On June 6th 2016, the China Food and Drug Administration (CFDA) published the final rule of Administrative Measures for Registration of Recipes for Formula Powder Product for Infants and Young Children (abbreviated as Infant Formula Measures), six months after the draft measures were notified to the World Trade Organization (WTO) for comment. The final rule to register the infant formula in China will come into force on October 1st 2016.1 Compared to the previous infant formula filing system, several significant changes have been added, including the fact that imported infant formulations now fall under the regulation, which will have a huge impact on overseas manufacturers. Infant formula manufacturers who intend to sell their products on the Chinese market will now be required to register with CFDA and provide the agency with sufficient supportive information to demonstrate their capacity to ensure the safety of the final infant formula products. After the final rule is implemented, all infant formula products will have to be approved by CFDA before they can be marketed in China. In this article, we compare and contrast the regulation of infant formula in China versus that in the U.S., and provide insightful information to help manufacturers better understand and comply with the CFDA’s updated policy.
In addition to elaborating on the requirements for labeling and descriptions, the Infant Formula Measures set several specific requirements for infant formula registration.2 The applicant, including the infant formula manufacturer previously allowed to sell products in China, would be required to submit to CFDA a report describing the research and development (R&D) of the product and the manufacturing process, a product testing report, documentation to demonstrate its capacities in R&D, production, and testing, and other materials that support the science and safety of the formula (Table 1). A CFDA authorized panel will then inspect the manufacturing facility, and a government-certified food laboratory would test product samples. Application materials, inspection outcomes, and testing results will be reviewed by an expert panel organized by CFDA. There are proposed timelines for review, including five working days to inform the applicant of acceptance of the application, 20 days for the on-site inspection (no such limit for overseas manufacturers), 30 days for the product inspection report, 60 days for expert review, and 20 days for CFDA to decide whether to approve the application. The domestic manufacturers would expect to receive the conclusion from CFDA in six months if all the materials are appropriately submitted, while the timeframe for the overseas manufacturers is to be determined, due to the uncertain length of the overseas on-site inspection. To some extent, the new CFDA draft deserves its title as the strictest regulation on infant formula in China’s history, as described by Life China.3
Note that the Infant Formula Measures is the general regulation that is legislated by CFDA according to Food Safety Law 2015, which only provides general rules. The implementation would mainly rely on the existing or upcoming sub-level regulations such as national standards (i.e., GBXXX) and provincial regulations*[1]. Prior to the Food Safety Law 2015, several national standards were set up and are still effective for infant formulas in China. For example, infant formula manufacturers must comply with national standard of GB 10765-2010, which include macro and micro nutrient requirements, specific contaminant requirements, sensory requirements and specific labelling requirements, as well as GB13432-2013, the national standard for the labeling of pre-packaged foods for special dietary uses.4 In 2015, China’s new Food Safety Law made numerous amendments specifically to regulate the infant formula. For example, article 81 in the Food Safety Law, requires infant formula manufacturers to file the information on food raw materials, food additives, production formulation and labels with the local district CFDA.5 These administrative measures drafted by CFDA provide the general rules for CFDA to implement the food safety measures. The implementing detail is still waiting to be made and is estimated to be fulfilled by the upcoming national standards or local regulations. Compared with CFDA, FDA has set forth several federal rules to oversee the manufacturers on infant formulas since 1980s.The regulations are very complete and detailed, and are primarily included in the Code of Federal Regulations (CFR). For example, according to 21CFR106.96, a manufacturer of an eligible infant formula must show that a formula supports infant normal physical growth by conducting, in accordance with good clinical practice, an adequate and well controlled growth monitoring study of the infant formula, where the conditions of the study are stringently controlled such as duration, and ages of infants6.
CFDA versus FDA Infant Formula Registration
Significant differences can be identified by comparing the infant formula regulations in China versus that in the U.S. (Table 1). In the CFDA measures, the maximum number of infant formula brands that a company can market in China will be limited to three (with nine formulae) for each manufacturer. There is no such limit in the U.S., under the U.S. Food and Drug Administration’s (FDA) regulation. The on-site inspection in China would be conducted once every month,7 while infant formula manufacturers are inspected for Good Manufacturing Practices (GMPs) yearly in the U.S. In China, infant formula products must get the approval from CFDA before they can be marketed; however, no such pre-approval step is needed in the U.S. Infant formula manufacturers in the U.S., on the other hand, are required to go through a three-step process prior to marketing a new formula 1) register with FDA; 2) provide the agency with a notification 90 days in advance; and 3) submit a written verification that summarizes test results complying the specific requirements of the United States Federal Food, Drug, and Cosmetic Act (FFDCA).8
Compared with the previous filing system, one major change occurs with regards to the registration dossier for infant formula products in China (Table 2). In the new infant formula measures, CFDA requires manufacturers to provide several materials to demonstrate that the manufacturer is qualified to manufacture the product, and ensure the final product is safe. Compared to FDA regulations, CFDA requires infant formula manufacturers to register with an application form, which is similar to the registration step in the U.S. The required CFDA documentation shares some significant similarities with their counterparts in the U.S. For instance, the description of production process required by CFDA can be compared to the description of any reformulation or changes in processing required by FDA; the CFDA test report is similar to the verification of testing results for FDA; documentation of capacity for production and testing is like manufacturing assurance (e.g., GMP) for FDA; while science and safety supporting material for CFDA and nutrition assurance for FDA are similar (Table 2). However, note that the R&D reports required by CFDA are unique and introduced by the new regulation as necessary documents. Due to the fact that many companies may not be willing to share too many in-depth details about their manufacturing secrets, there may be extensive bargaining between the manufacturers and CFDA about how many details should be disclosed in these R&D reports. Also, distinctive from FDA regulations, the new draft requires CFDA to carry out on-site due diligence reports, submit an inspection report to confirm GMPs and HACCP in the manufacturing facilities. Additionally, CFDA will sample infant formula product from the facilities and require extra test reports to be submitted from a government-authorized laboratory as part of the product application process.
Opportunities and Challenges for Infant Formula Manufacturers
The new regulation will be implemented through the month of October in 2016, although it is likely that many technical details may still be under discussion by the deadline. Therefore, CFDA granted 15 months for the infant formula manufacturer to adapt the transition (January 1st, 2018 is the final compliance date). However, it is important for manufacturers to be proactive and gain a thorough understanding of the changes happening at CFDA. Manufacturers that take a wait-and-see attitude will literally have to play the cards dealt by CFDA and possibly have to take their product off China’s market if their product is determined non-compliant with the new regulation. There are three steps manufacturers can take during the registration for the infant formula product in order to ensure compliance with CFDA.
Make a detailed timeline for the new registration.
According to new infant formula measures, it will take more than half of a year for the overseas manufacturers to get approval, if everything goes well. This means that the manufacturers need to prepare the registration dossier as well as an on-site inspection approximately one year ahead of the final compliance date. Considering the time left, there may be only one chance for the overseas manufacturer to get qualified, otherwise, they may lose out to China’s market in the near term, if their application is denied. Engaging in a dialogue with CFDA may be needed to become familiar with CFDA’s working style and possibly speed up the time for the on-site inspection.
Make good use of any existing documentation and scientific information that may support the registration.
To some extent, the rules employed by FDA are mature and may possibly be used by CFDA as examples – manufacturers, especially those in the U.S, may be able to look at their product’s safety dossiers to support information that will be needed under the new regulation. For example, since 2014, manufacturers in the U.S. have had to demonstrate to FDA that their formulas support normal physical growth and are stable for nutrition content in the final product stage.9 Obviously, any information involved in this part of the vetting process, including clinical studies and stability tests, might also be employed as support for science and safety for an application with CFDA. For example, some extra data (which is generally required for FDA approval) might also be used as supplemental material for the application with CFDA, such as the growth rates and nutrition requirement specifically for Chinese infants. However, because there is always a chance that “extra” information may become “extraneous” information and a distraction to the CFDA approval process, care should be taken to ensure relevance and helpfulness of the information.
Learn from other successful CFDA or FDA application examples.
Although there are many similarities between the regulations in CFDA and those in FDA, one thing the manufacturers need to keep in mind is that the rules for infant formulas set up by CFDA are unique, and no exact precedent can be used as a reference. However, manufacturers can always learn from previous successful applications. For example, the procedure of an infant formula application can be compared to the Generally Recognized as Safe (GRAS) notification process for the following reasons*[2]. First, both the FDA and CFDA require description of product (specifications) and method of manufacture for the product. Second, the scientific and safety supporting material required by CFDA, like a GRAS dossier, must be carefully considered and thoughtfully documented to ensure its approval (or in the case of a GRAS notification, a letter of no objection from FDA). Third, both will be reviewed and approved by an expert panel (keep in mind, though, that while in the U.S. the manufacturer can choose the expert panel; in China the panel is decided by CFDA). Therefore, experience in successfully handling safety dossiers similar to GRAS notifications will be very helpful to gain the approval of an expert committee, and CFDA, in a timely manner.
The final compliance date for the infant formula registration is January 1st, 2018.10 Considering all the material required for registration, the timeline is very limited for manufacturers to prepare for the changes introduced by this new regulation. If manufacturers act quickly, they will be able to gain approval from CFDA in a timely manner. In addition, the manufacturer’s sales and marketing personnel will be able to quickly notify customers that their infant formula is safe and approved by CFDA. The U.S. and other infant formula manufacturers importing to China will also be able to get onto market quickly by becoming CFDA approved earlier than their competitors. Meanwhile, non-compliant competitors’ products will not be available to the Chinese market, or will be subject to recall or litigation. For more information, consult the references provided below or contact Burdock Group.
*The author has a Doctor of Philosophy degree in Nutritional Science and a Master’s degree in Food Science specializing in dairy processing; he is not an attorney, and this article does not provide legal advice. With over 25 years of documented experience in regulatory compliance, Burdock Group has the knowledge and experience to quickly and succinctly to determine your product’s needs, milestones, and challenges. We can provide insightful assessments and feasibility plans for your infant formula products to economically and timely pass the review of regulatory agencies.
*[1] In China, the food safety law 2015 is legislated by China’s National People’s Congress and provides major statutes to regulate infant formula. The department of State Council is responsible to promulgate general rules (named as administrative measures) to enable and interpret the statutes. Under that, the national standards or local regulation are issued to provide the detailed administrative rules for implementation.
*[2] Note that GRAS notification process is an ingredient based application for non-food additives, which is different from the product based application such as infant formula application in China. Here, we only compare the similarities in their procedures.
Table 1. The regulation of infant formula in China vs. U.S.2,8 ChinaU.S.Regulatory authorityCFDAFDARegulated productsDomestic and imported infant formula productsDomestic and imported infant formula productsApplicantDomestic and imported infant formula manufacturerDomestic and imported infant formula manufacturerMaximum number of brands
to sell3 brands, 9 productsNo limitPre-approval requiredYesNo, but a three step process including registration, notification, verification requiredOfficial On-site inspectionMonthlyYearlyRegistration timeframeSix months for domestic manufacturer; To be determined for overseas manufacturerRegister and notify FDA within 90 days before marketing; Submit a written verification for compliance to FDA before introduction into interstate commerce
Table 2. Requirements of registration dossier for infant formula in China vs. U.S.2,8China registration dossier U.S. required dossier 1. Application form for registration of infant formula recipes1. Registration with FDA2. Applicant’s credential documents2. Quantitative formulation (for notification)3.Quality and safety standards for raw materials and auxiliary materials3. Description of any reformulation of the formula or change in processing (for notification)4. Reports about research and development of the formulation4. Nutritional Assurances (for notification)5.Description of production process5 .Manufacturing Assurances (e.g., GMP) (for notification)6.Test report of the product6. Written verification that summarizes test results complying with specific requirements of FFDCA7. Documentation of capacities for R&D, production and testing8. Other documents evidencing science basis and safety of the recipe
References
CIRS. CFDA released administrative measures on product formula registration of infant formula milk powder. http://www.cirs-reach.com/news-and-articles/cfda-released-product-formula-registration-administration-measures-on-infant-formula-milk-powder.html. Updated 2016. Accessed August 27, 2016.
CFDA. Administrative measures for the registration of recipes for formula powder products for infants and young children (translated into English by USDA). http://gain.fas.usda.gov/Recent%20GAIN%20Publications/CFDA%20Publishes%20Measures%20for%20Registration%20of%20Infant%20formula%20Recipes_Beijing_China%20-%20Peoples%20Republic%20of_6-17-2016.pdf. Updated 2016. Accessed August 27, 2016.
Life China. The strictest regulation for infant formula in history: Infant formulas must register (in Chinese). http://life.china.com.cn/2015-09/29/content_36707531.htm. Updated 2015. Accessed March 25, 2016.
SGS Offices & Labs. Infant formula – recent issues and regulatory changes. http://www.sgs.com/en/news/2015/12/infant-formula-recent-issues-and-regulatory-changes. Updated 2015. Accessed March 25, 2016.
CIRS. The strictest “Food safety law” in china. http://www.cirs-reach.com/news/The_Strictest_Food_Safety_Law_in_China.html. Updated 2015. Accessed March 25, 2016.
FDA/CFSAN. Guidance for industry: Demonstration of the quality factor requirements under 21 CFR 106.96(i) for “eligible” infant formulas. http://www.fda.gov/RegulatoryInformation/Guidances/ucm400036.htm. Updated 2014. Accessed March 25, 2016.
U.S.-China Health Products Association. CFDA to launch monthly check on infant formula. China Updates. February 4 2016;179.
FDA/CFSAN. Guidance for industry: Frequently asked questions about FDA’s regulation of infant formula. http://www.fda.gov/Food/GuidanceRegulation/GuidanceDocumentsRegulatoryInformation/InfantFormula/ucm056524.htm. Updated 2006. Accessed March 25, 2016.
FDA. FDA takes final step on infant formula protections. http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm048694.htm. Updated 2014. Accessed March 25, 2016.
REACH24H Consulting Group. China CFDA finalizes infant formula registration rules. https://food.chemlinked.com/news/food-news/china-cfda-finalizes-infant-formula-registration-rules. Updated 2016. Accessed August 27, 2016.