Department of Community Health Sciences, Cummings School of Medicine, O'Brien Institute of Public Health, University of Calgary, Calgary, AB, Canada.
Program on Regulation, Therapeutics, and Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Clin Transl Sci. 2021 Sep;14(5):1917-1923. doi: 10.1111/cts.13046. Epub 2021 May 31.
Before the first generic version of a drug is marketed, patent litigation often occurs. The process begins when generic manufacturers notify the US Food and Drug Administration (FDA) of their intent to market a generic copy of a brand-name drug protected by patents, which they allege to be invalid or not infringed (called a Paragraph IV certification). Assuming the brand-name manufacturer responds with litigation within 45 days, a 30-month stay period is triggered, which bars the FDA from authorizing generic entry until the stay period expires or litigation is resolved in favor of the generic manufacturer. To understand whether 30-month stays delay generic entry, we examined the timing of major legal events leading to generic entry for a cohort of 46 generic drugs, including the timing of Paragraph IV certification filings, stay period expirations, the FDA approvals of generics, and generic product launches. We found Paragraph IV certifications were filed a median of 5.2 years after the brand drug's FDA approval. There was a median of 3.2 years between the stay period expiration and subsequent generic launch. Because stay periods generally expire well in advance of when generic entry typically occurs, 30-month stays are unlikely to delay the timing of generic entry. Patent litigation could begin even earlier, however, if litigation was allowed to start immediately following a brand-name drug's FDA approval; but by law currently, the soonest this can begin is 4 years after the brand drug's FDA approval. Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? Before generic versions of new drugs reach the market, patent litigation often occurs. Once litigation has been initiated, a 30-month regulatory stay period is triggered that bars the US Food and Drug Administration (FDA) from approving the generic application until litigation resolves or the stay period expires. WHAT QUESTION DID THIS STUDY ADDRESS? What is the timing of key legal events in the regulatory approval process for generic drugs in relation to the eventual launch of the generic product? WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? We identified the typical timing of the initiation of patent litigation and expiration of the 30-month stay period prior to the eventual launch of generic products. Litigation is often initiated as soon as legally possible (i.e., 4 years after the launch of the brand product), and stay periods typically expire well before generic entry occurs. HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE? Stay periods are unlikely to delay generic entry directly because stay expirations often occur well before the time of generic launch. Allowing the submission of generic drug applications immediately following a brand drug's FDA approval would facilitate earlier patent dispute resolution and prevent unnecessary delays in the anticipated generic product launch date.
在首个仿制药上市之前，通常会发生专利诉讼。这一过程始于仿制药制造商向美国食品和药物管理局（FDA）通知其打算销售受专利保护的品牌药物的仿制药，他们声称这些专利无效或未被侵犯（称为第 IV 段认证）。假设品牌制造商在 45 天内回应诉讼，那么将触发 30 个月的中止期，在此期间，FDA 禁止批准仿制药进入市场，直到中止期届满或诉讼有利于仿制药制造商为止。为了了解 30 个月的中止期是否会延迟仿制药的上市，我们检查了为 46 种仿制药的一大类药物进入市场的主要法律事件的时间安排，包括第 IV 段认证申请的提交、中止期的到期、FDA 对仿制药的批准以及仿制药产品的推出。我们发现，第 IV 段认证的提交时间中位数为品牌药物获得 FDA 批准后 5.2 年。从中止期届满到随后的仿制药推出，中位数为 3.2 年。由于中止期通常在仿制药通常进入市场之前很久就到期，因此 30 个月的中止期不太可能延迟仿制药的上市时间。然而，如果允许在品牌药物获得 FDA 批准后立即开始诉讼，专利诉讼可能会更早开始；但是根据法律规定，最早可以在品牌药物获得 FDA 批准后 4 年开始。研究重点 关于这个主题，目前的知识是什么？ 在新药物的仿制药进入市场之前，通常会发生专利诉讼。一旦提起诉讼，就会触发 30 个月的监管中止期，在此期间，FDA 禁止批准仿制药申请，直到诉讼解决或中止期届满。 这项研究提出了什么问题？ 与仿制药产品最终推出相关的仿制药监管批准过程中关键法律事件的时间安排是什么？ 这项研究增加了我们的哪些知识？ 我们确定了专利诉讼的发起时间和 30 个月中止期的到期时间，以确定最终推出仿制药产品的时间。诉讼通常尽快提起（即品牌产品推出后 4 年），中止期通常在仿制药进入市场之前很久就到期。 这将如何改变临床药理学或转化科学？ 中止期不太可能直接延迟仿制药的上市，因为中止期通常在仿制药推出之前很久就到期了。允许在品牌药物获得 FDA 批准后立即提交仿制药申请，将有助于更早地解决专利纠纷，并防止仿制药预期推出日期的不必要延迟。
