Questions are hanging over the role of a Chinese manufacturing facility in the Baxter heparin scare after it has emerged that the US Food and Drug Administration (FDA) has never inspected the facility.
Baxter has this week suspended the production of its blood-thinning drug heparin in multi-dose vials, following the deaths of four patients in the US who were given the drug in high doses, along with 350 reports of severe allergic reactions to the drug, with symptoms including a rapid drop in blood pressure, burning sensations, headaches, throat swelling and a shortness of breath.
At the time of the announcement, the FDA said it "is vigorously investigating to determine the root cause of these serious reactions associated with the use of heparin made by Baxter."
It has since come to light that Baxter sources the drug's active pharmaceutical ingredient (API) from an undisclosed US supplier who operates the plant in China, as well as another one in the US.
However, what is concerning is that the FDA has now revealed that the Chinese plant in question did not actually undergo a pre-approval inspection by the agency as is required before a manufacturing facility is authorised to supply drug ingredients to the US.
An FDA spokesperson told the Wall Street Journal that the plant making the API "was supposed to be inspected" but "our understanding is that, due to human error, and inadequate information technology systems, a pre-approval inspection, which would normally be conducted, was not."
"While no FDA inspection of the facility has been conducted to date, preparations are being made to perform an inspection as soon as possible. We have already requested expedited access to the facility, facilitated through a recently signed agreement with the Chinese State Food and Drug Administration (SFDA). FDA also has requested the facility's inspectional data and adverse event reports connected to the product," said the spokesperson.
According to the report, both Baxter and the FDA said "it wasn't clear that the ingredient from the Chinese supplier was tied to the bad reactions".
The finished heparin product is packaged in a plant owned by one of Baxter's subsidiaries in New Jersey and the FDA indicated it would also be conducting an inspection of this plant following the scare.
Outsourcing-Pharma was unable to obtain further comment from the FDA or Baxter by the time of publishing.
The Chinese facility may or may not be behind the heparin adverse reactions, however, this situation highlights another example the add fuel to the fire of concern in the US over the mounting number of foreign-sourced drug ingredients and the FDA's questionable ability to effectively monitor the quality control and adherence to good manufacturing practice (GMP) of each and everyone of them with the limited resources that it has.
The agency is struggling to keep abreast of the intensifying outsourcing trend - 75-80 per cent of all APIs used by US (and EU) drug manufacturers are now imported, mainly from India and China.
This issue is high on the radar of the two trade associations of the world's two largest pharma economies - Europe and the US - who have taken the unusual step of banding together to condemn their regulatory authorities for poor regulation of foreign API manufacturers.
They claim that the FDA and the European Agency for the Evaluation of Medicinal Products (EMA) do not regularly inspect all foreign facilities manufacturing APIs serving them (generally only at intervals of five years or longer) and many foreign facilities have never been inspected at all, as this latest incident proves.
Furthermore, 90 per cent of the inspections carried out by the FDA are pre-approval inspections, while only 10 per cent are for GMP compliance purposes, according to Joe Acker, President of SOCMA.
Moreover, in a recently-released Government Accountability Office (GAO) audit report, China, which has the largest number of drug manufacturers eligible for FDA inspection (714) was earmarked for only 13 regulatory visits by the FDA in 2007, meaning only less than 2 per cent of the country's drug exporters will have had their facilities examined.
The winds of change are blowing, with the first steps in tightening the safety controls on the pharmaceutical ingredients imported to the US from China being taken in December following months of negotiations between the regulatory bodies of the two countries.
From now on, Chinese manufacturers that export to the US any of the APIs listed on a newly drawn up list are required to register with the Chinese drug regulators. Gentamicin sulphate (an antibiotic), atorvastatin (the API in Lipitor) and sildenafil (the API in Viagra), are among the big-name ingredients included on the list.
However, the agreement is only a small step in the direction of a number of measures that need to be taken to secure the supply chain, especially considering that in the past year the majority of top tier pharma firms have pledged their resolve to increase outsourcing to Asia.
Commenting on the issue on Tuesday, Bart Stupak, the Michigan Democrat who is head of the House Energy and Commerce Subcommittee on Oversight and Investigations said: "American lives will remain at risk until the FDA commits the resources necessary to inspect imported drugs and drug ingredients."