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【讨论】虽然目前用的不多，但还是想弄清新药（NDA）申请中的505(b)(2)，505(j)和ANDA的关系。

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这个帖子发布于6年零330天前，其中的信息可能已发生改变或有所发展。

亲们，在园子里搜索了一下“505b”，资源屈指可数，不知道是因为是NDA有关知识的缘故，还是因为太简单不值一提，但我是真的有点被搞晕了，所以想请哪位大侠，高人点拨点拨。
说到505b，FDA专门有发布一篇指南，感谢@zhigezhe
http://www.fda.gov/downloads/Drugs/Guidances/ucm079345.pdf
在该指南中，提到505法案包括NDA的3种申请：
第一种： 505b1 ：申报者进行所有药学研究
第二种： 505b2：同样也是申报者进行所有药学研究，但不同的是部分信息不实由申报者自己完成（by），或者这些研究不是为了申报者而完成的（for）；以及申报者没有引用的权利（我觉得这里指的就是文献）
第三种：505j：欲申报制剂在API，剂型，给药途径，标签，质量，检验，适应症上都和已有品种一样。
原文如下：“Section 505 of the Actdescribes three types of new drug applications:
(1) an application that contains full reportsof investigations of safety and effectiveness (section 505(b)(1)); (2) anapplication that contains full reports of investigations of safety andeffectiveness but where at least some of the information required for approvalcomes from studies not conducted by or for the applicant and for which theapplicant has not obtained a right of reference (section 505(b)(2));
and(3) an application that contains information to show that the proposed productis identical in active ingredient, dosage form, strength, route ofadministration, labeling, quality, performance characteristics, and intendeduse, among other things, to a previously approved product (section 505(j)).Note that a supplement to an application is a new drug application.”
该指南也指明了为什么要这么分类“This approach isintended to encourage innovation in drug development without requiringduplicative studies to demonstrate what is already known about a drug whileprotecting the patent and exclusivity rights for the approved drug.”这样分类，主要是为了在不影响已申报药物专利和独家权的基础上，鼓励药物开发者，无需对已有事实再进行重复研究。
在谈到505b2和505j的区别时，指南里有说“An applicant should file a505(b)(2) application if it is seeking approval of a change to an approved drugthat would not be permitted under section 505(j), because approval will requirethe review of clinical data.”，即当待申报产品与已批准制剂有差异，需要做临床时，就需要走505b2，而不是505j。
而@tinybayonet说到“主要化学成分相同，不同酸根或不同盐基的化学药品，全新药可按505（b）(1)申请，包括上述情形在内的多种情况（如改剂型、改适应症等）可按505（b）(2)申请，仿制药按505（j）申请。”
另一方面，从市场独占期也可以看出，505b2（3年）和ANDA（首仿为180天）还是有很大差别的。指南中规定“A 505(b)(2)application may itself be granted 3 years ofWaxman-Hatch exclusivity if one or more of the clinical investigations, otherthan BA/BE studies, was essential to approval of the application and wasconducted or sponsored by the applicant (21 CFR 314.50(j); 314.108(b)(4) and(5)). A 505(b)(2) application may also be granted 5 years of exclusivity if it isfor a new chemical entity (21 CFR 314.50(j); 314.108(b)(2)). A 505(b)(2)application may also be eligible for orphan drug exclusivity (21 CFR314.20-316.36) or pediatric exclusivity (section 505A of the Act).”
然后在橙皮书里，谈到市场独占期豁免（Waived exclusivity）也有这么一段文字，
Ifa new drug application (NDA) submitted under section 505(b) of the FederalFood, Drug, and Cosmetic Act (Act) qualifies for exclusivity under sections505(c)(3)(D) and 505(j)(5)(D), the exclusivity is listed in the Patent and Exclusivity Section of the Orange Book. If a drug product has receivedthis exclusivity, the FDA will delay the approval of a 505(b)(2) application or an abbreviated new drug application (ANDA) under section 505(j) of the Act until the expiration of the exclusivity（从这句可以看出，原研药的市场独占期时间都会影响505b2和505j的通过，还有红字证明505j是走ANDA程序的）. If the listed drug is also protected by one or more patents, theapproval date for the 505(b)(2) application or ANDA will be determined by thelatest expiring patent or exclusivity listed in the Orange Book.
However,the holder of the NDA may waiver its exclusivity as to any or all 505(b)(2) andANDA applications referencing the protected drug product. If an NDA sponsor waivers its right to theexclusivity protection, qualified 505(b)(2) or ANDA applications may beapproved without regard to the NDA holder's exclusivity.（这种市场独占期解除什么情况下才会发生呢？）
通过以上，得出结论：新药中的505j等同于ANDA申请，505b2是对已有药品的更改（剂型等）。
不知自己这样的分析是否正确，还请@ zhulikou431等大侠指点。
此外，还有一个问题想请高人解答，橙皮书上的市场独占期解除什么情况下才会发生呢？