美国付费法案修订2017年实施，本文为修订版中费用结构的简述。ToachieveGDUFAIIcommitments，FDAmustincreasetheoverallcapacityandcapabilitiesofthegenericdrugapplicationreviewprogramthroughauserfeestructurethat provides stable， predictable funding， is efficient in design and feasible to execute. FDA and industry agreed to jointly recommend these proposed changes for GDUFA II.为了实现GDUFA II 的承诺， FDA必须增加仿制药申请评审工作的能力，通过用户付费提供稳定的和可预测的资金，以保证能执行其设计和可行性。FDA和企业同意共同推动完成GDUFA II 的提议变革。I.Agreed Upon Enhancements约定增强A.Increased Funding资金增加GDUFA I was built on the assumption that FDA would receive 750 Abbreviate New Drug Applications (ANDAs) per year. ANDAs are the primary workload driver of the program. Over the first 4 years of GDUFA I， ANDA receipts have averaged approximately 1000 per year. To address the increased workload， FDA hired additional staff and is projected to spend about $430 million in the final year of GDUFA I. In order to maintain FDA’s current productivity and implement negotiated improvements， Industry and FDA agreed that user fees should total $493.6 million annually adjusted each year for inflation. GDUFA I 建立假定在每年接受750件ANDAs的基础上，ANDAs是工作压力的主要来源。在过去执行GDUFA1的第一个4年，每年平均大约接收到100件ANDA.这表明工作压力在增加，FDA雇佣了额外的人员并且计划在GDUFA1最后一年用$4.3亿美元去解决该问题。为了维持FDA现有的生产能力和实现改进商谈，企业和FDA达成共识，考虑到通货膨胀每年用户缴费总额应达到4.936亿美元。B.Modifications to the User Fee Structure用户缴费结构的修改1.Introduction of GDUFA Program FeesGDUFA项目费用介绍In order to maintain its generic drug review program， FDA’s user fee collections must be predictable. Whereas application volume can fluctuate from year to year， there is a relatively stable universe of generic drug facilities and ANDA sponsors. Therefore， in order to improve the predictability of the fee base and to more closely align fee responsibility with program costs and fee-paying ability， FDA and industry have agreed to shift the burden more toward annual program fees.为了维护仿制药评审工作，FDA的用户收费必须进行预算。虽然申请的数量每年都有波动，但是仿制药设施和ANDA的赞助商有一个相对稳定的领域。因此，为了改进缴费基础的可预见性和费用交付能力和评审项目成本更加紧密的结合，FDA和企业同意每年承担更多的费用。Firms that sponsor one or more approved ANDAs will pay an annual fee. Finished Dosage Form (FDF) and Active Pharmaceutical Ingredient (API) facilities will continue to pay annual fees as they did under GDUFA I.赞助了一个或多个批准的ANDAs的公司将付年费，在GDUFA 1条件下，已上市剂型（FDF）和API设施要持续付年费。2.Elimination of Supplement Fees消除补充费用In GDUFA I， ANDA sponsors making changes to an already approved ANDA through a Prior Approval Supplement (PAS) were required to pay a fee. Because the number of annual PAS submissions is unpredictable， FDA was unable to accurately project fee collections. In addition， collecting those fees required administrative resources. Moreover， some PAS submissions were solicited by FDA. In those instances， it seemed unwarranted to charge the filer a fee. Finally， the new ANDA program fee is meant to be an investment in the program， and encompasses what were supplement fees. For those reasons， industry and FDA agree that the PAS fee should be eliminated.在GDUFA 1 中， ANDA赞助商通过PAS(Prior Approval Supplement)对已经批准的ANDA进行主动变更就要求付费。因为年度PAS 提交的数量是不可预知的， FDA不能准确计划这部分缴费。另外，收集这些费用需要行政资源，并且一些PAS提交是FDA 提出的。在这些情况下，看起来一些文职工作的费用不能得到保证。最后，一个ANDA评审费用意味着是一个评审的投资，并且包含了所有补充申请的费用。基于这些理由，企业和FDA达成共识PAS费用将取消。3. Small Business Considerations小型企业的顾虑As part of the negotiations， FDA and industry convened a working group to discuss small business considerations. The group did extensive research on the issues confronted by small businesses and others under GDUFA I. Pursuant to its conclusions and other lessons learned through GDUFA I and the negotiation process， FDA and industry have agreed to three distinct small business considerations:作为谈判的一部分，FDA 和企业召集了一个工作组来讨论小型企业的顾虑。工作组广泛研究小型企业面对的问题和其他在GDUFA I执行时的问题。依照他们的调研结论和其他GDUFA I的执行问题，在谈判过程中，FDA和企业对小型企业的顾虑达成了以下三个共识：1.Under GDUFA I， a facility would pay an annual fee if it was listed in an ANDA， regardless of whether it was listed in any approved ANDAs. As a result， a facility that is listed only in pending applications could be charged an annual GDUFA fee even though it had no generic drug revenue stream. Under GDUFA II， no facility or ANDA sponsor would be charged an annual fee until an ANDA in which it is listed is approved.在GDUFA I的情况下，一个工厂如果列入ANDA中就应该缴年费，无论 它是否被任何一个批准的ANDAs使用。因此，一个被登记的工厂在申请期间就要缴纳年费，即使没有仿制药收入来源。但是在GDUFA II中，企业和赞助商只用缴纳一次年费直到ANDA被引用。2.The ANDA sponsor landscape varies dramatically from firms that own hundreds of approved ANDAs to new market entrants that own only one approved ANDA. Under the GDUFA II fee structure， a firm and its affiliates will pay one program fee commensurate with the number of approved ANDAs that the firm and its affiliates collectively own. Firms will not pay a per-ANDA fee， but will be split into three tiers that represent different positions held by the firms and their affiliates within the market. Industry’s negotiation representatives consulted with ANDA sponsors to determine the parameters for each tier.ANDA赞助商和拥有数百个上市ANDAs的公司有很大不同，对于市场的竞争赞助商仅有一个ANDA。GDUFA II 的费用结构中，一个公司和他的附属企业可以对几个已经批准的他们共同拥有的ANDAs进行一次付费。公司将不用预付AND费用，但是需要分为三等级代表公司和附属公司在市场上占有的不同位置。企业的讨论代表和ANDA赞助商经过讨论决定每个等级的参数。3.Within the FDF facility category， there are two distinct business types. Contract Manufacturing Organizations (CMOs) are hired by ANDA sponsors to manufacture their generic drugs. Alternatively， some ANDA sponsors manufacture their own drugs. Under the GDUFA II fee structure， CMOs willpay one third the annual fee paid by firms that manufacture under ANDAs which they or their affiliates own. The foreign fee differential will still apply.对于FDF（已上市剂型）的设施类别，有两个不同的业务类型。ANDA 的赞助商雇佣CMOs（委托生产组织）去生产他们的仿制药。或者一些ANDA的赞助商自己生产他们的仿制药。在GDUFA II的收费结构中，CMOs需要付三分之一的年费通过ANDAs生产公司或他们的附属企业。国外缴费差仍然适用。GDUFA I v. GDUFA II Fee Structure法案I和法案II收费结构对比Fee CategoryGDUFA IGDUFA II1-time Fees:?ANDA Application?24%?33%?DMF Application?6%?5% Annual Program Fees:?API Facility?14%?7%?FDF Facility?56%?20%?CMO FacilitySame as FDF?One-third FDF?ANDA HolderN/A?35%?Small (1-5 ANDAs)N/A?One-tenth Large?Medium (6-19)N/A?Four-tenths Large?Large (20+)N/A?Full FeeSmall business considerations收费种类法案1法案II一次性收费ANDA 申请?24%?33%DMF 申请?6%?5%年费API工厂识别?14%?7%FDF识别?56%?20%CMO识别Same as FDF?Onethird FDFANDA 持有者N/A?35%II.Other Technical Improvements其他技术改进1.Fee relief for non-commercial drug distribution非商业药物分布费用减免State or Federal Government entities which sponsor or manufacture drugs but do not distribute them commercially will not be assessed user fees.政府企业赞助和生产的药物不进行商业销售，也不进行费用评估。2.Refund for Withdrawal撤销退款Currently， there exists a disincentive for an ANDA sponsor to withdraw an application that it knows will not be received by FDA for some fatal flaw. GDUFA II will allow a sponsor to receive a partial refund if it withdraws an ANDA voluntarily before FDA makes a decision on whether the ANDA may be received. This will save FDA work and the sponsor time.当前，对于撤回一个已知有不能被FDA接受致命弱点的申请，对于ANDA的赞助者存在一些抑制因素。GDUFA II将允许赞助者自动撤回FDA没有做出结论的申请，无论这个ANDA是否能被接受。这将减少FDA的工作和节约赞助商的时间。3.One fee per Facility以工厂为单位缴费Under GDUFA I， a facility that qualified as both API and FDF would pay both fees. Such a facility will pay just the FDF fee under GDUFA II.在GDUFA I中，一个工厂同时有API 和制剂都需要付费，但是在GDUFA II中仅需要付上市制剂的费用。4.Foreign Fee Differential国外费用差异Under GDUFA I， FDA could charge foreign facilities anywhere from $15，000 to $30，000 more per facility than domestic facilities， depending on FDA’s calculations each year concerning relative costs of foreign and domestic inspections. For each year under GDUFA I FDA determined that the differential would be $15，000. Under GDUFA II， the foreign fee differential will be set at $15，000.在GDUFA I中，FDA收取国外任何地方的工厂识别费从$15，000 到 $30，000均高于本土企业的工厂识别费用，这取决于FDA每年对国内外检查的相关费用成本的计算。在GDUFA I中FDA每年的费用差为$15，000，在GDUFA II中没有改变。