China's Marketing Authorization Holder (MAH) System

• Manufacturing and selling the registered drug (sales only allowed when the MAH has a drug distributor license).

• Entrusting manufacture and sales to other companies; Notes: For the limits on what products can an MAH entrust to manufacturers, please refer to this article's fifth part about MAH entrusting manufacturing to others.

• Transferring the marketing authorization (MAH change);

• Renewing the drug registration certificate;

• Advertising the drug.

• Be responsible for the drug's non-clinical research, clinical trials, manufacturing and sales, post-market research, adverse event monitoring and management.

• Establish a drug quality assurance (QA) system; periodically inspect the quality management systems of the entrusted manufacturers and distributors in the downstream supply chain.

• Establish a marketing release protocol for the manufactured drugs. Audit the drug products before they enter the market; release the pharmaceuticals to the market only after the quality manager signed.

• Establish and implement a drug traceability system.

• Establish an annual report system, submitting drug information to competent regulators yearly.

Notes: If the MAH is a foreign company outside China, the company shall appoint a legal corporate entity in China to fulfill MAH's responsibilities. The foreign MAH and the Chinese agency shall take joint liability.

Obligations of the Local Chinese Agent for a Foreign MAH:

Ÿ     Establish a drug quality assurance system;

Ÿ     Establish and implement a drug traceability system;

Ÿ     Establish a drug annual report system;

Ÿ     Establish a system for managing post-marketing changes, and make changes in compliance with relevant regulations;

Ÿ     In the post-marketing stage, be responsible for product recall, quality complaints, compensation for quality defects, etc., and report the situations to the provincial medical products administration of the province where the agent got registered;

Ÿ     Establish a pharmacovigilance (PV) system and make post-marketing risk management plans;

Ÿ     Submit standard substances to the National Institutes for Food and Drug Control (NIFDC); accept sampling inspections by medical products administrations;

Ÿ     Keep contact with the MAH outside China; assist medical products administration in inspection, investigation, and handling of illegalities at manufacturing sites outside China

Ÿ     Record-filing and management of pharmaceutical representatives, who are professionals that represent the foreign MAH in China to deliver, communicate on, and submit drug information.

Products

Regulation

Drugs

MAHs can entrust the manufacture of drugs to qualified pharmaceutical manufacturers.

Blood products, anesthesia, antipsychotics, toxic drugs for medical use, chemical precursors

MAHs shall NOT entrust the manufacture of these products unless permitted by NMPA.

APIs that have been registered, approved independently, or approved in association with relevant drug products.

MAHs shall NOT entrust the manufacture of these products.

Vaccines

• The vaccine MAH shall have capabilities to manufacture vaccines.

• If the demand exceeds the production capabilities, the MAH shall apply for NMPA's approval for entrusting the manufacture to others.

MAH

Manufacturer

Regulation

Chinese

Another Chinese company

• The entrustment is regulated by provincial medial products administrations;

• The MAH and the manufacturer shall obtain drug manufacturing licenses first.

*Drug product manufacturing license has three different types:

- License A  is for an MAH that manufactures products by itself;

- License B is for an MAH that entrusts manufacture to contract manufacturers;

- License C is for a contract manufacturing organization (CMO) that manufactures products for MAHs.

Overseas

Another overseas company

• The entrustment is regulated by NMPA;

• The drug shall have overseas marketing authorization;

• The overseas MAH shall appoint a Chinese legal corporate entity as its local agent.

Chinese

Overseas

Lack of legal basis.

Overseas

Chinese

Lack of legal basis.

*MAHs in Hong Kong SAR or Macao SAR can entrust manufacture to qualified companies in nine cities in the Greater Bay Area, including Guangzhou, Shenzhen, Zhuhai, Foshan, Huizhou, Dongguan, Zhongshan, Jiangmen and Zhaoqing.

MAH Transfer

Details of Changes

Procedures

Review Time

Between Chinese MAHs

- Only changing the MAH entity; and

- NO technical changes involved.

Step 1: The new MAH shall obtain the drug manufacturing license within the corresponding manufacturing scope.

Step 2: The new MAH shall submit supplemental application to NMPA's Center for Drug Evaluation (CDE).

20 workdays

- Changing the MAH entity; and

- Changing the manufacturing site; and

- NO technical changes involved.

- Changing the MAH entity; and

- Changing the manufacturing site; and

- Changing the manufacturing process, including manufacturing facilities, active pharmaceutical ingredients, excipients, packaging materials, technical parameters, and quality standards.

Step 1: The new MAH shall first submit the supplemental application to CDE.

Step 2: After the MAH transfer is approved, the new MAH shall conduct research, evaluation and necessary verification according to relevant technical guidelines.

Step 3: The new MAH shall submit supplemental application, file a record, or send a report to the competent provincial medical products administration.

(1) For supplemental application: 60 workdays;

(2) For supplemental application together with other items for application: 80 workdays;

if the application items involve clinical data review or verification & inspection for drug registration, the review will be completed within 200 workdays.

Between overseas   MAHs

- Only changing the MAH entity; and

- NO technical changes involved.

Step 1: The new MAH shall obtain the drug manufacturing license within the corresponding manufacturing scope

Step 2: The new MAH shall submit a supplemental application to CDE.

*In principle, the new MAH shall obtain overseas marketing authorization documents before submitting the supplemental application to CDE.

60 workdays

- Changing the MAH entity; and

- Changing the manufacturing site; and

- NO technical changes involved.

- Changing the MAH entity; and

- Changing the manufacturing site (still overseas); and

- Changing the manufacturing process, including manufacturing facilities, active pharmaceutical ingredients, excipients, packaging materials, technical parameters, and quality standards.

Step 1: The new MAH shall conduct research, evaluation and necessary verification according to relevant technical guidelines.

Step 2: The new MAH shall submit supplemental application or file a record to CDE.

*In principle, the new MAH shall obtain overseas marketing authorization documents before submitting the supplemental application to CDE.

(1) For supplemental application: 60 workdays;

(2) For supplemental application together with other application items: 80 workdays; if the application items involve clinical data review or verification & inspection for drug registration, the review will be completed within 200 workdays.

Marketing authorization   documents and their copies

(1) Drug registration certificate;

(2) Approval documents for the supplemental application;

(3) Approval documents for renewing the drug registration certificate.

Evidence documents

Change of MAH's name or registered address

Chinese

(1) The previous MAH's and the new MAH's drug manufacturing licenses;

(2) The change records on the licenses;

(3) A copy of both MAHs' business licenses.

Overseas

For MAHs that appointed a Chinese agent for drug registration:

(1) Letter of authorization from the MAH to the agent;

(2) The notarization document;

(3) The accreditation document;

(4) Chinese translation of the three documents above;

(5) A copy of the Chinese agent's business license.

(6) Evidence documents of the competent overseas authority approving the MAH change, and the notarization and accreditation documents with their Chinese translation.

Change of MAH entity

Chinese

(1) The previous MAH's and the new MAH's drug manufacturing licenses;

(2) The change records on the licenses;

(3) A copy of both MAHs' business licenses;

(4) The original document of the MAH transfer agreement (with trade secrets concealed).

Overseas

Same as the documents for changing MAH's name and address.

Applicant's commitment

The new MAH shall promise that it will not change the drug's new manufacturing site, formulation, manufacturing techniques, and quality standards.

Others

Other documents required by NMPA.

R&D company without production or sales lines

The company can be an MAH itself, entrust Chinese manufacturers to produce drugs, and sell the drugs by itself or entrust Chinese suppliers for sales.

Giant listed company with abundant R&D investments

The company can choose to cooperate with Chinese original equipment manufacturers (OEM) to reduce the costs for building manufacturing sites.

Small-sized company with production lines for its own drugs

The company can choose to cooperate with Chinese OEMs to better practice GMP compliance and optimize the production.

Sales company

The company can be an MAH by collaborating with R&D companies & drug manufacturers and establishing corresponding quality management system.