Examining issues and methods in analytically characterizing the materials of medical devices including catheters and drug coated balloons.

1. Chemical and Bioanalytical
Approaches for the Analysis of
Catheters and Drug Coated Balloons
Erik Foehr, Ph.D.
Vice President
Pacific BioLabs

2. Pacific BioLabs
• BioPharmaceutical and
Medical Device CRO
• Three Functional Areas
• Toxicology
• Microbiology
• Analytical
• Focus on personalized,
attentive service
• 30-year history
• GMP and GLP Compliant
Laboratories
Chemical Characterization of Catheter Devices – Pacific BioLabs, 2014

3. Why chemical characterization of
medical device materials?
• Analytical chemistry studies help to evaluate
hazards that are associated with the device or
manufacturing process
• Support process control in manufacturing
• Demonstrate equivalency of proposed
materials to a clinically established material
Chemical Characterization of Catheter Devices – Pacific BioLabs, 2014

4. Approach to characterization
• Review regulatory guidances for device type
• Design chemical characterization study
• Identify instrumentation and analysis
• Perform chemical classification and possible
identification
• Provide risk assessment with chemical and
biocompatibility data
• Support regulatory filing
Chemical Characterization of Catheter Devices – Pacific BioLabs, 2014

5. Regulatory guidance
• ISO Guidance for Biological Evaluation of Medical
Devices
• 10993 Part 12: Sample preparation and reference
materials
• 10993 Part 18: Chemical characterization of materials
• FDA
• GLP 21 CFR Part 58
• GMP 21 CFR Part 210 & 211
• USP and ICH
• Elemental Impurities by USP <232> and <233>
• Elemental Impurities Guideline ICH Q3D
Chemical Characterization of Catheter Devices – Pacific BioLabs, 2014

6. Chemical characterization
• Considerations for the analytical approach
• Intended use of device
• Contact time (blood, mucosal, skin contact)
• Material composition
• Surface area calculations
• Extractables
• Design study and choose solvents, temperature, and
duration
• Leachables
• Consider drug formulation (buffer, salts, etc)
• Storage and handling of drug and delivery device or
container
Chemical Characterization of Catheter Devices – Pacific BioLabs, 2014

7. Instrumentation and analysis
• Gas Chromatography (GC) for volatile organics
• GC with Mass Spectrometry (MS) detection for
analyte identification
• High Performance Liquid Chromatography (HPLC)
• HPLC with MS detection for non-volatile /semi-volatile
analyte identification
• Inductively Coupled Plasma Mass Spectrometry
(ICP-MS) for elemental analysis -heavy metals and
other process impurities
Chemical Characterization of Catheter Devices – Pacific BioLabs, 2014

8. Chemical classification and
identification
• Heavy Metals and other elements from the
needle or tubing may leach or be extracted
from the device.
• Polymers/Lubricants from the device or
manufacturing process can be monitored by
HPLC with laser light scattering or LC/MS.
• Solvents, plasticizers, and degradation
products are often identified by GC/MS.
Chemical Characterization of Catheter Devices – Pacific BioLabs, 2014

9. Compound classification and risk
assessment
• Gather information about the device material,
processing, cleaning, packaging, storage
• Test material for Leachables & Extractables
• A toxicologist can help assess risk. They can
search chemical compound databases and
calculate safe exposure levels.
Chemical Characterization of Catheter Devices – Pacific BioLabs, 2014

10. Case studies of catheter material
• Long History of Use
• Types of materials
• Silicones
• Polyvinyl Chloride
• Latex Rubber
• Polymeric coatings
• Chemical characterization
Chemical Characterization of Catheter Devices – Pacific BioLabs, 2014

11. Catheters for chemotherapy
• Many chemotherapy agents
need to be delivered via
catheters to ensure proper
dosage and localized delivery
• The catheter may be a
temporary angiocatheter or
implanted/tunneled catheter.
• The catheter must be safe, have
minimal extractables &
leachables and effectively deliver
the chemotherapy agent.
Chemical Characterization of Catheter Devices – Pacific BioLabs, 2014

12. Leachables, Extractables, and
Adsorption
• Analysis of commonly used chemotherapy agents
in catheter assemblies
• Do chemicals from the catheter assembly leach into
the formulated drug?
° Measure semi-volatile and volatile organics by GC/MS
° Measure inorganics (heavy metals) by ICP-MS
• Extract chemicals from the catheter assembly
° Place catheter into solvents such as water or ethanol at
elevated temperature (50 °C) for 24-72 hours and test for
chemical “fingerprints” with GC, GC/MS, LC/MS, or ICP-MS.
• Does the drug adhere to the catheter surface?
° Measure drug concentration before and after incubation
with catheter using HPLC or other analytical approach.
Chemical Characterization of Catheter Devices – Pacific BioLabs, 2014

13. Drug coated balloon catheter
• Paclitaxel coated balloon
catheter
• Analysis of paclitaxel
concentrations in blood from
animal studies using LC/MS.
• Measurement of residual
paclitaxel from balloon surface by
HPLC.
• Analysis of matrix or coating
components
° Measure kinetics of paclitaxel release
from catheter surface
Chemical Characterization of Catheter Devices – Pacific BioLabs, 2014

14. • Paclitaxel coated
balloon catheter
• Animal study of
catheter safety
and efficacy.
• Measurement of
residual paclitaxel
from balloon
surface by HPLC.
Chemical Characterization of Catheter Devices – Pacific BioLabs, 2014
Paclitaxel Concentration
Area Counts

15. Summary
• Biocompatibility and chemical
characterization of medical devices is key to
success
• Follow the guidances and use a solid scientific
rationale
• Utilize modern analytical techniques and
instrumentation
• Provide risk assessment using chemical,
biocompatibility and patient exposure data
Chemical Characterization of Catheter Devices – Pacific BioLabs, 2014