AP

Navigating China’s regulatory environment can be challenging for medical device and diagnostic companies. That challenge, however, just became easier thanks to new guidelines that may allow approval of products in China without conducting additional clinical trials. This new approval path provides an opportunity for developers to strike quickly and deliver new products to market ahead of their competitors – but only if they can present clear evidence demonstrating the device can meet their strict approval criteria.

This new option came about in May 2015 when the China Food and Drug Administration (CFDA) released new technical guidelines governing medical device clinical evaluation for registration of Class II and III devices in China. The guidelines specifically cover principles for clinical evaluation of these devices, including which ones are exempted from clinical studies and which may be eligible for a clinical study waiver. The key to determining whether a device will require additional clinical studies is if the developer can demonstrate that the product is substantially equivalent to an already registered predicate product on the market in China or the rest of the world.

Currently there are five paths to registration for Class II and Class III medical devices (the highest in terms of risk of China’s three medical device classes): 

  1. Devices listed in the CFDA’s “Catalogue of Medical Devices Exempted from Clinical Trials” could be exempted and proceed to registration.
  2. The applicant conducts a traditional in-country trial to demonstrate safety and performance of the device.
  3. The applicant provides non-clinical evidence of the new device to demonstrate safety and performance of the device.
  4. The applicant conducts a study, using and analyzing foreign (i.e. outside China) pre-registration clinical trial data in either the origin country or license-holder country, to prove no difference in populations of different ethnic makeup.
  5. The applicant (under new rules that took effect in May 2015) assembles a clinical evaluation report (CER) demonstrating substantial equivalence to an approved device, including the composition, material, and safety and performance requirements.

For devices not included in the first path (listed in the catalogue), the fifth option is by far the fastest, most economical and feasible.  It is especially useful for companies bringing new iterations of existing devices to market because they can use the first-generation product as the comparator.

This path requires developers to produce a comprehensive CER that provides clear clinical evidence establishing the safety and performance of the device.

The CER required by the CFDA is mainly based on US Food and Drug Administration (FDA) guidelines to demonstrate substantial equivalence, as well as biostatistical and meta-analysis used for CER registrations in the EU. But the resulting guidelines are unique to China, and clearly lay out what companies need to compile to avoid a full clinical trial as part of the registration process.

To meet the CER guidelines, developers need to assemble a team of experts that includes:

  • A biostatistician who, using data collected from related trials worldwide, can create a profile demonstrating that the safety and performance measures fall within an acceptable range to the comparator.  The biostatistician also conducts a meta-analysis to analyze data quantity and quality.
  • A regulatory expert who understands the regulatory environment in China and the country of origin for the device, and can guide the team in gathering the evidence that will be required to support approval.
  • A medical writer who has the expertise to conduct a global literature review and assemble the data from related trials conducted anywhere in the world. This piece of the CER is critical for collecting the necessary data to demonstrate equivalence related to safety, performance and efficacy.

Ideally, medical device manufacturers should assemble the expert team early in the development process and conduct a gap analysis to determine whether the device can meet the strict criteria for a CER approval path. This is especially important if there is any question as to whether there is an appropriate comparator to demonstrate equivalence, or if the new device varies significantly from the original.  In many cases, organizations might not have all three of these skill sets in-house, and have to work with a third party provider who has the depth of expertise to deliver an effective CER as efficiently as possible.

These new guidelines can deliver a significant competitive advantage for device manufacturers interested in bringing new products to market in China, but only if the companies get it right. A well-developed CER that takes all of the regulatory, biostatistical and literature review requirements into account, will increase the chance of approval by the CFDA, ensuring developers generate the most market value for their product.