Parametric Release Program vs. Sterility Testing For Medical Devices And Products
What are sterilization and sterility?
Sterilization is any process that removes, kills, or deactivates all forms of life. Sterilization is related to the term sterile, which means a complete absence of viable microorganisms or microbes that have the potential to reproduce. Thus, sterile products that undergo sterilization 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.
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 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.
What is a parametric release program?
Parametric release programs use robust manufacturing process controls to allow a finished product to be immediately released instead of going through end-product testing to establish a product batch’s sterility. For parametric release to be an option for your product, in-process manufacturing conditions must show that regulatory and process control acceptance criteria are attained and maintained throughout the manufacturing process. If the in-process controls can prove a certain level of sterility, no end-product sterility testing is necessary. Parametric release programs that are well-designed, validated, and controlled have a very low probability of microbial contamination. Indeed, the likelihood of a nonsterile unit (PNSU) is less than one in a million.
What are the differences between parametric release programs and sterility testing?
Sterility testing evaluates a product for live microbes and ensures that microbes have been appropriately excluded from a product through aseptic processing or that microbes have been effectively killed through a terminal sterilization method. Sterility tests are performed at time zero (immediately after manufacture) and after stability testing for a period (such as six months or a year). The United States Pharmacopeia and European Pharmacopeia specify two basic methods for performing sterility tests: direct transfer (also known as direct inoculation) and membrane filtration methods. In some cases, the membrane filtration method may be the only choice for sterility testing.
In contrast, parametric release programs use process controls to ensure that sterility acceptance criteria are attained and maintained throughout the manufacturing process. These process controls eliminate the need for post-manufacturing sterility testing of product batches. Sterilization methods that have been successfully used in parametric release processes to sterilize drug products, medical products, and medical devices in their primary package are moist heat, dry heat, gas (such as ethylene oxide), and radiation. While parametric release programs can offer time and cost savings (by eliminating the need for end-product sterility testing), they also require real-time data monitoring and acquisition systems in addition to in-process controls to ensure product sterility during processing. These in-process control and monitoring can be expensive to develop. Further, if any process in the parametric release program does not meet the acceptance criteria or data systems are unable to collect the data necessary to prove that in-process controls are being met, the processed product will need to be discarded. Traditional batch sterility testing cannot be performed on parametric release products that did not meet their in-process control criteria. However, well-designed parametric release programs have a probability of less than one nonsterile unit in a million, which exceeds the requirements needed for traditional batch-to-batch sterility testing.
Why are sterility testing and parametric release programs important?
Sterility tests are used as product safety tests to evaluate product sterility after manufacturing or stability testing. Viable (living) microorganisms are of concern for the sterility of medical products since only live microorganisms can reproduce in the human body, on the medical product surface, or within the medical product itself to cause sickness or disease. Sterility tests ensure these viable microorganisms do not exist or grow in the medical products and keep patients safe throughout product use.
Parametric release programs are important for the same reason as sterility tests. Parametric release programs fulfill the requirements of USP 71. Further, parametric release process controls often exceed USP 71 sterility requirements since all manufactured products are passing the parametric release testing requirements, compared to a sampling of products being tested for sterility testing as a representative of the entire product batch. Due to the advantages of parametric release programs, parametric release programs are commonly used for medical product release and should be used instead of sterility testing when feasible. Note that the application of parametric release requires prior regulatory approval. Parametric release programs must demonstrate a PNSU of equal to or less than one in a million.
Summary
Overall, both parametric release programs and sterility testing are options to prove the sterility safety of medical devices or products after manufacture. These tests ensure that medical devices, medical products, therapeutics, and packaging are free from viable microbial contaminants. Ensure you choose a contract manufacturing organization that can support you with appropriate sterility testing options for your unique medical device or product needs.
MycoScience is a contract manufacturing organization that specializes in filling sterile syringes and vials for parenteral products. MycoScience also offers Sterilization Validations, Bacterial Endotoxin Testing, Preservative Efficacy Testing, Bioburden Testing, Cleaning Validations, Microbial Aerosol Challenge Testing, Accelerated Aging, Microbiology Testing, Cytotoxicity Testing, EO Residual Testing, Package Integrity Testing & Environmental Monitoring services for medical device companies, and allied industries. MycoScience is an ISO 13485 certified facility.
References
Michael J. Akers. Sterile Drug Products Formulation, Packaging, Manufacture, and Quality. Drugs and the Pharmaceutical Sciences. Informa Healthcare. 2010.
United States Pharmacopeial Convention. <1211> Sterility Assurance. Rockville, MD, USA. 2021. (USPC <1211>).
United States Pharmacopeial Convention. <1222> Terminally Sterilized Pharmaceutical Products- Parametric Release. Rockville, MD, USA. 2021. (USPC <1222>).
