# Presentation: 225604

## David W. Feigal, M.D., M.P.H.
Director
Center for Devices and Radiological Health, US Food and Drug Administration

- David W. Feigal, M.D., M.P.H.
- Director
- Center for Devices and Radiological Health, US Food and Drug Administration

- September 20, 20008th GHTF Conference
- Ottawa, Canada

**PVC and DEHP**

## Dr. Lloyd Tepper, Associate Commissioner for Science at FDA in the early 1970’s, once characterized DEHP as “an etiology in search of a disease”. 

## Assessment of DEHP

- The Health Question:
- Does exposure to PVC medical devices result in adverse health effects ?
- Risk Assessments
- American Council on Science and Health (chaired by C. Everett Koop)
- Eastman Chemical (chaired by John Doull)
- Health Care Without Harm
- NTP Center for the Evaluation of Risks to Human Reproduction (chaired by Robert Kavlock)

## Assessment of DEHP

- Citizen’s Petition:
- June 99 - Health Care Without Harm
- 	requesting:
- warning labels on all PVC devices that may leach phthalate plasticizers, and
- expedite the development and usage of substitute materials

## FDA Risk Assessment

- Executive Summary
- Introduction
- Exposure Assessment
- Hepatic Effects
- Renal Effects
- Pulmonary Effects
- Reproductive Effects
- Developmental Effects
- Cardiovascular Effects
- Hematological Effects
- Cancer
- Miscellaneous Effects
- Risk Characterization
- References

## FDA Approach

- Risk Assessment Approach Used:
- 	“Margin of Exposure”   **MOE**
- Ratio of the lowest dose that produced adverse effects in experimental animals
-        	   (LOAEL)/dose of DEHP received by
-        	   patients
- Avoids the need to define uncertainty factors

## Interpretation of the MOE

- Not “bright line” values, intended to provide a general index of risk
- Large values (> 1000), little likelihood of adverse effects in humans
- Values close to 1, expose humans at the level adverse effects observed in animals
- Values between 10 and 100, risk management activities depends on various factors (nature of adverse effect, size and sensitivity of the affected population, availability of alternatives, etc.)

## Risk Assessment Approach

- Identify factors that move the exposure towards 1
- Size of patient
- Duration of exposure
- Characteristic of PVC device
- Surface Area
- Coatings
- Use with substances that increase release of DHEP

## Risk Assessment Approach

- Assess Common Clinical Exposures
- Intravenous fluid administration
- Intravenous drug administration
- Total Parenteral Nutrition
- Enteral feeding
- Dialysis, Apheresis, ECMO
- Blood and blood product transfusion

## Risk/Benefit Assessment

- Product by product assess:
- Potential for exposure at levels associated with toxicity in animals
- Potential impact of toxicity in the clinical setting
- Benefit associated with use of product causing the exposure
- Potential alternative products and their risk/benefits

## Potential Approaches

- Most products with PVC are not durable goods with long use life-times so changes in products will have rapid market effects;
- Market forces are resulting in the development of alternative materials for many products;
- Precedents exist to require labeling, for example latex containing devices where knowledge of exposure would allow choice of an alternative product

## FDA Regulated Products and PVC

- Issues
- Drugs: consistent labeling of products that
- affect release of DEHP, or
- require dose modification when administered through alternative tubing
- Blood: impact on red cell half-life
- Devices:
- how will performance be affected by material changes;
- what is the toxic potential of the new materials

## FDA: Next Steps

- Internal review of risk assessment
- Public comment on risk assessment
- Determine which product areas warrant attention
- Develop strategies to improve risk/benefit for specific product areas