Guidance for Industry

Possible Dioxin/PCB

Contamination of Drug and

Biological Products

U.S. Department of Health and Human Services

Food and Drug Administration

August 1999

Compliance
Guidance for Industry

Possible Dioxin/PCB

Contamination of Drug and

Biological Products

Additional copies of this Guidance are available from:

 Office of Training and Communications

 Division of Communications Management

Drug Information Branch, HFD-210

Center for Drug Evaluation and Research

Food and Drug Administration

 5600 Fishers Lane, Rockville, MD 20857

(Phone 301-827-4573)

Internet: http://www.fda.gov/cder/guidance/index.htm.

or

 Office of Communication, Training and

Manufacturers Assistance, HFM-40

Center for Biologics Evaluation and Research

 Food and Drug Administration

1401 Rockville Pike, Rockville, MD 20852-1448

Internet: http://www.fda.gov/cber/guidelines.htm.

Fax: 1-888-CBERFAX or 301-827-3844

Mail: the Voice Information System at 800-835-4709 or 301-827-1800

or

Communications Staff (HFV-12)

Center for Veterinary Medicine (CVM)

7500 Standish Place, Rockville, MD 20855

(Tel) 301-594-1755

http://www.fda.gov/cvm

U.S. Department of Health and Human Services

Food and Drug Administration

August 1999

Compliance
Guidance for Industry1

Possible Dioxin/PCB Contamination

of Drug and Biological Products

I. INTRODUCTION

This guidance is intended for manufacturers using materials derived from animal sources

in the manufacture of human or animal drugs or biological products. During the period

from January through June 1999, some poultry, swine, and ruminants (cattle, sheep, and

goats) in several EU (European Union) countries were fed feed contaminated with

dioxins and PCBs (polychlorinated biphenyls). As a result, animals that received the

contaminated feed became contaminated with dioxins and PCBs. Manufacturers who are

using materials from such animal sources in the manufacture of their products should

verify that the materials they are using are not from animals affected during the

contamination incident, or conduct suitable testing of the materials.

II. RECOMMENDATIONS FOR ASSESSING ANIMAL DERIVED

MATERIALS

Because of the potential contamination of animals in Belgium, France, and the

Netherlands, manufacturers should investigate the origin of animal derived materials

(e.g. egg yolk lecithin, egg phospholipids, pancrelipase) they are using to manufacture

human or animal drugs or biological products. This includes drug substances and

excipients. If materials are found to be derived from poultry, swine, or ruminants,

manufacturers should obtain certification from their suppliers that the animal derived

materials (including the eggs from chickens) used in drugs or biological product

manufacturing do not come from animals raised in any of these three countries during the

period January through June 1999. If the animal source of manufacturing materials

cannot be certified, the material should not be used to manufacture human or animal

drugs or biological products. Alternatively, the materials should be tested for the presence

of dioxins or PCBs prior to use. One analytical method suitable for foods that may be

adapted for analyzing PCBs in pharmaceuticals can be found in the FDA's Pesticide

Analytical Manual, Vol. 1, Chap. 3, sect. 303 or 304.2

 1 This guidance has been prepared by the Food and Drug Administration. This

guidance represents the Agency’s current thinking on possible dioxin/PCB contamination of animal source

material in EU countries. It does not create or confer any rights for or on any person and does not operate

to bind FDA or the public. An alternative approach may be used if such approach satisfies the

requirements of the applicable statutes, regulations, or both.

2 This is available on the FDA Web site (www.cfsan.fda.gov/~frf/pamil.html).
If products have already been produced using materials that cannot be certified, PCB or

dioxin testing of the final product should be performed. If the presence of PCBs or

dioxins is detected, manufacturers should contact the appropriate contact person listed

below to discuss whether the release of the product is acceptable.

The Agency is conducting a sampling and testing program for dioxins and PCBs in drugs

and biologics originating from EU countries.

Contact Persons

For animal drug products, contact John Matheson, Center for Veterinary Medicine, 301-

827-6649.

For human drug products, contact Eric Duffy, Center for Drug Evaluation and Research,

301-827-7310.

For biological products, contact Christopher Joneckis, Center for Biologics Evaluation

and Research, 301-827-5138.