Posted 28 March 2017
By Nick Paul Taylor
Welcome to our Asia Regulatory Roundup, our weekly overview of the top regulatory news in Asia.
India Offers Fast-Track Approvals to HIV, Hepatitis Combination Products
The Drug Controller General of India (DCGI) is offering fast-track approvals to combination products to treat HIV and hepatitis B and C. DCGI Dr GN Singh is prepared to waive the need to run clinical trials and truncate the regulatory submission process to cut the time it takes for sponsors to bring combination products to market.
Singh is offering an array of regulatory benefits to companies that develop combination products of HIV and hepatitis drugs. The fast track program is primarily aimed at antivirals recommended for concomitant use by World Health Organization (WHO) guidelines, but Singh will also accept and assess expressions of interest from manufacturers of other rational combinations.
The goal is to ensure drugs WHO sees as working effectively together are available as combination pills in India, regardless of whether other regulators have approved co-formulations of the constituent antivirals. Singh thinks the risks and benefits support the fast tracking of drugs never previously formulated together, provided WHO recommends the concomitant use of the current, individual products.
Companies with experimental products that meet these criteria will receive special treatment. Importantly, Singh is open to using the “extreme urgency” provision of the Drugs and Cosmetics Rules to waive clinical trials of combination products. Singh is also encouraging sponsors to apply for their bioequivalence no-objection certificate and new drug application (NDA) simultaneously.
The regulator may accept NDAs featuring “abbreviated” data for pre-screening if the manufacturer commits to generating more evidence on the combination before approval. For the bioequivalence filing, companies can initially seek clearance on the basis of batches made at pilot scale before adding results from commercial lots following the scale up of their manufacturing operations.
Singh put forward the fast-track pathway at the recommendation of the apex committee, which thinks it is in the public interest to single out HIV and hepatitis combination treatments for special attention. The recommendation stems from recognition the viruses are major health problems in India. An estimated 52 million people are chronically infected with hepatitis B or C. More than 2 million people live with HIV. Less than half of patients eligible for free antiretroviral treatment receive the medication, suggesting the problems run deeper than a lack of combination products.
TGA Tweaks, Finalizes Antibiotic Resistance Guidance
The Therapeutic Goods Administration (TGA) of Australia has finalized guidance to help sponsors of antibiotics generate pre and postmarket data on the risk of microbes developing resistance to their products.
TGA first introduced guidelines on antibacterial resistance risk data in 2007, before going on to propose a revised set of interim recommendations in 2014. The final text adopted this week draws heavily on the earlier proposals. TGA described the changes it has made as minor amendments in response to feedback and editorial revisions.
The goal of the document is to advise manufacturers on when to include antibiotic resistance data and what to do in these situations. Manufacturers of antibiotics should use the guidance whenever they register a new medicine or make changes to an existing drug. Filings for the use of a drug in a new indication, introduction of a new dosage form and changes to the product information are covered by the guidance.
TGA has provided manufacturers with a list of information they should include in these situations, from basic details such as the chemical name through to characterizations of the hazard, exposure, impact and risk associated with the product. The guidance also offers an overview of how firms should approach the characterizations. For hazard characterization, for example, TGA recommends sponsors look at antibiotic resistance patterns and the genetics of resistance.
TGA Guidance, Interim Draft
CFDA Faults GMPs at Swiss Manufacturer, Blocks Imports After On-Site Inspection
China Food and Drug Administration (TGA) has found fault with the good manufacturing practices (GMPs) of a Swiss manufacturer. CFDA inspectors made the observations during a visit to the OM Pharma facility that makes lyophilized bacterial lysates.
A summary of the inspectors’ findings published by CFDA lists issues with the fermentation process as being among the ways in which the operation fell short of expectations. The inspectors assessed the plant against China’s quality management practices for pharmaceuticals. Having found the site lacking in this regard, CFDA has blocked the import of the products.
OM Pharma is a company with an 80-year history, the past eight years of which have been spent as part of Galencia. The manufacturer attracted the interest of Galencia on the strength of bacterial formulations designed to rally the immune system against respiratory and urinary infections. CFDA’s observations relate to the respiratory product, Broncho-Vaxom.
The publication of details of the inspection of OM Pharma comes 14 months after CFDA signalled its intention to increase oversight of foreign manufacturers. In January 2016, CFDA issued notices detailing GMP failings at three overseas plants and criticizing a fourth — run by India’s Aurobindo Pharma — for impeding the work of inspectors. Those notices also led to import blockades.
Since then, CFDA has proposed inspection guidelines and schedules for oversight of overseas generic production plants.
CFDA Notice (Chinese)
NPPA Chides Manufacturers for Approach to Pharmaceutical Database
The National Pharmaceutical Pricing Authority (NPPA) of India has written to drug manufacturers to ask them to change their behaviour regarding its database. Having been compelled to pressure manufacturers to register, NPPA now finds itself inundated with requests to change records.
In a circular to manufacturers and trade groups, NPPA has asked companies that want to correct or delete an entry on the Integrated Pharmaceutical Database Management System (IPDMS) to send it an email. The request comes in response to the actions of manufacturers.
NPPA said “many” companies are requesting to change entries, which, it notes, they themselves filed originally. The requests relate to duplicate and incorrect entries. As NPPA needs to verify the requests, it wants companies to contact it via email, not send staff in person “without any prior intimation or appointment” as is happening at the moment.
The problems began in January when NPPA asked manufacturers to register themselves and their products on the database. NPPA said the response to that request “was not very encouraging” and consequently the price watchdog changed tack the following month. The revised approach made compliance with IPDMS a prerequisite for certain pricing processes. That prompted action from the industry but created the problems NPPA is seeking to address in its latest circular.
NPPA has stepped up its investigations into allegations of overcharging for stents by hospitals. With many hospitals either providing unsatisfactory responses to NPPA’s initial inquiry or failing to respond at all, the price watchdog has begun full audits into some of the institutions. NPPA is also continuing to add new hospitals to the probe, which now covers 40 sites. NPPA List
TGA is analyzing two-year data from clinical trials of Abbott Vascular’s Absorb BVS. The product became the first bioresorbable stent to come to market last year. Since then, two-year data on the use of the stent has revealed an increased risk of major adverse cardiac events. That prompted TGA to follow United States officials in issuing a notice about the safety of the device. TGA Notice