Megan Anderson, QTS Project Engineer. March 8 10, 2011 Hyatt Regency Cincinnati, OH

Transcription

1 Megan Anderson, QTS Project Engineer March 8 10, 2011 Hyatt Regency Cincinnati, OH

2 Megan Anderson, QTS Project Engineer 2

3 Medical devices that are oxygen sensitive must be packaged using equipment that can modify the atmosphere of the package, otherwise known as modified atmosphere packaging (MAP)

4 Product Development What we know today about improving the process Equipment M.A.P. Difficulties Encountered Testing Case Study

5 Agenda QTS Background Medical Device Packaging Level of complexity Usage Requirements UHMWPE MAP Case Study 5

6 QTS Overview Cleanroom Assembly and Packaging Product Life Cycle Package Design Clean Assemble Package Sterilize Quality Focused ISO Certified Compliant FDA Registered 6

7 Medical Device Packaging Packaging complexity driven by the device

8 Dental Implants Common coatings Similar geometry

9 Spinal Implants Metals / Ceramics Pre-oxidized (Passivated) Common size / shape

10 Orthopedic Implants Increasing sophistication of ortho devices Different material UHMWPE Sterilization difficulties Blind Holes Long term storage considerations not a simple piece of metal

11 Agenda QTS Background Medical Device Packaging UHMWPE MAP Case Study 11

12 UHMWPE Ultra High Molecular Weight Polyethelene First used clinically in 1962 by Sir John Charnley Modified to highly-crosslinked UHMWPE in late 1990 s Cross-linked with gamma/beam radiation and then thermally processed to improve its oxidative resistance 12

13 UHMWPE Ultra High Molecular Weight Polyethelene Subset of thermoplastic polyethylene Has extremely long chains 2-6 million MW Highest impact strength of any thermoplastic presently made 13

14 UHMWPE Material Why is UHWMPE Used Self-lubricating Low friction Superior wear resistance Biocompatability Think of articulating bearing surface in orthopedics Bearing surface of choice for TKA & THA A Stable Polymer (as opposed to degradable polymers (i.e. used in degradable suture)), a lasting polymer 14

15 UHMWPE Con s Sterilization (Gamma, EO) EO in an oxygen free environment Gamma radiation sterilization in the presence of oxygen What does O 2 do to UHWMPE? Oxygen binds to free radicals from the high-energy radiation process which breaks the long chains of UHMWPE Long term storage impact over time more oxygen into pkg more degradation More oxygen more the oxidation process will continue Decrease in molecular weight decrease mechanical properties implant fracture/failure.

16 Agenda QTS Background Medical Device Packaging UHMWPE MAP Case Study 16

17 What s Modified Atmosphere Packaging (MAP)? Practice of modifying the composition of the internal atmosphere of a package in order to improve the shelf life. Lower the amount of available oxygen (O2), moving it from 20% to 0%, in order to slow down the growth of aerobic organisms and slow the speed of oxidation reactions. Removed oxygen can be replaced with nitrogen (N2), commonly acknowledged as an inert gas, or carbon dioxide (CO2). 17

18 Where is MAP used? Food Pharma Commercial Medical Device

19 What s being done in the industry Food Goal to reduce oxidative rancidity, oxidation of vitamins, discoloration Vacuum packaging Vacuum and nitrogen purging ACTIVE PACKAGING SYSTEM O2 Absorbers as part of the packaging 19

20 What s being done in the industry Why no O2 absorbers Not tolerant Cost Resilience concerns Validation difficulties Medical Device Industry Films on packaging as an oxygen barrier (Silicone oxide, Aluminum oxide) Vacuum/nitrogen purging 20

21 OTR Barrier ability against oxygen Oxygen Gas Transmission Rate ASTM D1434, ASTM D < <4.0 Material Selection Tyvek vs Foil vs??? Measures 02 transmission rate through film OTR

22 Medical Device Packaging with MAP/UHMWPE Tyvek header foil pouch Double pouch (not double barrier) package (Tyvek inner, 2 nd phase foil outer) Double SiOx Pouch (Gamma)

23 Agenda QTS Background Medical Device Packaging UHMWPE MAP Case Study 23

24 Modified Atmosphere Packaging Case Study Femoral project that contained metal and UHMWPE material Gamma Sterilization (EO Failed) QTS set-up sealing process on standard vacuum sealer because no oxygen requirements at onset of project Previously packaged at another location 24

25 Original Sealer Selection / Specifications

26 Original Sealer Selection / Specifications QTS had other UHMWPE projects that only required a tight vacuum and had no oxygen requirements Impulse Heat Sealer (Pump) 1 cycle for nitrogen purge / vacuum Vacuum time, purge(gas) time, vac/gas order, low pressure One nozzle Nitrogen regulator Could adjust: Sealer bar closing pressure Nozzle retracting speed

27 Sealer 1 (Shrek)

28 Specification changed to Under 1% We stayed on the same sealer (Shrek) Set samples to outside service to test for O 2 samples were between 8 18% Another vacuum sealer available in house to try

29 2 nd Sealer

30 2 nd Sealer (Tarzan) Impulse Heat Sealer Multiple cycles for nitrogen purge / vacuum (either one first) Parameters include vacuum time, purge(gas) time, purge pressure, last purge time, cycle count, vacuum pressure regulator One nozzle 30

31 Why switch to 2 nd Sealer? Multiple vacuum cycles greatly lowered oxygen Consistent in relation to the cycles More variables to control

32 Sealer 2 (Tarzan) 32

33 More package testing required Testing in-house instead of sending samples out more cost-effective would be needed for in-process inspection during production Mocon Analyzer 33

34 Mocon Analyzer Specs Mocon Oxygen tester Pac Check Requires 5cc for automatic or 3cc for manual sampling Accuracy +0.1% O2 or 2% of reading, whichever is larger

35 Mocon Analyzer Testing Method Needle Foam septum Having enough air/volume Automatic vs. Manual Variability in Testing w/rigid specification

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37 Under 1%! 0.4%?!

38 Why under 0.4% Used in validations Validated at arbitrary value 510K submission callout Functionality Time vs. Requirement 38

39 What we did to achieve 0.4% Slower and Lower Start/end with vacuum Modify Nozzle Durometer of Sealer Bar Operator Manipulation

40 10 samples pass! sweet spot of vacuum / purge cycle, time, and pressure selected Operator manipulation of package required ERROR -1 ERROR %

41 Project Delayed!

42 Project delayed 6 months for unrelated reasons Used previous determined settings to test packages again Can t Get 10 In a Row! Under 0.4% was not achieved consistently 42

43 Now What?! How do we modify without breaking current production Have ambient air go out one line and nitrogen in separate line instead of having it the same line (not implemented) Leave the pouch slightly puffed (end on purge cycle) Press pouch down during cycle. Try and excavate more air than the nozzle will vacuum out. 43

44 Theories why samples were Analyzer not repeatable Calibration? Test Method? Tolerance? False positive Ambient/environment variables Pouches 6 months older Difficulty in validation sealing process Equipment moved in cleanroom New equipment in cleanroom Nitrogen tank low 44

45 MAP Case Study No Oxygen Spec initially sealer #1 Under 1% - sealer #2 Under 0.4% - 10 samples work 6 Month Delay outcome not repeatable New solution 45

46 Vacuum Chamber Sealer (proposed new sealer) Sealer removes oxygen from the entire environment, diffuses the purge gas, and creates a package seal. 46

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48 Vacuum Chamber Sealer (proposed new sealer) Sealer removes oxygen from the entire environment, diffuses the purge gas, and creates a package seal. 48

49 In Conclusion 49

50 Thank you!! Booth #37