Top 9 Sterilization Process Controls You Need Before Your Next Audit
How does the United States Food and Drug Administration (FDA) define sterile?
Under the strictest definition of sterility, an item or product is sterile when there is a complete absence of viable microorganisms (bacteria, yeasts, viruses, and molds). For regulatory purposes, sterility is defined by acceptance criteria based on calculated contamination probability. An acceptable level of contamination risk for most items is the probability of contamination for one in a million products. However, sterility criteria may be more stringent or lax depending upon the intended use of the medical device or product.
What are sterilization validations, and why are they important?
Since the sterility of a medical device or product is based on acceptance criteria, the process that a product or device undergoes to become sterile must be validated to prove that sterility acceptance criteria are consistently met. Sterility can be assured only using a validated sterilization process under current good manufacturing practices (cGMP). Sterility cannot be demonstrated by reliance on periodic sterility testing of final products alone. Thus, sterilization validations are tests that accumulate data about a sterilization process and statistically prove that the sterilization process can consistently sterilize medical devices or products under “worst-case scenario” conditions.
What are the five sterilization validation stages?
Knowledge of sterilization technologies, instrumentation, and equipment is needed to control and verify sterilization process metrics appropriately. Thus, sterilization validations require multiple formally documented stages. General principles for validation programs (cleaning validations and the like) apply to all sterilization processes. Each sterilization mode (e.g., dry heat sterilization, wet heat sterilization, gaseous sterilization, etc.) has individual criteria that must be met. The first sterilization validation stage is the process development stage. In the process development stage, operating parameters and controls used for the sterilization process are investigated and selected. The next stage is the installation qualification stage, which ensures that equipment controls and instrumentation are installed and calibrated appropriately. As part of the installation qualification, systems to regulate steam, water, and air should be verified and documented. The third sterilization validation stage is the operational qualification stage. Operational qualification makes sure that installed equipment functions within the set sterilization process parameters. After the operation of the equipment is verified, the performance qualification stage begins. Performance qualifications assess the sterilization of materials, items, and biological indicators that pass through the sterilization process under validation. Performance qualifications measure sterilization cycle controls and the effectiveness of the sterilization cycle in overcoming worst-case biological challenges. The fifth and final sterilization validation stage is the routine process control stage. This final stage ensures that sterilization processes are continuously monitored and controlled to maintain the efficacy of product sterilization.
Which process controls are necessary for maintaining a validated sterilization process?
After a sterilization process has been validated, maintenance of the process is needed to ensure continual product sterility. There are nine categories of process controls required to keep a sterilization process appropriately validated. These process controls are detailed below.
#1: Calibration
All sterilization equipment and instrumentation (including instruments that regulate the operation of equipment) must be regularly calibrated against recognized standards. All calibrations are to be recorded.
#2: Physical Measurements
Recorded data from equipment sensors and computers must be verified through comparison to predetermined acceptance criteria after each sterilization cycle finishes. Records of equipment data for all cycles must be kept for audits.
#3: Physical Integrators/Indicators
Integrators (and sometimes indicators) verify a specific level of sterilization lethality. An example of an integrator is a radiation dosimeter used to provide a radiation reading indicating the products have met an appropriate level of lethality.
#4: Parametric Release
See USP 1222 for details on the release of finished products without sterility testing.
#5: Sterilization Type Dependent Special Considerations
Examples of additional requirements to confirming sterilization method efficacy are bioburden sampling, bioburden resistance testing, biological indicator resistance testing, and supplier audits.
#6: Change Control
Sterilization processes are validated under strict parameters and conditions. A change to any element of the process (materials, material suppliers, procedures, equipment, etc.) can compromise the sterilization process’s integrity. Thus, all changes are monitored, recorded, and evaluated for their impact on the sterilization process. Change controls are processes made to assess the risk and effect of any alteration made to the validated sterilization process. The results of the change control process determine if revalidation of a sterilization process is necessary following a recorded modification.
#7: Preventive Maintenance
Equipment malfunction leads to the creation of unusable products. Thus, preventative maintenance based on the manufacturer’s recommendation should be performed regularly on all equipment and instrumentation to avoid the costs of equipment failure. Note that preventive maintenance does not require evaluation under change control.
#8: Periodic Reassessment
Even without modifications to the validated sterilization process, the effectiveness of sterilization processes should be reconfirmed periodically. Periodic reassessments account for the possible impact of undetected changes to the validated sterilization process.
#9: Personnel Training
Two types of individuals require regular education and training to keep sterilization processes operating effectively. The first type is the sterilization process development team, which is composed of scientists and engineers. Sterilization processes rely on current microbial science and scientific principles from other disciplines to efficiently kill or eliminate microorganisms from manufactured devices. Thus, it is critical for scientists and engineers involved in developing sterilization processes to have a depth of knowledge in microbiology, physics, chemistry, engineering, and cGMP regulations. Scientists and engineers need regular training to stay abreast of current science and cGMP or FDA regulations changes.
Also critical to the sterilization process’s long-term success, personnel responsible for maintenance and operation must be trained to ensure standard operating procedures are completed correctly and consistently. Furthermore, operating personnel training ensures hiccups with process performance are noticed and reported since these individuals are often the first to identify upsets and shifts in process performance. Effective training programs for both the process development team and operating technicians should be established and documented.
Summary
Since the sterility of a medical device or product is based on acceptance criteria, the process that a product or device undergoes to become sterile must be validated (through a sterilization validation) to prove that sterility acceptance criteria are consistently met. Sterility can be assured only by using a validated sterilization process under current good manufacturing practices (cGMP). Sterilization validations have five stages: process development, installation qualification, operation qualification, performance qualification, and process control. There are nine categories of process controls necessary for appropriately monitoring a validated sterilization process. Calibration, physical measurements, physical indicators, parametric release, special considerations based on sterilization type, change control, preventative maintenance, periodic process reassessment, and personnel training are the nine process controls. Overall, ensure you choose a contract testing organization that can provide appropriate sterilization validations for your unique medical device or product needs.
Ethide Labs is a contract testing organization specializing in Sterilization Validations & Bioburden Testing. Ethide Labs also offers Microbiology Testing, Bacterial Endotoxin Testing, EO Residual Testing, Sterility Testing, Cytotoxicity Testing, Environmental Monitoring & Package Integrity Testing services for medical device companies and allied industries. Ethide is an ISO 13485 certified facility.
References
United States Pharmacopeial Convention. <1229> Sterilization of Compendial Articles. Rockville, MD, USA. 2021. (USPC <1229>).
