The Chinese drug regulatory authority (the “CFDA”) has recently issued two policy documents to reform the review and approval system for drugs and medical devices, with the objective of improving the quality and transparency of the drug review and approval system, resolving the long standing backlog of drug registration applications, improving the quality of generic drugs and to encourage the research into and development of new drugs.

First, the Opinions on the Reform of the Review & Approval System for Drugs and Medical Devices (State Council [2015] No. 44) (the “Opinions”) issued by the State Council on 9 August 2015 sets out 12 measures to be implemented.  Secondly, the Announcement on Several Policies Pertaining to the Review & Review of Drug Registration ([2015] No. 230) (the “New Policies”) was issued by the CFDA on 11 November 2015, and set out particular details of the reform of the drug registration system.

The New Policies were implemented on 11 November 2015, so overseas drug manufacturers may wish to note the new requirements for the registration of generic drugs in China as discussed below.

Key reforms to the review and approval system for generic drugs are highlighted below.

New classification of drugs

Pursuant to the Opinions, drugs are classified into “new drugs” and “generic drugs”.  The definition of “new drugs” has been revised from the current definition (“drugs which have not been marketed in China”) to the new definition “drugs which have not been marketed in or outside of China”.  “New drugs” have been further divided into ‘innovative drugs’ and ‘improved new drugs’.

The definition of “generic drugs” has been revised from the current definition (“drugs generic to established national standards”), to the new definition “drugs generic to brand-name drugs with similar quality and efficacy”.  Accordingly, the review and approval of generic drugs will now take the brand-name (originator) drug as the reference to ensure that the quality and efficacy of the generic drug is consistent with that of the originator drug.

Quality and efficacy evaluation for new registration of generic drugs

Under the New Policies, the acceptance, review and approval of generic drug registration applications is based on assessing the quality and efficacy of the generic drug compared to the originator drug. 

For the registration of generic versions of drugs that have been marketed only outside of China, bioequivalence studies comparing the generic drug to the originator drug and clinical trials that conform to internationally accepted standards are required.  The originator drug that is used for conducting the relevant studies is required to be procured and imported by the generic drug applicant with prior approval from the CFDA for the one-off importation.  An application for the approval of a generic drug for which the applicant has failed to carry out comparative studies with the originator drug will be evaluated as if the application were for an innovative drug.

Before approving a generic drug for marketing, the CFDA will evaluate the pharmaceutical studies undertaken by the applicant.  An application will be rejected if it fails to meet the requirements for pharmaceutical studies without further review of other materials.  Once an application is accepted, the registration process will then proceed as follows:

  1. generic drugs with inconsistent quality and efficacy compared to the originator drug that was approved for marketing in China will not be approved for registration;
  2. where the originator drug has been marketed overseas but not in China, the process for review and approval of the generic drug will follow the process provided under the previous regulations, provided that the quality and efficacy consistency evaluation (the “consistency evaluation”) is conducted within a period of three years of the date that the originator drug was approved for marketing in China.   Where the drug has failed the consistency evaluation, a market approval will not be granted.  Alternatively, the applicant can withdraw the original registration application and re-apply when the consistency evaluation has been passed.  Such re-applications will be considered on a priority basis.

Quality and efficacy evaluation for approved generic drugs

For generic drugs which have been approved for marketing in China prior to the reform, the requirement for the consistency evaluation will be rolled out in phases, starting with generic drugs approved for marketing before the adoption of the 2007 edition of Drug Registration Provisions.  Drug manufacturers may also apply for the new procedure and standards voluntarily, and a so-called “green channel” will be established to expedite the review and approval process for such applications.

Drug manufacturers are required to conduct the consistency evaluation (as compared to the reference formulation) in accordance with a prescribed method.  The appropriate reference formulation will be determined with expert advice from the CFDA. Where a reference formulation is not available, clinical studies will be required to show efficacy. A generic drug that has failed the consistency evaluation within the prescribed period will not be re-registered, whereas drugs that have passed the consistency evaluation will be allowed to say so on the drug insert and label.

Where a change of the production process of an approved generic drug is needed for completing the consistency evaluation, the drug manufacturer is required to submit a supplementary application, and the CFDA will establish ”green channels” to expedite the review and approval process of such applications.