From quantity to quality innovation and speed up - 2020 drug regulatory policy progress

In the past 2020, the year when China has comprehensively built a well-off society and the 13th Five-Year Plan has been completed, China's medical reform has continued to advance into deep-water areas and deepened the reform of the three-medical linkage.
also an extraordinary year in 2020, when the country responded positively to the new crown outbreak and issued a large number of outbreak policies in the first half of the year.
July, the State Council issued a Notice on the Issue of Key Tasks for Deepening the Reform of the Medical and Health System in the Second Half of 2020.
these two factors make 2020 the year with the largest number of health-care policies released.
This year, more than 600 policies related to the pharmaceutical industry were issued at the national level, of which pharmaceutical-related policies accounted for about half of the total, and the Drug Administration, as the main department of pharmaceutical policy issues, ranked first in the number of policy issues issued by various agencies.
in the face of a vast number of policy documents, this paper focuses on the pharmaceutical policy and drug review and approval related to the main policies, especially to speed up the innovation of drug review and approval of the supporting rules.
. On March 30, 2020, the State Administration of Market Supervision and Administration announced the new version of the Measures for the Administration of Drug Registration and the Measures for the Supervision and Administration of Drug Production in 2020, in which the Measures for the Administration of Registration and Administration were significantly revised on the basis of the 2007 edition, after 13 years.
this revision involves the reform of drug registration classification, optimizing the review and approval process, strengthening accountability and so on.
the two programme documents were put into effect on 1 July 2020.
of the Measures for the Administration of Drug Registration (the "Measures") include the following five areas.
and improving the efficiency of reviews emphasizes clinical value orientation, encourages research and innovation in pharmaceuticals, and actively promotes the development of generic drugs.
the State Drug Administration continues to push forward the reform of the review and approval system, optimize procedures, improve efficiency, and establish a drug registration management system supported by evaluation-led, inspection, verification, monitoring and evaluation.
four channels to speed up the listing of new drugs to the U.S. FDA, the State Drug Administration has established four special review channels: breakthrough therapeutic drugs, conditional approval, priority review and approval, special approval procedures.
the clinical development phase of drugs is a breakthrough therapeutic drug procedure, the drug market registration stage is targeted at conditional approval and priority review approval procedures, special approval procedures for public health emergencies.
further shorten the review time The application for clinical trial of the drug shall be changed to a decision on whether to agree within 60 days from the date of acceptance, and the bioethicity test can be implemented for the record.
drug listing license application review time limit is 200 days, of which the priority review and approval is 130 days, clinical urgent need for overseas listed rare disease drugs for 70 days;
Fully implement the drug listing license holder system Clear listing license holder (MAH) for enterprises or drug development institutions that can assume corresponding responsibilities, etc., requires the establishment of a drug quality assurance system, the drug's full life cycle management, post-market research, to assume the safety, effective and quality responsibility of listed drugs.
emphasizes that the original auxiliary package related approval In the approval of pharmaceutical preparations, chemical raw materials, accessories and packaging materials and containers directly in contact with drugs for related review.
to copy the chemical raw materials used in domestic listed drugs, they may apply for separate review and approval.
In order to ensure the smooth implementation of the 2020 edition of the Measures for the Administration of Drug Registration, the State Drug Administration has issued a series of drug registration classification, drug review and other supporting documents for comments, speed up the drug review and approval work, improve drug accessibility and enterprises to develop new drugs enthusiasm.
, 2020 edition of chemical drugs, biological products, Chinese medicine registration classification issued on June 30, 2020, the State Drug Administration issued a chemical drugs, biological products registration classification and declaration information requirements notice, registration classification from July 1, 2020, the declaration data requirements from October 1, 2020.
September 2020, the State Drug Administration issued a circular on the registration classification and declaration of Chinese medicines, and from January 1, 2021, all declarations will be submitted in accordance with the new requirements.
Chart 1. Basic Framework for drug registration classification for the 2020 edition Source: State Drug Administration, China Health Industry Capital Research Center 2020 Edition Of the Chemical Drug Registration Classification This version is not very different from the 2016 edition of the Chemical Drug Registration Classification, with three major changes: "API" The terms "preparation" and "preparation" are uniformly defined as "drugs", consistent evaluation is emphasized in the definitions of classes 2, 3 and 4 drugs, and improved new drugs and new adaptations of overseas original research drugs listed in China are added to the classification 5.1.
2020 version of the chemical drug registration classification is divided into 5 categories, the basic content is: 1 category is domestic and foreign are not listed innovative drugs;
2020 version of the biological products registration classification prevention biological products, therapeutic biological products, as well as by biological products management of in-body diagnostic reagents are classified according to the degree of innovation and domestic and foreign listing.
biological products for prevention are classified into innovative vaccines (category 1), modified vaccines (category 2), domestic or overseas vaccines listed (category 3), and sub-categories are included under each category.
, therapeutic biological products are divided into three categories.
drug registration classification is an important index for drug positioning, which has an impact on drug clinical trials, declaration, pricing, access and so on.
in the context of encouraging innovation, new class 1 drugs can be included in the priority review and approval process, market access after listing is smooth, and has relatively high pricing.
class 4 generics have little preferential treatment, and need to go through the baptism of volume procurement, after a sharp price reduction can hardly only obtain production profits.
the new version of the drug registration classification more strictly based on the degree of innovation, the joint new version of the "Drug Registration Management Measures" and "Drug Production Supervision and Management Measures", so that different levels of innovation of drugs are properly managed.
2020 version of chinese medicine registration classification in the registration of Chinese medicine is divided into four categories: innovative Chinese medicine, Chinese medicine improved new drugs, ancient classic prescriptions of Chinese medicine compound preparations, the same name prescription drugs, of which the first three categories belong to chinese medicine new drugs.
the classification of Chinese medicine does not represent the level of drug development and efficacy, only indicates that the registration and declaration information requirements are different.
In order to strengthen the combing and excavation of the essence of classical medicine, 3 categories of Chinese medicine are subdivided into Chinese medicine compound preparations (3.1 categories) and other Chinese medicine compound preparations (3.2 categories) managed according to the ancient classical prescription catalogue, of which 3.2 categories include ancient classical prescription Chinese medicine compound preparations not managed according to the ancient classical prescription catalogue and Chinese medicine compounding agents based on the ancient classical prescriptions.
also reflects the state's support and encouragement to the Chinese medicine industry.
3. On September 11, 2020, the State Drug Administration and the State Intellectual Property Office issued the Measures for the Implementation of the Early Settlement Mechanism for Drug Patent Disputes (Trial) (Draft for Comments) (hereinafter referred to as the "Opinion Draft") to further improve the patent link system.
the purpose of this policy is to resolve drug patent disputes as far as possible before patent litigation, in order to reduce waste of resources and accelerate the reasonable replacement of generic drugs for patented drugs.
promote the development of high-level generic drugs (first generics) on the premise of protecting the legitimate rights and interests of drug patent holders, while stimulating the development of new drugs that are more original.
In October 2017, the China Office and the State Office issued one of the program documents on the reform of China's drug regulatory policy, "Opinion on Deepening the Reform of the Review and Approval System to Encourage Drug Medical Device Innovation", the famous No. 42, which calls for the exploration of the establishment of a drug patent link system.
the following years, several agencies sent several messages to advance.
this release of the opinion draft is a continuation of the previous policy, but also China's first introduction of drug patent disputes early settlement mechanism.
In order to promote the development of high-quality generic drugs in China, the opinion draft explores early solutions to drug patent disputes from many aspects, including establishing a platform for the classification of patents for listed drugs in China, clarifying the scope of patent information level for pharmaceutical patents, establishing a patent status declaration system for generic drug applicants, clarifying the realization of objections from patenters or stakeholders, setting a waiting period for the examination and approval of chemical drugs, implementing classification processing for drug review and approval, and giving patent challenges to the exclusive market for the first generic drug.
It is worth highlighting that Article 11 of the opinion draft stipulates: "For the first successful patent challenge and the first approved generic drug to be approved for listing, the drug regulatory department under the State Council shall no longer approve the listing of the same generic drug within 12 months from the date of approval of the drug, and the exclusive period of the market shall not exceed the patent term of the challenged drug."
drug review agencies do not stop technical reviews during the exclusive period of the national drug market.
the application for registration of chemical generic drugs approved by the relevant technical application shall be transferred to the administrative examination and approval process 20 working days before the expiration of the exclusive market period."
opinion draft basically refers to a series of FDA practices, but the incentive for generic patent challenges is even greater, with a maximum 12-month market exclusive period of twice the six-month market exclusive period for successful U.S. patent challenges.
this will greatly mobilize the enthusiasm of pharmaceutical companies for research and development, with the patent challenge model layout, to help improve the quality of generic drug research and development, while at a lower price than the original drug under challenge to benefit patients.
4. On July 8, 2020, the State Drug Administration issued three supporting rules, "Breakthrough Therapeutic Drug Review Procedures (Trial)," "Drug Conditional Approval review and approval Procedures (Trial)" and "Drug Listing License Priority Review and Approval Procedures (Trial)", in line with the implementation of the 2020 version of the Drug Registration And Administration Measures.
These three work procedures are the three special review channels established to encourage the development of new drugs and accelerate the launch of new drugs in China, with reference to the four special review channels of the FDA: breakthrough therapy channel, accelerated approval, priority review, and fast track.
"Breakthrough Therapy" requires that drugs be seen in preliminary clinical trials as significantly better than existing treatments at one or more clinically significant endpoints, "accelerated approval" may be approved based on alternative or intermediate endpoints in clinical trials, "priority reviews" reduce the review cycle for listing applications from the standard 10 months to 6 months, and "fast track" allows pharmaceutical companies to roll over listing applications during the development process.
Chart 2. The FDA accelerates the listing of innovative drugs 4 special review channels Source: FDA, Zhongkang Industrial Capital Research Center FDA set up special review channels to promote the rapid market of innovative drugs with important therapeutic value, while ensuring that the review process does not compromise the safety and ability of drugs standards.
one of the main reasons why the U.S. is the world's largest annual approved for innovative drugs is the fda's accelerated access to new drug reviews.
Although China's drug regulatory agencies have learned the FDA's accelerated channel model, the introduction and development of several special review channel policies in China are closely related to the development of China's innovative drug research and development in general, reflecting the shift in emphasis from "quantity" to "quality".
One of china's accelerated channels for innovative drugs: priority review and approval Priority review and evaluation of wholesale end of China's drug regulatory policy reform, one of the program documents, issued in August 2015, "No. 44" "State Council on the reform of drug medical device review and approval system", which proposed to speed up the review and approval of innovative drugs.
In February 2016, the former State Administration of Food and Drug Administration (CFDA) issued a priority review on priority resolution of the backlog of drug registration applications, covering domestic and foreign unlisted innovative drugs, clinically urgently needed high-quality level generic drugs, cancer, children's drugs, rare diseases, tuberculosis, viral hepatitis and other diseases in the field of innovative drugs.
2020 Edition of the "Priority Review and Approval Procedures for Drug Listing Permits (Trial)" is based on the Opinions on Encouraging Priority Review and Approval of Drug Innovation, issued on December 28, 2017.
the 2020 edition of the work program, the policy tends to address the "quantity" of innovative drugs with clinical value and the high level of generic drugs that are clinically urgently needed, in conjunction with the problem of a backlog of drug registration applications.
after the backlog of reviews has been basically resolved and the domestic clinical needs have been basically met, the scope of application of the priority review approval procedure is more inclined to new drugs with obvious clinical value.
Chart 3. The scope of application of the priority review and approval procedures for 2020 and 2017 Source: State Drug Administration, China Health Industry Capital Research Center China Innovation Drug Acceleration Channel II: Breakthrough Therapeutic Drug Procedure China Drug Administration Introduces "Breakthrough Therapeutic Drug Procedures" similar to the FDA's "Breakthrough Therapeutic Pathway" late, and in November 2019 the Drug Review Center (CDE) released the Breakthrough Therapeutic Drug Work Procedure (Draft) for Comments.
the 2020 edition of the Drug Registration Management Measures, the relevant provisions of breakthrough therapeutic drugs, issued in July 2020 "breakthrough treatment drug review procedures (trial)" is the supporting rules.
The drug identified as a breakthrough treatment requires two conditions: (1) for the prevention and treatment of diseases that are seriously life-threatening or seriously affect the quality of life;
drug review center to include breakthrough treatment drug procedures for the priority allocation of resources to communicate, strengthen guidance, and in the market application stage to include priority review and approval.
treatment means that the screening of breakthrough drugs is more rigorous.
breakthrough therapeutic drug identification requires preliminary clinical trials to prove that the drug is clinical in one or more