由學名藥侵權訴訟評估均等論在生物相似藥侵權訴訟的影響—以美國為例

Abstract

BPCIA在2010年三月生效後，生物相似藥廠商開始可以利用簡化的文件向美國食品和藥物管理局（FDA）申請藥品許可證，這個新醫療法賦予FDA決定如何落實法案的權力。基於不同生物製劑之間缺乏比較性這個已知的事實，加上公眾安全的考量，在還沒有累積大量經驗可以歸納出哪些是比較分析必要的資訊之前，FDA會保守的要求生物相似藥廠商以BPCIA提出申請時，必須提供臨床試驗資料來證明與參照藥品之間沒有臨床上有意義的差異。\n雖然BPCIA給出了解決專利糾紛的框架，俗稱專利舞蹈(patent dance)，依照目前聯邦巡迴上訴法院對BPCIA的解釋，認為BPCIA法案不強制生物相似藥申請者遵循其規定之專利糾紛解決程序，雖然就目前的最新發展來看，迴避專利舞蹈可以避免一些程序上的麻煩，但真正參照藥品廠商和生物相似藥公司的輸贏仍是在訴訟戰場上見真章。\n美國FDA在2015年3月6日核准了的一個生物相似藥-Zarxio( filgrastim-sndz)，目前尚不清楚均等論這種不確定性在生物相似藥上影響的程度，但藉由簡化新藥申請上市的小分子藥物所涉入的侵權訴訟做有限度的推論可以發現，小分子藥物的均等謬論案件是牽涉到外圍專利，當專利不再提供足夠的誘因去激勵專利權人時，學名藥廠商就會贏得均等論謬論案件。因為生物製劑是一種製程決定的產物，因此其專利通常是集中在製程。以BPCIA和專利法為框架來分析過去的相關侵權訴訟，可以預測生物相似藥廠商在轉化前步驟、轉化步驟、調劑、或包裝做改變，其成功的機會較大，而在細胞培養會純化步驟做改變，成功的機會最小。然而，最終還是要看法院將來如何解決生物相似藥的侵權問題，各方都要意識到科學與法律議題的複雜性，及妥適解決侵權訴訟的重要性。\n台灣廠商要進入生物相似藥的領域，是困難重重的。生物相似藥的開發及法規成本，不如想像中低，鑒於蛋白質藥『產能』一直被看作是市場發展受阻的主要原因，藥廠委外合作(CRO、CMO或NRDO) 的模式能快速與國際藥廠接軌，逐步奠定台灣在藥物開發的供應鏈合作利基並提昇國際知名度。

The Biologics Price Competition and Innovation of 2009 was activated on March in 2010. Now the US Food and Drug Administration (FDA) can approve biosimilars and was empowered to how to practice. Given the known issues with lack of comparability between different biologics preparations, and the Agency’s strong interest in protecting public safety, it is probable that, until it has developed a body of experience with regards to the amount and kind of data needed to make comparability evaluations, the FDA will adopt a conservative approach and require at least some clinical studies before approving biologics under BPCIA. \nThough BPCIA provide the frame for resolving patent issues, that is so-called patent dance, Federal Circuit said that parties were not compelled to dance. Thus the law uncertainty was shifted to patent infringement. \nFDA approved the first biosimilar, Zarxio (filgrastim-sndz), on 6, March, 2015. It is unclear how biosimilar will be treated in court based on doctrine of equivalence. Based on the experience from generics, courts tends to adjust the scope of equivalents to improve the correspondence between patent scope and desired patent incentives. In contrast, biologics is path depended. That is to say process decided what biologics would be. Both the BPCIA and patent law guide the shape of infringement suits. Follow-on biologics companies will be most successful when they make a change in the pretransformation process, the transformation process, the formulation, or the packaging. They will be least successful when they make a change in the cell culture conditions or the purification process. It remains to be seen how courts will address issues of infringement for follow-on biologics, but all parties should be aware of the complexity of the scientific and legal issues and the importance of addressing them properly.\nThe cost for development and the complexity of regulation in biosimilars were tremendously high. Thus it is difficult for biopharmaceutical industries in Taiwan to enter this field. In the light of unmet production capacity in protein drug, pharmaceutical industries in Taiwan could apply the mode of CRO, CMO or NRDO to integrate into global biopharmaceutical community.