The China Food and Drug Administration (CFDA) has been busy publishing draft orders in the first half of 2017. Some of the draft orders and decisions are extremely important and will have far reaching impact on the drug registration system in China. The draft orders and decisions, if passed, will speed up the entire drug registration procedure in China, benefiting foreign drug manufacturers.

The most important draft orders are:

  • Decision on Change of Several Issues Regarding the Administration of Imported Drug Registration (published on 17 March 2017, Draft Decision);
  • Relevant Policies to Encourage Innovation and Accelerate Review Process for Drug and Medical Device Market Approval (published on 11 May 2017, Order 52);
  • Relevant Policies to Encourage Innovation and Reform Clinical Trial Management (published on 11 May 2017, Order 53);
  • Relevant Policies to Encourage Innovation and Implement Administration on Life Cycle of Drugs and Medical Devices (published on 11 May 2017, Order 54); and
  • Relevant Policies to Encourage Innovation and Protect Innovators' Rights (published on 12 May 2017, Order 55).

Background

The State Council issued an Opinion on the Reform of Review and Registration Process for Drugs and Medical Devices in August 2015 (“State Council Opinion”). The State Council Opinion identified a number of issues relating to the current drug and medical device registration system, in particular, long registration times, significant application backlog, poor generic drug quality assessments, low quality/incomplete drug application clinical data, and a difficult registration system for innovative drugs.

In response to the State Council Opinion, the CFDA has issued a series of orders and measures to address those concerns over the past two years, and has implemented a series of enforcement actions in relation to drug registration, including, among others, carrying out equivalence evaluations on the quality and efficacy of generic drugs, cracking down on clinical trial data fraud, and introducing a pilot market authorization system.

The five draft orders mentioned above are high-level documents addressing a wide range of issues and seek to speed up the drug registration process, provide a more efficient registration system for foreign drugs, establish a catalogue of rare diseases and expedite registration for their treatment, and address compliance issues in drug promotion and data integrity issues in clinical trials, etc.

The main regulatory changes are summarized below.

Shortened Registration Process for Imported Drug License (IDL)

The Draft Decision proposes to make the following changes to clinical trials and the registration of imported innovative drugs which have not previously been approved in any overseas country, so as to expedite the entry of an imported new drug into the Chinese market:

  • An overseas applicant can apply to conduct an international multicentre clinical trial (IMCT) in China for a new drug where no clinical trial has been conducted and no market approval has been obtained elsewhere in the world. Currently, an imported drug must have already been approved for marketing, or at least have entered into the Phase II or III trial in an overseas country before an application to conduct an IMCT can be filed in China; and
  • An overseas applicant can proceed directly to the IDL registration filing for a new drug after finishing an IMCT in China. Currently, the applicant will have to apply for an additional waiver of a Phase III trial with the CFDA before the IDL filing.

The above changes, if implemented, may effectively shorten the registration period for an imported new drug by at least two years.

In addition, Order 53 further states that clinical trial data generated overseas, or bioequivalence testing data from the EU, US or Japan, will be considered acceptable for IDL registration in China if the data complies with the CFDA's requirements.

Innovative Drug Registration

Among the series of updates on the registration procedures for the IDL registration of innovative drugs, the most important change is that under the Draft Decision, overseas applicants will no longer need to wait until the drug is first approved in an overseas country before it can file for IDL registration in China.

This will significantly change the existing re-registration system where an applicant can only file for IDL registration in China after the drug has been approved for marketing in another jurisdiction.

CTA Approval

Order 53 proposes the adoption of a negative notification system for clinical trial approvals (CTA) in place of the existing positive approval system. Order 53 proposes a mechanism for an applicant to discuss with the CDE (Centre for Drug Evaluation, group within the CFDA in charge of technical review) before filing the CTA application. If the applicant does not receive negative comments within 60 business days after the CDE accepts the CTA application, the applicant can proceed with the clinical trial directly based on the protocol submitted without the need for approval.

Currently, CTA must be obtained before the clinical trial can start and the approval process has been lengthy (6-18 months). Order 53 proposes there to be deemed approval after 60 business days.

Data Exclusivity

China currently allows a six-year data exclusivity period for drugs that contain new chemical entities. Order 55 proposes additional data exclusivity periods for orphan drugs, pediatric drugs, therapeutic biological products and first generics.

Notably, it is also proposed that data exclusivity period will also be available to a new drug filed in China within one year after approval in the EU, US or Japan. For drugs filed in China after the one-year period, data exclusivity protection will be available but the protection period will be reduced by the period of time delayed.

Expedited Orphan Drug Registration Process

So far, there is no official definition for rare diseases in China and no special expedited orphan drug approval process is available. In terms of clinical trial, the PRC Drug Registration Measures only mention the possibility of applying to the CFDA for a clinical trial waiver or for a reduction in the number of test subjects. Such applications will be considered on a case-by-case basis.

The following regulatory changes for orphan drugs are proposed in Order 52:

  • The National Health and Family Planning Commission will issue a catalogue of rare diseases;
  • A rare disease patient registration system will be established;
  • The approval process for orphan drugs will be streamlined (application to the CFDA to reduce the number of test subjects and expedited approval will be available); and
  • For orphan drugs that have been approved overseas, the CFDA will have the discretion to consider granting conditional approval for marketing and the applicant can supplement trial data after approval.

Patent Linkage System

Order 55 proposes a patent linkage system for generic drugs:

  • A generic drug applicant shall notify the CFDA of relevant patent rights it knows or should have known at the time of drug filing;
  • If a generic drug applicant challenges the relevant patent, it shall declare to the CFDA that the drug does not infringe the relevant patent and shall notify the patent owner within 20 days after the drug registration filing;
  • The patent owner shall initiate a patent infringement litigation within 20 days after receiving the notification from the generic drug applicant if it believes that the generic drug is infringing its patent, and inform the CFDA of the litigation;
  • The CFDA then has the discretion to set a waiting period of no more than 24 months before approval, but will not suspend the technical review during the waiting period; and
  • If there is no judicial decision finding infringement or the case does not settle within the waiting period, the CFDA can approve the generic drug after the waiting period is over.

Other Key Proposals

The drafts also include the following key proposals:

  • Strengthening supervision on the conduct of medical representatives for academic promotion - medical representatives are prohibited from undertaking sales roles and from contacting doctors in private;
  • Accelerating the review process for urgently needed drugs - conditional approval will be available as needed for effective drugs for serious diseases or drugs with significant clinical values;
  • Tightening the approval process for injectable drugs - injectable drugs, especially those with equivalent oral drugs, as well as intravenous injections will be strictly controlled for approval; and
  • Improving ethics committee mechanisms - ethics committees are expected to take on more responsibilities in ensuring good clinical trial practice.
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