# Presentation: 735839

## The Least Burdensome Provisions of the FDA Modernization Act of 1997

**Presented by:**
**Linda Kahan**
**Joanne R. Less**
**Philip J. Phillips**
**Heather Rosecrans**

**The CDRH Staff College**

## AGENDA

**I.****	****	****References to Least **
**       ****Burdensome Requirements**
**II.   FDA Implementation**
**III.****	****Least Burdensome and the        ****	****   510(k) Program**
**IV.****	****Least Burdensome and the  ****	****	****   PMA Program**
**V.****	****Key Points**

## I. References to “Least Burdensome” Requirements

-    Section 205 of FDAMA amended the FD&C Act to incorporate 2 references to “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, specified in writing by the Secretary for demonstrating reasonable assurance of device effectiveness 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 with differing technological characteristics 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.”**_

## Standard for Premarket Clearance and Approval Has Not Changed

## II.  FDA Implementation

- Open public meeting
- – January 4, 1999 meeting in Rockville, MD
- Dr. Henney’s reference to “Most Reasonable”
- Memorandum to ODE Staff from Susan Alpert dated September 2, 1999

## FDA Implementation (con’t)

- Draft agency guidance document entitled, _**“Evidence Models for the Least Burdensome Means to Market”**_
- Federal Register Vol. 64, No. 169, Sept.1, 1999
- http://www.fda.gov/ohrms/dockets/98FR/090199g.pdf
- Comment period ended Nov. 30, 1999

## “Evidence Models for the Least Burdensome Means to Market” (con’t)

- A decision algorithm to determine the need for clinical data
- Focuses on two questions:
- Does available VSE provide a basis for clearance when used as indicated in target population?
- What is most appropriate and reasonable way to obtain these data?

## FDA Implementation (con’t)

- _“__**The Least Burdensome Industry Task Force Proposal”**_
- Task Force convened by HIMA
- Proposal dated March 11, 1999
- Incorporated in Appendix D of FDA guidance document - subject to same comment period

**Promoters of “Least Burdensome” concept**
- Application of appropriate risk/benefit criteria in decision-making
- Acceptance of historical data
- Premarket/postmarket balance, particularly when addressing long-term S&E issues
- Acceptance of “state of the art” scientific principles and methods (including clinical study design)
- Consistent use of guidance documents and standards

**Least Burdensome Task Force Proposal **

**Promoters of “Least Burdensome” concept **
- Consistent requirements for manual methods v. automated methods
- Application of a hierarchical approach to least burdensome
- Consideration of “accepted medical practice” in decision-making
- Communication across FDA regarding least burdensome approaches

**Least Burdensome Task Force Proposal (con’t)**

**Deterrents to the “Least Burdensome” concept**
- Necessity of submission in question
- Ineffective communication leads to prolonged decisions and to delays
- Requirements exceeding expectations in guidance documents and recognized standards

**Least Burdensome Task Force Proposal (con’t)**

**Deterrents to the “Least Burdensome” concept**
- Clinical testing in 510(k)s when bench testing shows SE
- Unclear justifications for NSE decisions
- Lack of reviewer familiarity with new technology
- Lack of clarity for FDA rejection of industry approach or proposal

**Least Burdensome Task Force Proposal (con’t)**

## An “Interim” FDA Definition

**	****“****Least Burdensome” - a successful means of addressing a premarket issue that involves the smallest investment of time, effort and money on the part of the submitter**

## Regulatory Indicators of Burden

**Time** to market reflected in cumulative review days and number of review cycles
**Expense ($)** associated with obtaining FDA marketing authorization
**Effort** required to meet regulatory requirements**  **

## Least Burdensome Requires a Change in FDA Culture

- Recognize that there are _**multiple approaches to satisfying regulatory requirements**_
- Communicate, collaborate and** **compromise_** in the interest of public health**_
- Understand not just the letter of the law, but also _**the spirit of the law**_
- Factor _**“time, effort and money”**_ as considerations in decision-making

## Least Burdensome and Scientific Integrity

- All scientific endeavors are affected by the availability of resources
- Good science includes cost-effectiveness
- Compromise is a necessity for successful research
- Lessening regulatory burden may serve to enhance scientific progress and advance medicine

## Pre-Submission Activities: PMA and 510(k) 

**Informal Activities**
- Simple Inquiries (DSMA and ODE)
- Guidance Document Development Activities
- Pre-IDE Program
**FDAMA Early Collaboration Activities**
- Determination meetings
- Agreement meetings

## Pre-IDE Program

**1995 Guidance:**
- Informal advice on pre-clinical testing and/or clinical protocol
- Letter, phone, fax, meeting
**1999 Guidance:**
- Goal is to benefit the sponsor
- Not a pre-requisite for an IDE
- Single Cycle

## Pre-IDE Program (con’t)

**Pre-IDE is appropriate:**
- During testing or protocol development
- NSR Studies
**Pre-IDE is not appropriate:**
- If device or Indications for Use are not well-characterized
- For complete IDEs
- For an in-depth review of data

## Early Collaboration:Determination Meeting

- Section 520(g)(7)(A)
- Any PMA sponsor can request
- Determine valid scientific evidence to demonstrate effectiveness
- Focus on clinical trial design
- Document discussion/determination
- Binding -- unless contrary to public health

## Early Collaboration:Agreement Meeting

- Section 513(a)(3)(D)(i)
- Class III devices and implants eligible
- Agree on Investigational Plan
- Document discussion/determination
- Binding -- unless substantial scientific issue essential to determining S or E is identified _and_ after opportunity to meet

## III.  Least Burdensome and the 510(k) Program

**Review of the 510(k) decision-making process**
**Mechanisms to lessen burden**
- Use of standards/guidance/special controls
- Use of design controls
- Use of  “de novo” classification process
**Recent clearances using least burdensome principles**
**Areas outside the scope of 510(k) review**

## Review of the 510(k) decision-making process [513(i)(1)(A)]

**New device is SE if it has:****	**
- Same intended use and same technological characteristics; _**or**_
- Same intended use and different technological characteristics, but:
- 		- It does not raise different questions of 	  	  safety and effectiveness, and			- Data demonstrates it is as safe and effective

##  Use of Standards/Guidance/ Special Controls

- “Recognition and Use of Consensus 		   Standards” (Feb. 19, 1998)
- Modified guidance on the use of standards to issue soon
- “The New 510(k) Paradigm” (March 20, 1998)

## Use of Design Controls

**The New 510(k) Paradigm -- Special 510(k)s**
- Summary of design control activities
- Declaration of conformity to design controls
- Relies on QSR requirements
- Final decisions in 30 days

## Use of  “de novo” Classification Process

- Section 513(f)(2)
- Risk-based classification process
- When a device cannot be found SE
- Is less burdensome than PMA or PDP

## Recent Clearances Using Least Burdensome Principles 

- Topical non-invasive wound closure devices
- Appeal of request for AI
- Use of class I exemption
- Immediate application to new devices
- 510(k)HDE510(k)
- Sterilization solutions

## Areas Outside the Scope of 510(k) Review 

- Verifying conformance with standards (Section 514, RCHSA, or voluntary standards)
- Ensuring adherence to quality systems requirements, e.g., *special 510(k)s*
- Claims substantiation activities (draft guidance to issue soon)

## IV.  Least Burdensome and The PMA Program

- Reasonable Assurance of Safety and Effectiveness
- Valid Scientific Evidence
- 45% are RCTs; 48% are not RCTs, 7% had no control

## Mechanisms to Lessen Burden in PMA

- Declarations of conformity to standards
- Use of surrogate endpoints
- Reliance on non-clinical testing
- E.g., Needle destruction devices
- Reliance on literature and/or non-active controls
- Paper PMAs
- IOL (historical control)
- Lithotriptors (patient as own control)

## V. Key Points

**In general**
- Factor least burdensome concepts into all premarket activities, e.g., guidance development
- Discuss need for additional studies with colleagues and management _before_ making requests of industry
- Remain open-minded to alternative proposals for satisfying regulatory requirements

## Key Points (con’t)

**In 510(k)**
- Consider what information was envisioned by the statute to demonstrate SE
- Learn from previous 510(k) decisions, i.e., consider whether additional studies are necessary for decision-making
- Use the tools provided by FDAMA and reengineering, e.g., special and abbreviated 510(k)s, exemptions and other FDA guidance

## Key Points (con’t)

**In PMA**
- Factor recognized standards into the decision-making processes
- Consider non-clinical alternatives for low risk devices or device modifications
- If clinical data is needed, consider alternatives to RCTs
- Make a conscious effort to factor in all relevant publicly available information to reduce regulatory burden.