Bioburden Testing vs. Sterility Testing
What is bioburden?
The “bio” in bioburden refers to live biological organisms, and the “burden” in bioburden refers to the concentration of the viable biological organisms. Thus, bioburden is the concentration or quantity of microorganisms in a given area or from a particular sample. The higher the concentration of viable organisms on a device or product, the higher the burden is to kill those organisms, whether it is killing the organisms through sterilization procedures or killing the organisms through the effort of the human immune system.
What is sterility?
The term sterile means a complete absence of viable microorganisms or microbes that have the potential to reproduce. Thus, sterile products are often chemically or heat sterilized after being placed in their final packaging. The chemical or heat sterilization kills any microorganisms inside the products (obtained during manufacturing and packaging). This chemical or heat sterilization process after final product packaging is known as terminal sterilization. Sterility can also be obtained through removing viable microorganisms from a product versus killing them.
What is the difference between sterile and aseptic?
While both sterile and aseptic products will prevent microbial contamination following use, the processes by which microbial contamination is prevented are different. An aseptic process prevents contamination by the exclusion of microorganisms. In contrast, products created using a sterile process use a terminal sterilization process (such as radiation, ethylene oxide gas, steam, vapor, or dry heat) to kill live microbes before product use. Though the definitions for aseptic and sterile are not the same, sterile is used interchangeably with aseptic. Indeed, many products labeled as sterile are manufactured by aseptic processing rather than terminal sterilization.
How do bioburden and sterility relate?
Bioburden has to do with identifying the microbial burden in a sample. The microbial burden is the quantification of all live microorganisms (fungi, bacteria, etc.) using colony-forming units (CFU’s). Sterile refers to verifying the absence of live microorganisms in a product or product-packaging system. Sterile is a condition of the death of all microbes (or exclusion of all live microbes) in a product. At the same time, bioburden is the quantification method for identifying the number of microorganisms in a sample. The reason that viable (living) microorganisms alone are of concern for sterility is that only live microorganisms have the potential to reproduce, whether in the human body, on the product, or within the product itself.
What are the differences between bioburden and sterilization validations?
Bioburden testing measures the viable organisms present in a sample. The total viable organisms present is expressed as a total viable count. This total viable count (expressed as CFU’s) provides a value for the microbial contamination level within a particular sample. Combined bioburden and microbiology testing can identify what types of live microorganisms are present in a sample from a product, package, or manufacturing environment.
Though bioburden testing may be referred to synonymously with microbiology testing, microbiology testing allows for the specific type of live microorganism to be identified and quantified. Bioburden testing follows the methods outlined in USP 60, USP 61, and USP 62. A comparison of all bioburden-related USP documents can be found HERE.
The most popular method for sterilization validation is an overkill method. Overkill methods are used to verify that a specific sterilization process can achieve a certain level of sterility even if the bioburden is higher than expected, in a difficult to sterilize location, or the sterilization cycle runs inefficiently. Depending on the goals of the sterilization validation, either a full-cycle approach or a reduced level of treatment known as a partial cycle approach will be performed. An example of a partial cycle approach is a half cycle approach. Overkill sterilization validations are governed by ISO 17655-1.
Overall, bioburden testing is used to determine the level of sterilization needed for a particular medical product after manufacturing and used as a quality control metric to ensure manufacturing bioburden levels stay consistent.
Sterilization validations are used to ensure that the end sterilization process can appropriately kill any viable microorganisms in a sample.
Why are bioburden testing and tests for sterilization validations important?
Bioburden testing and sterilization validations are essential quality control steps that detect the level of contamination of a product at any stage (from initial product manufacture to final distribution). They verify those terminal sterilization methods are effective at killing the live bioburden in a sample after manufacturing. As microorganisms exist on every surface (including our body), bioburden can be accidentally introduced during the manufacturing or packaging process in many ways. Some of the most common examples are contamination through the raw materials used, technicians, tubing/piping used to transfer product between development stages in a process, or the manufacturing environment itself. With such abundant sources of contamination, regular bioburden testing supports the long-term control of bioburden levels in manufactured products. Sterilization validations verify that the chosen sterilization process adequately kills the bioburden that products and packaging accumulate during manufacturing.
Summary
Overall, both bioburden testing and sterilization validations are imperative for regulatory approval of medical devices or products. These tests ensure that medical devices, products, manufacturing environments, and packaging are free from viable microbial contaminants and maintain sterility. Maintenance of sterility ensures that patients will not be at risk of infection following device exposure or product implantation. Ensure you choose a contract manufacturing organization that can support you with appropriate bioburden and sterilization validations for your unique medical device or product needs.
References
Frank R. Noyes. Noyes’ Knee Disorders: Surgery, Rehabilitation, Clinical Outcomes. Elsevier. 2010.
United States Pharmacopeial Convention. <60> Microbiological Examination of Nonsterile Products- Tests for Burkholderia Cepacia Complex. Rockville, MD, USA. 2021. (USPC <60>).
United States Pharmacopeial Convention. <61> Microbiological Examination of Nonsterile Products: Microbial Enumeration Tests. Rockville, MD, USA. 2021. (USPC <61>).
United States Pharmacopeial Convention. <62> Microbiological Examination Of Nonsterile Products: Tests For Specified Microorganisms. Rockville, MD, USA. 2021. (USP <62>).
United States Pharmacopeial Convention. <1115> Bioburden Control of Non-Sterile Drug Substances and Products. Rockville, MD, USA. 2021. (USPC <1115>).
United States Pharmacopeial Convention. <1116> Microbiological Control & Monitoring of Aseptic Processing Environments. Rockville, MD, USA. 2021. (USPC <1116>).
United States Pharmacopeial Convention. <1211> Sterility Assurance. Rockville, MD, USA. 2021. (USPC <1211>).
International Organization for Standardization. Sterilization of health care products- Moist heat- Part 1: Requirements for the development, validation, and routine control of a sterilization process for medical devices. Geneva (Switzerland): ISO; 2006. (ISO 17665-1:2006/(R)2016).
