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have been deleted (related concepts such as the New Drug License and the New Drug Monitoring Period are officially withdrawn).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.

1.On June 24, 2020, the NMPA government website will release a new version of the drug registration application software for applicants.

2. From June 28 to June 30, in order to carry out the new and old system switching and joint debugging test, the NMPA and the provincial (regional, municipal) drug regulatory bureaus will suspend the use of existing drug registration related systems, and the corresponding drug registration Acceptance and certification services will also be suspended. During an emergency during this period, please contact the relevant department of NPMA.

3. From July 1, 2020, NMPA will launch a new version of the drug registration related system. Drug registration applicants are reminded to download the latest version of the application software and submit registration applications as required.

For more details on how this may impact you. Please contact: info@accestra.com

• Drugs that have been marketed overseas (not yet in China)

Whether it is chemical drugs, traditional Chinese medicines or biological products, they are mainly classified according to the classification of innovative new drugs, improved new drugs and generic drugs. Traditional Chinese medicines and biological products both have the overseas and domestic classification according to specific situations, while chemical drugs that have been marketed overseas are classified independently.

In the “Clinical Trial Technical Requirements for Drugs that Have Been Marketed Overseas but Not yet in China (Draft for Public Review)”, CDE has listed 4 types of scenarios whereby clinical trials can be exempted and another whereby the drug can be directly approved for marketing depending on the characteristics of the drugs and racial differences.

Specifically, three of the four types of criteria where clinical trials can be reduced or exempted directly are related to overseas original drugs.

Exemptions (Criteria 1)

The first criteria for exemption of clinical trials is that after evaluation the original drug is safe, effective without racial sensitivity. The overseas data can be accepted as one of evidences for China market approval, if global data support the safety, efficacy, and when there is no racial influence at the same time.

If the global data of the original research already contain PK and/or PD, safety and efficacy data of the Chinese population, and it is analyzed that the benefits for Chinese patients are greater than the risks, it can be directly approved for marketing.

If the original overseas drug is evaluated to be safe and effective, but lacks racial sensitivity data or data show there is racial sensitivity, relevant bridging clinical trials may be considered to conduct. If the global data lack relevant researches and data of racial differences, it is required to conduct PK and/or PD, efficacy and safety researches to support marketing approval. If global data can support the safety and efficacy of the drug, but due to racial factors have influence on the safety and efficacy evaluation, then dosage exploratory and confirmatory clinical trials shall be conducted to support the drug’s marketing application.

If the safety and efficacy data of original overseas drug is evaluated to be insufficient, it’s mandatory to conduct exploratory and confirmatory clinical trials according to the requirements of NDA application.

On the whole, from a policy perspective, China NMPA encourages the overseas innovative new drugs that have been approved overseas to conduct global clinical trials simultaneously.

If a drug that has not been approved overseas applies for China market approval simultaneously, the drug can be classified as an innovative new drug, which can benefit from data protection (monitoring) for 5 years, meaning this drug have 5 years of exclusivity in China.

Exemptions (Criteria 2)

The second criteria: China approved marketed drugs that have been approved overseas for new indications.

If the original drug has been approved for one indication for over 5 years, a series of conditions shall be met for the additional indication which has been approved overseas.

Therefore, when considering the overseas data as a support of new indication application, applicant shall also conduct in vitro antibacterial test for Chinese clinical isolates. The submitted clinical trial data can be on-site inspected or can be inspected by FDA, EMA and PMDA, in order to support the authenticity, liability and integrity of the clinical data. The clinical trial can be reduced or exempted based on the evaluation situation of overseas clinical trial data.

Please note that if the differences of disease etiology and pathological changes are significant, the efficacy of original drugs for different indications are quite different, then the overseas data for application of new indication is not applicable.

Exemptions (Criteria 3)

The third criteria is for the single drugs of overseas compound drugs are all marketed and approved in China.

The Chinese patients clinical trial data and overseas clinical trial data of the single drugs have been marketed show that, the benefits of this single drugs for Chinese patients are greater than the risks and there is no obvious racial factor compared with the data of overseas population. The submitted overseas clinical trial study of this compound drug shall conform to the relevant technical guidelines of China and foreign countries, and the relevant clinical trial data can be used for evaluating the drug’s safety and efficacy sufficiently. The submitted clinical trial data can be on-site inspected or can be inspected by FDA, EMA and PMDA, in order to support the authenticity, liability and integrity of the clinical data. Based on above situations, the clinical trials can be reduced or exempted.

• Overseas improved drugs

This draft for public review of registration classification has classified overseas approved original drugs and improved drugs as class 5.1 in China.

The “Clinical Technical Requirements for Drugs that Are Marketed Overseas Already But Not Marketed in China (Draft for Public Review)” proposes the situations of clinical trial reduction/exemption for improved drugs marketed already includes the addition of new dosage form, new administration routes and new strengths as follows:

If the original drug has been already marketed for over 5 years, the situations of additional new dosage form, new administration routes and new strengths for approved indication of original drug like the clinical trial study data of Chinese and overseas patients shows that, the benefit of this drug outweighs risks on Chinese patients and racial influence cannot be obviously observed compared with the data of overseas population. The submitted overseas clinical trial data of new dosage form, new administration route and new strength of the compound can be on-site inspected or can be inspected by FDA, EMA and PMDA, in order to support the authenticity, liability and integrity of the clinical data. Based on above situations, the clinical trials can be reduced or exempted.

• Generic drugs

If there are sufficient evidences to prove that the overseas original overseas drug has no efficacy or serious safety problem, then conducting clinical trial in China shall not be approved. It is worth noting that the draft for public review mentioned that the clinical data resources not only focus on registered clinical trial data, but also post-marketing clinical data including the dynamic evaluation of original drug by foreign regulatory agencies.

• API (Active Pharmaceutical Ingredients) Policy Improvements

The APIs of finished drugs that have been already marketed in China can apply for separated review and approval, and approval timeline is 200wds.

API Supplier Change Improvements

The clarification of the process of changing API supplier is one of the highlights of this draft for public review. Based on risks, changing suppliers of APIs can be classified as major change and medium change.

For the medium change, the physical property and impurity of API shall be consistent and shall have no influence on the quality of the preparations.

A comprehensive quality comparison research of API shall be conducted. And it is required to verify the method of this research, which emphasizes on comparing whether the impurity of API, the indexes (such as crystal form, size distribution, molecular weight distribution and viscosity) related to in vivo absorption and efficacy of API and preparation before and after change remains consistent.

The quality comparison research of preparations shall prove importantly that the dissolution/release testings of samples, or the significant physicochemical properties and indexes, and impurity related to in vivo absorption and efficacy are consistent before and after the change.

The consecutive 3 batches of preparations manufactured by the API after change shall be tested. The 1 batch of preparation manufactured by the changed API shall be conducted an accelerated and long-term stability observation, and it is required to provide stability study materials of over 3 months which has also been compared with that of the preparation before change when submitting application.

If the physical properties and impurity of the API are inconsistent before and after change, the impact on the quality of the preparation is a major change. For a major change, in vivo bioequivalence study shall be conducted when necessary. This means it’s unnecessary to conduct in vivo bioequivalence study for suppliers who change APIs if they are medium change, also means non-preparation-API enterprises may have two or more API enterprises file simultaneously for the same API product.

This article is originally translated from Y-LP.com.

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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

It has been almost 13 years since the implementation of China’s “Provisions for Drug Registration” (SFDA Order No.28) on Oct 1st, 2007. Over the past ten years, these provisions have played a very important role in ensuring drug’s safety, efficacy and controllable quality, and regulating behaviors in drug registration. But with the continuous improvement of global harmonization efforts around the world and the need for reform and development of China’s pharmaceutical industry, this was followed by the beginning of groundbreaking promulgation of “Review & Approval System of Drugs and Medical Device” (No. 44 [2015] by the State Council). Against this background, the Order No.28 implemented in 2007 could not meet the requirements of drugs’ registration application and review under the new situation. Based on the “Drug Administration Law” issued and implemented on Dec 1st, 2019, the new “Provisions for Drug Registration” has has finally been implemented after 4 months. This clarification is a significant market access milestone for international pharmaceuticals community.

This article mainly illustrates the issuance and implementation of new version of “Provisions for Drug Registration” (hereinafter referred to as “Provisions”) has multiple obvious effects on the applications of FDF (finished dosage form) products.

Q1: The interpretation of MAH (Market Authorization Holder) system in “Provisions”

A: The current “Drug Administration Law” introduce the “MAH” chapter for the first time, and stipulate the definition, responsibility, right and obligation of MAH in detail. The Article 3 in “Provisions” writes that “After obtaining drug registration certification, the applicant could be a MAH”. And the following chapter also illustrates the responsibility and obligation of MAH in the administration of drug registration.

Q2: With the post-implementation of “Provisions”, the overseas applicants (applicants of FDF products) of China could also be MAH. Then what are the conditions overseas applicants shall have simultaneously?

A: It is clearly stated in Article 38 of Chapter 3 of “Drug Administration Law” that if the MAH is an overseas enterprise, this enterprise shall appoint its legal person in China perform the obligations of MAH and bear joint responsibilities.

Q3: What is the impact of the new classification on the registration work, as drug registration is managed according to the classification of traditional Chinese medicine, chemical drugs and biological products?

A: The “Provisions” unifies the classification standard of traditional Chinese medicine, chemical drug and biological product, which means they are classified to innovative new drugs, improved new drugs and generic drugs by innovation degree. And different generic products have different name of its category as the table below shows.

At the same time, the “Provisions” mentions that the detailed classification and corresponding requirements for application materials will be formulated and issued by NMPA in accordance with product characteristic, innovation degree of drug and management need of review&approval. As for the application of chemical drug, NMPA will update the announcement on the work plan for the reform of the classification of chemical drug registration (namely No.51, 2016). We’ll continue to focus on what the specific writing requirements for registration materials of each category.

Q4: Is there any difference between the clinical trial negative approval timeline in the “Provisions”, that applications for clinical trials shall be decided whether or not within 60wd from the date of acceptance, and that of No.50, 2018? And what is the impact of this difference on the real registration application?

A: Here is basically the same as “Announcement of NMPA on Adjusting the Review&Approval Procedure of Drug Clinical Trials” (No.50, 2018) promulgated by NMPA on July 7th, 2018. However, the details have some obvious changes. For example, the timeline of clinical trial mentioned in No.50, 2018 is “Within 60wd from the date of application acceptance and payment, while “Applications for clinical trials shall be decided whether or not within 60wd from the date of acceptance” in the “Provisions”. Especially for 80% of imported FDF items, it may take almost 2 months for an applicant to complete the step of payment, as the several rounds of communication between CDE and applicant for exchange rate and influences of domestic and foreign holidays. “Provisions” will really benefits overseas applicants, if it is implemented and counted time from acceptance.

Q5: What is the significance of proposing the safety update report during the development for the clinical trial study?

A: This item echoes the negative approval system of 60wd in “Announcement on Adjusting the Review&Approval Procedure for Clinical Trials of Medical Device”, which has provided definite evidence for applicants’ standard operation during clinical trials.

Q6: What is the specific impact of the implementation of BE study filing system and promulgation of “Technical Guidance for the Acceptance of Overseas Clinical Trial Data of Drug” on drug registration work?

A: This item corresponds perfectly to the No.257, 2015, that is “Announcement on Management of Implementing BE Study Filing System of Chemical Drugs by CFDA”, and provides a very good policy entry for the registration of generic drugs. The long process of “Applying for clinical trial” is not a mandatory requirement for oral solid generic drug applicant to deploy BE study. The applicant can conduct BE study after BE filing according to current regulations, which not only greatly saves power of review but also shortens the timeline of application of generic drugs.

In addition, the implementation of the two policies is very favorable for the application of imported oral solid preparations. With the promulgation of “Technical Guidance for the Acceptance of Overseas Clinical Trial Data of Drug” by NMPA on July 6th , 2018, imported oral solid preparation applicants can apply for market approval directly by using the BE study data that has been completed and approved abroad. The applicants have more advantages in obtaining review&approval in advance compared with the application of domestic generic drugs. Herein please note that the quality of overseas clinical trial must meet the relevant requirements of regulations and laws in China. For instance, an overseas applicant has only conducted fasting BE study when applying for EMA approval. But according to the domestic requirements of regulations and laws, it’s mandatory to provide both fasting and fed BE study data. As a result, in order to obtain the final approval, this overseas applicant shall supplement fed BE study with the availability of BE study data.

Q7: What is the influence of the implementation of drug-related associated review&approval system of API, pharmaceutical excipients and packaging materials (hereinafter referred to as AEP) on FDF registration application? What are the contents FDF applicants shall take in consideration?

A: The implementation of FDF review and drug-related associated review&approval strengthens FDF applicants’ main responsibility, and reminds FDF applicants that they shall consider from all aspects when choosing supplier of AEP. FDF applicants shall not only consider whether the quality of their AEP meet the process of FDF products, but also confirm whether the enterprise of AEP is willing to cooperate with FDF application to register on CDE platform and other possible inspections. Since these factors are related to whether the FDF products could be approved successfully.

Q8: The Article 42 of “Provisions” stipulate that if FDF applicant choose the AEP has not been registered, the relevant materials of AEP shall be applied together with FDF registration. What are the main effects of this provision on the acceptance link of FDF products application?

A: The spotlight of this item is the effect on acceptance link. For applicants especially for overseas applicants, it is not necessary for them to communicate repeatedly with supplier of AEP, and persuade the supplier to file on the CDE platform. According to the acceptance policy implemented about half a year ago, if the eligible AEP does not file on the platform, FDF applicant is required to provide an exclusive statement in the certification documents section and submit the full set of materials of AEP in the preparation documents when submitting the application for registration. Which means no exclusive statement will not be accepted. Actually AEP suppliers always provide their goods simultaneously to multiple FDF enterprises. In that case, it will be a fake statement if provided. Recently, with the adjustment of acceptance policy and the promulgation of “Provisions”, applicants and their AEP suppliers will no longer face this kind of embarrassing situation.

This article is originally translated from Canny.

Glossary

FDF Finished Dosage Form
MAH Marketing Authorization Holder
AEP API, Pharmaceutical Excipients and Packaging Materials

Note:
Here the NDAs are the drugs approved by NMPA in China for the first time, which includes NMEs (and compounds consisted of NME), biological products, traditional Chinese medicines and vaccines. The NMEs are mainly the category 1 and category 5.1 of chemical drugs. The biological products are mainly the category 1 and category 2 biologics, excluding biosimilars, new indications and new dosage forms.

The following is a brief introduction of some selected NDAs：

• The first ADC drug approved in China

Roche’s Trastuzumab Emtansine injectable (Kadcyla®) was approved in China on January 21, 2020, becoming the first antibody-drug conjugated(ADC). Its indication is for the adjuvant treatment of people with HER2-positive early breast cancer with residual invasive disease after neoadjuvant treatment. Kadcyla has been approved by FDA in May 2019, EMA in December 2019 and now also parallel approval of China.

• The first approved traditional Chinese medicine for diabetes in recent 10 years

Mulberry Twig Alkaloids Tablet of Wehand was approved by NMPA on March 17, 2020. The main ingredient is twig alkaloids extracted from mulberry. This tablet is applied for the treatment of type 2 diabetes in combination of diet control. The phase III clinical trial has demonstrated the efficacy of the drug is similar with that of acarbose. Mulberry twig alkaloids tablet is the first new traditional Chinese medicine approved for diabetes in recent 10 years.

• The first Chinese approved 3^rd generation EGFR-TKI drug

Hansoh’s Almonertinib mesilate tablets obtained approval from NMPA on March 18, 2020 for the treatment of adult patients, who have progress with or after the treatment of EGFR-TKI and are confirmed with the presence of locally advanced or metastatic non-small cell lung cancer (NSCLC) positive for EGFR T790M mutation by detection. Almonertinib mesilate tablet is the third 3^rdgeneration EGFR-TKI new drug in the world , and also the first 3^rd generation EGFR-TKI drug in China.

Besides the above drugs, NMPA has approved another two clinical urgently needed overseas new drugs, namely Pfizer’s Tafamidis meglumine soft capsules and Takeda’s Vedolizumab for injection. In addition, the nasal freeze-dried influenza live vaccine of BCT is the first nasal spray influenza vaccine in China, and Atezolizumab injection of Roche is the second PD-L1 drug approved by NMPA.

This article is translated from Pharmcube.

In terms of safety, Favipiravir has been approved by PMDA of Japan in 2014 and there is no obvious adverse reaction found since marketing. In the clinical study for the treatment of COVID-19(Corona Virus Disease 2019), no obvious adverse reaction has been found.

In terms of efficacy, the Third People’s Hospital of Shenzhen carried out an efficacy and safety study for the treatment of COVID-19 with Favipiravir combined with interferon. This study has enrolled 80 subjects including 35 subjects of Favipiravir group and 45 subjects of control group. The study result shows, in the aspect of transforming the viral nucleic acid into negative, the median time of Favipiravir group (4 days) has been shortened compared with control group (11 days) with a significant difference. In terms of improvement in chest imaging, the improvement rates of Favipiravir group and control group are 91.43% and 62.22% respectively.

Zhongnan Hospital of Wuhan University led a multi-center, randomized, open and positive parallel controlled clinical study of Favipiravir for the treatment of COVID-19, and has enrolled 120 subjects of each group and observed clinical treatment. This clinical study displayed the therapeutic efficacy of treatment group on COVID-19 was significantly better than that of control group. In terms of primary endpoint assessment, the clinical recovery rate in common type subjects of treatment group was significantly better than that of control group (71.43% and 55.86% respectively) at the end of treatment. In terms of secondary endpoint assessment, average antifebrile time of treatment group and control group was 2.5 days and 4.2 days, which means the treatment group is better. The time in relieving cough of treatment group was also significantly better than that of control group, with the average time of relieving cough 4.57 days and 5.98 days respectively. In the auxiliary oxygen treatment or noninvasive mechanical ventilation rate of common type subjects during the therapy, the treatment group was significantly lower than control group, respectively with 8.16% and 17.12%. The assessments above all have statistical differences between the two groups.

In terms of accessibility, a domestic enterprise has obtained drug registration certificate from NMPA this February and achieve mass production. Therefore, the supply of clinical drug could be guaranteed.

This article is translated from The Beijing News.

In terms of approval, in 2019, the acceptance number has obtained review comment is 1,855. Among them, there are 834 approval clinical acceptance numbers, 427 approval manufacturing acceptance numbers and 99 imported acceptance numbers have been approved. Compared with the approved number in 2017 and 2018, the overall is in a fluctuation condition, which has a direct connection with the changes in registration approval policies and the increase of domestic review in recent years.

According to the statistics, it takes 427 days (50% shorter than 2018) for NDA and 1,205 days for ANDA (13% shorter than 2018). Among them, for imported new drug applications, the products has got priority review can be reviewed in 363 days, non-priority review products need 570 days to complete their reviews. However, it takes 422 days to complete the review of a domestic new drug has been given priority review.

1.Chemical drugs application statistic information in 2019

In 2019, 6,106 application acceptance numbers of chemical drugs involve 1,263 active ingredients and 1,470 enterprises. In the 6,106 numbers, the number of domestic chemical drugs is 3,256, accounting for 53%, and the imported chemical drugs application acceptance number is 2,850 which accounts for 47% (as the image below shown).

Note: Others in application content include: re-registration application, re-review, supplementary application and other applications. Other types include: supplementary application, re-review and other applications.

From the perspective of application type in recent 3 years, the NDA acceptance number has gradually increased and grown steadily, which has a close relation with China’s encouraging innovation policy. And the imported application acceptance number decreased slightly in 2018 has begun to increase substantially in 2019.

Note: Data based on Insight application progress database statistics to Dec. 31th 2019.

From the point of view of registration type, in 2019, there are 516 acceptance numbers of type 1 new drugs involving 221 products. In which, domestic type 1 NDA acceptance numbers are 332 involving 143 products, and 184 acceptance numbers of imported type 1 new drugs involving 78 products. For the improved type 2 new drugs, the number is 176 which involves 8 products. The number of type 3 and type 4 generic drugs are 221 (123 products) and 699 (201 products) respectively. And there are 271 acceptance numbers of type 5.1 and 129 acceptance numbers of type 5.2.

2. Chemical drugs approved statistic information in 2019

Among the 1,855 chemical drug acceptance numbers approved for CDE review and approval in 2019, domestic products acceptance numbers are 1,289, and import products acceptance numbers are 566. In terms of clinical approval, the number of clinical approvals started to increase in 2019 due to the negative comment clinical system, has reached a total of 827. In terms of marketing approval, 427 numbers are approved and 99 imported numbers are approved in 2019.

As of January 3 2020, the largest number approved of 2019 is supplementary application, followed by imported drug approval.

Note: The statistic time is Jan.3st 2020, statistics at different time points will cause differences in the number review comments. (This data is from Yaozhi)

This article is referenced and translated from Insight database and Yaozhi. We’ll get further detailed information at mid 2020 when CDE release official annual report of 2019.