16.5.41 Are three successive succes

16.5.41 Are three successive successful simulations carried out per shift for the initial validation? Yes No N/A A. Are process simulation tests repeated twice a year per shift and process? Yes No N/A B. Is the number of containers used for media fill sufficient for valid evaluation? For small batches at least equal to the product batch size? Yes No N/A 16.5.42 Are the process simulations repeated at defined intervals and after every significant change to ventilation systems, equipment, process or number of shifts? Yes No N/A 16.5.43 What is the contamination rate? Has the manufacturer specified alert and action limits? 16.5.44 Is every contamination investigated? Yes No N/A A. Does investigation include potential impact on batches manufactured since the last successful media fill? Yes No N/A 16.5.45 Is it ensured that the validations do not compromise the manufacturing procedures? Yes No N/A 16.5.46 Are the water sources, water treatment systems and treated water regularly monitored for impurities and endotoxins and are these results archived? Yes No N/A 16.5.47 Do personnel carrying out aseptic work move in a controlled and methodical manner to avoid excessive shedding of particles and organisms? Yes No N/A 16.5.48 Are starting materials tested for their microbiological quality? Yes No N/A 16.5.49 Is the use of materials and containers liable to generate fibers avoided in clean areas? Yes No N/A 16.5.50 Are there measures in place to keep particle contamination of the final product to a minimum? Yes No N/A 16.5.51 Are containers and equipment handled in such a way that they are not re-contaminated after final cleaning? Yes No N/A 16.5.52 Is the period between washing, drying, sterilizing and use of material restricted depending on the storage conditions? Yes No N/A 16.5.53 Is the period between manufacturing solutions and sterilization/sterile filtration kept short or restricted depending on the storage conditions? Yes No N/A 16.5.54 Is the bio-burden monitored before sterilization? Is the absence of pyrogens tested? Yes No N/A 16.5.55 Are all solutions filtered through a microorganism retention filter immediately before filling? Yes No N/A 16.5.56 Are containers and accessories brought in only via sterilizers in aseptic work areas? Yes No N/A 16.5.57 Are non-combustible gases filtered through micro-organism retentive filters? Yes No N/A 16.5.58 Is the efficacy of every new procedure validated and the validation verified at scheduled intervals based on performance history or, in case significant changes are made, to the process or equipment? Yes No N/A 16.5.59 Are all sterilization procedures validated? Yes No N/A 16.5.60 Does the selected sterilization procedure correspond with the marketing and manufacturing authorizations Or Regulatory Filing? Yes No N/A