Pharmaceutical products are required to provide a therapeutic effect on the patient with a minimum of adverse side effects. These products are also expected to be safe for patient use which includes expectations of freedom from microorganisms potentially causing disease. 


In addition, microorganisms may have an adverse impact affecting the physicochemical properties and therapeutic value of the product. The FDA cGMP regulations include the following expectation: 

“Appropriate written procedures, designed to prevent objectionable microorganisms in drug products not required to be sterile, shall be established and followed”.


Non-sterile products pose challenges because they are not sterile but cannot contain too many microorganisms and any potentially harmful microorganism. 


Bioburden Control of Non-sterile Drug Substances and Products 〈1115, became official in 2015 and outlines the concepts and principles necessary to protect products from adventitious microorganisms. 


More recently, USP revised the content of Sterility Assurance 〈1211〉 following the principles outlined in 〈1115〉. 


The USP Microbiology Expert Committee is considering revision of the current content related to microbial control of non-sterile products. The objective will be to refine both its process recommendations and microbial testing expectations to improve patient safety. 


The possible revisions and potential additions may include:

  • Microbiological Examination of Nonsterile Products: Acceptance Criteria for Pharmaceutical Preparations and Substances for Pharmaceutical Use 〈1111〉
  • Bioburden Control of Non-sterile Drug Substances and Products 〈1115〉
  • Increase focus on control of microbial populations throughout the production cycle of excipients, APIs, and finished drug products. 
  • Place greater emphasis on water activity; Increase the emphasis on water for pharmaceutical use and process equipment cleaning.
  • Introduce content that raises awareness of housekeeping and sanitization as control measures.


Microbiological Best Laboratory Practices 〈1117〉

  • Introduce recommendations for aseptic sampling and handling of microbial samples taken from non-sterile materials.


Microbial Characterization, Identification, and Strain Typing 〈1113〉

  • Update the chapter considering recent technological advancements to assist in microbial identification in required microbial assessments.
  • Recovered Microorganism Decision Tree

Microbial Risk Identification/Assessment

  • Provide a concise scientific means for stakeholders to consider the risk associated with microbial contamination of non-sterile products. 


An objective will be to clarify terms such as objectionable, specified, indicator microorganisms, etc., which have no scientific meaning within microbiology, and which is a source of confusion for USP stakeholders.


Resource Persons: Barbara Pirola