Recently, according to the National Medical Products Administration’s Cosmetic Ingredient Filing Information Platform, a new ingredient called “Asivatrep” filed by Amorepacific Corporation (referred to as “Amorepacific”) has been deregistered. The reason for the deregistration of this new ingredient has not been disclosed as of now.
It is worth mentioning that as the first deregistered new ingredient since the implementation of the new regulations for cosmetics, this incident has drawn widespread attention from the industry. Many industry professionals believe that this event may indicate a strengthening of regulatory oversight throughout the entire process of new ingredient management.
The ingredient has been registered for nearly a year and was voluntarily deregistered by Amorepacific.
On March 3rd of last year, Amorepacific registered and filed a new ingredient called “Asivatrep” with the filing number “GZYBZ(国妆原备字)20230007”. The domestic responsible party for this ingredient is Hangzhou Ruiou Chenxing Technology Co., Ltd. (referred to as “Ruiou Chenxing”). This is currently the only cosmetics new ingredient filed by Amorepacific in China.
According to the technical requirements for the cosmetic new ingredient “Asivatrep”, with an ID number of “36188,” and its CAS number is “1005168-10-4.” It is a non-animal and non-plant-based ingredient. The preparation process of Asivatrep involves the condensation and acylation of (R)-N-(4-(1-aminoethyl)-2,6-difluorophenyl) methanesulfonamide hydrochloride and (E)-3-(2-propyl-6-(trifluoromethyl)-pyridin-3-yl)acrylic acid, resulting in a composition of 100% Asivatrep.
It is reported that the intended use of “Asivatrep” is as a skin protectant and is applicable to various skincare cosmetics (excluding spray products). The maximum permitted concentration of this ingredient in cosmetic products is 0.08% for body products, 0.4% for facial products, and 0.3% for hand products.
In early February of this year, the filing information for “Asivatrep” showed that it was deregistered on February 1st. It can be seen that this new ingredient filed by Amorepacific was deregistered less than a year after its successful filing.
The question arises as to whether the above-mentioned new ingredient was deregistered voluntarily by the company or by the National Medical Products Administration, and what the reason for its deregistration was. CHAILEEDO contacted Ruiou Chenxing for inquiries, and a staff member stated that “the deregistration was voluntarily initiated by the company. Amorepacific expressed that they no longer intend to use this ingredient in the cosmetics field and entrusted us with the deregistration process.”
It is well-known that applying for the filing of a new ingredient incurs significant costs. So why did Amorepacific voluntarily deregister this new ingredient after a successful filing? CHAILEEDO also contacted Amorepacific for a response but, as of the time of writing, no reply has been received.
The ingredient “Asivatrep” currently has no cosmetic applications and has not entered the the monitoring period
Several research and development engineers have informed CHAILEEDO that Asivatrep is a specific TRPV1 antagonist developed by Amorepacific and has successfully passed phase I and II clinical trials. As early as October 2021, the results of the phase III clinical trial on this ingredient were published in the top journal in the field of allergy/immunology, J Allergy Clin Immunol. The paper, titled “Asivatrep, a TRPV1 antagonist for topical treatment of atopic dermatitis: A phase III randomized controlled study (CAPTAIN-AD),” listed Amorepacific Research Center as one of the authors.
The results showed that patients with mild-to-moderate atopic dermatitis (AD) who received 1% Asivatrep treatment had effectively controlled symptoms, improved disease scores, and significant improvements in sleep quality compared to the placebo group. According to the findings, Asivatrep is effective in treating patients with mild-to-moderate AD.
So why is “Asivatrep” listed as a “skin protectant” instead of an antagonist in the technical requirements for cosmetic new ingredients? An experienced regulatory engineer stated, “This may be related to the limited purposes allowed for cosmetic use, where many effects can only be described as skin protectants.”
In addition, when searching for “Asivatrep” as a keyword on the Beauty Journey app, no beauty products utilizing this ingredient were found.
Furthermore, according to Article 19 of the “Administrative Measures for the Registration and Filing of Cosmetics,” “Registered and filed cosmetics new ingredients are subject to a safety monitoring system for a period of three years, starting from the date of the first use of the cosmetics new ingredient for registered or filed cosmetics.”
Therefore, it can be seen that cosmetic new ingredients do not enter a three-year monitoring period simply by filing, but they need to be applied in cosmetics to truly start the three-year “countdown.” Currently, “Asivatrep” has not been applied in cosmetics, which means that this new ingredient has not entered the three-year monitoring period.
“It may be canceled at any time if it does not pass the monitoring period.”
It is well known that China has always taken a cautious approach to the registration of new cosmetic ingredients. Between 2004 and 2016, only 14 cosmetic new ingredients were approved for use. It was not until the new regulations were implemented in 2021 that this situation began to change, and the registration of cosmetic new ingredients entered a period of rapid growth.
According to CHAILEEDO’s research, from May 1, 2021, to the present, 130 cosmetic new ingredients have completed the registration process, and the number of registered ingredients has been increasing year by year. Specifically, there were 6 new ingredients registered in 2021, 42 in 2022, and a total of 69 in 2023. In less than two months this year, 13 new ingredients have already been registered or updated. Many industry experts have predicted that the number of newly registered ingredients in 2024 will continue to reach new highs and may exceed 500 within a few years.
In the midst of the fervor surrounding the registration of new ingredients, the cancellation of “Asivatrep” has also attracted widespread attention in the industry. Some senior industry insiders believe that while the government has opened the “gateway” for new ingredients, it has also started to tighten regulations on their supervision.
It is worth noting that from the cancellation of the first registered ingredient, it can be seen that newly registered ingredients that have not passed the monitoring period can be canceled at any time. A senior regulatory engineer stated that the registration process for new ingredients is only the most basic checkpoint. Companies only need to prepare the required materials and submit them for review by the regulatory authorities. If there are no issues, the authorities will directly make the registration public. The key to whether a new ingredient can successfully pass lies in the three-year monitoring period. During this period, the regulatory authorities will conduct on-site data audits, supplementation, modifications, and corrections. Companies are also required to submit reports on the use of new ingredients each year. In short, there is uncertainty surrounding new ingredients until they pass the three-year monitoring period. It is highly possible for companies to voluntarily cancel or for the regulatory authorities to cancel the registration.
Regarding newly registered ingredients that have entered the monitoring period (i.e., have been applied in cosmetics), if they are canceled before the end of the monitoring period, what should be done with products that have used that ingredient? The aforementioned expert stated, “If the product has not caused any adverse reactions, the brand can continue to sell the existing stock but cannot produce more. If the product has adverse reactions, a recall should be conducted immediately based on the severity.”
Furthermore, according to the “Announcement of the National Medical Products Administration on Encouraging Innovation and Regulating the Management of Cosmetic New Ingredients (No. 143 of 2023),” the registrant of a cosmetic new ingredient should fulfill the responsibilities of the enterprise, conduct self-inspections of the ingredient registration in accordance with the regulations, guidelines, and relevant technical specifications, and if any issues are found that indicate that the registration of the new ingredient is not within the scope of registration, the registrant can proactively request the cancellation of the registration from the National Medical Products Administration.
From this, it can be seen that successful registration of new ingredients is not a one-time event. Post-registration, the self-inspections conducted by companies, the scrutiny of regulatory authorities, and market feedback are all crucial aspects that should not be overlooked.
