Liaoning Publicly Solicits Opinions on the Implementation Rules for the Administration of Post-marketing Changes in Drugs

On April 16, the Liaoning Provincial Food and Drug Administration publicly solicited an announcement on the "Implementation Rules for the Administration of Post-marketing Drugs in Liaoning Province (Draft for Solicitation of Comments)".

These implementation rules are applicable to post-marketing drug filing changes and drug production site changes that are implemented by the provincial drug regulatory authority, where laws and regulations and related technical guidelines are clear, and are approved by the holder and the Liaoning Provincial Drug Administration (below (Referred to as the Provincial Bureau) to communicate and confirm that they belong to the post-marketing filing-type changes that the provincial bureau is responsible for implementing.

In the third chapter communication procedures.

The original text is as follows:

To implement the "Drug Administration Law", "Administrative Measures for Drug Registration", "Administrative Measures for Drug Production Supervision" and "Administrative Measures for Post-Marketing Change of Drugs (Trial)" and other laws and regulations, strengthen post-market change management and standardize post-market change behavior , The Provincial Drug Administration drafted the "Liaoning Province Drug Administration Implementation Rules for Post-marketing Modification Recording (Draft for Solicitation of Comments)", which is now open to the public for comments.

Liaoning Provincial Drug Administration

April 16, 2021

Implementation Rules for Post-marketing Drugs Change Management in Liaoning Province

(Draft for comments)

Chapter One General Provisions

Article 1 is to standardize the post-market change management of drugs in our province, strengthen the main responsibility of drug marketing license holders (including the registrant of APIs, hereinafter referred to as holders), and strengthen the connection between drug registration and production supervision.

Article 2 These implementation rules are applicable to the post-marketing drug registration changes and drug production site changes that are implemented by the provincial drug regulatory department, and the relevant laws and regulations and related technical guidelines are clear, as well as those approved by the holder and the Liaoning Provincial Drug Supervision and Administration.

Article 3 The change of a drug after it is marketed shall not adversely affect the safety, effectiveness and quality controllability of the drug.

Chapter II Procedures for Recordation of Changes in Registration Management Matters

Article 4 The filing application is filed.

Article 5 Signing for the filing materials.

Article 6 Publicity of filing information.

Holders can inquire about the publicity content of relevant filing information on the official website of the State Drug Administration, and the publicity date is the filing date.

Article 7 Review of filing materials.

After the audit meets the requirements, the Provincial Certification and Evaluation Institute will submit the audited opinions to the Provincial Bureau for review.

The Provincial Bureau shall, within 10 days from the date of receiving the review opinions of the Provincial Certification Review Institute, make a conclusion on whether the review is approved or not, and if the review fails, the record shall be revoked in accordance with the procedures.

Chapter III Communication Procedures

Article 8: Holders in the province initiate changes, and after full research, evaluation and necessary verification, they can apply for communication under the following circumstances:

(1) Where the change situation does not specify the change management category in laws, regulations or technical guidelines, the change category cannot be determined on the basis of sufficient research, evaluation and necessary verification;

(2) The holder has clearly defined the type of change management in the technical guidelines for the reduction of technology;

(3) Lowering the category of change management in the holder's change list.

In principle, only one communication application can be submitted for a change item (including related related changes).

Article 9 The holder shall determine a designated person to be responsible, and submit the "Communication Application Form" and communication materials to the Provincial Bureau in writing, at least including the communication application, relevant supporting materials and the holder’s self-assessment opinions on the relevant change categories .
After the provincial bureau receives the above materials, the provincial bureau manager should complete the preliminary review within 5 working days and inform the holder whether the relevant materials are complete.
The provincial bureau and the holder jointly agree on the form of communication based on the complexity of the research materials for the change.
The communication can be carried out by telephone, written, online or conference (video conference or on-site meeting), etc.
, if a communication meeting is required , And discuss matters related to the meeting with the holder.
When necessary, experts in related fields are invited to participate in the communication, and expert opinions serve as an important support and reference for communication and exchange of opinions.

Article 10 After receiving the communication materials, the provincial bureau conducts a preliminary review.
If there is no self-assessment opinion, relevant supporting materials are not enough to support the corresponding change category, etc.
, the holder may be required to complete the relevant materials and resubmit the communication application.
.

Article 11 The communication shall be conducted in accordance with the established format and agenda, and the provincial bureau shall give a written reply within 20 days after the communication is completed.

Communicate the results.
In accordance with relevant regulations such as the "Administrative Measures for Post-Marketing Changes of Drugs (Trial)", if the holders and the provincial bureaus agree on their opinions after communication, they shall submit supplementary applications, filings or reports in accordance with the change procedures.
If there is a disagreement on whether the changes are subject to approval, the holder shall submit a supplementary application to the Center for Drug Evaluation of the State Drug Administration (hereinafter referred to as the National Administration) in accordance with the approval changes; laws, regulations and technical guidelines clearly indicate minor changes , In principle, it is not acceptable to adjust it as a record item.
Based on risk management requirements, in principle, biological products, special injections (such as multi-component biochemical injections, traditional Chinese medicine injections, liposome injections, etc.
) and the existing technical guidelines for the adjustment of varieties included in the "List of Listed Drugs in China" are not accepted Except for the clearly stipulated change level, the holder himself adjusts the filing or annual report to a supplementary application for declaration.

Article 12 The opinions issued by the provincial bureau are based on the current laws and regulations and the technical guidelines issued by the national bureau.
If the laws, regulations and the technical guidelines issued by the national bureau are revised, follow their provisions.

Chapter IV Procedures for Change of Drug Production Site

Article 13 If the holder changes a drug production site, he shall conduct full research, evaluation and necessary verification of the change.
The same prescription, process and quality standards shall be implemented for the same drug produced at different production sites.

Article 14 When the drug production site is changed, if one or more intermediate changes occur in registration management matters such as drug production prescriptions, processes, and quality standards and involve changes in licensing matters, the holder may first follow the "Registration Management Matters" of these rules.
Change filing procedures" for change filing.
After the change is filed, the holder submits an application for "Drug Production License" to the provincial bureau for "changes in the approved items of the drug production license (excluding changes in the production site of listed drugs)", and the provincial bureau handles the changes in the original drug production license procedures.

Article 15 When the drug production site is changed, if one or more major changes occur in registration management matters such as drug production prescriptions, processes, and quality standards and involve changes in licensing matters, the holder shall first submit to the provincial bureau the "Pharmaceutical Production "License" application for changes in licensing items (excluding changes in the production site of listed drugs)", the provincial bureau shall handle the changes in the original drug production licensing items.
After the modification of the "Drug Production License" is approved, the holder submits a supplementary application for the modification to the National Center for Drug Evaluation.
After the change application is approved, if the GMP conformity inspection is involved, the holder shall submit an application for conformity inspection in accordance with the procedures.

Article 16 If the holder or the drug manufacturer changes the drug production site internally, the holder changes the drug manufacturer, etc.
, the drug production site is changed in parallel with the drug production license change procedure in the "Drug Production License" Technical review and on-site inspection procedures.
License change inspection, drug production site change inspection, and GMP compliance inspection (if necessary) can be implemented in combination.

Article 17 If the holder or the drug manufacturing enterprise builds, rebuilds, or expands on the original site or in a different place, and involves the change of the production site for self-produced drugs, the holder shall submit the "Drug Production License" through the provincial government affairs network approval platform.
Change of production site for listed drugs)” application, the provincial bureau organizes technical review and on-site inspection of the change of drug production site.
The holder simultaneously filed an application for GMP compliance inspection and implemented the inspection together.
If the subsequent workshop or production line only involves the change of the drug production site, the provincial bureau will organize the technical review of the drug production site change in accordance with the above procedures, and conduct site change inspections and GMP compliance inspections when necessary.
If the holder changes from entrusted production to self-production, it shall be implemented with reference to this article.

Article 18 If the holder changes a drug manufacturing enterprise and the entrusted party is a drug manufacturing enterprise in the province, the entrusting parties shall simultaneously propose the "Drug Production License" through the provincial government affairs network approval platform to change the licensing items of the "Drug Production License" )"Application.
The provincial bureau organizes technical review and on-site inspections for changes in drug production sites.
In the case of drug GMP compliance inspection, the application for compliance inspection shall be submitted simultaneously, and the inspection shall be implemented together.

Article 19 If the holder changes a drug manufacturing enterprise, the entrusted party is a drug manufacturing enterprise outside the province, and the holder submits an application for "Drug Production License" permission changes (changes in the production site of listed drugs), and the provincial bureau organizes the drug The technical review of the production site changes, and the provincial bureau will implement on-site inspections of the drug production site changes to the entrusted production enterprises when necessary.

Article 20 For high-risk varieties such as multi-component biochemical drugs, traditional Chinese medicine injections, special injections, and production site changes that have passed the consistency evaluation of generic drugs, on-site inspection should take 1-3 batches of samples and send them to the Liaoning Provincial Inspection and Certification Center The Drug Inspection and Testing Institute conducts inspections, and aseptic products can select representative varieties for sampling inspection.
Other drugs can be sampled and tested as needed.

Article 21.
If one or more moderate changes in drug production prescriptions, processes, quality standards and other registration management matters are found in the technical review or inspection of the change of the drug production site, the holder shall follow the “Changes in Registration Management Matters” in these rules.
The “Recording Procedure” provides for simultaneous change filing; if one or more major changes are made to drug production prescriptions, processes, quality standards and other registration management matters, if the provincial bureau approves the changes to the "Drug Production License", they should be filed The system information indicates that “the drug can be produced and marketed only after major changes (drug production process, prescription, quality standards, etc.
) occur at the same time.
After the change application is approved, if the GMP compliance inspection is involved, the compliance inspection application shall be filed according to the procedures.

Article 22 Where there are special regulations for the change management of biological products, medical toxic drugs, narcotic drugs, psychotropic drugs, radioactive drugs, etc.
, those regulations shall prevail.

Article 23 Prior to the implementation of the "Administrative Measures for Post-Marketing Change of Drugs (Trial)", the holder or the drug manufacturer has been approved for entrusted production, but the holder’s drug registration approval document and its attachments contain the production address information If it has not been updated, it shall undergo sufficient research, evaluation, and verification to ensure that the relevant information can prove that the prescription and process are consistent, and the relevant information shall be updated in the online office system.

Article 24 In accordance with the "Administrative Measures for Post-Marketing Change of Drugs (Trial)", Chapter II, Section 1 of the Holder Change Management Regulations, after the holder obtains the supplementary application notice for changing the holder, the change of the drug manufacturer is involved, Refer to the relevant requirements of this chapter for implementation.

Article 25 If the registration items of the "Drug Production License" are changed, such as the name of the holder, the name of the drug manufacturer, and the name of the production address, the provincial bureau shall follow the original procedures after completing the changes to the registration items of the "Drug Production License", and then the online office Update drug-related information in the system.

Article 26 The technical review and on-site inspection of the change of the drug production site shall not be included in the time limit for the change of the drug production license.
Where the combined implementation of GMP compliance inspection is involved, it shall be implemented in accordance with the GMP compliance inspection time limit.

Chapter V Supervision and Administration of Change Filing

Article 27 The holder shall bear the relevant legal liabilities caused by improper management of the change.
The holder shall conduct a risk assessment of the changes that have been publicized for the record and are still in the review stage of the record.
For records that have been implemented but have been reviewed and revoked, the holder shall take corresponding risk control measures, and the provincial bureau will conduct research and judgment on relevant issues and deal with them in accordance with laws and regulations depending on the situation.

Article 28: Failure to record changes in the drug production process as required shall be dealt with in accordance with the relevant provisions of the "Drug Administration Law".

Chapter VI Supplementary Provisions

Article 29 The registrant of APIs in these implementation rules refers to the registrants of APIs that have passed the examination and approval.

Article 30 The holder shall submit the application materials in accordance with the classification of changes determined by the "Measures for the Administration of Post-Marketing Changes of Drugs (Trial)" and related technical guidelines.

Article 31 The days specified in these rules are calculated as working days.

Article 32 The implementation rules shall come into force on the date of promulgation, and the subsequent State Administration shall issue and implement new policy documents and follow its provisions.