Exploring China’s new pilot regulatory program for rare disease drug development

CARE (patient-Centered Action for Rare diseases Encouragement) aims to implement a patient-focused approach. 

This blog is part of The Regulatory Navigator series, where we explore the evolving regulatory landscape with actionable insight from Parexel's experts, sharing their experience to maximize success for clinical development and patient access.

China continues to increase efforts to accelerate the review and approval of drug registration and to support the research and development of drugs to treat rare diseases. A new program, the "CARE Plan" (patient-Centered Action for Rare diseases Encouragement), is a pilot to implement the "patient-centered" concept in the field of rare disease drug research and development. It aims to:  

• Help sponsors to incorporate the patient voice throughout drug research and development; 
• Improve the scientific basis, standardization and rationality of "integrating patient experience data into clinical research and development of rare disease drugs"; and 
• Enhance the communication and cooperation between regulators, sponsors, patients, and other parties focusing on rare disease drug research and development. 

The goal is to promote the research, development and listing through the national reimbursement plan of quality, efficacious drugs to meet urgent clinical needs in rare diseases.  

CARE Plan pilot program: Project types and application process  

On May 24, 2024, the National Medical Products Administration (NMPA) Center of Drug Evaluation (CDE) announced the process for feedback on the application guidelines and implementation framework of the "Patient-Centered Rare Disease Drug Research and Development Pilot Work Plan (CARE Plan).¹  

In this pilot program, CDE will select 1~2 projects in each of the below development stages: 

Stage A: research stage 
Stage B: pre-clinical trial stage 
Stage C: pre-pivotal study stage 
Stage D: pre-NDA/BLA/MAA stage 
Stage E: post-approval stage 

The following table lists additional criteria CDE will use to select the projects. While there is no specific definition provided by the agency for “understanding of disease”, it is the scientific judgment by the Key Opinion Leader (KOL) that will be the key reference for the CDE reviewer.  

Table 1.  Criteria for CARE Plan project selection 

Sponsors who are interested in submitting their project for inclusion in the CARE Plan pilot should do so through the CDE website.2 After internal discussion, CDE will inform the sponsor whether the project is included in the pilot, or if further consultation is required.  Based on our previous CDE consultation experience, we believe that the CDE respond in 10-30 days.  

The application dossier for the CARE Plan pilot program must include the following details: 

• General introduction of the project, disease background, China-specific epidemiology, clinical development plan, clinical summary, overview of patient participation plan in clinical development. 
• For stage B and stage C of clinical trial implementation, it is recommended to include relevant elements of digital health technologies (DHT) / decentralized clinical trials (DCT). 

To submit the CARE Plan application on the CDE website², a valid China account is required. Parexel, as a China regulatory agent can apply on behalf of foreign sponsors.  

Key considerations for global sponsors preparing a development plan that includes China 

1. Participation in the CARE Plan pilot program affords increased interaction with CDE 

The pilot CARE Plan presents a significant opportunity for sponsors running a rare disease program in China. For products included in this pilot, the CDE will stay in close communication with the applicant during their clinical development, provide timely feedback on the applicant's clinical plans for patient participation, and methods for applying patient perspectives to drug development. At the same time, consultation meetings may be organized during the review process, and patient representatives may be invited to participate, to incorporate patient perspectives in the review and regulatory decision-making process. 

2. CARE Plan program participation may increase the efficiency of CDE’s review of the future marketing application 

To accelerate the development of rare disease products, for varieties included in stage C or D, applicants can communicate with CDE based on the primary results (top-line data, i.e. the effectiveness and safety results of clinical studies before the completion of research reports) and datasets after database lock. This supports CDE in initiating the review of clinical data as early as possible, enabling reviewers to identify data quality and identify potential review issues earlier, and may provide early feedback to applicants, thereby making the review and development process more efficient. 

3. There are limitations to China’s rare disease policies that have implications for companies’ product development planning  

At present, the NMPA has not defined "rare diseases" in relevant laws, regulations and guidelines. In theory, the number of diseases that could be categorized as “rare” could be as high as several thousand; however, the current published government list only includes 207 rare diseases.^3,4 For diseases that are not on the government list, a company applying for the CARE Plan program could demonstrate that their target indication qualifies as a rare disease by leveraging China KOL interviews and literature research. 

Additionally, there are limited regulatory incentives for companies to pursue development of rare disease treatments in China.  China is the only member of ICH (The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use) without relevant measures of "financial incentive (including market exclusivity, reduction and exemption of registration fees) in the policy toolkit. 

Also, specific requirements to support marketing authorization may be perceived as disincentives.  China registration will require sample testing which may result in a cost burden, especially for high-priced rare disease products such as cell or gene therapies that are not produced in large quantity.  

Finally, patient or patient group involvement in clinical development planning for rare disease drugs is still in early stages. Nevertheless, there are efforts to increase patient education and participation in clinical trials, as well as their input into design of and important outcomes for clinical trials.⁵ This is especially important for rare diseases. Therefore, companies with programs that include China should consider and strategize for the challenges of ensuring patient engagement during clinical development planning. 

In summary, the CARE Plan pilot program represents an important path forward for rare diseases.  The program will promote research and development of new rare disease drugs to address urgent unmet clinical needs in China. It also offers the opportunity to involve Chinese patients in rare disease product development.  Finally, the CARE Plan pilot program is a valuable opportunity for local and foreign companies to have increased interactions with and input from the CDE during the development of their rare disease drugs. 

Parexel’s team of ex-regulators and industry experts can partner with rare disease drug product developers to navigate this new initiative and interpret CDE approaches in their implementation of the program. We’re always available for a conversation.  

References: 

1. Process for feedback on the application guidelines and implementation framework of the "Patient-Centered Rare Disease Drug Research and Development Pilot Work Plan (CARE Plan)”: https://www.cde.org.cn/main/news/viewInfoCommon/55f3e6ce1198d6be0f65cfc477d46c05 
2. CARE Plan application portal: https://tyrz.cde.org.cn/am/UI/Login?realm=%2F&service=initService&goto=https%3A%2F%2Ftyrz.cde.org.cn%2Fam%2Foauth2%2Fauthorize%3Fservice%3DinitService%26response_type%3Dcode%26client_id%3Dshenqingrenzhichuang%26scope%3Dall%26decision%3DAllow%26redirect_uri%3Dhttps%3A%2F%2Fwbca.cde.org.cn%2Fwbca%2Fauth%2FoAuthWbcaClient  
3. China’s published list of 207 rare diseases – first batch: 
   https://www.gov.cn/zhengce/zhengceku/2018-12/31/content_5435167.htm  
4. China’s published list of 207 rare diseases – second batch: 
   https://www.gov.cn/zhengce/zhengceku/202309/content_6905273.htm 
5. https://www.parexel.com.cn/newsroom/parexel-announces-innovative-partnership-rare-disease-foundation-china 

Return to Insights Center