QTS Confidential March 8 – 10, 2011 Hyatt Regency Cincinnati, OH 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) Product Development What we know today about Equipment improving the process M.A.P. Difficulties Testing Encountered Case Study Agenda QTS Background Medical Device Packaging • Level of complexity • Usage Requirements UHMWPE MAP Case Study QTS Overview • Medical Device Outsourcing, including: Cleanroom Assembly and Packaging • Product Life Cycle • Package Design • Clean • Assemble • Package • Sterilize • Quality Focused • ISO 13485 Certified • 11607 Compliant www.qtspackage.com • FDA Registered • JPAL Compliant Medical Device Packaging • Packaging complexity driven by the device Dental Implants • Common coatings • Similar geometry Spinal Implants • Metals / Ceramics • Pre-oxidized (Passivated) • Common size / shape Orthopedic Implants • Increasing sophistication of orthopedic devices Different material – UHMWPE Sterilization difficulties – Blind Holes • Long term storage considerations – not a simple piece of metal UHMWPE • Ultra High Molecular Weight Polyethylene • First used clinically in 1962 by Sir John Charnley • Modified to highly-cross linked UHMWPE in late 1990’s • Cross-linked with gamma/beam radiation and then thermally processed to improve its oxidative resistance UHMWPE • Ultra High Molecular Weight Polyethylene • Subset of thermoplastic polyethylene • Has extremely long chains • 2-6 million MW • Highest impact strength of any thermoplastic presently made UHMWPE Material • Why is UHWMPE Used • Self-lubricating • Low friction • Superior wear resistance • Bio-compatability • 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 www.qtspackage.com UHMWPE Con’s • Sterilization (Gamma, EO) • EO in an oxygen free environment • Gamma radiation sterilization in the presence of oxygen • What does O2 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 packaging more degradation • More oxygen more the oxidation process will continue • Decrease in molecular weight decrease mechanical properties implant fracture/failure. 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). Where is MAP used? • Food • Pharmaceutical • Commercial • Medical Device 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 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 OTR • Barrier ability against oxygen • Oxygen Gas 300 250 Transmission Rate 200 150 <.006 260 <4.0 100 • ASTM D1434, ASTM 50 D3985 0 Material Selection Tyvek® vs. Foil vs. ??? OTR Measures 02 transmission rate through film Medical Device Packaging with MAP/UHMWPE • Tyvek® header foil pouch • Double pouch (not double barrier) package (Tyvek® inner, 2nd phase foil outer) • Double SiOx Pouch (Gamma) 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 www.qtspackage.com Original Sealer Selection / Specifications 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 Sealer 1 Specification changed to Under 1% • We stayed on the same sealer • Set samples to outside service to test for O2 • samples were between 8 – 18% • Another vacuum sealer available in house to try 2nd Sealer 2nd Sealer • 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 Why switch to 2nd Sealer? • Multiple vacuum cycles greatly lowered oxygen • Consistent in relation to the cycles • More variables to control Sealer 2 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 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 Mocon Analyzer • Testing Method • Needle • Foam septum • Having enough air/volume • Automatic vs. Manual • Variability in Testing w/rigid specification Under 1%! Under 0.4% ?! Why under 0.4% • Used in validations • Validated at arbitrary value • 510K submission callout • Functionality • Time vs. Requirement www.qtspackage.com What we did to achieve 0.4% • Slower and Lower • Start/end with vacuum • Modify Nozzle • Durometer of Sealer Bar • Operator Manipulation 10 samples pass! • “Sweet spot” of vacuum / purge cycle, time, and pressure selected • Operator manipulation of package required 0.4 0.35 0.3 0.25 +1 ERROR 0.2 -1 ERROR 0.15 % 0.1 0.05 0 1 2 3 4 5 6 7 8 9 10 Project Delayed! 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 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 www.qtspackage.com excavate more air than the nozzle will vacuum out. Theories why samples were not repeatable • Analyzer • 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 www.qtspackage.com MAP Case Study 6 Month No Oxygen Under Delay – Spec Under 1% 0.4% - 10 New outcome initially – - sealer #2 samples solution not sealer #1 work repeatable www.qtspackage.com Vacuum Chamber Sealer Sealer removes oxygen from the entire environment, diffuses the purge gas, and creates a package seal. Vacuum Chamber Sealer Sealer removes oxygen from the entire environment, diffuses the purge gas, and creates a package seal. Questions? [email protected] | www.qtspackage.com .