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 contd

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 FDAs regulations
7

Regulatory Background contd

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

Detailed Design Review

User or Device
Requirements Concept

Pre-Human Safety Testing

High Level Design Review

Human Testing / Clinical

User Requirements
Design Input Document

Performance Specifications

Prototype Design with

Preliminary Specifications

Final Product Testing

Validation

Bench Testing

Non Clinical
Evaluation

Iterative

Design Modifications

Manufacturing / Production
Process / Records

Design / Technology Transfer

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 contd

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 contd

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 contd

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.