Regulatory Challenges During Device Development

July 25th, 2012

Center for Clinical Trials & Product Development

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Regulatory Challenges During Device Development

Regulatory Background Development Process Overview Critical Decision Points Clinical Data Considerations Guiding Principles Recent FDA Guidance Conclusion

Regulatory Background Development strategy and pathway significantly influenced by device classification: – Class I & II – Predicate and substantial equivalence (flexibility /

challenge) – Class III PMA device has rigorous, significant FDA oversight,

demands robust clinical evidence of safety and effectiveness, generally lengthy process, and costly!

In-Vitro Diagnostics (IVDs) present additional unique challenges

Evaluation based on typical production batches,

FDA also issues specific guidance documents for most devices

Regulatory Background – cont’d Design Controls – 21 CFR Part 820.30

Regulation offers a framework for FDA expectations during development: – Regulations not meant to be prescriptive, but require

manufacturers to comply with the “spirit and intent”. – Adapt to fit device development needs. – Formal, documented, somewhat structured approach that

provides traceability and links from inception (design inputs) to finished distributed device.

– Records should result in a Design History File

Initial challenge for the device developer – to what extent do I comply, and how – Process must seamlessly integrate with FDA’s regulations

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Regulatory Background – cont’d Intended Use Statement

Intended use is critical to the definition and classification of a device (development pathway): A novel intended use can force a Class III designation Distinction between intended use and indication for use Selection of initial intended use based on marketing and business reasons (speed to market) – Follow on indications / intended uses

Basic Development Model

Ideation/ Discovery

Bench Testing • Non Clinical

Evaluation • Iterative

• Design Modifications

Design / Technology Transfer

User or Device Requirements Concept

User Requirements Design Input Document

Prototype Design with Preliminary Specifications

Pre-Human Safety Testing

Human Testing / Clinical

Performance Specifications

Final Product Testing Validation

Manufacturing / Production Process / Records

High Level Design Review

Detailed Design Review

Critical Decision Points

Ideation Phase – It is never too early – Regulatory classification dictates development pathway

Predictability of regulatory pathway – Take advantage of competitive intelligence – Monitor regulatory trends, legislative climate – When and how should I approach FDA? – Take a critical, unbiased approach

Look for pitfalls, and how “FDA” as audience might react

Review predicates, both favorable and unfavorable to strategy, evaluate pros and cons, take a position and provide unbiased support. – Tendency for most evaluators is to seek devices supportive of

desired strategy Obtain expert regulatory input

Critical Decision Points – cont’d

Development Phase What data is required to support the submission – 510(k)? – Preclinical / Bench test data? – Human clinical data – how robust a trial? Review predicates in FDA database – What if there are no predicates? – How predictable is the de Novo Pathway? Review MAUDE database for adverse events

Critical Decision Points – cont’d

Is an IDE appropriate? Significant versus non-significant risk device questions – How to make determination – IRB issues – How many studies? – Is a small pilot appropriate before a confirmatory

study? When to approach the Agency

Clinical Data Considerations

How is the device going to be used, and by whom? Unlike systemic drugs, devices may fail in a clinical setting due to user related issues. How large a clinical trial, RCT, or single arm, historical controls, etc What type of trial design is appropriate? – Open, Blinded (single, or double) To what extent do GCPs apply? Are foreign trials / data acceptable, and if so under what circumstances?

Guiding Principles Regulatory framework and strategy as early as possible in the development process Intended Use Statement is critical to strategy, development plan Field intelligence provides useful tips (competitive devices, FDA databases, trends). FDA input earlier on provides useful insights, but the manufacturer still has the burden to support position. Clinical trials for the most part should be robust, and well controlled. Develop key milestone “check-ins” for potential regulatory risks

Recent FDA Guidance - The Pre-Submission Program

Replaces Pre-IDE program and broadens scope to include NSR devices. Provides mechanism for obtaining FDA input on development programs in addition to the traditional IDE process. Specific language around clinical trial guidance when trials are not mandated by the regulation. Overall goal is to provide a level of predictability to the regulatory process.

Conclusion

Regulatory challenges should be identified and addressed as early in the concept phase as possible, and throughout the development process: – Intended Use Statement – Regulatory Classification – Clinical Data

Incorporate independent expert opinion Fall back / contingency plan essential.

Questions, Comments??

Thank you

Critical Decision Points – cont’d When to approach Agency

Necessity of a meeting must be carefully considered, and possibly done for early collaboration, significant development strategic issues – Currently no real mechanism for early feedback (proposed guidance)

Play out all the possible outcomes and fallback positions Is it to obtain agreement, guidance, or current FDA thinking on a subject matter? Remember, there is no such a thing as an “off the record” meeting with FDA – There is no current mechanism for providing “binding” FDA opinion prior to a

formal submission – New guidance attempts to mimic drug PDUFA Meeting and pre-IND Meeting

paradigm – Critical to craft a position, provide support (pros and cons – unbiased) and present

to FDA, no open ended questions: – Format similar to drug development positioning and requesting concurrence

Reputable regulatory consult a “must”.