Introduction
On August 25, 2023, the National Medical Products Administration (hereinafter referred to as the "NMPA") issued the "Working Procedures for the Review and Approval of Drug Conditional Approval of Marketing Applications (Trial) (Revised Draft for Solicitation of Comments)" (hereinafter referred to as the "Working Procedures"), accompanied by the "Working Procedures", and simultaneously issued the "Working Procedures for the Review and Approval of Drug Conditional Approval of Marketing Applications (Trial) Policy Interpretation (Consultation Draft)" (hereinafter referred to as the "Policy Interpretation"), which is combined with the "Working Procedures" to be referred to as the "New Regulations for Conditional Listing" ）。 The NMPA is soliciting public comments from all walks of life on the new conditional listing rules until September 25, 2023. This article is divided into two parts, the first part mainly interprets the key points of the new rules for conditional approval of listing; The second part will analyze the policy development background and industry development status of the new conditional listing regulations, and discuss the response of innovative pharmaceutical companies in the future R&D process.
Next
According to the key interpretation of the policy in the previous part, compared with the 2020 version of the "Working Procedures", the new regulations on conditional listing have tightened the adjustment of the caliber of drug approval and conditional post-marketing supervision. Looking at the development and evolution of domestic and foreign policies, combined with the performance of the industry since the implementation of the conditional approval procedure in 2020, it is not difficult to see the trend expectation of the NMPA for the effect of the new regulations. For innovative pharmaceutical companies, grasping the trend of policy evolution and gaining insight into the development situation of the industry is the only way to compete and stand at the forefront of the trend.
First, the policy evolution is expanding vertically and horizontally
(1) The evolution of the domestic policy for the review and approval of conditional approval of listing applications
Since China joined the International Council for Harmonization of Drugs for Human Use (ICH) in 2017, the NMPA has introduced a series of regulatory policies to promote the alignment of China's drug regulatory system with international standards. The Food and Drug Administration requires from the policy review document (Pharmaceutical Policy Communication|Interpretation of the "Technical Guidelines for New Drug Benefits-Risk Assessment" (Part I) (Part II)), Medical Insurance Negotiation Access (Pharmaceutical Policy Communication).Interpretation of the 2023 "Rules for Negotiating Drug Renewals" and other aspects of improving regulations reflects a strong determination to promote and support the differentiated R&D capabilities and achievements of domestic innovative drugs.
Focusing on the conditional approval and marketing procedures for drugs, it first appeared in the "Measures for the Administration of Drug Registration", which came into effect on July 1, 2020, which includes the conditional approval procedure, the breakthrough ** drug procedure, the priority review and approval procedure and the special approval procedure in the chapter on the accelerated marketing and registration procedure for drugs. On July 8, 2020, the NMPA issued the "Working Procedures for the Review and Approval of Drug Conditional Approval Application for Marketing". On November 19, 2020, the Center for Drug Evaluation (CDE) of the NMPA issued the Technical Guidelines for Conditional Approval of Drugs for Marketing (Trial). Until August 2023, three years after the implementation of the 2020 version of the Working Procedures, the NMPA issued new rules for conditional listing, reflecting the overall trend of stricter supervision of the conditional approval listing procedure.
Figure 1: China's policy development path for conditional approval of listing.
(2) Comparison of international conditional approval of listing application review and approval policies
Judging from the comparison of the key points of the conditional approval policies of China, the United States and the European Union, China has absorbed the essence of the United States and the European Union, and has made corresponding adjustments and clarifications based on China's development foundation, especially in the scope of application and preferential policies.
Figure 2: Comparison of conditional approval policies in China, the United States and Europe[1].
Second, industry trends to respond to challenges
Since the implementation of conditional approval in 2020, as of the end of 2023, a total of 95 drugs (involving 107 indications) in China have been conditionally approved [2], including some blockbuster products of industry stars.
(1) Research clusters in the field and uneven distribution of clinical resources
Based on the statistics of the 2023 CDE, pharmaceutical companies' applications for conditional approval for listing have obvious characteristics such as proactive and field-focused. The conditions for conditional marketing approval have an innate preference for oncology drugs, and pharmaceutical companies focus on the indications in the field of anti-tumor based on the strategic trade-off of resources and return on investment, while there is little interest in the field of pediatric and rare disease drugs.
Figure 3: Coverage of conditionally approved drugs since 2020 (by indication) [3].
In addition, in recent years, pharmaceutical companies have been flocking to popular targets represented by PD-1, which is also an important reason for the aggregation of clinical studies, and a large number of homogeneous clinical trials have flocked to it for a while. Considering the "28 principle" of clinical trials, the aggregation of fields means that clinical resources cannot be reasonably allocated, and over-saturated clinical trial projects appear in first-tier cities, with long queuing time, scattered PI (principal investigator) energy, and poor quality of clinical trial data, which directly causes the waste of pharmaceutical companies' funds and clinical resources in the industry.
Figure 4: Clinical trial undertaking in the top 10 provinces of filing institutions [4].
(2) Slow progress after conditional approval of listing
It is worth mentioning that as of the end of statistics in 2023, only 19 varieties that have been conditionally approved for marketing in China have completed post-marketing research and turned into routine approval, accounting for only 20%. Although there are reasons why the conditional procedure has only been implemented for more than 3 years and the time is still short, it is compared to the conversion rate of 50% in the United States and 38 in the European UnionThe 98% conversion rate and the lack of follow-up in post-marketing research of some pharmaceutical companies are also unavoidable facts.
Figure 5: NDA conditional approval for listing conversion as of 2023[5].
Figure 6: FDA Conditional Approval Conversion as of 2021[6].
The release of the new conditional listing rules is obviously a wake-up call for enterprises, and the days of treating the conditional approval listing channel as a "fast and regular listing channel" are gone, and the new regulations have greatly clarified the obligations and requirements after the conditional approval of listing. With the shortening of the window period, the limited scope of dividends, and the tightening of supervision, planning the steady pace of post-marketing clinical trials will be the top priority for pharmaceutical companies with conditional qualifications.
Fourth, summary
In the three years since the introduction and implementation of the conditional approval listing procedure, various innovative pharmaceutical companies have actively or passively been involved in the hot track, competing for speed and seizing the opportunity. However, chaos will eventually return to order, and the introduction of the new rules on conditional listing is a clear signal that the survival methods of me-too and me-worse will eventually be difficult to survive. Although the new regulations have not yet been officially drafted, and it is still unclear whether it will only be able to "hit the line first" in the future and whether the time limit requirement is indeed 4 years, the first concept of the new regulations is that conditional approval is to encourage clinical value-oriented drug innovation and accelerate the listing of clinically urgently needed drugs with outstanding clinical value. The NMPA is guided by clinical value and its original intention of encouraging differentiated innovation remains unchanged. Innovative pharmaceutical companies need to abandon the luck mentality, actively respond, and carefully weigh the track selection and pipeline layout under the trade-off between new regulations and capital, and win a place by strength.
Note: 1].Source** in China Pharmaceutical Affairs Magazine.
2].Relevant data** in CDE's 2023 Drug Evaluation Report
3].Data** is reported in the CDE.
4].Relevant data** on the filing platform and CDE publicity platform.
5].Relevant data** in CDE's 2023 Drug Evaluation Report
6].Relevant data** from the FDA platform.
Reference: 2023 Annual Drug Evaluation Report, CDE
Implementation of Conditional Approval Procedures for Drugs in China and Related Reflections, Lijia Yuan, Xiaoming Chen, Ning Zhang, China Pharmaceutical Affairs, 2022, 36(10).
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