# Presentation: 532610

## Staff Update: The Least Burdensome			    Provisions of FDAMA

- Presented
- by
- Philip J. Phillips
- Deputy Director
- Office of Device Evaluation
- April 4, 2000

## References to the “Least Burdensome” 					Requirements

- 	Section 205 of FDAMA amended the FD&C Act to incorporate two references to the “least burdensome” decision threshold
- Section 513(a)(3)(D)(ii)
- Section 513(i)(1)(D)

## Section 513(a)(3)(D)(ii)

- 	“Any clinical data, including one or more well-controlled investigations, ... shall be specified as the result of a determination by the Secretary that such data are necessary to establish device effectiveness.  _The Secretary shall consider, in conjunction with the applicant, the __*least burdensome*__ appropriate means of evaluating device effectiveness that would have a reasonable likelihood of resulting in approval._”

## Section 513(i)(1)(D)

- 	“Whenever the Secretary requests information to demonstrate that devices ... are substantially equivalent, the Secretary shall only request information that is necessary to making substantial equivalence determinations.  _In making such requests, the Secretary shall consider the __*least burdensome*__ means of demonstrating substantial equivalence and request information accordingly_.”

## FDAMA did not change the standard

- 	For premarket approval or clearance:
- Reasonable assurance of safety and _effectiveness_ (PMA)
- Substantial equivalence (510(k))

## Past Activities

- Public meeting - January 4, 1999
- Least Burdensome Industry Task Force Proposal - Spring 1999
- Draft FDA guidance document - Fall 1999
- LBITF requested meeting with FDA - January 2000

## The Least Burdensome Provisions of the FDA Modernization Act of 1997Concepts and Principles

- Prepared by representatives of the LBITF and FDA
- Draft - Not for Implementation
- Released on March 20, 2000
- Comment period ends May 20, 2000

## What is the Least Burdensome Concept?

- The Least Burdensome Concept is defined as a successful means of addressing a premarket issue that involves the smallest investment of time, effort, and resources on the part of the submitter and FDA.
- The Concept applies to all devices regulated by FDA (including *in vitro* diagnostics (IVDs))

## What is the Least Burdensome Concept?

- The Concept should be integrated into all premarket as well as postmarket activities, as appropriate
- Activities such as:
- Simple inquiries regarding device development
- Pre-submission activities (e.g., early collaboration meetings and the Pre-IDE process)
- Premarket submissions
- Panel review and recommendations
- Post-approval studies
- Guidance development and application
- Regulation development

## What Basic Principles Underlie the Least Burdensome Concept?

- 1)  The spirit and the letter of the law
- 		  should be the basis for all regulatory
-       decisions;
- 2)  Information unrelated to the regulatory
-      decision should not be part of the
-      decision-making process;

## What Basic Principles Underlie the Least Burdensome Concept?

- 3)  Alternative approaches to all regulatory
-       issues should be considered to optimize
-       the time, effort, and cost of reaching
-       proper resolution of the issue; and
- 4)  All reasonable mechanisms to lessen review
-       times and render regulatory decisions within
-       statutory timeframes should be used.

## How Do The Principles Apply to PMAs (Originals and Supplements)?

- Focus on the statutory criteria for approval of the PMA, i.e., reasonable assurance of safety and effectiveness
- Information unrelated to the decision should not be submitted to nor requested by the Agency.
- Consider whether pre-clinical data (well-designed bench and/or animal testing) could meet the statutory threshold for approval.

## How Do The Principles Apply to PMAs (Originals and Supplements)?

- If clinical data are needed, alternatives to randomized, controlled clinical trials should always be considered.
- If clinical data are needed, the Agency should consider the use of surrogate endpoints.

## How Do The Principles Apply to PMAs (Originals and Supplements)?

- The role of postmarketing information should be considered in deciding what type of premarket data or information is needed for approval of the PMA.
- Reviewers should evaluate a manufacturer’s claims in a PMA only when the claims affect the safe and effective use of the device.

## How Do The Principles Apply to 510(k)s?

- Manufacturers and reviewers should focus their attention on those issues that affect the substantial equivalence (SE) determination.
- Information unrelated to the SE decision should not be submitted to nor requested by the Agency.

## How Do The Principles Apply to 510(k)s?

- In making SE determinations, reviewers should follow longstanding policy:
- SE is based on comparative device descriptions
- Performance testing will not normally be required
- Reviewers should rely on a manufacturer’s statement that a device will meet a recognized standard.

## How Do The Principles Apply to 510(k)s?

- Postmarket controls (e.g., compliance with the Quality Systems regulation) should be considered as a mechanism to reduce the premarket requirements.
- Reviewers should not request information regarding changes observed in a new 510(k) that were previously incorporated without the need for 510(k) clearance.

## How Do The Principles Apply to 510(k)s?

- Manufacturing information should not be part of a 510(k) submission unless the information directly relates to the equivalency determination.
- Reviewers should limit their analysis of claims in a 510(k) to those that present a major impact on the intended use of the device.

## What Are Some General Applications of the Least Burdensome Principles?

- FDA and industry should use all regulatory tools available through FDAMA and reengineering, such as the *de novo* risk-based classification process and *The New 510(k) Paradigm*.
- Manufacturers should incorporate by reference other premarket submissions rather than re-submitting duplicative information.

## What Are Some General Applications of the Least Burdensome Principles?

- Manufacturers should make effective use of FDA-recognized standards and submit declarations of conformity to these standards, as appropriate.
- Reviewers should avoid attempting to ensure compliance with FDA statutes or regulations unrelated to the decision.

## What Are Some General Applications of the Least Burdensome Principles?

- When requesting additional information to resolve a regulatory issue, reviewers should:
- Identify the specific issue that the request is attempting to address;
- Acknowledge information submitted and why the information is deficient;
- Establish the relevance of the request to the determination (SE or S&E); and
- Remain open-minded to alternatives to address the issue or question.

## What Are Some General Applications of the Least Burdensome Principles?

- In responding to the reviewer's request for additional information, industry should state the Agency issue and provide:
- Information requested;
- Alternative information that addresses the issue; or
- An explanation why the issue is not relevant to SE or S&E.

## What Are Some General Applications of the Least Burdensome Principles?

- Reviewers should attempt to resolve minor questions/issues by phone, fax, or e-mail.
- Reviewers should limit deficiency letters to the more complicated issues unless minor deficiencies have not been adequately addressed.
- Industry should promptly respond to questions regarding minor deficiencies so as to avoid requests for this information in deficiency letters.

##            The Bottom Line

- The spirit and letter of the law should be the basis of all regulatory decisions.
- Factor least burdensome concepts into all premarket activities (e.g., pre-submission and review activities, guidance document use and development, regulation development).
- Remain open-minded to alternative ways for satisfying all regulatory requirements.

## Next Steps

- Continue collaboration with industry
- Develop a LB website
- Further illustrate LB concept by examples
- Add LB language to boilerplate letters and guidance documents
- Develop a LB thought process for industry/FDA
- Identify a working level appeals process
- LB Teleconference - Summer 2000