Cleaning Validations Vs. Sterilization Validations For Medical Devices
What are cleaning validations?
Cleaning validations are protocols that ensure items, equipment, or areas are consistently cleaned to certain acceptance criteria. For reusable devices, cleaning validations prepare devices to undergo sterilization and ensure that tissues, proteins, lipids, bacteria, and cellular debris are removed from used devices to acceptable levels. Cleaning validations have internationally accepted standards that must be met. These cleaning standards can be verified using test soils that simulate contaminants that the reusable devices would collect during use. For example, cleaning validations specify how contaminants like blood, tissues, and feces are removed from reusable medical devices during reprocessing.
What are sterilization validations?
Sterilization validations prove the efficacy of sterilization processes by verifying the presence or absence of microorganisms on the product after undergoing a sterilization cycle. Sterilization cycles can include heat, chemical gas, radiation, and other sterilization mechanisms such as filtration. The most popular method for sterilization validation is an overkill method.
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 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. Please see our sterilization comparison chart for more information on which sterilization method is best for your medical device.
What is the importance of cleaning validations for reusable devices?
Medical devices are extremely diverse in their shape, size, and use. Reusable medical devices require cleaning, disinfection, and sterilization before they can be used again. Each of these processes (cleaning, disinfection, and sterilization) must be validated to ensure patient safety and prevent hospital-acquired infections due to inadequate cleaning (and subsequent inadequate sterilization) of reusable devices.
Why Are Sterilization Validations 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 by 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.
Sterilization validations are an important quality control step proving that sterilization methods effectively kill any microbes in a product. As microorganisms exist on every surface (including our body), microbes can be accidentally introduced in many ways during the manufacturing or packaging process. Some of the most common examples are contamination through raw materials, technicians, tubing/piping used to transfer product between development stages in a process, or the manufacturing environment. Sterilization validations are used to ensure that the sterilization process can appropriately kill any viable microorganisms that accidentally enter the product during manufacturing and keep patients safe during parenteral product use.
What are the keys to a successful cleaning validation?
Cleaning validations are used to simulate “worst-case” contaminant conditions and verify that certain cleanliness levels can be met consistently following a set cleaning protocol. Generally, the following six steps are taken to set up a successful cleaning validation. At least 10 devices are tested during cleaning validations.
#1: Define the reusable device and device family (if applicable)
Defining reusable devices based on device materials, porosity, surfaces, device design, etc., supports discovering areas that will be difficult to clean and where biological contaminants will gather. Product families play a role in defining cleaning validations. Medical devices with common attributes and features can be grouped into product families. Product families only require a single validated cleaning process and acceptance criteria for the entire family of products. The medical device within a product family used for cleaning validation testing should be the most difficult device to clean. Selection criteria for this “worst-case scenario” medical device (often referred to as the master product) must be documented so that the FDA and other governing bodies can verify the selection rationale. An example of a “worst-case scenario” medical device within a product family would be the longest endoscope within a product family, where all features are the same except for the length. After a master product is verified, additional members of the product family can be validated by equivalency.
#2: Identify clinical contaminants
In order to assess clinical contaminants, data on bodily areas the device will touch, parts of the device that will be in contact with contaminated body fluids, the types of body tissue and fluids contacting the device during use, and any chemical contaminants during device use and reprocessing are accounted for. Chemical contaminants might be lubricants, drying aids, detergents, etc.
#3: Choose an appropriate test soil
No single test soil is appropriate for all medical devices due to their unique methods of use. The ratios, viscosities, and densities of the applicable body tissues and fluids in contact with the device must be assessed to determine an appropriate test soil. The chemical composition of worst-case scenario soil (e.g., types of proteins, bacteria, virus, volumes, and ratios) must be considered. Literature reviews are often performed to support creating representative physical and chemical compositions for the cleaning validation test soil. In cases (such as endoscopes) where bacteria may be encountered, bacterial soil challenges are often 1×104 colony-forming units per device.
#4: Select appropriate methods for contaminant removal
TIR 30 is the penultimate cleaning document for the medical device industry and contains charts with test methods and acceptance criteria for cleaning reusable medical devices. Specific methods for contaminant removal (such as hydration, friction, digestion, and solubilization) can be found in TIR 30. It is important to determine how long the device will sit with dried soil between patient use and cleaning when determining contaminant removal processes and presoak, scrubbing, or rinsing times.
Cleaning times for selected cleaning methods should be the worst-case during the validation. For example, soil drying times should be the maximum amount to allow the soil to adhere or absorb into the device as much as possible. On the other hand, rinse times and manual scrubbing times should be performed for the minimum time in the validation protocol.
#5: Select appropriate methods to test for residual soil contaminants
Soils can be evaluated through visual inspection and lab-based test methods. If performing visual soil inspection, determine if the visual inspection should be with magnification, without magnification, or with a borescope (for internal components such as device lumens). Further, manufacturers must decide if biomarkers or other contaminants will be metrically assessed to ensure device cleanliness. If metrics are needed, available test methods and their detection levels will need to be assessed. Test methods must have an adequate detection level to measure each specific soil marker acceptance criteria to the required precision. In some cases, detergent chemical residues on devices are assessed following the completion of the cleaning validation rinsing process. Cleaning chemicals and scrubbing tools may need to be assessed with frequently used devices to assure that they will not affect device function after multiple rounds of use. National standards and scientific literature can be used to determine a justified “standard” for test methods, soil markers, and chemical residue expectations.
As a part of soil test method selection, a method must be created for contaminating the device with the worst-case scenario test soil. Test method results must be expressed in the same units as the set acceptance criteria. Further, extraction volumes for soil assessment must be large enough for the test method selected. Otherwise, post-cleaning soil samples will fall below the level of detection for the test method. Generally, the level of detection for tests is set at three times the standard deviation of the negative control.
#6: Set scientifically justified acceptance criteria
First, set checkpoints for examining devices for visual cleanliness. Then, document information on toxicity, biocompatibility, and other device elements that could be hazardous to patient safety. Next, show that the soil marker levels are acceptable based on TIR/ISO requirements and scientific literature. Prove that any device lumens and channels can be cleaned effectively. Some methods for cleaning these elements are flushing or using a borescope. Examples of acceptance criteria for microbes (bioburden), proteins, and other soil components are given in TIR-30.
How are sterilization validations performed?
Knowledge of sterilization technologies, instrumentation, and equipment is needed to control and verify sterilization process metrics appropriately. Appropriate biological indicators are selected and placed at strategic locations to cover “worst-case” microbial scenarios. General principles for validation programs (cleaning validations and the like) apply to all sterilization processes. Each sterilization mode (e.g., dry heat sterilization, steam sterilization, ethylene oxide sterilization, vapor sterilization, liquid phase sterilization, sterilization by filtration, and radiation sterilization) 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 ensures 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. Often, the worst-case biological challenges are bacterial spores. 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.
In order to pass sterilization validation acceptance criteria, sterile processes must have a one in a million probability of unit contamination (or less). Sterility acceptance criteria are also known as sterility assurance levels (SALs). Sterilization validations for microbial inactivation processes can be performed via overkill methods, bioburden-biological indicator methods, and bioburden-based methods. All three techniques are equally accurate. The overkill method is the simplest. However, it is the most stressful for the materials undergoing sterilization. The bioburden-based method requires the greatest method control but allows sterilized materials to undergo the least stressful conditions. All three sterilization validation techniques are described in greater detail below.
#1: Overkill Sterilization Validation Method
Due to its simplicity, the overkill method is preferred for medical devices and items unaffected by the sterilization processes. Items that could be damaged by extended sterilization process exposure should not be assessed via an overkill method. With an overkill method, the destruction of a “higher-than-expected” concentration of resistant microorganisms (i.e., bacterial spores) supports killing the bioburden present during typical medical device or item sterilization. An overkill validation is passed if any of the following criteria are met: a defined minimum lethality, a defined set of method conditions, or confirmation of minimum log reduction of a resistant biological indicator. For overkill methods, biological indicators are placed in locations that are difficult to sterilize.
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.
#2: Bioburden-Biological Indicator (Combination) Sterilization Validation Method
A combination bioburden-biological indicator sterilization validation is an approach where the partial destruction of a resistant biological indicator can be used to demonstrate the ability of the sterilization process to reliably destroy the routine bioburden present during medical device (or product) sterilization. A combination approach requires detailed knowledge of the anticipated product bioburden, biological indicator populations, and the relative resistance of the anticipated bioburden and biological indicator populations.
#3: Bioburden-Based Sterilization Validation Method
The bioburden-based method is used when material stability is poor or when no suitable biological indicator microorganisms are available to use with the sterilizing process. Traditionally, radiation sterilization processes are validated using a bioburden-based method. In a bioburden-based method, bioburden samples from the device or product are routinely evaluated for resistance to the sterilization process. Lack of device resistance to the sterilization process can then be utilized to demonstrate its effectiveness. For this sterilization validation method, routine monitoring of the product bioburden population (and any resistance to the sterilization process) is required.
Summary
Overall, reusable medical devices require cleaning, disinfection, and sterilization before being used again. Each process (cleaning, disinfection, and sterilization) must be validated to ensure patient safety and prevent hospital-acquired infections due to inadequate cleaning (and thus sterilization) of reusable devices. Cleaning validations simulate “worst-case” contaminant conditions and verify that certain cleanliness levels can be met consistently following a set cleaning protocol. Indeed, a cleaning validation specifies how blood, tissues, and feces are removed from reusable medical devices during reprocessing. Sterilization validations prove the efficacy of sterilization processes (e.g., steam, heat, ethylene oxide gas, radiation) by verifying the presence or absence of microorganisms on the product after undergoing a sterilization cycle.
Generally, cleaning validations follow the following steps: 1) Define the reusable device and device family; 2) Identify clinical contaminants; 3) Choose an appropriate test soil; 4) Select appropriate methods for contaminant removal; 5) Select appropriate methods to test for residual soil contaminants; 6) Set scientifically justified acceptance criteria. Unlike cleaning validations, sterilization validations utilize biological indicators instead of test soils. Sterilization validations for unique devices are performed by one of three methods. The simplest method is overkill sterilization validation. However, bioburden-biological-indicator and bioburden-based sterilization validation methods can also be used. The acceptance criteria for sterilization validations is the probability of contamination for one in a million products. MycoScience specializes in quickly creating effective cleaning validations and sterilization validations for their client’s reusable components and devices. Ensure you choose a contract testing organization that can support you with your unique sterilization and cleaning validation needs.
MycoScience is a contract manufacturing organization specializing in sterile syringe and vial filling for parenteral products. MycoScience also offers testing services, including Preservative Efficacy Testing/Suitability Testing, Bioburden Testing, Microbial Aerosol Challenge Testing, Cytotoxicity Testing, Cleaning Validations, Accelerated Aging, Microbiology Testing, EO Residual Testing, Bacterial Endotoxin Testing, Package Integrity Testing, Sterilization Validations & Environmental Monitoring services medical devices and allied industries. MycoScience is an ISO 13485 certified facility.
References
Association for the Advancement of Medical Instrumentation Technical Information Report. A compendium of processes, materials, test methods, and acceptance criteria for cleaning reusable medical devices. Arlington, VA, USA. AAMI; 2011. (AAMI TIR30-2011).
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).
Michael J. Akers. Sterile Drug Products Formulation, Packaging, Manufacture, and Quality. Drugs and the Pharmaceutical Sciences. Informa Healthcare. 2010.
Steven G. Richter. Cleaning Validations of Medical Products. Chapter 10: The Medical Device Validation Handbook 2nd Edition. RAPS.
United States Pharmacopeial Convention. <1229> Sterilization of Compendial Articles. Rockville, MD, USA. 2021. (USPC <1229>).
