Originator: Barbara Tou

Re: Feasibility Study for Replacement Adhesive in Codman 3000 Refill Kit

Date: October 21, 2015

Objective:

Find a replacement adhesive for Loctite 3011 in the Codman 3000 Refill Kit (Catalog number AP-07014,
DWG-981 Rev H).

Purpose:

The Loctite 3011 that is currently used to attach the male and female luers to the tubing in the Codman
Refill Kit has been discontinued. The purpose of this study is to find another adhesive to replace Loctite
3011 while maintaining the pull force specification of 5 lbs that is required on this Refill Kit. The best
adhesive to replace Loctite 3011 can be identified by pull testing tube sets made with these various
potential alternative adhesives and comparing the resulting data. These potential alternatives were
determined to be Loctite 3301 and Loctite 3921. The pre-made Codman 400 Refill kit was also pull force
tested because it contains the same luers on a similar tubing material but is attached with different
adhesives from a manufacturer called Aqua Solutions.

Procedure:

Thirty sample Refill Tube sets were assembled for each alternative Loctite adhesive at Contech Medical,
the manufacturer of the Codman 3000 Refill Kit Tube Set. Both Loctite 3301 and 3921 have viscosities
that are similar to Loctite 3011 and as a result could be set to the flow at the same rate as the
discontinued Loctite 3011 and used the same size needle to dispense the adhesive.

To attach the luers in this experiment we followed the same process used at Contech to produce the
Codman 3000 Tube Sets. Two droplets of adhesive were placed 180 degrees from each other around the
tube and a few millimeters apart on the ends of the tubing as seen in Figure 1. The luer was then slipped
onto the tube in a twisting motion to allow the adhesive to wick and contact the maximum amount of
surfaces between the luer and tube. The setup of this process is displayed in Figure 2. All of these tube
sets were cured by UV lighting for 15 seconds from above the sample followed by another 15 seconds
from below the sample. Once cured, the tube sets were pull tested to destruction. The type of failure, in
the bond or in the tube, was noted along with the force at which each tube failed.
Results:

Normality
Average Maximum Minimum
n Standard Deviation Test
(lbs) (lbs) (lbs)
p-value
Loctite 3301 Female Luer 30 9.438 0.57 10.19 8.43 0.05
Loctite 3301 Male Luer 30 9.94 1.11 11.97 7.85 0.174
Loctite 3921 Female Luer 30 9.57 0.41 10.23 8.55 0.223
Loctite 3921 Male Luer 30 9.78 1.47 12.28 7.37 0.397
Codman 400 Female Luer 10 9.017 0.393 9.57 8.31 0.644
Codman 400 Male Luer 10 8.526 0.484 9.53 7.99 0.257
n = number of samples

Discussion:

There are three tests that the Codman 3000 Refill Kit Tube Set must pass: flow, pressure and pull (DWG-
981 Rev H). According to Contech, the manufacturer of these tube sets, the first two tests rarely result
with non-conformists while the third generally causes the most failures. During the pull tests for Loctite
3301 and Loctite 3921, it was observed that the majority of the failures were a result of the tube breaking,
not the bond failing. The trend was also that the male luers tended to fail at the bond more often than the
female luers did. This could be attributed to the male luer having a slightly larger inner diameter than the
female luer with its dimensions of .090 /.085 inches while the female luer has its inner diameter
dimensions of .088/.079 inches. This difference affects the ease with which the luers are attached to the
tubing and could be related to how much or how little strength is required to pull the tube set to failure.
The table in the Results section shows that the male luer has a larger range of strengths that it fails in
compared to the female luer. A cause for this discrepancy in bond strength could also be due to the
difference in materials that the luers are made of; the male luer is acrylic while the female luer is
polyester.

Each data set reported in the table above was tested for normality. A standard acceptance criteria was
used where the reported p-value was required to be great than or equal to .05 (i.e. 5%). The results show
that all of the data sets met or exceed this criteria. The Probability Plots associated with each data set
can be found in Figures 3 through 8.

Taking the strengths at which each tube failed for both Loctite 3301 and Loctite 3921 the estimated pull
test failure rates gave values of 0.0005%, or 1 in 200,000 and 0.0245%, or 1 in 5,000 respectively.
According to the data, seen in Table 1, collected from April 2015 until October 2015, the failure rate of the
current tube set using Loctite 3011 is 0.128% or 1 in 1,000. Both Loctite 3301 and 3921 have lower failure
rates than Loctite 3011, therefore, either one would be an improvement to the performance of the tube set
according to these estimates. The average strength it took for the tube sets to fail, where they failed and
their standard deviations can be seen in Table 2 for Loctite 3301 and Table 3 for Loctite 3921.

The adhesives in the Codman 400 Refill Tube set are 25% Cyclohexanone/ 75% Ethylene Dichloride on
the male luer and 50% Cyclohexanone/ 50% Methylene Chloride on the female luer. This tube set is
assembled at Command Medical located in Ormond Beach, FL. Based on these low pull test results the
Codman 400 Tube Set is not believed to be a viable replacement option for the Codman 3000 Tube Set.

In the next phase of testing, some factors that may affect the strength of the bond and potentially warrant
investigation are: droplet volume, the number of droplets applied to the tubing, the duration and intensity
of the cure, how far the luer is twisted when attaching it to the tube, the needle size through which the
adhesive is dispensed, and the distance and placement of the droplets on the tubing.
Conclusion/Recommendation:

In this feasibility test, we were able to use the current standard process settings and equipment at
Contech Medical to successfully produce tubes sets with both Loctite 3301 and Loctite 3921. Both Loctite
3301 and Loctite 3921 will likely improve the performance of the tube set with regards to the pull test,
especially in the male luer which generally had less consistent positive results than the female luer Loctite
3301 is the recommended material of choice because it had the lowest pull test failure rate (estimated at
1 in 200,000 vs. Loctite 3921s rate of 1 in 5,000). Further process development and process validation
will be required before Loctite 3301 can be approved for production.
Figure 1: Adhesive Droplet Placement

Figure 2: Work Bench Set Up

Figure 3: Probability Plot of Loctite 3301 on Female Luer

Figure 4: Probability Plot of Loctite 3301 on Male Luer

Figure 5: Probability Plot of Loctite 3921 on Female Luer

Figure 6: Probability Plot of Loctite 3921 on Male Luer

Figure 9: Probability Plot of Loctite 400 on Female Luer

Figure 10: Probability Plot of Loctite 400 on Male Luer

Table 1: Pull Test Data for Current Tube Set with Loctite 3011 from April to October

Lot Number Number

Test Date Total
Number passed Failed
15D391CT 4/29/2015 58 0 58
4/29/15 -
15D392CT 58 0 58
4/30/15
15D495CT 5/27/2015 58 0 58
15E393CT 5/27/2015 58 1 59
15E394CT 5/28/2015 58 0 58
5/28/15-
15E395CT 58 0 58
5/29/15
15E485CT 5/29/2015 59 0 59
15E486CT 5/29/2015 26 0 26
15J271CT-
9/23/2015 58 0 58
1
15K012CT 10/5/2015 58 0 58
15K013CT 10/6/2015 58 0 58
15K056CT 10/6/2015 58 0 58
10/6/15-
15K057CT 58 0 58
10/7/15
15D389CT 4/28/2015 60 0 60
Total 4/28 - 10/7 783 1 784
 Table 2: Pull Test Data for Loctite 3301 on Male and Female Luers

Loctite 3301 Female Luer Loctite 3301 Male Luer

Sample Failure Type Strength (lbs) Sample Failure Type Strength (lbs)
1 Tube 10.01 1 Tube 8.52
2 Tube 10.19 2 Bond 8.09
3 Tube 9.39 3 Tube 11.49
4 Tube 9.43 4 Bond 10.22
5 Tube 10.19 5 Tube 10.5
6 Tube 9.93 6 Tube 10.88
7 Tube 9.86 7 Tube 8.8
8 Tube 9.82 8 Tube 10.35
9 Tube 10.07 9 Tube 10.41
10 Tube 8.84 10 Tube 10.56
11 Tube 10.14 11 Bond 8.67
12 Tube 8.52 12 Bond 8.46
13 Tube 9.71 13 Tube 9.32
14 Tube 8.77 14 Tube 11.97
15 Tube 10.01 15 Tube 10.44
16 Tube 9.6 16 Tube 9.18
17 Tube 9.76 17 Tube 11.3
18 Tube 9.4 18 Tube 9.57
19 Tube 9.84 19 Tube 10.99
20 Tube 8.85 20 Tube 10.47
21 Tube 8.43 21 Bond 7.85
22 Tube 8.64 22 Tube 10.37
23 Tube 9.38 23 Tube 11.36
Test failed 24 Tube 10.52
24 to start n/a 25 Tube 11.39
25 Tube 9.57 26 Tube 9.53
26 Tube 9.23 27 Tube 8.68
27 Tube 9.26 28 Tube 10.17
28 Tube 8.58 29 Bond 9.04
29 Tube 10.1 30 Tube 9.11
30 Tube 9.04 Total Tube Failures: 24
31 Tube 8.58 Total Bond Failures: 6.00
Total Tube Failures: 30 Average: 9.94
Total Bond Failures: 0 Standard Deviation: 1.11
Average: 9.438 Z-score -4.4334
Standard Deviation: 0.57
Z-score -7.7856
 Table 3: Pull Test Data for Loctite 3301 on Male and Female Luers

Loctite 3921 Female Luer Loctite 3921 Male Luer

Sample Failure Type Strength (lbs) Sample Failure Type Strength (lbs)
1 Tube 9.26 1 Bond 7.51
2 Tube 9.64 2 Tube 11.05
3 Tube 10.05 3 Tube 9.23
4 Tube 9.11 4 Tube 11.97
5 Tube 9.26 5 Tube 8.29
6 Tube 9.3 6 Tube 10.64
7 Tube 10 7 Tube 11.19
8 Tube 9.76 8 Tube 12.28
9 Tube 10.09 9 Tube 12.16
10 Tube 9.62 10 Tube 11.43
11 Tube 10.11 11 Tube 9.68
12 Tube 10.23 12 Bond 9.45
13 Tube 9.62 13 Tube 10.26
14 Tube 9.95 14 Tube 9.79
15 Tube 9.04 15 Tube 9.62
16 Tube 9.31 16 Tube 10.11
17 Tube 9.83 17 Tube 8.21
18 Tube 8.93 18 Tube 11.74
19 Tube 10.03 19 Bond 8.13
20 Tube 8.55 20 Tube 10.46
21 Tube 9.77 21 Tube 9.93
22 Tube 9.96 22 Tube 10.73
23 Tube 9.41 23 Bond 8.2

24 Tube 9.74 24 Bond 7.6

25 Tube 9.17 25 Bond 10.69
26 Tube 9.28 26 Bond 7.37
27 Tube 9.38 27 Bond 8.46
28 Tube 9.26 28 Bond 7.72
29 Tube 9.44 29 Tube 9.6
30 Tube 9.97 30 Tube 10.07
Total Tube Failures: 30 Total Tube Failures: 21
Total Bond Failures: 0.00 Total Bond Failures: 9
Average: 9.91 Average: 10.1115625
Standard Deviation: 0.41 Standard Deviation: 1.466122457
Z-score -11.8717 Z-score -3.4864
 Table 4: Pull Test Data for Codman 400 on Male and Female Luers

Codman 400 Female Luer Codman 400 Male Luer

Failure Strength Strength
Sample Type (lbs) Sample Failure Type (lbs)
1 Bond 8.31 1 Bond 8.39
2 Bond 8.94 2 Bond 9.53
3 Bond 8.9 3 Bond 8.2
4 Bond 9.57 4 Bond 8.17
5 Bond 9.34 5 Bond 8.38
6 Bond 8.99 6 Bond 9.01
7 Bond 8.51 7 Bond 8.89
8 Bond 9.44 8 Bond 7.99
9 Bond 9.17 9 Bond 8.59
10 Bond 9 10 Bond 8.11
Average: 9.017 Average: 8.526
Standard Deviation: 0.392995618 Standard Deviation: 0.484428644
Z-score -10.2215 Z-score -7.2787