Letters Sent to Baxter and FDA Request Answers on Heparin Situation

On February 21, 2008, a congressional committee sent letters to Baxter Healthcare (Deerfield, IL) and the Food and Drug Administration (FDA, Rockville, MD) seeking information related to the recent heparin recall.

In a letter to Robert Parkinson, Jr., CEO of Baxter, John Dingell, chairman of the House Committee on Energy and Commerce, asks, “Was your firm misled by FDA into believing that the Chinese firm was an approved supplier of an active ingredient for Heparin? If not, then we are concerned that your company was knowingly distributing an unapproved drug.”

Dingell goes on to request all records since January 1, 2002, that are related to active pharmaceutical ingredient (API) suppliers, inspection documents, regulatory correspondence, marketing and pricing policies, all due diligence performed on heparin and its manufacturing facilities, and information on drug recalls and adverse events.

The FDA also received correspondence from Dingell’s Committee, which sought clarification on the apparent lapse in its pre-approval inspection policy. In a letter to FDA Commissioner Andrew von Eschenbach, Dingell requested clarification on that. He also requested interviews with Janet Woodcock, FDA deputy commissioner; Margaret Glavin, associate commissioner for regulatory affairs; and the reviewers responsible for the approval for the API in heparin.

Baxter halted production and recalled multiple-dose vials of heparin on February 11 after receiving reports of four deaths and approximately 350 adverse events involving patients receiving a high bolus dose of the product. The reactions included difficulty breathing, nausea, vomiting, excessive sweating, and rapidly falling blood pressure. The causes of the adverse reactions are still unknown but the manufacturer and the FDA are investigating whether manufacturing problems were at fault. Tests have shown variability in the lots connected to the adverse advents.

The FDA acknowledged in a February 18 conference call with reporters that it never inspected the plant in China where the drug’s API is made. FDA facility inspections are normally conducted prior to approvals of new drug applications (NDAs) and supplemental applications. In this case, according to Joseph Famulare, deputy director with the Office of Compliance at CDER, the FDA evaluated the wrong plant because of an internal error at the agency.

He also said that it is not yet clear who entered the incorrect name and whether this error would have been detected had the adverse reactions to heparin not occurred.
During the conference call, Michael Rogers, director of the Division of Field Investigations with the FDA, said that the FDA would be in later China that week to conduct inspections of the Scientific Protein Laboratories (SPL, Waunakee, WI) facility in Changzhou, China, which manufacturers the active ingredient in Heparin.

Heparin has been on the market in some form since 1972. In 2004, Baxter filed a supplemental NDA indicating that the source of the API had changed to the SPL facility in China. It is at this time that the Chinese facility should have been inspected.

FDA release

Committee letter to Baxter

Committee letter to FDA