論生物相似性藥品之上市規範與智慧財產保護

Abstract

製藥產業，一種高成本、高風險、高利潤的特殊產業，因著醫藥品與人類健康息息相關以及科學的不確定性，使得製藥產業具有國家制度高度依賴之特性；也因著技術密集與技術整合的本質，使得製藥產業成為一種以知識經濟為基礎的高科技產業。這樣的本質特性，不僅反映在醫藥產品高單價的市場現象，也同時體現在藥品上市審查規範及專利保護制度的法制需求。過去，在化學藥品的時代，因著學名藥的發展，促成藥價的平抑以及醫療成本的降低，各國政府對於學名藥的研發上市，乃至於對照新藥的保護措施均有其完整的規範，藉以達到公眾健康、創新研發和控制醫療成本三方利益的平衡。 隨著生物技術與醫藥的結合，生技藥品徹底改革了以往化學藥品對於某些疾病治療的有限性，彌補了化學藥在治療領域中的不足；生技藥品的重要性，使得其在全球醫藥市場占有率逐年攀升，高額的藥價亦使得人民的醫藥成本與政府療療保險的支出所費不貲。隨著1980年代研發上市的第一批生技藥品專利權陸續到期，一種與化學學名藥具有相當市場地位的藥品─「生物相似性藥品」成為各家藥廠覬覦搶食的目標；然而，由於生技藥品的本質差異性，使得過去對於傳統化學新藥、化學學名藥之相關規範，無法一體適用於生技新藥與生物相似性藥品；於此，生物相似性藥品的上市審查規範，以及其對照生技新藥的專利、非專利保護措施制度的改革，在人民用藥需求及平衡藥價的政策目標下，成為各國政府發展生技製藥產業的重點任務。 自2004年起，歐盟即針對生物相似性藥品制定相關上市審查之指令及指導方針；我國政府亦於2008年底公告發布「藥品查驗登記審查準則－生物相似性藥品之查驗登記」，其為鼓勵國內產業發展生物相似性藥品之決心尤為昭然；然而，除上開原則性的審查規範外，我國並未就生物相似性藥品上市審查之細節事項併予制定明確之規則，使得國內藥廠發展生物相似性藥品時，有欠缺預見可能性之風險，甚或導致上市申請成本過高，不僅缺乏發展之誘因，更使平抑藥價之功能不復存在。此外，或因我國向來就學名藥上市審查規範與醫藥專利制度採取割裂的態度，於2008年公告生物相似性藥品之查驗登記審查準則時，並未就相關專利議題併予修法；惟，生物相似性藥品的發展與生技新藥專利保護的衝突將是無可避免的，而現行法下是否提供足夠的規範以協調、衡平生物相似性藥品之廠商與生技新藥之專利權人雙方利益，殊值深究。 針對上開問題，本論文針對生技藥品的本質差異性對於傳統化學學名藥上市審查規範及相關專利、非專利保護措施之影響，進行探討；藉由歐、美生技製藥產業環境與相關法制之觀察與比較，我國現行法制以歐盟審查規範為藍本，制定生物相似性藥品之查驗登記審查準則，在公眾用藥安全與生物相似性藥產業發展的衡平上，或許是尚屬妥適的方法。然而，本於促進生物相似性藥品盡早上市，以及發揮其平抑藥價功能之目的，對於生物相似性藥品上市所需試驗資料之規模與條件，應當具有更為簡化及明確的標準，以促成上開目的之實現。另外，就生技新藥的保護措施方面，由於生物相似性藥品與其對照新藥僅具生物相似性，其可能發生生物相似性藥品具備上市申請所需生物相似性，而未落入對照新藥之專利權範圍，導致專利制度對於生技新藥未能提供較完整的保護，因此，非專利保護措施對於生技新藥而言，相對有其重要性。而就生物相似性藥品涉及之專利爭議方面，美國相關法律提案揚棄舊有的專利扣合機制，採取專利資訊交換與專利清單之制度，並對於相關專利訴訟之提起與爭訟標的均有所限制；此等措施的建構，對於我國推動生物相似性藥品產業發展之政策目標而言，實具有立法方向之參考價值。 此外，本論文亦藉由美國學名藥之專利訴訟案例分析，俾能就生物相似性藥品發展時可能面臨之專利訴訟，提供我國藥廠在拓展海外市場時，擬定訴訟防禦策略之參考。

Pharmaceutical industry, one of a high-cost, high-risk and high-revenue earning industry, is characterized by highly depending on governmental policy and regulation because of the closed relationship between pharmaceuticals and human health, and implications of scientific uncertainty. It is also characterized as the technology- intensive industry so that the pharmaceutical industry shall be based on the knowledge economy. Consequently, such natures of the pharmaceutical industry result in not only the high price of pharmaceuticals, but also the requirement for constructing drug regulation process and patent protection system. In the past, the Generic drug competition typically brings prices down and saves the cost of the health-care providers. In order to striking a proper balance among protecting the public interest, encouraging innovation and controlling medical cost, all governments implement proper norms for generic drugs approval regulations and patent protection policies. As the integration of biotechnology and medicine, biologics overcome many limitation of chemical drug therapy and have significantly advanced over traditional treatments. As a result, the share of biologics in the pharmaceutical market is increasing rapidly and the problems about the increasing drug prices and cost of medical insurance are also emerged. With many first-generation biologics off patent or soon to come off patent, there are increasing moves for “Biosimilar”, which has a similar market position with generic drugs. However, the natural differences of biologics and chemical drugs result in existing regulations unsuitable for biosimilars. Accordingly, in view of the medical demands of people and the drug price control policy, enactment of biosimilars approval regulations, the patent protection and non-patent protection regimes is a major task of all governments for promoting domestic biopharmaceutical industry. Since 2004, Europe has been pioneering legislation for the approval of biosimilars. For encouraging domestic pharmaceutical industry to develop biosimilar drugs, in 2008, Taiwan government has issued the examination guideline related to biosimilars application. However, this guideline is only a fundamental rule and this guideline does not provide details for biosimilars approval. It may result in the standards of examination being unforeseeable, and, in turn, increasing the cost of drug approval. It may also result in declining the motivation to develop biosimilars, and the purpose of decreasing the biologics prices may not be achieved. Additionally, from beginning, Taiwan government never implements the practice of linking the regulatory approval for a generic medicinal product, to the status of a patent for the reference drug. Hence, there is no consequential amendment in Patent Act as the said guildline issed in 2008. Nevertheless, the conflict occurring between development of biosimilars and patent protection of reference biologics is inevitable. Therefore, it is worthy of exploring whether the existing regulations has provide a sufficient mechanism to balance the interests of the biosimilar applicant and the patentees. In the light of the issues above, this thesis focuses on the influence on existing drug approval regulations, the patent protection and non-patent protection regimes from the nature of the biologics. By comparing the related regulations of Taiwan with those of United States and European Union, this thesis indicates that the said examination guideline, which refers to the newly guidances issued by the EU, may be acceptable for getting a balance between public health and development of biosimilars. Furthermore, for the purpose of introducing the biosimilars sooner into the market and decreasing the biologics prices, this thesis indicates that clearer, objective standards in the light of the requirements of clinical and non-clinical trial, such as the sample size for clinical trials, are necessary. In respect to the protection of brand biologics, biosimilar product that is merely required to be “similar” to the innovator reference might be similar enough under regulatory standards to obtain approval as a biosimilar, but different enough under intellectual property law to avoid infringing issued patents on the innovator product. As a result, patent protection is not sufficient in the field of biologics. Non-patent protection is relative important to the innovative biologics. In addition, the new bills introduced in U.S. Congress relating to biosimilars do not adapt the patent linkage system, but instead of creating a mechanism for information exchange between the innovator and the biosimilar applicant. These bills also restrict the patent lawsuits brought by patentee or biosimilar applicant, and the object of such litigation is limited. In these regards, these legislative measures are role models of biosimilar legislation with great policy implications, which deserve attention from policy-makers and academics in law in Taiwan. Moreover, the thesis also explores the related judgements of U.S. courts for the purpose of assessing relevant judicial trends and providing Taiwan pharmaceutical companies effective defensive strategies for patent litigation under a future Biosimilars Act.