Baxter Expands Heparin Recall, FDA Issues 483 to China Facility

Following the partial recall initiated on January 25, 2008, Baxter Healthcare (Deerfield, IL) has expanded its recall of heparin. In addition to multi-dose vials, the recall now includes single-dose vials and HEP-LOCK heparin flush products. Although there have been no reports of adverse reactions related to the single-dose vials of heparin or HEP-LOCK, as had been reported with the multi-dose vials, Baxter has recalled them as a precaution because they have the same active pharmaceutical ingredient (API) as the multi-dose vials.

In a February 28, 2008 conference call, FDA officials said that the full recall could proceed because adequate heparin supplies have been ensured. Sandra Kweder, deputy director of the Office of New Drugs, in the Center for Drug Evaluation and Research, said that the FDA’s shortage supply team had been working with the other main supplier of heparin, APP Pharmaceuticals (Schaumburg, IL), to ensure that the recall would not cause a severe shortage of heparin. According to Kweder, “APP is now able to adequately supply the US market.”

In the same call, the FDA said it had observed several violations of good manufacturing practices (GMPs) during its inspection of the Scientific Protein Laboratories (SPL, Changzhou, China) facility where the API for the recalled heparin is made. Michael Rogers, director of field investigations, FDA Office of Regulatory Affairs, said that the inspectors had “identified a number of potentially objectionable conditions related to the firm’s manufacturing process.” The inspectors presented SPL with a 483 form, which is the form used by FDA investigators to record their observations of non-compliance with cGMPs. In the 483, the agency cited important compliance failures related to a lack of standard steps for the removal of impurities, basic process control, and investigations into out-of-specifications test results.
Specific violations in the form include:

• The facility’s manufacturing instructions were incomplete

• No critical processing steps had been identified and no annual test results available

• No impurity profile had been established for heparin

• No test method verifications performed to show that they are suitable under actual conditions of use

• Investigations into failed lots and out of trend lots did not show cause for the problems

• Certain heparin crude lots received in August 2006 included materials from an unacceptable workshop vendor.

• Raw material inventory records were incomplete; prior to March 2006, there were no records from a certain vendor to show the source of its crude materials

• Waste material flow into the processing area was not controlled.

Rogers said that the facility is not currently manufacturing, and that the inspection team is still “working to determine the level of significance associated with these observations.” The inspection team remains in China, and is following up on other facilities involved with the API.

FDA 483 on Heparin