While the industry is still waiting to see whether the "zombie" approvals will really be eliminated, the new regulations of the National Medical Products Administration have provided a policy basis for the elimination of "zombie" approvals-On October 12, 2024, the National Medical Products Administration issued a notice on the application procedures and application materials requirements for re-registration of domestically produced drugs (No. 38 of 2024), which will be implemented from January 1, 2025. According to the new regulations on re-registration, three types of approvals will face the risk of delisting.

The first type of risky products: "zombie" approvals, especially those with missing production scope and production address

The "zombie" approvals mentioned above are very likely to be delisted: The "Application Procedures for Re-registration of Domestically Produced Drugs" clearly requires "strengthening the management of drugs that have not been produced on a commercial scale during the period from the approval of drug marketing authorization or the previous approval of drug re-registration to the current application for drug re-registration." Although this document has not explicitly stated that products that have not been produced on a commercial scale will not be re-registered, judging from the policy trend, it is very likely that a certain "window period" will be given, and "no re-registration" may be granted when the next document is released.

According to the application procedure, "drug re-registration application forms and application materials are complete and in compliance with the legal form, and they will be accepted." It has not yet been determined whether products that have not been produced on a commercial scale are considered to have incomplete application materials. Although there is no clear explanation, the "Re-registration Application Materials Requirements for Domestic Drugs" mentions that "the "Drug Production License" should be within the validity period and have the corresponding production scope and production address." This means that products with missing production scope and production address due to historical reasons are likely to be delisted due to incomplete application materials. If the exclusive "zombie" approval documents in the hands of pharmaceutical companies still have value, then they must start commercial production as soon as possible within the window period, otherwise the approval documents are likely to be lost during the next re-registration period.

The second category of risk products: products of competing manufacturers with the same generic name have passed the consistency evaluation, but the consistency evaluation research of their own products has not been initiated on time

One of the favorable policies for the consistency evaluation of generic drugs in that year was to clear a large number of approval documents that did not initiate the consistency evaluation, so companies began to invest in starting the consistency evaluation. According to the "Opinions of the General Office of the State Council on Conducting the Quality and Efficacy Consistency Evaluation of Generic Drugs" (Guobanfa [2016] No. 8), "Oral solid preparations of chemical generic drugs approved for marketing before October 1, 2007 in the National Essential Medicines List (2012 Edition) should complete the consistency evaluation before the end of 2018. Among them, varieties that require clinical effectiveness trials and special circumstances should complete the consistency evaluation before the end of 2021; those that are not completed within the deadline will not be re-registered. For other generic drugs approved for marketing before the implementation of the new registration classification of chemical drugs, the same varieties of other pharmaceutical manufacturers should, in principle, complete the consistency evaluation within 3 years after the first variety passes the consistency evaluation; those that are not completed within the deadline will not be re-registered."

The first product that passed the consistency evaluation has been approved for three years, but the corresponding approval withdrawal policy for products that did not pass the consistency evaluation has not been issued yet. In addition, some companies still applied for consistency evaluation and were accepted. After three companies passed the consistency evaluation, the provincial drug procurement platform still purchased products that did not pass the evaluation, which made many companies that invested in the consistency evaluation feel that the withdrawal period is delayed and the policy benefits cannot be enjoyed. Moreover, retail terminals prefer low-priced products that have not passed the consistency evaluation, forcing manufacturers that have passed the consistency evaluation to only compete in the centralized procurement, which also makes many companies lose the motivation to invest in consistency evaluation.

The "Requirements for Application Materials for Re-registration of Domestically Produced Drugs" mentioned that "if the consistency evaluation of the quality and efficacy of generic drugs is not completed within the prescribed time limit, there should be reasonable reasons. The explanation of the situation includes but is not limited to work requirements, work progress, conclusive opinions and supplementary applications, filing or reporting, etc." This means that in the next re-registration in 2025, if the products of competing manufacturers with the same generic name have passed the consistency evaluation but their own products have not started the consistency evaluation research on time, they are very likely to be withdrawn.

All companies should once again take stock of their products based on the existing competition landscape of generic drugs to see which "slippery fish" have not started consistency evaluation, and promote the application of consistency evaluation for products with market value as soon as possible. Category III risk products: Products with "unclear" [contraindications], [adverse reactions], and [precautions] in the instructions for Chinese patent medicines After July 1, 2026, products with "unclear" [contraindications], [adverse reactions], and [precautions] in the instructions for Chinese patent medicines may be withdrawn.

According to the "Special Provisions on the Registration and Administration of Traditional Chinese Medicines" (No. 20 of 2023, effective July 1, 2023) issued by the State Food and Drug Administration in February 2023, holders are required to strengthen the management of the entire life cycle of drugs, strengthen the monitoring, evaluation and analysis of safety risks, and refer to relevant technical guidelines to promptly improve the [contraindications], [adverse reactions], and [precautions] of Chinese medicine instructions. If any of the [Contraindications], [Adverse Reactions], and [Precautions] in the TCM instructions are still "unclear" when applying for drug re-registration three years after the implementation of these regulations, re-registration will not be granted in accordance with the law.

The fee for this type of supplementary application is estimated to be 100,000 yuan each. It is expected that companies will apply for changes to the instructions based on the value of the approval documents. Varieties that are voluntarily abandoned by companies may exit the market. With the promulgation of the new re-registration regulations, the value of "zombie" approval documents, approval documents that have not passed the consistency evaluation, and product approval documents with defects in the TCM instructions will be greatly reduced. As a bunch of approval documents are cleared, some companies will also be gradually cleaned up, and Chinese pharmaceutical companies will face new integration.

https://mp.weixin.qq.com/