19 November, 2015
The long awaited and wide-ranging Opinions on Reforming the Review and Approval Process for Drugs and Medical Devices (the Opinions'), were recently issued by China's State Council, and set out a series of measures aimed at overhauling the regulatory approval regime. The Opinions set out a new classification system for medicinal products. 'New drugs' are defined as those not marketed anywhere in the world, in contrast to the current definition of drugs not marketed in mainland China, and are further classified into 'innovative new drugs' and 'improved forms of new drugs'.
A key focus of the Opinions is to accelerate the approval process for innovative drugs. China's regulatory body, the China Food and Drug Administration (CFDA), has suffered a backlog of applications over recent years which has delayed the launch of some drugs onto the Chinese market. In particular, the current regulatory review process can often lead to long delays for the approval of foreign products, even when their safety and efficacy has been well established in other international markets. The CFDA is urged to deal with all unprocessed drug applications by the end of 2016 and to process applications according to statutory review and approval timelines by the start of 2018. Certain innovative drugs will be subject to a new fast-track approval process by the CFDA, the exact details of which have yet to be announced in detail. The Opinions state that in order to benefit from an accelerated procedure, companies must agree to not charge prices that are higher than those in the originating or comparable market. The following categories of products may be eligible for fast-track approval:
- drugs to treat HIV, malaria, malignant tumours, severe infectious diseases and rare diseases;
- drugs to respond to urgent clinical demand;
- innovative drugs with advanced formulation techniques, and
- innovative and paediatric drugs whose manufacturing has been transferred to China
Applications for innovative medical devices with patented core technologies and significant clinical value will also be reviewed using a fast-track procedure. Furthermore, domestic technical standards concerning medical devices will be adapted to international standards.
The Opinions also call for changes to the regulations concerning clinical trials for innovative drugs. In particular, in the future companies will be permitted to conduct trials in China at the same time as trials are conducted in other countries and any clinical data obtained from international multicentre clinical trials involving a Chinese institution can be accepted as part of the application dossier.
Currently, only drug manufacturers can obtain regulatory approval. However, the Opinions also provide for the introduction of a market authorisation holder (MAH) regime on a trial basis, enabling R&D institutions, small biotech companies, and researchers etc. to apply for marketing authorisations in their own name. The marketing approval may then be transferred to a manufacturer with minimal on-site inspection and product testing in contrast to the current requirement for the manufacturer to submit an entirely new drug approval application.
While the stated objective of the Opinions will be widely welcomed by the pharmaceutical and medical device industry, many uncertainties remain over how the changes will be implemented and what the fast-track process will mean in practice. As the Opinions only set out the general principles of the reforms to be implemented, further detailed measures and guidance is expected to be announced shortly by the CFDA with relevant laws and regulations being amended in due course.
Chinese authorities announce surprise inspections of medical device and pharmaceutical manufacturers
According to a recent announcement by the China Food and Drug Administration (the 'CFDA'), pharmaceutical and medical device manufacturers should in the future expect regular surprise inspection visits from officials. In its announcement of the release of the 'Measures for Unannounced Inspection on Drugs and Medical Devices' (the 'Measures'), the CFDA states that the inspections will commence on or after 01 September 2015, and affected companies will not be notified in advance. It is understood that the CFDA's latest initiative is part of a wide-ranging plan to raise the quality of healthcare products for both the local and foreign market.
The Measures stipulate the circumstances under which an unannounced inspection may be initiated, which include the identification of safety risks in products, complaints received and adverse reaction monitoring. Unannounced checks will also be initiated when the authorities are contacted by whistle-blowers or have suspicions concerning certain companies. The CFDA has stated that it will carefully assess information by whistle-blowers and adverse events and other factors before deciding whether to conduct a surprise inspection. By conducting surprise visits it is expected that the CFDA will be able to respond quickly to concerns, and the opportunity for manufacturers to destroy any incriminating evidence onsite will be eliminated.
During an inspection, the inspectors will not provide any information concerning the reason for the visit or any problems identified whilst onsite. Only when all the appropriate evidence has been collected and analysed, and the exact nature of the problem has been identified will the local CFDA inform the manufacturer and issue the specific rectification instructions to be followed. The Measures state that in addition to requiring rectification within a stipulated time period, the CFDA may, in accordance with the law, issue warning letters, interview individuals at the company under inspection, require products to be recalled, and / or withdraw or cancel any relevant quality authentication and accreditation certificates. Once the risk factors have been eliminated and the identified problems remedied, the relevant risk control measures will be lifted in a timely manner.
This latest announcement by the CFDA demonstrates the agency's commitment to improving the manufacturing quality of products in the healthcare sector with follow-on potential benefit to patients and end users in terms of safety and clinical efficacy. The effectiveness of the new strategy depends upon the CFDA's ability to prevent news of impending inspections being leaked to targeted companies. As such, the Measures provide for disciplinary action, including potential criminal prosecution, to be taken against any CFDA or law enforcement official found to be deliberately leaking confidential information or 'tipping off' companies with information about impending inspections.
It is hoped that surprise inspections will encourage companies operating in China to raise local manufacturing standards to international standards. By doing so, it is expected that China's domestic pharmaceutical and device companies will be better placed to compete with foreign competitors over the long-term in terms of quality rather than on pricing alone.
Hong Kong government renews commitment to the introduction of a regulatory regime for medical devices
The Secretary for Food and Health has stated that the Hong Kong government (the Administration), will soon complete a study on how to regulate high-risk medical devices. It is expected that the proposed regulations will enter the legislative process next year.
There is currently no legislation to regulate the manufacture, import, sale and use of medical devices in the territory. However, certain pharmaceutical-containing devices, or radiation-emitting devices may be regulated under the existing Pharmacy and Poisons Ordinance (Cap. 138) and the Radiation Ordinance (Cap. 303), respectively.
The proposed regulatory framework for medical devices is based upon the concept of risk management and is largely modeled on the recommendations made by international organisations such as the Global Harmonization Task Force (GHTF) (now the International Medical Device Regulators Forum (IMDRF)) and the World Health Organisation (WHO). With a risk-based classification the level of regulatory control applicable to a medical device takes account of the risk associated with the device, according to GHTF's recommended classification scheme. The proposed Hong Kong scheme is divided into three main areas of regulation: pre-market control, post-market control, and specific use control. The Department of Health will be responsible for the administration and enforcement of the scheme.
Pre-market controls will be put in place to ensure that medical devices conform to requirements on safety, performance, and quality. The Administration will continue to impose registration requirements for medical devices and in vitro diagnostic medical devices (IVDMDs) with risk levels of Class II or above and Class B or above, respectively. Device registration will be valid for a 3 year renewable period. Conformity Assessment Bodies (CABs) will be empowered to perform conformity assessment audits on medical devices. The regulations will also prohibit any misleading or fraudulent advertising of medical devices or the promotion for a non-approved use. The supply of a device for off-label use, except by a registered healthcare professional, will be considered an offence.
Under the proposals, post-market controls will enable swift control measures to be enacted against defective or unsafe medical devices. The regulations require the Department of Health to establish a post-market surveillance system to monitor the safety, performance and quality of medical devices in the local market, as well as maintain vigilance on medical devices safety alerts issued by overseas regulatory authorities.
The eventual introduction of a regulatory system for medical devices in Hong Kong will help bring the territory in line with the medical device regulations adopted by other major jurisdictions and raise industrial and clinical standards. The final implementation is predicted to result in broader economic benefits in terms of reduced morbidity and mortality.
Alison Wong, Partner, Bird & Bird
alison.wong@twobirds.com
