By Jennifer Johnson
Routine microbiological testing carried out by the pharmaceutical, cosmetics and toiletry manufacturing industries is determined by regulatory requirements. This applies not only to what should be tested and when, but also to the methods that should be used. Whether the final product is sterile or non-sterile, the bioburden exists from the raw materials, throughout the process and/or within the product’s environment (e.g. water) to the final product. A critical review of the overall microbiological process will determine whether the final product will meet its acceptance criteria. In addition, any “objectionable” or “specified” microorganisms that may be encountered during the procurement of raw materials and the processing must be considered.
Whether you are testing a raw material, an in-process sample, final product, or the environment, you should be aware of the critical role that microorganisms play throughout the process. You should also be familiar with the various microbiological related documents needed to determine whether the SOPs, validations, and regulatory body documents are being maintained to assure the control required to permit the final product to enter the marketplace as safe.
The Unites States Pharmacopeia (USP) is a non-governmental organization. Their documents are recognized as an official compendia book of methods and standards for Pharmaceutical, nutraceutical, dietary supplements, cosmetics, and toiletries. The USP offers a variety of documents such as monographs (published standards) and general chapters. General chapters with numbers <1000 are mandatory chapters and numbers >1000 are considered informational chapters.
Pharmaceutical USP Chapters
USP offers some standardized test methodologies and material specifications relating to microbiological quality and control so as to ensure product quality and safety.
<1111> Microbiological Examination of Nonsterile Products: Acceptance Criteria for Pharmaceutical Preparations and Substances for Pharmaceutical Use – It is suggested that certain categories of products should be tested routinely for total microbial count and for specified indicator microbial contamination. The relevant tests for determining the total count of viable aerobic microorganisms and the total combined yeast and mold count and for detection and identification of designated species are given under Microbial Limit Tests <61>.
<1115> – Bioburden Control of Nonsterile Drug Substances and Products – This chapter deals with the bioburden of non-sterile drug substances and products. The chapter states that the biggest manufacturing risk for these products is the ingredient water. Process water is the single most important risk factor contributing to the contamination of nonsterile products. The purified waters that are used in manufacturing are deionized and do not contain chlorine that helps control microbial growth. Purified water is capable of supporting growth of gram negative rod shaped bacteria and many different molds.
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<1116> Microbiological Control and Monitoring of Aseptic Processing Environments – The purpose of this chapter is to review the various issues that relate to aseptic processing of bulk drug substances, dosage forms, and to the establishment, maintenance, and control of the microbiological quality of controlled environments.
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<1117> Microbiological Best Laboratory Practices - This general information chapter outlines what is needed to improve the effectiveness, efficiency and inspection-readiness of a Microbiology Laboratory in respect to media preparation, microbiological cultures, lab equipment, laboratory layout, lab records, interpretation of results, training, and documentation.
<1223> Validation of Alternative Microbial Methods – The purpose of this chapter is to provide guidance for validating methods for use as alternatives to the official compendial microbiological methods. Validation of microbiological methods is the process by which it is experimentally established that the performance characteristics of the method meet the requirements for the intended application, in comparison to the traditional method. Traditional plate methods for microbiological testing require long time to results, highly trained microbiologists, is labor intensive, and creates a bottleneck for product release. Rapid microbiological methods (RMMs) offer a high degree of automation, significant reduction in time to results, reduced staff training, faster product release, and improved process control.
<1227> Validation of Microbial Recovery from Pharmacopeial Articles – This chapter
provides guidelines for the validation of methods for the estimation of the number of viable microorganisms, for the detection of indicators or objectionable microorganisms, for the validation of microbiological methods used in antimicrobial effectiveness testing, and for the sterility testing of Pharmacopeial articles. It is generally understood that if a product possesses antimicrobial properties because of the presence of a specific preservative or because of its formulation, this antimicrobial property must be neutralized to recover viable microorganisms. This neutralization may be achieved by the use of a specific neutralizer, by dilution, by a combination of washing and dilution, or by any combination of these methods.
<1231> Water for Pharmaceutical Purposes – According to USP <1231>, although there are no absolute microbial standards for water (other than water intended to be sterile), the cGMP regulations require the establishment of appropriate specifications. The specification must take into account the intended use of the water; i.e., water used to formulate a product should contain no organisms capable of growing in the product. Action or alert limits should be established based upon validation data and must be set low enough to signal significant changes from normal operating conditions.
BioLumix Rapid Microbiology Methods offer innovative new testing solutions that are designed specifically for the challenges of the pharmaceutical industry, including a multitude of microbial tests for raw materials, in-process and finished products, as well as, the capacity to perform environmental and water testing. This simplifies, expedites, and reduces the cost of performing microbiological assays.
The BioLumix Drug Master File (DMF) entitled “Microbiological Rapid Method for the Detection and Enumeration of Microorganisms in Pharmaceutical Products” has been accepted by the US Food and Drug Administration (FDA). The DMF provides specific technical and regulatory information to the FDA which allows companies planning to use the BioLumix Rapid Microbiological System to obtain regulatory approvals for prescription drugs. The DMF can be referenced by drug manufacturers, reducing FDA review times and accelerating the regulatory approval process for use of the BioLumix System. In addition, Over the Counter (OTC) products can be tested in conjunction with the BioLumix Validation Package.
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