Drug-Device Combination Product Development: INDs for Device Companies

Transcription

1 Drug-Device Combination Product Development: INDs for Device Companies David Armbruster Global Program Manager April 24, 2013

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3 Drug-Device Combination Product Development -or- The scenic route to an IND

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5 Introduction Problem: implant related infection Solution: local antibiotic delivery

6 Local antibiotic delivery

7 Local antibiotic delivery Antibiotic delivery is separate from implant

8 Drug-Device Combination Products at FDA Office of Combination Products (OCP) Reviews Request for Designation (RFD) Designates Primary Mode of Action (PMoA) Provide guidance for cgmp, regulatory Regulatory Pathway follows PMoA, Both CDRH and CDER will review

9 Drug-Device Combination Products at FDA Primary mode of action the most important therapeutic action the greatest contribution to the overall intended therapeutic effects - 21 CFR 3.2(m)

10 What we learned Leverage consultants Understand NDA submission and cgmp requirements early in the process Count the cost

11 Development history 2006: Product conceived as medical device 1 engineer and a lab technician 2008: Hired microbiologist, chemical process engineer, analytical chemist 2009: Designation from OCP: Primary Mode of Action (PMoA) = Drug

12 Synthes regulatory experience 510(k): over 490 PMA: 3 NDA: 0

13 Synthes regulatory experience There are things we don't know we don't know

14 Development Team Internal Team Analytical chemist Process Engineer Preclinical Study Coordinator Project Manager Marketing Manager Microbiologist Regulatory Quality Expertise Needed Toxicologist Pharmaceutical Scientist Regulatory Affairs Consultant GMP Manufacturing Engineer GMP Manufacturing Site Quality Systems Consultant Animal Testing Lab (GLP) Analytical Lab (GLP) Medical Director (MD) Clinical Affairs Reimbursement

15 Development Team Key Consultants Project Team BIO MKT RA/ CLIN PRE CLIN GROUP MGR PM ENG ANALYT. Consultants CLIN. MICRO Pharmaceutical Scientist PD/ PK PHARM TOX ANIMAL TESTING Quality QUALITY GMP MANUF GLP LAB Regulatory Affairs REG AFFAIRS MD CRO Development Manufacturing Clinical & Regulatory

16 Development Team Key Consultants Identify key consultants early in the process

17 What we learned Leverage consultants Understand NDA submission and cgmp requirements early in the process Count the cost

18 IND Requirements Terminology: Target Product Profile Compendial excipient CMC Section CTD module Primary pharmacodynamics PK/PD

19 IND Requirements Electronic Common Technical Document (ectd) - CDER s standard format - IND vs. NDA - Software requirements

20 IND Requirements Chemistry Manufacturing and Controls (CMC) - Details of manufacturing - Drug substance - Excipients - Raw materials - Analytical methods - Container closure

21 IND Requirements Preclinical Testing - Pharmacology - Toxicology - Microbiology

22 cgmp FDA rule on cgmp for combination products published January 2013 Outlines minimum requirements for combined quality system QSR and cgmp Specifies which parts of 21 CFR parts 210 and 211 must be added to 21 CFR part 820

23 cgmp if a manufacturer chooses to demonstrate compliance with the QS regulation, that manufacturer must also demonstrate compliance with the following provisions of the drug CGMPs Testing and approval or rejection of components, drug product containers, and closures Calculation of yield Tamper-evident packaging requirements for over the-counter (OTC) human drug products Expiration dating Testing and release for distribution Stability testing Special testing requirements Reserve samples.

24 cgmp Quality by Design - Risk based product and process characterization - Quality Target Product Profile - Criticality Analysis CQAs - Design Space - Control Strategy Device NPD Process Business Case Analysis Functional & Design Requirements Design Verification/ Validation Engineering Specifications Validation Master Plan

25 What we learned Leverage consultants Understand NDA submission requirements early in the process Count the cost

26 Count the Cost Clinical trials - NDA approval requires two Phase III studies - Combination product studies often are more costly - >> $10 Million

27 Count the Cost Contract manufacturing - Pharma contract manufacturers can be expensive - Find site with device experience (difficult) - Cost of cgmp consultants

28 Count the Cost FDA fees (2013) NDA: - Application fee: $1,958,800 - Establishment fees: $526,500 - product fees: $98,380 - PMA: $248, (k): $4,960

29 Count the Cost Understand the Market Potential Do market research early get outside input The more innovative the product, the more difficult this is Maximize the Market Potential Broadest indication possible = largest market Keep costs low to maximize profit Consider the benefit to other products

30 Count the Cost Get management buy-in from the start on the full cost of the project $ investment and manpower A strong business case is essential to overcome the inevitable resistance

31 Net Present Value (NPV) Risk adjusted NPV uses lower risk values at later stages Combination products are less risky than new chemical entities Old drugs, new delivery route; known PK, toxicology May be difficult to estimate sales price Other methods Comparables, real options analysis No method is perfect De-risk the project early Keep it simple use proven technologies, old drugs Preclinical animal models Phase II studies

32 Summary Leverage consultants Understand NDA and cgmp requirements early in the process Count the cost Enjoy the ride