WFI Distribution - PDF

Distribution of WFI Dr. Shatavari Kulshrestha Ring main or loop system WFI is fed into a sealed storage vessel, often made from stainless steel The water is circulated via a series of pipework throughout the building, and from which a number of outlet valves are available The pipewor...

Distribution of WFI Dr. Shatavari Kulshrestha Ring main or loop system WFI is fed into a sealed storage vessel, often made from stainless steel The water is circulated via a series of pipework throughout the building, and from which a number of outlet valves are available The pipework leads back to the storage tank, allowing constant recirculation of the water throughout the facility Measures to eliminate microbial contamination While circulating, the WFI is maintained at a flow rate of the order 9 ft/s. This ensures constant turbulent flow, discouraging microbial attachment to internal surfaces of the distribution pipes The WFI is constantly maintained at temperatures of the order of 85°C Water collected from the WFI hot loop is generally allowed to cool before use for biopharmaceutical processing  In some instances a separate loop system is constructed in which WFI is circulated at ambient temperature allowing its immediate use in processing operations To maintain water quality this entire circulating system must be emptied and sanitized every 24 h  Design Circulating pipework lengths are fused together by welding, as opposed to the use of threaded fittings, which could harbor bacteria ‘Dead-legs’ are avoided, and bends in pipes are smooth and curving, as opposed to the use of abrupt T-junctions UV cells are also fitted on-line in the system, subjecting circulating water to their continual bactericidal influence  Upon initial installation, the pipework is cleaned by passage of detergent or other cleaning agents, followed by a water rinse ‘Passivation’ (exposure of the internal pipework surfaces to chemical agents, rendering the surface less reactive subsequently) is then undertaken, usually by oxidation using nitric acid or certain organic acids WFI is quite corrosive, especially at 85°C, and it can promote leeching from even high-grade stainless steel piping Addition of ozone to the WFI can alleviate this, as the ozone’s microcidal properties facilitate prolonged storage/circulation of the water at 25°C Replacement of stainless steel pipework with chemically inert plastics (innovation under testing)  Purified water is generally circulated at ambient temperatures, via stainless steel or sometimes plastic- based tubing Samples of WFI and purified water are usually collected daily by quality control personnel and tested for conformance to specification Failure to meet specification results in the system being emptied and fully sanitized, before generation of fresh water Documentation Documentation is essential in order to help prevent errors/misunderstandings associated with verbal communication facilitate the tracing of the manufacturing history of any batch of product ensure reproducibility in all aspects of pharmaceutical manufacture  Standard operating procedures (SOPs) Specifications Manufacturing formulae, processing and packaging instructions Records  ensure they are written/worded in a clear and unambiguous fashion usually written by supervisory personnel and inspected by senior technical personnel (often the production or QC manager or both) before their final approval for general use Such documents are reviewed regularly, and updated as required SOPs SOPs are a set of step-by-step instructions compiled by an organization to help workers carry out routine operations SOPs detailing step-by-step operational procedures for specific items of equipment SOPs detailing maintenance/validation procedures for specific items of equipment or facility areas SOPs relating directly to personnel SOPs relating to testing/analysis Specifications Specifications are normally written by QC personnel They detail the exact qualitative and quantitative requirements to which individual raw materials or product must conform Specifications for chemical raw materials will set strict criteria relating to the percentage active ingredients present, permitted levels of named contaminants, etc Specifications for packing materials will lay down exact dimensions of product packaging cartons Specifications for product labels will detail label dimensions and exact details of label text, etc Specifications for all raw materials are sent to raw material suppliers and, upon their delivery, QC personnel will ensure that these raw materials meet their specifications before being released to production (the raw materials are held in ‘quarantine’ prior to their approval) Final product specifications Many of the specifications set for raw materials/finished product are simply transcribed from the appropriate pharmacopoeia Manufacturing formulae, processing and packaging instructions Manufacturing formulae should clearly indicate the product name potency or strength exact batch size It lists each of the starting raw materials required the quantity in which each is required The processing instructions should contain step-by-step manufacturing instructions The processing instructions should also indicate the principal items of equipment utilized during manufacture, and the precise location in which each step should be undertaken It will also list any specific precautions which must be observed during manufacture Each product will also have its own labelling and packing instructions, indicating: the label to be used, and its exact text exact packing instructions (e.g. how many units of product per pack, how may packs per shipping carton, etc.) Records Records will include: Specification results obtained on all raw materials Batch manufacturing, processing and packaging records QC analysis results of bulk and finished product  These records, along with samples of finished product, must be retained in the facility for at least 1 year after the expiry of that batch Should any difficulty arise regarding the finished product, the records should allow tracing back of all direct manufacturing steps, as well as indirect procedures which might influence the quality/safety of the product During inspections, regulatory inspectors usually examine the records relating to a number of randomly chosen batches in detail, in order to help them assess ongoing adherence to GMP in the facility Generation of manufacturing records Production personnel will print/photocopy the manufacturing formulae, processing and packaging instructions associated with that product The responsible individual fills in the batch number in the space provided (a batch number is a unique combination of numbers and/or letters assigned to that batch, in order to distinguish it from all other batches) A space is provided after each manufacturing/packing instruction When that step is completed, the responsible operator initials the space and includes the exact time and date undertaken  Additional supporting documents may include computerized print-outs from weighing equipment used to dispense chemical raw materials, or recorder charts obtained, e.g. from a freeze-drier upon completion of freeze-drying that batch of product Adequate back-up files should always be retained. Also, restricted access to computerized systems is required to ensure that data/documentation is only entered/amended by persons authorized to do so