In Vitro Diagnostic Reagents refer to products and services outside the human body that obtain clinical diagnostic information by testing human samples (blood, body fluids, tissues, etc.) to determine diseases or body functions. In vitro diagnostic products are mainly composed of diagnostic equipment (instruments) and diagnostic reagents.
In vitro diagnostic reagents, as a product under the supervision of the national drug regulatory system, are explained by the "In vitro diagnostic reagent registration management measures (trial)": in vitro diagnostic reagents managed by medical devices, including in vitro diagnostic reagents that can be used alone or combined with instruments, appliances, equipment or systems Used in the process of disease prevention, diagnosis, treatment monitoring, prognosis observation, health status evaluation, and genetic disease prediction, reagents and reagents for in vitro detection of human samples (various body fluids, cells, tissue samples, etc.) Boxes, calibrators (objects), quality control products (objects), etc.
For the general population, it can be explained as follows: After the kits used by the laboratory or other departments cooperate with specific equipment or environment to promote the reaction of human blood and urine and other body fluids with the components in these kits, judge based on the data results Whether the human body is in a healthy state .
Based on national regulatory classification, most in vitro diagnostic reagent products belong to medical device management, and very few belong to drug management. At the same time, according to the degree of supervision, the National Drug and Medical Device Supervision and Administration Agency defines in-vitro diagnostic reagent products as the second category mostly, and some of them are classified into the first and third categories. In addition, according to product types and methodology, in vitro diagnostic reagent products are generally divided into: immune, biochemical, and genetic testing.
The raw materials of in vitro diagnostic reagents are generally based on antigens, antibodies, secondary antibodies, enzyme conjugates, probes/primers, etc. corresponding to various products.
2 Status quo and problems of in vitro diagnostic reagent raw material enterprises
How to judge the quality of the raw materials of in vitro diagnostic reagents: According to the "Guidelines for the Analysis and Evaluation of In Vitro Diagnostic Reagents", the indicators that need to be analyzed and evaluated include detection limit, linear range, reportable range, accuracy (recovery experiment, methodological comparison), and precision , Interference test, stability, reference value, etc. At present, in the process of developing in vitro diagnostic reagent products , the basic solidification of the process or the limited selection of several modes has become a trend, so the most critical issue that determines the quality of the product focuses on the selection of raw materials.
Domestic in-vitro diagnostic reagent manufacturers started in the 1980s and basically used imported raw materials from abroad, such as products from Merck, Sigma, and GE . Domestic in vitro diagnostic reagent product raw material companies have emerged one after another since the 1990s, and have developed for more than 30 years. As the domestic biological industry was optimistic at the beginning of this century, a number of relatively large-scale biological enterprises were born. For example, only Feipeng Biological Technology Co., Ltd., Novozan Biological Technology Co., Ltd., Shenzhen Riyali Group Co., Ltd., Tianjin Kangyuan Biological Technology Co., Ltd. and other companies have formed a certain market scale , but they are far from satisfactory. For the needs of domestic manufacturers, foreign raw materials still account for more than 60% of the domestic market .
Why the domestic raw material companies have not developed well? The author believes that there are the following problems:
2.1 In-vitro diagnostic reagent raw material enterprise management system and external demand and environmental issues
2.1.1 The user's raw material introduction ideas and technological level
To develop a new product of in vitro diagnostic reagent raw materials, often in the initial stage, use a mature system including the formulation and process flow of various component substrates, and look at it as you go to screen and match the raw materials. However, the current raw material research and development companies lack comparisons with imported similar products in terms of application, and it is difficult to guide users to make different treatments . In addition, most manufacturers’ early-stage products and many processes are based on imported raw materials to explore the process, seldom consider the characteristics of the raw materials themselves, each raw material has its own unique requirements for the process and formula, which may bring some deviations. , Miss some very good raw materials.
The immunodiagnostic materials are mainly divided into antigens, antibodies and other special components. Among them, the quality of antigen and antibody directly affects the core quality of the product: in actual production, all the antigens to be tested are natural antigens, but the current raw materials for immune antibodies are basically expressed and recombinant, so it will bring many application problems and must be obtained. Pay attention ; in addition, other special components in the reagents, such as Triton, Tween, blocker, mouse serum, etc., although the performance is evaluated in the initial stage of research and development, they generally lack systematic experiments and therefore lack Supporting data for user research and development is not recognized by the largest number of users. Even many raw material manufacturers are unable to provide product manuals. Not to mention guiding users to use raw materials, it means that the raw materials themselves cannot be achieved, which further affects the research and development effect.
In addition, due to the limitation of experimental conditions, some original work was not done, which made it impossible to provide data or instructions, such as the affinity constant of the antibody, the determination of antibody subtypes, and the pairing of monoclonal antibodies. Solid R&D data can give users a solid feeling, but domestic manufacturers are not doing enough. The biggest problem is that the products of many manufacturers do not have enough clinical data to support them and are not enough to win the trust of most customers. Therefore, many domestic raw materials have been eliminated at the starting line .
2.1.2 Raw material manufacturing workshop management
The on-site management level of laboratories or production workshops is low and cannot meet the on-site assessment requirements of medical device suppliers. The author has been to some companies to study and study, and found that domestic companies such as Fei Peng, Modus, Riale and other companies are still relatively strict on-site management. However, most domestic companies still need to improve their sites. At present, there is a big gap in three aspects: the standardization of quality control discussed later (the main problem is whether the inspection, whether the inspection is strict, whether the inspection standard is higher than the national standard, etc.), The management of controlled materials such as products (mainly whether the management is truthfully declared, the supervision of use links, and whether the waste treatment is in compliance) and the production environment control (such as process water, clean workshop, three waste treatment, etc. ).
2.1.3 Management specifications for raw material packaging
18.104.22.168 Verification of inner packaging materials
The inner packaging material refers to the packaging material that is in direct contact with the raw material. The author has been engaged in the production of in-vitro diagnostic reagent products for many years and realized from practice that the quality of many raw materials, especially the stability, is related to the packaging materials of the stored raw materials. However, from the published information, few domestic raw material companies have achieved internal packaging materials. verify. At present, the internal packaging materials of domestic raw materials are generally divided into glass bottles, plastic bottles and rubber stoppers of different materials. As far as I know, the antigens of some of the Jiagong series products cannot be stored in bottles with butyl rubber stoppers, but can only be stored in bottles with natural rubber stoppers. I believe this is also unknown to many manufacturers .
22.214.171.124 Standardized management of packaging issues
- Labels, instructions, outer packaging, inspection reports, invoices, invoices, etc. involve inconsistencies in product names, or even different from the national standard names, causing unnecessary trouble in the later use of users.
- Labels, manuals, and outer packaging are missing items. The correct content should include but is not limited to product name, specification, quantity, concentration, unit, whether to avoid light, name of manufacturer, matters needing attention, etc.
- Quality problems with labels, manuals, and outer packaging. Because most of the biological raw materials need to be stored at a low temperature, even placed in an environment below minus 80 degrees, the quality of labels, instructions and outer packaging is required to be high, otherwise they will not be able to adapt to the low temperature environment and cause confusion during delivery.
2.1.4 Raw material quality inspection and standardized management
126.96.36.199 Quality standard management and implementation issues
At present, domestic in vitro diagnostic reagent raw material companies have problems with imperfect quality standards and non-standard quality inspection reports. The quality standard must be specified in the raw material purchase and sale contract in accordance with laws and regulations, and this quality standard must exceed or be equal to the quality standard of the product using the raw material, and the quality inspection report of the corresponding batch must be provided during the supply period. For example, if the first three collagen-coated monoclonal antibodies are used in luminescent products, its quality standard must be higher than or equal to the national standard of the first three collagen luminescent kits. After there are quality standards, the quality of products must meet the agreed quality standards before they can be shipped. This requires companies to increase quality risk control, quality control, and products.
In fact, this is also a common problem of biological raw materials in the world, because many raw materials did not think of becoming the core material of a certain medical device when they were developed. Therefore, there is no clear quality standard and standardized quality inspection report, which also leads to the purchase and sale of the market. When new demands are generated, some companies cannot keep up with the new demands.
188.8.131.52 Quality information lacks clinical data support
The industrial chain of raw material companies, manufacturers, and clinical users has not formed a good feedback mechanism to meet clinical needs. However, because clinical trials are difficult to do, many companies do very little, so in fact, raw materials have not undergone rigorous clinical verification. At present, many in-vitro diagnostic reagent raw material manufacturers at home and abroad produce a wide variety of raw materials, and even many manufacturers have launched seven or eight monoclonal antibodies for a certain variety. It is difficult to make the best recommendation except for the lack of clinical data due to methodological reasons. As for how users use the whole Relying on the user's own screening and evaluation, in this way, the user's research and development is taken up most of the time by the raw material screening.
184.108.40.206 Quality data fraud
The quality inspection data may be falsified, which is also the current status of some IVD raw material companies. This problem is not much analyzed.
2.1.5 User demand management
220.127.116.11 Qualification issues.
The in-vitro diagnostic raw material industry has its particularities, so there will be some special places in national supervision, such as dangerous goods business license, drug package certificate, etc. In-vitro diagnostic reagent manufacturers need suppliers to provide these qualifications, but some suppliers are unwilling to provide such qualifications or are unwilling to bear possible costs, so they are unwilling to provide these qualifications. There are also some companies that cannot provide users with the latest qualifications due to their sense of responsibility, which also affects the user experience.
18.104.22.168 After-sales technical use guidance and feedback
In the materials provided to users, the lack of technical guidance makes users lack of guidance in the process of using raw materials, thus missing the best process system, and then affecting product quality.
22.214.171.124 Transportation issues
At present, the conditions for the transportation of in-vitro diagnostic reagent product raw materials are gradually being paid attention to and checked by the national regulatory authorities. The best thing is that the professional cold chain transportation process must be verifiable, traceable, and recordable. The cost is shared or negotiated between the supplier and the buyer. Some companies may not realize this yet and have low requirements for product transportation. Some companies are aware of the impact of refrigeration or freezing conditions on the label, but do not pay attention to isolation, which affects the quality of the product label. The above operations may bring quality risks, and may bring regulatory troubles to in vitro diagnostic reagent manufacturers.
2.1.6 Sustainable production capacity of raw materials and R&D investment
At present, most of the domestic in vitro diagnostic reagent raw material manufacturers are still in the era of small workshop economy, and the non-standard laboratory animal breeding has caused the continuous production capacity of related enterprises to be insufficient, and the output of each batch of products is not large, which affects the stability of the product for a certain period of time.
However, due to the outbreak of the new crown epidemic, many companies have obtained sufficient funds and have thick shoulders and want to make their debut. However, I think that many companies buy land to cover floors, but not much money is actually spent on research and development. This is also a strange aspect of Chinese investment.
2.1.7 Difficulties in customs declaration for some biological raw materials
Part of the biological raw materials are difficult to declare, and the approval time is long, which is also one of the reasons for the inability to obtain effective materials in time.
2.1.8 With the influx of a large amount of hot money, how to choose which raw materials to make has also become a difficult point.
The influx of hot money is good for the research and development of new raw materials to a certain extent, but the current antibody sequencing technology has discouraged many raw material research and development manufacturers. Choosing which raw materials to develop and how to protect property rights have become the most troublesome issue for the raw material industry in the IVD industry.
2.2 The current situation facing the industrialization process of domestic in vitro diagnostic reagent raw materials
2.2.1 The importance of advancing and improving the industrial chain of in vitro diagnostic reagent raw materials
The trade war between China and the United States is raging. The Western camp is helping the allies openly and secretly. The two sides call on each other, but the most striking thing is the related battles in the supply chain. The leaders of domestic in vitro diagnostic reagent manufacturers must also fully realize that if they want to develop and grow, they must master the supply chain, and it is best to produce them by themselves. However, I believe that most companies do not have the energy to produce upstream raw materials and can only rely on domestic companies, which brings business opportunities to domestic raw material manufacturers. At the same time, some foreign companies have established experimental platforms in China to directly carry out production and transformation in China, which can also guarantee domestic emergency needs. In addition, the country has already carried out pilot projects in Shenzhen, such as the cooperation between the customs and Shenzhen Ruiali Group to create a one-step customs declaration platform for biological products, which has attracted the attention of many companies.
2.2.2 The promotion of relevant policies to the domestic in vitro diagnostic industry chain
From the relevant national policies to the cost promotion of medical institutions, coupled with the fact that domestic in vitro diagnostic reagent manufacturers have indeed made great progress, domestic in vitro diagnostic reagents have begun to appear in the mainstream market. However, long-term use of imported raw materials will bring about cost problems, often unable to obtain a cost-effective advantage in competition with foreign products, and may also bring about the risk of raw material supply and product supply shrinkage. Therefore, the great development of domestic in vitro diagnostic reagents has also brought huge demand to raw material companies.
2.2.3 The urgent need of enterprises for the introduction and optimization of modern management
Profit is the foundation of the development of an enterprise. Business management is to optimize the allocation of resources and maximize profits under the same resource conditions. China's in vitro diagnostic reagent raw materials manufacturers are also facing the problem of survival and development. Starting from actual needs, they must also increase revenue and reduce expenditure. Therefore, they need to improve their management level and optimize each link process to adapt to the development of modern enterprises.
2.2.4 Market evaluation of the in vitro diagnostic reagent raw material industry
China’s population accounts for 22% of the world’s total population, but the share of in vitro diagnostic reagents only accounts for 2% of the world’s total. In recent years, the rise and integration of various new technologies and methods has promoted the development, application and update of in vitro diagnostic reagents. After the replacement, it is estimated that the size of the raw material market will be between 2 and 3 billion . In this context, the original products may no longer meet the needs of the market, and raw material companies should act as a pioneer and build roads and bridges for the development of subsequent diagnostic reagents. For example: the current drug tracking and animal testing products have just begun to become popular, but some of the relevant raw materials have been developed more than ten years ago, especially some foreign companies have already set foot in them.
2.2.5 The capital market needs to see blood
Since 2020, the IVD industry, including the raw material industry, has continued to explode news of successful listings and large-scale acquisitions. In the past, this industry had low attention and seldom received the appreciation of capital. Basically, each company relied on its own accumulation to develop and grow. Therefore, the pace is very stable and will not easily move in a certain direction. But the scourge of capital doesn't care about this. When it comes, I will be born on the spot. The existing product systems and models will definitely need to be reformed, breakthroughs, and new products will come out. This is an inevitable trend.
3 Development prospects and suggestions of domestic in vitro diagnostic reagent raw material manufacturers
Domestic in vitro diagnostic reagent manufacturers are facing new situations and opportunities and should make the following adjustments:
3.1 Management optimization of domestic raw material production enterprises
In fact, it is not just to improve the management level of on-site laboratories and production workshops, but to improve the management level of the entire system, including system documents, on-site management, and on-site records. To achieve this, the author thinks that regulations, personnel training, implementation of sop, equipment guarantee, supervision, rewards and punishments must be made. Improving the level of enterprise management is not simply to welcome users' on-site assessments, but to demand benefits from management and quality from management, so as to effectively solve the inherent problems of the enterprise.
Manufacturers of in vitro diagnostic reagent raw materials should not be limited to the following aspects:
3.1.1 Verification of internal and external materials
First of all, the relevant content must meet the requirements of national regulations and related policies. Secondly, we must design a rigorous plan, actively carry out internal and external material verification, and eliminate hidden quality hazards in the bud. It is also necessary to proceed from the subtle points, carefully review the company's relevant packaging and ticket compliance, strictly control the quality, consult relevant personnel, and improve the information.
3.1.2 Make quality standards and issue quality inspection reports rigorously
The quality standard must be based on the relevant product national standard and combined with the actual situation of the company’s products to formulate an internal quality standard not lower than the national standard. After the company produces the raw materials, it shall be inspected in accordance with the requirements on the designated equipment in accordance with the inspection methods and methods stipulated in the quality standards.
During the inspection process, if the inspection result of the enterprise is qualified, the quality inspection department can issue a qualified report and issue a release form, and the business department can conduct sales; if the inspection fails, it should issue a non-conforming report to strictly control the entry of unqualified products into the sales channel.
3.1.3 Qualification certification and timely update issues
Strictly abide by national regulatory requirements, actively carry out relevant certifications, and provide users with relevant qualifications in a timely manner. For some certifications that are not mandatory by the state, if users need them, try their best to cooperate with related work. After the certification is completed, the relevant materials should be copied and stamped with the official seal of the company before being delivered to the user, and no copying is allowed again. At the same time, it is necessary to establish user information usage records, and update the qualifications of users in need according to the validity period of the qualifications in a timely manner.
3.1.4 Thoroughly solve the environmental problems of transportation and storage
Strictly comply with legal requirements, prepare cold chain transportation regulations, plan and upgrade cold chain related equipment, and add wireless monitoring and alarm devices. Choose cold chain suppliers carefully, verify and confirm the transportation plan they provide, sign a contract after meeting the requirements, and cooperate with users in cold chain transportation as required.
3.1.5 Professional Marketing
New business perspectives, different user groups, marketers must undergo professional training. Different from the marketing of in-vitro diagnostic reagents, the marketing of raw materials is more professional, so it is necessary to be equipped with technical experts and receive professional marketing training to maintain the continuous growth of business capabilities.
3.1.6 Co-construction of laboratories at home and abroad
At the same time, there are also some foreign companies that have established experimental platforms in China to directly conduct experiments and production transformations in the country, which can also guarantee domestic emergency needs.
3.2 Establish a third-party evaluation platform for in vitro diagnostic reagent raw materials
To do a good job in internal management of an enterprise, it is also necessary to strengthen mutual trust between the enterprise and its users. The author believes that the current in-vitro diagnostic reagent raw material industry products are still in the link of comparison with other manufacturers in terms of obtaining users, and there is no breakthrough, which is not conducive to the development of the industry . Therefore, it is recommended that companies emerge as a third-party role in the raw material evaluation center, do objective positions, evaluate raw materials from the perspective of the third party's fairness and fairness, and use practical actions to support the credit construction of both raw material purchase and sales. On the one hand, the third party represents the basic point of independent expression of opinions; secondly, a platform-based professional evaluation center will form a scale effect, form a stable experimental idea, and form a more professional perspective.
The following opportunities and problems may exist in establishing a third-party evaluation center:
3.2.1 Platformization brings the possibility of multi-platform inspection of raw materials
Industry practice has proved that many raw materials cannot be applied or not easily used on one platform. This does not mean that they have failed to use on other platforms. However, a company also takes into account luminescence, POCT, enzyme labeling, turbidity, time resolution, radioimmunity, and radioimmunity. gold and other standard methodology is too hard, it can work through more than the construction of a third-party assessment center model form a new industrial chain, to solve this problem, to win the trust.
3.2.2 Co-construction of a third-party testing center and a third-party in vitro diagnostic reagent raw material evaluation center
With the vigorous construction of independent third-party testing centers in China, I think it has brought the possibility of platform-based raw material evaluation. The division of labor is well done. The raw material companies provide evaluation raw materials to specify evaluation methodology and comparison standards or other manufacturers’ products according to their needs; third-party evaluation companies are responsible for designing plans for sample preparation; third-party testing companies conduct testing and evaluation, and then reverse the results level by level Return, and finally communicated by the raw material manufacturer to the user. In this way, new services are introduced for the temporary inspection center, which may bring new growth points. In addition, the innate advantage of the clinical inspection center is that it is rich in clinical samples, and a very important part of the raw material inspection is the accuracy and stability of the clinical measurement values, which may solve the problem of the clinical compliance rate of the raw material inspection.
3.2.3 The evaluation center needs to conduct market research
Market research for this project is very necessary, and market operations must be conducted after research. Because the business is divided into three service objects: raw material manufacturers, reagent manufacturers and some research institutions. In order to evaluate their products, raw material manufacturers may accept business in order to have a "third-party evaluation" signboard; in order to develop new products, reagent manufacturers may take shortcuts or fail to accurately evaluate the initial research and development conditions, so they entrust external parties. Evaluation: In order to publish papers, evaluate raw materials or verify processes, scientific research institutions do not have corresponding staffing and experimental conditions, so they entrust external institutions to conduct them. In order to clarify the above needs and to form the demand into the market, professional market research is required, the idea of the target group needs to be understood, and the work needs to be carried out first.
3.2.4 Application of platform data
Through third-party verification data, raw material manufacturers can obtain comparison information with competing products of other companies, and can be used as marketing materials on a comprehensive and balanced basis. Companies that use raw materials can eliminate the need to select raw materials during the development of new products, and select the most cost-effective raw materials based on third-party verification results. Scientific research institutions can integrate part of the experimental process and results as experimental steps into scientific research projects to test scientific research results.
3.3 Personnel trust
At present, there is still very little communication between domestic in vitro diagnostic reagent raw material companies and users, but analysis shows that more than 85% of sales tasks are achieved mainly from active communication to gain trust. This view may not be correct or not reach such a high ratio in the purchase and sale of in vitro diagnostic reagents raw materials, because some good products really don’t take the initiative to attack, but most of the products do not belong to this category, so it must be proactive. Marketing.
3.3.1 Treat people sincerely
In order to achieve trust, the relevant raw material sales staff must first treat others sincerely. As the saying goes, buying is not the essence of selling. In fact, many people have misunderstood this sentence. What this sentence really expresses is that salespersons have to do a lot of work to be more fully prepared. Buyers want to know what salespersons need to know. Know more in order to reach deeper deals. Both buyers and sellers do this, and at least they can smoothly express their thoughts and communicate effectively.
3.3.2 Continuously provide valuable information
In order to increase trust, salespersons must continue to provide a lot of valuable things. In order to increase sales, salespersons must let users know about new products and the latest promotional information, and consider how to let others know the purpose of the salesperson's visit.
3.3.3 Other issues
Only with sufficient trust, adequate communication in the early stage, and the point of mutual agreement can we reach the stage of actual procurement. From the perspective of marketing, there must be an environment in which transactions occur. In fact, there needs to be an intersection between the purchaser and the seller. The essence of the intersection is that the user's needs and sales can be met, and the user has the ability to pay for the expenses generated by the demand, so that it will be substantive. Trading behavior. For in-vitro diagnostic reagent companies, the trading environment includes not only the intersection of the two parties, but also the allowable by regulations, the supplier’s assessment and review through entering the qualified supplier list, the possible settlement of previous disputes or the reluctance to accept, the support of third-party data and comparison data , The unification of the research and development ideas of the purchasing enterprise and the expected use of the products of the sales enterprise, and so on. The completion of the purchase and sale business, or even the completion of the payment, is not the end of this type of business. If there is a problem, communicate and solve it in time; if there is no problem, you must also strive for feedback on the experience to facilitate the marketing of similar users.
At the beginning of 2020, a sudden epidemic brought grief to all parts of the world, but it also brought opportunities to Chinese companies related to in vitro diagnostic reagents. Due to the large number of cases in China at the initial stage of the epidemic, in vitro diagnosis poses a strong challenge. In this process, hundreds of manufacturing companies have obtained international and domestic sales licenses, and on this basis, there has also been a huge demand for upstream raw materials. Related in-vitro diagnostic reagent raw material companies have risen to the challenge and basically met the vast majority of the world’s raw material requirements for new crown products, verified the company’s research and development capabilities, verified the company’s rapid response capabilities, and verified the company’s production capacity. Therefore, we believe that domestic In vitro diagnostic reagent companies are a group with potential to be tapped.
This article analyzes some of the problems that currently exist in China's in vitro diagnostic reagent raw material manufacturers, and introduces some of the opportunities that currently exist. In response to the above situation, the author proposes some measures to strengthen the mutual trust between buyers and sellers. In particular, it is recommended that people with lofty ideals set up a professional platform-based "in vitro diagnostic reagent raw material evaluation center" to meet new challenges!
Reprinted: Xiaojudeng.com Brief analysis of the commercial situation of China's in vitro diagnostic reagent raw material enterprises