Design and Manufacturing Considerations for

Medical Device CoatingsKeith Edwards, President

Biocoat, Inc.

Devices that benefit from a coating:Guide wires

PTCA catheters

IOL insertion cartridges

Micro-catheters

Clot retrieval wires

Delivery Sheaths

Stent delivery systems

Embolic delivery

Implant delivery

Endoscopes

Why have a coating?

• Common device substrates are not lubricious on their own.

– Nylon

– Pebax

– Urethanes

– Metals: SS, Pt, Ni, Ti

– Nitinol

– Silicones– Plasma treatment may be required

Ability to navigate complex vasculature

Improved patient comfort

Lubricity and durability

Guide wire example:

Multiple passes

Rotational tracking

Biocompatibility

Low particle counts

Regulatory Considerations

• Design Inputs should include several options that meet your design requirements:

Lubricity

Durability

Biocompatibility – ISO 10993

• Cytotoxicity (MEM Elution)

• Hemolysis (Direct Contact Method)

• Irritation (Intracutaneous Reactivity)

• Systemic Toxicity (Systemic Injection)

• Partial Thromboplastin Time (PTT)

• USP 788 - Particulates

Thickness

Test method: is the test environment reflective of the use?

Case Example: FDA Examiner Inquiry

• Coating Integrity: FDA recommends that you provide quantitative analysis of the presence/absence of coating pre- and post-simulated use. In your coating integrity test reports you should include a detailed discussion of the surfaces using any practical methods to quantify defects. This may include counting the number of total defects per unit area, measuring representative defect areas, and measuring worst-case defect areas. You should support your discussion with representative images (including worst-case) at a sufficient magnification to characterize the defects. Multiple magnifications may be needed to visualize and adequately characterize the product. The discussion of acceptable coating integrity should include a justification that the number and size of defects observed will not impact clinical performance.

Technical Coating Considerations

• Will my coating stick?

• What particle counts may I anticipate?

• Verification of coating presence

• QA/QC testing & sampling

• PVP vs. HA

• Surface Energy

• Contact angle

• Unreacted monomers

• Plasticizers & bloom

• Humidity

• Sterilization methods

• Heat cure vs. UV cure

7

HA Coating Platform

Covalent bondsIsocyanate linkage

Mechanical AdhesionAdsorption

ElectrostaticMechanical interlock

PVP – A matrix of cross-linked polymers of various molecular weights

Hydrophilic Coating Flow chart

Catheterswith coating

mandrels

Top coat cure

Apply Base coat

Apply Top coat

Base coat Dry

Base coat formulation

Inspection and QC testing

Packaging

Enemies of Adhesion

Surface preparation & Fixturing

Unclean surface . Too fast cure . Substrate contact angle too high

Performance: Pinch Friction test

• Pinch testing on 10 uncoated and 10 coated tubes to evaluate frictional forces. Pinch testing parameters:

– Load : 470 grams

– Number of cycles: 30

– Pinch pad material: Delrin or Silicone

– Phosphate Buffered Saline (PBS) bath at 37C

• Trackability testing on 10 coated tubes to measure insertion and pulling forces

• Design team to define friction specification and failure mode• Comment: Delrin pads harder on coating; display better lubricity. Silicone pads

softer on coating; display higher friction.

Other tests: Bound top coat,Swelling ratios &

rotational tracking

-40

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20

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80

-0.5 0 0.5 1 1.5 2 2.5 3 3.5

Friction, gram_force

Distance, inch

PETG T67 pbs-1 pinch force 770 gram __TRACES

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30

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60

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Friction, gram_force

Cycle

PETG T67 pbs-1 pinch force 770 gram __Pulling Stage

Dyn.

Static

Peak

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-50

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Friction, gram_force

Distance, inch

PETG T70/B23 E-12w-1 pinch force 770 gram __TRACES

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0 5 10 15 20 25 30 35

Friction, gram_force

Cycle

PETG T70/B23 E-12w-1 pinch force 770 gram __Pulling Stage

Dyn.

Static

Peak

Head to Head Comparison

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Cycle

Dynamic Friction Pulling Over 30 Cycles

N=3, delrin pads, 470g load, 30 cycles

Got Slick?Hydration is part of the procedure.

Biocoat Research: Dry pinch test protocol

• Immerse coated guide wire into DI H2O (or PBS) for 1min. Note

humidity.

• Remove GW from water and test lubricity of the wetted GW

imminently (initial point) by pulling through the pinch tester pads

(using silicone pads or delrin pads and 470G load)

• Test lubricity after kept the GW out of DIW at room temperature for 1,

2, 3, 4, 5 min. or until the coating shows high friction

• Immerse the tested GW into PBS or DI H2O for 1min

• Test the lubricity (Re-hydrate)

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age

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Distance (inch)

A-14: Delrin-pads & 470G

Initial

1min

2min

3min

4min

5min

Re-hydrate

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Stag

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(g)

Distance (inch)

A-14: Silicone-pads & 470G

Initial

1min

2min

3min

4min

5min

Re-hydrate

Open air Time Pinch Test

Humidity: 66.5-67% & Temp.: 21-22oC

DIW H2O Hydrated

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A-14: PBS Hydrated

initial

1min

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3min

Re-hydrate

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A-14: DIW Hydrated

initial

1min

2min

3min

4min

5min

Re-hydrate

Open air Pinch Test: Delrin-pads & 470g

Humidity: 53-55% & Temp: 21-21.5oC

Weight gained after soaking in PBS for 1 min.:

0.007g

After 3min.: 0.002g remained

(4” length GW: 0.0323” OD)

Weight gained after soaking in DIW for 1min.:

0.0077g

After 5min.: 0.0016g remained

(4” length GW : 0.0323” OD)

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Distance (inch)

A-14: PBS Hydrated(Humidity: 44%)

initial

1min

2min

3min

4min

Re-hydrate

Open air Pinch Test: Silicone-pads & 470g

Humidity: 41-44.5% & Temp: 21-21.5oC

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Pu

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age

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g)Distance (inch)

A-14: DIW Hydrated(Humidity: 41%)

initial

1min

2min

3min

Re-hydrate

Weight gained after soaking in PBS for 1 min.:

0.0057g

After 4min.: 0.0009g remained

(4” length GW : 0.0323” OD)

Weight gained after soaking in DI H2O for 1min.:

0.0092g

After 3min.: 0.0033g remained

(4” length GW : 0.0323” OD)

Particulates ≥ 10µmLow Friction - Low particulate

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Number of Particles ≥ 10 µm

Small Particle Correlation to Lubricity

USP 788 limits = 6000 particle/mlParticles are Hyaluronic acid, will degrade in-vivo

Particulates ≥ 25µmLow Friction - Low particulate

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Number of Particles ≥ 25 µm

Large Particle Correlation to Lubricity

USP 788 limits = 600 particle/ml

Coating Business Models

• Cost of Reagents

• Royalty & rate

• Tiered or flat rates

• Term and amount

• Quarterly minimums

• License fee

• One time or for each device?

• Cost per device

• Batch size/throughput per shift

• Waste

• Equipment

• Service agreements

Coating Economics

• Actual cost of coating per device is $0.25 to $1.75

• Cost of application – fully loaded- may be $6 to $50 per device

• For costs under $5 high volume is required

• Minimize waste

• Annual volumes under 30,000 – contract coating service

• Higher volumes – coat in house or at a tubing/wire vendor

• International manufacturing locations

• Investments vary & clean room needed

R&D & Innovation

• R&D

– Cost reduction initiatives: shorter cycle times, waste reduction & shelf life of reagents.

– Characterization of coatings: particle counts and related testing parameters on a wide variety of substrates.

• Innovation

– Gamma and e-Beam sterilization

How do I know my coating is there?

Without destructive testing?

Coated

Uncoated