The CFTA proposed a specification of not more than 500 organisms per ml. if a hose is usually attached the sample should be taken at the end of the hose. In those facilities observed without updated prints, serious problems were identified in these systems. Because WFI can pass the LAL endotoxin test and still fail the above microbial action limit, it is important to monitor WFI systems for both endotoxins and microorganisms.For purified water systems, microbiological specifications are not as clear. Positive pressure such as in vapor compression or double tubesheet design should be employed to prevent possible feedwater to distillate contamination in a leaky heat exchanger.An FDA Inspectors Technical Guide with the subject of "Heat Exchangers to Avoid Contamination" discusses the design and potential problems associated with heat exchangers. The Guide To Inspections of Microbiological Pharmaceutical Quality Control Laboratories (May, 1993) provides additional guidance.One of the basic considerations in the design of a system is the type of product that is to be manufactured. With colder systems (65 - 75oC), any drops or unused portion of any length of piping has the potential for the formation of a biofilm and should be eliminated if possible or have special sanitizing procedures. 4, in the General Notices Section, allows drug substances to be manufactured from Potable Water. 3. Information and translations of purified water in the most comprehensive dictionary definitions resource on the web. In lieu of stringent water action limits in the system the manufacturer can add a microbial reduction step in the manufacturing process for the sensitive drug product(s).A basic reference used for the validation of high purity water systems is the Parenteral Drug Association Technical Report No. There should be n o threaded fittings in a pharmaceutical water system. These valves are not considered sanitary valves since the center of the valve can have water in it when the valve is closed. The rationale used by USP to establish its conductivity specification took into consideration the conductivity contributed by the two least conductive former attributes of Chloride and Ammonia, thereby precluding their failure had those wet chemistry tests been performed. Sampling is performed according to routine procedures and frequencies. None of the limits for water are pass/fail limits. However, there may be other issues. We can meet all of your USP purified water requirements. A major problem with PVDF tubing is that it requires considerable support. There have been attempts by some to establish meaningful microbiological specifications for purified water. Any variations in the quality of the feedwater that could affect the operation and ultimately the water quality will be picked up during this phase of the validation. Since sampling frequently is performed in non-sterile areas and is not truly aseptic, occasional low level counts due to sampling errors may occur.

ReAgent is a well-established chemical manufacturer with over 40 years’ experience. For example, in an inspection, it was noted that a firm had to install a drain from the low point in a pump housing. This guide discusses, primarily from a microbiological aspect, the review and evaluation of high purity water systems that are used for the manufacture of drug products and drug substances.

Open menu. For Water for Injection systems the samples should be taken daily from a minimum of one point of use, with all points of use tested weekly. It is up to each manufacturer to evaluate their product, the way it is manufactured, and establish am acceptable action level of contamination, not to exceed the maximum, for the water system, based on the highest risk product manufactured with the water.In the review and evaluation of Water For Injection systems, there are several concerns.Pretreatment of feedwater is recommended by most manufacturers of distillation equipment and is definitely required for RO units. Sampling should be daily after each step in the purification process and at each point of use for two to four weeks. These logs should also be reviewed so that problems with the system and equipment can be evaluated.In addition to reviewing test results, summary data, investigation reports and other data, the print of the system should be reviewed when conducting the actual physical inspection. Also, new construction or fires can cause a depletion of water stores in old mains which can cause an influx of heavily contaminated water of a different flora.A water system should be designed to operate within these anticipated extremes. In a few situations, pinholes formed in the tubing after they were drained (on the cooling water side) and not in use. If filters are used in a water system there should be a stated purpose for the filter, i.e., particulate removal or microbial reduction, and an SOP stating the frequency with which the filter is to be changed which is based on data generated during the validation of the system.As previously discussed, because of the volume of water actually tested (.1ml for endotoxins vs. 100ml for WFI), the microbiological test offers a good index of the level of contamination in a system. As pointed out in the Guide to Inspections of Microbiological Pharmaceutical Quality Control Laboratories, the specific contaminant, rather than the number is generally more significant.Organisms exist in a water system either as free floating in the water or attached to the walls of the pipes and tanks. A very long system (over 200 yards) with over 50 outlets was found acceptable. et USP EPU de qualité optimale. It comments that any dosage form must be manufactured from Purified Water, Water For Injection, or one of the forms of Sterile Water. 2.

However, such water systems used in the final stages of processing of drug substances for parenteral use should be validated to assure minimal endotoxin/ microbiological contamination.In the bulk drug substance industry, particularly for parenteral grade substances, it is common to see Ultrafiltration (UF) and Reverse Osmosis (RO) systems in use in water systems.