The China Food and Drug Administration has issued more than 20 guidance documents on medical device regulation over the last two years as it tightens its oversight of the device industry in the fast-growing market.
The chief concern and area of uncertainty revolves around the country's clinical trial regime, especially for devices that are not on an "exempt list." Adding to the confusion, some devices on the list may still require a clinical trial, while others not on the list could get registered and approved without a trial.
Med tech consultant Chang-Hong Whitney described the Chinese regulatory paradigm last month during a talk sponsored by the Regulatory Affairs Professional Society at Babson College in Babson Park, MA. Whitney's been advising device companies seeking to do business in China and interacting with the CFDA reviewers for 22 years.
All but the simplest Class I devices need to convince the CFDA that there is a predicate device on the market in China, or they must conduct a clinical trial in the country to secure approval. "The majority of the products we are working with right now are facing the fact that you will have to do a clinical trial in China," Whitney told the audience of med tech stakeholders from industry bigwigs like Medtronic ($MDT), as well as several startups and med tech consultants.
Beware, while the CFDA classifies devices into three risk-based categories like the FDA, individual devices may be classified differently in each country. Similarly, China's definition of predicate device is stricter than that used by the FDA in the 510(k) clearance pathway.
|Chang-Hong Whitney, president, Whitney Consulting|
Whitney prefers the terminology "same type device." "They really do mean same type. Actually meaning to the bones. Not only must the design be the same, but also material, packing and sterilization have to be the same. This is very narrowly defined predicate," she said.
Even the CFDA knows its regulatory definition of predicate is too narrow, she said, saying, "Somewhere down the line I'm hoping that they're going to change this. But the regulation right now says that. The reviewer can use a little discretion, but technically they are not able to move too far from this definition."
"Our job is to point out the minor little difference and evaluate that minor little difference," she added.
There are 488 Class II devices and 79 Class III devices on the "exempt list," which is comprised of older, legacy technology, according to the consultant. The good news is that devices not on the list may avoid trials if they convince CFDA of the existence of a predicate. But while devices on the list are less likely to require clinical trials, sponsors must still convince CFDA of the existence of a predicate.
"You still have to take a look at the description of that product in the list to see whether you can comply, or the application of the product can match (the description in the list). If you don't match that you have to be prepared to argue about the differences and if there's any clinical trials you have to do," Whitney said.
She said she's currently working on securing approval of an ECG device for monitoring the heart. ECGs are on the exempt list. But, "one is a regular ECG and another is for stress testing. We're having a conversation with CFDA and saying this is virtually the same product, but they're saying the intended use is different so we need to evaluate it differently," she said.
Overall, the regulations are not industry friendly, in case that wasn't clear already.
Industry feels the clinical trial requirement is duplicitous, but Whitney said, "I don't see CFDA saying that if you do a European trial you don't have to do one in China."
She does expect the CFDA to "loosen up" its application of the predicate device concept. "By the current definition everything has to go through a trial and that's just unreasonable," she said, adding that there have been few submissions using the predicate device comparison, in part because it requires sponsors to include information about competing devices that is often proprietary.
For example, one of the items of comparison to a predicate device includes biocompatibility testing, but companies don't typically share the results of their bench tests with each other voluntarily. The audience members said the CFDA should already have access to such information.
Whitney agreed, and said industry will just have to cope with the state of affairs for now, "until things change."
There have been a few notable developments that favor industry. The CFDA no longer requires biocompatibility testing to be conducted in China, and simple Class I devices can be registered in about a month for no fee, Whitney said.
Most notably, some foreign devices are being reviewed through the so-called Green Channel pathway for innovative devices. Whitney said entrance into the accelerated review pathway is akin to skipping the line. Although the approval standards are the same, the milestone can be achieved in perhaps half the usual time.
The 2013 draft Green Channel proposal had a made-in-China provision for eligibility, but the U.S. Department of Commerce successfully lobbied their Chinese counterparts to remove that condition, arguing that it violated World Trade Organization rules and bilateral treaties between the countries.
Industry worries that the rules are rigged to favor local competitors. For example, by requiring devices to have a virtually identical predicate to avoid the clinical trial requirement, CFDA appears to be favoring copycat devices at the expense of innovative ones.
Whitney gave no indication that CFDA reviewers treat foreign companies differently from local manufacturers during her talk at Babson College.
Building good relationships with the submission reviewers is crucial, she said, for they can use discretion when interpreting the CFDA relevant regulations. Whitney praised the professionalism of the reviewers, for whom she has the "highest respect."
She concurred with the audience that some of the regulations are perplexing, notably the strict definition of a predicate device and requests for proprietary information.
Clearly, the biggest regulatory question facing med tech companies is whether they will need to conduct a Chinese clinical trial to secure approval of their devices. In a nutshell, companies need to carefully consider which CFDA-approved devices to propose as a predicate device in order to try and avoid the clinical trial requirement. If sponsors are unable to convince the CFDA of an adequate predicate, the magnitude and type of trial must be negotiated with the agency.
And Whitney pointed out that CFDA has released few guidance documents about proper conduct of the trials. "So that's really a big rock hanging over our head," she said.
-- Varun Saxena (email | Twitter)