Quality Considerations for Breakthrough Therapies-FDA Perspective

Transcription

1 Quality Considerations for Breakthrough Therapies-FDA Perspective DIA June 17, 2014 Ramesh K. Sood, Ph.D. Acting Division Director and Angelica Dorantes, Ph.D. xxx ONDQA/OPS/CDER/FDA 1

2 Background Outline FDASIA Breakthrough therapies (BT) Expedited programs for serious conditions Draft guidance Quality expectations and risk considerations CMC challenges for expedited submissions Best practices and submission strategies 2

3 FDASIA (2012) Section 901 Fast Track Drug Products Facilitate development and expedite the review of drugs for the treatment of a serious or life-threatening disease or condition that demonstrates the potential to address unmet medical need Section 902 Breakthrough Therapy Drugs Expedite the development and review of a drug for serious or life-threatening disease or condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies Provide timely advice and interactive communication with the sponsor regarding the development of the drug Provide a collaborative cross disciplinary review utilizing senior managers and experienced review staff, as appropriate Section 905 Risk Benefit Framework Implement a structured risk-benefit assessment framework in the new drug approval process and regulatory decision making 3

4 Guidance for Industry (Draft) Expedited Programs for Serious Conditions Drugs and Biologics (2012) Communication is critical Typically involve a rapid manufacturing development program to accommodate the accelerated pace of the clinical program Importance of early communication to ensure that the manufacturing development programs and timing of submissions meet the Agency s expectations for licensure or marketing approval Proposal of a commercial manufacturing program that will ensure availability of quality product at the time of approval 4

5 BT Submissions As of 7-May Applications submitted 44 granted 73 denied 17 withdrawn 5 NDAs approved (includes efficacy supplement) 5

6 Expectations for Quality Patients and caregivers assume that their drugs: Are safe and efficacious Deliver the same performance as described in the label Perform consistently over their shelf life Are made in a manner that ensures quality Will be available when needed 6

7 Stakeholder s Expectations Quality expectations not based on the approval process (accelerated vs regular) Willing to accept inherent potential risk/harm as long as benefit outweighs the inherent risk Package insert has no section to include quality related risk Does not expect patient harm related to drug quality Shared responsibility to meet these expectations 7

8 Product Risk Considerations Keep patient in mind while considering quality risk Delineate identified risks and potential unidentified risks to quality at IND stage and in NDA submission Proactive and transparent discussions are more effective than retroactive or reactive steps Save time during review Can be initiated by Applicant or Agency Proactively incorporate elements of risk mitigation Propose and discuss risk mitigation strategies as soon as possible with FDA 8 8

9 Challenges for Expedited Reviews Accelerated manufacturing development likely to have less information than typically available Poses challenge for both applicant and regulatory bodies Typically warrants a risk-benefit assessment regarding risk of less CMC information vs. patient benefit May require innovative risk-mitigation strategies to ensure product safety and reduce quality related product risk to an acceptable level 9

10 Challenges for Expedited Approvals Alignment of clinical and product development timelines Limited available data is submitted Commercial site manufacturing batch data Stability data to support long shelf-life Data to bridge clinical and commercial materials Review timing constraints Frequent communication needs during review Commercial supply/availability considerations 10 10

11 The Risk/Benefit Balance Availability to patients Risks to Quality 11

12 How to Avoid Surprises COMMUNICATION is the key IND stage preind, EOP1, EOP2, prenda Additional meetings upon request CMC-specific meetings are an option Formal written feedback to information requests NDA stage Regular PDUFA V interactions (e.g. LCM) Teleconferences during review clock, as needed 12 12

13 Best Practices-at IND Stage Starts at IND/Pre-NDA stage Start thinking about accelerated product development strategies at IND stage Focus on clinical/commercial product comparability Discuss Strategy and data required with FDA Stability data package to be submitted Need for proposed stability amendments Available supporting stability data Commercial manufacturing sites information Will sites be ready for inspection Plans for treatment protocols/expanded access submissions 13 13

14 Best Practices-NDA Submission Discuss NDA submission strategy/timing as soon as possible Early assignment of CMC review team Allows proactive communication between review and inspection staff Early submission of manufacturing site information Submit with expanded access submission Submit with first piece of rolling review 14 14

15 Best Practices-NDA Submission Discuss any amendments to be submitted during review e.g stability amendments Unique application specific aspects New technologies Novel approaches Significant QbD aspects Proposed regulatory flexibility Opportunities for early submission of certain CMC information 15

16 Best Practices-During Review Stay engaged Quick turn around time for any information requests Information requests may be staggered Availability for quick teleconference Agency or applicant initiated Early discussion CMC labeling Discussion of residual product quality risk and appropriate mitigation strategies Possible PMC/PMRs Discussion on launch challenges 16 16

17 Conclusions FDASIA provides for expedited the development and review of a drug for serious or life-threatening disease Patient expectations for the quality and performance of drug is independent of approval process Accelerated approval process can result in misalignment of clinical and CMC development This poses challenges both for the applicants and the Agency Need to overcome these challenges for the greater benefit of patients 17

18 Conclusions We can overcome these challenges: Identification of Risk and Communication is the key Proactive communications regarding risk identification, evaluation and risk management is encouraged during development and review identification of opportunities for early submission and/or dialog, as well as effective communication of risk to quality Stay engaged throughout development and review process 18

19 Thank you! Questions, comments, concerns: 19