Food Partner Network: Analysis of the R&D ideas and precautions of special medical food

Core tip: So how to carry out the research and development of special medical food oriented by registration and approval in accordance with the product registration requirements has become one of the issues that have attracted much attention in the industry. Based on relevant regulations, Q&A requirements and registration service experience, the Food Partner Network briefly analyzes the R&D ideas and precautions of special medical food, so as to help enterprises better carry out the research and development of special medical food.

Food Partner Network (www.foodmate.net)

　　　As we all know, formula food for special medical purposes (hereinafter referred to as special medical food) has clarified the requirements for registration management since the introduction of the 2015 version of the Food Safety Law of the People's Republic of China. The Administrative Measures for the Registration of Formula Food for Special Medical Purposes set out detailed provisions on enterprises that produce and sell special medical food in mainland China, as well as overseas manufacturers that export special medical food to China. Under strict regulatory measures, enterprises should put risks in advance and implement registration requirements in the R&D stage of special medical food, so as to avoid discovering many loopholes in the early R&D stage at the stage of organizing registration materials, resulting in a certain degree of loss. Therefore, how to carry out the research and development of special medical food oriented by registration and approval in accordance with the requirements of product registration has become one of the issues that has attracted much attention in the industry. Based on relevant regulations, Q&A requirements and registration service experience, the Food Partner Network briefly analyzes the R&D ideas and precautions of special medical food, so as to help enterprises better carry out the research and development of special medical food.

　　1. Clinical needs research

　　Enterprises should conduct research on clinical needs according to the determined direction. The Administrative Measures for the Registration of Formula Food for Special Medical Purposes (2023 Revised Edition) emphasizes that "the registration management of formula food for special medical purposes is guided by clinical nutritional needs, follows the principles of science, openness, fairness and justice, and encourages innovation". The results of this process can be used to describe the "basis for determining the applicable population" in the registration dossier (specific whole nutrition formula and non-full nutrition formula food are required).

　　Second, the initial design of the product formula

　　According to the identified target population, literature was collected, the nutritional needs of the target population were studied, and the nutritional content table and formula scale were preliminarily designed. In this process, enterprises should have enough understanding of the characteristics of the product formula, find a detailed formula design basis, and pay attention to the purpose, coordination and rationality of the formula, so that the product is easier to pass the registration review, such as the formula characterized by easy digestion, and the content of dietary fiber should not be designed to be higher.

　　When forming the formula scale, the names and dosages of food raw materials and food additives used should comply with the corresponding national food safety standards and/or relevant regulations, and it is necessary to pay attention to "no other bioactive substances other than the nutrients and optional ingredients specified in the standard", and try to choose food raw materials with single nutrients and clear nutrients, while paying attention to the cost.

　　In terms of the selection of raw materials, enterprises can investigate the names and frequency of raw materials used in similar products that have been approved. The Food Partner Network has recently launched a special medical food query visualization system, which can quickly find the information of approved products, and count the approval status over the years, the approved enterprises, the frequency of ingredient use, the energy supply ratio of energy supply nutrients, etc., and generate visual charts, which is convenient for enterprises to quickly and accurately obtain information and improve R&D efficiency.

　　3. Product laboratory research and product pilot test

　　3.1 Production process design

　　First of all, the design of the production process should be carried out, and the product process route and process parameters should be selected according to the product form, which needs to be determined according to the literature and actual data, and pay attention to keeping the corresponding records and materials to be used in the registration application link.

　　3.2 Screening of raw and auxiliary materials

　　Based on the preliminarily determined formula scale, the qualifications of suppliers or distributors should be reviewed to screen suppliers of raw materials, such as business licenses, production licenses, internal/external inspection reports, process flow diagrams, distributor import qualifications, cooperation agreements with manufacturers, etc., and it is recommended that enterprises inspect the degree of cooperation of suppliers or distributors to facilitate the corresponding technical support in the process of product development.

　　Obtain samples of raw materials from suppliers or distributors who have passed the qualification review, test and screen the physical and chemical properties of raw materials, and finally determine at least three suppliers or distributors for alternatives. It should be noted that the determination of the test index of raw material screening is related to the production process, such as the dry production of products, the microorganisms of raw and auxiliary materials must be paid attention to, because it cannot be sterilized in the later stage, followed by particle size, angle of repose, bulk density, tap density, hygroscopicity and other indicators; For wet production products, it is necessary to pay more attention to the physical and chemical properties of raw and auxiliary materials, such as solubility, thermal stability, emulsification, etc., and also consider the reaction of different materials.

　　3.3 Product Formula Adjustment

　　Use the selected qualified raw and auxiliary materials, conduct a small test according to the determined process route and parameters, and test the trial samples, evaluate the deviation against the nutritional composition of the preliminary design, and adjust the formula. Repeat the above operations until the trial sample meets the requirements of the nutritional composition, and then carry out the pilot test, and if the deviation is found in the pilot process, the formula can be fine-tuned to ensure that the trial sample produced according to the final product formula meets the requirements of the nutritional content. After the formula is determined, product standards should be formulated in time to ensure that there are standards to follow for subsequent testing.

　　Enterprises should have detailed records of the process of determining product formulas, and should also have corresponding records of the process of experimental screening of raw and auxiliary materials, as the source of registered materials for product formula screening (specific full nutrition formula food and non-full nutrition formula food need to be submitted).

　　Fourth, commercial trial production

　　On the commercial production line that has been verified by equipment and meets the requirements of the National Food Safety Standard Good Manufacturing Practice for Formula Food for Special Medical Purposes (GB 29923), commercial trial production is carried out in accordance with the operating procedures of formal production and the determined product formula, and the realization of the production process and product realization is evaluated, and the process verification and deviation correction of the proposed production process are required to ensure the reproducibility of the entire process and the controllability of product quality. Pay attention to keep relevant records and materials, such as equipment verification plan/record/report, registered batch trial production process verification plan/report, production record of 3 batches of commercial trial production, equipment use record, warehousing ledger, etc., which will be reflected in the registration materials "Product R&D Report" and "Production Process Materials".

　　5. Product inspection and stability research

　　5.1 Full-item inspection

　　Enterprises need to inspect all the items specified in the product standard requirements for the above three batches of commercial trial production samples. The inspection report shall contain the inspection data of all items, and clarify the inspection conclusion, which shall be determined according to GB 25596 or GB 29922, product standard requirements and GB 13432.

　　5.2 Stability Studies

　　Stability studies should be reasonably set according to different research purposes, combined with the physical and chemical properties, product forms, product formulas and process conditions of food raw materials, food excipients, nutritional enhancers and food additives.

　　The product should be subjected to influencing factor test, accelerated test and long-term test, and other types of tests should be selectively designed according to product characteristics, packaging and use, such as stability test for use after opening. Enterprises shall organize and carry out stability research tests in accordance with the Requirements for Stability Research on Formula Food for Special Medical Purposes (Trial) (2017 Revised Edition), and retain relevant sampling and inspection records, environmental records, inspection records, inspection reports and other materials for registration needs. Apply for the registration of specific full nutrition formula food and non-full nutrition formula food products, and submit the stability test report of the test sample.

　　The test samples can be inspected by the applicant himself, or he can entrust a third-party inspection agency with legal qualifications (CMA and CNAS) for inspection, if the third-party inspection is entrusted, the inspection report issued shall be stamped with the official seal of the third-party inspection agency.

　　6. Clinical trials

　　If the special medical food developed by the enterprise is a specific full nutrition formula food, the clinical trial shall be conducted in accordance with the "Good Clinical Practice for Formula Food for Special Medical Purposes" and the relevant clinical trial technical guidelines, and the clinical trial report and clinical trial related materials shall be issued at the time of product registration. Test samples used in clinical trials shall be inspected to meet the corresponding national food safety standards and technical requirements.

　　7. Registration and declaration

　　After the above links are completed, it can enter the registration and declaration stage, and enterprises can refine, sort out and compile the above product research and development process into registration materials in accordance with the "Items and Requirements for Application Materials for the Registration of Formula Food for Special Medical Purposes (Trial) (2017 Revised Edition)", and carry out online system declaration and on-site submission of paper materials in accordance with the "Administrative Measures for the Registration of Formula Food for Special Medical Purposes", and officially enter the registration review and approval process. If there are organizational difficulties in the registration materials and inconvenience in submitting materials on site in this process, the Food Partner Network can provide professional technical support services.

　　brief summary

　　As an important way to provide clinical nutritional support, each nutritional ingredient of special medical food must be accurately designed, and enterprises need to fully consider the needs and characteristics of specific groups in research and development. During the product registration review, the company's R&D capabilities and product R&D process will be comprehensively examined, which is also a key issue in the R&D work of the enterprise.