Medical network - December 5, if is upstream of the gene sequencing industry company, product sales target customers widely, across the scientific research, medical treatment, the inspection field, including sequencing, DNA extraction kit, capture kit/baryon amplification kit, database construction kits, computer sequencing kit. Sequencing machine, computer sequencing kit both of them are binding, DNA extraction kit, capture kit/baryon amplification kit, the kit can be used for building a third-party products, domestic enterprises can be cut from the three directions, but the most critical tool enzyme and separation of the kit materials are mainly imported products, the barriers is higher, if we can achieve these two products import substitution, suggests that the enterprise has strong technical strength.
Involved in the whole country at present company has more than 200, of the concept of genetic testing in accordance with the scope of business, the company can be divided into:
(1) the upstream gene testing instrument development enterprise (sequencing machine, chip scanner, PCR equipment);
(2) provide sample processing reagents and consumables shelter-forest enterprise (building kit, testing kits, tool enzyme, gene chip);
(3) provides third-party genetic testing services middle enterprises;
(4) provide sequencing data storage, analysis and report of the downstream enterprises;
(5) and the three parts together CRO services business company
Allow, of course, if the company research and development strength and economic power, most companies will choose upward downstream industry chain extension, to further improve their profitability.
According to genetic testing company service content, the main can be divided into four classes: scientific research services, third-party clinical genetic testing services, direct testing services for individuals, not medical and genetic testing services, such as food, environmental and forensic applications).
Today we share content focus on or genetic testing used in medical diagnosis, the field wide audience, added value is high, the market space is large. Including the following aspects:
1, in the name of scientific research, medical diagnosis service for the patients with:
In which the doctor plays a leading role, recommend that patients need to do genetic testing, in which doctors benefit is gained by the guidelines on the basis of, the scientific research data, get the sales commission, which is currently adopted widely in tumor gene sequencing method, because the present domestic only NIPT approved clinical tumor high-throughput detection kits, other can only be disguised in the form of scientific research in medical diagnosis so as to obtain benefits. In pure scientific research genetic testing market level.
2, approval testing outsourcing service for the hospital of the third party independent medical test laboratory:
These institutions can conduct molecular diagnostic services (by raids (center of the PCR laboratory certification), such as QPCR, ddPCR, gene chip, etc., but the application of high-throughput sequencing in clinical detection current is restricted, only the pilot list institutions can issue a formal visit report, currently issued the first batch of pilot in four areas of list, respectively is a genetic disease diagnosis and prenatal screening and diagnosis, human preimplantation embryo genetic diagnosis, tumor gene sequencing, list of pilot unit by health development planning commission medical administration hospital authority and the women's and children's department to work out. Clinical genetic testing market space in billions of level.
3, the commercialization of B2C genetic testing:
Provide personal genetic testing services oriented business company usually provide diagnostic of genetic testing, but our country has many directly to individual genetic testing agency business, the business scope including genetic disease risk, talent, personality characteristics analysis and a series of genetic analysis service, are under pressure to strengthen regulation and integration in the future. Market space in the billions.
4, the medical and genetic testing services:
Including food, environmental microbiology, forensic testing, inspection and quarantine, etc., belong to the fragmented market, involving areas, more space in the billions.
A, genetic testing industry regulation and trend analysis
Gene industry in China in the early stages of the market rise supervision system is not perfect, also gives person's feeling is very chaotic.
2014 years ago, the gene sequencing industry in our country is in a state without supervision;
In February 2014, the CFDA all gene sequencing and health development planning commission to stop business, focus on industry consolidation;
In March 2014, the health development planning commission issued "about clinical application for high-throughput gene detection technology pilot unit declaration work notice, notification request has been to develop high-throughput gene sequencing technology, and conform to the requirements as prescribed in the declaration of medical institution may apply for a pilot and specific application pilot gene sequencing projects at the same time.
In December 2014, the health development planning commission medical hospital authority issued a genetic disease diagnosis, prenatal screening and diagnosis of genetics, human preimplantation embryo in the diagnosis of the three professional the first batch of gene sequencing clinical trial;
Then in January 2015, the health development planning commission for women's and children's department approval 108 health service agencies to carry out clinical trial NIPT high-throughput sequencing technology, and to review the genetic diagnosis by 13 in human preimplantation embryo in clinical trial;
In March 2015, the medical administration hospital authority has released the first batch of tumor diagnosis and treatment of the high-throughput sequencing project pilot list.
Since the CFDA approved a few for high-throughput sequencing instrument, test reagents, etc.
Who, then, by genetic testing industry regulation, how to regulate, what is the scope of regulation? We have done the following.
Regulators: the genetic testing industry involves subdivision is numerous, including hospitals, visit center, instruments and reagents, commercial companies, different technology platform, etc., so involves more regulators.
(1) the national development and reform commission, from the macroscopic and the genetic testing industry development plan:
In June 2015, the national development and reform commission issued "the national development and reform commission notice on major projects package emerging industries, which will focus on developing new medical technology such as genetic testing, and will be in 3 years time 30 genetic testing technology application demonstration center construction, rapid advance gene detection of clinical application and testing instrument reagent of localization;
In addition to the local development and reform commission is also involved in genetic testing project pricing, such as sichuan province development and reform commission (NDRC) pricing noninvasive prenatal 2400 yuan/times.
(2) health development planning commission, mainly is to carry out genetic testing agency qualification review and standardize, regulation of concrete consists of three parts, respectively is medical health bureau, women's and children's department, visit:
Medical health bureau has issued a genetic disease diagnosis, prenatal screening and diagnosis, human preimplantation embryo genetic diagnosis, tumor diagnosis and treatment of the four major list of the first gene sequencing of clinical trial, the drug metabolic enzymes and drug targets for gene detection technology guidelines (trial) ", "the tumor detection technology guide individual therapy (try out)" and other specifications;
Women's and children's department for the prenatal detection in medical administration bureau of health reform pilot list added 108 on the basis of medical service institutions to carry out clinical trial NIPT high-throughput sequencing technology, and to review the genetic diagnosis by 13 in human preimplantation embryo in clinical trial;
Visit the center is the responsibility of the clinical laboratory quality management and control work, running between the national clinical checkout room quality evaluation plan, establish reference system, the application of clinical inspection, to evaluate genetic testing services of medical laboratory and acceptance.
(3) the CFDA for genetic testing instruments, reagents on the chain, analysis software to regulate:
Such as EGFR, KRAS, mutated BRAF, C - KIT, CYP2C9, CYP2C19 gene detection kits, such as gene chip, etc.;
In terms of high-throughput sequencing, the CFDA has approved a few applied to NIPT sequencers and testing reagent, but in the diagnosis of the tumor, there is no high throughput sequencing machine and high flux detection kit, pilot unit can only be carried out in the form of homemade reagent (LDTs) detection.
Technical regulation: the technology platform in genetic testing mainly include PCR (qPCR, ddPCR), FISH (fluorescence in situ hybridization technique), gene chip, sequencing (generation sequencing, high-throughput sequencing), now in addition to clinical service for high-throughput sequencing restrictions, only pilot unit can visit report, issued by other genetic testing techniques, such as the use of PCR, FISH, such as generation sequencing without limit, visit the unit just passed the certification of the PCR lab, pathology lab can apply these technologies.
Agency regulation: what kind of organization to carry out high throughput sequencing clinical services? In addition to the medical health care and maternal and child department released pilot clinical pilot unit list high-throughput gene sequencing technology, and development planning commission approval of "individual medical test pilot unit" (often referred to as pilot LDT), the first batch of pilot units including central south university xiangya medical institute, Beijing bo medical institute and the China medical university first affiliated hospital this three institutions, individual pilot the breadth and scope of medical detection, more than the high-throughput gene sequencing pilot; In addition to some of the local health department approved the establishment by the institute, such as "nanjing high accurate medical examination center".
But even without such qualification, sequencing service agencies can also provide testing services in the form of scientific research report (avoid medical test limits), or set up a joint laboratory and pilot hospital, enjoy the profit sharing.
All this reflects the current immaturity of regulatory genes in our country, the United States visit institutions to take the form of CLIA/CAP is certification, most likely will be similar in our country in the future certification qualification.
Application in the field of regulation: currently, high-throughput sequencing clinical application of pilot also can only be applied to the genetic disease diagnosis, prenatal screening and diagnosis, human preimplantation embryo genetic diagnosis and tumor diagnosis and treatment of four professional direction.
But in the field of cardiovascular, infectious disease, intestinal microbes macro genomics and other fields, the second generation sequencing has good application prospect, the current clinical trial high-throughput sequencing just LDT pilot in a professional direction of the practical application, the future will be more and more wide application field.
For approval by regulatory instruments and reagents: by CFDA high-throughput sequencing to declare a sequencing machine in computer reagent (binding), database construction kits, test kits, analysis software, etc.
NIPT aspect, the CFDA has approved the Genomics (BGISEQ - 100 Ion Torrent technology based on life, based on Genomics BGISEQ - 1000 before purchase Complete Genomics sequencing technology), Ann gene (DA Proton technology based on Ion Torrent of life), bo the biological (4000) based on Ion Torrent of life technology BioelectronSeq, berry and kang (cooperation with Illumina NextSeq CN500) NIPT the second generation of gene sequencing machine and auxiliary reagent (13, 18, 21 chromosome three body detection kits, computer sequencing reagent);
In terms of tumor, at present there is no high throughput sequencing machine and high throughput detection kit, pilot unit can only be carried out in the form of homemade reagent (LDTs) testing services.
In the long run, a multi-objective genetic panel (tens of hundreds of genes or targets) high flux detection kit basic did not approved, because the locus mutation rate is very low, it is difficult to find enough patients in clinical trials, and also can't to verify the test results, so this kind of kit can only be used in raids in the form of LTDs laboratory, not sales;
And a small amount of target gene () a number of genes, and a small amount of mutations detection kit may be CFDA examination and approval, but from the testing cost, a small amount of target gene testing cost will not lower than the multi-objective genetic testing, so the terminal price difference is not big, with multi-objective genetic panel when marketing, do not have advantage.
Conclusion: the current domestic in the clinical applications of high-throughput sequencing regulation is still very immature, pilot list is nominally has clinical inspection report issued by qualified institutions, not other institutions to carry out the sequencing service constraints (can be in the form of scientific research to carry out the service), instruments, reagents for examination and approval of also do not have restricted, market shakeout stage, genetic testing company needs to carry out hedging, on the one hand, preparation of raids qualification declaration, positive hospital terminal layout, on the one hand to instruments, reagents for examination and approval. Our country and the United States may be taken by the future similar CLIA/CAP for examination and approval, first hospital channel layout is expected to benefit.
Case (the CLIA certification) :
In the United States, as long as by CLIA (Clinical Laboratory Improvement Amendments, Clinical Laboratory Improvement act) certification, the third party lab can according to the market demand, developed a variety of new diagnostic reagents and/or services, namely the self-built project or homemade reagent (LDTs).
This test can only be used in the laboratory, not gaiden or sold to any other lab or medical and health institutions, to risk control in a limited range, and therefore not need FDA approval. At the same time, because of CLIA certification is lab, so don't need to make request for approval for each new service or product. Hospitals and patients can choose according to their own needs, the corresponding diagnosis project. This policy to a third party laboratory of free space, also brought the prosperity of the independent laboratory.
CLIA authentication is the most unique place, self-built lab project even in the absence of the FDA's approval, can completely within the scope of the laboratory also provide molecular detection business to guide clinical. As long as it is had a lab of CLIA license, their own research and development of preparation and technology may also be legally in clinical, reasonable charge.
The advantage is that the huge medical needs, and the front of the new technology with each passing day, all the CLIA laboratory can according to market demand, rapidly developed all sorts of new diagnostic applications. At the same time, the United States government don't have to respond to inundated with each new application. And patients can need according to oneself, instant get new diagnostic service. At the same time, the FDA can choose to think really good diagnostic methods for further certification to the FDA, and publish them in the name of the FDA certification, to speed up the FDA think good diagnostic method in the application of the market. Declaration enterprise as long as it has passed the certification of CLIA and can guarantee the quality of the product, then can be directly applied to clinical.
Second, gene sequencing of industry focus: focus on service
Gene sequencing is service, it is difficult to separate on commodity (detection kits, chip) to establish the advantage, that are different from immune diagnosis, chemiluminescence, because genetic testing in the final analysis is a DNA sequence detection, has nothing to do with the secondary and tertiary structure, testing principle is relatively simple, by DNA primers target sequences, and then through the primer extension to realize sequence determination; On the contrary, the sample of DNA extraction, library and capture the operation is more tedious, need professional and technical personnel to operate.
Upstream instrument has been monopolized by a few companies, a hierarchical kit product does not have high technical barriers (of course, if you are under construction in library link and capture link form obvious technical advantage, or to develop more efficient tool enzyme, is also very promising), and the examination and approval of high-throughput genetic testing kit there is a big uncertainty (future reference to the American way of CLIA certification, has the qualification of testing institutions in the form of LTDs homemade reagent used, but not by the food and drug administration for examination and approval can't foreign sales), hospital sample size is limited, to enter the first certainly will occupy a lot of advantages, NIPT markets are close to saturation, cancer hospital competition heats up, so take the lead to preempt the market by service, this may be a more reliable choice.
Hospital will purchase sequencing machine itself in high throughput sequencing? If the hospital yourself sequencing, then visit sequencing institutions will inevitably difficult to compete, so think about this factor is necessary. The problem to be separate, on the one hand, consider the number of users and demand, on the one hand, consider the cost of sequencing. At the current high-throughput sequencing NIPT and tumor diagnosis and treatment is of the most widely used for analysis, for example:
In the field of noninvasive prenatal diagnosis, newborn in about 15 million people each year in China, the potential customer base, NIPT can give definite diagnosis and the corresponding prevention measures, and the results related to the next generation of health, detection in 2400 yuan price, wide audience;
NIPT, moreover, the precision requirement of sequencing is not particularly high (at present mainly for 13, 18, 21 chromosome three body check), detection is a process of quantitative, usually adopt life ion torrent platform (currently approved 5 instruments in which there are three declare ion torrent, and the United States has been using gene chip to do NIPT), many large hospitals can do NIPT service, sequencing on the target market should be in the middle and small hospitals.
But high-throughput sequencing applications in the field of tumor is not the same, our country each year around 4.5 million tumor patients, tumor sequencing panel prices between 8000 and 20000, and now do a panel of tumor sequencing of main goal is to have targeted drugs in patients with medication guide, targeted drug prices more expensive (the medical expenses of each month at around $50000), so the target population is much more narrow;
In addition, the tumor detection for sequencing accuracy is higher, mainly aimed at the point mutation or micro lack micro repeat, tall to the requirement of technology platform, usually adopt Illumina Hiseq/next Seq sequencing machine, instrument and equipment is expensive, and the cost of the boot reagent consumables high (a boot in 150000 or so), if not enough sample size, basically every boot is loss;
And according to the analysis of the tumor is more complex, need special talent of bioinformatics and the database, so in the field of tumor (this is especially true in the field of other patients less), we think the high-throughput sequencing is given priority to with third visit organization, target market in a large hospital.
Three, the development direction of gene sequencing (NGS) company: sequencing is starting point, not a destination
If is upstream of the gene sequencing industry company, product sales target customers extensive, across the scientific research, medical treatment, the inspection of areas, including sequencing, DNA extraction kit, capture kit/baryon amplification kit, database construction kits, computer sequencing kit, including sequencing machine, computer sequencing kit is binding, both DNA extraction kit, capture kit/baryon amplification kit, the kit can be used for building a third-party products, domestic enterprises can be cut from the three directions, but the most critical tool enzyme and separation of the kit materials are mainly imported products, the barriers is higher, if we can achieve these two products import substitution, suggests that the enterprise has strong technical strength.
In the field of scientific research and the commodity inspection, kit the examination and approval of the threshold is low, but the need to provide customized services; In the field of medical diagnosis, polygenic capture kit/baryon amplification kit is unlikely by CFDA approval (it has already been the reasons why), only through certification to be able to visit lab homemade reagent used, so this part of the enterprise (thinking, ii and genetic, burning stone, etc.) to do hedging, preparatory construction raids (center, to the service side layout.
Sequencing is the starting point, not an end, middle sequencing service agencies, the biggest market is in the field of medical diagnosis, in addition to make a profit by providing services, sequencing the biggest potential advantage is able to obtain special patients of tissue samples, and the accumulation of genetic data obtained, it is very convenient conditions for drug development.
Tumor patients, for example, in the use of a targeted drug resistance, after sequencing institutions by gene sequencing found new drug resistance loci (this is PCR, gene chip, the detection of known mutations do not have the advantage of technology), then this site is under the development direction of a targeted drugs, and sequencing institutions can also get the patient's tumor tissues, to develop the original generation cell lines, as a cell model of drug development, it is more than the other drug research and development institutions, the first-mover advantage.
Personally, I watch the train of thought of development mode in its own sequencing service for Bridges, to patients, hospitals, CRO enterprise, the sequencing results provide guidelines, at the same time, in turn, links to the downstream drug development and clinical trials, form good feedback mechanism.
Case (the tumor sequencing company Foundation Medicine) :
Foundation Medicine is a focus on the tumor high-throughput sequencing business company, the company's proprietary platform can be produced to the patient's individual operable cancer genome information, make the doctor can optimize treatment in clinical practice, to make biological pharmaceutical companies to develop more effective targeted cancer therapy.
The company on the basis of the second generation of gene sequencing technology, according to the cancer gene sequencing results provide accurate medication guide for cancer patients. The gene sequencing technology of the company can be found mutations that lead to cancer patients, "individualized medication" into the new field, let physicians according to patients' genetic information for targeted cancer therapy.
Order Foundation service needs to be a doctor of Medicine, patients need to offer more than 10 cases of biopsy or a tube of a few milliliters of blood. Extracted from the DNA of tumor cells to the final report, the duration of the 14-21 days, which contains the detected cancer gene mutation, as well as for each given a gene mutation guidelines are suggested.
Foundation Medicine provides two kinds of products, FoundationOne and FoundationOne Heme. Two kinds of products are based on second generation sequencing, using sequencing machine including Illumina HiSeq 2000 system and Life Technologies' Ion Torrent. FoundationOne detection applicable to all solid tumor, 315 cancer related gene coding region and 28 gene rearrangement of introns, fee is $5800. FoundationOne Heme detection for hematological malignant diseases, such as lymphoma, leukemia, testing 405 gene coding sequence and 31 gene rearrangement of introns, and 265 genes RNA sequences to detect gene fusion, fee is $7200. FoundationOne detection method in October 2013 was published in Nature Biotechnology.
Detection of cancer gene sequencing requires cancer gene database, thus established the database FoundationCORE. Company launched the browser in December 2014, the ICE is 2, the browser is a feature of the patients with "match" function. Clinicians can search in the existing knowledge base FoundationCORE, looking for other similar to that of the patients with tumor genome information of patients. ICE is a new part of PatientMatch 2, is a kind of using FoundationCORE to increase FoundationOne and FoundationOne Heme utilization technology tools. By PatientMatch, doctors use ICE 2 network can and in the treatment of patients with similar genetic data of doctors, and they share the diagnosis and treatment. According to the company in the third quarter of 2015, 60000 cases of clinical information is included in the FoundationCORE.
Foundation Medicine has been trying to it is a field of health care. In 2014, Michigan, city priority health department announced the Foundation of Medicine are cancer genome analysis service coverage; Google said Google company will be the company's cancer gene DNA testing services, as part of its employee benefits plans. Exchange Foundation Medicine also passed the McKesson diagnosis and recognition of the national comprehensive cancer network, can carry on the whole genome of non-small cell lung cancer detection, and received a unique Z - code identifier. In addition, the Foundation Medicine's chief financial officer, Jason, Ryan said coverage gradually expanding in the lung cancer, not only will gradually involved in other diseases.
Foundation Medicine's revenue mainly comes from two aspects, one is from biological pharmaceutical companies, the other one is from clinical diagnosis. In the third quarter of 2015, from a biological pharmaceutical company's revenue was $11.7 million, compared with the same period last year growth of 75%; From the clinical diagnosis of revenue was $13.7 million, compared with the same period last year growth of 40%, revenue growth is very obvious. |
