Change the new regulations after the drug is on the market! Official answers to 30 focus questions

On January 14th, the official website of the State Drug Administration published the Measures for the Administration of Changes after the Listing of Drugs (Trial) (hereinafter referred to as the Measures).
the document aims to implement the relevant provisions of the Drug Administration Law and further strengthen the management of changes after the drug is released, effective from the date of publication.
State Drug Administration pointed out: First, the holder should be fully studied to ensure that the changed drugs and the quality and efficacy of the original drugs consistent.
provincial drug regulatory authorities should strengthen the supervision of drug after-market changes, in particular, the quality and efficacy of generic drugs have been evaluated by the change supervision.
, the drug has been accepted before the publication of the supplementary application and filing matters after the listing can continue to be handled in accordance with the original procedures and relevant technical requirements.
may also voluntarily withdraw the original application and make a supplementary application, filing or reporting in accordance with the requirements of the Measures.
, the implementation of Article 10 of the Measures to set up a transitional period.
In order to avoid policy changes affecting the rights and interests of administrative relatives, the former State Food and Drug Administration issued the "Notice on the Issuance of Regulations on the Registration and Administration of drug Technology Transfer" (State Food and Drug Administration Note No. 518, hereinafter referred to as No. 518) in the overseas production of drugs (formerly imported drugs) through the transfer of drug production technology for domestic production, domestic holders may continue to carry out research and report supplementary applications by January 15, 2023 in accordance with the requirements of No. 518.
the State Drug Administration, in accordance with the requirements of Document No. 518, to complete the review and approval within the prescribed time limit, does not meet the requirements or fails to meet the requirements of the request to correct the non-approval.
Fourth, the holder through the State Drug Administration drug registration online declaration function in the "drug business application system" for the record category changes, the drug review center and provincial drug regulatory departments in the "drug business application system" to complete the receipt of relevant information.
5 days from the date of filing, the official website of the State Drug Administration shall make public the filing information.
can check the filing information in the official website of the State Drug administration --- "inquiry" and "drug".
addition, the State Drug Administration has answered 30 questions surrounding the Measures: First, what is the purpose and practical significance of the formulation of the Measures for the Management of Changes after the Listing of Drugs (Trial)? With the progress of science and technology, new technology, equipment, new scientific and technological achievements are more and more applied in the field of drug research and production, which plays an important role in drug research and development and the improvement of the quality of listed drugs.
to give full play to the role of advanced production technology and scientific and technological achievements in promoting the pharmaceutical industry, while strengthening the management of drug post-market changes and ensuring the safety of people's drug use is an important task for changing scientific supervision after drug market.
based on the current situation of the pharmaceutical industry and the actual work of drug supervision, it is not only the development of industry but also the regulatory need to formulate change management regulations for drug market under the new situation.
the State Drug Administration has formulated the Measures for the Administration of Changes after the Listing of Drugs (Trial) in accordance with the Drug Administration Law, the Vaccine Administration Law, the Measures for the Administration of Drug Registration and the Measures for the Supervision and Administration of Drug Production.
The Measures implement the requirements of the Drug Administration Law for the classification and management of changes in the drug production process according to risk, further clarify the principles and common circumstances of changes after the drug is listed, specify the obligations of the holders and the responsibilities of the regulatory authorities, and provide a basis for the change management after the drug is marketed.
On the one hand, holders are encouraged to use new production technologies, new methods, new equipment and new scientific and technological achievements to continuously improve and optimize production processes, continuously improve the quality of medicines, and improve the safety, effectiveness and quality control of medicines.
On the other hand, we will resolutely implement General Secretary Xi Jinping's "four most stringent" requirements for drug supervision, standardize drug change behavior and change supervision, crack down on illegal changes, implement the main responsibility of holders, and ensure the safety of drug use by the people.
the adoption of public comments during the drafting of the Measures? During the drafting process, the Measures went to Shanghai, Beijing, Jiangsu and other places to conduct research, hold symposiums, fully listen to the views of some provincial drug regulatory departments, representative enterprises, and from August 1 to 15 on the website of the State Drug Administration for public comments.
received a total of 1116 opinions from units directly under the State Drug Administration, provincial drug regulatory departments, trade associations, domestic and foreign holders, research and development institutions, etc.
The Bureau combed, studied and discussed the feedback article by article, and adopted most of the opinions, which were not adopted mainly in the following areas: (1) The proposed changes to the holders were approved by the provincial drug regulatory authorities.
reasons for not accepting the drug: According to Article 40 of the Drug Administration Law, "with the approval of the drug regulatory department under the State Council, the holder of a drug listing license may transfer the drug market license."
...", the approval of the holder's change shall be the authority of the State Drug Administration and shall be approved by the Drug Review Center.
(2) In the application for change of holder, the licensee is required to have a "drug production license" for the corresponding production range, and it is recommended that the type of "drug production license" be refined or that the requirement for obtaining a "drug production license" be deleted.
Reasons for not accepting: In order to implement the requirements of the Drug Administration Law on holders and implement the responsibilities of holders, Article 7 of the Measures for the Supervision and Administration of Drug Production clearly elaborates the conditions that holders who entrust others to produce preparations, and requires holders to obtain a Drug Production License.
the type of drug production license has been specifically stipulated, the holder in accordance with the relevant provisions can be implemented.
(iii) recommends that the procedures for annual reports, the format of the archives of drug varieties, etc. be clarified.
reasons for not accepting: the annual report procedure, the file format of drug varieties are not directly related to the Measures, and the relevant departments of the State Drug Administration are studying and formulating the relevant document requirements, the relevant content will be clearly defined in the special document.
(4) it is proposed to set up communication procedures for overseas production of drugs in drug review centers, taking into account the communication procedures between domestic production of drugs and provincial drug regulatory departments on the category of change management.
not accepted: at present, the Drug Audit Center has established and optimized the communication system, and run smoothly, this "Measures" will not be repeated.
(v) recommends that the specific steps and procedures for the holder to correct and carry out the risk assessment in article 31 be clarified.
Reasons not to accept: the specific steps and procedures for the holder to correct and carry out risk assessment are common practices in the post-market management of the drug, not a special link in the management of changes, and the holder should carry out the relevant work in accordance with the requirements of the post-market supervision of the drug.
(vi) proposes to clarify changes to plant facilities, warehouses, etc.
reasons for non-adoption: Changes to factories and warehouses shall be carried out in accordance with the Measures for the Supervision and Administration of Drug Production and the Regulations on Quality Management of Pharmaceutical Production, and shall not be repeated in these Measures.
, what are the responsibilities and obligations of the holder in the post-drug change management? The general provisions of chapter I of the Measures make clear the responsibilities and obligations of the holder in managing the changes after the drug has been marketed.
is the subject of change management after the drug is marketed.
The post-market change management obligations of the holder include: taking the initiative to carry out post-market drug research, realizing the full life cycle management of the drug, establishing the post-market drug change control system, formulating the implementation of the internal change classification principles of the holder, the list of changes, working procedures and risk management standards, determining the change management category, reporting and implementing or reporting after approval, filing and approval in accordance with the regulations and the change management category.
, how to apply for holder changes? What more needs to be done after the holder change is approved? In order to meet the needs of the management of the holder system, the Measures for the Supervision and Administration of Drug Production specify the conditions for the holder to apply for a Drug Production License, and if the holder who entrusts another person to produce the preparation meets the requirements, he may obtain a Drug Production License.
If an application is made to change the holder of a drug produced in China, the licensee shall first apply to the provincial drug regulatory department of the place where it is located for the approval of the Drug Production License for the corresponding scope of production, and after approval, the granting party shall, in accordance with the provisions of the Drug Administration Law, make a supplementary application for the change of the holder to the Drug Review Center.
change only the drug holder is an approval matter that does not require technical review, therefore, the applicant shall provide a commitment not to change the production site, prescription, production process, quality standards, etc. of the drug.
approval of the change of the drug holder, the follow-up work shall be done in accordance with the relevant provisions of Article 8 of the Measures.
, in the course of drug transfer, only the holder changes, the production site, production process and other matters have not changed, after the change of holder is approved, do you need to check the compliance of the drug production quality management norms? The change of the quality management system of the holder is one of the important factors affecting the quality of the drug, after the change of the holder, although the drug production site, production process, etc. have not changed, but the quality management system of the holder has changed, whether the changed holder can continuously and steadily produce drugs consistent with the quality and efficacy of the original drug in accordance with the requirements of GMP, and assume the main responsibility of the whole life cycle of the drug is related to the safety of public drug use.
Therefore, even if the drug production site, production process, etc. have not changed, the changed holders and pharmaceutical production enterprises should meet the requirements of the drug production quality management standards of compliance inspection, the transfer of drugs through the drug production quality management norms of compliance inspection, in line with the requirements of product release, can be listed for sale.
, drug transfer process, at the same time the holder changes, drug production site, production process changes, how to declare? If only the change of holder occurs in the course of drug transfer and no change in other registration management matters occurs, the approval of the matter without technical review shall be handled within 20 working days in accordance with the procedures stipulated in Article 8 of the Measures.
If the drug to be transferred needs to change the drug production site, production process, prescription, etc., the supplementary application, filing or report may be reported as required by the changed holder (transfere) after the change of holder has been approved and the study is carried out in accordance with the requirements of the change technical guidelines.
, due to special needs, it is proposed to file the change of holder with other supplementary applications, the time limit for technical review shall be implemented in accordance with the provisions of Article 96 of the Measures for the Administration of Drug Registration.
changes to overseas production of drugs be handled? Changes in the examination and approval or filing categories of overseas production of drugs shall be submitted directly to the Drug Review Center for supplementary applications or filing.
drug produced abroad is transferred between the licensed holders of the overseas drug market, a supplementary application shall be made by the transfer to the Drug Review Center of the State Administration.
the production site of a drug produced abroad is changed and the site is still outside the country after the change, a supplementary application or record shall be submitted to the Drug Review Center in accordance with the relevant technical guidelines for research, evaluation and necessary verification.
the transfer of overseas-produced drugs that have been listed in China to domestic production, how shall they be handled after the release of the change measures? In order to avoid policy changes affecting the rights and interests of administrative relatives, the former State Food and Drug Administration issued the "Notice on the issuance of drug technology transfer registration regulations" (National Food and Drug Administration Note No. 518, hereinafter referred to as No. 518), the overseas production of drugs (formerly imported drugs) through the transfer of drug production technology for domestic production, our Bureau set up a two-year transition period, during which domestic holders may continue to comply with the requirements of Article 518.
the circumstances in which Article 10 of the Measures applies? Article 10 of the Measures stipulates that the transfer of overseas-produced drugs that have been listed in China to domestic production, although declared by classification of generic drug registration, can simplify the requirements for reporting information, and special provisions are given in the areas of reference formulation identification, and specific policy measures shall be formulated and issued separately.
changes occur after the listing of overseas-produced drugs, is it allowed to apply simultaneously to domestic and foreign regulatory authorities? Changes after the listing of overseas-produced drugs mainly involve changes in administrative information and technical categories.
is related to changes in administrative information categories, the approval of supporting documents by relevant departments abroad is an important reference document, and in principle, foreign holders should provide supporting documents approved abroad when submitting their applications.
With the deepening of the reform of the drug review and approval system, China's technical review force has been strengthened, more and more innovative drugs choose to declare and list in China and other countries simultaneously, for such drugs after the listing of technical changes involving can be simultaneously declared in domestic and foreign regulatory authorities, our Bureau will be based on the supervision of different drugs in the follow-up supporting documents.
, in order to implement the requirements of the newly revised Measures for the Administration of Drug Registration and the Measures for the Supervision and Administration of Drug Production, what optimizations have been made in the Measures for the procedures for the change of drug production sites? The 2007 edition of the Measures for the Administration of Drug Registration stipulates that changing the production site of a drug shall be subject to the holder's application to the provincial drug regulatory department for the alteration of the Drug Production License and the certificate of approval of the drug registration, respectively, and approval shall be obtained before the drug can be produced, to a certain extent increasing the burden on the holder.
In order to implement the requirements of "discharge and service", give full play to the role of provincial drug regulatory departments, optimize the declaration procedures for drug market changes, the newly revised Measures for the Administration of Drug Registration and Management of Drug Production, the Measures for the Supervision and Administration of Drug Production re-established the procedures for the change of drug production sites after the listing of drugs, and according to Article 16 of the Measures for the Supervision and Administration of Drug Production, if a change in the production site of a drug occurs after the listing of a drug, only an application for a change of "Drug Production License" shall be made to the provincial drug regulatory department.
Article 14 of the Measures specifies the specific procedures, and after the change of the Drug Production License has been approved, the provincial drug regulatory department shall update the information on the change of the drug production site on the drug registration approval document and its attachments directly in the change system, simplify the declaration procedures of the holders and improve efficiency.
special provisions for biological products, etc.
changes in the work undertaken by provincial drug regulatory authorities in the work of changing drug production sites? If a change in the drug production site occurs after the drug is listed, the holder shall conduct a full study in accordance with the Measures for the Administration of Drug Production Supervision and Administration and the relevant provisions of the Guidelines for the Change of the Drug Production Site, and file an application for a change of the Drug Production License in accordance with the procedures.
examination of the application for change of the Drug Production License, the provincial drug regulatory department shall, in accordance with the Measures for the Supervision and Administration of Drug Production, the Measures for the Administration of Drug Registration and the Guidelines for the Change of Drug Production Sites