The Target Product Profile (a Regulatory Perspective)

Transcription

1 The Target Product Profile (a Regulatory Perspective) ISCT 18 th Annual Meeting June 8, 2012 Seattle Wilson W. Bryan Division of Clinical Evaluation and Pharmacology / Toxicology Office of Cellular, Tissue, and Gene Therapies Center for Biologics Evaluation and Research

2 Target Product Profile (A Regulatory Perspective) 1) Target Product Profile 2) Steps in Drug Development 3) Inefficient (Slow) Drug Development 4) Efficient Drug Development 2

3 Target Product Profile (TPP) Guidance for Industry and Review Staff: Target Product Profile A Strategic Development Process Tool (2007) A TPP is a format for a summary of a drug development program described in terms of labeling concepts. The TPP embodies the notion of beginning with the goal in mind. 3

4 Drug Development Objectives 1) Evidence of Effectiveness 2) Evidence of Safety 3) Product Approval (Label) 4) Efficient Development 4

5 Drug Development Process Knowledge of the disease process Drug discovery Nonclinical (animal) study objectives: Toxicity, biodistribution, carcinogenicity, proof-of-principle Guide design (including dosing, population, and monitoring) of subsequent Phase 1 studies Phase 1 objectives: Safety, tolerability, maximum tolerated dose (MTD), pharmacokinetics (and activity / efficacy, if feasible) Guide dosing and monitoring of subsequent Phase 2 studies Phase 2 objectives: Determine dose, route, regimen, population, endpoints, and estimated magnitude of effect Guide design of subsequent confirmatory (Phase 3) studies Phase 3 objectives: Evidence of effectiveness and safety to support a marketing application (Biologics Licensing Application (BLA)) LABEL 5

6 Target Product Profile (TPP) The ideal version of what the sponsor would like to claim in labeling guides the design, conduct, and analysis of clinical trials to maximize the efficiency of the development program. (from TPP Guidance, 2007) 6

7 Drug Development Timeline IND Submitted BLA Submitted Drug Discovery Preclinical Phase 1 Phase 2 Phase 3 LABEL Clinical Trials IND = Investigational New Drug Application BLA = Biologics Licensing Application 7

8 Drug Development Timeline Drug Discovery Preclinical Phase 1 Phase 2 Phase 3 LABEL Clinical Trials SLOW DEVELOPMENT 8

9 Drug Development Timeline Solutions Drug Discovery Preclinical Phase 1 Phase 2 Phase 3 LABEL Clinical Trials SLOW DEVELOPMENT 9

10 Drug Development Timeline Drug Discovery Preclinical Phase 1 Phase 2 Phase 3 LABEL Clinical Trials The preclinical studies do not provide sufficient data to support the proposed Phase 1 study. 10

11 Slow Drug Development The preclinical studies do not provide sufficient data to support the proposed Phase 1 study. For example: Used the wrong animal model(s) or species. Design of animal studies does not mimic the proposed human study (e.g., route of administration, regimen). Preclinical toxicology studies of insufficient duration or did not escalate to a high enough dose. Insufficient proof-of-concept data to provide rationale for Phase 1 study. 11

12 Drug Development Timeline Solution: Pre-pre-IND telecon Solution: Pre-IND meeting Drug Discovery Preclinical Phase 1 Phase 2 Phase 3 LABEL Clinical Trials The preclinical studies do not provide sufficient data to support the proposed Phase 1 study. 12

13 Drug Development Timeline Drug Discovery Preclinical Phase 1 Phase 2 Phase 3 LABEL Clinical Trials The available data are insufficient to guide the design of the Phase 3 studies. 13

14 Slow Drug Development The available data are insufficient to guide the design of the Phase 3 studies. For example, The disease population is not well-characterized, so that there is insufficient information to select the study population, study duration, and endpoints. This is a common issue with rare diseases. There is insufficient data regarding the activity of the study agent to select the study population, study agent dose and regimen, and study endpoints. 14

15 Drug Development Timeline Solution: Natural History study Solution: Phase 2 studies Drug Discovery Preclinical Phase 1 Phase 2 Phase 3 LABEL Clinical Trials Draft Design Phase 1, 2, and 3 studies The available data are insufficient to guide the design of the Phase 3 studies. 15

16 Drug Development Timeline Drug Discovery Preclinical Phase 1 Phase 2 Phase 3 LABEL Clinical Trials The available data are insufficient to support the use of a device or analytical test that is critical to the conduct or interpretation of the Phase 3 study. 16

17 Slow Drug Development The available data are insufficient to support the use of an analytical test or device that is critical to the conduct or interpretation of the Phase 3 study. For example: Use of an investigational device to administer the product. Investigational use of a marketed device to administer the product. Use of an investigational analytical test to select the study population. Use of an investigational analytical test as an endpoint to demonstrate efficacy of a product. 17

18 Drug Development Timeline Meetings with CBER/CDRH Meetings with CBER/CDRH Meetings with CBER/CDRH Drug Discovery Preclinical Phase 1 Phase 2 Phase 3 LABEL Clinical Trials The available data are insufficient to support the use of a device or analytical test that is critical to the conduct or interpretation of the Phase 3 study. 18

19 Drug Development Timeline Drug Discovery Preclinical Phase 1 Phase 2 Phase 3 LABEL Clinical Trials The Phase 3 study results do not provide sufficient evidence to support a BLA. 19

20 Drug Development Timeline Special Protocol Assessment Drug Discovery Preclinical Phase 1 Phase 2 Phase 3 LABEL Clinical Trials End of Phase 2 meeting with CBER The Phase 3 study results do not provide sufficient evidence to support a BLA. 20

21 Special Protocol Assessment (SPA) Objective: To reach agreement on the design and size of a clinical trial. PDUFA: having agreed to the design, execution, and analyses proposed in protocols reviewed under this process, the Agency will not later alter its perspective on the issues of design, execution, or analyses unless public health concerns unrecognized at the time of protocol assessment under this process are evident. Designed to evaluate a specific protocol, not the overall development program. 21

22 Target Product Profile (TPP) An efficient dialogue between a sponsor and the FDA during the drug development process can minimize the risk of late-stage drug development failures, and possibly decrease the total time involved with drug development. (from TPP Guidance, 2007) 22

23 Efficient Drug Development Begin with a Target Product Profile (i.e., begin with the goal in mind) Early draft design of Phase 1, 2, and 3 studies Early and regular Meetings with CBER / OCTGT Natural history study(ies) Phase 2 studies If a device or analytical test is critical to the clinical study: Early and regular meetings include CDRH Special Protocol Assessment PLAN AHEAD! 23

24 Acknowledgements Division of Clinical Evaluation and Pharmacology / Toxicology Pharmacology / Toxicology Branch General Medicine Branch Oncology Branch Mercedes Serabian **, MS Ilan Irony **, MD Ke Liu **, MD, PhD Pakwai Au, PhD Changting Haudenschild * Peter Bross *, MD Alex Bailey, PhD Bruce Schneider *, MD Bindu George *, MD Theresa Chen, PhD Mark Borigini, MD Chaohong Fan, MD, PhD Shamsul Hoque, PhD John Hyde, PhD, MD Sadhana Kaul, MD Ying Huang, PhD Agnes Lim, MD Robert Le, PhD, MD Wei Liang, PhD Steve Winitsky, MD Lydia Martynec, MD Jinhua Lu, PhD Rachel Witten, MD David Maybee, MD Allen Wensky, PhD Lei Xu, PhD, MD Maura O Leary, MD Yongjie Zhou, PhD, MD Michael Yao, MD Kevin Shannon, MD Yao-Yao Zhu, MD, PhD ** Branch Chief; * Team Leader

25 OCTGT Contact Information Regulatory Questions: Contact the Regulatory Management Staff in OCTGT at or or by calling (301) OCTGT Learn Webinar Series: ucm htm

26 Public Access to CBER CBER website: Phone: or Consumer Affairs Branch (CAB) Phone: Manufacturers Assistance and Technical Training Branch (MATTB) Phone: Follow us on Twitter

27 Efficient Drug Development Natural History Study Meetings include CDRH Phase 2 studies Special Protocol Assessment Drug Discovery Preclinical Phase 1 Phase 2 Phase 3 LABEL Pre-pre- IND Telecon Pre-IND Meeting Clinical Trials End of Phase 2 Mtg Pre BLA Mtg 27

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