# Presentation: 170607

## CDRH:A Vision for 2005 and BeyondMassMEDIC’s FDA UpdateDecember 2004

**Dan Schultz, MD**
**Director, CDRH**

## Drugs Yesterday

**Drugs Yesterday**

## Drugs Today

## Drugs Tomorrow

## Critical Path Research  

**Leverages basic science knowledge**
**Leverages cumulative research experiences**
***Does not compromise safety and effectiveness evaluations***

## Areas that FDA’s Critical Path Research Can Impact

**Areas that FDA’s Critical Path Research Can Impact**

## Critical Path is Different for Devices

**Device Regulation**
- Least Burdensome Provision of FDAMA
- Quality Systems and Design Controls
**Device Innovation Process**
- Biocompatibility
- Iterative Process
- User learning curve
- Performance and durability
**Device Industry is Represented by Small Manufacturers**

## What is a “Device”?

**What is a “Device”?**

## A Computer You Can Swallow

**Notes:**
And today we don’t only take images by putting the patient in an imaging device, we also swallow the imaging devices and the computer circuitry that not only saves the image but also transmits it to a storage device worn on the belt.

A disposable endoscope in a capsule!

## A Computer That Helps You Hear

## Devices that Measure Glucose Levels and Deliver Insulin to “Communicate”

## Miniaturized Electrical Stimulators

**Pacemakers**

**Notes:**
But today we all know that we put computers in the devices that we put inside our bodies.  And the cardiac pacemaker is an example of a device that was once so large it was placed on a cart outside the body.  Today it gets smaller and smaller, with more and more functions, with batteries that last longer than ever.

## Drug-Eluting Stents

_**Components**_
**Stent Platform & Delivery System**
**Carrier(s)**
**Drug**

## Medical Device Industry GrowthNumber of Manufacturers by Year

**Dun & Bradstreet Medical Device Firm Data**

**Medical Device Industry Growth****Number of Manufacturers by Year**

## Sales Volume Growth(Billions of Dollars)

**Note: No Economic Adjustment to Dollar Value**

## Device Industry Continues to Grow in FY 04

**Dun and Bradstreet FY 04 data shows the device industry grew from 13,579 to 14,937 firms with about $320 billion in sales.**
**Innovation is alive and well!**
**20% annual turnover in individual device firms. **
**FDA-industry interaction is more important than ever.  FDA needs to keep guidances and reviewers up to date.**

## CDRH Vision – Total Product Life Cycle

**CDRH Vision – Total Product Life Cycle**

**Notes:**
In fact, it is most helpful to think of medical devices as a pipeline of innovation and constant improvement.  This creates a very different regulatory challenge than regulating a pharmaceutical with a long patent life, and few if any modifications.

## Role of FDA

**Establish **_***reasonable***_** assurance of the safety and effectiveness of medical devices marketed in the U.S.**

## PerformancePMA Review Times and Number of FTE’s

**Assuming appropriations on track by 2005**

**Performance****PMA Review Times and Number of FTE’s**

## Medical Device ProgramCDRH: Types and Numbers of Submissions

**Medical Device Program****CDRH: Types and Numbers of Submissions**

| TYPE OF SUBMISSION | FY1999 | FY2000 | FY2001 | FY2002 | FY2003 | ESTIMATED
FY2004 |
| --- | --- | --- | --- | --- | --- | --- |
| Original PMA* | 64 | 67 | 71 | 48 | 54 | 50 |
| PMA Supplement* | 552 | 545 | 641 | 645 | 669 | 619 |
| Original IDE | 304 | 311 | 284 | 312 | 242 | 310 |
| IDE Amendment | 275 | 240 | 206 | 252 | 216 | 240 |
| IDE Supplement | 4,127 | 4,388 | 4,811 | 4,724 | 4,425 | 4,388 |
| 510(k) – 10% with clinical data* | 4,458 | 4,202 | 4,248 | 4,320 | 4,247 | 3,533 |
| Original HDE | 12 | 11 | 5 | 5 | 10 | 9 |
| HDE Supplements | 4 | 10 | 16 | 16 | 29 | 29 |
| Total | 9,792 | 9,774 | 10,281 | 10,321 | 9,872 | 9,178 |

***  The majority of PMAs and 510(k) applications are subject to fees.  Exceptions include small business and pediatric applications.**

## CDRH’s Workload is Changing

**In FY 04, CDRH received a record high of 9 expedited PMAs, compared to 3 in FY 03.**
**Expedited PMAs and combination products require more resources, especially with the challenging MDUFMA time-frames.**
**Real-time PMA supplement receipts increased from 139 in FY 02 to 193 in FY 03. **
**In FY 03, CDRH received 73 PMA modules, compared to 32 in FY 01.**
**Modular reviews require re-assembling the review team many times and use more resources than traditional PMAs.**
**The number of 510(k)s with clinical data has increased.**

## Anticipated Medical Device Resources(Adjusted As Required by MDUFMA)

## CDRH MDUFMA Hires in FY03 and FY 04 as of 6/30/04

| Office | Hired
 FY 03  | 
Hired  
 FY 04
 | Two Year Totals
Total MDUFMA Hires (#Shared) |
| --- | --- | --- | --- |
| Total | 75 | 30 | 105    (19 Shared) |
| OC | 10 | 1 |   11    (1 Shared) |
| ODE | 29 | 10 |   39    (6 Shared) |
| OCER | 4 | 0 |     4    (0 Shared) |
| OIVD | 11 | 2 |   13    (0 Shared) |
| OSB | 6 | 7 |   13    (1 Shared) |
| OMO/OCD | 4 | 1 |     5    (0 Shared) |
| OSEL | 11 | 9 |   20    (11 Shared) |

***76 CDRH MDUFMA Hires Projected for FY 04***
***Over 90 of the CDRH MDUFMA hires made in FY 03 and FY 04 were two year appointments**** *

**CDRH MDUFMA Hires in ****FY03 and FY 04 as of 6/30/04**

## CDRH MDUFMA Hiring by Category FY 03 and the First Nine Months of FY 04 as of 6/30/04

**CDRH MDUFMA Hiring by Category FY 03 ****and the First Nine Months of FY 04 as of 6/30/04**

**9**

**20**

**40**

**6**

**7**

**9**

**13**

**1**

## Medical Device Fellowship Program

**What is the Role of Medical Device Fellows?**
**Premarket reviews and consults, especially in specialized areas, such as vascular grafts and stents, spinal implants, software, etc.**
** ****Human factors issues**
** ****Analyzing device failure modes**
** ****Standards and guidance development**

**By end of FY 04, CDRH expects to have 66 participants in the program.**

## Training

**CDRH Staff College**
- Science Leadership Education Program
- Leadership Forum
**Site Visits**
**Scientific Conferences**
**Online Resources**

## Improved IT Infrastructure

**Current IT Needs**
- Tracking
- Reviewing
- Collaborating
- Managing correspondence
- Archiving - Image

**Electronic Submissions?**

**And maybe one day....**

## Completed Documents(Partial Listing)

**Assessing User Fees**
**Small Business Certification**
**Third Party Accreditation **
**FR Notice for *****Critical ***** and *****Semi-critical  *****SUDs**
**PMA Actions and Fees**
**510(k) Actions and Fees**

**Bundling**
**PMA Filing**
**Modular PMA**
**Expedited Review**
**2 Pediatric Documents**
**Validation Data for Reprocessed SUDs**

## Status of FY03 PMA/O & PT-PMA/S receipt cohort 

**Status of FY03 PMA/O & PT-PMA/S receipt cohort **

- Complete

- In Process

- (November 17,  2004)

***95% of those with final decisions completed in     < 320 days***

## CDRHPMA PerformanceFY 2003 Receipt Cohort as of 9/30/2004

**47 Original PMAs and P-T Supplements filed **
**41 FDA decisions; 6 pending applications**
- % of decisions meeting goal:  95%
- % of cohort meeting goal (to date):  83%
- % awaiting MDUFMA decision:  13%
- FY 2006 Goal:  80% of FDA decisions within 320 FDA days
-   (Decision = approval, approvable, approvable pending GMP, not approvable, denial)

## CDRHPMA PerformanceFY 2003 Receipt Cohort as of 9/30/2004

**25 1****st**** action = major deficiency letter**
- % of actions meeting goal:  84%
**	****	****FY 2005 Goal: 75% within 150 FDA days**
**22 “all other” 1****st**** actions**
- % actions meeting goal:  96%
**	****	****FY 2005 Goal: 75% 180 FDA days**
**FY 2003 first action cohort is *****closed***

## Status of FY04 PMA/O & PT-PMA/S receipt cohort 

**Status of FY04 PMA/O & PT-PMA/S receipt cohort**** **

- Complete

- In Process

- (November 17, 2004)

***100% of those with final decisions completed in < 320 days***

## CDRHPMA PerformanceFY 2004 Receipt Cohort as of 9/30/2004

**41 Original PMAs and P-T Supplements filed **
**11 FDA decisions; 30 pending applications**
- % of decisions meeting goal:  100%
- % of cohort meeting goal (to date):  27%
- % awaiting MDUFMA decision:  73%
- FY 2006 Goal:  80% of FDA decisions within 320 FDA days
-   (Decision = approval, approvable, approvable pending GMP, not approvable, denial)

## CDRHPMA PerformanceFY 2004 Receipt Cohort as of 9/30/2004

**20 1****st**** action = major deficiency letter**
- % of actions meeting goal:  85%
**	****	****FY 2005 Goal: 75% within 150 FDA days**
**12 “all other” 1****st**** actions**
- % actions meeting goal:  100%
**	****	****FY 2005 Goal: 75% 180 FDA days**
**9 with first action pending (22% of cohort)**

## Improving PMA performance

**Goal: Shorten both cycle and total decision times**

**... ****which will improve predictability and decrease time-to-market.**

## Original PMA Milestones:1-cycle Scenario

- Filing Review

**Scientific Review**

**Panel Planning**

**Closeout Review**

**PMA Received`**

**Panel **
**Go/NoGo**

**Panel Meeting**

**Filing Letter**

**Final Decision**

**180 days**

**Status**
**Letter**

**Consults Complete**

**Interactive Review**

## Original PMA Milestones:2-cycle Scenario

- Filing Rev

**Scientific Review**

**Panel Planning**

**Closeout Review**

**PMA Received**

**Panel Go/NoGo**

**Panel Meeting**

**Filing Letter**

**Final Decision**

**320 days**

**Major **
**Def. **
**Letter**

**Scientific Review**

***Clock Stops***

**Status Letter**

**Interactive**
** ****Review**

**Consults Complete**

## 510k Goals

## FY03 510k Performance

|  | FY03 Performance | FY05 Goal |
| --- | --- | --- |
| Final decision <90 days | 76% | 75% |
| First action <75 days | 58% | 70% |
| Second action < 60 days | 50% | 70% |

- Need to improve performance on cycle goals

## Meeting the MDUFMA goals: Review Process for Traditional 510ks

**Meeting the MDUFMA goals: ****Review Process for Traditional 510ks**

**Preliminary determination that no ****significant**** additional info needed**

**FDA Initial Review**

**Interactive Review**

***Final Decision ******(***_***<***_***90 total days)***

***Scenario #1***

## Meeting the MDUFMA goals: Review Process for Traditional 510ks

**FDA Initial Review**

**Interactive Review **

**Determination that  significant additional info needed**

***Hold ***

***Final Decision ******(***_***<***_***90 total days)***

***Scenario #2***

**Preliminary determination that no ****significant**** additional info needed**

## Meeting the MDUFMA goals: Review Process for Traditional 510ks

**FDA Initial Review**

** ****Review **

**Determination that  significant additional info needed**

***Hold***

***Final Decision ******(***_***<***_***90 total days)***

***Scenario #3***

***Hold***

** ****Review **

**Determination that  significant additional info needed**

## Preliminary FY04 510k Performance

|  | FY04 Performance | FY05 Goal |
| --- | --- | --- |
| Final decision <90 days | 89% | 75% |
| First action <75 days | 78% | 70% |
| Second action < 60 days | 81% | 70% |

- Preliminary data suggests improvement in performance on cycle goals

**29% of cohort awaiting final decision as of 9/30/04**

## What about the Science?

## Program to Assess Quality of Premarket Reviews

**Focuses on selected cross-cutting areas (e.g., biocompatibility)**
**Retrospective (post-decision) peer assessments of sampled reviews**
**Quality assessment teams with defined criteria**
**Pilot underway**

## Where have we been?

- We’ve made progress in meeting the goals, but it has come at a price.

## The price of early success

**Our staff are working at the limits of their abilities**
**“****Luxuries” such as training, standards, and guidance development have been neglected**

## Where are we now?

- We’ll continue to improve performance, but there are additional challenges ahead.

## The number of combination products is growing...

*Drug-eluting*

*Steroid-eluting*

- Coronary Stent

- Pacing Lead

*rhBMP*

- Bone graft

**... ****necessitating new kinds of technical expertise and new regulatory paradigms.**

## The number of 510ks with clinical data is growing...

**Embolic protection devices**

**... ****requiring more in-depth review, including occasional Panel input.**

**Vascular anastomosis devices for CABG**

- Image-guided bronchoscopes

**Barbed sutures**

- Glaucoma shunts

***Daily wear contact lenses***

***CPAP devices for apnea***

## The number of expedited submissions is growing....

**expedited PMAs in FYO4**

- vs.

**3 expedited PMAs in FYO3**

**14**

**... ****shortening timeframes and bringing increasingly complex scientific questions.**

## The rest of the story...

## Drug-coated stents may face additional FDA scrutiny

**Drug-coated stents may face additional FDA scrutiny**

**FDA Advises Physicians of Adverse Events Associated with Cordis Cypher Coronary Stents**

## Compliance Trends

** **

## Device GMP/QS Inspection Trends

**Device GMP/QS Inspection Trends**

**Statutory Requirement**

## Links Between Process (GMP) Risks and Patient Risks are Lost

- RISK ** **

**Processes**
** ****Inspection Risk **

**cGMP**

- RISK ** **

**Quality Patient) Factors **

**Patient**

**Correlation?**

## Goal:  Prioritize Actions on GMP Risks Correlating to Patient Risks

- RISK 

**Processes Inspection Risk **

- RISK 

**Quality (Patient) Factors**

**GMP**

**Patient**

**Notes:**
I say “re-link” because it is a given that the links were there historically.  In general, there was a valid health and safety reason for each of the product GMPs.  Promulgations of the standards was based on an analytic-deliberative process in risk assessment.  What has happen is a loss of prioritized relevance to how drugs are manufactured today and with what we know about patient risks, today.

## Postmarket Questions of Interest

**Long Term Safety**
**Performance in Community Practice**
**Change in User Setting**
**Rare/Unexpected Events**
**Rates of Anticipated Adverse Events**
**Human Factors Issues – Use Error**
**Off-Label Use**

## When To Respond

**Previously Unrecognized Complications**
**Higher Complication Rate than Expected**
**Use Error**
**New Effectiveness Data**
**Update to Previous Communication**
**When CDRH Has Information Worth Sharing**

## Public Health Response

**Safety Alerts**
**Public Health Notifications**
**Labeling Changes**
**Scientific Publications**
**FDA Patient Safety News**
**Patient Safety Portal**
**Recalls and Other Regulatory Actions**

## Achieving Pre/Postmarket Balance

## Why Balance Works

**Speeds Product to Market by Moving Some Premarket Requirements to Postmarket**
**Offers Added Assurance to FDA and Advisory Panel **
**Free Up ODE Staff for Premarket Review **
**Generates Data for Next Generation**
**Generates Data for Enhanced Labeling**

## Postmarket Studies - Present

**Ill-Conceived**
**Not Initiated**
**Not Completed**
**Not Tracked**
**Not Enforced **

## Postmarket Studies - Future

**Better Designs **
**Standardized Reporting System**
**Better Tracking**
**Make Status of Studies Public**

## Life Sciences Laboratory

**Awards**
**2004, GSA Construction Excellence, Projects Over **
**$25 Million**
**2004, Washington Building Council, Craftsmanship Award (Mechanical / HVAC-Sheet Metal, Mechanical / Plumbing, Mechanical / HVAC-Piping)**

## International Programs

**Educate Foreign Government Officials on the U.S. Regulatory Process**
**Support Global Harmonization, Mutual Recognition Agreements (MRAs) and Other International Agreements**
**Manage US/EC Mutual Recognition Agreement  **_**[www.fda.gov/cdrh/mra](http://www.fda.gov/cdrh/mra)**__** **_

## Industry Assistance

**Division of Small Manufacturers, International, and Consumer Assistance **
- Phone:  800-638-2041 or 301-443-6597
- Email:   _[DSMICA@cdrh.fda.gov](mailto:DSMICA@cdrh.fda.gov)_
- Website www.fda.gov/cdrh
**Educational Programs**
- Guidance
- Teleconferences
- Labeling
- Human Factors

## Summary

**Steady progress towards meeting review performance goals**
**Plans in place to meet goals and solidify center infrastructure**
**Success is achievable but highly resource-dependent**
**Cannot lose track of other challenges and opportunities to meet our public health mission throughout the product lifecycle**

## CDRH Vision – Total Product Life Cycle

**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.