# Presentation: 904784

## The FDAModernization Act

- David W. Feigal, Jr., M.D., M.P.H.
- Director
- Center for Devices and Radiological Health
*ASAIO, New York City, June 29, 2000*

## The FDA Modernization Act 1997

- Context
- Origins of FDA Consumer Protection
- International device development and regulation
- FDAMA Elements
- Agreement Meetings / Dispute Resolution
- Modular PMA
- New 510(k) paradigms
- 3rd Party 510(k) review
- Least Burdensome Pathway to Market
- Future Directions

## Origins of the Centers’ Culture

- Unsafe Manufacturing – Adulteration
- Horse Jim
- Morphine Cough Syrup
- Ethylene Glycol
- Heart Valves
- “False and Misleading”
-  Fraud

## Origins of the Centers’ Culture

- Unethical Research
- Tuskegee
- Willowbrook
- Long Island Jewish Hospital
- Research Fraud
- IBT (animal)
- Clinical Fraud

## The Goods (Regulations and Guidance)

- The Problems:
- Manufacturing Fraud
- Laboratory Fraud
- Clinical Research Abuse
- Poor Tissue Screening
- Poor Regulatory Practice

- Part of the Solution:
- Good Manufacturing Practice
- Good Laboratory Practice
- Good Clinical Practice
- Good Tissue Practice
- Good Review Practice
- Good Guidance Practice

## Origins of the Centers’ Culture:Performance Anxiety

- “Drug Lag”
- Backlogs
- Drugs
- Generic Drugs
- Device 510(k)’s
- Blood Devices
- Reinventing Government (NPR)
- PDUFA
- Re-engineering

## Origins of the Centers’ Culture:Evidence Standards

- Biologics
- Safe Pure and Potent (1904)
- Drugs
- Unadulterated, Not Misbranded (1906)
- Safe (1932)
- Safe and Effective (1962)
- Adequate and well controlled trials
- Devices
- Well Controlled Investigations ... and other valid scientific evidence ... sufficient to determine effectiveness (1976)

## International Device Regulation

**Standards Conformance**

**Global Harmonization Task Force**

**Mutual Recognition Agreements**

- FORCES:

## Global Harmonization	Task Force

- Four study groups:
- Regulatory Requirements / Premarket Review
- Device Vigilance / Post-Market Surveillance
- Quality System Requirements and Guidance
- Auditing
- Next Meets:  September 18-22, 2000  Ottawa, Canada
- www.ghtf.org

## International Standards Organizations

|  | ANSI | BSI | DIN | Centralized European |  |  | CDRH |
| --- | --- | --- | --- | --- | --- | --- | --- |
|  |  |  |  | CEN | CENLAC | ETSI |  |
| Budget
(Millions $) | 15 | 293 | 100 | 10 | 4 | 21 | 140 |
| Staff | 79 | 4000 | 1000 | 115 | 36 | 107 | 1200
Including field |
| Committees | 262 | 2888 | 4600 | 1844 | 387 | 64 |  |
| Standards | 14202 | 19129 | 24000 | 5131 | 2863 | 709 | 600
Recognized |

## International Standards

- Role in US Device Regulation
- Quality Standards
- Cross-product performance standards
- Product specific standards
- Can replace portions of 510(k) applications
- E.g.,  A mechanical wheel chair 510(k) application can consist of declaration of conformance to 12 standards.

## FDAMA

## Regulatory Hierarchy

- Statute
- FD&C / FDAMA  (1904;1936;1962;1997)
- PHS Act (1902;1944)
- Regulations
- Enforceable implementation of Statute
- Guidance
- Best Advice
- Non-enforceable when not regulation based
- Recognized Standard
- A way to meet a regulation or guidance

## Laws Enforced by FDA					http://www.fda.gov/opacom/laws/lawtoc.htm

- Food Drug and Cosmetic Act
- Public Health Services Act
- National Vaccine Program
- Federal Advisory Committee Act
- Administrative Procedures Act
- Orphan Drugs
- Trademark Act
- Federal Trade Commission Act
- Controlled Substances Act
- ... and others

## FDA Modernization Act of 1997 (FDAMA)

- Signed into law November 21, 1997
- Amends the Food, Drug & Cosmetic Act
- Amends the Public Health Service Act
- Renews the Prescription Drug User Fee Program with amendments (PDUFA 2)

## Themes of FDA Modernization Act 

- Interactive process for product review
- Decisive action
- Patient access
- Codifies reengineering
- Agency discretion, not mandatory requirements
- FDA review accountability/timeliness

## FDAMA: Interactive Processes	

- Pre-PMA & Pre-IDE Meetings
- Meetings:
- 24 pre-IDE
- 12 pre-PMA
- 3 both
- CDRH gets very few requests
- CDRH requests that companies bring detailed, comprehensive information and allocate enough time to produce an agreement where possible

## FDAMA: Interactive Processes	

- Dispute Resolution
- § 404 of FDAMA
- Guidance on available dispute resolution practices, Feb. 1998:
-  http://www.fda.gov/cdrh/modact/dispresl.pdf
- Final agency rule in Nov. 1998 amending                 21 CFR 10.75
- Draft guidance on resolving scientific disputes using special Dispute Resolution Panel – April 1999

## FDAMA: Interactive Processes

- Dispute Resolution
- Dispute Resolution Panel chartered
- Recruitment and selection of Panel members     	underway
- CDRH  recruited an  Les Weinstein as Ombudsman for the Center
- Disputes and common problem areas
- Reports directly to the Center Director
- Outreach
- Follow-up
- Quality Systems relating to common problem areas

## Performance:  510(k)s - Alternatives	

| Type of 510(k) | Reviews
Completed
12 months
FY99 | Average Total
Time (days) |
| --- | --- | --- |
| Abbreviated | 75 | 99 |
| Special | 361 | 29 |
| Traditional | 4155 | 108 |

**Based on conformance to Standards**

## Disappointing review times?	

- Abbreviated 510(k)s
- New guidance will help.   See: http://www.fda.gov/cdrh/ode/guidance/1131.html
- Manufacturers may submit:
- A declaration of conformity to a recognized standard
- A statement that product will conform to a recognized standard when finally marketed
- A statement that the product will conform to a non-recognized standard  – decided case-by-case
- Standards development is key

## Performance:  510(k)s - Alternatives	

| Type of 510(k) | Reviews
Completed
12 months
FY99 | Average Total
Time (days) | Reviews
Completed
1st 9 months FY00 | Average Total
Time (days) |
| --- | --- | --- | --- | --- |
| Abbreviated | 75 | 99 | 75 | 60 |
| Special | 361 | 29 | 389 | 33 |
| Traditional | 4155 | 108 | 2637 | 115 |

## 3rd Party Review

- Qualifications
- Not a Federal Government employee
- Independent organization, not controlled by industry
- Legally constituted entity permitted to conduct 3rd party review
- Will not design, manufacture, promote or sell devices
- Operates under accepted professional & ethical business practices -- specifics agreed to in writing

## Who Are the 3rd Parties ?

| Third Party | Number | % total |
| --- | --- | --- |
| TUV Product Service | 37 | 45 % |
| Underwriters Labs.  | 13 | 16 % |
| CITECH | 10 | 12 % |
| TUV Rheinland of North America | 7 | 8 % |
| California Dept. of Health Services  | 6 | 7 % |
| Intertek Testing Services | 3 | 4 % |
| Entela - | 1 | 1 % |
| 5 other Accredited 3rd Parties | none |  |

## 3rd Party Reviews: Who is using it ?

- 19 Ultrasound  6 Diagnostic X-Ray  1 Emission CT

-   6 Drug of Abuse Tests  1 Epstein Barr Test

- GeneratorsFiberoptic LightsViewing Monitors

**Fiscal Year 1999:  52 3****rd**** Party Approvals**

## 3rd Party Review

- Performance
- 154 device classifications - mostly class II
- Represented 1200 eligible 510(k)s
- Only 32  submitted to 3rd parties in FY 99
- Comparison of total elapsed review time:	                                                                        	3rd party review     	         	  57 days                                           	Comparable 510(k)s		105 days
- Plans for expansion

## 3rd Party Review

- Current program expanding even as pilot is launched
- List of eligible class II devices with guidance includes 40 additional class II categories
- 609 products in 203 classifications now eligible
- http://www.fda.gov/cdrh/thirdparty

## 3rd Party Review

- Expansion Pilot
- Proposal issued June 12, 2000
- http://www.fda.gov/cdrh/thirdparty
- All class II devices not prohibited by statute could be eligible, whether or not specific guidance is available
- List accompanies draft  guidance and includes 958 additional products in 470 class II device types

## Least Burdensome Path to Market 

- Interpretation
- Goal:  To get the right information to support submissions -- not more, not less
- Data:  Needed and appropriate to product
- Process:  Interactive and transparent

## Least Burdensome Concept

- Working Definition:
-  “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 Least Burdensome Concept should be integrated into all FDA and industry interactions, as appropriate, not just premarket review.

## Least Burdensome Path to Market

- Center Initiatives
- Training classes for
- CDRH review staff
- Advisory Committee Panels
- First live webcast
- Adding language to correspondence with industry to raise least burdensome concerns
- Adding least burdensome consideration to Good Guidance Practices

## Least Burdensome Path to Market

- Projects with Industry Task Force
- Revised guidance on early collaboration meetings
- Standardized approaches to identifying and communicating deficiencies
- Guidance on appeals under least burdensome

## Center for Devices and 		Radiological Health

- Mission:
- CDRH promotes and protects the
- public health by ensuring the
- safety and effectiveness of medical devices and the safety of radiological products.

## Science fuels the regulatory engine

- CDRH Materials Engineering Program
- Characterization
- Applicability and reliability
- device performance
- Durability
- identification of methods and modes of failure

## Characterization

- Fabrication methodologies
- effects on properties and microstructure
- Additives
-  intentional and unintentional
- Leachants
- hydrophobic/lipophilic
- hydrophilic/lipophobic
- Degradation products

## Applicability and Reliability

- Device Performance
- CDRH regulates devices not materials
- Is the correct material used in the proper application ?
- Silver Coated Heart Valves
- Aluminum oxygen regulators
- Development of appropriate accelerated test methodologies to predict long-term performance and/or shelf life

## Durability

- Identification of Methods & Modes of Failure
- Corrosion
- galvanic
- fretting
- Abrasion and wear
- Over stress and fatigue (fracture)
- Material breakdown
- Biological effects

## Opportunities for Partnerships and Leveraging

- Standards Development
- Need to develop standards with clinically relevant performance criteria
- Device Retrieval and Analysis
- Need to evaluate both successful and failed devices
- Links with clinical records
- Links with FDA databases