Background: The Change of API Approval Process in 2017
To understand the active pharmaceutical ingredient (API) registration renewal, it's necessary to know how APIs get registration approval in the first place.
Before Nov. 30, 2017, API manufacturers were required to register APIs. The approved APIs were granted with approval numbers, which are valid for five years from the approval dates.1
As the DMF (drug master file) system extended to APIs since Nov. 30, 2017, API manufacturers shall first file DMFs on the Center for Drug Evaluation (CDE)'s online platform. All the previously approved APIs have been transferred to the online filing platform. Each filed API has a filing number.
The on-file APIs shall go through the below two reviews to get the approval notification, which is valid for five years from the approval date.
(1) technical review separated from other products, or
(2) associated technical review together with excipients, packaging materials, and finished dosage forms
Each approved API's filing status will be marked with "A" while the unapproved ones are marked with "I".
Approval Time
API Approval Process
Filing Status
Approval Document
Before Nov. 30, 2017
Registration based on the independent technical review
A
Approval number
Since Nov. 30, 2017
Step 1: Filing DMF to get a filing number;
I
-
Step 2: Registration based on the independent/associated technical review
A
Approval notification
On Nov. 4, China National Medical Products Administration (NMPA) released the draft of Announcement on the Administration of Chemical API Registration Renewal (hereafter referred to as the Announcement).2
Requirements for API Registration Renewal Application
NMPA designates a 1-year transition period from the date when the Announcement takes effect. The timing requirements for submitting the renewal application during the period are shown in the table below:
API Registration Renewal Requirements During the 1-year Transition Period | ||
API | The left validity period of the original approval document | The timing to submit renewal application |
API with approval number | More than 6 months when the Announcement takes effect | At least 6 months before the original approval number expires |
Less than 6 months when the Announcement takes effect | Within 1 year from the Announcement's implementation date | |
None when the Announcement takes effect | ||
API with approval notification | More than 6 months when the Announcement takes effect | At least 6 months before the original approval notification expires |
Less than 6 months when the Announcement takes effect | Within 1 year from the approval notification's issuance date | |
None when the Announcement takes effect | ||
After the transition period, all manufacturers of approved APIs shall apply for registration renewal more than 6 months before the expiration of the approval number/notification.
Competent authorities:
For APIs manufactured in China, filers shall apply for renewal from the local provincial-level medical products administrations. For APIs manufactured overseas, filers shall submit the renewal application to CDE.
Results of API Registration Renewal Application
The provincial-level medical products administration (MPA) or CDE will review the renewal application, mark the API's filing status, and decide whether to issue the renewal approval notification.
Review and Approval of API Registration Renewal Application | |||
API | Review for renewal | Filing status | Renewal approval notification |
Renewal application submitted in time | Passed | A | Granted |
Failed | I | Not granted | |
In process | In process | Not granted | |
Renewal application not submitted in time | N/A | I | Not granted |
For API that fails the renewal review, NMPA will mandate the cancellation of the corresponding filing number.
Mandatory Cancellation of API Filing Number | ||
API | Disapproval of the renewal application | Cancellation of the filing number |
Manufactured in China | By local provincial-level medical products administration | By NMPA |
Manufactured overseas | By CDE | By NMPA |
Voluntary Cancellation of API Filing Number
API filers can apply for canceling the filing number voluntarily.
Voluntary Cancellation of API Filing Number | |
API | Competent Authority |
Manufactured in China | Local provincial-level medical products administration |
Manufactured overseas | CDE |
BaiPharm's Comment
China is a hub for chemical API production and sales. In 2021, China produced 3,086,000 tons of APIs, up by 12.87% year on year. The total revenue reached 426.5 billion yuan (circa 59 billion USD), a yearly growth of 8.1%.3
The Announcement can help regulate such an API production hub by strengthening the API manufacturer as a main responsibility entity for registration renewal. Manufacturers of approved APIs should pay special attention to the renewal application requirements so that their APIs can keep a valid filing number and approval document.
Any public comments and advice on the Announcement can be sent to hxypc@nmpa.gov.cn before Dec. 3, 2022. Any enquiries about API filing and registration are welcomed for professional answers and solutions from BaiPharm.
