n June 2, 2017, China officially joined the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) and truly began to integrate into the international drug regulatory system. Only one year later, in June 2018, China’s health regulatory authority (National Medical Products Administration, NMPA) was elected as a member of the ICH Management Committee to further participate in international drug development and registration.

By translating and implementing ICH guidelines in the four years between June 2017 and DIA China 2021, NMPA has helped lead overall positive change to China’s drug regulatory system and thus to innovation in China’s drug review reform, promotion of China’s local drug development innovation, and enhancement of Chinese patients’ access to urgently needed drugs marketed abroad. During the COVID-19 pandemic, China’s Center for Drug Evaluation (CDE) under NMPA has implemented flexible regulatory measures to facilitate rapid clinical and market entry of new coronavirus drugs.

Between August 2018 and May 2021, 69 NMPA experts participated in a total of 1,026 ICH expert working group teleconferences, an average of almost 30 per month; in addition, the Chinese pharmaceutical industry sent 17 experts to participate in the ICH through the International Pharmaceutical Federation (IPF).

According to the latest ICH “Assembly Rules of Procedure,” Tier 1 guidelines must be implemented once a regulator becomes a member. Tier 2 guidelines must be implemented within five years of becoming an ICH member. As of May 2021, China has fully implemented all three ICH Tier 1 guidelines (ICH Q1, Q7, and E6) and three of the five ICH Tier 2 guidelines (ICH M4, E2A, and E2B), with the other two Tier 2 guidelines (ICH E2D and M1) scheduled to be implemented on July 1, 2022.

After China joined ICH, its regulators expeditiously introduced new concepts, methods, tools, and standards of regulation. For example, CDE introduced a comprehensive project management system, including a communication system, expedited evaluation and approval system, therapeutic area team system, expert consultation system, and information disclosure system, and drafted about 200 guidelines by the end of 2020.

NMPA has aligned itself with the ICH guidelines through three principles. The first is to ensure that its own content does not conflict with the ICH guidelines. The second is to fully draw on the guidelines of developed regulatory agencies in Europe (EMA), the US (FDA), and Japan (PMDA) to ensure that China aligns with international standards. The third is to accumulate and share China’s wisdom from experience for subsequent international ICH harmonization.

New Drug Administration Law and Registration Regulation

China implemented the new Drug Administration Law in December 2019, fully implemented China’s Marketing Authorization Holder (MAH) system, and established a pharmacovigilance system. On July 1, 2020, it implemented the new Drug Registration Regulation and proposed four drug registration acceleration pathways. As a result, by May 2021:

• 28 domestic products were granted “breakthrough designation”
• 20 foreign and 18 domestic enterprises were granted “conditional approval”
• 74 foreign and 52 domestic enterprises were granted “priority review”
• Many COVID-19 vaccine projects were granted “special review and approval.”

Implementing ICH M4 (Common Technical Document, or CTD) in 2018 allowed Chinese applications to align directly with and use FDA’s and EMA’s application format. Since then, a series of guideline requirements such as E5 (Ethnic Factors in the Acceptability of Foreign Clinical Data) and E17 (General Principles for Planning and Design of Multi-Regional Clinical Trials) have further enabled early clinical studies in China as well as international strategies to achieve simultaneous R&D and registration. According to China RDPAC (R&D-based Pharmaceutical Association Committee) data, Chinese NDA applications have increased exponentially since 2018: the number of NDA applications for innovative chemical products increased 100% compared with 2017, and the number of NDA applications for innovative biologics increased 62% compared with 2017. As China’s regulations converge with international standards, Chinese drug development has entered a new phase, changing innovative drug development from a single, local enterprise to simultaneous global registration.

Cell and Gene Therapies

In April 2019, China included Research on the Technical Evaluation and Regulatory System of Cellular and Gene Therapy Products in the first issuance of China’s Pharmaceutical Regulatory Science Action Plan, and has since issued a series of pharmacological, nonclinical, and clinical guidelines (including drafts) to regulate and guide the development, declaration, and evaluation of cell and gene therapy products in China. New technical guidelines for cell and gene therapy products are planned for finalization and implementation throughout the rest of 2021. Many observers expect China to approve the marketing of two local CAR-T cell/gene therapy products by the end of 2021, a breakthrough of these product types into China’s market.

Therapeutic Drugs and Companion Diagnostics

Unlike the Chinese drug regulatory system, regulatory development of companion diagnostic medical devices in China remains very slow. Most of these and related products have been registered as Class III medical devices and approved based on current medical device regulations. To encourage codevelopment between discovery research laboratories and pharmaceutical companies, China’s Center for Medical Device Evaluation (CMDE, a division of NMPA) has announced preparation of its Technical Review Guideline of Clinical Trial for Co-Development of CDx Reagents and Anti-Tumor Drugs.

In July 2020, China’s CMDE published the draft version of Guidelines for Package Insert Update and Technical Review Principle of CDx for the same type of therapeutic drugs. In August 2020, CMDE issued the draft Guidance for Clinical Study of CDx for the Marketed Oncology Drugs. As these national guidelines and regulations continue to create favorable conditions for development of drug-CDx reagents in China, industry has responded with calls for China’s companion diagnostic products regulation to keep pace with drug regulation reform, to learn from advanced regulatory systems like those in Europe and the US, and for regulators to introduce corresponding regulations to facilitate the simultaneous development of concomitant diagnostic products and drugs.

Regulatory Response to COVID-19

China, as elsewhere, demonstrated exceptional regulatory agility and flexibility as it quickly and effectively responded to the pandemic with the rapid development, testing, and approval of COVID-19 medical products. During the pandemic, NMPA published a series of special technical guidelines and evaluation procedures that ensured both the quality and accelerated development of these products.

Key Takeaways:

• China has fully and well fulfilled its responsibilities as an ICH member state and management committee: NMPA has sent experts to all active ICH working groups, and China has almost fully implemented ICH Tier 1 and Tier 2 guidelines.
• New regulations have further increased the possibility of China’s participation in simultaneous global drug development and simultaneous registration.
• Like many global health authorities, NMPA demonstrated exceptional regulatory agility and flexibility during the COVID-19 pandemic to ensure rapid development and testing of COVID-19 medicinal products, while maintaining development continuity for non-COVID therapeutics and other medical products for patients worldwide.
• New regulations are facilitating local development of advanced or innovative drugs and continue to strengthen China’s focus on cell/gene therapy products.