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Asia Regulatory Roundup: Australia Aligns Sartan Rules to EMA as Singapore Finds NDMA in Ranitidine Drugs

Posted 17 September 2019 | By Nick Paul Taylor 

Asia Regulatory Roundup: Australia Aligns Sartan Rules to EMA as Singapore Finds NDMA in Ranitidine Drugs

Welcome to our Asia Regulatory Roundup, our weekly overview of the top regulatory news in Asia.
 
Australia Aligns Sartan Rules to EMA as Singapore Finds NDMA in Ranitidine Drugs
 
Australia’s Therapeutic Goods Administration (TGA) has aligned its requirements for sartan medicines with those adopted in Europe. The action coincided with news from Singapore about the presence of N-nitrosodimethylamine (NDMA), one of the key sartan impurities, in GlaxoSmithKline’s Zantac and other ranitidine medicines.
 
NDMA and related N-nitroso compounds have been a focal point for regulators since the substances were found in the sartan class of medicines. To ensure patients are not exposed to dangerous levels of the carcinogens, TGA has set interim acceptable limits that will apply for a two-year period. During that transition period, TGA will apply the interim limits set by the European Medicines Agency (EMA) and deal with manufacturers that exceed them on a case-by-case basis.
 
The approach enables TGA to push for the elimination of contaminants without the risk it will cause more harm than good by taking a very hard line from the start. TGA wants manufacturers to tell it if they find N-nitroso contaminants during the transition period. Manufacturers should not release products that exceed the interim limits, but TGA will consider the circumstances of each case.
 
TGA wants manufacturers to use the transition to review their manufacturing processes and perform risk assessments to show whether the conditions for N-nitroso compound formation are present. The reviews should pay particular attention to the use of nitrite and secondary or tertiary amines. By the time the transition ends in September 2021, TGA expects N-nitroso tests to have quantification limits of 0.03 parts per million, at most. The interim acceptable limits are far higher.
 
News of TGA’s plan emerged the day before Singapore’s Health Sciences Authority (HSA) stopped the sale of eight products containing ranitidine, an active ingredient used in medicines to lower stomach acid. HSA took the action after finding NDMA in the products. The United States Food and Drug Administration has also found NDMA in ranitidine medicines.
 
TGA Notice, HSA Alert
 
TGA Seeks Feedback on Plans to Clarify Regulatory Status of Assistive Technologies
 
TGA has begun a consultation about the regulation of technologies designed to assist people with disabilities. The consultation covers proposals intended to clear up confusion about when a product can be excluded from regulations on therapeutic goods.
 
Today, TGA exempts “household and personal aids, or furniture and utensils, for people with disabilities” from therapeutic good regulations. However, the wording of the criteria for exemption has caused “significant confusion,” TGA said, leading to inconsistent application of the regulations. To address the confusion, TGA has put forward three different proposals.
 
TGA is considering replacing the current “household and personal aids” exemption language with the terms “assistive technology” or “low-risk assistive technology,” or a list of specific products outside the scope of therapeutic goods regulation.
 
Each of the proposals has different implications for companies that sell assistive technologies. TGA thinks the adoption of the term “assistive technology” may expand use of the exemption. In contrast, limiting the exemption to “low-risk” devices could force the manufacturers of some currently exempt products to seek premarket approval under the medical device regulations.
 
TGA wants people and organizations that would be affected by the changes to provide feedback on all the proposed options. The comment period is open until 25 October.
 
Consultation Document
 
China Shares Drug Traceability Standards Documents for Consultation
 
China’s National Medical Products Administration (NMPA) has shared a clutch of documents on drug traceability standards for consultation. The documents detail the datasets NMPA wants members of the drug supply chain to include in their traceability systems.
 
NMPA and other parts of the Chinese state have taken a series of actions this year to put legislation and regulations in place to support a drug traceability system. Those actions include the recent passage of changes to the drug administration law that mandated the introduction of a system for tracing drugs through the supply chain.
 
To further the initiative, NMPA has published guidance on basic drug traceability datasets aimed at a range of players in the supply chain, including manufacturers and distributors of medicines.
 
NMPA is accepting feedback on the documents until 11 October.  
 
NMPA Notice (Chinese)
 
Pakistan Sets Fees for Regulatory Requests Related to Clinical Trials
 
The Drug Regulatory Authority of Pakistan (DRAP) has set the fees for a range of regulatory services related to clinical trials. The fees apply to organizations that want to operate as bioequivalence study centers, sponsors that want to run clinical trials and other groups involved in human research.
 
Under the structure, the highest possible charge applies to applications to renew licenses to work as a bioequivalence study center, contract research organization or bioanalytical laboratory for clinical research. If DRAP receives the application on time, it will charge the same PKR 300,000 ($1,900) fee as for new filings. However, DRAP will add PKR 100,000 to the fee if the filing is late.
 
DRAP will treat applications received 60 days after the expiration of a license as a fresh filing. The agency applied a similar model to other fees. For example, filings to renew clinical trial site licenses are subject to a PKR 100,000 fee, plus a further PKR 50,000 for late submissions.
 
The publication of the fee structure follows the adoption of the Bio Study Rules, 2017. The rules mandated the payment of fees in association with clinical trial applications but lacked details of how much DRAP would charge.
 
DRAP News
 
TGA Advertising Actions Lead to $20,000 in Penalties for Drug Promoters
 
TGA has shared details of fines paid by two companies in relation to advertising therapeutic goods. Redback SARMs paid the bigger of the two fines, handing over AU$15,210 ($10,455) after TGA hit it with infringement notices for the alleged advertising of prescription-only substances.
 
The infringement notices covered substances including selective androgen receptor modulators (SARMs) and melanotan II. TGA has repeatedly gone after SARMs since taking responsibility for the handling of complaints about the advertising of therapeutic goods in Australia.
 
TGA’s second notice related to PharmaCare, which paid AU$12,600 after allegedly continuing to advertise Sambucol Cold & Flu Kids Liquid after it was removed from the Australian Register of Therapeutic Goods (ARTG).
 
The cancellation of the ARTG listing followed a TGA investigation that found, “The scientific evidence PharmaCare held to support some of the indications for the medicine was inadequate.” That led TGA to rule the ARTG application was “false or misleading.” 
 
Redback Notice, PharmaCare Notice
 
Other News:
 
TGA has extended the fee-free period for companies transitioning existing listed medicines to permitted indications. The 18-month fee-free period was due to end earlier this month. However, TGA has extended the fee-free period out to the end of the transition to the permitted indications in March 2021. TGA took the action to “minimize impacts on industry and help ensure continued market access for transitioning listed medicines.” TGA Notice
 
China’s Center for Drug Evaluation (CDE) has translated ICH guidelines on the guiding principles for elemental impurities into Chinese. ICH finalized the English-language version of the document earlier this year to provide the industry with a process to assess and control elemental impurities based on risk management principles. CDE is accepting feedback on the translation for the next month. CDE Notice (Chinese)
 

Tags: CDE, DRAP, HSA, NMPA, TGA

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