Managing the potential microbial risks when manufacturing non-sterile products can be a complex task. Risk-based assessments are used to help determine the manufacturing areas that may contribute to product contamination by objectionable microorganisms. The contamination areas are important to identify because of the risk to the final product. The risk analysis is used to determine the product acceptance criteria which may include quantitative limits, qualitative requirements and/or other specific criteria that must be achieved during a determined sampling and testing plan.  

USP <1111> Microbiological Examination of Non-Sterile Products: Acceptance Criteria for Pharmaceutical Preparations and Substances for Pharmaceutical Use guidance chapter outlines a list of microbial acceptance criteria for pharmaceutical non-sterile use products. The acceptance criteria listed in USP <1111> gives guidance for the minimal qualitative and quantitative requirements in correlation with testing methods described in USP <61> and <62> testing.

Depending on the sample, an additional risk-based assessment should be performed by reviewing these three areas:

  • Route of administration – The route of administration is important when determining the acceptance criteria because of the higher risk of infection from objectionable microorganisms in the specific area the product is used. It is essential to understand what microorganisms can be opportunistic pathogens during the use of the product.
  • Characteristics of the product end-user – Evaluate the intended user to determine additional risks that may be associated with the use of the product. For example, consideration will be needed when evaluating products with users that are immunocompromised.
  • Physical and chemical characteristics – An evaluation of the product characteristics helps determine areas of risk that may cause problems such as supporting microbial growth.
  • Preservatives- It is important to understand that the product’s antimicrobial properties are properly maintaining an environment that isn’t supporting or allowing microbial growth. Antimicrobial testing is outlined in USP <51> Antimicrobial Effectiveness Test and is used to ensure preservatives are working correctly. The USP <51> testing is important with products that are used multiple times, due to the possibility of contamination during each use.
  • A review of the chemical characteristics may also be needed. For example, the use of immunosuppressive agents in the product or any other chemical hazards that can cause harm to the product recipient must be identified.

It is important for manufacturers to establish and understand acceptance criteria and risk based assessments for their products. The suggested acceptance criteria listed in USP <1111> and the testing available with USP <61> and <62> can be used as a starting point for setting product specifications; however, all possible objectionable organisms should be evaluated by a microbiologist familiar with the product. Specifications need to be justified by the manufacture to maintain consistent high quality production and minimize the potential risk to the intended user by following Good Manufacturing Practice guidelines.