Posted 10 January 2017
By Nick Paul Taylor
Welcome to our Asia Regulatory Roundup, our weekly overview of the top regulatory news in Asia.
CFDA Posts Guidance on Quality Control of Medical Devices
China Food and Drug Administration (CFDA) has posted guidance on quality control and finished product release for medical devices. The document details the procurement control procedures, finished product inspection rules and other processes CFDA wants companies to establish to ensure medical devices meet mandatory standards.
Most of the guidance document focuses on these processes, which CFDA splits into four groups: purchase control and inspection; process control and inspection; finished product inspection and release; and other relevant requirements.
The section on purchase control refers readers to separate guidance on vendor examination. CFDA wants enterprises to review that document when establishing procurement control procedures capable of ensuring purchased items meet requirements. In doing so, CFDA expects enterprises to subject purchased raw materials and components to verification processes commensurate with the influence they could have on product quality.
Inspection rules for incoming goods specifying names, sampling procedures, acceptance criteria, reference standards and other information are also needed.
The process control section establishes similar requirements for other aspects of product quality. CFDA covers management of the quality of intermediate products and production processes in the process control section. Specific points made by CFDA include a request for enterprises to consider the effect of computer software on quality when establishing processes.
CFDA uses the finished product inspection and release section to lay out basic requirements similar to those established for other quality control processes before going into greater detail into factors specific to this final step. Specific points include a demand for statistically-valid sampling programs.
Publication of the guidance document adds to a growing repository of up-to-date CFDA advice for the medical device sector. Last year, CFDA addressed a range of medical device topics, including the reporting of adverse events, a priority approval pathway and traceability. The activity was supported by the rapid growth of the medical device budget at CFDA.
CFDA Guidance (Chinese)
Missing Evidence in GMP Clearance Filings Prompts TGA to Restate Requirements
The Therapeutic Goods Administration (TGA) of Australia has restated the documents companies must include in good manufacturing practice (GMP) clearance applications. TGA took the action in an attempt to bring down the proportion of compliance verification applications that fail to include all of the necessary materials.
Companies use the compliance verification pathway to leverage reports from overseas regulators to gain GMP clearance in Australia without undergoing an inspection by TGA.
Currently, TGA estimates more than 60% of applicants for GMP clearance through the compliance verification pathway fail to provide a complete dossier. TGA contacts these applicants to ask them to provide the missing supporting evidence. With TGA now fielding approximately 2,000 compliance verification applications a year, chasing down materials for incomplete filings “is having a significant impact on [the agency’s] overall processing timelines,” the regulator said.
In an attempt to improve the quality of applications, TGA has listed the documents companies typically forget to include in their filings. The list includes the GMP agreement, a copy of the most recent inspection report, an up-to-date product quality review and a manufacturer’s declaration for active pharmaceutical ingredients (API). Other often-forgotten documents include lists of the inspections and regulatory actions related to the facility from the past three years.
TGA guidelines on GMP clearance require sponsors to include these documents in compliance verification filings. Failure to do so can result in TGA rejecting the request for clearance.
CFDA Follows TGA in Revising Stance on Codeine-Containing Drugs
CFDA has revised its position on drugs containing the painkiller codeine. The update, which follows shortly after TGA revised its regulation of the substance, tasks manufacturers with studying adverse reactions and calls on doctors to base prescribing decisions on updated risk-benefit analyses.
Faced with a painkiller linked to adverse events and prone to misuse, CFDA has enacted a suite of measures designed to ensure the safe use of codeine or alternative products.
CFDA’s measures include changes to the drug specifications for codeine. Notably, the text now warns long-term use of codeine can cause dependence, whereas the earlier version only said use of large doses can cause death. The new specifications also add populations in which the drug is contraindicated and situations in which it should not be used, such as when driving vehicles.
The onus for making some of the improvements falls on manufacturers. CFDA wants producers of codeine-containing medicines to take an in-depth look at how and why adverse events occur. In parallel, manufacturers should take steps to guide physicians toward rational painkiller use.
Physicians also have a role to play in the strategy outlined by CFDA. The agency expects doctors to carefully read the revised information on codeine and take the latest advice on the benefits and risks of the painkiller into account when deciding which product to prescribe.
CFDA Notice (Chinese)
DCGI Establishes Pathway for First-Time Imports of Certain APIs
The Drug Controller General of India (DCGI) has established a regulatory pathway for first-time imports of APIs used in already-approved finished formulations. Creation of the pathway brings clarity to a gray area that has been under consideration at the Indian regulator for “quite some time now,” DCGI Dr. GN Singh said.
In a letter to Indian regulatory offices, Singh said companies in this situation should use Form 44. The form covers applications for permission to import or manufacture a new drug. Companies should also submit Form 45A, which covers new bulk drug substances, and provide the necessary fees and supporting information. Details requested by Singh include the product specification with limits of impurities and published literature.
The Central Drugs Standard Control Organization reached the position on the pathway for importers facing the scenario after assessing the situation in light of the existing requirements and guidelines.
AstraZeneca, Bristol-Myers Among Latest Drugmakers to go Through CFDA Verification Scheme
CFDA has released the names of 14 more products that have gone through its clinical trial data verification program. The latest batch of drugmakers to have their data verified by the regulatory agency includes AstraZeneca, Bristol-Myers and Merck.
Officials published a list of the first 55 products to undergo verification in November. That list was skewed toward foreign companies that applied to import products into China. The latest update is similarly balanced, with nine of the 14 applications being for the right to import. Astellas, Eisai and Pharmacyclics, now owned by AbbVie, sit alongside AstraZeneca, Bristol-Myers and Merck on the list.
Five of the applications are from Chinese companies. Of these, three are supplementary filings and two relate to generic drugs.
The verification of the clinical trial data is another step in a campaign to improve the quality of drugs made and sold in China.
CFDA Release (Chinese)
CFDA has created guidelines on clinical trials of cochlear implants. The guideline is intended to standardize and guide clinical trials of the class of medical devices, which replace the function of damaged inner ears. Subject selection, clinical trial duration and evaluation criteria are among the topics addressed in the guideline. CFDA Notice (Chinese)
China has released a document discussing the administrative measures relating to CFDA capital construction projects. The document is an attempt to ensure project quality by standardizing construction practices. Other goals include improved decision making and returns on investment. CFDA Notice (Chinese)