Technical Report No. 67: Exclusion of Objectionable Microorganisms from Pharmaceutical and OTC Drug Products

This training course, derived from the work of the PDA Objectionable Microorganism Task Force, covers the exclusion of objectionable microorganisms from non-sterile pharmaceutical drug products, over-the-counter drug products, medical devices, cosmetics and personal care products in the Pharmaceutical, Medical Device, Cosmetics and Consumer Healthcare Industries. Objectionable microorganisms, as cited in 21 CFR 211.113, are those microorganisms that, if they persist and grow in non-sterile products, can cause harm to the user of the products and degrade the physicochemical, functional and therapeutic attributes of the products. The contamination of marketed products with so-called objectionable microorganisms continues to be an infrequent but chronic problem for both regulators and our industry.

This training course will provide guidance on how to manage the microbial risks associated with objectionable microorganisms within a specific product that meet the microbial limit requirements for release to the market. No definitive list of objectionable microorganisms will be provided in this training course, but microorganisms of potential concern will be highlighted from the literature regarding product contamination, infection outbreaks, product recalls, and the clinical experience with canonical pathogens and other opportunistic microorganisms at the site of administration of the non-sterile product. Attention will be given to the proposed USP chapter <60> Microbiological Examination of Nonsterile Products—Tests for Burkholderia cepacia Complex. Risk mitigation including ingredient selection, the effect of unit manufacturing processes on product bioburden, environmental controls, product formulation, microbial specification setting, release and stability testing, risk assessment and product failure investigation will be highlighted using recent industry case histories.

1. Describe the regulatory requirements surrounding objectionable microorganisms
2. Conduct risk assessments for ingredients, packaging components, product design and formulation, manufacturing processes, facility design and product testing to address the exclusion of objectionable microorganisms
3. Conduct risk assessments to determine if microorganisms found in a specific product are objectionable
4. Develop risk-based microbiological specifications and testing programs that address a range of products
5. Establish a corporate objectionable microorganism policy