China Releases Guidance for Declaration of Chemical Drug Changes

by Grace Wang Mar 19, 2021

On Feb. 10, 2021, the Center for Drug Evaluation (CDE) of China National Medical Products Administration (NMPA) issued and started implementing the Guidance for Acceptance and Review of Chemical Drug Changes (Trial) 1. The document addresses supplemental applications that entail the reviews of state-level drug regulatory authorities, including those submitted during clinical trials.

Requirements vary for different supplemental applications

  1. For drugs which received conditional marketing approval during clinical trials, the marketing authorization holders (MAHs) shall first finish the trials and other relevant studies complying with applicable requirements within the given time. After that, the MAHs shall submit supplemental applications to complete the materials for marketing authorization.

  2. For changes of approved chemical drugs, the MAHs shall assess the changes according to relevant technical guidelines and then choose the change type following Requirements on Change Items and Declaration Materials for Approved Chemical Drugs 2.

  3. If an applicant intends to continue the drug clinical trial which was suspended for safety issues or other risks, the company shall submit a supplementary application for resuming the clinical trial after resolving the problems.

  4. If an overseas drug is transferred to China for production, it is the drug's Chinese holder that shall file an application in accordance with the requirements and procedures of marketing authorization application.

Application materials required for overseas companies

  1. Copies of the drug's overseas registration certificate and its attachments.

  2. If an overseas applicant designates a legal person in China to conduct drug registration, the foreign holder shall provide entrusted documents, the notarial certificate and its Chinese translation, and a copy of the business license of the registration agency as well.

  3. An MAH can apply for changing an overseas-marketed drug in China only if having received the change approval from the drug regulatory authority in its home country. For changes taking place in China, the MAH shall submit the certificates issued by its home regulatory authority, the notarial certificate and its Chinese translation.

  4. Applicants shall provide a copy of the trademark registration certificate in the case of applying for a drug's brand name.

  5. In case of changes of the overseas production site, the MAH shall submit the certification document issued by the local drug regulatory agency proving that the manufacturing site conforms to Good Manufacturing Practices (GMP). If a new drug's overseas manufacturing site changes during the period of clinical trial, the MAH shall provide the information stating that drugs used for clinical trial were made in compliance with GMP.

  6. Copies of legal source documents and authorization letters for active pharmaceutical ingredients (APIs), excipients and packaging materials.

In addition, a foreign-made drug's original certificates issued by its local drug regulatory agency don't have to be notarized by the local notary office and the Chinese embassy or consulate in the country if the certificates conform to the uniform format recommended by the World Health Organization. The certificates include:

  1. The certificate of marketing approval.

  2. The certificate of compliance with GMP standards.

  3. The permit of changes to the drug.

CDE will finish checking the materials' format within five days on receipt of an application. If the application is not compliant, the applicant will be notified by CDE and shall correct the materials within 30 days. If the application is in line with the requirements, CDE will send notifications of acceptance and payment to the applicant and conduct technical review and approval of drugs accordingly.

On the same day, CDE also published another two technical guidelines on medical product changes –Technical Guideline for Studies of CMC Changes of Approved Chemical Drugs 3 and Technical Guideline for Clinical Changes of Approved Chemical Drugs and Biological Products 4. BaiPharm will stay tuned on the updates of drug changes in China.

Grace Wang
ChemLinked Regulatory Analyst
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