Welcome to our Asia Regulatory Roundup, our weekly overview of the top regulatory news in Asia.
TGA Analysis of Paclitaxel-Coated Device Data Finds no Safety Signal
The Therapeutic Goods Administration (TGA) has analyzed Australian adverse event data on patients with paclitaxel-coated devices in light of a meta-analysis published last year. The meta-analysis found a link between the devices and increased risk of death, but no safety signal was seen in the TGA data.
TGA and its regulatory peers around the world have spent the eight months since the increased risk of death was identified in a paper published in the Journal of the American Heart Association
working to understand what, if any, threat paclitaxel-coated balloons and stents pose to patients. The devices are used to improve and maintain blood flow to the legs, thereby reducing the need for surgery to reopen blocked blood vessels.
The United States Food and Drug Administration (FDA) added weight to the meta-analysis when it concluded that, “There was a higher rate of mortality for the paclitaxel-coated stents and balloons.” However, TGA has not replicated the signal in its analysis of Australian data.
TGA’s dataset covers 10 paclitaxel-coated devices cleared for use in Australia and mainly features adverse events linked to problems with the deployment of the balloons and stents. These events typically took place on the day of the procedure. No deaths have been reported in Australia. It is possible that the adverse event data failed to capture deaths related to paclitaxel-coated balloons and stents, for example if the link between the death and a device was not apparent at the time.
In response to its findings and the other analyses, TGA has issued recommendations that are in line with those adopted by other agencies. TGA is advising healthcare professionals to “continue diligent monitoring” of patients previously treated with paclitaxel-coated devices and inform people who are considering receiving a balloon or stent that there may be an increased risk of long-term mortality.
Among patients with peripheral artery disease, TGA thinks alternative treatment options should be preferred until the safety signal has undergone further analysis. However, TGA noted that in some patients, notably people at high risk of the recurrence of vessel narrowing after surgery, the benefits of using paclitaxel-coated devices may outweigh the risks based on the current evidence.
China Approves Gilead HIV Drug Within 18 Months of EMA and FDA
China’s National Medical Products Administration (NMPA) has approved Gilead Sciences’ HIV-1 drug Biktarvy. The approval comes less than 18 months after regulators in the US and Europe authorized the treatment.
Biktarvy combines the dual nucleoside reverse transcriptase inhibitor backbone found in Descovy with an integrase strand transfer inhibitor designed to block the action of an enzyme that encourages viral replication. The drug is the latest in a line of treatments for HIV-1 developed by Gilead. FDA and the European Medicines Agency approved Biktarvy in February 2018 and June 2018, respectively.
Now, Gilead has added China to the list of territories in which Biktarvy is approved. Gilead won the approval on the strength of data from four ongoing Phase III clinical trials. According to the listings on ClinicalTrials.gov, none of the trials involved study sites in China. Gilead said the “trials are comprised of a diverse population of 2,414 participants ... including a wide range of adult age groups and races/ethnicities.”
The short lag, by historical standards, between approval in China and the West is further evidence of changes in NMPA’s approach to the authorization of new medicines. John Tsai, the head of global drug development at Novartis, discussed those changes in an interview with the Financial Times
this week, noting that, whereas the company once took an extra six years to get drugs to China, today, “The lag is pretty close to gone.”
, Financial Times
TGA Imposes ‘Liaison Fee’ on Some Filings That Rely on Health Canada Reports
TGA has imposed a liaison fee on compliance verification clearance applications that use exit notices from Health Canada. The fee reflects the additional burdens these applications place on TGA.
A mutual recognition agreement between TGA and Health Canada permits the use of inspection exit notices from the latter regulatory agency as supporting good manufacturing practice (GMP) evidence in Australian clearance applications. However, that option only applies when the exit notice covers a manufacturing facility located in Canada.
The divergence stems from differences in the information Health Canada includes in exit notices for sites inside and outside its borders. As there is less information in the notices for overseas sites, the materials fall short of the inspection report requirements set out in TGA’s GMP clearance guide.
TGA said it has been “actively collaborating” with Health Canada “to explore options for utilizing their evidence.” The current situation is that clearance submissions that use Health Canada exit notices for overseas sites require TGA to liaise with its counterpart in North America to gather extra details on the inspection.
To cover the cost of these activities, TGA has imposed a $700 fee for “obtaining evidence from an overseas regulatory authority.” The fee is per manufacturer, per site and per sponsor and will apply to compliance verification clearance applications currently under review at TGA, as well as all future submissions.
As Transition Nears End, TGA Starts Accepting Standalone Reformatted PI Filings
TGA has begun accepting the submission of reformatted product information as standalone filings. The change in approach comes around 17 months before the end of the transition to the new form.
After the approval of the new form late in 2017, TGA established a three-year transition period and told companies to adopt the new format whenever they updated their product information. At that time, TGA said it would permit standalone submissions of reformatted product information toward the end of transition period. The change would allow companies that had not needed to update their information to become compliant before the transition ended.
TGA has now opened up the submission process to standalone applications. Companies that want to make standalone submissions can file minor editorial change applications through the TGA eBusiness Services portal. TGA will exempt standalone applications from fees next year.
The agency shared details of the change in an update to its frequently asked questions about reformatting product information. TGA also used the update to change its advice on when companies can reformat their product information and whether other editorial changes are permitted.
Malaysia Moves License Renewal Process Over to Online Portal
Malaysia’s National Pharmaceutical Regulatory Agency (NPRA) has opened up its online portal to renewals of licenses to manufacture, import and wholesale medicines.
To use the portal, called Quest 3+, companies must buy and install a valid digital certificate in the form of a USB token. The certificate authenticates the user and identifies them in transactions that take place on the portal. NPRA also uses digital signatures for the purposes of authentication and integrity.
NPRA is now accepting manufacture, import and wholesale license renewal applications for 2020 via the portal. The portal is also used for transactions including product registration, variation, licensing, market sampling and renewal.
’s Center for Drug Evaluation
(CDE) published a notice about the examination of generic reference preparations. The notice features advice for applicants. CDE Notice