Heparin API Manufacturer SPL Draws Warning for Complaint Handling and Supplier Auditing

Inadequate follow up to customer complaints – a key theme in recent FDA drug GMP warning letters – was again on the front burner in a warning letter issued in late January to Scientific Protein Laboratories (SPL) in the wake of the agency’s continuing investigation into the 2008 heparin contamination crisis.

As a primary supplier to Baxter of heparin API that was found to be contaminated with oversulfated chondroitin sulfate (OSCS), the GMP controls in place at SPL – particularly over raw material supplies and laboratory testing – have been a focal point in FDA’s effort to understand the causes of the heparin contamination problem and the oversight needed to prevent similar problems in the future.

At the time the heparin OSCS contamination surfaced, SPL was manufacturing API in a facility in China from raw heparin sourced there. SPL has subsequently closed the China plant and moved all of its heparin API manufacturing to its Waunakee, Wisconsin plant, where the inspection referenced in the January warning letter occurred.

The substitution of OSCS – a less expensive substance that mimics heparin in routine identity testing and is relatively benign when not injected – occurred at the raw heparin supply level in China as sources dried up under the impact of a “blue ear” swine epidemic that resulted in the slaughter of millions of Chinese pigs. Raw heparin is extracted from porcine intestines.  The substitution was not uncovered at either the heparin API nor final product manufacturing levels prior to the adverse event outbreak.

The health impact of the heparin contamination worldwide drew an intensive inquiry and crisis management effort by regulators working together at the international level. In late April 2008, the U.S. Congress held two weeks of hearings to assess the causes and what was needed to upgrade FDA’s oversight of an increasingly complex global supply chain.

[Editor’s Note: An in-depth analysis of the impact of the heparin crisis and the Congressional hearings on the future direction of FDA and international GMP enforcement policy is provided in a 44-page IPQ special report issued in mid-2008.]

Both Baxter and SPL have been dealing with lawsuits stemming from the deaths and injuries from the contaminated heparin sourced from China.  A class action lawsuit against Baxter has been scheduled to go to trial in May in Chicago.

Coincidentally, Baxter was also issued a warning letter in late January addressing GMP issues at its sterile product manufacturing operations in Puerto Rico (IPQ “In the News” Feb. 6).  While those issues did not involve heparin manufacturing, the investigation and follow-up of complaints potentially involving product contamination was a key focal point of concern at Baxter as at SPL.

[A discussion of the recent SPL warning letter and the concerns raised by FDA including complaint handling, oversight of contract laboratory testing, and supplier auditing is provided for subscribers here. Non-subscribers can purchase the full story for $95 and both the story and 2008 special report for $250 by contacting Jonathan Trethowan (Jonathan@ipq.org). For subscription information click here.]