Posted 14 October 2014
By Alexander Gaffney, RAC
A Chinese-based manufacturer of heparin products has been sent a Warning Letter by the US Food and Drug Administration (FDA) after regulators accused the company of preventing FDA inspectors from accessing the facility earlier this year, and possibly manufacturing contaminated products.
In its 29 September 2014 Warning Letter to Beijing Shunxin Meihua Bio-technical Co., Ltd, FDA said its inspectors were unable to access the majority of the company's Beijing-based manufacturing facility.
"[Shunxin] barred the [FDA] investigators access to the production area and other parts of the manufacturing facility," FDA explained in its letter. "In several instances, the investigators requested to inspect the facility, but were repeatedly denied access to the production area. Your firm also limited FDA access to certain requested records. For example, the FDA investigators requested batch production records for review, but were refused access to these records repeatedly."
And what few records were provided to FDA contained alarming information, regulators said. A list of suppliers provided by the firm contained a company with an address identical to another firm subject to an FDA import alert, likely implying that a company was providing raw ingredients to Shunxin under an alias.
Heparin Scandal Throwback
The alert is particularly concerning in that Shunxin is a manufacturer of heparin active pharmaceutical ingredients (APIs). In 2007 and 2008, heparin sourced from Chinese manufacturers was linked to the deaths of nearly 150 US citizens, leading to outrage and FDA adding 22 companies to its import alert list. FDA's concern, then, is that some of those same companies are now circumventing its import alert ban by operating under new aliases and supplying their products to third parties like Shunxin.
And while FDA and the US Pharmacopoeia have both taken pains to improve the quality of heparin products being imported into the US, FDA's letter implies that there are still major holes in the supply chain.
"If your firm is being directly or indirectly supplied by establishments that are associated with historical OSCS contamination or that otherwise lack adequate CGMP, your firm could be manufacturing heparin and heparin-related drugs that could be subject to import alert," FDA wrote.
Import Alert, Concerning Findings
Shunxin itself has been subject to an import alert banning its products from entering the US since July 2014 following FDA reports of problems at the facility. FDA's Letter, in addition to describing the agency's difficulty accessing the facility, also describes concerning findings from FDA tests on the company's products.
"FDA test results confirmed the presence of ruminant DNA in one of two samples of porcine crude heparin produced at your site and collected at the facility of one of your customers in China," FDA wrote. The sample, in other words, was contaminated with non-porcine material. Such contaminants, which sometimes originate from cows, goats or sheep, can dramatically change the safety and efficacy profile of the finished heparin.
FDA's Warning Letter to the company is at least the second in two weeks alleging that a company failed to provide proper access to a facility. A 26 September 2014 letter to Pennsylvania-based Nova Products alleged the company failed to allow an FDA inspector to access a "complete inventory of all products previously sampled." Those products, FDA alleged, were adulterated with undeclared prescription drugs used to treat erectile dysfunction.
Shunxin's products are considered adulterated under new authority recently given to FDA under Section 707 of the Food and Drug Administration Safety and Innovation Act (FDASIA). As explained in the July 2013 guidance Circumstances that Constitute Delaying, Denying, Limiting, or Refusing a Drug Inspection, FDASIA gave FDA the authority to deem products adulterated if a firm obstructs FDA's ability to inspect—or fully inspect—a facility.
In the past, some firms have sought to refuse or delay entry of FDA inspectors into their facility, hoping the additional time could be used to either clean up a facility or expunge certain records. Under the new rules, any attempts to prevent FDA from accessing parts of a facility it has the legal right to access—including records—will cause the agency to deem its products adulterated, thereby revoking the company's ability to legally market the product until violations are corrected.
[For a full explanation of FDA's inspection authority under FDASIA, please see our explanation here.]
Until Shunxin allows FDA to inspect its facility, the agency will withhold the approval of any product listing Shunxin as a manufacturer and will continue its import alert, FDA said.
FDA Warning Letter to Shunxin