?-System Design
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Annex 1: Manufacture of Sterile Medicinal Products 2022 Final Version
8.5 Processing of the bulk solution should include a filtration step with a microorganism retaining filter, where possible, to reduce bioburden levels and particles prior to filling into the final product containers and there should be a maximum permissible time between preparation and filling.
interpretation
this article compareddid.Extension
are requiredfiltrationcontrol to avoid the risk of microbial growth
highlightedBefore fillingfilteringReduced microbial loadandparticulate matter
8.79 If the product cannot be sterilised in its final container, solutions or liquids should be sterilised by filtration through a sterile sterilising grade filter (with a nominal pore size of a maximum of 0.22 μm that has been appropriately validated to obtain a sterile filtrate) and subsequently aseptically filled into a previously sterilised container. The selection of the filter used should ensure that it is compatible with the product and as described in the marketing authorization (see paragraph 8.135).
interpretation
this article and2008 edition is similar.
are clarified inwhat situationselectionsterilization filtrationas a terminal sterilization method
(click to view the big picture, one picture to understand how to choose the sterilization method)
8.80 Suitable bioburden reduction prefilters and/or sterilising grade filters may be used at multiple points during the manufacturing process to ensure a low and controlled bioburden of the liquid prior to the final sterilising filter. Due to the potential additional risks of a sterile filtration process, as compared with other sterilisation processes, an additional filtration through a sterile sterilising grade filter, as close to the point of fill as possible, should be considered as part of an overall CCS.
interpretation
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emphasizes the selection of appropriatepre-filter(usually a filter for reducing microbial load, or a sterilizing grade filter) to ensure that the sterilization of the feed liquid before filtrationMicrobial loadat low level and controllable range
Before filling, it is recommended to useadditional sterilizing grade filterand as close as possible to the filling pointPollution Control Strategy
8.81 The selection of components for the filtration system and their interconnection and arrangement within the filtration system, including pre-filters, should be based on the critical quality attributes of the product, justified and documented. The filtration system should minimize the generation of fibres and particles, not cause or contribute to unacceptable levels of impurities, or possess characteristics that otherwise alter the quality and efficacy of the product. Similarly, the filter characteristics should be compatible with the fluid and not be adversely affected by the product to be filtered. Adsorption of product components and extraction/leaching of filter components should be evaluated (see paragraph 8.135).
interpretation
this article compared, did.AddandExtension
emphasisfiltration system, includingpre-filter screeningshall be based on CQA confirmation of the product and shall be evaluated and documented
reiterated the filtration system relatedValidation
review please stamp:sterilization and filtration verification regulations?-EMA
8.82 The filtration system should be designed:
I. Allow operation within validated process parameters.
ii. Maintain the sterility of the filtrate.
iii. Minimize the number of aseptic connections required between the final sterilising grade filter and the final filling of the product.
iv. Allow cleaning procedures to be conducted as necessary.
v. Allow sterilisation procedures, including sterilisation in place, to be conducted as necessary.
vi. Permit in-place integrity testing, of the 0.22 μm final sterilising grade filter, preferably as a closed system, both prior to, and following filtration as necessary. In-place integrity testing methods should be selected to avoid any adverse impact on the quality of the product.
interpretation
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elaborated on the filtration systemDesign Considerations: validated process parameters, sterility assurance, reduced aseptic connections, cleaning procedures, sterilization procedures (including SIP), in-line integrity testing
8.93 Bioburden samples should be taken from the bulk product and immediately prior to the final sterile filtration. In case where a redundant filtration set-up is used, it should be taken prior to the first filter. Systems for taking samples should be designed so as not to introduce contamination.
interpretation
this article compareddid.Extension
more emphasis on sterilization filtration should be carried out beforeAseptic Samplingto control and monitorMicrobial load
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