E9-18952. Guidance for Industry on Pharmaceutical Components at Risk for Melamine Contamination; Availability

AGENCY:

Food and Drug Administration, HHS.

ACTION:

Notice.

SUMMARY:

The Food and Drug Administration (FDA) is announcing the availability of a guidance for industry entitled “Pharmaceutical Components at Risk for Melamine Contamination.” This guidance provides recommendations that will help pharmaceutical manufacturers of finished products, repackers, other suppliers, and pharmacists who engage in drug compounding avoid the use of components that are at risk for melamine contamination. As of the date of this announcement, FDA is not aware of any pharmaceutical components that are contaminated with melamine.

DATES:

Submit written or electronic comments on the guidance by October 6, 2009. General comments on agency guidance documents are welcome at any time.

ADDRESSES:

Submit written requests for single copies of this guidance to the Division of Drug Information, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, rm. 2201, Silver Spring, MD 20993-0002; or the Communications Staff (HFV-12), Center for Veterinary Medicine, Food and Drug Administration, 7519 Standish Pl., Rockville, MD 20855. Send one self-addressed adhesive label to assist that office in processing your requests. Submit written comments on the guidance to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852. Submit electronic comments to http://www.regulations.gov. See the SUPPLEMENTARY INFORMATION section for electronic access to the guidance document.

FOR FURTHER INFORMATION CONTACT:

Frank W. Perrella, Center for Drug Evaluation and Research (HFD-320), Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, rm. 4337, Silver Spring, MD 20993-0002, 301-796-3265; or

Brian Hasselbalch, Center for Drug Evaluation and Research (HFD-320), Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, rm. 4364, Silver Spring, MD 20993-0002, 301-796-3279; or

Diane Heinz, Center for Veterinary Medicine (HFV-6), Food and Drug Administration, 7519 Standish Pl., Rockville, MD 20855, 240-276-9031.

SUPPLEMENTARY INFORMATION:

I. Background

FDA is announcing the availability of a guidance for industry entitled “Pharmaceutical Components at Risk for Melamine Contamination.” This guidance provides recommendations that will help pharmaceutical manufacturers of finished products, repackers, other suppliers, and pharmacists who engage in drug compounding to better control their use of at-risk components that might be contaminated with melamine. The guidance explains that the agency is recommending that at-risk components be properly tested for melamine contamination before they are used in the manufacture or preparation of drugs or drug products. This recommendation applies to nitrogen-based components.

As discussed in the guidance, FDA has posted on its Web site methods for measuring melamine contamination in foods using liquid chromatography triple quadrupole tandem mass spectrometry (LC-MS/MS) and gas chromatography/mass spectrometry (GC-MS). Although these methods have been evaluated using dry protein materials, they can also be applicable to other material, including at-risk components. Manufacturers are encouraged to validate test methods that are suitable for detecting melamine contamination in at-risk components down to 2.5 parts per million (ppm) to give a high degree of assurance that they are not contaminated. At this time, FDA has not established an appropriate level of melamine in drug products.

As explained in detail in the guidance, there have been repeated instances of melamine contamination in food articles, including in the U.S. market. In 2007, FDA learned that certain pet foods were sickening and killing cats and dogs. In September 2008, FDA received reports of melamine-contaminated infant formula in China. These two incidents share the following similarities:

• Melamine, a nitrogen-based compound, was apparently added to bolster the apparent protein content in foods or in ingredients used in processed food products intended to contain protein.
• The recipients of the ingredients using a test for nitrogen content would not have been able to distinguish between melamine and the desired protein.
• Melamine contamination became public only after numerous adverse health events, including deaths, were reported and associated with the use of contaminated products.

These incidents illustrate the potential for drug components to be contaminated with melamine; therefore, it is important for drug manufacturers to be diligent in assuring that no component used in the manufacture of any drug is contaminated with melamine. As of the date of this guidance, FDA is not aware of any pharmaceuticals that are contaminated with melamine. However, because of the potential risk of drug contamination, it is important that manufacturers take steps to ensure that susceptible components are not contaminated with melamine.

We are issuing this level 1 guidance for immediate implementation, consistent with FDA's good guidance practices regulation (21 CFR 10.115). The agency is not seeking comment before implementing this guidance because of the potential for a serious public health impact if melamine-contaminated pharmaceuticals were to enter the domestic market. The guidance represents the agency's current thinking on this issue. 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 and regulations.

II. Comments

Interested persons may submit to the Division of Dockets Management (see ADDRESSES) written or electronic comments regarding this document. Submit a single copy of electronic comments or two paper copies of any mailed comments, except that individuals may submit one paper copy. Comments are to be identified with the docket number found in brackets in the heading of this document. Received comments may be seen in the Division of Dockets Management between 9 a.m. and 4 p.m., Monday through Friday.

III. Electronic Access

Persons with access to the Internet may obtain the document at http://www.fda.gov/​Drugs/​GuidanceComplianceRegulatoryInformation/​Guidances/​default.htm, http://www.fda.gov/​AnimalVeterinary/​GuidanceComplianceEnforcement/​GuidanceforIndustry/​default.htm, or http://www.regulations.gov.

Dated: July 31, 2009.

Jeffrey Shuren,

Associate Commissioner for Policy and Planning.