Chemical and Bioanalytical Approaches for the Analysis of

Catheters and Drug Coated Balloons

Erik Foehr, Ph.D.Vice PresidentPacific BioLabs

Chemical Characterization of Catheter Devices – Pacific BioLabs, 2014

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

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

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

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

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

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

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

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

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

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

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

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

• Paclitaxel coated balloon catheter• Animal study of

catheter safety and efficacy.

• Measurement of residual paclitaxelfrom balloon surface by HPLC.

Paclitaxel Concentration

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Chemical Characterization of Catheter Devices – Pacific BioLabs, 2014

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