Panoramic interpretation of compensation system for patent period of drugs: five suggestions for domestic pilot

Source: medical economic news 2018-01-25 In order to put forward clear paths and suggestions for the pilot design of drug patent link and patent period compensation system, the international food and drug policy and law research center of Shenyang Pharmaceutical University held the "high end Forum on drug patent link and patent period compensation system" in Beijing in mid January, which was jointly discussed by experts from all relevant functional departments, industries and enterprises, How to design the system, how to implement it, how to establish the balance mechanism of innovation and imitation and other key issues have formed a certain consensus In order to protect drug innovation, encourage innovative drugs to enter China's market as soon as possible, and meet the growing demand of the public for drug use, the opinions on deepening the reform of review and approval system and encouraging innovation of drug and medical devices put forward: to carry out the pilot of drug patent term compensation system Select some new drugs to carry out the pilot, and give appropriate compensation for the patent period occupied by clinical trials and review and approval This is an important institutional innovation in the field of medicine in China It is necessary to learn from the international experience and speed up the establishment of the patent period compensation system for drugs According to Abraham Lincoln, "patent system is the oil of interest to the fire of genius." Why should the patent period of drugs be compensated?   Because drugs are a special commodity, the core patents of drugs are mostly applied for and authorized in the early or middle stage of drug research and development The patent period is generally 20 years, while the R & D of innovative drugs generally takes about 10 years In the process of drug research and review and approval, the effective patent period is occupied to some extent Some studies show that the average remaining patent period is only 6-9 years when drugs are on the market 。 In order to encourage the enthusiasm of innovative drug research and development in the pharmaceutical industry, we should give appropriate patent period compensation to maximize the expected return of drug research and development investment, so as to promote the continuous investment in innovative drug research and development, and resist the threat of human health diseases In 1984, the United States took the lead in establishing the patent period compensation system Subsequently, Japan, the European Union, Australia, Israel, South Korea, Russia and Taiwan all set up patent period compensation system The design of the system is different, and the emphasis and effect of encouraging innovative drug research and development are different From the industrial point of view: it has the characteristics of high investment, high risk and long cycle to encourage drug innovation and new drug research and development The intensity of R & D investment in pharmaceutical industry is largely affected by the expected return of R & D investment, which is determined by the market monopoly time and market demand after the innovative drugs are listed Extending the patent period is to extend the market monopoly time of innovative drugs, so as to improve the profit expectation of enterprises, promote the continuous R & D investment of enterprises, and continue to encourage drug innovation In the early 20th century, a study by the European Pharmaceutical Industry Association concluded that the hatch Waxman act had completely lost the traditional leading position in the field of pharmaceutical innovation in Europe, realized the strategic transfer of innovative drug research and development bases from Europe to the United States, and the United States pharmaceutical industry was at the international leading level After the introduction of patent period compensation system in 1987, Japan strengthened the protection of drug patents, and the pharmaceutical industry gradually realized the strategic transfer from "imitation" to "creation" 2 Trade Perspective: encourage innovative drugs to enter China Currently, innovative drugs have been defined as "global new", that is, "innovative drugs that are not listed at home and abroad" Innovative drugs are usually heavily protected by basic and peripheral patents The review and approval reform carried out in China has basically solved the backlog of drug review, greatly improved the efficiency of review and approval, coupled with the large population of our country, the potential of innovative drug research and development that has not yet met the demand for treatment is huge If the new drugs are given appropriate compensation for the patent period, it can greatly improve the attraction of our country as the preferred place for the listing of innovative drugs, and promote the early entry of innovative drugs into our country China's market, to meet the vast majority of the people's unmet treatment needs, for the benefit of the people 3 Review and approval angle: promote review and approval and improve efficiency The period of compensation for the patent period of drugs is subject to multiple restrictions Generally, the period of compensation does not exceed 5 years, and there is a ceiling limit on the period of effective patent of drugs after the approval of marketing, usually 14 years That is to say, the time limit for the extension of the patent period of drugs is the reasonable time for clinical trials and review and approval, excluding unreasonable delay, such as the time limit for delay due to failure of duty This restriction urges the applicant to be more serious and rigorous in the process of submitting application and supplementary information, and try to meet the review requirements, so as to improve the quality of application materials and reduce the review delay caused by the applicant's failure to fulfill his duties The review agency will also strictly review the time limit and improve the efficiency of review and approval In 1984, the United States passed the hatch Waxman act, which established a creative balance mechanism, in which the main system design to encourage innovation is the drug patent extension system (PTE), that is, to extend a patent period to compensate for the time spent in clinical trials and drug market review (NDA) 2 In order to encourage the research and development of innovative drugs, Japan revised the patent law in 1987, and established a system of extending the period of drug patents to compensate for the time when the patents could not be implemented due to the review of the market According to a study conducted by Tokyo University, 15 of the 21 blockbuster drugs produced in Japan in recent years are produced by local enterprises, and the 15 blockbuster drugs benefit from the extension of patent period, with the exclusive period from initial approval to generic drug listing ranging from 11 to 21 years 3 EU issued EC regulation 1768 / 1992 "supplementary protection certificate act" in 1992 to provide supplementary protection certificates (SPCs) for drugs, that is, to extend the patent period for drug patents that meet the requirements Regulation (EC) 469 / 2009 was issued on 6 May 2009 to amend the SPC act 4 Canada signed the comprehensive economic and trade agreement (CETA) with the European Union in February 2017 In order to meet the requirements of the agreement, Canada issued the supplementary protection certificate regulation of Patent Law on September 1 Unlike other countries, Canada's CSP system is accepted, approved and certified by the Canadian Ministry of health To correct the misunderstanding 1: it is only for the benefit of foreign enterprises The patent period compensation itself does not aim at the tendency of foreign enterprises Whether the drug patent meets the compensation conditions depends on the approval and listing of drugs in China, the effective patent situation and the patent period compensation rules From the perspective of different countries, patent extension rules are different, with the United States and Europe as the representative to encourage breakthrough innovative drug research and development through patent compensation system, while Japan has made appropriate adjustments in patent extension rules, and the innovation ability and profitability of local enterprises have been greatly improved Error 2: due to the low efficiency of review and approval, the compensation for patent period of drugs is not to compensate for the patent period delayed due to the low efficiency of review and approval, but to compensate for the loss of effective patent period of drugs due to the need of review and listing Because drugs are special commodities, they must be strictly tested and approved for marketing, which is an inevitable and indispensable process, occupying a part of the valid patent period According to international experience, the normal occupation time of this process is about 5 years In general, the compensation period is no longer than 5 years, which is also based on this consideration Error 3: it will inevitably lead to the delay of generic drug listing when the patent period of generic drugs is extended It should be noted that the compensation system for the patent period of drugs is not a single system This system, together with patent link, first imitation exclusive system, compulsory licensing system and data protection system, can achieve the goal of creating a balance of imitation The patent extension system can encourage the research and development of breakthrough or improved innovative drugs, reduce low-level repeated imitation During the patent period and patent extension period, the generic applicant can also accelerate the listing of generic drugs and achieve the dynamic balance of innovation through patent challenges, compulsory licensing or signing patent settlement agreements The elements of pharmaceutical patent compensation system, the basic elements of system design, 1 The product scope and patent scope of patent compensation, the products and patent types included in the compensation scope, have the guiding role of encouraging innovation The scope of patent period compensation in various countries is different, and the innovation orientation is also different From the perspective of encouraging drug innovation, the United States, the European Union, Canada and other countries encourage breakthrough innovation, while Japan encourages both breakthrough innovation and improved innovation In principle, the product scope of patent compensation is applicable to all products occupying the valid patent period due to research or review, including chemicals, biological products, traditional Chinese medicine, etc The scope of compensation patent is mainly basic patent, including product patent and use patent Different countries have different system designs The main difference lies in whether the preparation patent and process patent are included in the scope of compensation The United States, the European Union, Canada and other regulations stipulate that the preparation patent and process patent are not included in the scope of compensation, but the process specific product patent is an exception, which can also be compensated In Japan, the process patent and preparation patent of active ingredients are also included in the scope of patent that can be applied for compensation The EU also provides for an additional six months of compensation for paediatric indications while extending the patent period 2 Conditions for granting the extended period of the patent: the conditions for granting the extended period of the patent generally include three basic conditions: the product has passed the review of the regulatory authority before it is put on the market or sold for use; the product has been approved for the first time to be put on the market or sold for use; and the patent has not expired before the application is submitted Other conditions for granting a patent: different countries have different requirements The United States requires that the patent applying for compensation patent period must be registered in the orange book The United States, the European Union and Canada stipulate that the patent period of each drug licensed for marketing can only be extended once Japan grants patent period compensation for the same active ingredient drug based on different patents under different marketing licenses, i.e multiple patent periods can be compensated 3 The core of compensation period calculation and patent period compensation is the valid patent period occupied by clinical research and review and approval of drugs From the international experience, there are two ways of thinking: accurate calculation and calculation The United States belongs to the accurate calculation mode, while the European Union, Japan and Canada adopt the calculation mode Relatively speaking, the latter is easier to operate and easier to implement The flexibility of compensation method is reflected in the definition of compensation period The definition of compensation period is limited by three factors: first, the compensation period of single patent shall not exceed 5 years; second, the maximum time limit of effective patent period after drug listing is 14 years in the United States, 15 years in the European Union and no maximum time limit in Japan Third, the calculation method of the extended time limit is different in different countries Patent extension period in the United States = 1 / 2 of clinical trial time + FDA listing application review time - applicant's time of failure to fulfill his duty Patent period of Japanese drugs = date of approval of drug listing - [date of registration of relevant patents or date of commencement of clinical research (whichever is later)] As Japan allows multiple patents of drugs to be extended for many times, there is no upper limit for the effective patent period after the drug is listed Take leuprorelin, a blockbuster drug of Takeda pharmaceutical, as an example The drug was approved to be listed in 1992 and the generic drug was approved to be listed in 2013