Skip to main contentSkip to footer

Why Use Liquid Chemical Sterilization for Medical Devices Utilizing Animal Tissue?

Single-use medical devices containing animal tissue may not be compatible with traditional sterilization methods such as ethylene oxide, steam, or radiation, but may instead utilize a liquid chemical sterilization agent.

The liquid chemical sterilizing agent is characterized by its concentration, pH, expiration date, storage conditions, and processing parameters to be used during routine processing.

What are the ISO 14160 Testing Requirements for a Liquid Chemical Sterilization Validation?

Several tests are required when performing a liquid chemical sterilization validation per ISO 14160 to ensure the validation and routine control of the liquid chemical sterilization process. 

The testing that may be performed for tissue-based medical devices can include:

What are Filtration Neutralization Studies in Liquid Chemical Sterilization Validation?

Filtration neutralization studies evaluate whether the organism recovery process is acceptable for each liquid chemical solution, based on USP <1227>. 

These studies enable the identification of a neutralizer solution and filtration process for subsequent filtration studies.

What is Adverse Substance Testing for Animal Tissue-Based Medical Devices?

Adverse substance testing evaluates the recovery of the organism from a directly inoculated tissue to ensure that the qualification result is not adversely influenced by the carryover of the liquid chemical sterilizing agent into the recovery system. 

Through this testing, the recovery percentage is compared for both pre-rinsed and un-rinsed samples, and the inoculation procedure is identified for subsequent studies.

What is the Sterility Test Method Validation for Liquid Chemical Sterilization Validation?

Bacteriostasis/fungistasis (B/F testing) is the sterility test method validation performed for both the product and the terminal sterilizing agent solution. 

The method validation demonstrates the test's ability to detect a low level of the organism (<100 colony-forming units (CFU)). 

Inoculated products are later tested using the validated sterility method during the microbial performance qualification (MPQ).

What is the Bioburden Test Method Validation for Liquid Chemical Sterilization Validation?

Bioburden test method validation evaluates the bioburden recovery percentage and resulting correction factors. 

All liquid chemical solutions and the product are tested for bioburden at each significant processing stage to estimate the bioburden present in the sterilant and on the product at critical stages.  

Additional guidance on bioburden recovery, correction factors, and method suitability is available in our related TechTips on bioburden and sterility testing, go here to learn more.

What is the Microbicidal Effectiveness Testing for Resistant Microorganisms when Performing Liquid Chemical Sterilization?

Microbicidal effectiveness testing is performed to identify the worst-case, most resistant organism used for subsequent studies.

This test is performed against a range of representative microorganisms from product bioburden and environmental monitoring in the manufacturing environment. 

The worst-case, most resistant organism identified in testing is typically a spore-forming Bacillus. 

Ongoing screening studies may be performed for potentially resistant isolates encountered in the manufacturing process and environment to demonstrate that they are not, or have not become, more resistant than those used during the original validation studies.

What are the Equipment Qualification Definitions for Liquid Chemical Sterilization Systems?

Installation qualification (IQ): Confirms proper installation of the sterilization incubator per specifications

Operational qualification (OQ): Demonstrates that the incubator operates as required and delivers the specified sterilization parameters through empty chamber mapping, recovery testing, and calibration

Physical performance qualification (PPQ): Validates that the equipment operates in accordance with the predetermined specifications during routine use through full chamber mapping

What are Inactivation Kinetics and D-Value Determination?

Inactivation kinetics evaluate the rate of microbial inactivation to determine D-value and for linear inactivation to determine the minimum half-cycle time for MPQ.

Requirements include:

  • Minimum of five timepoints
  • Demonstration of at least a 1,000-fold log reduction
  • Linearity with a coefficient of determination (r2) of at least 0.8

Two approaches may be used:

  • Direct enumeration approach: Filtration of multiple dilutions (both for the sterilant and extract) for a minimum of four samples at each time point
  • Fraction negative approach: Testing of a minimum of 20 samples at each timepoint, with at least two timepoints showing no growth

What is Microbial Performance Qualification (MPQ) and Sterility Assurance Level (SAL) as it Relates to Liquid Chemical Sterilization?

Microbial performance qualification (MPQ) will demonstrate the sterility assurance level (SAL) of the sterilization process by testing products inoculated at the worst-case location and exposed to the worst-case sterilization conditions. 

Three consecutive half cycles are performed with the product and sterilant solution tested for sterility.

Conclusion

After completing validation of liquid chemical sterilization for single-use medical devices with animal-derived components, a validation report will be issued that contains or references a complete process specification, including the process parameters and their tolerances. 

At defined sampling intervals, routine monitoring of bioburden immediately preceding sterilization must occur. 

To ensure the validation and routine control of the liquid chemical sterilization process, for each batch data must be recorded and retained to demonstrate the sterilization process specification has been met.  

Product release may occur through:

  • Conventional release, which includes sterility testing of a sample set from the sterilized product  
  • Parametric release, based on process data without product sample testing

The rationale for any deviation or modification to the process plan or validation needs to be justified and documented. 

The validation and any requalification data must be reviewed at least annually, and a rationale must be documented for whether a requalification is required.

References:

  1. BS EN ISO 14160 
    British Standards Institution. (2021). BS EN ISO 14160: Sterilization of health care products — Liquid chemical sterilizing agents for single-use medical devices utilizing animal tissues and their derivatives — Requirements for characterization, development, validation and routine control of a sterilization process for medical devices. London: BSI.
  2. ISO 11138-1 
    International Organization for Standardization. (2017). ISO 11138-1: Sterilization of health care products — Biological indicators — Part 1: General requirements. Geneva: ISO.
  3. ISO 11138-7 
    International Organization for Standardization. (2019). ISO 11138-7: Sterilization of health care products — Biological indicators — Part 7: Guidance for the selection, use and interpretation of results. Geneva: ISO
  4. USP <1227> Validation of Microbial Recovery from Pharmacopeial Articles 
    United States Pharmacopeial Convention. (2023). General Chapter <1227> Validation of Microbial Recovery from Pharmacopeial Articles. In the United States Pharmacopeia and National Formulary (USP–NF). Rockville, MD: USP.www.uspbpep.com
  5. USP <61> Microbial Examination of Nonsterile Products: Microbial Enumeration Tests 
    United States Pharmacopeial Convention. (2023). General Chapter <61> Microbial Examination of Nonsterile Products: Microbial Enumeration Tests. In USP–NF. Rockville, MD: USP.
  6. USP <71> Sterility Tests 
    United States Pharmacopeial Convention. (2023). General Chapter <71> Sterility Tests. In USP–NF. Rockville, MD: USP.
Download Pdf

RELATED TECHTIPS

See All