FDA Reaches Out

Government officials from the U.S., Europe, Australia, and Singapore descended on the Chinese pharmaceutical chemical manufacturer Zhejiang Cheng Yi Pharmaceutical last fall to conduct a joint inspection of its manufacturing facilities. According to Cheng Yi, the visit marked the first time that inspectors from the U.S. and Europe jointly evaluated and approved a drug plant outside their borders.

Both the U.S. and Europe regularly inspect only a fraction of the manufacturing units abroad that supply them with pharmaceuticals—a fact that raises concerns about the safety of imported drugs. For instance, in 2009, the U.S. Food & Drug Administration inspected just 11% of the foreign drug plants that supplied the U.S. that year (C&EN, May 16, page 11).

In an effort to remedy their weak oversight, FDA and the European Medicines Agency agreed to launch a joint inspection pilot program last fall. The initiative marks the beginning of a process that may lead to multiple jurisdictions agreeing to recognize each other’s certifications of drug manufacturing facilities. Industry participants, however, aren’t holding their breath.

Joint inspections fall under a broad plan that FDA announced last month to raise the safety of imported foods and drugs (C&EN, June 27, page 22). FDA and the European Medicines Agency said in an earlier statement that the object of joint inspections “is to see whether greater international collaboration can help to better distribute inspectional capacity, allowing more sites to be monitored.” The two agencies acknowledge that they have long been criticized both for duplicating efforts and for not inspecting enough drug manufacturing facilities abroad.

From the viewpoint of Cheng Yi’s executives, the joint inspection process is extremely drawn out. It took more than a year to coordinate the inspectors’ visit, recalls Lion Sun, a Cheng Yi sales executive. “The Australian Therapeutic Goods Administration started to schedule an inspection with us in September 2009, and then it was delayed to April 2010 because the Europeans said they’d join. Then a few months later, the FDA said they wanted to come too,” he says. The long-awaited inspection took place in September 2010, with Singaporean inspectors also present as observers.

After arriving at Cheng Yi’s site in Zhejiang, the inspectors spent the first two days of their visit in private meetings with each other, recalls Jenny Zheng, manager of Cheng Yi’s import and export department. In the three days that followed, the inspectors looked at the firm’s manufacturing facilities “while comparing their standards and methods,” she recalls. Cheng Yi is a diversified producer of active pharmaceutical ingredients and drug intermediates that are exported to the U.S., Europe, Australia, and other countries.

The joint visit did not mean streamlined paperwork for Cheng Yi. For the purpose of getting approval from all the authorities involved, Cheng Yi had to submit documentation satisfying the separate requirements of the U.S., Europe, and Australia. The company’s facilities were finally approved by the three authorities in February. Zheng says she does not know why Cheng Yi was selected as the first company to be jointly inspected.

The U.S., Europe, and Australia are nowhere close to agreeing to recognize each other’s inspections, Zheng reckons. “There are a lot of issues they need to solve before they can substitute for one another,” she says. “This implementation of a system of international cooperation will take at least three to five years to smooth out.”

Even five years is an optimistic estimate, contends Peter Saxon, chief executive officer of Saxon International, a New Jersey-based firm that helps pharmaceutical producers outside the U.S. comply with FDA requirements. It took 15 years, from 1979 until 1994, for the U.S. and Europe just to agree on common standards for stability temperatures for pharmaceuticals, Saxon recalls.

Still, it’s not surprising that the U.S. and Europe have begun to conduct joint inspections, says Jeffery A. Hangartner, Shanghai-based manager of regulatory affairs and current Good Manufacturing Practices compliance at the U.S. active pharmaceutical ingredients marketer ChemWerth. Before joining ChemWerth, Hangartner himself inspected pharmaceutical plants for FDA. He recalls once conducting a joint inspection with counterparts in Switzerland with the purpose of determining “whether our inspection methods were acceptable to each other.” The Swiss-U.S. joint inspections eventually led to a bilateral agreement reached in the spring of 2009 to pool data from inspections of pharmaceutical plants.

It’s almost inevitable that the U.S. will come to accept inspections of pharmaceutical plants performed by other countries, Hangartner adds. “When I was at the agency, lack of funding was an issue, and I imagine it still is,” he says. “If FDA could come to an agreement with some other countries, it could be of assistance to reduce the great workload at the agency.”