# Presentation: 706028

## David W. Feigal, Jr., M.D., M.P,H,
Director, Center for Devices and Radiological Health

- Director, Center for Devices and Radiological Health

## Workload

- Submissions: Fiscal Year 2000

| PMA Original | 67 |
| --- | --- |
| PMA Supplements | 545 |
| IDE’s Original | 311 |
| IDE Amendments | 240 |
| IDE Supplements | 4388 |
| 510(k)s | 4202 |
| Humanitarian DE | 11 |
| HDE Supplements | 10 |
| “Minor” Submissions | 7145  |
| Total | 16919 |

- 65 Submissions per day

## PMAs, Supplements and IDEs

## Performance

- PMA’s

- * First 6 months 2000

- *

## PMA Total Approval Times

-  * Year to date

-  *

**Performance**

## PMA Supplement Total Approval Times

**Performance**

## Pre-market Notifications (510k)

## 510(k) Decisions

**Performance**

## 510(k) Total Decision Times

**Performance**

## 510(k) Total Decision Times

- Not reached Yet

**Performance**

## Submissions: Fiscal Year 2000 

| PMA Original |  | 67 | 2831 Hours |
| --- | --- | --- | --- |
| PMA Supplements |  | 545 | 175 Hours |
| IDE’s Original |  | 311 | 256 Hours |
| IDE Amendments |  | 240 |  |
| IDE Supplements |  | 4388 | 18 Hours |
| 510(k)s |  | 4202 | 62  Hours |
| Humanitarian DE |  | 11 |  |
| HDE Supplements |  | 10 |  |
| “Minor” Submissions |  | 7145  |  |
| Total |  | 16919 |  |

**Performance**

## Workload: Fiscal Year 2000 

| Advisory Panel Meetings | 927 hours /day |
| --- | --- |
| Standards | 1470 hours |
| Regulations | 2520 hours |
| Registration & Listing | 4 hours |
| MDR | 42 Minutes |
| Agreement & Determination   Meetings | 717 hours |
|  |  |

**Performance**

## New types of 510(k) applications 
Third Party 510(k) Review
Dispute Resolution:
Ombudsman:  Les Weinstein
Dispute Resolution Panel
Least Burdensome

- Third Party 510(k) Review
- Dispute Resolution:
- Ombudsman:  Les Weinstein
- Dispute Resolution Panel
- Least Burdensome

**FDAMA Implementation**

## Three alternatives:
FDA recognized standard with a declaration
Mfr. has data now
FDA-recognized standard without declaration
Mfr. does not have supporting data at time of submission but will before marketing
Non-recognized standard
Less assurance that standard will be acceptable
FDA may need to request additional information

- FDA recognized standard with a declaration
- Mfr. has data now
- FDA-recognized standard without declaration
- Mfr. does not have supporting data at time of submission but will before marketing
- Non-recognized standard
- Less assurance that standard will be acceptable
- FDA may need to request additional information

**Using Standards in 510(k)’s**

## Performance:  510(k)s - Alternatives

| Type of 510(k) | Reviews
Completed

FY99 | Average Total
Time (days) | Reviews
Completed

FY00 | Average Total
Time 
(days) |
| --- | --- | --- | --- | --- |
| Abbreviated
(Standards) | 75 | 99 | 118 | 109 |
| Special | 361 | 29 | 583 | 32 |
| Traditional | 4155 | 108 | 3699 | 115 |

**ODE Performance**

## A “Fee-for-Service” User Fee                             

Reviewer must be acceptable to both FDA and manufacturer.
Cost must be acceptable to manufacturer
Review quality must be acceptable to FDA
Use of the program frees FDA resources at the primary reviewer level while keeping the supervisory oversight.

- Reviewer must be acceptable to both FDA and manufacturer.
- Cost must be acceptable to manufacturer
- Review quality must be acceptable to FDA
- Use of the program frees FDA resources at the primary reviewer level while keeping the supervisory oversight.

**Third 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

- 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

**Third Party Review**

## Third Party Review

| Who are they? | Number | % total |
| --- | --- | --- |
| TUV Product Service | 59 | 41 % |
| Underwriters Labs.  | 23 | 16 % |
| CITECH | 21 | 15 % |
| TUV Rhineland of North America | 15 | 10 % |
| California Dept. of Health Services  | 12 | 8 % |
| Intertek Testing Services | 7 | 5 % |
| Entela - | 4 | 3 % |
| Center for Measurement Standards ITRI | 1 | <1% |
| NV Kema | 1 | <1% |
| 3 other Accredited 3rd Parties | none |  |

**Third Party Review**

## Who is using it ?

**Applications  Received Through September 2000**

**Third Party Review**

## 510(k) Eligibility      www.fda.gov/cdrh/thirdparty
November 1998
154 device classifications - 104 class II
1200 eligible 510(k)s 
June 2000
211 device classifications – 154 class II
1600 eligible 510(k)s
February 2001
674 device classifications – 617 class II
2700 eligible 510(k)s 
> 70%of all 510(k)s are now eligible which trips the trigger for the 5 year sunset provision of the law in February 2006

- November 1998
- 154 device classifications - 104 class II
- 1200 eligible 510(k)s
- June 2000
- 211 device classifications – 154 class II
- 1600 eligible 510(k)s
- February 2001
- 674 device classifications – 617 class II
- 2700 eligible 510(k)s
- > 70%of all 510(k)s are now eligible which trips the trigger for the 5 year sunset provision of the law in February 2006

**Third Party Review**

## Performance     
1999  (n=32)
3rd Party Total Time 	  57 days
FDA Total Time*		105 days
2000 (n=47)
3rd Party Total Time 	  68 days
FDA Total Time*		  99 days
2001 (projected n = 92)

- 1999  (n=32)
- 3rd Party Total Time 	  57 days
- FDA Total Time*		105 days
- 2000 (n=47)
- 3rd Party Total Time 	  68 days
- FDA Total Time*		  99 days
- 2001 (projected n = 92)

| * Matched by 510(k) product code |
| --- |

**Third Party Review**

## First Year Experience
Complaints:  24
Disputes:      11
Complaint about or Dispute with: (Some Complaints/Disputes were about more than one Office)
ODE:	23 (61%)
OC:  	  6 (18%)
Other: 9 (24%)
 About:	
 510(K): 18 (51%)
 PMA:      2 (6%)
 Registration & Listing:  2 (6%)
 Other:  13 (37%)

- Complaints:  24
- Disputes:      11
- Complaint about or Dispute with: (Some Complaints/Disputes were about more than one Office)
- ODE:	23 (61%)
- OC:  	  6 (18%)
- Other: 9 (24%)
-  About:
-  510(K): 18 (51%)
-  PMA:      2 (6%)
-  Registration & Listing:  2 (6%)
-  Other:  13 (37%)

**Ombudsman**

## First Year Experience
Complaints:  24
Disputes:      11
Complaint about or Dispute with: (Some Complaints/Disputes were about more than one Office)
ODE:	23 (61%)
OC:  	  6 (18%)
Other: 9 (24%)
 About:	
 510(K): 18 (51%)
 PMA:      2 (6%)
 Registration & Listing:  2 (6%)
 Other:  13 (37%)

- Complaints:  24
- Disputes:      11
- Complaint about or Dispute with: (Some Complaints/Disputes were about more than one Office)
- ODE:	23 (61%)
- OC:  	  6 (18%)
- Other: 9 (24%)
-  About:
-  510(K): 18 (51%)
-  PMA:      2 (6%)
-  Registration & Listing:  2 (6%)
-  Other:  13 (37%)

- If ODE:
- DRARD:  1     (4%)
- DCLD:    2      (9%)
- DGRND: 9   (39%)
- DDIGD:  5   (22%)
- DCRD:    6   (26%)
- DOED:   0      (0%)

**Ombudsman**

## Issues: (Some complaints/disputes had more than issue.)
Communication:  17 (23%)
Evidence Requirements (data, testing):  11 (15%) 
Timeliness:  10 (13%)
 Conflict of Interest, Bias, Retaliation:  5 (7%)
 Rudeness/Difficulty Working With:  5 (7%)
 Procedures:  5 (7%)
 Disclosure:  4 (5%)
 Level Playing Field:  3 (4%) 
 Competence:  2 (3%)
 Drug/Device:  2 (3%)
 Other:  11 (15%)

- Communication:  17 (23%)
- Evidence Requirements (data, testing):  11 (15%)
- Timeliness:  10 (13%)
-  Conflict of Interest, Bias, Retaliation:  5 (7%)
-  Rudeness/Difficulty Working With:  5 (7%)
-  Procedures:  5 (7%)
-  Disclosure:  4 (5%)
-  Level Playing Field:  3 (4%)
-  Competence:  2 (3%)
-  Drug/Device:  2 (3%)
-  Other:  11 (15%)

**Ombudsman**

## Outcome: 
Resolved and/or Satisfied:  18 (51%). 
  in industry’s favor 	15 (83%)
  in FDA’s  favor	  3 (17%)
Pending:  13 (37%)
Referred or Unknown:  4 (11%)

- Resolved and/or Satisfied:  18 (51%).
-   in industry’s favor 	15 (83%)
-   in FDA’s  favor	  3 (17%)
- Pending:  13 (37%)
- Referred or Unknown:  4 (11%)

**Ombudsman**

## Dispute Resolution Panel 
First Meeting October 31, 2000
Orientation and Organizational Agenda
Second Meeting June 4, 2001
First manufacturers request for an appeal
PMA application heard before an FDA panel with recommendation not to approve
New analyses to address concerns did not reverse FDA decision to concur with initial recommendation
Dispute Resolution Panel’s recommendation will decide the issue unless there are compelling public health issues to disagree.

- First Meeting October 31, 2000
- Orientation and Organizational Agenda
- Second Meeting June 4, 2001
- First manufacturers request for an appeal
- PMA application heard before an FDA panel with recommendation not to approve
- New analyses to address concerns did not reverse FDA decision to concur with initial recommendation
- Dispute Resolution Panel’s recommendation will decide the issue unless there are compelling public health issues to disagree.

**Ombudsman**

## Agreement Meetings
Determination Meetings
Pre-IDE Meetings
Real Time Review

- Determination Meetings
- Pre-IDE Meetings
- Real Time Review

**Working with CDRH**

## Meetings

|  | 1998 | 1999 | 2000 | Total |
| --- | --- | --- | --- | --- |
| Agreement Meetings | 7 | 16 | 2 | 25 |
| Determination Meetings | 3 | 8 | 4 | 15 |
| 100 Day Meetings | 5 | 15 | 7 | 27 |
| Total | 10 | 24 | 6 | 67 |

| Pre IDE | 300 | 299 | 315 |
| --- | --- | --- | --- |

- (24 reached agreement)

- (14 reached agreement)

**Meetings**

## Meetings

- 315

- 299

- 300

- 106

|  | 1998 | 1999 | 2000 | Total |
| --- | --- | --- | --- | --- |
| Agreement Meetings | 7 | 16 | 2 | 25 |
| Determination Meetings | 3 | 8 | 4 | 15 |
| 100 Day Meetings | 5 | 15 | 7 | 27 |
| Total | 10 | 24 | 6 | 67 |

- (24 reached agreement)

- (14 reached agreement)

- 1997

- 1996

**Meetings**

## Real Time PMA Supplements
146 requests for Real-Time PMA Supplements 
Representing 27% of all PMA supplements
134 were approved
Most by telephone conference

- 146 requests for Real-Time PMA Supplements
- Representing 27% of all PMA supplements
- 134 were approved
- Most by telephone conference

**Meetings**

## Ombudsman Survey
1.  In the meeting, were the least burdensome principles applied in determining the need for prospective data in the following:
Was pre-clinical testing considered in lieu of clinical data?  Yes:  2    No:  9
Was the use of previously collected non-US data, literature, and/or registry data considered? Yes:  5    No:  6

- 1.  In the meeting, were the least burdensome principles applied in determining the need for prospective data in the following:
- Was pre-clinical testing considered in lieu of clinical data?  Yes:  2    No:  9
- Was the use of previously collected non-US data, literature, and/or registry data considered? Yes:  5    No:  6

**Least Burdensome**

## Ombudsman Survey
2.      In the meeting, were the least burdensome principles applied in designing the clinical trial in the following:
Were alternatives to an actively controlled trial considered?   Yes:  5    No:  4   n/a: 1
     If yes, check the following:
          Literature control     		 Yes:  1  No:  3
          Historical control      		  Yes: 2   No:  3
          Non-active control    		  Yes:  1  No:  3
          Patients as their own control  	  Yes:  1  No:  3
          Objective Performance Criteria  Yes:  1 No:  3
          Other      			  Yes:  1  No:  3

- 2.      In the meeting, were the least burdensome principles applied in designing the clinical trial in the following:
- Were alternatives to an actively controlled trial considered?   Yes:  5    No:  4   n/a: 1
-      If yes, check the following:
-           Literature control     		 Yes:  1  No:  3
-           Historical control      		  Yes: 2   No:  3
-           Non-active control    		  Yes:  1  No:  3
-           Patients as their own control  	  Yes:  1  No:  3
-           Objective Performance Criteria  Yes:  1 No:  3
-           Other      			  Yes:  1  No:  3

**Least Burdensome**

## Ombudsman Survey   
Was the use of surrogate endpoints considered?    	Yes:  1  No:  8    	n/a:  1  
 Was a least burdensome approach considered in determining how the primary and secondary endpoints will be measured?      	Yes: 4    No:  3	n/a:  1
  Was early submission of the application considered?  That is, could the application be submitted after a mutually agreed to percentage of the patients had been followed for a pre-defined period of time?       	Yes:  3   No:  6	n/a:  1
 Was the role of post marketing information considered as a mechanism for reducing the premarket requirements?             	Yes:  2     No:  8
Were the least burdensome principles applied in other areas of the trial design not mentioned above?  Yes:  2     No:  6	n/a:  1 

- Was the use of surrogate endpoints considered?    	Yes:  1  No:  8    	n/a:  1
-  Was a least burdensome approach considered in determining how the primary and secondary endpoints will be measured?      	Yes: 4    No:  3	n/a:  1
-   Was early submission of the application considered?  That is, could the application be submitted after a mutually agreed to percentage of the patients had been followed for a pre-defined period of time?       	Yes:  3   No:  6	n/a:  1
-  Was the role of post marketing information considered as a mechanism for reducing the premarket requirements?             	Yes:  2     No:  8
- Were the least burdensome principles applied in other areas of the trial design not mentioned above?  Yes:  2     No:  6	n/a:  1

**Least Burdensome**

## Global Quality System Standards
Global Regulation
Global Scientific Leadership
Evidence Based Medicine

- Global Regulation
- Global Scientific Leadership
- Evidence Based Medicine

**Global markets – Global Standards**

## Global Harmonization	Task Force

- Next Meets:  October 11-16, 2001  Barcelona, Spain
- Four study groups:
- Regulatory Requirements / Premarket Review
- Device Vigilance / Post-Market Surveillance
- Quality System Requirements and Guidance
- Auditing
- www.ghtf.org

**Harmonization**

## 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 | 500
Recognized |

## Guidant Global Compliance

**# of **
**Inspections**
**all Guidant**
**locations**

**Inspections 1997-August 2000**

**Guidant**** ****Global Compliance**

**12**
**37**
**26**

*Courtesy Michael Gropp, Guidant*

## 2000 Device Inspections

**Resources**

## Device Establishment Inspections

**Device Establishment Inspections**

**3602**

**1841**

**Resources**

## Enforcement ActionMedical Devices and Radiological Health

- Fiscal Years

- * Prior to 1976 Injunctions and Prosecutions were combined

## Mission:

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

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

**CDRH’s Strategic Plan**

## Consumer Protection

- Safe experimentationPremarket safety Premarket effectivenessResearch Inspection

- Truthful promotionAdverse Event Reporting Postmarket studiesManufacturing Inspection

**Consumer Protection**

**Notes:**
Product Life Cycle  (note this is an animated slide with the postmarket graphic initially not shown)

Historically FDA’s role has focused on the consumer protection provided during the premarket evaluation of new products.  Even congressional budgeting language will often earmark this phase of drug and device development.  In the FY 2000 budget the appropriation specified a floor of effort of slightly more than half of the Center’s budget and FTE’s for the premarket program. Logically then  we are able to divide a product life around the pivotal marketing decision and can describe a product life cycle as a two cycle: pre and post.  (hit the forward to show the post market graphic)

This graphic is a little misleading for a number of reasons.  First it doesn’t proportionally reflect the scale of the FDA efforts in these areas.

## CDRH Vision - Total Product Life Cycle

**Notes:**
And they interconnect.  They interconnect because all parts of the cycle inform and are pathways to other parts.  They interconnect because products further along in the cycle inform and affect new products earlier in the cycle.  They interconnect because a safe and effective device or radiological health product can’t be developed without some knowledge of all the parts.

## CDRH Vision - Total Product Life Cycle

**The Pipeline**

## Slide 45

**Notes:**
Of course there is the regulatory life cycle which roughly corresponds to the total product life cycle.  Each of these regulatory tools corresponds roughly to a time in the product life cycle.  In the details of regulatory life cycle it is easy to burrow down and lose the big picture and lose the fact that the regulatory steps are tied to the total product life cycle and that the regulatory processes are linked together.

## Human Factors

**Notes:**
Of course there is the regulatory life cycle which roughly corresponds to the total product life cycle.  Each of these regulatory tools corresponds roughly to a time in the product life cycle.  In the details of regulatory life cycle it is easy to burrow down and lose the big picture and lose the fact that the regulatory steps are tied to the total product life cycle and that the regulatory processes are linked together.

## Center for Devices     and Radiological Health

*Strategic Goals*
- Total Product Life Cycle
- Magnet for Excellence
- Knowledge Management
- Meaningful Metrics

## Consumers increasingly independent
Direct to Consumer Sales
Directed Advertising
Internet
FDA Internet Site
Increase from 30 million to 45 million hits per month in the last 6 months
Some consumer brochures are downloaded a million times per year
Home Care
Self Care

- Direct to Consumer Sales
- Directed Advertising
- Internet
- FDA Internet Site
- Increase from 30 million to 45 million hits per month in the last 6 months
- Some consumer brochures are downloaded a million times per year
- Home Care
- Self Care

**Information Empowered Consumers**

## Center for Devices and Radiological Health

*Question:*
*	**What will we lose if the scientific and regulatory **leadership and credibility of FDA is lost ?*
* **will the needs of Evidence Based medicine be met by “substantially equivalent to a pre-1976 device”?*
* **risk based inspection with decreasing assurance of conformance to quality standards?*
* **expansion the EU CE-mark clout as the de facto quality standard?*
*world-wide impact by regional concerns and experiences?*
* **will “precaution” replace “risk-benefit”*

## Center for Devices and Radiological Health

*Vision:*
*	**	**Ensuring the health of the public **	**	**throughout the *
*	**	**Total Product Life Cycle*

*	**	**	**	**	**— **it’s everybody’s business*