Highlights for pharmaceutical excipients registration under the new policy

Following the announcement on adjusting the review and approval of APIs, pharmaceutical excipients and drug packaging materials (No. 146 in 2017) (hereinafter referred to as "No. 146"), the announcement on further improving the related review, approval and supervision of drugs (No. 56 in 2019) (hereinafter referred to as "No. 56"), the State Food and Drug Administration published the "chemical APIs, pharmaceutical packaging materials" on April 30, 2020 There are some changes in the management of pharmaceutical excipients in the draft for comments (hereinafter referred to as "draft for comments"). Xin'anrun Consulting Co., Ltd. hereby summarizes the key points of registration and management of pharmaceutical auxiliary materials under the draft for the reference of customers and friends.            

1、 Scope of registration           

 Article 29 of the draft for comment: "pharmaceutical excipients and drug packaging materials (including packaging system and functional accessories not in direct contact with liquid medicine) used in various drug registration applications as well as pharmaceutical excipients and drug packaging materials involved in changes in supplementary applications shall be registered on the registration platform, and relevant materials meeting the requirements may also be submitted together with the drug preparation registration application".            

That is to say, registration of pharmaceutical excipients by non compulsory manufacturing enterprises can only be submitted when applying for registration of preparations.           

 Compared with the current document No. 56, which can not be registered on the platform due to special reasons, the applicant for registration of pharmaceutical preparations can also provide the research data of the original auxiliary package together with the application for registration of pharmaceutical preparations. The requirements for registration of pharmaceutical auxiliary materials under the draft for comments are more flexible and give enterprises more choice space.           

 Article 30 of the draft for comment: "pharmaceutical excipients and drug packaging materials that have been used in food and drug for a long time and whose safety has been recognized, and whose usage, dosage and function are within the scope of conventional use, can simplify the data requirements. The drug preparation registration applicant shall list the product information in the preparation application data and submit the relevant data that meet the requirements (see Annex 1-4 for details). If the drug evaluation center considers it necessary during the evaluation of the application for drug preparation registration, it may require the applicant for drug preparation registration to provide the corresponding technical information. The list of such varieties shall be updated and announced by the drug evaluation center in due time. "          

  That is to say, enterprises of category 2.2-2.4 in the current No. 56 Pharmacopoeia at home and abroad who have included non high risk excipients, category 3.1 and category 3.2 can choose whether to register or not, which can simplify the requirements for registration data of pharmaceutical excipients and further reduce the burden of enterprises.          

  2、 Registrant            

Article 4 of the draft for comments In principle, the original auxiliary package registrant shall be the original auxiliary package production enterprise, and the overseas original auxiliary package enterprise shall designate the enterprise legal person in China to handle the relevant registration matters... "            

That is to say, the domestic enterprise directly acts as the registrant when registering, and the overseas enterprise needs to appoint the legal person agent of the domestic enterprise in China. There is no significant change between this item and the current 56.           

 3、 Registration management            

Article 6 of the draft for comment: "if the production process and quality standards of the same original auxiliary package products produced by the same enterprise in the same production site are the same, they shall be registered according to the same registration number.". Please pay attention to the query of auxiliary materials registration            

The same original auxiliary package product can only have the same registration number, and different registration numbers can exist for different quality standards.          

  4、 Responsibilities of registrant            

Article 8 of the draft for comments: "the original subsidiary registrant is responsible for maintaining the registration information of the registration platform, and is responsible for the authenticity and integrity of the registration information. The original overseas auxiliary contracting enterprise and the designated enterprise legal person in China shall be jointly responsible for the authenticity and integrity of the registration data. "            T

That is to say, the responsibility to ensure the authenticity and integrity of registration materials falls on the registrant and / or agent, which is more targeted. This item is consistent with the current document No. 56.          

  5、 Post registration management            annual report            

Article 12 of the draft for comments "the original manufacturer of the auxiliary package shall submit an annual report to the drug review center within three months after the original auxiliary package passes the technical review. The annual report shall include product change and relevant research data. If there is no change, relevant statement shall be provided. The API shall indicate whether the change application has been made after the change and relevant information. For pharmaceutical excipients and drug packaging materials, relevant change research data shall be provided, and the use of all new authorized drug marketing license holders in the year shall be explained (see Annex 1-2 for requirements). If the original auxiliary contract manufacturer fails to submit the annual report on time, the registration platform will no longer publicize the registration number. "           

 This item defines the main body of the annual report as the production enterprise, and clearly puts forward the corresponding punishment measures for failing to submit the annual report on time, that is, the registration number will not be publicized. Compared with the current No. 56 document, the main body of the annual report is the registrant and there is no clear punishment measures, the enforceability is further improved.           

 Changes of excipients for traditional Chinese medicine of listed preparations           

 Article 10 of the exposure draft: "if the original source of the supplementary package of the listed pharmaceutical preparations is changed, the holder of the pharmaceutical listing license shall carry out research in accordance with the relevant guiding principles and other requirements, and report in accordance with the relevant registration management regulations. If the original auxiliary package to be used for the preparation fails to pass the examination and approval of the associated review, an application shall be submitted to the National Bureau, and the original auxiliary package identification shall be updated according to the review results after the associated review with the preparation. "            

For the pharmaceutical excipients in "I" status that have not been approved by association after the change in the preparation, it is required to conduct Association review and approval.     

      

 To sum up, some changes have been made in the management of pharmaceutical excipients under the draft for comments, mainly focusing on the corresponding materials provided when the enterprise can choose to register the pharmaceutical excipients or conduct the associated review with the preparation; the non high risk pharmaceutical excipients included in the Pharmacopoeia at home and abroad or the pharmaceutical excipients used for a long time and having safety are exempt from registration and required to be provided in the associated review stage of the preparation A new definition of the responsibilities of registrants, agents and / or producers is proposed.