This document discusses validating that medical devices are clean after manufacturing. It notes that being sterile does not necessarily mean being clean. It recommends establishing acceptance criteria for residue levels on devices through testing methods like gravimetric analysis, total organic carbon measurement, and particulate counting. Test results should be monitored over time according to a routine schedule and sampling plan to ensure manufacturing processes control residue levels and meet regulatory standards for patient safety and compliance. Process validations can reduce risk by limiting unnecessary contamination sources and making contaminants easy to remove from devices.

1. © Nelson Laboratories 2014
Process Validations for
Newly Manufactured
Devices
Is Your New Device Clean?
BIOMED Boston
26 March 2014
1:40pm
Tech Theater #921
Alexa Tatarian
Chemistry Study Director
Nelson Laboratories

2. MedTech Clinical Significance
© Nelson Laboratories 2014
Clean
Biocompatible
Sterile
Just because
something is
sterile, it does
not mean that it
is necessarily
clean
WHAT?: Device Cleanliness

3. Standard Information
• 21 CFR Part 820: Production and Process
Controls (manufacturing material)GMP Requirement
• Standard Practice for Reporting and
Assessment of Residues on Single Use ImplantsASTM F2847
• New Guide for Validating Clean Lines for
Medical DevicesASTM WK33660
• New Practice for Establishing Limit Values for
Residues on Single Use ImplantsASTM WK32535
© Nelson Laboratories 2014

4. Regulatory Concern
Recalls
Liability from
manufacturing
material being
introduced to the
patient
Increased
awareness in
GMP audits for
manufacturers
© Nelson Laboratories 2014
WHY?: Patient Safety and Regulatory Compliance

5. Mock Manufacturing and
Cleaning Process
© Nelson Laboratories 2014
Machining
De-
Burring
Grit
Blast
Rough
Clean
Polish
Rough
Clean
Laser
Mark
Passivation
Final Clean
with
Detergent
Oil
Particulates
Detergent
Water
Contamination
Polishing
Compound
Nitric/Citric
Acid

6. Reduce Risk in the Process
Choose
biocompatible
agents
Easy to
remove
Streamline
processes
© Nelson Laboratories 2014
Limit introduction of
unnecessary sources
of contamination

7. How to Validate
Test Options Benefit Types of
Residuals
Result
Gravimetric
Extractable Residue
(ASTM F2459)
Quantify Residue Oils, lubricants,
detergents, coatings,
particulates, etc.
Weight of residue (mg,
mg/device, or mg/cm²)
Total Organic Carbon
(TOC)
Quantify Residue Detergents, alcohols,
organics, etc.
TOC readout
(ppb, µg/device, µg/cm²)
Detergent Residuals
(UV/VIS)
Quantify Residue Detergents mg/device, mg/cm²
Particulates (USP 788) Quantify Residue Particulates Count ≥10µm and ≥25µm
Cytotoxicity
(ISO10993-5)
Show if residue is
cytotoxic
Anything cytotoxic Pass/Fail
Bioburden Microbiological
examination
Aerobic bacteria and
fungi
Quantitative CFUs
Bacterial Endotoxin Microbiological
examination
Gram-negative
bacteria
Pass/Fail
Quantitative EUs
© Nelson Laboratories 2014
HOW?

8. Acceptance Criteria
Positive
Controls
Unclean
devices
compared to
clean devices
Historical
Data
Trend data
Alert and
Action
Levels
Additional
Tests
Cytotoxicity
Microbiological
Tests
Compare to
Toxicological
Data
NOAEL,
LOAEL, LD50,
etc.
© Nelson Laboratories 2014

9. Routine Monitoring
Schedule
Routine
Monitoring
Weekly Monthly Quarterly
Semi-
annually
Control
process
Alert
Levels
Action
Levels
Change Evaluate Accept Reject
© Nelson Laboratories 2014
Once acceptance criteria has been established:

10. Sampling Plan
Group together when possible
Material types
• (SS, Ti, PEEK, etc.)
Processes
• Similar contaminants
Worst Case
Most difficult to clean Most concerning residuals
© Nelson Laboratories 2014

11. Thank you!
© Nelson Laboratories 2014
Alexa Tatarian
Study Director
Nelson Laboratories
801-290-7910
atatarian@nelsonlabs.com