Pharmaceutical Microbiology


Written by MicroDok

A meaningful discussion on the use of microbiological criteria for foods and food ingredients requires a precise description of terms used when applying microbiological limits to foods and other products including pharmaceuticals and cosmetics.


A criterion is a yardstick on which a judgment or decision can be made. A microbiological criterion therefore, will stipulate that a type of microorganism, group of microorganisms, or toxin produced by a microorganism must either not be present at all, be present in only a limited number of samples, or be present as less than a specified number or amount in a given quantity of a food or food ingredient.

Components of a Microbiological Criterion

A microbiological criterion should include the following:

  1. a statement describing the identity of the food or food ingredient,
  2. a statement of the contaminant of concern, i.e., the microorganism or group of microorganisms and/or its toxin or other agent,
  3. the analytical method to be used for the detection, enumeration, or quantification of the contaminant of concern,
  4. the sampling plan, and
  5. the microbiological limits considered appropriate to the food and commensurate with the sampling plan used.

Mandatory and Advisory Criteria

A mandatory limit is one that the food cannot exceed. Food that does not meet the criterion must be subjected to some action. For example, it may be rejected by the purchaser, destroyed, reprocessed, sold as an inferior grade, or diverted to a use where the contaminant is not of concern. As far as human and animal health is concerned, contamination of products and other consumables including food and pharmaceuticals is an important factor that must be taken care of and properly handled to avoid disease outbreak in human or animal population. Certain mandatory criteria also may result in the loss of license to process food when limits are consistently exceeded.

Advisory criteria often serve as an alert to deficiencies in processing, distribution, storage, or marketing. They are not mandatory but permit judgments to be made when limits are not met.


The terms standard, guideline, and specification are widely used to describe microbiological criteria for foods. This is also applicable to other products including pharmaceuticals, vaccines and cosmetics among other products or consumables used by humans. There appears to be no need for additional terms.


A microbiological standard is a microbiological criterion that is a part of a law, ordinance, or administrative regulation. A standard is a mandatory criterion. Failure to comply with it constitutes violation of the law, ordinance, or regulation and will be subject to the enforcement policy of the regulatory agency having jurisdiction.


A microbiological guideline is a criterion that often is used by the food industry or a regulatory agency to monitor a manufacturing process. Microbiological guideline can also mean microbiological specification. Guidelines function as alert mechanisms to signal whether microbiological conditions prevailing at critical control points or in the finished product are within the normal range. Hence, they are used to assess processing efficiency at critical control points and conformity with Good Manufacturing Practices (GMPs). A microbiological guideline is an advisory criterion in that a given lot of food exceeding the limit for a nonpathogenic organism would not be taken off the market or even downgraded. Guidelines may be mandatory, however, in the sense that food company management and regulatory agencies may demand that the conditions responsible for persistent microbiological deficiencies be corrected without delay.


A microbiological specification is a microbiological criterion that is used as a purchase requirement whereby conformance with it becomes a condition of purchase between buyer and vendor of a food or ingredient. A microbiological specification can be either mandatory or advisory.


Microbiological criteria as described above may be used to assess:

  1. the safety of a food,
  2. adherence to good manufacturing practices,
  3. the utility (suitability) of a food or ingredient for a particular purpose, and
  4. the keeping quality (shelf-life) of certain perishable foods.

Evaluation of the safety of a food may involve tests for the pathogens or toxins of concern. Alternatively, it may involve tests for indicator organisms, where a relationship has been shown between the occurrence of the indicator organism and the safety of the food. For some pathogens and toxins, the numbers or concentrations present in a food are significant in that lower figures do not pose a health hazard whereas higher ones do. The purpose of these criteria is to protect the consumer’s health.

Criteria often are used for making decisions related to the acceptability of products since they may measure adherence to Good Manufacturing Practices. They can also be used to assess the utility of a food or food ingredient for a specific purpose; for example, canners of fruit products must limit the number of heat-resistant ascospores of Byssochlamys fulva in ingredients such as fruit juice concentrates and tapioca starch.

Industry quality control/assurance departments may use microbiological criteria to monitor the potential shelf-life of perishable foods. Products with small numbers of spoilage microorganisms are more likely to have a longer shelf-life than are those with larger numbers. Such results are of retrospective value: while they do not extend the shelf-life of the lot that was analyzed, they do alert the processor to problems that must be corrected in order to achieve satisfactory preservation of future production.

Need for Establishment

A microbiological criterion for a food or food ingredient should be established and implemented only when there is a need for it and when it can be shown to be effective and practical. The criterion must accomplish its objective, i.e., adequately measure the contaminants of concern, be technically attainable under commercial conditions by Good Manufacturing Practices, and be administratively feasible. There are additional factors that should be considered before the need for a specific microbiological criterion can be established. These should include:

  1. evidence of a hazard to health based on epidemiological data or a hazard analysis
  2. the nature of the natural and commonly acquired microflora of the food and the ability of the food to support microbial growth;
  3. the effect of processing on the microflora of the food;
  4. the potential for microbial contamination and/or growth during processing, handling, storage, and distribution;
  5. the category of consumers at risk;
  6. the state in which food is distributed, e.g., frozen, refrigerated, heat processed, etc.;
  7. potential for abuse at the consumer level;
  8. spoilage potential, utility, and GMPs;
  9. the manner in which the food is prepared for ultimate consumption, i.e., heated or not;
  10. reliability of methods available to detect and/or quantify the microorganism(s) and toxins of concern; and
  11. the costs/benefits associated with the application of the criterion.

Applications of Criteria

Microbiological Standards

Microbiological standards may be useful when epidemiological evidence indicates that a food is frequently a vehicle of disease. Several factors should be considered before a microbiological standard is established. Most important, the standard must attain its stated objective, namely the elimination or reduction of foodborne disease. (Although potpies have been involved in outbreaks of botulism, standards related to the presence of Clostridium botulinum spores in the frozen product would be highly impractical since in each outbreak, illness was caused by extreme abuse of the food by the consumer.) Currently existing “implied” microbiological standards for foods should also be considered.

A criticism of standards based on fixed numbers of nonpathogenic microorganisms is that they can result in the recall or downgrading of significant quantities of what otherwise may be wholesome food. One means of minimizing this would be the approach used in the Grade A Pasteurized Milk Ordinance (USPHS/FDA, 1978). Here a given lot is not automatically rejected when standard plate counts or numbers of coliforms exceed the prescribed limit, but penalty provisions, which can include suspension of the permit to process milk, may be instituted on repeated violations, e.g., when three out of five of the last analyses within a specified period of time exceed the standard. This system affords the correction of undesirable conditions with minimal loss of food, and thus with minimal cost to the consumer.

Microbiological Guidelines

Microbiological guidelines are used by food processors to monitor the microbiological condition of raw products, of a food at critical control points during processing, of process equipment surfaces, and of the finished product. Industry quality control/assurance departments commonly establish microbiological limits, often based on many years of experience, that should be achievable in foods at critical control points or in the finished product if good manufacturing practices are observed. Results that exceed these limits serve to signal some divergence from accepted good manufacturing practices and may suggest remedial measures. Industry guidelines often are of a proprietary nature and may vary from company to company, even for the same product.

Microbiological guidelines can aid regulatory agencies in the assessment of good manufacturing practices when analyses are conducted in conjunction with plant inspection. Before this can be done, a relationship between the microbiology of the food and the factory conditions would have to be established, usually for each product and process under consideration.

Microbiological Specifications

Microbiological specifications are used to determine the acceptability of a raw material or finished product in a contractual agreement between two parties (buyer and vendor). Specifications are used by governmental agencies to assess microbiological acceptability of foods purchased for use in government programs. As with other microbiological criteria, specifications should be based on relevant background data and should fill a need.

Attributes of Quality Amenable to Measurement by Microbiological Criteria

The term quality usually refers to the property, inherent nature, characteristic or attribute, or degree or grade of excellence of something. The term quality as commonly applied to food summarizes in one word its desirable characteristics. Quality of a food as perceived by the consumer can be described as a value related to flavor, color, and texture. It also includes imperceptible traits such as nutritional and aesthetic values and safety. Exclusive of discussions of safety, for the purpose of this report, microbiological aspects of quality include:

  1. shelf-life, as perceived by attributes such as flavor and appearance;
  2. adherence to good manufacturing practices;
  3. utility of a food.

Each of these attributes is measurable to some extent microbiologically; the decisive question, however, is to what extent. Although subsequent sections of this report will deal with this question in more detail, some discussion of the subject is presented below.

The ultimate shelf-life of a perishable product can be estimated to some degree through the application of microbiological criteria. Assuming identical storage conditions, a perishable food with a low number of spoilage microorganisms will have a longer shelf-life than the same product with larger numbers of such organisms. In practice, products with unacceptable shelf-life will soon be recognized and rejected by customers in the market place. Regulatory agency or industry use of microbiological criteria to grade foods for shelf-life often is an impractical task because of variable conditions during storage. Furthermore, relationships among common microbiological parameters such as total counts and coliform counts, and the shelf-life of a food are inexact. Some types of microorganisms, because of enzyme systems acting upon the constituents of the food, cause marked changes in perceptible quality characteristics of a food while others are relatively inert biochemically and thus produce little change. In addition, the effect of certain levels and/or types of microorganisms on perceptible quality characteristics often differs from food to food and is also subject to changes in environmental conditions such as temperature and gaseous atmosphere.

Lack of adherence to good manufacturing practices can often be related to levels and types of microorganisms in excess of those present in a product produced and held under good conditions. The use of poor quality materials, careless handling, or insanitation may result in a higher bacterial count in the finished product. However, a heat treatment or other lethal process can reduce the higher bacterial counts that result from malpractice; furthermore organisms may die off during storage of frozen, dried, or fermented foods. Low counts, therefore, do not necessarily indicate good commercial practices or even food safety. The absence of viable staphylococci in cheese, for example, does not guarantee the absence of staphylococcal enterotoxin. High aerobic plate counts (APC), on the other hand, do not necessarily mean careless handling or lack of wholesomeness. For example, ground beef is likely to yield a high APC, but this may merely reflect the growth of harmless psychrotrophic bacteria during refrigerated storage.

The relationship between the microbiology of a food and adherence to good manufacturing practices must be established by conducting repeated surveys of processing lines to obtain statistically valid data. The critical control points in the HACCP (Hazard Analysis Critical Control Point) approach must be identified and the microbiology of the food at different stages of processing must be determined. Through these studies, numbers and types of organisms that characterize the flora of a food produced under a given set of conditions can be identified and thus provide a basis for the establishment of a microbiological criterion. Even then, an allowance has to be made for variations due to differences in processing procedures and equipment.

Finished foods with microbial counts that exceed the criterion might reasonably be expected to have been mishandled in some manner during production and/or storage. As pointed out earlier, however, low counts do not always reflect good manufacturing practices because a lethal step in the process or significant die-off of microorganisms during storage may have occurred.

The relationship between good commercial practices and quality often is a question of aesthetics. A frozen food, for example, might be processed under conditions of sanitation that a discriminating person would find objectionable. While these conditions would be reflected in the microbiology of the food, the usual quality attributes of nutritional value, flavor, texture, color, safety, and shelf-life might not be altered. Microbiological criteria can be useful to determine the utility of a food or ingredient.

A common means for reducing the number of viable microorganisms on a food is to expose it to sprays or flumes containing relatively high concentrations of chlorine. While such treatments improve microbiological quality, other quality attributes may be affected adversely since chlorine reacts with numerous food constituents such as amino acids, lipids, and chlorophyll. At present it is not known whether these different chloro-organic compounds are completely innocuous.


  • FDA (Food and Drug Administration) 1972. Proposed microbiological quality standards. Federal Register 37(186):20038–20040.
  • ICMSF (International Commission on Microbiological Specifications for Foods) 1985. Microorganisms in Foods. 2. Sampling for microbiological analysis: Principles and specific applications. 2nd Ed. In preparation.
  • National Canners Association 1968. Laboratory Manual for Food Canners and Processors. Vol. 1. Westport, Conn.: AVI Publishing.
  • Pederson, C. S. 1947. Significance of bacteria in frozen vegetables. Food Research 12:1–10.
  • U.S. Congress 1938. Federal Food, Drug and Cosmetic Act of 1938. Pub. L. 717 (June 25) 52 Stat. 1040. Washington D.C.: U.S. Government Printing Office.
  • USDA (U.S. Department of Agriculture) 1960. Conference on frozen food quality, Western Regional Research Laboratory. Publication ARS-74-21. Washington D.C.: USDA.
  • USDHEW (U.S. Department of Health, Education and Welfare) 1965. National Shellfish Sanitation Program, Manual of Operations. Part 1. Sanitation of Shellfish Growing Areas. Washington D.C.: U.S. Government Printing Office.
  • USPHS/FDA (U.S. Public Health Service/Food and Drug Administration) 1978. Grade A Pasteurized Milk Ordinance. 1978 Recommendations. USPHS/FDA Publication No. 229. Washington, D.C.: U.S. Government Printing Office.

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