Asia Regulatory Roundup: CFDA Seeks Feedback on Guidance for Medical Device Clinical Trial Sites (8 August 2017)

Welcome to our Asia Regulatory Roundup, our weekly overview of the top regulatory news in Asia.

NPPA Moves to Block Manipulation of Stent Margins, Advance Knee Implant Price Probe

The National Pharmaceutical Pricing Authority (NPPA) of India has revised its rule on the pricing of coronary stents to stop manipulation of profit margins. NPPA’s addendum clarifies the definitions of “manufacturer” and “distributor” and prohibits that latter from making margins of more than 8% on the sale of stents.

The agency has added two paragraphs to the drug pricing rule India adopted in February. The first paragraph restates the definition of “manufacturer” as “any person who manufactures or imports or market drugs for distribution or sale in the country.” Having established that definition, the rules state anyone who “imports stents directly without having registration certificate in Form 41” is a distributor.

This affects the trade margins companies can set for coronary stents. As the second new paragraph states, distributor trade margins on stents are capped at 8%. Any company that charges more than 8% must pay back the excess plus interest. Bhupendra Singh, the chairman of NPPA, described the action as the agency “[plugging] the gap for ‘manipulating’ trade margins in coronary stents” in a post on Twitter.

The closing off of a loophole that enabled companies to increase their margins shows the NPPA’s willingness to act to ensure its stent pricing rules have the desired effect. NPPA also displayed that willingness in a separate action it took on the same day it published the rule change.

The other action took the form of a demand notice NPPA sent to Metro Heart Institute. NPPA accused the hospital of overcharging two patients. The patients underwent angioplasty before the pricing rules came into force and were charged the old, full price. However, as the hospital billed the patients on or after 14 February, the pricing rules apply. The hospital must repay the difference plus interest of 15% a year.

NPPA is enforcing the coronary stent pricing rules while working to analyze the markets for other medical devices. The agency advanced the latter agenda this week when it published the margins importers and distributors charge on femoral, tibial plate, insert and patella devices. NPPA found average total trade margins for the devices ranged from 211% to 449%. Distributors and hospitals account for the majority of the markup in price.   

The agency published the figures without comment. NPPA is now seeking feedback from industry.

Addendum, Singh Post, Demand Notice, NPPA Memo

CFDA Seeks Feedback on Guidance for Medical Device Clinical Trial Sites

China Food and Drug Administration (CFDA) has released draft rules detailing the capabilities sites need to run medical device clinical trials. The rules build on efforts to raise the standards of clinical trials of drugs by applying similarly rigorous rules to centers that test medical devices in humans. 

CFDA wants these centers to meet certain minimum requirements. The agency expects trial sites to have clinical trial management systems, principal investigators experienced in running device studies and meet good clinical practices. CFDA is proposing to restrict the testing of Class III devices to tertiary-level medical institutions. A slightly different set of criteria apply to the running of trials of in vitro diagnostics.

The guidance also calls on trial sites to submit self-inspection reports. CFDA wants these reports to include overviews of the clinical trial management personnel and system, ethical review setup and arrangements for dealing with serious adverse events and other emergencies. Sites must upload the reports along with documents such as their medical qualifications and licenses to a CFDA filing system. CFDA will publicly disclose basic information shared by the trial sites.

That is not the end of the reporting requirements. CFDA also wants trial sites to refile information whenever there is a change to their personnel or other aspects of their operations. If sites want to stop running trials, they must cancel their filing. Sites that continue running studies must submit annual summaries of their clinical trial activities.

CFDA is also working to ensure its own operation is equipped to enforce the rules. The agency wants its regional outposts to step up their oversight of medical device clinical trials and report back if they uncover evidence sites have failed to file accurate information about their operations. CFDA will bar sites found to have hidden relevant information or provided false records from running clinical trials.

The agency is accepting feedback on the draft until 25 August.

CFDA Notice (Chinese)

TGA Introduces New Package of Guidance on Licensing and Certification

The Therapeutic Goods Administration (TGA) of Australia has published a package of licensing and certification guidance documents. TGA thinks the package of new and updated documents clarifies the requirements for manufacturers of medicines and biologicals.

The documents do not change the regulatory processes and requirements governing licensing and certification. Rather, TGA has tried to better explain how existing processes apply to companies.

This has entailed the creation or modification of eight documents that apply to manufacturers of medicines and biologicals. One of the revised pages is a decision tree designed to help companies understand if good manufacturing practice (GMP) licensing or certification is needed. The new texts include documents covering declarations of intent to supply medicines to Australia, the transfer of manufacturing licenses and responsibilities linked to GMP clearance.  

One of the new documents covers the revocation of licenses. That text walks Australian companies through the process of requesting the suspension or revocation of a license. The document complements an existing text about the revocation of licenses when companies fail to pay their annual charges.

TGA Notice

CFDA Clarifies Position on Medical Device Clinical Trial Processes

CFDA has clarified two aspects of its rules on the clinical development of medical devices. The clarifications cover the window in which sponsors must initiate clinical trials and how study startup works when multiple local CFDA offices are involved.

Both updates seek to eliminate potential sources of confusion. In the case of study start deadlines, the confusion stems from when the one-year countdown starts in multi-center clinical trials. The CFDA update states the period begins once the lead clinical trial unit receives a registration test report. 

The second clarification covers the activation of multiple clinical trial sites. CFDA states sites can begin enrolling subjects once their own paperwork with the sponsor is complete. They do not need to wait until all sites have completed their paperwork.

In a post on its blog, regulatory consultancy Emergo framed the update as part of a broader increase in the frequency of clarifications made by CFDA.

CFDA Statement (Chinese), Emergo

Other News:

CFDA has released draft guidelines on the public disclosure of information about administrative punishment cases. The guidance is intended to ensure the timely and accurate release of details of such cases. CFDA has taken responsibility for coordinating the disclosure of information. One challenge raised in the guidance is the need to assess whether a piece of information is a trade secret or a threat to national security. CFDA is accepting comments until 5 September. CFDA Notice

CFDA has published a document about quality management practices in preclinical research. The text discusses the organizational features and personnel sites need to run preclinical research programs. CFDA also addresses the features preclinical research facilities must possess, such as the ability to effectively isolate different species of animals used in experiments. CFDA Guidance