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$35.39 billion) in 2021 to 306.1 billion yuan (circa US$44.4 billion) in 2025, with a compound annual growth rate of 5.3%.

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: Regional Administrative Information

  • Cover letter

  • Table of contents

  • Application form

  • Product information

  • Application status (if applicable)

  • Application for expediting approval (if applicable)

  • Meeting information (if applicable)

  • Change during the clinical trial (if applicable)

  • Risk management

  • Post-approval studies (if applicable)

  • Post-approval change (if applicable)

  • Applicant's/MAH's certificate and qualification documents

  • Small-and-micro enterprise certificate (if applicable)

For imported drugs:

  • Appointment letter for the Chinese agency

  • Drug approval from the authority of country of origin

  • GMP and production authorization letter from the country of origin

  • Application form filled out by the Chinese agency

M2: Summary Table for Main Study

  • Quality overall summary (QOS)

  • Non-clinical overview

  • Clinical overview: analysis of clinical data in common technical documents (CTDs)

  • Tabulated non-clinical summary

  • Clinical conclusion: conclusion of all the clinical data in CTDs

M3: Pharmaceutical Study

  • Drug substance

  • Drug product

  • Regional information

M4: Non-clinical Study

  • Review of non-clinical study

  • Primary pharmacodynamics

  • Safety pharmacology

  • Single-dose toxicity

  • Repeat-dose toxicity

  • Genotoxicity

  • Reproductive toxicity

  • Carcinogenicity

  • Dependence

  • Hypersensitivity, hemolytic, and local tolerance

  • Others

  • Non-clinical pharmacokinetics

M5: Clinical Study

  • BE study (if applicable)

  • Clinical trial (if applicable)

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.2

  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:

Category 1

Drugs having the same formulation and route of administration with the approved OTC drugs, but only with different dosage form or strength

Category 2

Compound preparations with active ingredients of approved OTC drugs

Category 3

Drugs not belonging to the above two categories

Documents: 

A. Summarized documents

1. Rx-to-OTC application form (electronic document)

2. Table of contents

3. Statements about the application (electronic document)

4. Draft (electronic document) of the medication package insert of the OTC drug

5. A minimum package unit of the drug currently on sale

6. Licenses (including drug manufacturing license, or imported drug license. In particular, the Chinese agency should provide the original authorization letter from the manufacturer)

B. Pharmacology

7. Legal quality standards of the finished drug product, its ingredients and excipients

8. Drug quality

C. Safety research

9. Toxicology research

10. Adverse reaction (event) research

11. Dependence research

12. Tolerance research

13. Interactions with food and other drugs

14. Safety research for the situation where consumers conduct self-diagnosis and   self-medication

15. Safety research based on the drug’s wide use cases

D. Efficacy research

16. Pharmacodynamic study

17. Clinical efficacy research

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, and “△” means voluntary for submission.

Document

Category 1

Category 2

Category 3

A. Summarized documents

1

+

+

+

2

+

+

+

3

+

+

+

4

+

+

+

5

+

+

+

6

+

+

+

B. Pharmacology

7

+

+

+

8

+

+

+

C. Safety research

9

+

10

+

+

+

11

-

-

+

12

-

-

+

13

-

-

+

14

-

-

15

-

D. Efficacy research

16

+

+

+

17

+

+

+

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.3

  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.4

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:

NDA service

  • Feasibility assessment or data gap analysis for the NDA applications to avoid deficiencies in application dossiers and minimize the risk of rejection by NMPA;

  • Preparation of the outline of NDA application dossier;

  • NDA application dossier review, translation, drafting and submission in CTD format;

  • All-the-way consulting service for NDA application until approval, including communications with CDE reviewers, reply to deficiency letters from CDE, as well as preparation and submission of supplemental applications;

  • Post-marketing services, including preparation and submission of post-marketing change applications and annual reports.

ANDA service

  • Local agency for ANDA and filing;

  • Application dossiers: application document checklist and data gap analysis for feasibility assessment; guidance for preparing dossiers and translation of the dossiers;

  • Customized risk evaluation and optimized application strategy to avoid deficiencies in the application dossier and minimize the risk of rejection by NMPA;

  • Support in communications with CDE reviewers;

  • Regulatory compliance consulting, on-site pre-audit and mock inspection; assistance in NMPA sample testing and on-site inspection;

  • Design and implementation of clinical trials or bioequivalence (BE) study; assistance in searching for clinical research organizations (CROs) in China, assessment of the CROs, and due diligence investigation of CROs;

  • Translation of documents for clinical studies, including pharmacology & toxicology documents, and referenced journal articles;

  • All-the-way consulting services until marketing authorization, including communications with CDE reviewers, reply to deficiency letters from CDE, as well as preparation and submission of supplemental applications;

  • Post-marketing services, including preparation and submission of post-marketing change 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
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