China Specifies GMP Regulations on Investigational Products Used in Clinical Trials

by Grace Wang Jun 06, 2022

On May 27, China National Medical Products Administration (NMPA) released the Appendix to Good Manufacturing Practice (GMP) for Pharmaceuticals: Investigational Products Used in Clinical Trials, which will take effect on July 1, 2022. The appendix gives more detailed GMP requirements for the preparation of investigational products.

Application Scope

The appendix applies to

Ÿ   the preparation of investigational products used in clinical trials, including the investigational drugs being tested or the comparator drugs/placebos used as a reference1; the clinical trials aim for China's marketing authorization of the investigational drugs.

Ÿ   changes to packaging/labels of marketed drugs that are used as comparator drugs or investigational drugs2;

Ÿ   adding correctants to comparator drugs for blinded experiments.

* The Appendix is also a reference for active pharmaceutical ingredients (API) used in investigational products.

* If early-phase clinical trials are carried out for adding a new indication to a marketed drug, without changes to the dosage form and manufacturing process, then the manufacturing quality control should comply with GMP for marketed pharmaceuticals instead of this Appendix.

Table of Contents

Appendix to GMP for Pharmaceuticals: Investigational Drugs Used in Clinical Trials3

Chapter 1


Chapter 2


Chapter 3

Quality Management

Chapter 4


Chapter 5

Factories, Facilities, and Equipment

Chapter 6

Management of Materials

Chapter 7

Management of Documents

Chapter 8

Management of Drug Preparations

Section 1: Preparation of Investigational Drugs

Section 2: Comparator Drugs

Section 3: Packaging and Labeling

Chapter 9

Quality Control

Chapter 10

Product Release

Chapter 11

Delivery and Transportation

Chapter 12

Complaint and Recall

Chapter 13

Retrieval and Destruction

Chapter 14

Supplementary Provisions


Compared to the main content of pharmaceutical GMP, the appendix raises special requirements for investigational drugs. ChemLinked complied several highlights that need your attention.

1. Factories, Facilities, and Equipment

Ÿ   The verification of factories, facilities, and equipment for early phase clinical trials can be conducted based on the clinical trial phase and risk evaluations. The validation doesn't need to be as complete as that of commercial production.

Ÿ   The factories making investigational drugs do not necessarily obtain the Drug Manufacturing License, but they should comply with GMP and its appendices.

Ÿ   The clinical trial sponsor should evaluate the investigational drug's characteristics, such as toxicity, pharmacological potency, potential allergenicity, target patients, administration route, and risks for clinical trial subjects. Only after the evaluation can the sponsor decide whether to manufacture an investigational drug in the same production line with other drugs used in clinical trials or with marketed drugs.

-      If it is feasible to manufacture multiple drug products on the same production line, then it is suggested to produce different types of products in separate phases.

-      If the sponsor doesn't have sufficient knowledge of the investigational drugs' characteristics, then it is recommended that such drugs should be manufactured by independent facilities and equipment.

2. Management of Documents

Ÿ   Clinical trial sponsors should set up investigational drug files.

Ÿ   The investigational drug files

- are a set of documents and records of R&D, preparation, packaging, quality inspection, the release of products in batches, delivery, and transportation.

- should be kept until at least two years after the candidate drug is withdrawn from the market, or at least two years after the termination of the clinical trial or the registration application if the candidate drug fails to get marketing authorization.

- should at least contain the known or potential key quality attributes and key process parameters in the current R&D stage, and be evaluated with the development of the product, and be updated when necessary.

- can be original documents' certified copies, in paper or electronic form.

3. Process Validation

Ÿ   In early-phase clinical trials, the investigational drug's manufacturing process, which has not been confirmed completely, should be monitored to comply with quality requirements.

Ÿ   In confirmatory clinical trials, the scope and degree of manufacturing process validation should be determined according to risk evaluations. Standard scope of validation is not mandatory.

Ÿ   Validation items should be conducted if they are relevant to the clinical trial subject's safety. For instance, the sterile investigational drugs should comply with technical requirements for sterilization process or sterile manufacturing process.

Contact BaiPharm if you'd like to know more about pharmaceutical GMP in China. 

Grace Wang
ChemLinked Regulatory Analyst & Editor
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