Asia Regulatory Roundup: Serious Injuries Linked to Devices in China Almost Double (31 May 2016)

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

TGA Reports Drop in Manufacturers Achieving Satisfactory Compliance

Australia’s Therapeutic Goods Administration (TGA) has reported a sharp drop in the proportion of domestic manufacturers achieving satisfactory levels of compliance during inspections. In the second half of 2015, no more than 81% of inspections identified satisfactory levels of compliance, compared to 97% in the same period of the preceding year.

As it stands, there is still some uncertainty about the exact proportion of inspections that identified subpar levels of compliance as close-out procedures are ongoing for 18% of the 114 of regulatory visits TGA conducted in the second half of 2015. However, even if compliance at all the outstanding sites is deemed to be satisfactory, the total proportion achieving this grade will be 81%. At worst, the proportion of inspections resulting in satisfactory levels of compliance could come in at 63%. Both figures are down on the corresponding period of 2014.

In the second half of 2014, TGA conducted 102 inspections, 97% of which resulted in rulings that the site achieved satisfactory compliance. The remaining 3% of sites were deemed marginal. In contrast, 18% of the closed-out inspections from the 114 TGA performed in the second half of 2015 led to rulings of marginal compliance. Unacceptable levels of compliance were identified at 1% of sites in the second half of 2015. Neither of the preceding periods included sites with unacceptable levels of compliance. The satisfactory compliance figure for the first half of 2015 was 89%.

The trends in the figures for TGA inspections of overseas manufacturers are less clear because 34% of site visits conducted in the second half of 2015 are yet to complete the closeout process. So far, 60% of sites have achieved satisfactory levels of compliance. The remaining 6% to complete the closeout process are split evenly between ratings of marginal and unacceptable compliance. This proportion of satisfactory, marginal and unacceptable ratings is in line with the results seen in the two preceding six-month periods.

TGFA Report

CDSCO Creates 40-Page Checklist for GMP, GLP Inspections

The Central Drug Standard Control Organisation (CDSCO) of India has released a 40-page checklist for use by its inspectors and the companies they oversee. CDSCO envisions the checklist improving the quality of drugs manufactured in India by ensuring facility inspectors across the country follow the same set of rigorous procedures.

In recent years, international regulators have repeatedly identified quality failings at manufacturing plants and testing laboratories in India before local officials have noticed anything is wrong. Equally, quality failings at some manufacturers serving the local market exclusively only came to light after their products were linked to adverse events. These events suggest Indian regulators have failed to effectively monitor the quality of medicines within their jurisdiction, a shortcoming CDSCO is seeking to address.

The latest step in the process is the release of a 40-page checklist for use by regulators during good manufacturing and laboratory practice (GMP/GLP) inspections. CDSCO has designed the document to ensure all aspects of Schedule M and Schedule L1 of the Drugs and Cosmetics Rules, 1945 are covered when its staff perform GMP and GLP inspections. As such, the checklist orders inspectors to provide unambiguous descriptions of the cleanliness of the manufacturing area, the quality of water used at the site and the composition of the sewage disposal system.

CDSCO has also included checklist entries related to requirements that, while outside the scope of Schedule M, are needed for compliance with the World Health Organization Technical Report Series (WHO TRS) and Pharmaceutical Inspection Co-operation Scheme (PIC/S). These entries, which are highlighted by the use of red text, are only applicable to manufacturers that plan to export products made at the facility to the international market, a subsection of Indian drugmakers that have been hit particularly hard by their regulatory shortcomings.

Equipped with the checklist, CDSCO inspectors should identify issues likely to result in punishment by international regulators. The international aspects of the checklist include a whole section on the use of security measures, additional requirements for water and compressed air systems and a major expansion of the list of cleaning validation points for assessment. Schedule M makes up one point in the cleaning section, namely “is a validation performed to confirm cleaning effectiveness?” WHO TRS covers a further nine points. The data integrity section only includes points based on local legislation.

To ensure officials understand the checklist and can use it to perform rigorous inspections, CDSCO is holding training sessions. In May, the regulator held two separate week-long training programs. The training programs and checklist are intended to ensure inspectors are prepared when they visit a site. CDSCO thinks the checklist could serve a similar purpose for manufacturers by providing them with a framework to base self-assessment programs on. CDSCO plans to refine the checklist as it receives feedback on the document. 

CDSCO Checklist, DCGI Notice

Number of Deaths, Serious Injuries Linked to Devices in China Climbs 88%

The China Food and Drug Administration (CFDA) has reported a year-on-year jump in the number of deaths and serious injuries linked to medical devices. Last year, CFDA received reports of 184 such events, compared to 98 in 2014, a difference that amounts to an 88% increase over 12 months.

One possible reason for the increase is that CFDA is receiving more reports of adverse events tied to medical devices in general, a trend that has developed over several years as China has expanded its materiovigilance activities. In 2015, CFDA received 47,249 reports of medical device-related adverse events, compared to 41,018 in the previous year. Deaths and serious injuries accounted for a slightly higher proportion of adverse event reports last year than in 2014.

CFDA reported the death and serious injury data without comment, but in other sections of its report it signaled the need for changes to be made on the basis of the results. For the second year running, the proportion of adverse event reports originating from manufacturers fell, a trend that again led CFDA to call for changes. CFDA sees manufacturers as key players in materiovigilance, but as it stands, this status is not reflected in their small and declining share of adverse event reports.

Whether anything will happen to change the trend is questionable. CFDA criticized the performance of manufacturers in 2013, a year in which they contributed a greater share of reports than in the preceding year, and in 2014.

CFDA Report (Chinese), Xinhua

Hunan FDA Commits to Strengthening Medical Equipment Inspection Capabilities

Hunan Food and Drug Administration (FDA) has outlined plans to strengthen its medical equipment inspection and testing capabilities. News of the plan comes one month after Hunan FDA committed to improving oversight of drug manufacturers and distributors.

The latest development at the regional regulator relates to its ability to inspect and test medical equipment, an area in which it thinks it can improve. Specifically, Hunan FDA is planning to build up its laboratory testing capabilities. The plan is in keeping with efforts at CFDA to improve the quality of medical devices sold in China.

Hunan FDA is already playing a role in this effort. Days before CFDA shared news of Hunan FDA’s plan to improve its testing and inspection capabilities, the regional regulator published an alert about its actions against two medical device manufacturers.

CFDA Notice, Hunan FDA Alert (both Chinese)