HIT Washington Editor

The State Food and Drug Administration in China may have started from scratch where regulations for drugs and devices are concerned, but government authorities in the world's most populous nation are making strides, as yesterday's conference call hosted by the DC law firm of Hogan & Hartson (H&H) made clear.

Some of the impetus behind tighter regulations may be the execution of a former SFDA commissioner over scandals related to drug manufacturing, but Beijing also must consider international opinion in order to blunt further fall-out from episodes such as the tainted heparin coming out of China.

Another motivator is that China's device sector has acquired enough expertise to have produced a drug-eluting stent, the Excel, made by JW Medical (Weihai, China), so SFDA must contend with a burgeoning domestic industry as well as a coming onslaught of imports.

According to Roy Zou, senior counsel for regulatory affairs at H&H's Beijing office, SFDA has bolted down on existing healthcare product clearances. "In 2008, SFDA conducted a concentrated review ... of about 25,000 drug applications submitted before Oct. 1, 2007, and approved only 9,200," or "about 37%," Zou said. Addressing devices specifically, he noted that SFDA will not permit the import of any devices that have not been approved or cleared in their home nations

"The most prominent change will be the eligibility to be registered," Zou said, noting that according to proposed regulations, would-be importers "must obtain marketing approval in the exporting country first. We are following closely whether this will be implemented," he said. SFDA requires that importers "appoint a legal entity to import" devices, and the agent of the device maker "will be responsible for taking regulatory actions" required by Chinese law.

The proposed measures include that the agent and manufacturer "are required to keep records" of adverse events "for no less than five years" and must also have procedures for dealing with these. "If there's an adverse event report, the rule requires that the manufacturer or distributor report the event to SFDA."

Zou noted that SFDA has about 48 testing centers "and they're aiming at about 10 such centers to expand" their capacities to full national testing capability. He said the agency also wants to "expand to another nine institutions to update their testing" technologies. He also pointed out that the size of this market is large and growing. "China issued its healthcare reform plan," Zou said, which is likely to involve $120 billion in annual spending. One of the "key elements is a reliable medial supply system," he said, hence the reforms in question.

Ted Wilson, a partner in the firm's DC office, warned device makers on the call that FDA is far from finished in its efforts to get a handle on supplier controls for medical devices. He led by pointing that the quality systems regulations (QSR) "applies to finished device manufacturers," but not directly to component makers. However, a smart client firm "can certainly require by contract that contract manufacturer's comply" with QSRs.

In this scenario, the device maker "serves as the gatekeeper over all components, materials and services" used in the manufacture, including any contract sterilization. Thus, "it's not just the product, it's also the service providers" who have to toe the line if devices are to carry a reasonable assurance of safety. This notion extends to third-party auditors as well, Wilson said.

Supplier qualification standards should detail the requirements for initial and periodic requalification, and even disqualification "if they have a significant compliance issue with FDA," Wilson said. He stated further that all such procedures must be backed by a documented rationale. "You need to establish acceptance criteria to demonstrate the suitability of the supplier," he restated. "You need to have objective evidence in your files that the supplier can meet quality requirements," even though the device maker is not specifically required to audit or inspect a contracting firm. "In the real world ... finished device makers will audit them periodically," Wilson stated "and if your procedure says you have to audit a supplier, you'd better do it" or a warning letter may be in the offing.

The level of control exerted by the client company is determined by "the supplier type and the risk of the product or service," Wilson stated, and "can range from 100% inspections of incoming products to annual audits." FDA can "criticize you for not having the correct controls," also. Firms must also have an approved vendor list, and the documentation requirements would include qualification documents and documents regarding any quality or regulatory problems.

Contractors should be required to contact the client about any changes or even proposed changes. "There have been a number of recalls ... where a contractor made a change that had an unintended effect" on quality and the customer was ignorant of the change until problems began to surface, Wilson reminded.

The Global Harmonization Task Force (GHTF) released a guidance in January for materials and parts obtained from suppliers. Wilson informed the listeners that he believes that "FDA is going to be looking more and more at the principles in that document as well." Purchasing controls are of much greater interest at FDA, he commented further, noting that 19 warnings issued in 2006 addressed such arrangements, but 35 warnings written to device makers last year 2008 cited such considerations.

As for import alerts and detentions, Wilson reminded the audience that "its easy for FDA to initiate an import alert/detention on products made overseas. The burden is less onerous" than for devices made at domestic plant, which would require the help of courts and state or federal prosecutors. "FDA can bar the entry of the product based on the mere appearance of adulteration and misbranding," he pointed out, and can get the job done simply by dialing up the U.S. Customs Service. "It can take nine to 12 months, or even longer to resolve" such issues, a condition that he said carries "potentially damaging repercussions."

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