Micro ftir3 end-recalls and shutdowns
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The document discusses the investigation and resolution of contamination issues in a bioresorbable implant caused by bubbles trapped in the molded polymer, which were linked to secondary amide deposits that formed during injection molding. A specific analytical method was developed to identify and understand the chemical reactions responsible for the contamination, ultimately leading to a successful market launch of the implant. Additionally, it describes a related problem with wrinkled injection molded parts in a factory, attributed to a resin supplier's error in product composition, which was resolved through a rapid infrared analytical method.
Micro ftir3 end-recalls and shutdowns
- 1. An unusually profitable Bioresorbable Implant with a brilliant Market-dominating future had its Market Launch endangered by the occurrence of foreign matter inside the tiny molded PolyLactide:Glycolide implant. A CERTAIN fix was required immediately: the cause had to be IDd with certainty and eliminated. Many Hypotheses were proposed: >The Resin Supplier suggested that Residual Monomer was boiling during molding. Extensive testing of residual monomer levels in retained lot samples vs amount of bubbles found from molding those lots was proposed. >Molding Engineers suggested that the bubbles were: Shrink Voids, Entrapped Air, Entrapped Condensation, Etc. Humidity archives were to be examined and production areas were to be desiccated. >”Shotgun Experiments” were about to be fired in every direction. Instead a “RIFLE BULLET” EXPERIMENT was aimed right at the bubbles themselves. >Contaminant was Bubbles Inflated while Flowing “COMET”. >Cut thin Cross-sections of the polymer through the Bubbles. >Micro-FTIR repeatedly found a single deposit of Secondary Amide localized in a small area on each Bubble’s inner surface. Part 4: Nailing the Answer and Preventing a Recall Flow Direction
- 2. Hazy Translucent Area on border of Bubble When a thin slice of the Part, containing the Bubble, was shaved off, the Hole in the shaving had a tiny region on its circumference that was Hazy Translucent while the rest of the circumference and of the part’s shaving was Clear Translucent Cross-section of Bubble Clear translucent polymer slice
- 3. 1534 1648 3060 3288 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0 2.2 2.4 2.6 2.8 3.0 3.2 3.4 Absorbance 1000150020002500300035004000 Wavenumbers (cm-1) “Zooming in” on Hazy deposit on Bubble’s circumference Increases the Secondary Amide Absorbance Peaks relative to the PLG’S... PLG PLG ...therefore the hazy area is a Secondary Amide FTIR Microscopy Zooming in
- 4. -1.0 -0.5 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 Absorbance 1000150020002500300035004000 Wavenumbers (cm-1) Three Amide deposits on Aluminum with PLG dissolved away. Two Amide deposits squashed onto Aluminum. Methylene Chloride removed most of the PLG Squashed onto Aluminum Squashed onto Aluminum Amide Amide ... so what is this Secondary Amide and what is it doing?
- 5. Synergistic Use of FTIR Microscope and Gas Chromatograph / Mass Spectrometer The two most powerful instruments In Analytical Chemistry ... so what is this Secondary Amide and what did it do?
- 6. The SIS Thermal Desorber A Heated Inlet for GC/MS sold by Scientific Instrument Services
- 7. Carrier Gas Flowpath to Mass Spec Detector Pure He flowing through glass lined steel tube that contains sample. Tube is injected into GC Inlet and heated. Volatiles separate on column and are analyzed by the MS.
- 8. Excised tiny intact Bubbles melted in THDSB pop and release CO2 (and NOT O2 or N2) PLG Hydrolysis in heated tube releases Lactide and Glycolide
- 9. Hydrolysis of PLG: The Chemistry Occurring The moisture in the amide flakes forms steam during injection molding, inflating the bubbles. The steam is consumed as it hydrolyzes the PLG, filling the bubbles with CO2. as per Dr. C. C. Chu of Cornell
- 10. Spectral changes of PLG hydrolyzed on Hotplate Carbonyl and Hydroxyl orbitals are formed as the controls hydrolyze on the hotplate.
- 11. Spectral changes of PLG vs proximity to amide deposit The concentration of the same Carbonyl and Hydroxyl orbitals is seen to increase with increasing proximity to the bubbles formed by the amide flakes. This large gradient in concentration occurs across a microscopic range of distance from the bubbles’ walls. It is in analyses like this one that the FTIR Microscope is the very best tool there is. No other instrument could do this work: easy and exact spatial localization of a chemical identification.
- 12. Preventing Recall - Conclusion >Skin Flakes boiled off their water, inflating the “comets” >As this steam inflated the PLG, it was immediately consumed by the PLG’s Hydrolysis Reaction >Hydrolyzing PLG emits CO2, the gas remaining inside the “comets” that was detected by GC/MS as the “comets” melted and popped >Hydrolyzing PLG on a hot plate using drops of water Darkened spots ranging from light brown to nearly black >FTIR spectra of these darkened regions peaks appearing near 1730 cm-1 and 1620 cm-1 >FTIR spectra obtained from microscopic regions as the area examined approached the hydrolyzed circumference of the “comet” slices peaks appearing near 1730 cm-1 and 1620 cm-1 >The polymer pellets were protected against any further contamination by skin flakes, there was no further problem with “comets”, the product launch was continued, and the implant dominated its market One Billion $ in $ales per year
- 13. Ending $100MM/yr Device Factory Shutdown caused by “wrinkled” Injection Molded Parts A $100MM per year device factory was shutdown because Injection Molded parts were slightly wrinkled. No one was going to make any money until the problem was fixed. Possible causes that were proposed for investigation: >Electrical supply fluctuations >Cooling Water Heat Transfer fluctuations >Press Horsepower fluctuations Many “Shotgun Experiments” were about to begin with no expense to be spared --- BUT --- >The Polypropylene (PP) Resin was supposed to contain Sodium Benzoate (NaBZT), an additive that makes the Polymer solidify at a higher temperature (faster) than normal. >This fact suggested that the best place to look for the cause was in the PP pellets themselves. >I developed an Infrared analytical method that measured very quickly the NaBZT concentrations of large numbers of individual pellet.
- 14. Plant Shutdown Ended “Wrinkled” Injection Molded Parts caused by Resin Supplier’s Error FREQ NaBZT Concentration This is one example of when to use the FTIR Mainbench instead of the Microscope: When you want to analyze as large of an area as possible per each scan. >The Resin Supplier by mistake had added different pellets to the Finished Material: pellets that contained a significantly higher concentration of NaBZT than the correct pellets. These wrong pellets were dumped into the Railcar on top of the correct Resin. >The resulting mixed resins received only the little bit of blending that occurred during transport from the Railcar to the Silo and then to the Hoppers. >The Parts wrinkled because the varying NaBZT concentrations caused varying degrees of Shrinking and Packing during molding. ...but some had too much Analytical Method developed to measure RAPIDLY the Concentration of individual pellets proving Bimodal Distribution Most Pellets had Right NaBZT amount