Real Time Communication Inception and Evolution

Transcription

1 Real Time Communication Inception and Evolution 2016 GPhA CMC Workshop May 17, 2016, Bethesda, MD Glen Jon Smith, M.S., M.A.S. Deputy Director (Acting) Office of Lifecycle Drug Products, OPQ, CDER 1

2 What is Real-Time Communication? Real-Time Communication means communication with an ANDA applicant and an exchange of information prior to the issuance of a formal FDA action. Action: Tentative Approval (TA), Approval (AP), or Complete Response (CR) Real-Time Communication does not replace formal communication methods such as CRs, but rather enhances the review process in an effort to increase transparency and decrease the number of review cycles. Note: when a formal FDA action issued, a review cycle is complete. 2

3 Why Real Time Communication? GDUFA establishes goal dates by which the Agency should take a formal action. Multiple review cycles are inefficient, resulting in a growing volume of pending applications, increasing the risk of missing future goal dates for multiple applications. Resources must be allocated to compile and issue a CR letter. Any easily addressed issues must wait for the Complete Response from the applicant. Multiple review cycles also make the resource allocation difficult due to the unpredictability of the response receipt. 3

4 What is a Review Cycle A review cycle is defined as a complete review of an application followed by a formal action such as AP letter, a TA letter or CR letter. If a CR letter is issued, work on the application is stopped until the applicant s response is received. An Information Request (IR) is not a formal action and review and GDUFA clock is not stopped. The issuance of an IR letter and the response to an IR letter does not constitute a Review Cycle. 4

5 Advantages of Real-Time Communication Transparent process and opens communication. Less time lost in multiple review cycles. Applicant and FDA work together to achieve better understanding and increased mutual trust. Applicant can better forecast production plans. The Office of Pharmaceutical Quality (OPQ) can allocate resources more efficiently since a response time is established. Encourages higher quality submissions. 5

6 Where We Were 6

7 How RTC Worked - Original The CMC/Quality reviewer would complete the review and compile a list of items for the IR. If the response to any of the items required substantial resources for review (e.g. Major Deficiency), an IR would not be issued and the items would be included in a CR letter. OPQ would contact the applicant and send the IR. An expected response date based on the number and nature of items in the IR would be proposed. OPQ would review the response and issue any additional IR as necessary until all issues were addressed or goal dates did not permit additional IRs. 7

8 ANDA Review Real-Time Communication Do deficiencies require substantial expenditure of FDA resources? NO YES Issue Major CR Encourages firms to get it right the first time; Long term impact of raising submission quality Will real-time communication result in missing a Goal Date? YES Issue Minor CR NO Issue requests to the applicant 8

9 Evolution OPQ quickly learned that partial responses were impractical. They were too labor intensive and extremely difficult to track. The decision to not accept partial responses was communicated to the industry (including the 2015 GPhA CMC Workshop). Industry frequently asked for more than 30 days in order to fully address the items in the IR. Sometimes this request would be made on Day 29! A clearer definition of what constitutes substantial resources for review was needed. At the 2015 GPhA CMC Workshop, OPQ asked for your input (Thanks to Lisa Tan and the GPhA) on how to improve RTC. Your comments were appreciated. 9

10 Evolution OPQ will not accept partial responses (Setting a date to submit the information is not a complete response). During the RTC process, OPQ will communicate a response date. The applicant has 7 calendar days to request an extension (The day the IR received is t=0). If reasonable, the response time can be extended, but not to exceed 60 calendar days total. Definitions of Major Deficiencies can be found in the Guidance for Industry: ANDA Submissions Amendments and Easily Correctable Deficiencies under GDUFA. 10

11 Where Are We Today Since the introduction of RTC, we have been issuing hundreds of IRs per month. Feedback suggests that the RTC process has been well received by Industry. To determine the impact now that we have experience with the RTC process, we started to track the number of CMC cycles needed for AP/TA in January, The results are encouraging! 11

12 Where We are Today 12

13 Future Improvements OPQ wants to work with Industry to increase submission quality. What is clear to you may not be clear to others. Quantity does not constitute quality. OPQ will work to increase the clarity of IR questions What we ask and why we ask may not always be clear to you. We are striving to add better context. OPQ and Industry should work towards conducting fewer, more focused IRs. OPQ wants to increase number of Tcons for the lingering one or two items at the end of the process. Everyone s goal - Increase the number of first cycle APs/TAs. 13

14 Real Time Communication Inception and Evolution Thank You 14