WASHINGTON • Last September, regulators in the United States faced a dilemma: whether to allow importation of drug ingredients from a Chinese factory with a history of poor quality controls, or face shortages of treatments for American cancer patients.
Six months earlier, visiting Food and Drug Administration (FDA) inspectors had uncovered what the agency later called "broad data manipulation" at the factory located in Taizhou, 300km south of Shanghai.
Information about the potency and purity of some product batches had been deleted, making it difficult to investigate a significant increase in customer complaints, the FDA said in a warning letter to the plant's owner, Zhejiang Hisun Pharmaceutical Co.
The agency issued an indefinite ban on the factory last September, a first for Hisun, one of China's leading exporters of pharmaceutical products. Yet, to avoid possible shortages of drugs, the FDA allowed the plant to continue exporting 15 ingredients for use in finished drugs in the US, including nine key cancer medicine components. Hisun says that it takes quality seriously and has complied with requirements.
How the FDA came to this compromise underscores the daunting challenge the agency faces in making sure that drugs are not only safe for US patients, but also that they are available.
DIAGNOSING THE PROBLEM
There is no transparency... We just have to take FDA's word that they think it's okay.
MS ERIN FOX, director of the University of Utah's Drug Information Service, which helps run a website listing shortages.
More than 80 per cent of drug ingredients are now produced abroad, mainly in China and India.
The FDA has stepped up inspections and added 13 Chinese plants this year to its banned list, but it is up to the drugmakers buying components exempted from its bans to control their quality. The agency does not test imported ingredients itself, and relies on pharmaceutical companies to ensure they are up to American standards.
"There is no transparency," said Ms Erin Fox, director of the University of Utah's Drug Information Service, which helps run a website listing shortages. "We just have to take FDA's word that they think it's OK."
Drugs sold in the US are held to the same standards regardless of manufacturing location, the FDA said by e-mail. When products are exempted from its import bans because of shortage concerns, manufacturers are often asked to perform additional testing, hire independent auditors, or take other steps, it said. Companies are not required to disclose to the public where they get their ingredients or where individual products are made, it added.
While 15 products made at the Hisun plant have been barred from the US, 15 others are still permitted because of the FDA's exemptions. These include the chemotherapy ingredients doxorubicin and daunorubicin - go-to treatments for leukaemia, breast cancer and ovarian cancer. Other exempt products are ingredients of antibiotics and a treatment for irregular heartbeats.
The FDA said that until last year, Hisun had addressed all issues to the agency's satisfaction.
Because of trade secret protections, it's difficult to obtain detailed information about the extent of shortages beyond an FDA database that lists drugs reported by pharmaceutical companies.
A powder form of doxorubicin has been in short supply since December 2011, according to the database. While a separate shortage on the liquid form was resolved last month, Hisun's doxorubicin remains exempt from the ban to help increase availability, according to the FDA.
Companies that have listed a shortage of the component include Pfizer Inc.
The New York-based drugmaker formed a joint venture with Hisun in 2012 to make generic drugs for the Chinese and global markets. The import ban at Hisun does not apply to products covered by the joint venture, Pfizer said.
Drugmakers buying imported ingredients are supposed to check them for purity, strength and quality, as well as conduct on-site audits of the components' manufacturers, said Mr Robert Fish, a 33-year veteran of the FDA who served as its head of domestic and international investigations 20 years ago.
"Not all US companies are doing that," said Mr Fish, who left the FDA in 1995 and now advises drugmakers on compliance at EAS Consulting Group. "It costs money."