INTERPRETATION

How to Get China's Marketing Authorization for OTC Drugs

by Grace Wang
Sep 16, 2022

In China, the marketed drugs have been divided into prescription drugs (Rx drugs) and non-prescription drugs since 2000.1 Non-prescription drugs, also known as over-the-counter (OTC) drugs, can be bought and used without prescription from a licensed physician.

According to the health information and clinical research service provider IQVIA, China's OTC drug market size is expected to grow from 244 billion yuan (circa US$33.64 billion) in 2021 to 306.1 billion yuan (circa US$42.1 billion) in 2025, with a compound annual growth rate of 5.3%.2

To enter such a market via general trade, OTC drugs usually need to go through complicated marketing authorization procedures that may last 2-3 years for drugs exempted from clinical trials, or even 4-5 years for drugs subject to clinical trials.

This article discusses how to market OTC drugs in China via marketing authorization application or Rx-to-OTC switch:

Contents:

1. China's Marketing Authorization for OTC Drugs

    1.1. NDA & ANDA Procedures

    1.2 NDA & ANDA Documentation

2. Application for Rx-to-OTC Switch

    2.1. Rx-to-OTC Application Scope

    2.2. Rx-to-OTC Application Procedures

    2.3. Rx-to-OTC Application Documentation

3. Future Regulation: OTC Drug Marketing Authorization Procedures May Be Simpler

4. BaiPharm's NDA and ANDA Preparation and Submission Services

1. China's Marketing Authorization for OTC Drugs

In China, OTC drugs are subject to the same marketing authorization procedures with prescription drugs. Though more widely used and safer than prescription drugs, OTC drugs do not have an independent marketing authorization system.

Currently, there are two routes for getting OTC drug marketing authorization from China National Medical Products Administration (NMPA).

  1. Unmarketed OTC drug applying for marketing authorization under the drug classification rules, which are the same for prescription drugs.

  2. Marketed prescription drug applying for Rx-to-OTC switch.

As of Sept. 1, 2022, China NMPA has approved 5,041 OTC drugs, including 1,111 chemical drugs, 3,921 traditional Chinese medicines, and 9 biological products.

Among the approved OTC drugs, 805 were former prescription drugs and granted OTC status via Rx-to-OTC switch, while 192 of the 805 having both Rx and OTC statuses.

1.1. NDA & ANDA Procedures

New drug applications (NDAs) are for innovative/improved new drugs, while abbreviated new drug applications (ANDAs) are for generic drugs. Their procedures are illustrated below:

China New Drug Application (NDA) ProceduresChina New Drug Application (NDA) Procedures

China Abbreviated New Drug Application (ANDA) ProceduresChina Abbreviated New Drug Application (ANDA) Procedures

1.2 NDA & ANDA Documentation

NDAs are required to include documents in M1-M5 modules. ANDAs should include M1, M2, M3, and M5 documents. However, M5 documents are not needed when the ANDA are exempted from BE studies and clinical trials.


M1: Administrative Documents and Drug Information

Ÿ   Cover letter

Ÿ   1.1 Table of contents

Ÿ   1.2 Application form

Ÿ   1.3 Product information (package insert, label, etc.)

Ÿ   1.4 Application status (if applicable)

Ÿ   1.5 Application for expedited program (if applicable)

Ÿ   1.6 Meeting with CDE (if applicable)

Ÿ   1.7 Change during the clinical trial (if applicable)

Ÿ   1.8 Pharmacovigilance and risk management (if applicable)

Ÿ   1.9 Post-approval studies (if applicable)

Ÿ   1.10 Post-approval change (if applicable)

Ÿ   1.11 Applicant's certificate and qualification documents

Ÿ   1.12 Small-and-micro enterprise certificate (if applicable)

For imported drugs:

Ÿ   Marketing authorization document from the authority of country of origin (if the drug has been approved overseas)

Ÿ   GMP and production authorization letter from the country of origin (if the drug has been approved overseas)

Ÿ   In-use medication package insert and label, and their Chinese translation (if the drug has been approved overseas)

Ÿ   The Chinese agency’s appointment letter, notarization document, and their Chinese translations

Ÿ   Copy of the Chinese agency’s business license

M2: CTD Summaries

2.1 CTD table of contents

2.2 CTD introduction

2.3 Quality overall summary

2.4 Non-clinical overview

2.5 Clinical overview

2.6 Non-clinical written and tabulated summaries

       Pharmacology, pharmacokinetics, toxicology

2.7 Clinical summary

       Biopharmaceutic studies and associated analytical methods

       Clinical pharmacology studies

       Clinical efficacy

       Clinical safety

       Literature reference

       Synopses of individual studies

M3: Quality

3.1 Table of contents of Module 3

3.2 Body of data

       Drug substance

       Drug product

       Regional information

3.3 Literature reference

M4: Non-clinical Study

4.1 Table of contents of Module 4

4.2 Study reports

4.3 Literature reference

M5: Clinical Study

5.1 Table of contents of Module 5

5.2 Tabular listing of all clinical studies

5.3 Clinical study reports

5.4 Literature reference



2. Application for Rx-to-OTC Switch

2.1. Rx-to-OTC Application Scope

Chinese MAHs and the Chinese agencies of foreign MAHs can submit Rx-to-OTC applications unless the drugs belong to any of the following 10 categories.3

  1. Drugs in the monitoring period (≤ 5 years since marketing authorization).

  2. Emergency drugs and other drugs for diseases that are inappropriate for self-medication. For example, drugs for treating tumors, glaucoma, peptic ulcer, mental diseases, diabetes, liver diseases, kidney diseases, prostate diseases, immunological diseases, cardiovascular diseases, or sexually-transmitted diseases.

  3. Drugs that are inconvenient for self-medication. For example, injections and implants.

  4. Drugs that entail monitoring and guidance from medical professionals during medication.

  5. Drugs that entail special storage conditions.

  6. Antiviral drugs and hormones (except contraceptive pills) that act on the whole body.

  7. Drugs containing toxic traditional Chinese medicine (TCM) ingredients whose safety cannot be proved;

  8. Active pharmaceutical ingredients (APIs), pharmaceutical excipients, TCM ingredients, and decoction slices.

  9. Toxic drugs for medical use, anesthetics, psychoactive drugs, radioactive drugs, and other drugs subject to special management.

  10. Other drugs that do not meet the OTC drug requirements.

2.2. Rx-to-OTC Application Procedures

  1. The Chinese MAH or the Chinese agency of the foreign MAH submits Rx-to-OTC switch application and the application form to the provincial medical products administration of the provincial administrative area where the MAH or agency is.

  2. The provincial medical products administration reviews the completeness and authenticity of the documents. Applications failing the review will be dismissed. The applications passing the review will be sent to NMPA with the application form stamped with the provincial administration's official seal.

  3. NMPA conducts medical and pharmacological evaluations of the proposed drug according to the principle of "safe for medication, clear in efficacy, steady in quality, and convenient in use". Eventually, NMPA will publish the list of drugs granted with Rx-to-OTC switch.

2.3. Rx-to-OTC Application Documentation

Documentation differs for the three categories of chemical drugs:

Drug Category for Rx-to-OTC Switch4

Category 1

Drugs announced by China National Medical Products Administration (NMPA) as OTC Drugs (listed in China's OTC Drug Catalog) whose dosage form and/or strength is changed, but the indication, dosage, or route of administration are NOT changed.

Category 2

New combination drugs containing active pharmaceutical ingredients (APIs) confirmed and announced by NMPA as APIs of OTC drugs.

Category 3

Drugs not belonging to either of the above two categories.

Required Document Items for Rx-to-OTC Switch Applications

A.   General documents

1. Rx-to-OTC switch application form

2. Table of contents (the documents' names and page numbers)

3. Summaries

 (1) R&D

(2) Manufacturing & sales

(3) Whether products having the same API as the that of the proposed drug with marketing authorization in China

(4) - Developer of the original version of the proposed drug;

 - the country/region which first granted marketing authorization to the original drug;

- situation about whether the original drug has acquired marketing authorization, its sales, and whether it's administered as an OTC drug in overseas counties/regions (at least covering   the US, the EU, the UK, Canada, Australia, and Japan)

  (5) Safety-concerning measures taken by overseas regulators and marketing authorization holders (MAHs) on the   products which have the same API with the original drug since the original drug acquired marketing authorization

  (6) Summary of application documents, summarizing the relevant researches and literature, and concluding whether the documents can support the proposed drug to be administered as an OTC drug

  (7) Literature retrieval dating back to the recent six months before the application is submitted

4.   Draft of the medication package insert for the drug to be sold as an OTC drug in China; the medication package insert for the drug currently sold as a   prescription drug in China

  - The overseas OTC medication package insert should also be submitted if the proposed drug is administered as an OTC drug in a foreign country/region.

5. Photo of the smallest package unit currently on sale

6.   Certificates

  - Copy of the drug registration certificate and its appendix.

  - Overseas MAHs should authorize its local agent in China to submit the Rx-to-OTC switch   application with the letter of authorization.

7.   Legal quality standards for the finished drug, its API(s), and excipient(s)

B.   Safety research documents

8. Toxicology research

    8.1 Research

    8.2 Literature

9. Clinical safety research

  -   Comprehensive analysis of all the clinical safety documents

  -   Research (including the research which involves safety study where the   proposed drug is used as a reference drug) and literature

  -   Adverse drug reaction/event report

10. Dependence research

    *Not needed if the API has no dependence

11. Tolerance research

12. Interactions with food and other drugs

13. Safety research for patients who conduct self-diagnosis and self-medication

14. Safety research based on the drug's wide use

Notes: Non-Chinese documents should be submitted with Chinese translations.

The below table illustrates the corresponding documents for the three categories of proposed drugs. “+” means mandatory, “-” means exempted, “” means voluntary for submission, and “*” means the item is subject to the its specification.


Document items

Drugs

Category 1

Category 2

Category 3

A. General documents

 

1

+

+

+

2

+

+

+

3

+

+

+

4

+

+

+

5

+

+

+

6

+

+

+

7

+

+

+

B. Safety documents

8.1

8.2

+

9

+

+

+

10

*

*

*

11

-

-

+

12

-

+

+

13

-

+

+

14

-

+

+

3. Future Regulation: OTC Drug Marketing Authorization Procedures May Be Simpler

Though there are no specific effective rules on OTC drug marketing authorization procedures, the Administrative Measures for Drug Registration has claimed that drugs meeting any of the following conditions can directly apply for OTC drug marketing authorization.5

  1. The proposed drug has the same active ingredient, indication (or main therapeutic function), dosage form, and strength with a marketed OTC drug in China.

  2. The OTC drug, previously approved by NMPA, is now applying for changing its dosage form or strength, without changing its indication (or main therapeutic function), recommended dose, or route of administration.

  3. The new compound preparation is composed of active ingredients of the OTC drugs approved by NMPA.

  4. Other situations permitted for direct marketing authorization applications for OTC drugs.

    • The OTC drug has overseas marketing authorization only and is applying for marketing authorization in China;

    • The proposed drug is a generic version of the OTC drug which has overseas marketing authorization only.

    • The proposed OTC drug has been marketed in China, and is applying for adding a new indication or target group.

    • The proposed OTC drug has been marketed in China, and is applying for adding a new route of administration.

    • The proposed OTC drug has a new active ingredient.

In addition, China Center for Drug Evaluation (CDE) has released the draft of Technical Guidelines on Marketing Authorization of Chemical OTC Drugs for public comments. The draft noted that the data on wide and long-term human use of overseas OTC drugs could be used in evaluating benefits and risks of marketing authorization in China.6

Based on the evaluation result, CDE will consider simplifying or exempting their pharmacology & toxicology studies, clinical pharmacology studies, clinical researches and other researches relevant to marketing authorization. Thus, overseas OTC drugs' marketing authorization procedures will probably take shorter time.

4. BaiPharm's NDA and ANDA Preparation and Submission Services

For companies intending to submit NDAs/ANDAs for drug marketing authorization in China, BaiPharm provides the following services:

  • Assessing the approval feasiblity (including the feasibility for expedited approval) for the NDA/ANDA;

  • Providing checklist for the application dossier;

  • Analyzing data gap, conducting pre-review, and offer advice on revising the documents;

  • Reviewing, translating, drafting, and submitting the dossier in CTD format;

  • Sending samples for pre-approval inspection;

  • Tracking the review progress;

  • All-the-way consulting service until approval, including communicating with CDE reviewers, replying to deficiency letters from CDE, as well as preparing and submitting supplemental applications;

  • Post-marketing services, including preparing and submitting change/variation applications and annual reports.

Related Article

In recent years, cross-border e-commerce (CBEC) has emerged as a fast approach to sell OTC drugs in China by not requiring marketing authorization. Please refer to the article to learn about how to sell OTC drugs via cross-border e-commerce.

Grace Wang
ChemLinked Regulatory Analyst / Editor
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