understanding how bioburden and sterilization affect medical devices
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Why Understanding Bioburden and Sterilization is Key to
Successful Device Development
Presented by: Aaron Burke -Pacific BioLabs and Jeff Sauter -Nutek Corporation
Hosted by: MDMR
Why Understanding Bioburden and SterilizationIs Key to Successful Device Development – April 2, 2015
What We’ll Be Covering Today
• Bioburden: what is it and how it can affect a device development program and sterilization validation program
• Sterilization: methods and the bioburden-sterilization connection
• Benefits of minimizing the sterilization dose for your device
• Importance of monitoring bioburden
• Case study: sterilization failure and tracking down root cause
• How to monitor and reduce bioburden levels
Why Understanding Bioburden and SterilizationIs Key to Successful Device Development – April 2, 2015
Why You Need to Know Bioburden
Bioburden and Sterilization Validation testing are not end-stage processes in device development.
Identifying and fixing a problem earlier is almost always better.
Why Understanding Bioburden and SterilizationIs Key to Successful Device Development – April 2, 2015
Device development requires coordination and fearlessness. It’s like juggling cats.
Why Understanding Bioburden and SterilizationIs Key to Successful Device Development – April 2, 2015
Sterilization Validation Program Steps
1. Determine the bioburden of your product
2. Select your sterilization method
3. (For radiation sterilization) Dose product samples at verification dose, check for sterility
If your product passes the sterility check after the verification dose, then your sterilization process is validated.
4. Periodically check bioburden, and verify sterilization is effective
Why Understanding Bioburden and SterilizationIs Key to Successful Device Development – April 2, 2015
Our Ultimate Goal:
Deliver an effective product that is safe to use.
Why Understanding Bioburden and SterilizationIs Key to Successful Device Development – April 2, 2015
Bioburden 101
Definition: The Bioburden test determines the total number of viable microorganisms in or on a medical device, container or component. It is performed on any product that requires control and/or monitoring of bioburden counts, usually as part of a sterilization program. This test acts as an early warning system for possible production problems that could lead to inadequate sterilization. It is also used to calculate the necessary dose for effective radiation sterilization and to monitor product routinely as part of quarterly dose audits.
Bioburden is NOT a Test Your Product Passes or Fails – it is information
Why Understanding Bioburden and SterilizationIs Key to Successful Device Development – April 2, 2015
What are “Viable Microorganisms”
Bacteria, Fungi: Yeast/Mold
Typical Microorganisms of Concern:
• Yeast: Candida albicans
• Mold: Aspergillus Niger
• Bacteria:
° E. coli (intestinal disease)
° Pseudomonas (can cause sepsis; common on medical equipment)
° Staphylococcus aureus (staph infection)
S. Aureus from Wikipedia.org
Why Understanding Bioburden and SterilizationIs Key to Successful Device Development – April 2, 2015
Bioburden Sources
• Air / particulate matter
• Human handling
• Contact with surfaces
• Contact with liquids (can be particularly dangerous –endotoxins)
• Bioburden can also come from previous use of a device on humans (in the case of reusable devices)
Why Understanding Bioburden and SterilizationIs Key to Successful Device Development – April 2, 2015
Consequences of Nonsterile Devices:
from CNN.com:
http://www.cnn.com/2015/02/18/health/california-deadly-bacteria/
Why Understanding Bioburden and SterilizationIs Key to Successful Device Development – April 2, 2015
Determining Bioburden – part 1
Methods described in ISO 11737
• First: Recovery (determines the best method to extract bioburden)
Factors Affecting Recovery:
° Antimicrobials
° Device geometry (nooks and crevices can impact recovery)
Why Understanding Bioburden and SterilizationIs Key to Successful Device Development – April 2, 2015
Determining Bioburden – part 2
• Second: Bioburden. Result reported in CFUs
CFU = a single macroscopic colony formed after the successful growth of one or more microorganisms to a solid microbiological growth medium.
Why Understanding Bioburden and SterilizationIs Key to Successful Device Development – April 2, 2015
Collecting Samples for Bioburden
• Select from production or representative lots
• NO special sampling methods – use product after it has gone through all production processes
Number of Samples Needed
• For large (>1000 products) and frequent production batches: 3 lots of 10 for initial bioburden
• For smaller or infrequent production batches: 10 products needed
Why Understanding Bioburden and SterilizationIs Key to Successful Device Development – April 2, 2015
Bacteriostasis / Fungistasis
• Some devices possess properties that inhibit the growth of microorganisms
• Bacteriostasis/ Fungistasis test is used to validate the Sterility Test (Dose Verification)
• The B-F test establishes that nothing in or on device inhibits growth of microorganisms which can cause false negatives
Why Understanding Bioburden and SterilizationIs Key to Successful Device Development – April 2, 2015
Verification Dose Ensures Sterility
• Study verifies irradiation dose is effective.
• Verification Dose at SAL level of 10-2.
• Sterilization Dose is established at SAL of 10-6
• Assuming all standards are met, the process is validated.
Why Understanding Bioburden and SterilizationIs Key to Successful Device Development – April 2, 2015
Sterilization Validation Methods and Test Samples Needed
• Validation Method
• VDmax versus Method I
• Full Validation versus Single Lot release
• Samples Needed
• Dose Map Study
• Bioburden Determination
• Verification Dosage
Why Understanding Bioburden and SterilizationIs Key to Successful Device Development – April 2, 2015
Most Common Sterilization Modalities
When applied correctly, EO, Gamma, E-beam/X-ray are all safe and effective technologies for sterilizing medical products, each having its own advantages and disadvantages.
• Ethylene Oxide• Highly reactive Gas Sterilant• Residuals and Environmental Concerns
• Gamma• Radioactive Cobalt 60 • Environmental and Security Concerns
• E-Beam /X-ray• Processing flexibility for Combination Devices and Sensitive Materials• Works quickly (a matter of minutes in small lots) which aids product
efficacy
Why Understanding Bioburden and SterilizationIs Key to Successful Device Development – April 2, 2015
How Radiation Sterilization Can Affect Devices
• Cross-Linking or Chain Scission
• Oxidation and Discoloration
Key Point: Minimizing damaging changes
Why Understanding Bioburden and SterilizationIs Key to Successful Device Development – April 2, 2015
Why 25 kGy is Not Always the Answer
• Combination devices and sensitive materials
• Low bioburden levels for these types of devices can be the difference in achieving successful sterilization
• Validating at 20 kGy, 17.5 kGy, 15 kGy
Why Understanding Bioburden and SterilizationIs Key to Successful Device Development – April 2, 2015
Optimizing Sterilization of Sensitive Materials With E-beam/X-ray
• Material Compatibility
• Customized Processing Conditions
• Dose Uniformity Ratio (DUR)
• MAP (modified atmosphere packaging)
Why Understanding Bioburden and SterilizationIs Key to Successful Device Development – April 2, 2015
Quarterly Bioburden and Dose Audits
• Frequency of Audits
• Quarterly, with possible reduction in frequency
• Bioburden Testing and Verification Dose
• Augmenting Dose if Product Audit Fails
Why Understanding Bioburden and SterilizationIs Key to Successful Device Development – April 2, 2015
Case Study-Microfluidic Plates
• Highly sensitive device
• Sterilization successful at Low Dose but not higher Dose levels
• Requires very low Bioburden levels in order to be validated at Dose level requisite for device
• ‘Spikes’ in Bioburden levels
Why Understanding Bioburden and SterilizationIs Key to Successful Device Development – April 2, 2015
Case Study-Microfluidic Plates
• Process Design
• Monitoring Bioburden
• Implementing Regimented Program to control Bioburden
Why Understanding Bioburden and SterilizationIs Key to Successful Device Development – April 2, 2015
How to Ensure a Successful Dose Audit
Q: How to we prevent events like in the case study?
A: Know as much about your production environment and process as possible, and potential sources of contamination
Why Understanding Bioburden and SterilizationIs Key to Successful Device Development – April 2, 2015
An effective program to control microorganism levels in the manufacturing environment is essential to minimize the bioburden on the medical device being manufactured.
Why Understanding Bioburden and SterilizationIs Key to Successful Device Development – April 2, 2015
Monitoring and Trending Bioburden –part 1
• Environmental Monitoring
• Air quality
• Water quality
• Surface cleanliness
• Product Bioburden Over Time
• Material / component bioburden
• Packaging bioburden
Why Understanding Bioburden and SterilizationIs Key to Successful Device Development – April 2, 2015
Monitoring and Trending Bioburden –part 2
Bioburden Spikes: an unexpected bioburden level well above the mean.
• Common in manually assembled devices
• If bioburden data shows extreme variability, process should be investigated
Why Understanding Bioburden and SterilizationIs Key to Successful Device Development – April 2, 2015
Monitoring and Trending Bioburden –part 3
Setting allowable limits• Alert levels: “An established microbial or nonviable particle level giving
early warning of potential drift from normal operating conditions…” (PDA TR #13)
• Action limits / levels: “An established microbial or airborne particle level that, when exceeded, indicates a process is outside of its normal operating range.” Needs investigations and corrective action.
Resources• ISO 11737 section A 8.5
• PDA Technical Report No. 13 – Fundamentals of an Environmental Monitoring Program
Why Understanding Bioburden and SterilizationIs Key to Successful Device Development – April 2, 2015
Changes in bioburden levels can alert you to a potential problem before it gets so large that it affects your sterility program.
Why Understanding Bioburden and SterilizationIs Key to Successful Device Development – April 2, 2015
How Can We Limit and Control Bioburden?
1. Personnel and training programs
• For medical devices, contamination resulting from human handling and contact makes up the bulk of bioburden
Training areas:• Personal hygiene / cleanliness• Patient safety hazards posed by a
contaminated product
Why Understanding Bioburden and SterilizationIs Key to Successful Device Development – April 2, 2015
How Can We Limit and Control Bioburden?
2. Cleaning Processes
Areas of Focus:•Production areas•Storage areas•Production equipment
Cleaning Agents:•Sanitizers•Disinfectants •Sporicides
Cleaning agent
InSpec OX Sporicide
Why Understanding Bioburden and SterilizationIs Key to Successful Device Development – April 2, 2015
How Can We Limit and Control Bioburden?
3. Control of the Device Itself
• Device Storage
• Components – how processed and stored before assembly
Contract manufacturing – may pose difficulties, but important to monitor
Why Understanding Bioburden and SterilizationIs Key to Successful Device Development – April 2, 2015
How Can We Limit and Control Bioburden?
4. Device Design – what are some device design choices that can lead to greater bioburden levels?
• Adhesives – selection and use
• Small crevices and nooks in device
• Channels – these can gather microorganisms
Why Understanding Bioburden and SterilizationIs Key to Successful Device Development – April 2, 2015
In Summary
• Know your device bioburden!• Bioburden levels affect your sterilization program• Bioburden must be monitored and tracked on a regular
basis• Be aware and catch issues before they require corrective
action• Monitoring, training, and controlling production areas are
key
Deliver safe and effective products to people that need them
Thank you for you attention!
Why Understanding Bioburden and SterilizationIs Key to Successful Device Development – April 2, 2015
References
• Bioburden Testing: ISO 11737-1
• Radiation Sterilization Program Validation: ISO 11137
• Environmental Monitoring: PDA Technical Report No. 13
• General Information:
• Pacific BioLabs Sterility Assurance Compliance Booklet
• Pacific BioLabs Website
• NUTEK Corporation Website
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