China’s provincial government for Hainan Province has two sets of medical devices going through the urgent medical device needs program, but leveraging this program for regulatory approval in China is still no small undertaking. One complication is that any real-world evidence gathered in Hainan might not suffice for nationwide regulatory approval, but patient recruitment is also difficult, suggesting that would-be participants have a solid back-up plan at the ready in case the data gathering effort in Hainan comes up short.

Grace Palma, of China Med Device LLC, in North Andover, Mass., said China’s National Medical Products Agency (NMPA) has been busy in the first seven months of this year, posting a number of documents and guidances. One of these is a guidance for certification of transfer of manufacture to China, and Palma explained that NMPA had previously required any manufacturers that open new manufacturing sites in China to re-register the product. The agency will now only require that the manufacturer validate the consistency of its adherence to good manufacturing practices across the original and new manufacturing sites.

Two series of devices already in the program

Palma said the Hainan urgent needs devices program has been a hot topic since NMPA announced the program in 2019. The Hainan government officially kicked off the urgent medical devices program in October 2019 with a small number of devices, allowing them to be used despite lack of approval by the NMPA. The program was rolled out in Boao, the site of the Boao Super Hospital in the island province of Hainan. The hospital is known as a destination for domestic medical tourism, and thus boasts a patient population from across China.

A second batch of devices was picked for the April 2020 extension of the program, which is intended to leverage real-world data to support an eventual application for marketing authorization. The candidate device must meet urgent clinical needs, but Palma noted that NMPA’s nation-of-origin rules still apply. A device need not be a novel device type, but should at least present a substantial clinical improvement over the existing suite of offerings.

Palma noted that the RWD study data gathered from Boao would be drawn from “the specific environment of medical tourism,” adding that the patient population in any such study would have to include patients from all over China. This mechanism should allow data to accumulate more quickly than would otherwise be the case, but another benefit of this program is that patients are often paying for their own care, and thus payers needn’t be billed.

Palma said the Hainan government is putting forth a considerable effort “to make Hainan the next Hong Kong,” promising a considerable international transportation infrastructure. The program is perhaps more appropriate for technologies that are fairly mature, and simpler medical conditions are also helpful compared to more complex disease states. Devices for neurological uses are sufficiently complex and hazardous that the provincial government may be unwilling to admit them into the program for the time being, however.

Jane Lin, director of regulatory affairs for the Asia Pacific market at Johnson & Johnson of Franklin Lakes, N.J., said manufacturers that want to use real-world data in Hainan and elsewhere should couch that RWD effort in an overall strategy. Lin said the hospitals and physicians in Hainan have much less experience with clinical trials than their counterparts in other parts of the country, however, one of several limitations on the sheer volume of enrollment in Hainan.

Palma said Allergan plc, of Dublin, had enrolled a study of the company’s Xen gel stent for refractory glaucoma with the intent of accumulating at least 120 patients, and won approval for this class III device “in record time” of only six months. Lin noted that trials run in Hainan through this program should be supplementary to an overall strategy because the patient sample size can be limited by several factors, including that patients may quickly relocate back to their home province. Hainan serves as a test bed for NMPA’s real-world evidence program, which Lin said is accompanied by a guidance that is easier to follow than the U.S. FDA’s approach, thanks in part to greater specificity.

Outside-China data okay, but communication the key

Shamiram Feinglass, vice president at Danaher Corp, of Washington, said the key for the use of non-China clinical data for the RWE program is clear communication with the NMPA, particularly given that this program is new to the agency as well as to sponsors. Device makers should carefully consider whether the use of non-Chinese data is the most efficient way to get to approval, however, given that NMPA reviewers are not familiar with the use of such data.

Feinglass noted that NMPA is still working on a guidance for the use of overseas data, another rate-limiting factor on this source of evidence, adding that “I would always consider a back-up plan” if the sponsor has any misgivings about whether NMPA reviewers will accept the overseas data sets. One possible advantage to a China-only approach is that enrollment in China might be smaller than would be required from trial data from other nations.

Lin said NMPA reviewers are concerned about the differences in device performance between the various ethnicities in China, another reason to consider enrollment of a substantial patient volume in China. Hainan is at present the only location inside China that offers access to this RWE program, Lin said.

No Comments