In response to the outbreak of a pneumonia-like disease caused by coronavirus (COVID-19), Chinese regulatory authorities adopted a few emergency measures under certain “Special Review and Approval Procedures” to fast-track the review and approval process for developing diagnostic kits, vaccines and therapies for combating COVID-19 infections.
Under the instruction of the China National Medical Products Administration (NMPA), the Chinese Center for Drug Evaluation (CDE) has promogulated guidelines for filing new drug applications (NDA) for anti-COVID-19 drugs and traditional Chinese medicines under a special review procedure, as well as technical guidelines on filing investigational new drug (IND) applications for anti-COVID-19 therapies and preventive vaccines. Under these guidelines, the time for obtaining an IND or NDA approval could be significantly reduced. Gilead received IND approval from the NMPA for its Remdesivir in two days, significantly shorter than the default 60-day review period. Zhejiang Hisun Pharmaceutical obtained a conditional NDA approval of its Favipiravir within 10 days., which allowed the company to launch the product before completing bioequivalence test and study on its efficacy in treating Covid-19 infections.
There are several types of “fast track” procedures available under the current Chinese regulatory framework. The most important three are Special Review and Approval Procedure of 2005, Special Review and Approval Procedure of 2007, and Priority Review and Approval Procedure of 2017, all of which are summarized below.
Special Review and Approval Procedure of 2005
The China Food and Drug Administration (predecessor of the NMPA) adopted a Special Review and Approval Procedure for Drugs in 2005 (the “Special Review and Approval Procedure of 2005”), creating a fast-track approval for urgently needed drugs in emergency cases such as a public health crisis. The Special Review and Approval Procedure of 2005 is applicable in the following situations:
a) In the event of a national or regional emergency declared by the State Council; b) In the event of a public health emergency; c) As proposed by national drug or health authorities, and the national drug standards of the proposed drugs must already exist. d) Other special circumstances approved by applicable regulatory authority.
Under the Special Review and Approval Procedure of 2005, the timeframe for IND or NDA review and approval will be reduced to about 30 days or even shorter. A comparable procedure for medical devices was established under the Emergency Procedures for Review and Approval of Medical Devices in 2009. The outbreak of Covid-19 in China has been identified as a public health emergency and given rise to the applicability of the Special Review and Approval Procedure of 2005. Gilead’s remdesivir obtained the IND approval in record time in China under this 2005 procedure.
Special Review and Approval Procedure of 2007
To promote availability of innovative drugs in the Chinese market, another expedited review and approval procedure (the “Special Review and Approval Procedure of 2007”) was promulgated in 2007 under the amended Administrative Measures for Drug Registration. If a drug candidate is shown to have significant clinical benefits and falls under one of following categories, it will be eligible for a fast-track treatment, subject to the CDE’s approval:
a) A new drug with its substance extracted from plants, animals or minerals (i.e traditional Chinese medicine); b) New chemical entities and biological therapeutics; c) New drugs for the treatment of diseases such as AIDS, malignant tumors and rare diseases, etc.; d) New drugs for the treatment of diseases, for which effective therapeutic methods are not available.
Drug candidates under (a) and (b) can apply for fast-track review pursuant to the Special Review and Approval Procedure of 2007 in as early as the IND stage, whereas drug candidates under (c) and (d) will only be considered for the expedited review procedure if they are in the NDA stage.
Priority Review and Approval Procedure of 2017
To relieve the backlog of the IND and NDA applications, NMAP published in December 2017 an Opinion on the Implementation of Priority Review Procedure to Foster Drug Innovation (the “Priority Review and Approval Procedure of 2017”), which has expanded the scope of drug applications that are qualified for the expedited review procedure. In addition to the types of drug candidates covered under the Special Review and Approval Procedure of 2007, the Priority Review and Approval Procedure of 2017 also encompasses innovative drug candidates that are expected to go off-patent in one year for NDA applications (three years for the IND application), drug candidates that will be concurrently developed in China and the US or EU, drug candidates that are urgently needed in China, and drug candidates for treating rare diseases or children’s diseases.
Set forth below is a complete list of the types of drug candidates that are covered under this Priority Review and Approval Procedures of 2017.
a) Drug candidates showing clear clinical benefits and:
1) new drugs that haven’t been approved in China or overseas; 2) the manufacturing of the approved drug will be moved to China; 3) using advanced preparation technologies and new therapeutic methods; 4) for an IND application, patents covering the drug will expire in 3 years; for an NDA application, patents covering the drug will expire in 1 year; 5) for an IND application, the drug candidate has obtained IND from US FDA or EMA, and its clinical trials will be conducted concurrently in China; for an NDA application, the production line for the drug candidate in China must be substantially the same as in its origin country, the NDA applications for the drug candidate are simultaneously filed with US FDA or EMA, and the applicant companies have passed on-site inspection performed by US FDA or EMA; 6) traditional Chinese medicine for treatment of major diseases and having clear clinical efficacy target; 7) included in the national major technology projects or national major development plan; or the clinical trials of the drug is conducted at and recognized by a national clinical research center.
b) NDA applications for drug candidates having evident clinical advantage and for treatment of: AIDs, tuberculosis, viral hepatitis, rare diseases, malicious tumors, children’s diseases, or common elderly diseases. c) Certain supplemental applications in connection with bioequivalence tests. d) Included as an urgently needed drug on a list maintained by regulatory authorities. e) Drug candidates that are subject to compulsory license in the event of a public health crisis.
Companies with IND or NDA applications that fall under one of the categories above may apply for expedited review when filing the applications with the CDE. Once accepted, such expedited applications will be prioritized over regular ones, which could significantly reduce the review time. Merck Sharp & Dohme obtained the market approval of its 9-valent HPV vaccine in China in record time – the technical review of its biologic license application took only nine days.
Proposed Framework to Unify Expedited Regulatory Review and Approval Procedures
In December 2019, the NMPA released its proposed amended Administrative Measures for Drug Registration to solicit public comments. A major proposal of this amended regulation is to adopt a unified framework for expedited review and approval procedures under different circumstances. Stay tuned for future updates.