首页 > 资讯 > 当企业在FDA的合规状态阻碍批准时应怎么办？

出自识林

2016-10-24 Lachman CONSULTANTS

美国仿制药使用者付费（GDUFA）计划促进了对仿制药申请人以及在申请中确定的设施检查次数的增加。随着检查次数的增加，需要由FDA检查员撰写、由其主管批准然后由药品审评和研究中心（CDER）合规办公室审查和批准的设施检查报告（EIR）随之增加。如我们在昨天的资讯【进入美国市场的制药企业最抓狂的问题是什么？】中所述，从EIR离开现场直到FDA的计算机系统更新以提供可接受的结果之间的时间越来越难以及时解决合规相关问题。

有企业称之为“合规黑洞”，还有企业称之为“无尽的夏天”，因为该企业自从今年三月份的重新检查没有收到483观察项以来，一直在试图弄清楚他们的合规状态什么时候将在FDA计算机中改变。

企业打给监管项目经理（RPM）或监管业务项目经理（RBPM）的电话也得到了相同的回复：“在计算机系统更新之前我们无法做任何事情。”许多这样回复是发生在发布完全回应函指出唯一悬而未决的问题是解决设施合规状态之后。因此企业陷入等待模式。打电话给合规办公室基本是相同的结果。企业表示收不到回复电话（或者他们只是被告知耐心等待）。

试图在FDA得到同情也很困难，尤其是当企业准备上市销售产品，但需等待最终的合规结果和批准行动时。此外，我们曾经听说一家企业已有潜在的明确上市日期（第181天或到期日期），他们收到FDA官员通知，申请的合规状态在FDA的计算机系统中仍未得到解决。但事实上FDA现场检查员在检查后已告知申办人或者没有483观察项，或者完成的EIR已被转发到CDER对该企业关于观察项的回复表示满意，或者已经给出批准建议。虽然我们知道从申办人那里听到这些抱怨时我们并不总是了解全局，但这类抱怨发生的频率正在快速增加。仅上周，Lachman咨询公司收到了四个关于这一问题的问询。每家公司都对于无法得到除“你只需要等待！”之外的答案表示愤怒，并询问了相同的问题：“我应该打给FDA的哪个人来讨论这个问题？”

这个问题没有简单的答案。根据愤怒程度，你可以从FDA合规办公室食物链的顶端或之下的某个地方开始，或许从制造质量办公室或从各药品质量部门之一开始。尚不清楚有多少申请由于被困在“合规黑洞”中而延迟，可能有几十个也可能只有几个。但是，如上所述，仅仅是打电话给FDA不太可能解决阻碍批准的合规状态问题。相反，申办人可以考虑通过请求与相关FDA官员会面来升级问题。毕竟，吵得凶的人更可能获得FDA的注意。

Lachman CONSULTANTS - Bob Pollock先生
编译：识林-椒
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Who you Gonna Call . . . . to Resolve a Compliance Status Block on Approval?
By Bob Pollock | October 24, 2016 原文地址

This blog post was coauthored by Kurt Karst, Director, Hyman, Phelps and McNamara

If there’s something strange in your neighborhood; Who you gonna call? If there’s something weird, and it don’t look good; Who you gonna call? Unfortunately, FDA doesn’t have a Ghostbusters-type unit to call when there’s something strange or weird compliance-wise going on in your neighborhood that’s holding up final ANDA (or 505(b)(2) NDA) approval. (Oh, and you’re welcome for the earworm!) https://www.youtube.com/watch?v=rarRiqWH8v4

The GDUFA program has spurred an increase in the number of inspections for generic drug applicants and the establishments identified in those applications. With the increasing number of inspections, comes an increase in Establishment Evaluation Report (EIRs) that need to be written by FDA investigators, cleared by their supervisors, and then reviewed and cleared by the Center for Drug Evaluation and Research’s Office of Compliance. As was noted in a blog posted on the Lachman Consultants blog website (here), there appears to be a growing problem in getting timely resolution of compliance-related issues from the time the EIR leaves the field and up until FDA’s computer systems are updated to provide an acceptable finding.

In speaking to Kurt Karst of Hyman, Phelps & McNamara, his firm is also hearing a rising chorus of complaints about being stuck in what one applicant called the “Compliance Black Hole.” Another company referred to it as the “Endless Summer,” because that company has been trying to figure out when their compliance status will change in the FDA computers after having received no 483 observations on reinspection since March of this year.

Firms note that calls to the Regulatory Project Managers (RMPs) or Regulatory Business Project Managers yield the same response: “There is nothing we can do until the computer system is updated.” Many of these responses come after the issuance of a Complete Response Letter (CRL) stating that the only outstanding issue is resolution of the status of a facility’s compliance. So the firm is stuck in a waiting mode. Simply calling the Office of Compliance has yielded basically the same result. Clients are telling us that they do not receive return calls (or that they are simply told to sit tight and wait).

Trying to find a sympathetic ear at FDA is also difficult, particularly when a firm is ready to launch but for the final compliance clearance and approval action. In addition, we have heard from firms with potential date-certain launch dates (either day-181 dates or settlement dates) that they were informed by FDA officials that the compliance status of their application remains unresolved in the Agency’s computer system, notwithstanding the fact that the sponsor was informed by an FDA field investigator that there were either no 483 observations following inspection, that a completed EIR was forwarded to CDER finding satisfactory the firm’s responses to inspectional observations, or that an approval recommendation had gone forward. While we recognize we don’t always have the full picture when we hear these types of observations from sponsors, the frequency of occurrence of such complaints is increasing in dramatic fashion. Last week alone, Lachman Consultants received four inquiries about such issues. Each company expressed exasperation in not being able to get an answer other than “You just have to wait!,” and asked the same question: “Who can I call at FDA to discuss the issues?”

There’s no easy answer to that question. Depending on your level of exasperation, you might start at the top of the FDA Office of Compliance food chain, or somewhere below that . . . perhaps at the Office of Manufacturing Quality, or at one of the various Divisions of Drug Quality. (Here’s the CDER List of Key Officials in case you need it.) It’s unclear how many applications are being delayed because they are stuck in the “Compliance Black Hole” . . . probably dozens, and perhaps several score. But, as noted above, a simple call to FDA is unlikely to do the trick in removing a compliance status block on approval. Instead, a sponsor might consider escalating the issue by requesting a meeting with the relevant FDA officials. After all, he who screams the loudest might be more likely to get FDA”s attention.