Process control, microbial

Justifications for the use of nonstandard (i.e., nonpreferred or nonpharmacopeial) methods of sterilization may include the heat instability of the active ingredient or an essential excipient. The choice of a method based on filtration through a microbial retentive filter and/or aseptic assembly should be justified, and the appropriate in process controls (including bioburden controls on active ingredients, excipients, bulk solutions, process time constraints etc) discussed in detail in the application. Commercial considerations should not form part of the argument for the application of a nonstandard sterilization process. The highest possible sterility assurance level should be achieved. 

Archer, D.B., The microbial basis of process control in methanogenic fermentation of soluble waste, Enz. Microbial. Technol., 6, 162-170, 1983. 

F Production and process controls Process control systems, reprocessing control of microbial contamination... 

Unlike the transformation processes that reduce the total amount of triazine present in soil, retention only decreases the amount available for weed control, microbial transformations, or transport. The amount retained or sorbed by soil can range from 0% to 100% of the amount applied, but sorption on silt loam, loam, or clay loam soils typically ranges from 50% to 80%. Triazine retention in soil is influenced primarily by organic carbon content, soil clay content and type, and soil pH. Other factors influencing retention include the amount of triazine applied, the amount of dissolved organic carbon (DOC) in soil solution, soil water content, and triazine to soil contact time (aging). 

Animal cell cultures, either from mammalian or insect cells, show specific characteristics that differ from microbial cultures (bacteria, yeasts, and filamentous molds). Among the characteristics that most interfere with monitoring methodologies and process control (and that will be approached with more detail in the present chapter), are the following. 

The manufacture of biological products, unlike that of pharmaceuticals, uses materials that present variability. The active substance is generally produced in small quantities and needs to be separated from complex mixtures containing several types of contaminants. Lots are generally small and quality control tests are usually based on biological techniques that present higher variability than physicochemical assays. The processes are also susceptible to microbial contamination. The in-process controls are of fundamental importance to detect quality deviations that cannot be assessed through assays performed only on the final products. 

Utilization of a Computer in On-Line Control and Optimization of a Batch Process for Microbial Conversion of Ethanol to Protein... 

The dynamics of microbial cultures have an important impact on the characteristics of measurement and process control. The typical time constant in a bioprocess is often erroneously anticipated to be equivalent to the entire duration of a cultivation. 

Preservatives In addition to those processing controls mentioned above (Section 3.1.4.3), the sterility of a product may be maintained through the addition of antimicrobial preservatives. Preservation against microbial growth is an important aspect of multidose parenteral preparations as well as other formulations that require preservatives to minimize the risk of patient infection upon administration, such as infusion products [52], Aqueous liquid products are prone to microbial contamination because water in combination with excipients derived from natural sources (e.g., polypeptides, carbohydrates) and proteinaceous active ingredients may serve as excellent media for the growth [57], The major criteria for the selection of an appropriate preservative include efficiency against a wide spectrum of micro-... 

Beef is aged at 4°C and is tenderized. A process involving surface irradiation controls microbial growth and permits somewhat higher temperatures to accelerate tenderization. 

During development of the manufacturing process, an experienced microbiologist should be consulted as to the potential for microbial contamination of the product. Issues may include the selection of appropriate pharmaceutical ingredients, the ability of the manufacturing steps to control microbial contamination, the validation of sterilization processes, the cleaning and sanitization of process equipment, the adequacy of... 

---