Interpretation of selected paragraphs of "sterilization and filtration technology and Application guide"

On September 11, 2018, the State Drug Administration issued the guidance on sterilization and filtration technology and application, which was implemented on October 1 The guide includes the design, selection, validation and use of sterilization and filtration system, which is applicable to the whole life cycle of sterile drugs from process development to production on the market This article mainly interprets from the aspects of the design of the sterilization and filtration process: Regulation 1: when designing the filtration process, we should select the appropriate filter and determine the process parameters according to the properties of the medium to be filtered and the purpose of the process Interpretation: what is the right filter? Regulatory requirements: according to the purpose of the process, a 0.22 μ m (smaller pore size or the same filtration efficiency) sterilization filter shall be selected for the sterilization and filtration process A 0.1 micron sterilizing filter is usually used to remove mycoplasma This article specifies the aperture and grade of the filter, which must be a sterilizing filter Regulation 2: microbial control shall be carried out in the whole process of aseptic drug production to avoid microbial pollution Before sterilization and filtration, the microbial pollution level of the medium to be filtered is generally less than or equal to 10 CFU / 100ml Interpretation: This article defines the microorganism level of the medium to be filtered before filtration If it fails to meet this requirement, it is necessary to reduce the microorganism load through pre filtration before sterilization and filtration Regulation 3: when selecting the filter material, the compatibility with the medium to be filtered shall be fully investigated The filter shall not have adverse effect on product quality due to reaction, release or adsorption with the product The filter shall not fall off the fiber, and the filter containing asbestos shall not be used Interpretation: this regulation stipulates that the solution to be filtered shall be compatible with the filter, and the filter shall not shed fiber The compatibility of filtration membrane refers to the deformation, dissolution, precipitation or strength change that may occur when contacting with liquid This is less common when filtering ordinary aqueous solutions However, a similar situation may occur in the presence of extreme pH or organic solvents Regulation 4: the selection of filter membrane material also needs to consider adsorption The adsorption of the filter is inevitable, but the filter with relatively small adsorption can be selected, or the adsorption situation can be investigated by small-scale experiments During aseptic filling, it may be necessary to discard the initial filtrate to ensure the concentration of the product after Zui Interpretation: reasonable filter membrane area needs to be evaluated by scientific methods Too large filtration area may lead to the decrease of product yield and the increase of filtration cost; too small filtration area may lead to the prolongation of filtration time, stoppage in the middle or even product scrap In general, before selecting a suitable filter device, it is necessary to carry out a small-scale Vmax test, and to determine the filter membrane area with a certain safety factor The determination of the safety factor is related to the nature of the sample and the difference between batches Regulation 5: when selecting filter, process parameters such as filter temperature range, Zui long filter time, filter flow rate, sterilization condition, inlet and outlet differential pressure range or filter flow rate range shall be determined according to actual process requirements, and whether these parameters are within the acceptable range shall be confirmed Interpretation: This article stipulates that the relevant parameters of the filtration process must be specified for the sterilization and filtration process, which also requires process validation Next time, we will explain the validation of the filter in detail.