Asia Regulatory Roundup: China Reports 25% Fall in Initial Medical Device Registrations

Welcome to our Asia Regulatory Roundup, our weekly overview of the top regulatory news in Asia.
 
China Reports 25% Fall in Initial Medical Device Registrations
 
China’s National Medicinal Products Administration (NMPA) has reported a 25% year-on-year drop in initial registrations of medical devices. The fall dragged the overall level of registration activity down to its lowest level since China began publishing data on the topic in 2013.
 
Last year, NMPA approved 1,128 initial medical device registrations. When renewals and changes are factored in, the overall number of registration approvals for the year totals 5,528. In 2017, NMPA approved 1,507 initial registrations and 8,579 filings overall. Since the start of records in 2013, China had never previously approved fewer than 7,530 registrations in a year.
 
NMPA provided no explanation for the sharp fall in registrations. The trend was driven by declining activity in multiple areas. The number of renewals approved was down 59% on the prior period.  There were similarly significant declines in the numbers of approvals of filings to import and register Class III medical devices. Registrations by provincial drug regulatory authorities fell sharply, too. 
 
The number of registration changes approved by NMPA was the exception to the downward trend. NMPA signed off on 21% more changes in 2018 than the previous year, potentially reflecting growth in the number of medical devices already registered for use in China.
 
NMPA shared the data in its report on medical device registrations. The report documents NMPA’s efforts last year to improve the registration system, for example through the creation of regulations on bringing in vitro diagnostics to market.
 
Those efforts have continued into 2019. This week, NMPA published technical guidelines on the electronic submission of medical device registration applications and an accompanying document on  its electronic declaration information system. NMPA published the documents as part of its work to implement a 2017 government order about the reform of the medical device approval system.
 
NMPA Report, Technical Guidelines, More (all Chinese)
 
India Demands Information From Manufacturers of Potentially Irrational FDCs
 
The Central Drugs Standard Control Organization (CDSCO) has asked manufacturers of fixed-dose combinations (FDCs) deemed irrational by an expert committee to share data on their drugs. 
 
CDSCO’s request continues its multi-year effort to stop the sale of irrational drug combinations that came to market via a regulatory back door. The Drugs Technical Advisory Board (DTAB) looked at the matter in April, leading to the formation of a subcommittee that will review the FDCs of disputed rationality. To support these assessments, the subcommittee has asked manufacturers for information.
 
Specifically, the subcommittee wants manufacturers to complete a form that requests information such as the therapeutic justification for each ingredient in the FDC and the rationale for giving them in combination. The form suggests several potential reasons for combining drugs, including reduced costs and increased efficacy.
 
Manufacturers will need to back up their claims. The subcommittee has requested one-page summaries of evidence to support claims of rationality, plus similar summaries of the pharmacokinetics and pharmacodynamics. Other requests for evidence include safety and efficacy data and, if available, details of recommendations in clinical guidelines and approvals in established markets such as the United States.
 
DTAB’s subcommittee has requested the information on around 300 products. The list features some FDCs that consist of 10 or more ingredients, alongside simpler combinations such as tablets made up of paracetamol and the non-steroidal anti-inflammatory drug aceclofenac.
 
The subcommittee has given manufacturers until the end of June to submit the information.
 
CDSCO Notice
 
China Seeks Feedback on Draft Real-World Evidence Guidance
 
China’s Center for Drug Evaluation (CDE) has published draft guidance on using real-world evidence to support drug development. The guideline features practical advice for companies that want to use data from outside randomized controlled trials to demonstrate the safety and efficacy of drugs.
 
There are precedents for the use of real-world evidence in Chinese drug development programs. Last year, NMPA cleared bevacizumab, sold under the trade name Avastin, for use in combination with platinum-based chemotherapy on the basis of evidence from three real-world studies. Yet, there is limited advice on the application of real-world evidence to Chinese drug development programs.
 
CDE has published several documents, including an English language text, to address that gap. In its key considerations for using real-world evidence, CDE outlines the current use of such data — both inside China and overseas — and discusses how to evaluate and use this source of information.
 
The document features sections describing the basics of pragmatic clinical trials, single-arm studies using historical controls and observational research. CDE identifies weaknesses with all the forms of real-world study but does not rule out their use in the generation of evidence to support regulatory decisions.
 
For example, while CDE notes that the presence of confounding factors in observational studies can make it hard to draw firm conclusions, it also describes the elements that can give it confidence in the reliability of the data they generate. These elements include the type of statistical analysis methods used. CDE dedicates an appendix to the guideline to the choice of statistical method.
 
Elsewhere in the guideline, CDE describes scenarios in which real-world evidence may be used to support drug development and regulatory decisions, citing the bevacizumab approval as an example, and discusses the evaluation of the evidence.
 
CDE is accepting feedback on the draft for the next three months.
 
CDE Notice (Chinese)
 
New Zealand Moves to Mitigate Confusion About Parkinson’s Drugs
 
The New Zealand Medicines and Medical Devices Safety Authority (Medsafe) has responded to the potential for confusion between levodopa-containing treatments for Parkinson’s disease. Medsafe fears the risk of confusion has been exacerbated by supply issues affecting Merck’s Sinemet.
 
Medsafe issued an alert about the need for healthcare professionals to take care when prescribing and dispensing levodopa-containing products in April and followed up with more information this week. The agency’s concerns stem from the availability of multiple drugs in a wide range of strengths and formulations. This diversity could lead to patients receiving the wrong drug.
 
Those risks are long standing, but the Sinemet supply issue and response to it create new challenges. The need to switch patients to new drugs has been implicated in five adverse event reports.
 
In an attempt to clarify the situation, Medsafe has added a table detailing suitable substitutes for the Merck products that are in short supply. Depending on the dose of Sinemet, physicians should either switch patients to a US import of the Merck drug, a generic drug sold by Mylan as Kinson or another Mylan medicine that is not approved in New Zealand. The unapproved generic has been made available to ensure the continuity of supply during the Sinemet shortage.
 
The substitution table is one of several changes to the prior advice made by Medsafe. The agency has also updated its list of levodopa-containing medicines available in New Zealand and revised its advice to patients, prescribers and pharmacists.
 
Medsafe Alert
 
Other News:
 
China’s NMPA has published advice on the importation of reference drugs for use in clinical trials of biosimilars. The advice covers the choice of reference drug and the work sponsors may need to do before starting clinical trials. NMPA Notice (Chinese)
 
Australia’s Therapeutic Goods Administration (TGA) is seeking feedback from the industry and other groups affected by its work. The feedback will inform TGA’s efforts to improve its service. TGA Notice