This is not only a response to external pressures, but also an inherent need for China’s own development.
Editor’s note: This article comes from WeChat public account “ Intellectual capacity ” (ID: zhichanli), authors Shao Wei, Kou Fei, Beijing Yongxin Zhicai Law Firm.
The first phase of the economic and trade agreement between China and the United States on January 15, 2020 is part of the intellectual property community in 2020 A major event, including the detailed protection of drugs is beyond the expectations of the industry. Although the word “pharmaceutical patent linkage system” does not appear throughout the agreement, the industry generally interprets it as further requirements for China’s pharmaceutical patent linkage system, and believes that the US version of the Hatch-Waxman Act is about to come to fruition.
Although the call for the establishment of a drug patent linkage system has appeared frequently in China’s high-level programmatic policy documents on pharmaceutical reform and intellectual property protection since 2017, and it has already begun to appear in the current draft law, in this regard, It is too early for the Hatch-Waxman bill to be implemented in China.
The author believes that the content of the first-phase economic and trade agreement between China and the United States has only made some agreements from the perspective of protecting the original research drug. It does not include all aspects of the Hatch-Waxman Act, and it does not include how to establish a drug patent linkage system in China Give a complete framework. Taking into account the current rapid development of China’s pharmaceutical industry and the continuous improvement of research and development, it is indeed time to consider how to establish a set of drug patent linkage system with Chinese characteristics. It is to cope with external pressures, and it is also an inherent demand for China’s own development.
In order to establish a drug patent linking system that conforms to the national conditions, it is necessary to do the following on the current drug patent linking system in the United States, the content agreed in the first phase of the Sino-US economic and trade agreement, and the existing drug patent linking in China [1]. With a full understanding, this article starts from this consideration and makes a comparison and comment on these three aspects.
The so-called drug patent linkage system generally refers toThe U.S. drug patent linkage system, which originated from the Hatch-Waxman Act that entered into force in 1984, is designed to comprehensively consider the interests of original research drug companies, generic drug companies, and the public, while encouraging new drug research and development and achieving drug accessibility. Get balanced.
Its main content generally includes the following nine mechanisms: compensation mechanisms for the duration of drug patent protection, patent infringement exemption provisions for collecting drug marketing authorization information (also known as “bolar exception”), and application for generic drug marketing authorization Of the proposed infringement regulations, drug patent information disclosure system (Orange Book System), simplified application requirements for generic drug marketing authorization, patent declaration mechanism for generic drug marketing permission application process, trial procedures for generic drug marketing applications, and patent dispute handling Coordination mechanism, exclusive mechanism of the first generic drug market, and protection mechanism of clinical trial data.
These mechanisms coordinate and cooperate with each other. On the one hand, generic drug companies are encouraged to resolve patent disputes before the approval of their listing applications, to maximize the protection of patent rights of original research drugs, and to reduce the possibility of lawsuits after the listing of drugs; The drug patent linkage system makes the approval process of drug marketing applications open and transparent, which helps the industry to correctly evaluate R & D risks and avoid unnecessary disputes.
At present, the intellectual property community has two views on the composition of the drug patent link system. One view believes that the drug patent link system is a collective term for the above nine mechanisms, and another holds that the drug patent link system includes only the following four types. Mechanism, namely the patent information disclosure system (orange book system), the patent declaration mechanism of the generic drug marketing permission application process, the coordination mechanism of the generic drug market application review procedure and the patent dispute handling mechanism, and the monopoly market’s exclusive mechanism, Other mechanisms are related or supporting measures for the drug patent linkage system.
The author believes that the above differences of opinion are only meaningful for the functional division of government departments, and there is no fundamental difference in a comprehensive understanding of the drug patent linkage system; and the author believes that only by clearly explaining these nine mechanisms can drug patents be The link system has a clear understanding, so the following will introduce the contents of these nine mechanisms one by one.
Compensation mechanism for drug patent term
In Section 1.12 (2) of the China-US Phase I Economic and Trade Agreement, “For patents on new drug products approved for marketing in China and their manufacturing and use methods, China shall respond to new drug product patents at the request of patentees. 2. The patent validity period or patent validity period of its approved use method or manufacturing method provides adjustments to compensate for the unreasonable reduction of the patent validity period caused to the patentee by the listing approval process of the product’s first commercial use in China.
Any such adjustment shall, subject to the same limitations and exceptions, grant all exclusive rights in the original patent to the patent claims of the product, its method of use or manufacturing method applicable to the approved product and its method of use. China can limit such adjustmentsIt shall not exceed 5 years, and the total validity period of the patent shall not exceed 14 years from the date of listing approval in China. “
Article 156 of the U.S. Patent Law stipulates that the patent period of a drug can be extended for a maximum of 5 years, and from the date of approval of the drug, the patent extension period plus the remaining patent term after listing must not exceed 14 years.
Article 43 (2) of the Draft for the Fourth Amendment of the Patent Law, published in January 2019, provides that “to compensate for the time for the review and approval of innovative drugs on the market, The State Council may decide to extend the term of the patent right for an innovative drug invention patent that is marketed simultaneously with overseas, and the extension period shall not exceed five years, and the total effective patent right period after the listing of the innovative drug shall not exceed fourteen years. “
Comparing to the above, it can be known that with the passage of Article 43 in the fourth amendment of the Patent Law in the future, the requirements of this Article of China-US Phase I Economic and Trade Agreement will be met. However, it should be pointed out that the prerequisites for such term compensation are “Chinese and foreign simultaneous application for marketing” for innovative pharmaceutical invention patents, how to understand the term “synchronous” in “synchronous application for marketing” and whether “drug invention patent” It is only limited to product patents, and whether it also includes patents on methods of production of pharmaceuticals and patents on the use of pharmaceuticals, which needs to be further clarified in the future Regulations on the Implementation of the Patent Law.
In addition, the English text of the first phase of the Sino-U.S. economic and trade agreement is “pharmaceutical product”, which includes not only drugs but also medical devices, while the Chinese text provided by the Chinese Ministry of Commerce uses the word “drug” The difference between the two terms’ conceptual extension still needs further clarification.
Also, the patent term that can be extended is not more than 5 years, and the extension of this period is related to the approval date of the marketing authorization, so the interaction between the State Drug Administration and the State Intellectual Property Office is required. To determine a reasonable period. Neither the current or the draft of the Drug Registration Administration Measures published in September 2019 did not address this issue, so this specific procedure also needs to wait for new and at least administrative regulatory documents For further explanation.
Patent exemption from patent infringement for the collection of drug marketing authorization information (hereinafter referred to as “bolar exception”)
In the third revision of the Patent Law in China in 2008, corresponding provisions have been added to Article 69 (1) (5), which is also the “bolar exception” often mentioned in the industry. The content is that “for the purpose of providing information required for administrative approval, manufacturing, using, or importing a patented drug or a patented medical device, and specifically manufacturing or importing a patented drug or a patented medical device for that purpose,” is not considered an infringement.
Section 271 (e) (1) of the U.S. Patent Act states that “pharmaceuticals are regulated in accordance with the U.S. Federal …Manufacturing, use, and sales-related regulations that manufacture, use, promise to sell, or sell a patented product in the United States for the purpose of developing and submitting the information required for an application are not infringements. “
There is no agreement in this regard in the first-phase economic and trade agreement between China and the United States. Therefore, it can be seen that China and the United States should recognize the legal provisions on the exemption of China’s preparation of listing permission information.
It is important to point out that, compared with China’s current Measures for the Administration of Drug Registration, the latest draft of the Measures for the Administration of Drug Registration has significantly revised the approval process for generic drugs. In the current effective management measures, the application for marketing authorization of generic drugs generally includes three stages: preclinical research, clinical trials, and review by the national drug regulatory authority, and the application date for marketing authorization is set before the preclinical research; and In the latest draft, the application date for the marketing authorization is set after the clinical trial. The clinical trial has become a pre-procedure for a generic drug marketing authorization application, and is no longer a part of it, so it is no longer the current patent law. Part of “Administrative Examination and Approval” in Article 69.1. (5). According to the literal interpretation, the behavior of generic drug companies using patented drugs in clinical trials is difficult to become one of the acts exempted by the law, and this legislative flaw needs to be repaired urgently.
In addition, comparing China and the United States’ “Bolar Exception” regulations, we can find that China considers the actions related to “Bolar Exception” as exceptions for patent infringement, and the US Patent Law directly recognizes them as legal acts. Therefore, in China’s infringement cases involving the “bolar exception”, the defendant can either defend on the basis of the “bolar exception” or on the basis of the invalidity or non-infringement of the patent. This has substantial control over the length and shortness of the patent infringement proceedings. significance.
Information disclosure system for pharmaceutical patents (orange book system)
According to Section 505 (J) of the US Federal Food, Drug, and Cosmetic Act, the original research pharmaceutical company needs to provide the new drug marketing authorization application (NDA) with the US Food and Drug Administration (FDA) at the same time. Drug-related patent information. After the NDA application is approved by the FDA, the relevant patent information submitted by the applicant will be registered by the FDA and disclosed in the book “Approved Drug Products with Therapeutic Equivalence Evaluation” As the cover of the book is orange, it is also called an orange book. The Orange Book includes three parts: (1) FDA-approved drug names; (2) multi-source prescription drug evaluation of therapeutic equivalence; (3) product patents and method patents related to the drugs listed on the Orange Book information. The bill also contains detailed regulations on the types of patents, how they are disclosed, and the addition and removal of patents.
In the US drug patent linkage system, the Orange Book System is an important supporting part of the proposed infringement system to be described later, and is the basis of the patent declaration mechanism for the generic drug marketing authorization application process. There is no agreement in this regard in the first phase of the China-US economic and trade agreement.
The current system in China to respond to this mechanism is the “China List of Listed Drugs.” The catalog set was released by the State Drug Administration on December 29, 2017. In its announcement, the State Drug Administration pointed out that the purpose of the catalog set was to protect public drug rights, improve drug quality, reduce drug burden, and encourage drug research and innovation. The catalogue released at that time contained 131 varieties and 203 varieties and specifications, including 13 varieties and 17 varieties and specifications that passed the consistency evaluation of the quality and efficacy of generic drugs. The listing list is still being updated in real time. The catalog has collected more than 1,000 pieces of pharmaceutical information. In some articles and writings, this catalog is called the Orange Book of China. [2]
It should be pointed out that after the publication of the above-mentioned catalog set by the State Drug Administration, the legal status of the catalog set, the corrections and amendments of the contents of the catalog set, and the addition and removal of patents in the catalog set have not yet been promulgated. A complete set of laws and regulations does not include this aspect in the latest draft of the “Administrative Measures for the Registration of Drugs”, and the legislation of this mechanism is urgent to be resolved.
Given that the original pharmaceutical companies are constantly renovating their strategic layout of patents, China must establish a complete set of restrictions when establishing a drug patent linkage system. Otherwise, the intimidating effect of patents caused by the listing of listed medicines will adversely affect the patent linkage system of Chinese medicines and increase the research and development costs of Chinese pharmaceutical companies.
Patent declaration mechanism for the generic drug marketing authorization application process
Section 1.11 (1) of the China-US Phase I economic and trade agreement states that “as a condition for approving the marketing of pharmaceuticals, including biopharmaceuticals, if China allows anyone other than the person who originally submitted safety and effectiveness information, Relying on evidence or information about the safety and effectiveness of previously approved products, such as evidence of market approval in China or other countries, regions, China should:
(a) Provision of notification system: to notify patentees, licensees, or marketing authorization holders that during the validity period of the patent for which the approved product or the approved use method is applicable, the other persons mentioned above are seeking to obtain Approval for marketing of this product; … “
According to Section 505 (J) of the U.S. Federal Food, Drug, and Cosmetic Act and Section 314.94 of Food and Drugs, Chapter 21 of the U.S. Federal Administrative Code, when generic drug companies apply to the FDA for the sale of generic new drugs, they should use orange peel For the patent content recorded in the book, submit one of the following four types of declarations to the FDA; (1) There is no patent registration information for related drugs in the Orange Book(2) The patent term of the original research drug in the Orange Book has expired; (3) the applicant promises that the patent published in the Orange Book will not be listed before the expiration; (4) the related original drug patent published in the Orange Book is Invalid, or the applicant’s generic drug does not infringe the patent right of the original drug. Applicants who submit a Type 4 declaration shall, according to the requirements of the FDA, notify the patentee of the content of their declaration within 20 days after the application is accepted.
The corresponding regulations in China currently are reflected in Article 18 of the current Measures for the Administration of Drug Registration. The 18th article states that “The applicant shall provide a description of the patent and the ownership status of the applicant or others in China for the drug or prescription, process, use, etc. for which registration is applied; if another person has a patent in China, the application shall A person shall submit a statement that the patent of another person does not constitute an infringement. For the description or statement submitted by the applicant, the drug regulatory authority shall make it public on the website of the administrative organ. “Since the above non-infringement statement was submitted to the drug regulatory authority, it is clear that It only corresponds to the fourth type of statement in the above-mentioned US practice, and the subsequent announcement by the drug regulatory authority on the website played a role similar to that of the original research pharmaceutical company.
It is worth noting that the above provisions have been deleted in the latest draft of the “Drug Registration Management Measures” consultation draft. In addition, if you log on to the website of the State Drug Administration, it can be found that, although the current Measures for the Administration of Drug Registration have not been abolished, during the protection period of patents for original research drugs, applications for various generic drugs have been accepted by the State Drug Administration. It even approved it, but the non-infringement statement of any generic drug company could not be found on the website of the State Drug Administration. The author was confused as to why the system had not been implemented. There is a saying in the industry that, because China has not formally established an orange book system, generic drug companies often ignore the existence of original research patents and do not submit non-infringement declarations when submitting marketing applications. Therefore, the national drug regulatory authority has not What can be publicized.
In fact, due to the high requirements of China’s patent examination practice for drug patent effect data, it is not a complicated task to ask a qualified patent lawyer to prepare a legal opinion on patent invalidation. Regrettably, even so, according to the above-mentioned industry statement, China ’s generic drug companies have adopted an “invisible” strategy on the one hand, and have not submitted a non-infringement statement when submitting a marketing authorization application, even as long as the original drug patent protection period has expired. During the first 10 years of the period, a generic drug application was submitted. On the other hand, the Patent Reexamination Board of the State Intellectual Property Office initiated an invalidation process for the patent of the original drug, trying to gain both ends. It is not uncommon for generic drugs to be approved for marketing before the patent expires. This approach violates the provisions of Article 30 of the TRIPS Agreement to a considerable extent [3], and provides an explanation for the United States to add drug patent link clauses in the first phase of the Sino-US economic and trade agreement. .
Special noteWhat’s more, according to Section 505j (B) (ii) of the US Federal Food, Drug and Cosmetic Act, generic drug companies must also explain in detail why the applicant’s generic drugs do not fall into the original drug patent when submitting the fourth statement Or the reasons why these patents are invalid, and these reasons must be “in the opinion of the applicant and to the best of its knowledge”, in other words, this “detailed description” must be based on the applicant’s objective good faith A complete third-party legal opinion, not a simple conclusive assertion by a generic drug applicant.
Comparing with the Chinese and American regulations, we can see that the current effective Article 18 of the “Registration Measures for Drug Registration” is not as high as the requirements of the United States. Such simple requirements have not been achieved in practice.
In fact, Article 18 of the current “Administrative Measures for the Registration of Drugs” deals with non-infringement declarations and publicity mechanisms, and Article 19 deals with applications for marketing authorization of generic drugs within two years before the patent expires, and the patent expires The system for approving the marketing authorization of generic drugs afterwards is a simple and feasible drug patent linkage system. The author did a statistic on the website of the National Center for Drug Evaluation (CDE) and found that a considerable part of the bioequivalence (BE) tests of generic drugs can be completed within 180 days, taking into account the actual review required by CDE Time, for most generic drugs, the marketing authorization review and approval of generic drugs can be completed within two years.
Obviously, the current system of connecting patents to drug registration is a practical, concise and practical system. On the one hand, it guarantees that original research pharmaceutical companies can fully enjoy the 20-year patent protection period, and that generic drugs can be used in original research. After the patent expires, the drug is marketed in time to achieve good drug accessibility. At the same time, the entire mechanism is simple and clear.
It is conceivable that no matter what kind of drug patent linkage system is implemented in the future, it will inevitably bring more complicated system construction, more complicated legal issues, and greater legal costs for Chinese pharmaceutical companies.
Returning to the notification obligation under Section 1.11 (I) of the China-US Phase I Economic and Trade Agreement, in view of the current actual situation, the notification content of China’s future drug patent linkage system should include the following two aspects: (1) generic drugs The procedural facts of the applicant’s application for the marketing authorization of the generic drug, and (2) the notification that the listed generic drug is “may be related” to the patent protection scope of the original drug, rather than a non-infringement statement. This point is fundamentally different from the content of the current Type IV declaration in the United States. Because China’s lawyer legal opinion system is not perfect, China must not copy the US system, otherwise our drug patent linkage system will easily fall into the stigma.
Preparation of infringement requirements for generic drug marketing authorization applications, as well as trial procedures and patent dispute handling procedures for generic drug applicationsCoordination mechanism
Section 1.11 (1) of the China-US Phase I economic and trade agreement states that “as a condition for approving the marketing of pharmaceuticals, including biopharmaceuticals, if China allows anyone other than the person who originally submitted safety and effectiveness information, Relying on evidence or information about the safety and effectiveness of previously approved products, such as evidence of market approval in China or other countries, regions, China should:
(a) …
(b) provide sufficient time and sufficient opportunities for the patentee to seek relief provided in paragraph (c) before the allegedly infringing product is placed on the market; and
(c) Provide judicial or administrative procedures and expeditious relief, such as conduct preservation measures or equivalent effective temporary measures, in order to resolve in a timely manner the validity of patents applicable to approved drugs or their approved methods of use, or Infringement disputes. “
According to the provisions of Section 271 (e) (2) of the US Patent Law, it is a patent infringement for a generic drug applicant to submit an application for a generic drug marketing authorization to the US FDA. If the U.S. court finds that it constitutes infringement, the U.S. court can order the FDA to delay the issuance date of the marketing authorization of the generic drug applicant, so that it cannot be earlier than the patent expiration date of the original drug patent, and can order the generic drug applicant to bear the patent. The litigation costs of rights holders, which is what the industry refers to as a tort system.
In terms of specific procedures, in accordance with Section 505 (J) of the US Federal Food, Drug, and Cosmetic Act and Section 314.94 of Food and Drugs, Chapter 21 of the US Federal Administrative Code, For pharmaceutical applications, the patentee can file a patent infringement lawsuit with the Federal District Court within 45 days of receiving the notification from the generic drug applicant, requesting the court to determine that the application of the generic drug applicant constitutes infringement; Within days of the lawsuit, the FDA will no longer suspend the review of the generic simplified drug application (ANDA), continue the review, and grant marketing authorization to eligible generics.
If the patentee initiates a patent infringement lawsuit, the FDA will allow 30 months for both parties to resolve the lawsuit and the review of the ANDA application will be temporarily suspended. If the court finds that the original drug patent is invalid or the generic drug is not infringing within 30 months, and the generic drug application meets other legal requirements for drug registration, the FDA will issue a marketing authorization. If the lawsuit is not resolved within 30 months, the FDA will issue a temporary license for a qualified generic drug application; thereafter, if the generic drug applicant finally wins, the FDA will issue a formal marketing authorization; if the applicant fails , The applicant’s temporary permission cannot be changed to a formal listing permission, and the applicant must also bear the corresponding lawyer’s fees.
Pharmaceutical companies with temporary marketing authorization are not formal marketing authorization. The FDA does not allow generic drugs with temporary marketing authorization to be marketed, but according to the US President ’s Emergency Plan for AIDS Rescue(President’s Emergency Plan for AIDS Relief), these generic drugs with temporary marketing authorization can be produced and purchased in an emergency.
In the third revision of the Patent Law in China in 2008, while introducing the “bolar exception”, it also faced external pressure to increase the presumptive infringement similar to the United States. The State Intellectual Property Office, in inviting the State Council to review the “Draft Patent Law Amendment (Submission for Examination)” stated that “the application of a patent application for a drug in the United States Patent Law itself constitutes an infringement of patent rights, which is extremely special in countries around the world This approach has not been unanimously approved by other countries. Therefore, there is no sufficient reason to add similar provisions in our patent law. “[4]
Therefore, China’s current patent laws do not contain provisions on infringement, and the act of submitting a listing registration application by a generic drug company is not any of the acts specified in Article 11 of the Patent Law, making the original research drug company unable to defend itself. Legal rights.
According to the agreement of Article 1.11 (a) of the first-stage economic and trade agreement between China and the United States, it will become inevitable to introduce a provision of infringement into the patent law. The original research pharmaceutical company will thus obtain the legal basis for filing a civil lawsuit against the submission of a listing application by a generic pharmaceutical company, and may trigger a large number of patent lawsuits in the short term. In the long run, by resolving patent disputes before the drug is launched on the market, it can have the effect of reducing the risk of infringement and social costs, and is expected to achieve the goal of encouraging innovation and promoting imitation.
In addition, in order to coordinate the relationship between the generic drug application review process and patent disputes with pharmaceutical companies, China needs to add a series of complex interactive procedures to the legal system for drug registration and the legal system for patents.
Taking US law as an example, Chapter 21 Food and Drugs Section 314.107 of the US Federal Administrative Code uses nearly 80,000 English words to define the relationship between patent invalidation procedures, patent infringement procedures and drug approval procedures, including Judgment of the district court, judgment of the court of appeal, invalidation procedure, request for confirmation of non-infringement, reconciliation between the parties, non-prosecution by the patentee, etc. Its complexity is evident.
Given the current dual-track system design of patent invalidation and patent infringement in China, it is difficult to solve the problem of patent stability in patent civil litigation procedures. In the future, the State Drug Administration, the State Intellectual Property Office and the judicial authorities will be required to implement the original Close communication and linkage on the basis of functions, so as to ensure the smooth landing of the drug patent linkage system.
Market exclusivity of the first generic drug
According to the provisions of Article 21, Section 314.107 (c) of the Federal Administrative Code of the United States, the first applicant for a generic drug is determined by the court to not constitute an infringement or the original drug patent is invalid, and enjoys a 180-day market exclusivity period.
The determination of the eligibility of the first applicant shall be submitted toThe earliest date the FDA submits a qualifying application shall prevail. As a reward for the first copycat, during this 180-day exclusivity period, the FDA did not approve other applicants’ marketing applications for the same generic drug. Once the 180-day imitation period is triggered, it will continue to be calculated and will not be suspended or interrupted for any reason. [5]
There is no agreement on this mechanism in the first-phase economic and trade agreement between China and the United States. The general article regards this regulation as a mechanism beneficial to generic drug companies, and I have different views on this.
The author believes that the purpose of this mechanism is to provide a clear signal to the subsequent generic drug producers through the lawsuit of the original generic drug and patentee on the original pharmaceutical patent, that is, whether the original pharmaceutical patent is genuine. The basic judgment of whether the generic drug is valid or not is valid. If the first imitator loses the lawsuit, subsequent imitators will have a clear understanding of the dangers of their own behavior, and if the first imitator wins the lawsuit, although the first imitator can get a reward of 180 days of market exclusivity, Subsequent generic drug applicants can still provide more generic drugs without infringing the patent of the original drug, giving patients more choices.
However, reality is often not as beautiful as theory. In the practice in the United States, after receiving the fourth type of statement from the first copycat, the original research pharmaceutical company, in accordance with its own circumstances, in order to maximize its own interests, in addition to choosing lawsuits to defend its rights, it can also choose to negotiate through settlement or not even prosecute Ways to resolve disputes. In these methods, because the subjective purpose of the original research pharmaceutical company cannot be known to outsiders, the legal nature of subsequent generic drug companies’ behaviors on generic drugs is still unknown, and litigation can only continue. This situation will likely defeat the purpose of the first generic drug award.
For example, in the case of Inwood Labs. v. Young in 1989, the first imitator obtained the marketing authorization without being sued by the patentee, but did not actually produce it; while the second generic drug applicant was denied The patentee sued but finally won the lawsuit, but was unable to obtain the FDA’s marketing authorization, because the FDA believes that the first imitator has not been sued by the patentee and has no success. Therefore, the first imitator’s 180 days have not yet begun.
The parties to the lawsuit disputed whether the first copycat should enjoy a 180-day monopoly period. The decision in this case eventually led to FDA amending its rules. The newly revised system stipulates that, in the case where the first copycat has not been prosecuted, the 180-day monopoly period starts from the date when the first copycat gets a marketing authorization.
A case was finally resolved, and another case occurred. In the subsequent Purepac Pharm Co., v. Friedman case, the first generic applicant was also not sued by the patentee or obtained marketing authorization, while the second generic drug applicant was sued by the patentee but finally won. In this case, the FDA reimbursedIt was not completed, and the 180-day exclusivity period had not yet been started. It refused to grant the second generic drug applicant with a successful marketing authorization.
The second generic drug applicant disputed this and launched a new lawsuit. This time, the court did not support the second applicant’s claim, and determined that the 180-day monopoly period was granted to the first copycat. Although the second applicant won the lawsuit in the infringement lawsuit, he still had to wait for the first copycat to obtain a marketing permission It is possible to obtain a marketing authorization 180 days after the first copycat has obtained a marketing authorization.
The above cases are just two of many US lawsuits. The author uses these examples to illustrate a problem, that is, it is not difficult in practice to use the market-exclusive mechanism of the first copycat to block the application for marketing permission of subsequent copycats.
Because China ’s current drug patent linkage system has just begun, the judicial authorities, the national drug regulatory authority, the Patent Reexamination Board of the State Intellectual Property Office, and domestic pharmaceutical companies still lack the corresponding experience. The previous monopoly drug monopoly mechanism also has a complex relationship with the protection of drug test data. In this case, the introduction of an unknown monopoly market monopoly mechanism is not effective in terms of total social costs.
Protection mechanism of clinical trial data
The introduction of Section III of the China-US Phase I Economic and Trade Agreement states that “the two parties shall provide valid information on pharmaceutical-related intellectual property rights, including patents, as well as undisclosed trial data or other data submitted to meet market approval conditions Protection and law enforcement. “Article 1.11 (1) states,” As a condition for approving the marketing of drugs, including biopharmaceuticals, if China allows anyone other than the person who originally submitted the safety and effectiveness information to rely on previously approved products, Evidence or information about the safety and effectiveness of China, such as evidence that it has been approved for listing in China or other countries and regions, China should: … ”
The evidence of the safety and effectiveness of the approved drugs involved in the Sino-US agreement is a new type of intellectual property object that is different from patent protection. Article 39, paragraph 3, of the TRIPS Agreement stipulates that “Each Member shall submit undisclosed test data or other data obtained through great efforts as a condition for approving the sale of pharmaceuticals or agricultural chemical products manufactured using new chemical entities. , The data shall be protected from unlawful commercial use. In addition, members shall protect such data from disclosure, unless necessary to protect the public, or unless measures are taken to ensure that the data is not used for improper purposes. Commercial use. “
According to section 355 (c) of the US Federal Food, Drug and Cosmetic Act, within 5 years since the original drug was approved for marketing, any person’s application for generic drugs will not be accepted, and a generic version of the fourth category of non-infringement declaration submitted Pharmaceutical applicants can file applications starting from the fourth year.
In China, the current Regulations for the Implementation of the Drug Administration LawArticle 4 states that “the state shall protect the undisclosed test data and other data submitted by the producer or seller who has obtained a license to produce or sell drugs containing new chemical ingredients, and no one shall And other data for improper commercial use. “
At the same time, paragraph 2 of this article stipulates that “within 6 years from the date when the drug manufacturer or seller obtains the license certification documents for the production and sale of new chemical ingredients, the other applicants have not obtained the consent of the applicants who have obtained the permission , If the data of the preceding paragraph is used to apply for a license to produce or sell new-type chemical ingredients, the drug regulatory department will not grant permission; however, other applicants who submit their own data will be excluded.
The above provisions are basically the same as the contents of Article 39 of the TRIPS Agreement and the US Federal Food, Drug, and Cosmetics Act. Therefore, at least China’s institutional construction of this mechanism should pass. It should be pointed out that drug test data is a new type of intellectual property protection object. The establishment and protection of such a new type of intellectual property protection object in an administrative regulation is obviously not high enough in legislative level. One area that needs improvement in drug data protection.
Simplified requirements for marketing authorization applications for generic drugs
The simplified application system of generic drug marketing authorization is the basis of the entire drug patent linkage system. The orange book system, the infringement system and the patent declaration mechanism mentioned above are all essential components, but It is easier to explain the issue of the requirement of simplifying the requirements for generic drug marketing authorization as a component of the drug patent linkage system.
Article 1.11 (1) of the China-US Economic and Trade Agreement states that “as a condition for approving the marketing of drugs including biopharmaceuticals, if China allows anyone other than the person who originally submitted the safety and effectiveness information to rely on the information previously obtained, Evidence or information about the safety and effectiveness of the batch of products, such as evidence that it has been approved for marketing in China or other countries and regions, China should:… ”.
Under section 355 (b) of the US Federal Food, Drug, and Cosmetic Act, US drug applications are divided into new drug applications (NDA) and simplified new drug applications (ANDA), where the ANDA application refers to the generic drug application , And also specifically stipulates that applicants who allow generic drugs do not need to submit data for a complete clinical trial that proves the safety and effectiveness of the drug, and only submitting the bioequivalence data of the applied drug and its generic drug is sufficient to meet the FDA’s clinical data Form requirements.
Correspondingly, the requirements for the definition, bioequivalence test, etc. of the marketing application of generic drugs in Article 12, Article 31, Chapter 5 and Annex 2 of China’s current effective Drug Registration Administration Measures are made Similar rules.
Literally, the generic drugs in China’s drug registration management measures
In the third revision of the Patent Law in China in 2008, corresponding provisions have been added to Article 69 (1) (5), which is also the “bolar exception” often mentioned in the industry. The content is that “for the purpose of providing information required for administrative approval, manufacturing, using, or importing a patented drug or a patented medical device, and specifically manufacturing or importing a patented drug or a patented medical device for that purpose,” is not considered an infringement.
Section 271 (e) (1) of the U.S. Patent Act states that “pharmaceuticals are regulated in accordance with the U.S. Federal …Manufacturing, use, and sales-related regulations that manufacture, use, promise to sell, or sell a patented product in the United States for the purpose of developing and submitting the information required for an application are not infringements. “
There is no agreement in this regard in the first-phase economic and trade agreement between China and the United States. Therefore, it can be seen that China and the United States should recognize the legal provisions on the exemption of China’s preparation of listing permission information.
It is important to point out that, compared with China’s current Measures for the Administration of Drug Registration, the latest draft of the Measures for the Administration of Drug Registration has significantly revised the approval process for generic drugs. In the current effective management measures, the application for marketing authorization of generic drugs generally includes three stages: preclinical research, clinical trials, and review by the national drug regulatory authority, and the application date for marketing authorization is set before the preclinical research; and In the latest draft, the application date for the marketing authorization is set after the clinical trial. The clinical trial has become a pre-procedure for a generic drug marketing authorization application, and is no longer a part of it, so it is no longer the current patent law. Part of “Administrative Examination and Approval” in Article 69.1. (5). According to the literal interpretation, the behavior of generic drug companies using patented drugs in clinical trials is difficult to become one of the acts exempted by the law, and this legislative flaw needs to be repaired urgently.
In addition, comparing China and the United States’ “Bolar Exception” regulations, we can find that China considers the actions related to “Bolar Exception” as exceptions for patent infringement, and the US Patent Law directly recognizes them as legal acts. Therefore, in China’s infringement cases involving the “bolar exception”, the defendant can either defend on the basis of the “bolar exception” or on the basis of the invalidity or non-infringement of the patent. This has substantial control over the length and shortness of the patent infringement proceedings. significance.
Information disclosure system for pharmaceutical patents (orange book system)
According to Section 505 (J) of the US Federal Food, Drug, and Cosmetic Act, the original research pharmaceutical company needs to provide the new drug marketing authorization application (NDA) with the US Food and Drug Administration (FDA) at the same time. Drug-related patent information. After the NDA application is approved by the FDA, the relevant patent information submitted by the applicant will be registered by the FDA and disclosed in the book “Approved Drug Products with Therapeutic Equivalence Evaluation” As the cover of the book is orange, it is also called an orange book. The Orange Book includes three parts: (1) FDA-approved drug names; (2) multi-source prescription drug evaluation of therapeutic equivalence; (3) product patents and method patents related to the drugs listed on the Orange Book information. The bill also contains detailed regulations on the types of patents, how they are disclosed, and the addition and removal of patents.
In the US drug patent linkage system, the Orange Book System is an important supporting part of the proposed infringement system to be described later, and is the basis of the patent declaration mechanism for the generic drug marketing authorization application process. There is no agreement in this regard in the first phase of the China-US economic and trade agreement.
The current system in China to respond to this mechanism is the “China List of Listed Drugs.” The catalog set was released by the State Drug Administration on December 29, 2017. In its announcement, the State Drug Administration pointed out that the purpose of the catalog set was to protect public drug rights, improve drug quality, reduce drug burden, and encourage drug research and innovation. The catalogue released at that time contained 131 varieties and 203 varieties and specifications, including 13 varieties and 17 varieties and specifications that passed the consistency evaluation of the quality and efficacy of generic drugs. The listing list is still being updated in real time. The catalog has collected more than 1,000 pieces of pharmaceutical information. In some articles and writings, this catalog is called the Orange Book of China. [2]
It should be pointed out that after the publication of the above-mentioned catalog set by the State Drug Administration, the legal status of the catalog set, the corrections and amendments of the contents of the catalog set, and the addition and removal of patents in the catalog set have not yet been promulgated. A complete set of laws and regulations does not include this aspect in the latest draft of the “Administrative Measures for the Registration of Drugs”, and the legislation of this mechanism is urgent to be resolved.
Given that the original pharmaceutical companies are constantly renovating their strategic layout of patents, China must establish a complete set of restrictions when establishing a drug patent linkage system. Otherwise, the intimidating effect of patents caused by the listing of listed medicines will adversely affect the patent linkage system of Chinese medicines and increase the research and development costs of Chinese pharmaceutical companies.
Patent declaration mechanism for the generic drug marketing authorization application process
Section 1.11 (1) of the China-US Phase I economic and trade agreement states that “as a condition for approving the marketing of pharmaceuticals, including biopharmaceuticals, if China allows anyone other than the person who originally submitted safety and effectiveness information, Relying on evidence or information about the safety and effectiveness of previously approved products, such as evidence of market approval in China or other countries, regions, China should:
(a) Provision of notification system: to notify patentees, licensees, or marketing authorization holders that during the validity period of the patent for which the approved product or the approved use method is applicable, the other persons mentioned above are seeking to obtain Approval for marketing of this product; … “
According to Section 505 (J) of the U.S. Federal Food, Drug, and Cosmetic Act and Section 314.94 of Food and Drugs, Chapter 21 of the U.S. Federal Administrative Code, when generic drug companies apply to the FDA for the sale of generic new drugs, they should use orange peel For the patent content recorded in the book, submit one of the following four types of declarations to the FDA; (1) There is no patent registration information for related drugs in the Orange Book(2) The patent term of the original research drug in the Orange Book has expired; (3) the applicant promises that the patent published in the Orange Book will not be listed before the expiration; (4) the related original drug patent published in the Orange Book is Invalid, or the applicant’s generic drug does not infringe the patent right of the original drug. Applicants who submit a Type 4 declaration shall, according to the requirements of the FDA, notify the patentee of the content of their declaration within 20 days after the application is accepted.
The corresponding regulations in China currently are reflected in Article 18 of the current Measures for the Administration of Drug Registration. The 18th article states that “The applicant shall provide a description of the patent and the ownership status of the applicant or others in China for the drug or prescription, process, use, etc. for which registration is applied; if another person has a patent in China, the application shall A person shall submit a statement that the patent of another person does not constitute an infringement. For the description or statement submitted by the applicant, the drug regulatory authority shall make it public on the website of the administrative organ. “Since the above non-infringement statement was submitted to the drug regulatory authority, it is clear that It only corresponds to the fourth type of statement in the above-mentioned US practice, and the subsequent announcement by the drug regulatory authority on the website played a role similar to that of the original research pharmaceutical company.
It is worth noting that the above provisions have been deleted in the latest draft of the “Drug Registration Management Measures” consultation draft. In addition, if you log on to the website of the State Drug Administration, it can be found that, although the current Measures for the Administration of Drug Registration have not been abolished, during the protection period of patents for original research drugs, applications for various generic drugs have been accepted by the State Drug Administration. It even approved it, but the non-infringement statement of any generic drug company could not be found on the website of the State Drug Administration. The author was confused as to why the system had not been implemented. There is a saying in the industry that, because China has not formally established an orange book system, generic drug companies often ignore the existence of original research patents and do not submit non-infringement declarations when submitting marketing applications. Therefore, the national drug regulatory authority has not What can be publicized.
In fact, due to the high requirements of China’s patent examination practice for drug patent effect data, it is not a complicated task to ask a qualified patent lawyer to prepare a legal opinion on patent invalidation. Regrettably, even so, according to the above-mentioned industry statement, China ’s generic drug companies have adopted an “invisible” strategy on the one hand, and have not submitted a non-infringement statement when submitting a marketing authorization application, even as long as the original drug patent protection period has expired. During the first 10 years of the period, a generic drug application was submitted. On the other hand, the Patent Reexamination Board of the State Intellectual Property Office initiated an invalidation process for the patent of the original drug, trying to gain both ends. It is not uncommon for generic drugs to be approved for marketing before the patent expires. This approach violates the provisions of Article 30 of the TRIPS Agreement to a considerable extent [3], and provides an explanation for the United States to add drug patent link clauses in the first phase of the Sino-US economic and trade agreement. .
Special noteWhat’s more, according to Section 505j (B) (ii) of the US Federal Food, Drug and Cosmetic Act, generic drug companies must also explain in detail why the applicant’s generic drugs do not fall into the original drug patent when submitting the fourth statement Or the reasons why these patents are invalid, and these reasons must be “in the opinion of the applicant and to the best of its knowledge”, in other words, this “detailed description” must be based on the applicant’s objective good faith A complete third-party legal opinion, not a simple conclusive assertion by a generic drug applicant.
Comparing with the Chinese and American regulations, we can see that the current effective Article 18 of the “Registration Measures for Drug Registration” is not as high as the requirements of the United States. Such simple requirements have not been achieved in practice.
In fact, Article 18 of the current “Administrative Measures for the Registration of Drugs” deals with non-infringement declarations and publicity mechanisms, and Article 19 deals with applications for marketing authorization of generic drugs within two years before the patent expires, and the patent expires The system for approving the marketing authorization of generic drugs afterwards is a simple and feasible drug patent linkage system. The author did a statistic on the website of the National Center for Drug Evaluation (CDE) and found that a considerable part of the bioequivalence (BE) tests of generic drugs can be completed within 180 days, taking into account the actual review required by CDE Time, for most generic drugs, the marketing authorization review and approval of generic drugs can be completed within two years.
Obviously, the current system of connecting patents to drug registration is a practical, concise and practical system. On the one hand, it guarantees that original research pharmaceutical companies can fully enjoy the 20-year patent protection period, and that generic drugs can be used in original research. After the patent expires, the drug is marketed in time to achieve good drug accessibility. At the same time, the entire mechanism is simple and clear.
It is conceivable that no matter what kind of drug patent linkage system is implemented in the future, it will inevitably bring more complicated system construction, more complicated legal issues, and greater legal costs for Chinese pharmaceutical companies.
Returning to the notification obligation under Section 1.11 (I) of the China-US Phase I Economic and Trade Agreement, in view of the current actual situation, the notification content of China’s future drug patent linkage system should include the following two aspects: (1) generic drugs The procedural facts of the applicant’s application for the marketing authorization of the generic drug, and (2) the notification that the listed generic drug is “may be related” to the patent protection scope of the original drug, rather than a non-infringement statement. This point is fundamentally different from the content of the current Type IV declaration in the United States. Because China’s lawyer legal opinion system is not perfect, China must not copy the US system, otherwise our drug patent linkage system will easily fall into the stigma.
Preparation of infringement requirements for generic drug marketing authorization applications, as well as trial procedures and patent dispute handling procedures for generic drug applicationsCoordination mechanism
Section 1.11 (1) of the China-US Phase I economic and trade agreement states that “as a condition for approving the marketing of pharmaceuticals, including biopharmaceuticals, if China allows anyone other than the person who originally submitted safety and effectiveness information, Relying on evidence or information about the safety and effectiveness of previously approved products, such as evidence of market approval in China or other countries, regions, China should:
(a) …
(b) provide sufficient time and sufficient opportunities for the patentee to seek relief provided in paragraph (c) before the allegedly infringing product is placed on the market; and
(c) Provide judicial or administrative procedures and expeditious relief, such as conduct preservation measures or equivalent effective temporary measures, in order to resolve in a timely manner the validity of patents applicable to approved drugs or their approved methods of use, or Infringement disputes. “
According to the provisions of Section 271 (e) (2) of the US Patent Law, it is a patent infringement for a generic drug applicant to submit an application for a generic drug marketing authorization to the US FDA. If the U.S. court finds that it constitutes infringement, the U.S. court can order the FDA to delay the issuance date of the marketing authorization of the generic drug applicant, so that it cannot be earlier than the patent expiration date of the original drug patent, and can order the generic drug applicant to bear the patent. The litigation costs of rights holders, which is what the industry refers to as a tort system.
In terms of specific procedures, in accordance with Section 505 (J) of the US Federal Food, Drug, and Cosmetic Act and Section 314.94 of Food and Drugs, Chapter 21 of the US Federal Administrative Code, For pharmaceutical applications, the patentee can file a patent infringement lawsuit with the Federal District Court within 45 days of receiving the notification from the generic drug applicant, requesting the court to determine that the application of the generic drug applicant constitutes infringement; Within days of the lawsuit, the FDA will no longer suspend the review of the generic simplified drug application (ANDA), continue the review, and grant marketing authorization to eligible generics.
If the patentee initiates a patent infringement lawsuit, the FDA will allow 30 months for both parties to resolve the lawsuit and the review of the ANDA application will be temporarily suspended. If the court finds that the original drug patent is invalid or the generic drug is not infringing within 30 months, and the generic drug application meets other legal requirements for drug registration, the FDA will issue a marketing authorization. If the lawsuit is not resolved within 30 months, the FDA will issue a temporary license for a qualified generic drug application; thereafter, if the generic drug applicant finally wins, the FDA will issue a formal marketing authorization; if the applicant fails , The applicant’s temporary permission cannot be changed to a formal listing permission, and the applicant must also bear the corresponding lawyer’s fees.
Pharmaceutical companies with temporary marketing authorization are not formal marketing authorization. The FDA does not allow generic drugs with temporary marketing authorization to be marketed, but according to the US President ’s Emergency Plan for AIDS Rescue(President’s Emergency Plan for AIDS Relief), these generic drugs with temporary marketing authorization can be produced and purchased in an emergency.
In the third revision of the Patent Law in China in 2008, while introducing the “bolar exception”, it also faced external pressure to increase the presumptive infringement similar to the United States. The State Intellectual Property Office, in inviting the State Council to review the “Draft Patent Law Amendment (Submission for Examination)” stated that “the application of a patent application for a drug in the United States Patent Law itself constitutes an infringement of patent rights, which is extremely special in countries around the world This approach has not been unanimously approved by other countries. Therefore, there is no sufficient reason to add similar provisions in our patent law. “[4]
Therefore, China’s current patent laws do not contain provisions on infringement, and the act of submitting a listing registration application by a generic drug company is not any of the acts specified in Article 11 of the Patent Law, making the original research drug company unable to defend itself. Legal rights.
According to the agreement of Article 1.11 (a) of the first-stage economic and trade agreement between China and the United States, it will become inevitable to introduce a provision of infringement into the patent law. The original research pharmaceutical company will thus obtain the legal basis for filing a civil lawsuit against the submission of a listing application by a generic pharmaceutical company, and may trigger a large number of patent lawsuits in the short term. In the long run, by resolving patent disputes before the drug is launched on the market, it can have the effect of reducing the risk of infringement and social costs, and is expected to achieve the goal of encouraging innovation and promoting imitation.
In addition, in order to coordinate the relationship between the generic drug application review process and patent disputes with pharmaceutical companies, China needs to add a series of complex interactive procedures to the legal system for drug registration and the legal system for patents.
Taking US law as an example, Chapter 21 Food and Drugs Section 314.107 of the US Federal Administrative Code uses nearly 80,000 English words to define the relationship between patent invalidation procedures, patent infringement procedures and drug approval procedures, including Judgment of the district court, judgment of the court of appeal, invalidation procedure, request for confirmation of non-infringement, reconciliation between the parties, non-prosecution by the patentee, etc. Its complexity is evident.
Given the current dual-track system design of patent invalidation and patent infringement in China, it is difficult to solve the problem of patent stability in patent civil litigation procedures. In the future, the State Drug Administration, the State Intellectual Property Office and the judicial authorities will be required to implement the original Close communication and linkage on the basis of functions, so as to ensure the smooth landing of the drug patent linkage system.
Market exclusivity of the first generic drug
According to the provisions of Article 21, Section 314.107 (c) of the Federal Administrative Code of the United States, the first applicant for a generic drug is determined by the court to not constitute an infringement or the original drug patent is invalid, and enjoys a 180-day market exclusivity period.
The determination of the eligibility of the first applicant shall be submitted toThe earliest date the FDA submits a qualifying application shall prevail. As a reward for the first copycat, during this 180-day exclusivity period, the FDA did not approve other applicants’ marketing applications for the same generic drug. Once the 180-day imitation period is triggered, it will continue to be calculated and will not be suspended or interrupted for any reason. [5]
There is no agreement on this mechanism in the first-phase economic and trade agreement between China and the United States. The general article regards this regulation as a mechanism beneficial to generic drug companies, and I have different views on this.
The author believes that the purpose of this mechanism is to provide a clear signal to the subsequent generic drug producers through the lawsuit of the original generic drug and patentee on the original pharmaceutical patent, that is, whether the original pharmaceutical patent is genuine. The basic judgment of whether the generic drug is valid or not is valid. If the first imitator loses the lawsuit, subsequent imitators will have a clear understanding of the dangers of their own behavior, and if the first imitator wins the lawsuit, although the first imitator can get a reward of 180 days of market exclusivity, Subsequent generic drug applicants can still provide more generic drugs without infringing the patent of the original drug, giving patients more choices.
However, reality is often not as beautiful as theory. In the practice in the United States, after receiving the fourth type of statement from the first copycat, the original research pharmaceutical company, in accordance with its own circumstances, in order to maximize its own interests, in addition to choosing lawsuits to defend its rights, it can also choose to negotiate through settlement or not even prosecute Ways to resolve disputes. In these methods, because the subjective purpose of the original research pharmaceutical company cannot be known to outsiders, the legal nature of subsequent generic drug companies’ behaviors on generic drugs is still unknown, and litigation can only continue. This situation will likely defeat the purpose of the first generic drug award.
For example, in the case of Inwood Labs. v. Young in 1989, the first imitator obtained the marketing authorization without being sued by the patentee, but did not actually produce it; while the second generic drug applicant was denied The patentee sued but finally won the lawsuit, but was unable to obtain the FDA’s marketing authorization, because the FDA believes that the first imitator has not been sued by the patentee and has no success. Therefore, the first imitator’s 180 days have not yet begun.
The parties to the lawsuit disputed whether the first copycat should enjoy a 180-day monopoly period. The decision in this case eventually led to FDA amending its rules. The newly revised system stipulates that, in the case where the first copycat has not been prosecuted, the 180-day monopoly period starts from the date when the first copycat gets a marketing authorization.
A case was finally resolved, and another case occurred. In the subsequent Purepac Pharm Co., v. Friedman case, the first generic applicant was also not sued by the patentee or obtained marketing authorization, while the second generic drug applicant was sued by the patentee but finally won. In this case, the FDA reimbursedIt was not completed, and the 180-day exclusivity period had not yet been started. It refused to grant the second generic drug applicant with a successful marketing authorization.
The second generic drug applicant disputed this and launched a new lawsuit. This time, the court did not support the second applicant’s claim, and determined that the 180-day monopoly period was granted to the first copycat. Although the second applicant won the lawsuit in the infringement lawsuit, he still had to wait for the first copycat to obtain a marketing permission It is possible to obtain a marketing authorization 180 days after the first copycat has obtained a marketing authorization.
The above cases are just two of many US lawsuits. The author uses these examples to illustrate a problem, that is, it is not difficult in practice to use the market-exclusive mechanism of the first copycat to block the application for marketing permission of subsequent copycats.
Because China ’s current drug patent linkage system has just begun, the judicial authorities, the national drug regulatory authority, the Patent Reexamination Board of the State Intellectual Property Office, and domestic pharmaceutical companies still lack the corresponding experience. The previous monopoly drug monopoly mechanism also has a complex relationship with the protection of drug test data. In this case, the introduction of an unknown monopoly market monopoly mechanism is not effective in terms of total social costs.
Protection mechanism of clinical trial data
The introduction of Section III of the China-US Phase I Economic and Trade Agreement states that “the two parties shall provide valid information on pharmaceutical-related intellectual property rights, including patents, as well as undisclosed trial data or other data submitted to meet market approval conditions Protection and law enforcement. “Article 1.11 (1) states,” As a condition for approving the marketing of drugs, including biopharmaceuticals, if China allows anyone other than the person who originally submitted the safety and effectiveness information to rely on previously approved products, Evidence or information about the safety and effectiveness of China, such as evidence that it has been approved for listing in China or other countries and regions, China should: … ”
The evidence of the safety and effectiveness of the approved drugs involved in the Sino-US agreement is a new type of intellectual property object that is different from patent protection. Article 39, paragraph 3, of the TRIPS Agreement stipulates that “Each Member shall submit undisclosed test data or other data obtained through great efforts as a condition for approving the sale of pharmaceuticals or agricultural chemical products manufactured using new chemical entities. , The data shall be protected from unlawful commercial use. In addition, members shall protect such data from disclosure, unless necessary to protect the public, or unless measures are taken to ensure that the data is not used for improper purposes. Commercial use. “
According to section 355 (c) of the US Federal Food, Drug and Cosmetic Act, within 5 years since the original drug was approved for marketing, any person’s application for generic drugs will not be accepted, and a generic version of the fourth category of non-infringement declaration submitted Pharmaceutical applicants can file applications starting from the fourth year.
In China, the current Regulations for the Implementation of the Drug Administration LawArticle 4 states that “the state shall protect the undisclosed test data and other data submitted by the producer or seller who has obtained a license to produce or sell drugs containing new chemical ingredients, and no one shall And other data for improper commercial use. “
At the same time, paragraph 2 of this article stipulates that “within 6 years from the date when the drug manufacturer or seller obtains the license certification documents for the production and sale of new chemical ingredients, the other applicants have not obtained the consent of the applicants who have obtained the permission , If the data of the preceding paragraph is used to apply for a license to produce or sell new-type chemical ingredients, the drug regulatory department will not grant permission; however, other applicants who submit their own data will be excluded.
The above provisions are basically the same as the contents of Article 39 of the TRIPS Agreement and the US Federal Food, Drug, and Cosmetics Act. Therefore, at least China’s institutional construction of this mechanism should pass. It should be pointed out that drug test data is a new type of intellectual property protection object. The establishment and protection of such a new type of intellectual property protection object in an administrative regulation is obviously not high enough in legislative level. One area that needs improvement in drug data protection.
Simplified requirements for marketing authorization applications for generic drugs
The simplified application system of generic drug marketing authorization is the basis of the entire drug patent linkage system. The orange book system, the infringement system and the patent declaration mechanism mentioned above are all essential components, but It is easier to explain the issue of the requirement of simplifying the requirements for generic drug marketing authorization as a component of the drug patent linkage system.
Article 1.11 (1) of the China-US Economic and Trade Agreement states that “as a condition for approving the marketing of drugs including biopharmaceuticals, if China allows anyone other than the person who originally submitted the safety and effectiveness information to rely on the information previously obtained, Evidence or information about the safety and effectiveness of the batch of products, such as evidence that it has been approved for marketing in China or other countries and regions, China should:… ”.
Under section 355 (b) of the US Federal Food, Drug, and Cosmetic Act, US drug applications are divided into new drug applications (NDA) and simplified new drug applications (ANDA), where the ANDA application refers to the generic drug application , And also specifically stipulates that applicants who allow generic drugs do not need to submit data for a complete clinical trial that proves the safety and effectiveness of the drug, and only submitting the bioequivalence data of the applied drug and its generic drug is sufficient to meet the FDA’s clinical data Form requirements.
Correspondingly, the requirements for the definition, bioequivalence test, etc. of the marketing application of generic drugs in Article 12, Article 31, Chapter 5 and Annex 2 of China’s current effective Drug Registration Administration Measures are made Similar rules.
Literally, the generic drugs in China’s drug registration management measures
Section 1.11 (1) of the China-US Phase I economic and trade agreement states that “as a condition for approving the marketing of pharmaceuticals, including biopharmaceuticals, if China allows anyone other than the person who originally submitted safety and effectiveness information, Relying on evidence or information about the safety and effectiveness of previously approved products, such as evidence of market approval in China or other countries, regions, China should:
(a) Provision of notification system: to notify patentees, licensees, or marketing authorization holders that during the validity period of the patent for which the approved product or the approved use method is applicable, the other persons mentioned above are seeking to obtain Approval for marketing of this product; … “
According to Section 505 (J) of the U.S. Federal Food, Drug, and Cosmetic Act and Section 314.94 of Food and Drugs, Chapter 21 of the U.S. Federal Administrative Code, when generic drug companies apply to the FDA for the sale of generic new drugs, they should use orange peel For the patent content recorded in the book, submit one of the following four types of declarations to the FDA; (1) There is no patent registration information for related drugs in the Orange Book(2) The patent term of the original research drug in the Orange Book has expired; (3) the applicant promises that the patent published in the Orange Book will not be listed before the expiration; (4) the related original drug patent published in the Orange Book is Invalid, or the applicant’s generic drug does not infringe the patent right of the original drug. Applicants who submit a Type 4 declaration shall, according to the requirements of the FDA, notify the patentee of the content of their declaration within 20 days after the application is accepted.
The corresponding regulations in China currently are reflected in Article 18 of the current Measures for the Administration of Drug Registration. The 18th article states that “The applicant shall provide a description of the patent and the ownership status of the applicant or others in China for the drug or prescription, process, use, etc. for which registration is applied; if another person has a patent in China, the application shall A person shall submit a statement that the patent of another person does not constitute an infringement. For the description or statement submitted by the applicant, the drug regulatory authority shall make it public on the website of the administrative organ. “Since the above non-infringement statement was submitted to the drug regulatory authority, it is clear that It only corresponds to the fourth type of statement in the above-mentioned US practice, and the subsequent announcement by the drug regulatory authority on the website played a role similar to that of the original research pharmaceutical company.
It is worth noting that the above provisions have been deleted in the latest draft of the “Drug Registration Management Measures” consultation draft. In addition, if you log on to the website of the State Drug Administration, it can be found that, although the current Measures for the Administration of Drug Registration have not been abolished, during the protection period of patents for original research drugs, applications for various generic drugs have been accepted by the State Drug Administration. It even approved it, but the non-infringement statement of any generic drug company could not be found on the website of the State Drug Administration. The author was confused as to why the system had not been implemented. There is a saying in the industry that, because China has not formally established an orange book system, generic drug companies often ignore the existence of original research patents and do not submit non-infringement declarations when submitting marketing applications. Therefore, the national drug regulatory authority has not What can be publicized.
In fact, due to the high requirements of China’s patent examination practice for drug patent effect data, it is not a complicated task to ask a qualified patent lawyer to prepare a legal opinion on patent invalidation. Regrettably, even so, according to the above-mentioned industry statement, China ’s generic drug companies have adopted an “invisible” strategy on the one hand, and have not submitted a non-infringement statement when submitting a marketing authorization application, even as long as the original drug patent protection period has expired. During the first 10 years of the period, a generic drug application was submitted. On the other hand, the Patent Reexamination Board of the State Intellectual Property Office initiated an invalidation process for the patent of the original drug, trying to gain both ends. It is not uncommon for generic drugs to be approved for marketing before the patent expires. This approach violates the provisions of Article 30 of the TRIPS Agreement to a considerable extent [3], and provides an explanation for the United States to add drug patent link clauses in the first phase of the Sino-US economic and trade agreement. .
Special noteWhat’s more, according to Section 505j (B) (ii) of the US Federal Food, Drug and Cosmetic Act, generic drug companies must also explain in detail why the applicant’s generic drugs do not fall into the original drug patent when submitting the fourth statement Or the reasons why these patents are invalid, and these reasons must be “in the opinion of the applicant and to the best of its knowledge”, in other words, this “detailed description” must be based on the applicant’s objective good faith A complete third-party legal opinion, not a simple conclusive assertion by a generic drug applicant.
Comparing with the Chinese and American regulations, we can see that the current effective Article 18 of the “Registration Measures for Drug Registration” is not as high as the requirements of the United States. Such simple requirements have not been achieved in practice.
In fact, Article 18 of the current “Administrative Measures for the Registration of Drugs” deals with non-infringement declarations and publicity mechanisms, and Article 19 deals with applications for marketing authorization of generic drugs within two years before the patent expires, and the patent expires The system for approving the marketing authorization of generic drugs afterwards is a simple and feasible drug patent linkage system. The author did a statistic on the website of the National Center for Drug Evaluation (CDE) and found that a considerable part of the bioequivalence (BE) tests of generic drugs can be completed within 180 days, taking into account the actual review required by CDE Time, for most generic drugs, the marketing authorization review and approval of generic drugs can be completed within two years.
Obviously, the current system of connecting patents to drug registration is a practical, concise and practical system. On the one hand, it guarantees that original research pharmaceutical companies can fully enjoy the 20-year patent protection period, and that generic drugs can be used in original research. After the patent expires, the drug is marketed in time to achieve good drug accessibility. At the same time, the entire mechanism is simple and clear.
It is conceivable that no matter what kind of drug patent linkage system is implemented in the future, it will inevitably bring more complicated system construction, more complicated legal issues, and greater legal costs for Chinese pharmaceutical companies.
Returning to the notification obligation under Section 1.11 (I) of the China-US Phase I Economic and Trade Agreement, in view of the current actual situation, the notification content of China’s future drug patent linkage system should include the following two aspects: (1) generic drugs The procedural facts of the applicant’s application for the marketing authorization of the generic drug, and (2) the notification that the listed generic drug is “may be related” to the patent protection scope of the original drug, rather than a non-infringement statement. This point is fundamentally different from the content of the current Type IV declaration in the United States. Because China’s lawyer legal opinion system is not perfect, China must not copy the US system, otherwise our drug patent linkage system will easily fall into the stigma.
Preparation of infringement requirements for generic drug marketing authorization applications, as well as trial procedures and patent dispute handling procedures for generic drug applicationsCoordination mechanism
Section 1.11 (1) of the China-US Phase I economic and trade agreement states that “as a condition for approving the marketing of pharmaceuticals, including biopharmaceuticals, if China allows anyone other than the person who originally submitted safety and effectiveness information, Relying on evidence or information about the safety and effectiveness of previously approved products, such as evidence of market approval in China or other countries, regions, China should:
(a) …
(b) provide sufficient time and sufficient opportunities for the patentee to seek relief provided in paragraph (c) before the allegedly infringing product is placed on the market; and
(c) Provide judicial or administrative procedures and expeditious relief, such as conduct preservation measures or equivalent effective temporary measures, in order to resolve in a timely manner the validity of patents applicable to approved drugs or their approved methods of use, or Infringement disputes. “
According to the provisions of Section 271 (e) (2) of the US Patent Law, it is a patent infringement for a generic drug applicant to submit an application for a generic drug marketing authorization to the US FDA. If the U.S. court finds that it constitutes infringement, the U.S. court can order the FDA to delay the issuance date of the marketing authorization of the generic drug applicant, so that it cannot be earlier than the patent expiration date of the original drug patent, and can order the generic drug applicant to bear the patent. The litigation costs of rights holders, which is what the industry refers to as a tort system.
In terms of specific procedures, in accordance with Section 505 (J) of the US Federal Food, Drug, and Cosmetic Act and Section 314.94 of Food and Drugs, Chapter 21 of the US Federal Administrative Code, For pharmaceutical applications, the patentee can file a patent infringement lawsuit with the Federal District Court within 45 days of receiving the notification from the generic drug applicant, requesting the court to determine that the application of the generic drug applicant constitutes infringement; Within days of the lawsuit, the FDA will no longer suspend the review of the generic simplified drug application (ANDA), continue the review, and grant marketing authorization to eligible generics.
If the patentee initiates a patent infringement lawsuit, the FDA will allow 30 months for both parties to resolve the lawsuit and the review of the ANDA application will be temporarily suspended. If the court finds that the original drug patent is invalid or the generic drug is not infringing within 30 months, and the generic drug application meets other legal requirements for drug registration, the FDA will issue a marketing authorization. If the lawsuit is not resolved within 30 months, the FDA will issue a temporary license for a qualified generic drug application; thereafter, if the generic drug applicant finally wins, the FDA will issue a formal marketing authorization; if the applicant fails , The applicant’s temporary permission cannot be changed to a formal listing permission, and the applicant must also bear the corresponding lawyer’s fees.
Pharmaceutical companies with temporary marketing authorization are not formal marketing authorization. The FDA does not allow generic drugs with temporary marketing authorization to be marketed, but according to the US President ’s Emergency Plan for AIDS Rescue(President’s Emergency Plan for AIDS Relief), these generic drugs with temporary marketing authorization can be produced and purchased in an emergency.
In the third revision of the Patent Law in China in 2008, while introducing the “bolar exception”, it also faced external pressure to increase the presumptive infringement similar to the United States. The State Intellectual Property Office, in inviting the State Council to review the “Draft Patent Law Amendment (Submission for Examination)” stated that “the application of a patent application for a drug in the United States Patent Law itself constitutes an infringement of patent rights, which is extremely special in countries around the world This approach has not been unanimously approved by other countries. Therefore, there is no sufficient reason to add similar provisions in our patent law. “[4]
Therefore, China’s current patent laws do not contain provisions on infringement, and the act of submitting a listing registration application by a generic drug company is not any of the acts specified in Article 11 of the Patent Law, making the original research drug company unable to defend itself. Legal rights.
According to the agreement of Article 1.11 (a) of the first-stage economic and trade agreement between China and the United States, it will become inevitable to introduce a provision of infringement into the patent law. The original research pharmaceutical company will thus obtain the legal basis for filing a civil lawsuit against the submission of a listing application by a generic pharmaceutical company, and may trigger a large number of patent lawsuits in the short term. In the long run, by resolving patent disputes before the drug is launched on the market, it can have the effect of reducing the risk of infringement and social costs, and is expected to achieve the goal of encouraging innovation and promoting imitation.
In addition, in order to coordinate the relationship between the generic drug application review process and patent disputes with pharmaceutical companies, China needs to add a series of complex interactive procedures to the legal system for drug registration and the legal system for patents.
Taking US law as an example, Chapter 21 Food and Drugs Section 314.107 of the US Federal Administrative Code uses nearly 80,000 English words to define the relationship between patent invalidation procedures, patent infringement procedures and drug approval procedures, including Judgment of the district court, judgment of the court of appeal, invalidation procedure, request for confirmation of non-infringement, reconciliation between the parties, non-prosecution by the patentee, etc. Its complexity is evident.
Given the current dual-track system design of patent invalidation and patent infringement in China, it is difficult to solve the problem of patent stability in patent civil litigation procedures. In the future, the State Drug Administration, the State Intellectual Property Office and the judicial authorities will be required to implement the original Close communication and linkage on the basis of functions, so as to ensure the smooth landing of the drug patent linkage system.
Market exclusivity of the first generic drug
According to the provisions of Article 21, Section 314.107 (c) of the Federal Administrative Code of the United States, the first applicant for a generic drug is determined by the court to not constitute an infringement or the original drug patent is invalid, and enjoys a 180-day market exclusivity period.
The determination of the eligibility of the first applicant shall be submitted toThe earliest date the FDA submits a qualifying application shall prevail. As a reward for the first copycat, during this 180-day exclusivity period, the FDA did not approve other applicants’ marketing applications for the same generic drug. Once the 180-day imitation period is triggered, it will continue to be calculated and will not be suspended or interrupted for any reason. [5]
There is no agreement on this mechanism in the first-phase economic and trade agreement between China and the United States. The general article regards this regulation as a mechanism beneficial to generic drug companies, and I have different views on this.
The author believes that the purpose of this mechanism is to provide a clear signal to the subsequent generic drug producers through the lawsuit of the original generic drug and patentee on the original pharmaceutical patent, that is, whether the original pharmaceutical patent is genuine. The basic judgment of whether the generic drug is valid or not is valid. If the first imitator loses the lawsuit, subsequent imitators will have a clear understanding of the dangers of their own behavior, and if the first imitator wins the lawsuit, although the first imitator can get a reward of 180 days of market exclusivity, Subsequent generic drug applicants can still provide more generic drugs without infringing the patent of the original drug, giving patients more choices.
However, reality is often not as beautiful as theory. In the practice in the United States, after receiving the fourth type of statement from the first copycat, the original research pharmaceutical company, in accordance with its own circumstances, in order to maximize its own interests, in addition to choosing lawsuits to defend its rights, it can also choose to negotiate through settlement or not even prosecute Ways to resolve disputes. In these methods, because the subjective purpose of the original research pharmaceutical company cannot be known to outsiders, the legal nature of subsequent generic drug companies’ behaviors on generic drugs is still unknown, and litigation can only continue. This situation will likely defeat the purpose of the first generic drug award.
For example, in the case of Inwood Labs. v. Young in 1989, the first imitator obtained the marketing authorization without being sued by the patentee, but did not actually produce it; while the second generic drug applicant was denied The patentee sued but finally won the lawsuit, but was unable to obtain the FDA’s marketing authorization, because the FDA believes that the first imitator has not been sued by the patentee and has no success. Therefore, the first imitator’s 180 days have not yet begun.
The parties to the lawsuit disputed whether the first copycat should enjoy a 180-day monopoly period. The decision in this case eventually led to FDA amending its rules. The newly revised system stipulates that, in the case where the first copycat has not been prosecuted, the 180-day monopoly period starts from the date when the first copycat gets a marketing authorization.
A case was finally resolved, and another case occurred. In the subsequent Purepac Pharm Co., v. Friedman case, the first generic applicant was also not sued by the patentee or obtained marketing authorization, while the second generic drug applicant was sued by the patentee but finally won. In this case, the FDA reimbursedIt was not completed, and the 180-day exclusivity period had not yet been started. It refused to grant the second generic drug applicant with a successful marketing authorization.
The second generic drug applicant disputed this and launched a new lawsuit. This time, the court did not support the second applicant’s claim, and determined that the 180-day monopoly period was granted to the first copycat. Although the second applicant won the lawsuit in the infringement lawsuit, he still had to wait for the first copycat to obtain a marketing permission It is possible to obtain a marketing authorization 180 days after the first copycat has obtained a marketing authorization.
The above cases are just two of many US lawsuits. The author uses these examples to illustrate a problem, that is, it is not difficult in practice to use the market-exclusive mechanism of the first copycat to block the application for marketing permission of subsequent copycats.
Because China ’s current drug patent linkage system has just begun, the judicial authorities, the national drug regulatory authority, the Patent Reexamination Board of the State Intellectual Property Office, and domestic pharmaceutical companies still lack the corresponding experience. The previous monopoly drug monopoly mechanism also has a complex relationship with the protection of drug test data. In this case, the introduction of an unknown monopoly market monopoly mechanism is not effective in terms of total social costs.
Protection mechanism of clinical trial data
The introduction of Section III of the China-US Phase I Economic and Trade Agreement states that “the two parties shall provide valid information on pharmaceutical-related intellectual property rights, including patents, as well as undisclosed trial data or other data submitted to meet market approval conditions Protection and law enforcement. “Article 1.11 (1) states,” As a condition for approving the marketing of drugs, including biopharmaceuticals, if China allows anyone other than the person who originally submitted the safety and effectiveness information to rely on previously approved products, Evidence or information about the safety and effectiveness of China, such as evidence that it has been approved for listing in China or other countries and regions, China should: … ”
The evidence of the safety and effectiveness of the approved drugs involved in the Sino-US agreement is a new type of intellectual property object that is different from patent protection. Article 39, paragraph 3, of the TRIPS Agreement stipulates that “Each Member shall submit undisclosed test data or other data obtained through great efforts as a condition for approving the sale of pharmaceuticals or agricultural chemical products manufactured using new chemical entities. , The data shall be protected from unlawful commercial use. In addition, members shall protect such data from disclosure, unless necessary to protect the public, or unless measures are taken to ensure that the data is not used for improper purposes. Commercial use. “
According to section 355 (c) of the US Federal Food, Drug and Cosmetic Act, within 5 years since the original drug was approved for marketing, any person’s application for generic drugs will not be accepted, and a generic version of the fourth category of non-infringement declaration submitted Pharmaceutical applicants can file applications starting from the fourth year.
In China, the current Regulations for the Implementation of the Drug Administration LawArticle 4 states that “the state shall protect the undisclosed test data and other data submitted by the producer or seller who has obtained a license to produce or sell drugs containing new chemical ingredients, and no one shall And other data for improper commercial use. “
At the same time, paragraph 2 of this article stipulates that “within 6 years from the date when the drug manufacturer or seller obtains the license certification documents for the production and sale of new chemical ingredients, the other applicants have not obtained the consent of the applicants who have obtained the permission , If the data of the preceding paragraph is used to apply for a license to produce or sell new-type chemical ingredients, the drug regulatory department will not grant permission; however, other applicants who submit their own data will be excluded.
The above provisions are basically the same as the contents of Article 39 of the TRIPS Agreement and the US Federal Food, Drug, and Cosmetics Act. Therefore, at least China’s institutional construction of this mechanism should pass. It should be pointed out that drug test data is a new type of intellectual property protection object. The establishment and protection of such a new type of intellectual property protection object in an administrative regulation is obviously not high enough in legislative level. One area that needs improvement in drug data protection.
Simplified requirements for marketing authorization applications for generic drugs
The simplified application system of generic drug marketing authorization is the basis of the entire drug patent linkage system. The orange book system, the infringement system and the patent declaration mechanism mentioned above are all essential components, but It is easier to explain the issue of the requirement of simplifying the requirements for generic drug marketing authorization as a component of the drug patent linkage system.
Article 1.11 (1) of the China-US Economic and Trade Agreement states that “as a condition for approving the marketing of drugs including biopharmaceuticals, if China allows anyone other than the person who originally submitted the safety and effectiveness information to rely on the information previously obtained, Evidence or information about the safety and effectiveness of the batch of products, such as evidence that it has been approved for marketing in China or other countries and regions, China should:… ”.
Under section 355 (b) of the US Federal Food, Drug, and Cosmetic Act, US drug applications are divided into new drug applications (NDA) and simplified new drug applications (ANDA), where the ANDA application refers to the generic drug application , And also specifically stipulates that applicants who allow generic drugs do not need to submit data for a complete clinical trial that proves the safety and effectiveness of the drug, and only submitting the bioequivalence data of the applied drug and its generic drug is sufficient to meet the FDA’s clinical data Form requirements.
Correspondingly, the requirements for the definition, bioequivalence test, etc. of the marketing application of generic drugs in Article 12, Article 31, Chapter 5 and Annex 2 of China’s current effective Drug Registration Administration Measures are made Similar rules.
Literally, the generic drugs in China’s drug registration management measures
According to the provisions of Article 21, Section 314.107 (c) of the Federal Administrative Code of the United States, the first applicant for a generic drug is determined by the court to not constitute an infringement or the original drug patent is invalid, and enjoys a 180-day market exclusivity period.
The determination of the eligibility of the first applicant shall be submitted toThe earliest date the FDA submits a qualifying application shall prevail. As a reward for the first copycat, during this 180-day exclusivity period, the FDA did not approve other applicants’ marketing applications for the same generic drug. Once the 180-day imitation period is triggered, it will continue to be calculated and will not be suspended or interrupted for any reason. [5]
There is no agreement on this mechanism in the first-phase economic and trade agreement between China and the United States. The general article regards this regulation as a mechanism beneficial to generic drug companies, and I have different views on this.
The author believes that the purpose of this mechanism is to provide a clear signal to the subsequent generic drug producers through the lawsuit of the original generic drug and patentee on the original pharmaceutical patent, that is, whether the original pharmaceutical patent is genuine. The basic judgment of whether the generic drug is valid or not is valid. If the first imitator loses the lawsuit, subsequent imitators will have a clear understanding of the dangers of their own behavior, and if the first imitator wins the lawsuit, although the first imitator can get a reward of 180 days of market exclusivity, Subsequent generic drug applicants can still provide more generic drugs without infringing the patent of the original drug, giving patients more choices.
However, reality is often not as beautiful as theory. In the practice in the United States, after receiving the fourth type of statement from the first copycat, the original research pharmaceutical company, in accordance with its own circumstances, in order to maximize its own interests, in addition to choosing lawsuits to defend its rights, it can also choose to negotiate through settlement or not even prosecute Ways to resolve disputes. In these methods, because the subjective purpose of the original research pharmaceutical company cannot be known to outsiders, the legal nature of subsequent generic drug companies’ behaviors on generic drugs is still unknown, and litigation can only continue. This situation will likely defeat the purpose of the first generic drug award.
For example, in the case of Inwood Labs. v. Young in 1989, the first imitator obtained the marketing authorization without being sued by the patentee, but did not actually produce it; while the second generic drug applicant was denied The patentee sued but finally won the lawsuit, but was unable to obtain the FDA’s marketing authorization, because the FDA believes that the first imitator has not been sued by the patentee and has no success. Therefore, the first imitator’s 180 days have not yet begun.
The parties to the lawsuit disputed whether the first copycat should enjoy a 180-day monopoly period. The decision in this case eventually led to FDA amending its rules. The newly revised system stipulates that, in the case where the first copycat has not been prosecuted, the 180-day monopoly period starts from the date when the first copycat gets a marketing authorization.
A case was finally resolved, and another case occurred. In the subsequent Purepac Pharm Co., v. Friedman case, the first generic applicant was also not sued by the patentee or obtained marketing authorization, while the second generic drug applicant was sued by the patentee but finally won. In this case, the FDA reimbursedIt was not completed, and the 180-day exclusivity period had not yet been started. It refused to grant the second generic drug applicant with a successful marketing authorization.
The second generic drug applicant disputed this and launched a new lawsuit. This time, the court did not support the second applicant’s claim, and determined that the 180-day monopoly period was granted to the first copycat. Although the second applicant won the lawsuit in the infringement lawsuit, he still had to wait for the first copycat to obtain a marketing permission It is possible to obtain a marketing authorization 180 days after the first copycat has obtained a marketing authorization.
The above cases are just two of many US lawsuits. The author uses these examples to illustrate a problem, that is, it is not difficult in practice to use the market-exclusive mechanism of the first copycat to block the application for marketing permission of subsequent copycats.
Because China ’s current drug patent linkage system has just begun, the judicial authorities, the national drug regulatory authority, the Patent Reexamination Board of the State Intellectual Property Office, and domestic pharmaceutical companies still lack the corresponding experience. The previous monopoly drug monopoly mechanism also has a complex relationship with the protection of drug test data. In this case, the introduction of an unknown monopoly market monopoly mechanism is not effective in terms of total social costs.
Protection mechanism of clinical trial data
The introduction of Section III of the China-US Phase I Economic and Trade Agreement states that “the two parties shall provide valid information on pharmaceutical-related intellectual property rights, including patents, as well as undisclosed trial data or other data submitted to meet market approval conditions Protection and law enforcement. “Article 1.11 (1) states,” As a condition for approving the marketing of drugs, including biopharmaceuticals, if China allows anyone other than the person who originally submitted the safety and effectiveness information to rely on previously approved products, Evidence or information about the safety and effectiveness of China, such as evidence that it has been approved for listing in China or other countries and regions, China should: … ”
The evidence of the safety and effectiveness of the approved drugs involved in the Sino-US agreement is a new type of intellectual property object that is different from patent protection. Article 39, paragraph 3, of the TRIPS Agreement stipulates that “Each Member shall submit undisclosed test data or other data obtained through great efforts as a condition for approving the sale of pharmaceuticals or agricultural chemical products manufactured using new chemical entities. , The data shall be protected from unlawful commercial use. In addition, members shall protect such data from disclosure, unless necessary to protect the public, or unless measures are taken to ensure that the data is not used for improper purposes. Commercial use. “
According to section 355 (c) of the US Federal Food, Drug and Cosmetic Act, within 5 years since the original drug was approved for marketing, any person’s application for generic drugs will not be accepted, and a generic version of the fourth category of non-infringement declaration submitted Pharmaceutical applicants can file applications starting from the fourth year.
In China, the current Regulations for the Implementation of the Drug Administration LawArticle 4 states that “the state shall protect the undisclosed test data and other data submitted by the producer or seller who has obtained a license to produce or sell drugs containing new chemical ingredients, and no one shall And other data for improper commercial use. “
At the same time, paragraph 2 of this article stipulates that “within 6 years from the date when the drug manufacturer or seller obtains the license certification documents for the production and sale of new chemical ingredients, the other applicants have not obtained the consent of the applicants who have obtained the permission , If the data of the preceding paragraph is used to apply for a license to produce or sell new-type chemical ingredients, the drug regulatory department will not grant permission; however, other applicants who submit their own data will be excluded.
The above provisions are basically the same as the contents of Article 39 of the TRIPS Agreement and the US Federal Food, Drug, and Cosmetics Act. Therefore, at least China’s institutional construction of this mechanism should pass. It should be pointed out that drug test data is a new type of intellectual property protection object. The establishment and protection of such a new type of intellectual property protection object in an administrative regulation is obviously not high enough in legislative level. One area that needs improvement in drug data protection.
Simplified requirements for marketing authorization applications for generic drugs
The simplified application system of generic drug marketing authorization is the basis of the entire drug patent linkage system. The orange book system, the infringement system and the patent declaration mechanism mentioned above are all essential components, but It is easier to explain the issue of the requirement of simplifying the requirements for generic drug marketing authorization as a component of the drug patent linkage system.
Article 1.11 (1) of the China-US Economic and Trade Agreement states that “as a condition for approving the marketing of drugs including biopharmaceuticals, if China allows anyone other than the person who originally submitted the safety and effectiveness information to rely on the information previously obtained, Evidence or information about the safety and effectiveness of the batch of products, such as evidence that it has been approved for marketing in China or other countries and regions, China should:… ”.
Under section 355 (b) of the US Federal Food, Drug, and Cosmetic Act, US drug applications are divided into new drug applications (NDA) and simplified new drug applications (ANDA), where the ANDA application refers to the generic drug application , And also specifically stipulates that applicants who allow generic drugs do not need to submit data for a complete clinical trial that proves the safety and effectiveness of the drug, and only submitting the bioequivalence data of the applied drug and its generic drug is sufficient to meet the FDA’s clinical data Form requirements.
Correspondingly, the requirements for the definition, bioequivalence test, etc. of the marketing application of generic drugs in Article 12, Article 31, Chapter 5 and Annex 2 of China’s current effective Drug Registration Administration Measures are made Similar rules.
Literally, the generic drugs in China’s drug registration management measures
The simplified application system of generic drug marketing authorization is the basis of the entire drug patent linkage system. The orange book system, the infringement system and the patent declaration mechanism mentioned above are all essential components, but It is easier to explain the issue of the requirement of simplifying the requirements for generic drug marketing authorization as a component of the drug patent linkage system.
Article 1.11 (1) of the China-US Economic and Trade Agreement states that “as a condition for approving the marketing of drugs including biopharmaceuticals, if China allows anyone other than the person who originally submitted the safety and effectiveness information to rely on the information previously obtained, Evidence or information about the safety and effectiveness of the batch of products, such as evidence that it has been approved for marketing in China or other countries and regions, China should:… ”.
Under section 355 (b) of the US Federal Food, Drug, and Cosmetic Act, US drug applications are divided into new drug applications (NDA) and simplified new drug applications (ANDA), where the ANDA application refers to the generic drug application , And also specifically stipulates that applicants who allow generic drugs do not need to submit data for a complete clinical trial that proves the safety and effectiveness of the drug, and only submitting the bioequivalence data of the applied drug and its generic drug is sufficient to meet the FDA’s clinical data Form requirements.
Correspondingly, the requirements for the definition, bioequivalence test, etc. of the marketing application of generic drugs in Article 12, Article 31, Chapter 5 and Annex 2 of China’s current effective Drug Registration Administration Measures are made Similar rules.
Literally, the generic drugs in China’s drug registration management measures