Asia Regulatory Roundup: CFDA Offers Draft Guidance on Generic Drug Manufacturing Inspections (3 January 2017)

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

TGA Ends OTC Status of Codeine Drugs Following Review

The Therapeutic Goods Administration (TGA) of Australia has reclassified codeine-containing drugs as prescription-only medicines. TGA decided to prohibit over-the-counter (OTC) sales of products containing codeine after reviewing the safety and efficacy of the painkiller and assessing how it is handled by foreign regulators.

In reaching the decision, TGA collated research regarding the safety and efficacy of codeine in a 101-page report, commissioned KPMG to assess the regulatory, social and economic implications of the reclassification and drew on feedback provided at two meetings of the Advisory Committee on Medicines Scheduling (ACMS). This led TGA to conclude the benefits of retaining the OTC status of codeine-containing medicines fail to outweigh the harm caused by such products.

ACMS provided details of the harm caused by codeine-containing medicines. The committee told TGA the active ingredient is associated with liver damage, stomach ulceration and perforations, low blood potassium levels, respiratory depression, death and other severe health outcomes. Some of the health problems associated with codeine stem from patients using it to treat chronic pain, despite the drug not being intended for long-term use.

Making patients go to doctors to get prescriptions for codeine-containing products should cut such misuse of the painkiller. The modeling report produced by KPMG forecast the reclassification of codeine would cut deaths from accidental or deliberate codeine overdose, improve quality of life and lower the risk of dependency. KPMG compared the consequences of reclassifying codeine to alternative approaches, such as reducing pack sizes and adding warning labels.

That TGA ultimately rejected these alternatives as, in part, a consequence of the availability of other OTC painkillers. Paracetamol, ibuprofen and non-codeine cold and flu treatments will meet the needs of some patients once the painkiller is reclassified. Some other patients will need to discuss their options with their doctors. TGA has given patients and industry time to prepare for the reclassification. The change will take place in February 2018. 

The delay between the decision and implementation is in keeping with the length of time it has taken TGA to move toward reclassification. ACMS discussed the topic in July 2015, and TGA made an interim decision three months later. That decision prompted complaints, compelling TGA to carry out a more comprehensive analysis of the implications of reclassification.

TGA Update, Safety Review

CFDA Posts Draft Guidelines on Generic Drug Site Inspections

China Food and Drug Administration (CFDA) is seeking feedback on draft guidelines about on-site verification of the quality and efficacy of generic drugs. The regulator has released four draft documents detailing its proposed stance on using field inspections to assess the quality of generic drug operations and confirm the authenticity of records kept at facilities.

The four documents cover the founding principles of on-site verification, when inspections should be performed and how the process applies to production plants and clinical trial sites. Collectively, the texts continue CFDA’s efforts to raise the standards of generic drugs developed, produced and sold in China. With earlier initiatives having weeded out substandard applications, the latest push seeks to establish a rigorous on-site inspection program capable of enforcing regulatory standards.

CFDA plans to send teams of two or three inspectors to assess sites. At least one member of the team should have laboratory experience of drug quality control. The proposed composition of the inspection team is the same for inspections of local and overseas facilities, but the strategy differs in other regards. Notably, CFDA is proposing a different inspection schedule for local and overseas sites that reflects the burden of assessing operations located outside China.

Situations in which the regulator will perform inspections include the discovery of problems during conformity assessments and the identification of issues with reporting. In some situations, CFDA will give the company advanced notice of its visit, but the regulator also plans to conduct surprise inspections. Organizations that interfere with CFDA’s ability to inspect their sites — for example by not providing access to documents or areas of facilities — will be deemed non-conformant.   

CFDA is accepting feedback on the drafts until 20 January.

CFDA Notice (Chinese)

CDSCO Sets out Risk-Based Schedule for Vaccine Facility Inspections

India's Central Drugs Standard Control Organization (CDSCO) has set out its schedule for the inspection of vaccine manufacturing facilities. CDSCO will send teams to conduct follow-up visits of manufacturers that fell short of standards in their most recent inspection, and embark on a fresh round of annual assessments of facilities.

Many vaccine manufacturers are set to undergo follow-up inspections in the first half of 2017 as a consequence of having failed to meet all requirements last time CDSCO visited. Exceptions include facilities run by GlaxoSmithKline, Serum Institute of India and Cadila Healthcare, all of which were found to be in compliance with vaccine regulations at their most recent inspections.

These organizations are only set to undergo annual inspections. Manufacturers with outstanding compliance issues will undergo annual inspections after CDSCO has performed a follow-up visit to assess corrections made since its last evaluation. Companies scheduled for follow-up visits include Panacea Biotec and Chiron Behring Vaccine.

Publication of the schedule of inspections comes weeks after CDSCO revised its position on the issuance of licenses to manufacture vaccines. Companies will now receive licenses within days of applying and undergo inspection later. The inspection schedule clarifies the new process will result in annual inspections, unless a risk analysis permits a different timetable.

Some manufacturers may also undergo inspections related to prequalification by the World Health Organization (WHO). CDSCO will schedule additional regulatory visits “as and when inspections are planned by WHO for prequalification.” The regulator will update the Central Inspection Plan once these additional assessments are scheduled.

CDSCO Schedule

India Steps up Enforcement of Radiopharmaceutical Regulations

The Drug Controller General of India (DCGI) has stepped up enforcement of regulations covering the import of radiopharmaceuticals. DCGI gave importers 45 days to comply with the regulations at a meeting late last year, and has decided against extending the transition period.

Radiopharmaceutical importers were given the 45-day ultimatum at a meeting with officials at CDSCO’s headquarters in November. Regulators called the meeting after becoming worried by the failure of organizations to comply with existing regulations. Given the low level of compliance at the time of the meeting, DCGI Dr. GN Singh gave importers 45 days to bring their operations up to standard.

The 45-day transition period ended on 21 December. Singh wrote a letter one week later to tell radiopharmaceutical importers the transition period will not be extended and strict compliance with the regulations is now expected. Importers of radiopharmaceuticals must obtain no-objection certificates from the Atomic Energy Regulatory Board, but, prior to the November meeting, compliance was falling short of DCGI expectations.

“This cannot be tolerated when we want to provide world class facilities to our patients,” Singh told DNA.

DCGI Notice, DNA

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