# Presentation: 135707

## Validating Sterilization of Medical  Devices

**CDR Martha O’Lone, RN, BSN **
**Infection Control Devices Branch**
**DAGID / ODE / FDA**

**Notes:**
Good Morning- I am Martha O’Lone, a medical device reviewer in FDA’s Office of Device Evaluation /Infection Control Devices Branch.  

Ms. Lillian Gill, our Senior Associate Director for Science, gave an introduction to FDA medical device reviews.

I am going to discuss approaches to reviewing medical device reprocessing and how that might relate to devices that would require reprocessing after exposure or potential exposure to CJD.

Hopefully this information will reinforce current knowledge that you have about medical device reviews and will assist with your discussion on the questions  that will be presented later in this section. 

## Objectives

**Provide background information on sterilization validation for medical devices**
**Obtain panel guidance on how to design and interpret sterilization validation studies for medical devices after exposure to TSE material**

**Notes:**
These are the objectives that I hope to accomplish.

## Questions

**For prion contaminated critical medical devices:**
**What is the acceptable sterilization process for prion removal/ inactivation?**
**What endpoint is appropriate? **
**Log reduction of infectivity? **
**Is there an indicator agent for prions? **
**  **

**Notes:**
When I complete this presentation we will hopefully have enough information to address the questions at the end of the time allotted for CDRH. 

## Validating Sterilization of Medical Devices 

**Spaulding Classification of Medical Devices**
**Sterilization Methods**
**Medical Device Reprocessing Steps**
**Healthcare Sterilization Processes **
**Medical Device Reprocessing Review**
**Validation  **
**Available Recommendations/Guidelines**

**Notes:**
These are the topics that I plan to cover during this presentation

## Spaulding Classification of Medical Devices

**BASED ON RISK OF INFECTION**

**Critical devices **
**	****Enter normally **_**sterile**_** body tissue: e.g., surgical instruments**
**	****	****-Sterilization**
**Semi- critical devices**** **
**	****Contact mucous membranes: e.g., flexible endoscopes**
**	****       ****-Sterilization, if not feasible- Minimally high level disinfection**
**Non- critical devices **
**	****Contact intact skin: e.g., stethoscopes, electrocardiogram electrodes**
**	****	****-Intermediate or Low level disinfection ****                                                                               - Block, 5****th**** edition**

**Notes:**
The science behind instrument classification has been described by Spaulding.. Spaulding Instrument Classification is based on risk of infection.  
This classification is used in medical device reviews to determine if devices should be  subject to sterilization or high level disinfection before use -depending on the area that the device will contact as shown here.
The medical device or product classification that the FDA uses aligns with the Spaulding classification. 
Critical devices are those devices that enter normally sterile body tissues- surgical instruments such as scalpels, neuro burrs are an example of devices that would be subject to sterilization prior to use.
Most of this presentation will center on critical devices because areas of concern for CJD such as brain tissue are considered sterile body tissue.  
When medical devices are used, their reuse is determined by their design and materials but most heavily by the ability to validate that these devices can be reprocessed. 

## Descending Order of Resistance  

**????  Prions  ????**
**Bacterial Spores**
**Mycobacteria **
**Non-lipid or Small Viruses**
**Fungi**
**Vegetative Bacteria**
**Lipid or Medium-Size Viruses**

**Notes:**
After considering the Spaulding Classification in medical device sterilization validation reviews, the  potential level of resistance of the infectious organism is considered. 
This order of resistance provides additional information that should be considered when determining the resistance to reprocessing and the level of resistance that should be validated for a review of a medical device that is to be reprocessed for multiple use. 
This slide is not new- it shows that the order of resistance to Prions is thought to be higher than bacterial Spores. 
Currently there have been no studies submitted that attempt to validate the safe reuse of medical devices after contamination with CJD. 

## Steps for Medical Device Reprocessing 

**Cleaning **
**Required for effective disinfection or sterilization**
**Goal:****	****Reduce bioburden **
**	****Remove organic / inorganic clinical contaminants **
**High Level Disinfection-semi critical devices**
**Endpoint- To kill mycobacteria and some spores**
**Sterilization- critical devices**
**Validated process used to render a product free of all forms of viable microorganisms (AAMI)**
**Endpoint- To kill spores (as an indicator microorganism)**

**Notes:**
The STEPS for Medical Device Reprocessing may include the items in bold: Cleaning, High Level Disinfection or Sterilization.

CLEANING- No standard definition/No standard procedure. Goal is to reduce bioburden by removal of organic and inorganic clinical contaminants.
Next is High Level Disinfection-Although high level disinfection is mentioned in this slide, the focus for this discussion is on reprocessing that is used for critical devices which would be reprocessed after exposure to potential or known CJD  
Sterilization for critical device reprocessing as defined by AAMI is a validated process used to render a product free of all forms of viable microorganisms. 
Currently the sterilization endpoint is to kill spores, but as the previous slide showed, resistance to prions is thought to be higher than spores.

## Sterilization Processes Currently Used in Healthcare Settings 

**Steam (Moist Heat) Sterilization **
**	****Gravity displacement cycles - 121****oC, 20-30 min**
**	****Prevacuum cycles – 132-134 ****oC, 3-5 min****      **
**Dry Heat Sterilization**
**Ethylene Oxide (EtO) Sterilization**
**Liquid Chemical Sterilization**
**Gas Plasma Hydrogen Peroxide Sterilization Process**

**Notes:**
These are the sterilization processes that are used in health care settings to reprocess medical devices that are currently on the market and available to the user. The FDA has reviewed devices according to these methods.

Bring to your attention that Steam or Moist heat sterilization is the most common method recommended for prion deactivation and removal. 
It is also the most common method used for sterilization of medical devices.  
For the Gravity displacement cycles,  steam is used at a temperature of 121C  for 20-30 minutes. 
The prevacuum cycles use steam temperatures of 132-134C for 3 to 4 minutes                                                           	
It is important to remember that in the U.S., these cycles are fixed in health care and it is rare for the healthcare user to reprogram the sterilizers- This will be important when discussing recommendations for reprocessing devices that are contaminated or potentially contaminated with CJD.

## Review of Reusable Medical Device Reprocessing

**FDA Guidance: **_**Labeling Reusable Medical Devices for Reprocessing In Health Care Facilities: FDA Reviewer Guidance**_**, April, 1996**
**Labeling for a reusable device that contacts the patient in some manner must include reprocessing instructions**
**The instructions must indicate the appropriate microbicidal process for the device**
**Critical - Sterilization**
**Semicritical – At least high level disinfection**
**Noncritical – Intermediate or low level disinfection**
**The reprocessing process must be feasible considering the intended location of reprocessing (e.g., health care facility or home use)**
**Reprocessing instructions must be validated           **
**   **

**Notes:**
If the manufacturer wants to label their product reusable, FDA will ask the manufacturer to follow this 1996 Reusable Labeling guidance.
This guidance recommends clear instructions to the user so that user can properly follow the manufacturers recommendations.
Instructions must include appropriate microbicidal processes for the device
Those reprocessing processes must be feasible- for example- users don’t have access to radiation so that is not a viable method.
The Reprocessing instructions must be validated. 

## Sterilization Validation

**Sterilization of critical medical devices **
**Objective: sterilization process should demonstrate a spore (BI) kill to achieve a sterility assurance level (SAL) of 1x10****-6**
**Standards/Guidance available to provide validation methods for traditional sterilization processes utilizing bacterial spores **

**Notes:**

As has been stated for medical device reprocessing, the sterilization process should demonstrate a spore (BI) kill to achieve a sterility assurance level (SAL) of 10-6 or twelve log kill as its endpoint for conventional critical medical devices.
 For medical devices exposed to potential or known CJD, this current approach to sterilization validation for medical device reprocessing with spores does not provide information that can be applied to removal/ inactivation of prions.  
These questions remain- what endpoint is appropriate?
Can log reduction be applied to determine safe use of a medical device and prevent transmission of prion infectivity? 
What indicator agent similar to the use of spores should be used for safe validation of sterilization of prion contaminated devices?

Can prion contaminated medical devices and the equipment used in reprocessing in health care facilities be safely used?

## Sterilization Validation

**For prion contaminated critical medical devices:**
**What is the acceptable sterilization process for prion removal/ inactivation?**
**What endpoint is appropriate? **
**Log reduction of infectivity? **
**Is there an indicator agent for prions? **
**  **

## Virus Validation

**For medical devices incorporating animal derived tissue**
**Objective: final product below one infectious particle per 10****6**** devices**
**Similar to SAL 1 X 10****-****6 ****in traditional   medical devices sterilization processes**

**Notes:**
CDRH requires a virus validation study for medical devices that incorporate animal derived tissue.
Since Virus Validation studies for medical devices with animal derived tissues were discussed at this panel’s July 2002 meeting I will not cover it in detail.  
For medical devices incorporating animal derived tissue the objective is a final product  that is below one infectious particle per 10  6 devices.
This is similar to an Sterility Assurance Level of 1X10-6 in traditional sterilization processes.
In the case of bacteria, fungi  and yeast there are published methods by the FDA, but for virus validation there are published standards but no accepted methods- virus validation is a step by step evaluation of an overall inactivation process that is carried out in a controlled manufacturing setting. 
The sterilization of reusable critical medical devices is performed in healthcare settings.  

## Virus Validation Studies

**Scaled down (e.g.1/100) manufacturing procedures**
**Relevant model viruses (DNA, RNA, single and double stranded enveloped and non-enveloped)**
**Spike virus in different steps in the manufacturing process and determine post-step PFU**
**Sum the viral clearance values for each manufacturing step**

**Notes:**
With bacterial inactivation or traditional sterilization of medical devices  it’s a full scale sterilization process. These are the details 

Virus validation is a model or scaled down approach with different steps in the manufacturing process to inactivate the virus. Then the steps are summarized for a total inactivation process. 

## WHO Recommendations Annex III(For reprocessing CJD contaminated instruments)

**Disposable Instruments: Incinerate ****(and all instruments exposed to high infectivity tissues.)**
**Heat Resistant Instruments: **
**Immerse in 1N NaOH **
**Heat in a gravity displacement autoclave at 121****°****C for 30 min,  or 132****o**** C for 3-5 min  **
**Rinse in water **
**Routine sterilization**** ****process****    **

**Notes:**
For Reprocessing CJD Contaminated Medical Devices, The WHO has provided recommendations. These recommendations begin with incineration for disposable instruments and those exposed to high infectivity tissues such as brain.
 The most stringent method is listed on this slide. 

Yesterday Dr. Brown mentioned his findings and recommendations on device material compatibility with reprocessing in Na OH.
These included the potential for damage or residue on many of the medical device materials tested. 
What the list does not do is provide an endpoint or indicator for the heat resistant instruments. No validation method.

## Draft CDC HICPAC Guidelines for CJD Decontamination

**Critical or Semicritical Devices Exposed to High Risk Tissues and/or High Risk patients**

_**Keep instruments wet or damp until they are decontaminated**_** **

**Options: **
**1. Clean and sterilize the contaminated devices by immersion in 1N NaOH, remove, rinse in water and autoclave (sterilizer)  in an open pan as recommended by WHO at 121****°**** C or 134****°****C depending on type of sterilizer- gravity displacement or prevac- for 1hr**
**2. **_**OR**_** immerse instruments in 1N NaOH for 1 hour and heat in a gravity displacement sterilizer at 121****°****C for 30 minutes, clean; and subject to routine sterilization **
**3. Clean thoroughly, then autoclave at 134****°****C for 18 minutes in a prevacuum sterilizer or 132****°****C for 1 hour in a gravity displacement sterilizer. **
**Discard contaminated medical devices that are impossible or difficult to clean **

**Notes:**
Recently CDC’s HICPAC has also made recommendations for CJD contaminated devices. These guidelines are not final.
They do provide some different information such as discard contaminated medical devices that are impossible or difficult to clean.
Options 1& 2 are similar to WHO recommendations.  Option #3 is a new recommendation from HICPAC. 

HICPAC Health Care Infection Control Practice Advisory Committee

## Slide 16