首页 > 资讯 > GDUFA下获取成功必需的产业文化变革

出自识林

2013-11-16 Lachman CONSULTANTS

确保仿制药公司变革文化，以适应仿制药使用者付费法案(GDUFA)间接施加的新的更严格的标准和要求，可能为时已晚。但是，亡羊补牢，未为晚也！

如果在GDUFA实施的第一年，仿制药公司尚未理解必须适当收缩研发计划以应用质量源于设计原则，如果还未理解所提交申请中的药品、生产工艺、生产场地、API供应商、检测实验室等不能准确反映商业化产品如何生产和在哪里生产，那么他们将会发现自己的处境岌岌可危。

收紧拒收要求和GDUFA的“受罚区”规定会带来直接和长期的经济处罚。记住，如果您的申请接收到一封拒收函，您可能损失25%的申请费，甚至更糟的是，如果该申请代表着首次提交申请的机会，您可能错失靠这个机会赚钱的良机。按照审评时钟研发产品，将要求公司提交对申请的增补。每次增补会带来与您的GDUFA目标日期和申请在审评队列的最终位置有关的重大时间处罚。如果在ANDA接收后有太多增补或一次重大增补，您的申请将不再受GDUFA目标日期保护。因此，初次提交的质量对于成功至关重要。

企业如何确保改善提交质量并最大程度减少将面临处罚的风险？在研发初期启动。厘清您的营销和商家真正的卖点。寻找合适的API供应商，并保证他们持有FDA可接受参照药品名单上的药物主文件（DMF），或确定他们在您的申请拟提交日期的至少6个月之前提交新的DMF。不要急于提交您的申请，如果有新化学实体-1(NCE-1)日期或首次提交申请机会，如果申请不会受到未能满足这一明确的最后期限影响，更早地启动整个过程。

还可以付费请另外的慧眼审查您的提交申请，例如，第三方咨询机构或甚至是来自其它内部部门的审评者。不要受骗上当认为这将足以避免处罚，因为不论OGD的ANDA检查清单有多好，由于一些审评员可能比起另外一些更加注重细节，拒收审评总会有一些主观性。记住，10个或更多的轻微缺陷将导致给您的一封RTR函。不要被任一预审将导致避免拒收函所欺骗，或期待一个保证；任何人能做到最好的的就是降低收到拒收函的风险。在提交之前更正申请中的问题也可以降低，但是不能保证申请审评时将不会有缺陷。但将缺陷数控制在在最低限度肯定会减少回复OGD第一封完全回应函的负担，甚至可能给您一个机会，我强调的机会—首轮批准。

底线是，开始着手提高提交申请的质量，并注意质量问题的企业，可免于被逐入受罚区，并最终成为批准比赛中的胜者。

Culture Change in Industry Necessary for Success Under GDUFA
Written by Bob Pollock • November 15, 2013

It may be almost too late to assure that the culture of generic companies can change to meet the new more demanding standards and requirements that the Generic Drug User Fee Act (GDUFA) indirectly imposes. But if now is almost too late, tomorrow is for sure!

If, over the first year of GDUFA implementation, generic firms have not figured out that they must push their development programs back a bit to permit applying the principles of Quality by Design (QbD) and if they have not figured out that the drug product, manufacturing process, site(s), API suppliers, testing labs, etc., that are the subject of the application they submit do not accurately represent how and where they want their commercial product to be made, then they will already find themselves behind the proverbial 8 ball.

The tightening of the Refuse-to-Receive (RTR) requirements (see previous post here) as well as the GDUFA “penalty box” provisions (see previous post here) can have both an immediate and long term financial penalty. Remember, if your application receives an RTR letter, you will lose 25% of your filing fee and even worse, if that application represents a first–to-file opportunity, you may lose cashing in on that chance. Developing your product on the review clock will require firms to submit amendments to their applications. Each amendment can have significant time penalties associated with your GDUFA goal dates and where your application ultimately is positioned in the review queue. Too many amendments or one major amendment after ANDA receipt and your application will no longer be subject to a GDUFA goal date! So the quality of your initial submission will be paramount to success.

What can firms do to assure improved submission quality and minimize the risk that you will be facing a penalty? Start early in development. Map out what your marketing and commercial folks really want to sell. Look for the proper API suppliers and assure they have Drug Master Files (DMFs) on the FDA’s Acceptable for Reference List or be certain they submit their new DMFs submitted at least 6 months prior to the proposed submission date of your application. Don’t rush your application to submission, and if there is a NCE-1 date or a first-to-file opportunity, start the entire process earlier than you would if the application would not be impacted by failing to meet a such a definitive deadline.

It also pays to have another set of eyes review your submission, for example, a third party consultant or even a reviewer from another internal department. Don’t get fooled into thinking that even that will be enough avoid a penalty because the RTR review, no matter how good the OGD’s ANDA checklist might be, will be somewhat subjective, given the fact that some reviewers may be more detail-oriented than others. Remember 10 or more minor deficiencies earn you a RTR letter. Don’t be tricked by or expect a guarantee that any pre-review will result in avoiding a RTR letter; the best anyone can do is reduce the risk of receiving one. Correcting problems in the application prior to submission will also reduce, but not guarantee that there will not be deficiencies upon review of the application. But keeping the number of deficiencies to a minimum will certainly lessen the burden of responding to the OGD’s first Complete Response Letter or may even give you a chance, and I emphasize chance, for a first-cycle approval.

The bottom line is the firms that get on board with improving the quality of their submissions and pay attention to the quality issues may avoid a seat in the penalty box, and will ultimately be the victors in the race for approval. For any additional regulatory questions, or to find out how Lachman Consultants can assist in reducing your risk for a seat in the penalty box, please contact Joan Janulis (j.janulis@lachmanconsultants.com)

原文请见 Culture Change in Industry Necessary for Success Under GDUFA