首页 > 资讯 > 中国企业对FDA仿制药提交意见函

出自识林

2013-11-04 CPIER

两个月前我们发表了关于FDA发布行业指南草案“ANDA申请提交 – 拒收标准”的资讯【RTR指南草案发布 识林资讯】。10月31日北京大学药物信息与工程研究中心针对该指南草案在www.regulations.gov上提交反馈意见。反馈意见如下：

【中文翻译】
“ANDA申请提交——拒绝接收标准”指南草案的第103到109行表述，如果FDA认为一个ANDA的轻微缺陷少于十个，FDA将以电话、电子邮件或传真的方式通知申请人。申请人有5个工作日的时限符合要求地修订ANDA，纠正指出的缺陷。指南草案提出，如果在5个工作日时限内未能提交所要求的信息，FDA将拒收此ANDA。

“5个工作日”时限的强制要求取代先前10个工作日的时限，这将对外国ANDA申请人产生严重的不利影响。对于外国申请人而言，FDA将缺陷通知申请人的美国代理人，代理人再通知给申请人。例如，美国与中国的时差导致工作时间的不重叠。所以每一个沟通周期都需要两个工作日进行。举例来讲，如果外国申请人的美国代理人在周一被通知正在处于接收审查的ANDA中的若干（但小于10个）轻微缺陷，代理人将发送通知给申请人，申请人在周二的工作日方能第一次看到。如果申请人要求澄清一个或多个缺陷点，他们将向美国的代理人寻求澄清。假设代理人能够立即提供澄清，那么申请人在周三的工作日才能第一次看到回复。如果任何缺陷提出需要，例如美国境内的供应商重新开具DMF引用函，那么同样需要两天的沟通周期。因此，由于诸如美国和中国的时间/日期差，在很多情况下，即便最勤奋的申请人也不能满足5个工作日的时限。这并不是未能尽快地纠正缺陷所造成的结果，而是因为相关方时间/日期上的差别所致的结果。注意指南草案第180到182行已经意识到全球时差对FDA和外国申请人的影响，将沟通描述为“具有挑战性”。

基于上述原因，我们诚挚地请求对十个以内的轻微缺陷回复时限定为10个工作日，而非指南草案中提出的5个工作日。可接受的方案是，希望外国ANDA申请人在10个工作日内对轻微缺陷做出回复。

【英文原文】
The draft Guidance for Industry on “ANDA Submissions – Refuse-to- Receive Standards” states at lines 103 to 109 that in the case of an ANDA with fewer than ten minor deficiencies, FDA will notify the applicant of these deficiencies by phone, e-mail, or fax. The applicant then has a time limit of five (5) business days to satisfactorily amend the ANDA to correct the deficiencies. The draft Guidance proposes that if the requested information is not submitted within the five business day time limit, FDA will refuse to receive the ANDA.

The imposition of a “five business day” time limit in place of the previous ten business day time limit will seriously adversely affect foreign ANDA sponsors. In the case of foreign sponsors, FDA notifies the sponsor’s US Agent of the deficiencies, who in turn then notifies the sponsor. Time differences between the US and, for example, China are such that there is no overlap in business hours. So each cycle of communication takes two business days to process. For example if the US Agent for a foreign sponsor is notified of several (but less than 10) minor deficiencies in an ANDA undergoing acceptance review on a Monday, the Agent then sends notification to the Sponsor which is first seen during business hours on Tuesday. If the sponsor requires clarification of one or more deficiency points, they ask for clarification from their US Agent. Assuming the Agent can immediately provide clarification, the response is first seen by the sponsor during business hours on Wednesday. If any of the deficiencies raised require, for example, reissue of a DMF Reference Letter from a US based supplier, the same two day communication cycle occurs. As a result of time/day differences between the US and, for example, China, even the most diligent sponsors will not be able to meet the five business day time limit in many instances. This is not a result of failure to act as quickly as possible to correct the deficiencies, but rather the result of the time/day differences between the parties involved. Note that the draft Guidance already recognizes the effect of global time differences on communication between FDA and foreign sponsors at lines 180 to 182 describing such communication as “challenging”.

For these reasons we respectfully request that a time limit for response to fewer than 10 minor deficiencies be ten business days, and not the proposed five business days. An acceptable alternative would be to allow foreign ANDA sponsors ten business days to respond to minor deficiencies.