Agency expedites approval of orphan drug and increases protections for users

The U.S. Food and Drug Administration today issued an expedited approval of a supplemental application that allows for changes in the manufacturing of Sucraid (sacrosidase) Oral Solution. The approval will prevent a product shortage by allowing the sole manufacturer of the drug, QOL Medical, to obtain Sucraid's active ingredient from a different manufacturer.

Sucraid provides drug replacement therapy for patients that have been diagnosed with a congenital (inherited) disease called Congenital Sucrase-Isomaltase Deficiency (CSID). Worldwide, approximately 400 CSID patients have been prescribed Sucraid, 140 in the United States alone. Patients who suffer from CSID lack the necessary enzyme sucrase located in their gut that is required to digest sucrose (table sugar) which is in many foods. A lack of this enzyme causes diarrhea, abdominal pain and severe cramping when eating these products. Sucraid enables them to digest sucrose containing foods more readily.

To avoid interruptions in treatment, on Oct. 24, 2008, the agency authorized QOL Medical to provide the newly manufactured product to patients prior to the FDA's final action on the manufacturing supplement. The FDA also has taken new steps to protect the patients who use this treatment. The agency is requesting the company implement measures designed to evaluate the risks of adverse events associated with the new supply of Sucraid.

"The FDA has expedited its approval of the newly manufactured Sucraid," said Julie Beitz, M.D., director, Office of Drug Evaluation III, the FDA's Center for Drug Evaluation and Research. "However the manufacturing changes could lead to more frequent allergic reactions. To continue our rigorous oversight, FDA is requiring the manufacturer to inform prescribers and patients of the changes, and conduct a postmarketing study."

Sucraid, was originally approved by the FDA as an orphan drug on April 9, 1998. CSID is found amongst Alaska Natives and people from Nordic populations. Some patients are as young as 5 months old.

The FDA is concerned that the newly manufactured Sucraid may contain increased levels of papain, an enzyme known to cause allergic reactions in some people. Papain could be introduced into the drug via the manufacturing process of its active ingredient, sacrosidase, a disaccharide-cleaving enzyme isolated from the yeast Saccharomyces cerevisiae. In order to extract the enzyme, the yeast cell wall is digested with papain, a proteolytic enzyme obtained from the papaya fruit. Papain is introduced early in the manufacturing process, and later removed by subsequent process steps. The new manufacturing process provides for an increased amount of papain used to digest the yeast cell wall. Since no tests for papain in the drug are performed either during manufacture or at release, FDA cannot exclude the fact that some level of papain contamination of the drug substance may be present.

The FDA informed the public about the risks associated with papain exposure on Sept. 22, 2008. It is now using its authority under the Food and Drug Amendments Act of 2007 to require a postmarketing safety study in patients receiving the newly manufactured Sucraid to evaluate the incidence of serious allergies and other adverse reactions. The FDA is also requiring a risk evaluation and mitigation strategy for this product. The company will be required to issue letters to patients with each initial shipment informing them of the manufacturing changes and requesting that they complete a survey about their experience using the product. Prescribers will receive a similar communication and be asked to complete a survey about their patients' experiences.

Health care professionals and consumers should report serious adverse events (side effects) or product quality problems with the use of this product to the FDA’s MedWatch Adverse Event Reporting program either online, by regular mail, fax or phone.
--Online: www.fda.gov/MedWatch/report.htm
--Regular Mail: use postage-paid FDA form 3500 available at: www.fda.gov/MedWatch/getforms.htm and mail to MedWatch, 5600 Fishers Lane, Rockville, MD 20852-9787
--Fax: (800) FDA-0178
--Phone: (800) FDA-1088

QOL Medical, LLC is based in Kirkland, Wash.

To read about the FDA’s public announcement on products containing papain, go to: www.fda.gov/CDER/news/papain/qa.htm.