[FSMP] FAQs: Eighteen Questions Related to Formulas for Special Medical Purposes

On December 5, 2024, China's Center for Food Evaluation (CFE) published eighteen frequently asked questions relating to formulas for special medical purposes (FSMP), covering various items including formulas, labels and instructions for use, production process, quality and safety, and clinical trails.

Formulas

Question 1: What are the formulation characteristics and technical requirements for thickening components?

Answer: The purpose of thickening components is to increase the viscosity of water and food and reduce their fluidity, thereby reducing the risk of swallowing difficulties and/or aspiration. The product formulation should focus on thickening, rather than providing energy or nutrients. One or more thickeners may be added to food products in accordance with GB 2760 and related laws and regulations. The rationale for the use of dietary fiber as a thickening agent should be sufficient. In principle, dietary fiber that does not contribute to thickening should not be added, and additional nutrients should not be added.

Evidence supporting the thickening effects and performance of the product should be provided, including the viscosity of the product after mixing with water and other foods and the corresponding swallowing difficulty food classification. Reference may be made to the "Chinese Expert Consensus on Nutritional Management of Dysphagia Diet" (2019 edition) and the International Dysphagia Diet Standardization Initiative (IDDSI) food classification standards. Research data on the product's uniformity and solubility should also be included. Any factors that affect the product's stability (such as temperature, storage time, and salivary amylase) should be addressed. An analysis and evaluation of factors that may affect the thickening effect and performance, such as the specifications and performance of raw materials or food additives, should be conducted.

The product label and instruction manual should specify the swallowing difficulty classification after mixing with water, the preparation method, mixing temperature, and storage time.

Question 2: What are the formulation characteristics and technical requirements for liquid formulations?

Answer: Liquid formulations are suitable for individuals under medical conditions that require restricted fat intake, gastrointestinal dysfunction, or malabsorption.

The formulation should cover carbohydrates and proteins, and fat should not be added for the purpose of providing energy. Protein sources can include whole proteins, protein hydrolysates, amino acids, and peptides. The proportion of high-quality protein should be no less than 50%, and evidence should be provided to meet the protein nutritional requirements of the target population. Carbohydrate sources can include monosaccharides, disaccharides, oligosaccharides, polysaccharides, maltodextrin, glucose polymers, or other raw materials allowed by laws and regulations. Vitamins and minerals should be added based on the needs of the target population, and relevant supporting evidence should be provided.

The product label and instruction manual should include expiration date guidelines, such as "should be adjusted according to the clinical situation of the target population under the guidance of a doctor or clinical nutritionist." The product's osmotic pressure in its ready-to-eat state should also be specified for reference.

Question 3: What are the formulation characteristics and technical requirements for fat components?

Answer: The purpose of fat components is to provide fat (acid) for populations with fat intolerance, poor fat absorption, or other fat metabolism disorders, or to adjust the dietary fat composition to meet their specific fat (acid) requirements. The main component of the fat component is fat (acid), and other food ingredients or food additives may be added according to the manufacturing process requirements, but such additions should be explained, and the potential impact on the fat component should be assessed.

The product label and instruction manual should include information on the fat (acid) composition and content. For example, if the fat source is medium-chain fatty acids, the target population can be described as "populations requiring medium-chain fats due to special medical conditions."

Labels and Instructions for Use

Question 1: How should the values for energy, nutrients, and optional ingredients be determined?

Answer: The values for energy, nutrients, and optional ingredients in the nutrition facts table can be determined based on product testing results, deviations, raw material conditions, production process losses, and stability study results. The measurement units should comply with national food safety standards, such as GB 29922 and GB 25596, and rounding intervals should not be less than the decimal places specified in the relevant food safety standards.

The energy, nutrient, and optional ingredient values per 100g, 100mL, and 100kJ of the product should correspond accordingly.

Production Process

Question 1: What materials should be provided when producing different varieties of products on the same production line?

Answer: When different varieties of products are produced on the same production line, the applicant should provide an explanation of the shared production line situation, the measures taken to prevent cross-contamination, and related materials. The applicant should thoroughly analyze food safety risks (including but not limited to food protein allergy risks), develop effective cleaning measures, and ensure they are verified. The product switch should not affect the subsequent batch of products and should comply with the relevant approval registration requirements. For products related to food protein allergies, lactose-free or low-lactose formulations, and amino acid metabolism disorders, a detailed risk assessment report must also be provided.

Question 2: What materials can the applicants provide to demonstrate that they have established a quality management system that meets the requirements of Good Manufacturing Practices (GMP)?

Answer: Applicants can provide materials that demonstrate that they have established a quality management system compliant with Good Manufacturing Practices for special medical purpose foods, such as a description of the production quality management system established according to the Good Manufacturing Practices for Foods for Special Medical Purpose (GB 29923-2023), a directory of quality management system documents.

Quality and Safety

Question 1: How should stability studies be conducted for products that require stability research?

Answer: For full-nutrition formula foods, special medical purpose infant formula foods, and products that meet the requirements of relevant registration guidelines (such as those for electrolyte formula foods, carbohydrate component foods, or protein component foods), stability studies should be conducted in accordance with the Stability Study Requirements (Trial) for Formulas for Special Medical Purpose and records should be kept for review. Stability studies should be completed after conducting accelerated tests before applying for registration.

Question 2: Is it possible for a third-party testing agency to provide product testing reports for three batches of products?

Answer: The applicant may conduct the testing and provide the report for three batches of products themselves, or may entrust a legally qualified testing agency to conduct the tests. For certain items, if testing is entrusted, the original and copies of the entrustment testing report should be provided.

Question 3: What are the requirements for the amino acid raw materials used in the product?

Answer: The amino acid raw materials or amino acid components in composite ingredients used in the product must comply with the relevant provisions of GB 29922 or GB 25596. The source of the compound, production process, quality specifications, and testing methods, should meet the requirements of the National Health Commission's Announcement on the Management of Amino Acids in Special Dietary Foods (2023 No. 11).

Question 4: How should product standards be set for products containing ingredients such as nucleotides?

Answer: For products containing ingredients like nucleotides, oligosaccharides, and edible fungi, corresponding standards and limits should be set in the product specification based on the ingredient quantity, nutritional component values, product formulation characteristics, and nutritional features.

Clinical Trial

Question 1: What should applicants focus on when submitting clinical trial materials?

Answer: The revised Quality Management Guidelines for the Clinical Trial of Formulas for Special Medical Purposes have detailed the content of clinical trial protocols and final reports. Applicants should submit clinical trial materials in accordance with the main content, general requirements, and format specifications of the clinical trial protocol and report.

Question 2: What are stamping requirements for the clinical trial summary report and sub-center clinical trial summaries?

Answer: The clinical trial summary report should be stamped with the signatures of the researcher, clinical trial institution, and applicant, along with the signature and stamp of the statistical manager.

For multi-center clinical trials, sub-center clinical trial summaries should be signed by the sub-center researcher and stamped with the sub-center's clinical trial institution stamp. Data management plans and statistical analysis plans should be signed by the data management and statistical analysis heads, with the unit's stamp.

Question 3: What are the design requirements for clinical trial protocols?

Answer: The applicant should comprehensively consider the product's formulation characteristics, nutritional features, and target population, and ensure the scientific and rational design of the clinical trial. The clinical trial observation indicators should be set based on the specific situation of the product formulation and the target population. For categories where the State Administration for Market Regulation has issued relevant clinical trial guidelines, those should be followed.

Question 4: How do you apply for clinical trial communication?

Answer: If the applicant encounters issues related to clinical trials for specific full-nutrition formula foods, they can send product information, clinical trial protocols or drafts, specific issues, and contact details to: tysp@cfe-samr.org.cn. The email subject should indicate “XXX (Manufacturer Name) Clinical Trial Communication Application.”

The product information should include the product category, formula composition, formulation features, and target population. The clinical trial protocol should include methods, control samples, trial duration, sample size, statistical methods, evaluation indicators, inclusion/exclusion criteria, principal researchers, and clinical trial units.

Question 5: Does a clinical trial institution for special medical purpose formula foods need to be registered?

Answer: According to the Quality Management Guidelines for Clinical Trial of Formulas for Special Medical Purposes, clinical trial institutions must be registered with the State Administration for Market Regulation's Special Food Validation and Evaluation Technical Agency Registry (https://tsspjg.gsxt.gov.cn).

The principal investigator should complete the registration on the Clinical Trial Registration Platform (National Medical Research Registration Platform https://www.yxyj.org.cn or Chinese Clinical Trial Registration Center https://www.chictr.org.cn) and obtain a clinical trial registration number. If applicable, the applicant must also provide approval or registration materials from the Human Genetics Office (https://apply.hgrg.net).

Other Questions

Question 1: What additional application materials are required when the net content and specifications change during registration?

Answer:

1. A process verification report for three batches corresponding to the proposed increase or change in net content. If key control points are involved, a process verification report should be provided according to new product registration requirements, such as for products with different net contents produced using post-sterilization processes.
2. Three batch product inspection reports.
3. If there are changes to the packaging materials that come into direct contact with the product, materials proving that the packaging materials comply with the relevant national food safety standards should be provided.
4. Generally, corresponding stability studies should be completed in accordance with the requirements for new product registration applications. If deemed feasible after a thorough evaluation, evidence demonstrating that the product stability meets the relevant requirements should be provided.

Question 2: What additional application materials are required when the product formulation changes during registration?

Answer:

1. When changes in the product formulation involve changes in raw material types and quantities, relevant process verification and product inspection reports for three batches should be provided.
2. For new ingredients, materials proving that the new ingredients comply with national food safety standards and corresponding inspection reports should be provided.
3. Generally, corresponding stability studies should be completed in accordance with the new product registration application requirements. If deemed feasible after a thorough evaluation, evidence demonstrating that the product stability meets the relevant requirements should be provided.
4. A detailed comparison of the product formulation before and after the change should be provided, along with materials that demonstrate that the formulation change does not affect clinical safety, nutritional adequacy, clinical efficacy for special medical purposes, or the continuity of clinical use.

Question 3: What additional application materials are required when the production process changes during registration?

Answer:

1. A detailed comparison of the production process before and after the change.
2. The basis for setting the process steps and parameters after the change.
3. Materials regarding the key steps and quality control measures in the new production process.
4. Process verification materials for three batches and inspection reports for three batches of products in the new production process. For steps that are thoroughly evaluated as not affecting the product's inspection results, relevant explanations and verification materials should be provided, such as for changes in foreign object control measures.
5. The new production process documentation and process flow diagram, with relevant technical parameters noted.
6. Generally, corresponding stability studies should be completed according to the new product registration application requirements. If deemed feasible after thorough evaluation, evidence demonstrating that the product stability meets the relevant requirements should be provided.

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