Validation of sterilization
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The document discusses validation of sterilization processes. It defines validation and sterilization. The commonly used sterilization methods are steam, dry heat, gas, and radiation. It then summarizes the validation process for each method. For steam sterilization, validation studies include qualification and calibration of equipment, heat distribution studies, and heat penetration studies. Dry heat validation involves air balance determination, heat distribution, and heat penetration studies. Gas sterilization validation is outlined for ethylene oxide and vapor hydrogen peroxide. Radiation sterilization validation focuses on determining the D-value of biological indicators.
Validation of sterilization
- 1. VALIDATION OF STERILIZATION PROCESS PREPARED BY: KASHF RASHEED M.PHIL. PHARMACEUTICS PUNJAB UNIVERSITY COLLEGE OF PHARMACY
- 2. VALIDATION • Validation is defined as: • Action of checking or proving the validity or accuracy of something. • Establishing documented evidence which provides high degree of assurance that specific process will be consistently produce a product meeting its predetermined specifications & quality attributes.
- 3. FDA PUBLISHED GUIDELINES 3 principles should be involved in validation process: • To build sterility into a product. • To demonstrate maximum level of probability that sterilization methods has established sterility to all batches of unit. • To provide greater assurance of result of end product sterility test.
- 4. STERILIZATION • “The act or process, physical or chemical, that destroys or eliminates all viable microbes including resistant bacterial spores from a fluid or a solid.” • Sterility: “The reduction of anticipated levels of contamination in a load to the point where the probability of survival is less than 10⁻⁶.” • This referred to as STERILITY ASSURANCE LEVEL (SAL)
- 5. COMMONLY USED STERILIZATION METHODS • Moist heat (Steam) • Dry heat • Gas (Ethylene oxide, Hydrogen peroxide) • Radiation (Gamma rays or electrons) • Others (UV, Steam & Formaldehyde, Filtration)
- 6. PROCESS OF MICROBIAL DESTRUCTION • D-value : • The time in minutes required for 90% reduction of a specific microbial population. • Z-value: • It is the number of degrees the temperature has to be increased to achieve a ten fold (i.e. 1 log10) reduction in the D-value. • F-value: • The F value is a measurement of sterilization effectiveness. • It is defined as number of minutes to kill number of microorganism with specified Z- value at a specific temperature
- 7. VALIDATION OF STEAM STERILIZATION • Describes sterilization techniques that utilize hot air that is heavily loaded to facilitate efficient sterilization by steam and pressure. • Its validation studies include: A. Qualification & calibration: 1. Mechanically checking, upgrading, qualifying the sterilizing units 2. Selection & calibration of thermocouples 3. Selection & calibration of Biological Indicator (BI) 4. Container mapping B. Heat distribution studies C. heat penetration studies
- 8. QUALIFICATION & CALIBRATION: Mechanically checking, upgrading, qualifying the sterilizing units: • Complete removal of air from chamber & replacement with saturated steam • Temperature & pressure instruments must be calibrated. Selection & calibration of thermocouples: • Copper constant wires coated with taflons are popular choice • Thermocouple should be calibrated before & after validation experiment at two temperature (0ᵒC & 125ᵒC)
- 9. Selection & Calibration of Biological Indicator: • B-Stearothermophillus spores are most commonly used BIs in steam sterilization process • Spores strips & spore suspensions are used in validation studies. Container Mapping: • The temp profile of container should remain constant among different sterilizing chamber in which sterilizing medium is steam heat • Repeat studies are required to establish cold point & temp profiles • Cold Spot/Point: Position in autoclave at which temp is lowest during heating period.
- 10. HEAT DISTRIBUTION STUDIES • Two Phases: 1. In empty autoclave chamber 2. In loaded autoclave chamber • The key is to identify cool spot, the effect of load size, configuration on cool spot location. • Mean temp difference b/w cool spot & chamber difference should not be greater than ±2.5⁰C.
- 11. HEAT PENETRATION STUDIES: • It is most critical component in which the container’s cold spot for containers ≥100ml is determined using container’s mapping studies • The effect of load-load variation on time, temperature profile must be determined
- 12. VALIDATION OF DRY HEAT STERILIZATION • Dry heat, as the name indicates, utilizes hot air that is free from water vapors. A. Batch oven/Tunnel sterilizer validation • Air balance determination • Heat distribution studies • Heat penetration studies • Mechanical repeatability B. Biological process validation and Endotoxin challenge of dry heat sterilization
- 13. BATCH OVEN/TUNNEL STERILIZER VALIDATION: Air Balance Determination: • Proper air balance is critical • Air must be particulate free Heat distribution studies: • Cold spot determination • Length of thermocouple
- 14. Heat Penetration Studies: • Test load variations • Temperature set point variations • Variations in the time of exposure Mechanical Repeatability: • Air velocity, temp consistency, reliability & sensitivity of all the oven & instrumental control must be verified.
- 15. BIOLOGICAL PROCESS VALIDATION AND ENDOTOXIN CHALLENGE OF DRY HEAT STERILIZATION • To prove the ability of dry heat to destroy microorganisms & microbial endotoxin. • Endotoxin validation: • Endotoxin destruction should be ascertained to investigate at the coolest location of the load.
- 16. VALIDATION OF GASEOUS STERILIZATION: 1. Validation of ethylene oxide sterilization cycle 2. Validation of vapor phase hydrogen peroxide (VPHP) sterilization process.
- 17. ETHYLENE OXIDE VALIDATION • 5 variables: • Ethylene oxide concentration • Relative humidity • Time • Temperature • Pressure Temperature is used as the indicator of the worst-case location within the loaded EtO sterilizer. Once the worst-case location is identified, the validation studies are conducted with the goal of inactivating a known concentration of indicator micro- organisms in the worst-case location using a specific loading pattern with a specific EtO cycle.
- 18. VALIDATION OF VAPOR PHASE HYDROGEN PEROXIDE STERILIZATION PROCESS: • VPHP is relatively new gaseous sterilization process. It has advantages over other agents that: • It doesn’t require temp above ambient. • There are no concerns about residual byproducts. • The basic step in process are dehumidification, conditioning, sterilization & aeration.
- 19. HYDROGEN PEROXIDE STERILIZATION PROCESS 5 Steps of validation: 1. Cycle development parameters include: Temp, Airflow rate, Humidity, Hydrogen peroxide concentration and hydrogen peroxide delivery rate 2. Temperature studies include use of temp. 3. Vapor distribution studies uses chemical indicators. 4. Biological challenge involves placement of biological indicators normally Bacillus stearothermophilus spore strips. 5. Aeration verification determines the parameters (e.g- time, air exchange rate)
- 20. VALIDATION OF RADIATION STERILIZATION • Major objective in validating a radiation sterilization process: to determine the D value of the indicator micro-organism used to monitor the process. • D value: The dose of radiation necessary to produce a 90% reduction in the number of indicator microbial cells. • It depends on factors such as: • Temperature • Moisture • Organism species • Chemical environment/physical surface on which indicator microorganism is attached. • Bacillus Pumilus spores are USP choice as biological indicator for radiation sterilization.
- 21. VALIDATION REPORT • Common elements of all reports : • Identification of the task report by number • Reference to protocol • A brief summary of the range of operational conditions experienced and how they were controlled • A procedure for maintaining control within the approved range • A summary and analysis of the experimental results • A brief description of any deviation • Conclusion • Review and approval
- 22. REFERENCES • Pharmaceutical Process Validation (Third Edition) Edited by Robert A. Nash and Alfred H. Wachter