China Updates Documentation Requirements for Rx-to-OTC Switch Applications

In China, Rx-to-OTC switch application means marketed prescription (Rx) drugs applying for over-the-counter (OTC) status. On Sept. 30, 2022, China Center for Drug Reevaluation (CDR) released the Documentation Requirements for Prescription (Rx) to Over-the-counter (OTC) Switch Applications (hereafter referred to as the Documentation Requirements).

The new Documentation Requirements will be effective from Nov. 1, 2022. Rx-to-OTC switch applications submitted before or on Oct. 31, 2022 are allowed to follow the old requirements in the Notification of Evaluating Rx-to-OTC Switch Applications.

Chemical drugs and biological products are subject to the same documentation requirements for Rx-to-OTC applications.

1. Drug Category for Rx-to-OTC Switch

Chemical and biological drugs are divided into three categories¹ for Rx-to-OTC switch:

Drug Category for Rx-to-OTC Switch
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.

2. Application Documents

Previously, China required four parts of documents in the Notification of Evaluating Rx-to-OTC Switch Applications²:

General documents;
Pharmacology documents;
Safety research documents;
Efficacy research documents.

Now the Documentation Requirements only requires two parts:

General documents;
Safety research documents.

Item 7 document about "legal quality standards for the finished drug, its API(s), and excipient(s)", previously in the pharmacology part, is now included in the general documents. Besides, drug quality document, previously in the pharmacology part, and efficacy research documents are no longer required.

Adverse drug reaction/event report is now under the item 9 clinical safety documents. Item 9 also covers clinical safety research literature and comprehensive analysis of all the documents under this item.

In general, the new Documentation Requirements reduces the items of required documents, and gives more detailed specifications under each item.

Updated 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

3. Required Documents for Corresponding Categories of Drugs

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
	Document items	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	-	+	+

4. Rx-to-OTC Switch: Current Data and Application Procedures

As of Oct. 8, 2022, 806 prescription drugs have obtained OTC status via Rx-to-OTC switch, including 595 traditional Chinese medicines (TCMs), 202 chemical drugs, and 9 biological products. Check China's OTC Drug Catalog for details.

For Rx-to-OTC switch procedures, please refer to part 2.2 of BaiPharm's insight "How to Get China's Marketing Authorization for OTC Drugs". For detailed application guidance and advice, please contact BaiPharm.