505(b)(2)： 美国新药开发捷径
目前国内外医药研发风起云涌，如何将在研药物尽快推进到临床愈发显得重要。通常在启动首次临床试验之前需要预先规划好最佳监管申报和产品开发途径。在美国，505(b)(2) 途径为传统制药企业提供了一条极具吸引力的药物临床开发捷径。最有名的一个通过该途径成功获得审批的经典案例是Abraxane (白蛋白结合型紫杉醇)，该药物在2020年第一季度的销售额就达到了3亿美元。
该途径创立于美国1984年的《药品价格竞争与专利期补偿法修正案》（Hatch-Waxman Amendments）；505(b)(2) 名字源于《联邦食品、药物和化妆品法案》中相关部分的标记。505(b)(2)途径的目的在于加速创新药物获得FDA入市审批。与505(j)（简略新药申请）相比，505(b)(2)是FDA传统的NDA与简略新药申请（ANDA）的混合产物。
符合505(b)(2)审批途径的药物包括但不限于以下几类：
- 剂型或配方发生改变的药物
- 给药途径发生改变的药物
- 给药方案发生改变（剂量、给药间隔）
- 复合制剂中活性药物成分（API）的替换
- 新分子实体（NME）药物
- 药物含有从动植物中天然提取或通过重组得到的新成分，且该成分尚未批准用于所列药物的适应症。
505(b)(2)途径的主要优势在于申办方可部分或完全借用先前已获批药物的临床安全性和有效性，从而减少入市申报所需的临床试验数量。多数情况下，申办方只需要开展药代动力学研究来确定药物暴露程度即可。该途径的另一优势在于通过505(b)(2)途径获批产品的美国市场独占时间为3~5年（具体时间取决于新产品的创新程度以及包含在获批新药上市申请（NDA）中的临床数据情况）。
近年来，在美国经505(b)(2)途径的获批药物数量经历了快速增长。仅2019年，该途径下的获批数就占美国FDA所有NDA获批总数的56%以上。而505(b)(2)途径成功的关键是在早期阶段就与FDA进行沟通，需要清晰地说明用于审批的既定开发计划。选择正确的新药申报途径是迈向成功的重要一步。我们的专业团队可帮助客户最大程度地利用与FDA的会议和交涉，以确保申办方明确掌握审批过程中的有利因素和可能需要进一步研究的内容。
随着“4+7”医改深入开展以及国内市场仿制药价格压力的不断上升，505(b)(2)为中国制药公司进入全球最大医药市场提供了有利契机。此外，若申办方将通过505(b)(2)途径获得FDA审批的产品带回中国市场，无疑能大大增强该产品获得国内监管部门审批和营销方面的信心和竞争力。
海洋之神优惠大厅主站团队在帮助韩国和印度制药企业在美国用505(b)(2)途径开发药物方面拥有丰富经验。我们的战略合作伙伴Alta Sciences在北美拥有完善的临床试验基地支持505(b)(2)临床开发。我们将共同为您提供一体化的解决方案，充分满足您通过505(b)(2)途径进行药物开发的需求。
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505(b)(2) Regulatory Pathway
In today’s age of drug development, the timeline from bench top to bedside is more important now than ever. Planning the right pathway for regulatory approval often begins before the first human trials are initiated. In the USA, the 505(b)(2) regulatory pathway offers a development shortcut (less expensive, faster timeline) that could be attractive to traditional pharmaceutical companies. A classic example of 505(b)(2) approval is Abraxane (albumin-bound paclitaxel), which raked in sales of $300MM USD in the first quarter of 2020.
This pathway was created by the Hatch-Waxman Amendments of 1984, with 505(b)(2) referring to a section of the Federal Food, Drug, and Cosmetic Act, to help initiate innovation with a faster timeline to approval. Contrary to the 505(j) (abbreviated new drug application), 505(b)(2) is a hybrid between the FDA’s traditional NDA and an abbreviated new drug application (ANDA).
Examples of products eligible for the 505(b)(2) approval process include but are not limited to the following:
- Change in dosage form or formulation
- Change in the route of administration
- Change in dose regimen (dose strength, dosing interval)
- Substitution of an active pharmaceutical ingredient (API) in a combination product
- New molecular entity (NME)
- Drug with new ingredients from animal or botanical sources (naturally derived or recombinant) for a not previously approved indication for a listed drug
A major advantage of the 505(b)(2) pathway is that it allows a sponsor to rely, at least in part, on the safety and/or effectiveness for the previously approved drug, thereby reducing the number of clinical trials required for approval. In most cases, the sponsor only has to perform pharmacokinetic studies to show the extent of exposure. Another incentive is three to five years of market exclusivity for 505(b)(2) products, depending upon the extent of changes to the reference product and the type of clinical data included in the approved New Drug Application (NDA).
In recent years 505(b)(2) approvals have experienced double-digit growth. In 2019, 505(b)(2) approvals make up more than half (56%) of all NDA approvals by the FDA. The key to the success in the 505(b)(2) pathway is planning at the early stages to interact with the FDA and clearly explain the intended plan for approval. Choosing the right regulatory pathway is critical to the success. Our dedicated team can help clients get the most out of interactions with the agency to ensure the sponsor knows what will be supported and what will likely need further investigation.
With the 4+7 reform and increasing pricing pressure of generic products in the domestic market, 505(b)(2) offers an attractive opportunity for China pharmaceutical companies to explore the previously untapped largest market in the world. Besides, an approved product via the 505(b)(2) pathway by the FDA confers great regulatory and marketing confidence if the sponsors brings the product back to the China market.
Amador team has extensive experience in helping Korean and Indian pharmaceutical companies to develop products under the 505(b)(2) pathway in the USA. Our strategic partner Alta Sciences specializes in conducting clinical trials in North America supporting 505(b)(2) applications. Together we can provide end-to-end solutions to fulfill your needs in the product development through the 505(b)(2) pathway.