, and to some extent, the patents of others came out. Don't give up easily here, it depends on how to avoid it and analyze it comprehensively.

Five, finished product cost factors

As the person in charge of the project, we must fully consider all kinds of costs, come up with a budget, and make a relevant cost accounting for the possible market price after the successful drug research and development. Special attention should be paid to modified drugs and generic drugs.

Six, the national administrative policy factors

In order to successfully complete the registration process, a drug must comply with the relevant national laws and regulations, as well as the drug registration procedures, key points of dosage form review, key points of drug evaluation, requirements for drug registration acceptance and some guiding principles of chemical drugs promulgated by the State Administration recently. Suggestion: In addition, check the homepage of the State Food and Drug Administration in time to see if there is any new information about this drug; The contents of the search include the drug, the registration classification, the review requirements of this kind of drug and the problems found in the review. In order to accurately grasp the trend of the national registration review policy and clarify the problems that should be paid attention to, especially the judgment of product ownership and registration category must be accurate! We should pay close attention to the application for registration of new drug research and development to avoid collision.

Seven,? Enterprise's own factors

The actual situation of enterprises, research and development of new varieties can not be divorced from the actual situation of enterprises The reality of the enterprise includes:

(1) production scope: whether there is a GMP-certified production line for this kind of drugs, and if the production is expanded, the risks brought by the expansion should be considered;

(2) Marketing network: If you have been doing antibiotics for a long time, the network in this field is sound and the channels are smooth, then you will switch to cardiovascular and cerebrovascular products. How to build a network and expand channels? Perhaps when it takes time, energy and money to build a good network, the market has changed;

(3) Capital strength: Ignoring the enterprise's own capital situation, blindly investing in new products or large projects will eventually lead to the break of the capital chain and the exhaustion of cash flow, making the enterprise unsustainable and having to be merged, bankrupt and closed.

Eight. Other factors

Some projects are provided by other units, and most of these units have done literature retrieval, or have gone through preliminary basic work such as synthesis route, preparation technology and quality standard research. As a partner, we should pay special attention to the synthetic strength and work quality of this unit. The research of technology is the foundation of foundation, and the problems here will affect the progress of the whole project and even lead to the failure of the project.

Second, some projects are entrusted to other research institutions for development. New drug development is a complex systematic project that requires multidisciplinary cooperation. In particular, the research on pharmacology, toxicology and clinical surgery that must be completed by designated units should carefully understand the strength of the entrusting party, whether it has research qualifications, whether it has conducted successful cases of new drug research and development, the experience of academic leaders in this field, and the overall research strength. These are all very important. When signing the new drug development entrustment agreement with the entrusting party, the contract development cycle, installment payment, liquidated damages and other contents should also be stipulated in detail.

For a product to succeed, it is not enough to have the above characteristics, but also to have obvious characteristics, which can be owned by the product itself or produced in a specific market environment, such as filling the market gap, which is not created by the product itself, but by the relevant market, but it is best not to be artificial, such as the outer packaging of the product. The characteristics of the product are not many, but fine, which is obviously different from other varieties. This feature is the most practical. Only with the characteristics different from other varieties can we have obvious competitiveness in the market. It is best not to go to featureless projects to avoid repeated investment.