The Breakthrough Therapy Designation in China: A Magnet for Foreign Companies

October, 2021

Despite being accessible for less than a year, China’s Breakthrough Therapy designation has been much more effective than previous classifications attracting foreign enterprises. So what is the China Breakthrough Therapy Designation? Who can benefit from it? And, how does the procedure fit into the drug registration process in China? 

Regulatory Drug Development Reforms in China

Significant modifications to China’s Drug Administration Law (DAL) and Drug Registration Regulation (DRR) have produced mixed results so far in the last 20 years. For example, in the brief period following the new DAL’s implementation in December 2019 and the subsequent implementation of the new DRR in July 2020, approval of such innovative drug products fell to 46 last year from 53 in 2019.

Despite higher expectations of previous reforms, local and international pharmaceutical companies still line up to capitalize on China’s expanding pharmaceutical industry. Let’s not forget that in 2016, the size of China’s pharma market was estimated at around 123.7 billion U.S. dollars and now projects to climb up to almost 574 billion U.S. dollars by 2022 – Statista

In 2015, the National Medical Products Administration (NMPA), China’s healthcare regulatory authority, began giving designations to promote pharmaceutical innovation and address unmet needs in the country. These tracks, including the Breakthrough Therapy Designation, present significant benefits, such as expedited development, simplified requirements, and approval processes. 

Through these actions, China joins other established big markets, such as the United States, the European Union, and Japan, offering drug development companies access to review designations. Note that other markets have had these designations for more than two decades already. For example, in 1983, the United States was the first to enact the Orphan Drug Act. China now provides the following options.

Fast Track Procedures for Drug Registration in China

Breakthrough Therapy Designation 

The Breakthrough Therapy Designation intends to expedite the evaluation of medicines for critical diseases for which there are no recognized treatments and when preliminary data indicates an advantage over currently available therapies. Drug candidates with the Breakthrough Therapy Designation are up for consideration for Conditional Approval and Priority Review when submitted for as a New Drug Application (NDA). The designation indicates that the development and review of a drug product may be expedited, to address patients’ unmet needs more quickly. Sponsors can seek the breakthrough therapy designation during Phase I and Phase II trials. 

The procedure’s guidance content includes administrative procedures and requirements and the scope of requirements for the designation application. Additionally, the guidance contains information on critical themes you should discuss as an applicant during your initial communication with the authorities.

Conditional Approval Procedure

The Accelerated Approval classification allows for earlier approval of pharmaceuticals that treat severe illnesses and meet an unmet need that is based on a surrogate endpoint, significantly reducing the time required to develop a treatment for approval.

• Drugs for the treatment of severe life-threatening diseases without adequate treatment, and the clinical trials of the drug have confirmed the efficacy and can predict its clinical value;
• Drugs urgently needed for public health and the clinical trials of medicines have data that have shown efficacy and can predict their clinical value;
• Vaccines urgently needed in response to major public health emergencies or other vaccines recognized by the National Health Commission as urgently needed and whose benefits outweigh the risks after assessment.

Priority Review & Approval Procedure

When applying for a drug marketing authorization, the following drugs with obvious clinical value may apply for the priority review and approval procedures:

• Shortage medicines urgently needed in clinical practice, innovative drugs and improved new medicines for the prevention and treatment of major infectious diseases and rare diseases;
• Varieties, dosage forms and specifications of medicines for children that meet the physiological characteristics of children;
• Vaccines and innovative vaccines urgently needed for disease prevention and control;
• Drugs included in the breakthrough treatment drug program;
• Drugs that meet the conditions for approval;
• The State Drug Administration stipulates other priority review and approval situations.

Special Designation

When the threat of a public health emergency occurs, and after a public health emergency occurs, the State Drug Administration may decide following the law to implement special approval for the prevention and treatment drugs required for the crisis of a public health emergency.

Guidance on the Breakthrough Therapy Designation

Support the implementation of the new regualtory framework for drug registration in China, the NMPA published interim regulatory decisions on drug conditional and priority review. More specifically, under Chapter IV ‘Accelerated Drug Listing Registration Procedures’ and the following issued working procedures for:

• Review & Approval of Breakthrough Therapy Designated Drugs;
• Drug Conditional Marketing Authorization Application Review & Approval;
• Drug Priority Marketing Authorization Review & Approval.

Benefits of The Breakthrough Therapy Designation

The new fast-track approval system has the potential to accelerate the commercialization of innovative drugs, benefiting both startups and big pharma. In addition, the companies benefit from expedited approvals, which enables them to engage with prominent international manufacturing partners, allowing them to focus on their expertise (developing life-saving therapies) rather than manufacturing scale-up.

Fast-Tracking

The Breakthrough Therapy Designation intends to expedite the evaluation of therapies for critical diseases for which no existing treatments exist and when preliminary data suggests a potential advantage over currently available treatments. The designation qualifies a drug candidate for expedited review by the NMPA’s Center for Drug Evaluation (CDE), which provides timely recommendations to applicants to expedite the approval and launch process. The other new pathway establishes a “special review” process for drugs that address public health issues. It complements the two existing channels (conditional approval” and priority review) implemented in the past few years to treat, e.g. orphan and innovative oncology drugs.

Manufacturing Outsourcing to Foreign Firms

A second significant component of the amended regulations was the countrywide expansion of the Marketing Authorization Holder (MAH) system beginning July 1, 2020, building on a 2015 trial program. This clause enables contract manufacturers, including foreign corporations, to develop innovative medications. Thus, when previously only large manufacturers could seek marketing authorizations for novel drugs, smaller businesses can now concentrate on product development rather than production/manufacturing capacity increases by outsourcing their manufacturing abroad.

Timelines for the Breakthrough Therapy Designation

The new methods will significantly reduce the time to evaluate and clear drugs submitted for priority evaluation and clearance within 130 days. Additionally, medications that address urgent clinical needs and rare illnesses may expedite the process to as short as 70 days.

Example Breakthrough Therapy Designations

The “breakthrough therapy” designation has benefited international companies in particular. The NMPA handed most designations to enterprises outside China, with over half of designations going to foreign companies of which U.S.-based companies received approximately a third. 

The decisions are available on the NMPA website. Some examples:

• Legend Biotech – The first to commercialize on the reforms received the breakthrough therapy status for ciltacabtagene autoleucel;for treating relapsed or refractory multiple myeloma.
• Amgen – Received the breakthrough therapy status for sotorasib;for the treatment of non-small cell lung cancer. 
• AstraZeneca & Sanofi(Joint-development) – Received the breakthrough therapy status for rnirsevimab; a long-acting antibody for immunity to infants against the respiratory syncytial virus (RSV). 
• Innovent Biologics – Received the breakthrough therapy status for parsaclisib; a small-molecule targeted therapy developed to treat follicular lymphoma.
• Boehringer Ingelheim– became the first multinational contract manufacturer (outside China) approved to provide its manufacturing services to make BeiGene’s monoclonal antibody tislelizumab.

Outlook

The new system will have a significant impact on the entire sector in China. When a firm is in its start-up phase, it may make the most use of its limited resources by concentrating on what sets it apart from the competition, and the Breakthrough Therapy Designation will undoubtedly attract more foreign pharmaceutical enterprises.

If you want to learn more about including China in your Global Drug Development Strategy, watch the webinar!

With the establishment of these rapid drug approval pathways, including the Breakthrough Therapy Designation but also Conditional approval, Priority Review, and Special Approval the NMPA made significant steps forward. And the approaches are certain to significantly speed the drug approval process, particularly for treatments that address unmet medical needs; ultimately saving more patient lives.