On February 10, 2021, The CDE (Center for Drug Evaluation) of the NMPA in China has recently released “Guidelines for Acceptance and Review of Chemical Drug Changes” with Information on requirements for completing a Chemical Drug Change.
The guidance provides information on the basic requirements for application materials, formatting, and review process along with a few attachments: a self-check form and a reference list. The document is divided into 3 major parts, and this blog will cover the basic requirements and the decision of approval.
GRP Blog will cover section III of the document, regarding how the NMPA reviews the application after receiving it and any necessary notes when preparing the application.
|Situation||Guidelines to Follow|
|Conditional Approval||Supplementary Application|
|Post-Market Research||NMPA Regulation Requirements in “Application Requirements and Marketed Pharmaceutical Product Changes”|
|Changes to Marketed Chemical Pharmaceuticals||Choose Type of Change according to “Application Requirements and Marketed Pharmaceutical Product Changes”|
|Restarting Chemical Drug clinical Trials after Discontinuation||Changes to be submitted in Supplementary Application|
|1. Protocol Changes 2. Significant Changes to Pharmacology 3. Significant Safety discover in non-clinical studies that may increase the participants safety risks during the conduct of a clinical trial.||Submission of Supplementary Application If there is a sponsor change during these changes during the trial, the final sponsor is responsible for submitting the supplementary application and documents to prove it. If the Local Representative changes at the same time, the MAH should provide appropriate documents, notarized documents and Chinese translations.|
|Imported drugs that have relocated to be produced within China||Local Chinese holder should follow the pharmaceutical registration requirements and procedures to complete submissions.|
Key points for the Application Form:
- Other than the change being suggested, all other information shall remain identical to approved application, and changes which have already happened should write “Information After the Change”
- Products of the same category which have been accepted or other formulations/strengths submitted during the same time period: fill that such product is already accepted/provide the names for the different formulations/strengths, including accepting number and names
- Concise application information: must be same as no. 5 on application form and contain change in the associated application
- Include the number of times application for this product type has been submitted, be concise.
Applicant and CRO
Information filled out must reflect that of the supplementary proofing document and have a select application agency to be responsible to provide registration fees for the national government, applicants that have filled in all relevant information have to ask their legal representative to sign with stamp (same name as its official name)
Documents which provide proof that the pharmaceutical changes are allowed:
API, excipients and proof for drug packaging
- API, excipients and proof for drug packaging should have appropriate supplier documents (such as supplier contract, receipts etc; photocopy of API, excipients and packaging letter of authorization and statement of right of reference.
- Nonclinical safety evaluation agencies should provide “Pharmaceutical Non-clincal Research Quality Management Standard” (GLP) approval or testing report or other document for providing proof.
- Clinical Trial organizations should provide of proof of filing (if appropriate).
- Clinical studies should report appropriate regulation requirements, clinical study reporting cover page should provide: applicant (along with signature and stamp), main or co-investigator (signature), site name, biostatistician (signature) and name of statistical company, as well as other information required in ICH E3; clinical trial report appendix II should provide the signature of the Medical Director of the applicant.
- The Trial data electronic file should be in the form of SAS XPORT (xpt), with two data discs (document level) in disc containers that are labeled “database, product name, application agency (with stamp of applicant/local representative), name of statistical software used, data management company, statistic analysis company, etc”.
- The disc box should be placed in a document file, with “name, applicant (stamp of applicant/local representative)” and be submitted along with the application materials
oversea production sites
- Changes to oversea production sites should submit overseas regulatory body and documents that indicate the quality management standard of the production site.
- New drugs that change overseas production site should provide explanation/indication that its drug preparation used in the clinical trial fits the pharmaceutical quality management standard requirements
Applicants must finish supplementary application within 30 days, otherwise, the application will be considered as renounced and the application material will be returned to the applicant
About Global Regulatory Partners
Global Regulatory Partners Inc, (GRP) is an American company that provides regulatory affairs, clinical, quality and safety services to medical devices , pharmaceutical, cosmetic and food supplement companies globally. GRP headquarters is located in Massachusetts USA and its main affiliates are located in China, Japan, Brazil, Mexico and Argentina. GRP helps many life science companies register their products in different countries in compliance with local regulations.