1.Drug Registration System

1.1Changes of the Registration System

In the “Provisions for Drug Registration (Version 2007)” different application programs were set up for new drugs, generic drugs, imported drugs and OTC drugs respectively. Drug products received different approvals of registration based on their application programs, i.e. a new drug application obtained both a New Drug License and a Drug Approval No. while a generic drug application obtained only a Drug Approval No., and an imported drug application obtained a License of Imported Drug Registration (or a License of Medical Product Registration).

Registration rules identified by the New Provisions based on the new version of the “Drug Administration Law” are as follows:

Change 1 of Drug Registration: related contents of the New Drug License have been deleted (related concepts such as the New Drug License and the New Drug Monitoring Period are officially withdrawn).

Change 2 of Drug Registration: the registration approvals of new drugs, generic drugs and imported drugs have been unified as the License of Drug Registration.

Change 3 of Drug Registration: the concept of “imported drugs” is no longer available, as it has been substituted by the concept of “Drugs Manufactured Overseas” (the relevant rules are remained to be published).

Change 4 of Drug Registration: the market approval pathways of three drug categories have been identified as, 1) an integrated pathway of pre-clinical research to clinical trials to application for market approval; 2) a direct pathway of exempted clinical trials for generic drugs, in vitro diagnostic products administrated as drugs and other eligible products; 3) a direct pathway for Over the Counter Drugs (OTCs).

Change 5 of Drug Registration: the sub-packaging registration of drugs manufactured overseas is no longer applied at the Provincial Medical Products Administration (PMPA) and reviewed by the NMPA for the Drug Approval No., instead, simply filed at the PMPA.

1.2 Changes of Drug Classification

The New Provisions have combined and followed the rules in the previous version of “Provisions for Drug Registration” and “Reform Scheme for Registration Classification of Chemical Drugs” to classify drug registrations as follows：

Furthermore, NMPA have released the draft for public review for the detailed classification and corresponding requirements of application materials of TCMs, chemical drugs and biological products on April 30^th, 2020.

2.Further Implementation of the MAH System

2.1 It’s clarified that MAH can be transferred

The Article 78 of the new Provisions clarify that the MAH transfer can be applied, approved and implemented by supplementary application pathway.

2.2 Make it clear that it’s mandatory to obtain production license for a MAH

The Article 50 of the new Provisions stipulate that the MAH shall obtain drug production license. Meanwhile, according to the relevant requirements in the new “Measures for Supervision and Administration of Drug Production”, it’s unnecessary for a MAH to have its own workshop, facility, equipment, hygienic environment and instruments, however it must be equipped with adequate technical staff as well as rules and standards which are complied with GMP guidelines.

3.Drug-related Associated Review & Approval

3.1 Introduction

The New Provisions continue to follow the drug-related associated review & approval system identified in the “CFDA Issued an Announcement on Adjusting the Evaluation and Approval for APIs, Excipients and Packaging Materials” (2017 No. 146). The detailed process is as follows:

Pathway 1:
(1) After AEP (hereinafter referred to as AEP: APIs + excipients +packaging) production enterprises file their products on CDE’s platform, CDE will announce the basic information (such as product name, enterprise name, address, source and strength) for the selection of MAHs. (2) After a MAH chooses AEP A, CDE will conduct the review and approval of AEP A together with its associated drug product. (3) CDE will announce the final result of review & approval on the registration platform publicly.

Pathway 2:
(1) A MAH can also choose an un-filed AEP D. However, it’s mandatory to submit relevant research materials of the AEP when applying for preparation registration. (2) CDE will announce the final result of review & approval on the registration platform publicly.

3.2 Implementation Status

Based on the data of CDE official database, until May 5th 2020, a total of 12,884 APIs are registered while 10,007 APIs are approved for their use in marketed FDF, including APIs produced overseas.

This article is summarized and translated from Jindu law firm.

A: Under the current background of the classification of chemical drugs, it’s unlikely for overseas OTC products to obtain approval from NMPA successfully. The main reason is that OTC is neither a category of innovative drugs, nor can it be applied strictly according to the concept of generic drugs. As there’s no definite original product, it’s difficult to develop OTC products according to the conceptual framework of general generic drugs.

Q10: What is significance of the implementation of the communication meeting policy for applicants?

A: The implementation of communication meeting policy is originated from “NMPA Announcement on Issuing Administration Law of Drug Development and Technical Review Communication” (No.74, 2018). This announcement stipulated that it is applicable to initiate the communication meeting relating to innovative drugs, improved new drugs, biosimilars, complex generic drugs and consistency evaluation products in the process of development and registration application. Generally, applicants will propose actively to apply for communication meeting. The main issues of application product could be solved previously by the CDE meeting or written letter, phone response from CDE, in order to accelerate the process of market approval.

Q11: What is “Catalogue of Chemical Drugs” and its value?

A: “Catalogue of Chemical Drugs” is also named as “Catalogue of China Marketed Drugs”, which is issued on Dec 29th, 2017. The catalogue has recorded the drugs with safety, efficacy and controllable quality, and confirmed RLD and RS (is short for Reference Standard). Similar to the Orange Book of FDA and PMDA, “Catalogue of Chemical Drugs” provides a good reference for the ongoing consistency evaluation work of chemical drugs in China.

Q12: What is the difference between the current trial of No.80 and “The applicant submits an application for approval of drug as Marketing Authorization Holder (MAH) after completing studies on pharmacy, pharmacotoxicology and clinical trials to support drug approval, confirming specifications, completing production process validation of commercial scale, and preparing to undergo drug registration inspection and testing, the applicant shall apply for market approval” mentioned in the new “Provisions”? Are there any new requirements in the new “Provisions”?

A: The implementation of this clause is clearly inconsistent with the specific requirements in current trial No.80 promulgated in May 2016 namely, “Requirements for application materials of chemical drugs’ new registration classification”. The chapter of process validation and evaluation of 3.2.P.3.5 in No.80 has mentioned that for non-sterile process procedure, applicant could submit the process validation report (No:_ , Version: ), or the process validation protocol (No: , Version: _) and commitment contract of the first three commercial production batches’ validation after marketing. As the conflicted situation, the No.80 might need to be subject to the current new “Provisions”.

Q13: How to understand the Article 35 of generic drugs, in vitro diagnostic reagents in accordance with drug management and other eligible conditions in “Provisions” that “The applicant can apply for drug market approval directly, after the evaluation by the applicant, and deems it unnecessary or impossible to conduct a clinical trial and conforms to the conditions of clinical trial exemption. The technical guidelines and relevant requirements of clinical trial exemptions are formulated and issued by the Center for Drug Evaluation (CDE)”? And how to understand and implement this in actual projects?

A: Currently this article has not been implemented yet. According to the article, the applicant could apply directly for market approval, after evaluating there’s no need to conduct clinical trial. Based on this, many imported injection of class 5.2 could apply for market approval directly from July 1st .2020.

However, the current actual situation is class 3 and 4 of chemical drugs can apply for production directly. As for imported class 5 chemical drugs, there are mainly two situations which can apply for market approval directly: (1) the class 5.2 oral solid preparations have completed BE study or have the BE study approved overseas can apply, (2) rare diseases and other conditions can apply for market approval directly. The process of clinical application firstly and then market approval is still work for other products.

Q14: How to understand the term “based on risks” that has been mentioned many times in the new “Provisions”?

A: “Based on risks” is frequency mentioned both in regulations and laws and the communications with CDE in these two years, which makes the review and approval more flexible than before. In the past, whether high risk products like class 5.1 injection or super low risk products like pharmaceutical excipients in topic use preparations will be issued a “Registration Inspection Notice”. Understandably, this causes a heavy burden on the resources of the national inspection center. The “Provisions” has further consolidated the industry reform of theses years, and is still being improved continuously.

Q15: What are the highlights of the registration inspection link in the new “Provisions”?

A: The biggest highlight is the applicant can decide to whether to apply for registration inspection in advance based on its product according to relevant clauses. If the product has a high risk, the possibility of registration inspection is very high. The applicant may propose the application in advance in order to ensure the registration inspection could be completed in time successfully.

Q16: What is the purpose and significance of adding chapter “Accelerated Drug Market Registration Procedure” in the new “Provisions”?

A: The “Chapter 4, Accelerated Drug Market Registration Procedure” has established four accelerated channels for breakthrough therapeutic drug procedure, approval procedure with condition, priority review&approval procedure and special review&approval procedure. Among them, breakthrough therapeutic drug procedure and approval procedure with condition are mainly for products in clinical trial phases. Priority review&approval procedure is applicable for products in market approval step. NMPA can decide to conduct special review&approval for drugs required for public health emergency, in the event of a threat from a public health emergency or after a public health emergency occurs in accordance with law.

For China drug regulatory or registration queries, you may contact us: info@accestra.com

This article is originally translated from Canny.

Glossary:

RLD Reference Listed Drug
RS Reference Standard

Taking in to account the important role of medicines in combating Covid-19. After investigation, CDE has decided to adjust the submission time and form of certifications of imported drugs (including clinical trial applications, marketing registration application, supplementary application and re-registration application) in order to ensure the smooth progress of imported drugs’ registration application. The details are as follows:

For the overseas drugs which cannot be notarized in foreign countries notarized or posted, the overseas holder or domestic registration agency shall illustrate in the special statement part of drug application form and submit electronically scanned version of certifications. In the statement, the applicant shall make a commitment to bear the corresponding legal responsibility of its authenticity, validity and consistency of original notarized certifications, and also promise that the original notarized certifications will be submitted completely before approval.

The registration applications according with the above situation could be accepted by CDE. The applicant shall take the responsibility of the rejection for not supplementing original notarized certifications according to relevant requirements before approval.

In addition, the electronic certifications issued by overseas drug administration departments will be approved.

The above content will be implemented since the release date. The time for normal submission time of certifications will be notified according to the pandemic situation.

Release Date: 2020.05.13