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Proactive vs. Reactive Glass
Delamination Testing in
Pharmaceuticals
Join Gateway Analytical Scientists as they discuss UP...
How to Interact with Us Today
You can submit a question at any time
using the chat box function.
Type your comments or que...
About Gateway Analytical
Located in Gibsonia, Pennsylvania, USA
Gateway Proprietary Information
©Gateway Analytical, LLC 2...
About Gateway Analytical
Gateway Proprietary Information
©Gateway Analytical, LLC 2016. All Rights Reserved. Gateway Produ...
Meet Today’s Presenters
Emily Landsperger
Scientist
Gateway Analytical
landspergere@gatewayanalytical.com
Gateway Propriet...
Outline of Today's Webinar
• Overview of Glass Delamination and common test
methods
• USP <1660> Guidelines
• Proactive vs...
Overview of Glass Delamination
What is it and why does it happen?
.
Gateway Proprietary Information
©Gateway Analytical, L...
Glass Delamination
• Phenomenon which occurs when top layers of a glass
surface flake off, due to breakdown of the glass s...
Factors Contributing to Glass Delamination
• Vial Conditions
– Time exposed to solution
– Temperature fluctuations
– Chemi...
Vial Conditions
• Time
– Shelf life
• Chemistry of solution
– pH
– Ionic strength
• Temperature
– Autoclaving/sterilizatio...
Nature of the Vial
• Vial Manufacture Process
– Tubing vs. molding
• Chemistry of the Glass
– Type I (COE)
– Glass = silic...
Poll Question #1
• Have you ever experienced glass delamination
in any of your products?
YES
NO
Gateway Proprietary Inform...
USP <1660>
Recommended Approach for Evaluation of the
Inner Surface Durability of Glass Containers
.
Gateway Proprietary I...
Purpose / Scope
• General information about factors that may
contribute to glass delamination (durability)
• Recommendatio...
Details Discussed
• Types of glass
• Formation of containers
• Supply Chain Practices
• Glass surface chemistry
Gateway Pr...
Source: USP <1660>, usp.org
Gateway Proprietary Information
©Gateway Analytical, LLC 2016. All Rights Reserved. Gateway Pr...
Things to look for during analysis…
• Changes in solution
• SiO2 content
• Number of lamellae in solution
• Changes in pH
...
Source: USP <1660>, usp.org
Gateway Proprietary Information
©Gateway Analytical, LLC 2016. All Rights Reserved. Gateway Pr...
USP<1660> Recommended
Analytical Methods
• DIC Microscopy/EM
• SIMS
• pH testing
• ICP-MS/OES
• Particle Size Analyzer
• S...
DIC/EM Microscopy
• Differential Interference Contrast Microscopy:
– An optical microscopy technique used to enhance
the c...
DIC/EM Microscopy
• Electron Microscopy
– Utilizing the Secondary Electron Detector
– Allows for detection of minute surfa...
SIMS
• Secondary Ion Mass Spec
• Surface analysis (sputter surface with ions,
analyze secondary ions coming off of the
sur...
pH Testing
• pH meter used to test solution
• Highly alkaline or highly basic solutions can
contribute to delamination
Aci...
ICP-OES/ICP-MS
• Analysis of solution contained by the vial
• Detect/quantify levels of trace elements
commonly found in g...
Particle Sizing and Counting
• Particle size analyzer
– HIAC/Accusizer
– CCSEM
Light
Source
Liquid
Sample
Detector
Gateway...
SEM Analysis
• Lamellae on Filters
– Morphology
– Elemental composition
Gateway Proprietary Information
©Gateway Analytica...
Screening Methods
Three Parameters to Keep in Mind:
1. Visual and chemical profile of inner surface layer
- DIC/EM and SIM...
Accelerated Testing
• Examples of models that can be used to
accelerate delamination
– Specific % of KCl (pH 8.0), Citric ...
Product Specific Model
Source: USP <1660>, usp.org
Gateway Proprietary Information
©Gateway Analytical, LLC 2016. All Righ...
Poll Question #2
• Do you currently perform glass delamination
testing in-house or do you outsource this
work?
In-house
Su...
Analysis Methods for Glass
Delamination
What analyses do we perform?
.
Gateway Proprietary Information
©Gateway Analytical...
• “Twinkling”
– Light reflected off lamellae
• Signs of extensive
glass breakdown
• Can be difficult to detect
Initial Ste...
Filtration of Vial Contents
• The liquid vial contents are filtered onto
polycarbonate filter membranes for further
analys...
Stereoscopic Evaluation
• Analysis of filter for the presence of
lamellae
– Co-axial lighting recommended
– Distinctive, t...
Stereoscopic Evaluation
• Analysis of filter for
the presence of
lamellae
– Variability in
appearance of
lamellae between
...
SEM-EDS of Lamellae
500 µm 200 µm
keV
1086420
Counts
2,000
1,500
1,000
500
0
C
O
Al
Si
filename=100515_Lamellae3.TIF
Manua...
Stereomicroscopy and SEM-EDS
• Stereomicroscopy with a coaxial light source
and SEM-EDS are used in conjunction to
confirm...
Particle Number and Size
• Quantity/Size of lamellae in solution
• Particle Size Analyzer
– Difficulty in detecting lamell...
Limitations of CCSEM of Lamellae
500 µm 200 µm
keV
1086420
Counts
2,000
1,500
1,000
500
0
C
O
Al
Si
filename=100515_Lamell...
EM of Vial Interiors
• Secondary Electron
Detector of EM
• Minute changes in
surface topology
detected
• Pitting, delamina...
EM of Vial Interiors
• Pitting, delamination, manufacture defects
• Addresses the USP<1660> test parameter “glass surface”...
Analyses Sent for Subcontract
• pH testing
– Changes in the pH of the solution
• ICP-OES
– Extracted elements in solution ...
Gateway Proprietary Information
©Gateway Analytical, LLC 2016. All Rights Reserved. Gateway Products and Services
are prot...
Analyses We Don’t Perform
• DIC
– SED allows us higher resolution and magnification
– More detail obtained using SED
• SIM...
Proactive vs. Reactive
Analytical Approaches
What’s the difference?
.
Gateway Proprietary Information
©Gateway Analytical,...
Proactive vs. Reactive
They are addressing different questions:
• Proactive: Will THIS drug cause THIS
vial/container to d...
Proactive Testing
• Durability testing
• Aggressive investigation to determine suitability
of a specific drug in a specifi...
So many factors…
• A good idea is to take a proactive approach
– Stability Studies
– So many variables, it is hard to stat...
Proactive Testing
• USP<1660> specifically addresses proactive
testing methods
• We utilize all available test methods for...
Proactive Testing
• Recommendations:
– At least three lots of drug product
– At least two different vial types
– Several t...
Proactive vs. Reactive
They are addressing different questions:
• Reactive: Is delamination already present in
this vial?
...
Reactive Testing
• Testing for presence of lamellae or surface breakdown
after it has been manufactured and put into circu...
Reactive Testing
• Drug product has already been manufactured
– The “study” phase is over
• Therefore, no need for:
– Extr...
Poll Question #3
• Has your lab ever performed a stability study
for glass delamination?
YES
NO
Gateway Proprietary Inform...
FDA Requirements
.
Gateway Proprietary Information
©Gateway Analytical, LLC 2016. All Rights Reserved. Gateway Products an...
FDA Requirements
• Unfortunately the FDA has not issued
requirements for glass delamination testing
• UPS<1660> is a guida...
Q&A Session
Please submit any questions using the chat box in the lower left of your screen
Gateway Proprietary Informatio...
Contact Us & Follow-up
For more information about our analytical services, please visit:
www.gatewayanalytical.com
Connect...
For Attending
Today’s Presentation!
Please remember to complete the short survey following this slide
Gateway Proprietary ...
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Webinar Presentation: Proactive vs Reactive Glass Delamination Testing in Pharmaceuticals

Join Gateway Analytical Scientists as they discuss UPS <1660> recommendations and Gateway’s approach to different types of glass delamination investigations.

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Webinar Presentation: Proactive vs Reactive Glass Delamination Testing in Pharmaceuticals

  1. 1. Proactive vs. Reactive Glass Delamination Testing in Pharmaceuticals Join Gateway Analytical Scientists as they discuss UPS <1660> recommendations and Gateway’s approach to different types of glass delamination investigations. How to Listen & Participate in Today’s Webinar: Streaming audio is available through your computer speakers Questions can be asked at any time though the chat function interface Duration: 45 min. + Q&A time Welcome to Today's Webinar!
  2. 2. How to Interact with Us Today You can submit a question at any time using the chat box function. Type your comments or questions here and hit send to submit them. Type your question here. We will answer as many questions as possible during the Q&A session at the end of the webinar. Gateway Proprietary Information ©Gateway Analytical, LLC 2016. All Rights Reserved. Gateway Products and Services are protected by U.S. and International issued patents and pending patent applications.
  3. 3. About Gateway Analytical Located in Gibsonia, Pennsylvania, USA Gateway Proprietary Information ©Gateway Analytical, LLC 2016. All Rights Reserved. Gateway Products and Services are protected by U.S. and International issued patents and pending patent applications.
  4. 4. About Gateway Analytical Gateway Proprietary Information ©Gateway Analytical, LLC 2016. All Rights Reserved. Gateway Products and Services are protected by U.S. and International issued patents and pending patent applications. Quality laboratory services making our world healthier and safer . . . one particle at a time!
  5. 5. Meet Today’s Presenters Emily Landsperger Scientist Gateway Analytical landspergere@gatewayanalytical.com Gateway Proprietary Information ©Gateway Analytical, LLC 2016. All Rights Reserved. Gateway Products and Services are protected by U.S. and International issued patents and pending patent applications.
  6. 6. Outline of Today's Webinar • Overview of Glass Delamination and common test methods • USP <1660> Guidelines • Proactive vs. Reactive Test Methods • Conclusions/Recommendations • Q&A Session Gateway Proprietary Information ©Gateway Analytical, LLC 2016. All Rights Reserved. Gateway Products and Services are protected by U.S. and International issued patents and pending patent applications.
  7. 7. Overview of Glass Delamination What is it and why does it happen? . Gateway Proprietary Information ©Gateway Analytical, LLC 2016. All Rights Reserved. Gateway Products and Services are protected by U.S. and International issued patents and pending patent applications.
  8. 8. Glass Delamination • Phenomenon which occurs when top layers of a glass surface flake off, due to breakdown of the glass surface. • Largely caused by the interactions between the glass surface and the liquid that it contains • Oxides leach out of the glass surface, which creates a less resistant layer. • Formation of flakes, which slough off into solution • Manufacturing defects already present in the vials can also be a catalyst of delamination Gateway Proprietary Information ©Gateway Analytical, LLC 2016. All Rights Reserved. Gateway Products and Services are protected by U.S. and International issued patents and pending patent applications.
  9. 9. Factors Contributing to Glass Delamination • Vial Conditions – Time exposed to solution – Temperature fluctuations – Chemistry of solution contained • Nature of the Vial – Vial Manufacture Process – Chemistry of the glass – Surface Treatments Gateway Proprietary Information ©Gateway Analytical, LLC 2016. All Rights Reserved. Gateway Products and Services are protected by U.S. and International issued patents and pending patent applications.
  10. 10. Vial Conditions • Time – Shelf life • Chemistry of solution – pH – Ionic strength • Temperature – Autoclaving/sterilization – Fluctuations over time/storage conditions Gateway Proprietary Information ©Gateway Analytical, LLC 2016. All Rights Reserved. Gateway Products and Services are protected by U.S. and International issued patents and pending patent applications.
  11. 11. Nature of the Vial • Vial Manufacture Process – Tubing vs. molding • Chemistry of the Glass – Type I (COE) – Glass = silicon dioxide (various additives) • Surface Treatments – Sulfur – Siliconization – Surface Treatments/coating Gateway Proprietary Information ©Gateway Analytical, LLC 2016. All Rights Reserved. Gateway Products and Services are protected by U.S. and International issued patents and pending patent applications.
  12. 12. Poll Question #1 • Have you ever experienced glass delamination in any of your products? YES NO Gateway Proprietary Information ©Gateway Analytical, LLC 2016. All Rights Reserved. Gateway Products and Services are protected by U.S. and International issued patents and pending patent applications.
  13. 13. USP <1660> Recommended Approach for Evaluation of the Inner Surface Durability of Glass Containers . Gateway Proprietary Information ©Gateway Analytical, LLC 2016. All Rights Reserved. Gateway Products and Services are protected by U.S. and International issued patents and pending patent applications.
  14. 14. Purpose / Scope • General information about factors that may contribute to glass delamination (durability) • Recommendations for predictive testing/detection of the phenomenon of delamination • CMO’s, fill/finish sites, glass manufacturers, pharmaceutical companies Gateway Proprietary Information ©Gateway Analytical, LLC 2016. All Rights Reserved. Gateway Products and Services are protected by U.S. and International issued patents and pending patent applications.
  15. 15. Details Discussed • Types of glass • Formation of containers • Supply Chain Practices • Glass surface chemistry Gateway Proprietary Information ©Gateway Analytical, LLC 2016. All Rights Reserved. Gateway Products and Services are protected by U.S. and International issued patents and pending patent applications.
  16. 16. Source: USP <1660>, usp.org Gateway Proprietary Information ©Gateway Analytical, LLC 2016. All Rights Reserved. Gateway Products and Services are protected by U.S. and International issued patents and pending patent applications.
  17. 17. Things to look for during analysis… • Changes in solution • SiO2 content • Number of lamellae in solution • Changes in pH Gateway Proprietary Information ©Gateway Analytical, LLC 2016. All Rights Reserved. Gateway Products and Services are protected by U.S. and International issued patents and pending patent applications.
  18. 18. Source: USP <1660>, usp.org Gateway Proprietary Information ©Gateway Analytical, LLC 2016. All Rights Reserved. Gateway Products and Services are protected by U.S. and International issued patents and pending patent applications.
  19. 19. USP<1660> Recommended Analytical Methods • DIC Microscopy/EM • SIMS • pH testing • ICP-MS/OES • Particle Size Analyzer • SEM-EDS of lamellae Gateway Proprietary Information ©Gateway Analytical, LLC 2016. All Rights Reserved. Gateway Products and Services are protected by U.S. and International issued patents and pending patent applications.
  20. 20. DIC/EM Microscopy • Differential Interference Contrast Microscopy: – An optical microscopy technique used to enhance the contrast in an unstained, transparent samples – Non-destructive – No need to cut vials http://journals.cambridge.org/action/display Abstract?fromPage=online&aid=9031607 Gateway Proprietary Information ©Gateway Analytical, LLC 2016. All Rights Reserved. Gateway Products and Services are protected by U.S. and International issued patents and pending patent applications.
  21. 21. DIC/EM Microscopy • Electron Microscopy – Utilizing the Secondary Electron Detector – Allows for detection of minute surface changes – Requires cutting of vials Gateway Proprietary Information ©Gateway Analytical, LLC 2016. All Rights Reserved. Gateway Products and Services are protected by U.S. and International issued patents and pending patent applications.
  22. 22. SIMS • Secondary Ion Mass Spec • Surface analysis (sputter surface with ions, analyze secondary ions coming off of the surface) • Depth profiling • Very sensitive Gateway Proprietary Information ©Gateway Analytical, LLC 2016. All Rights Reserved. Gateway Products and Services are protected by U.S. and International issued patents and pending patent applications.
  23. 23. pH Testing • pH meter used to test solution • Highly alkaline or highly basic solutions can contribute to delamination Acidic Neutral Alkaline Gateway Proprietary Information ©Gateway Analytical, LLC 2016. All Rights Reserved. Gateway Products and Services are protected by U.S. and International issued patents and pending patent applications.
  24. 24. ICP-OES/ICP-MS • Analysis of solution contained by the vial • Detect/quantify levels of trace elements commonly found in glass Gateway Proprietary Information ©Gateway Analytical, LLC 2016. All Rights Reserved. Gateway Products and Services are protected by U.S. and International issued patents and pending patent applications.
  25. 25. Particle Sizing and Counting • Particle size analyzer – HIAC/Accusizer – CCSEM Light Source Liquid Sample Detector Gateway Proprietary Information ©Gateway Analytical, LLC 2016. All Rights Reserved. Gateway Products and Services are protected by U.S. and International issued patents and pending patent applications.
  26. 26. SEM Analysis • Lamellae on Filters – Morphology – Elemental composition Gateway Proprietary Information ©Gateway Analytical, LLC 2016. All Rights Reserved. Gateway Products and Services are protected by U.S. and International issued patents and pending patent applications.
  27. 27. Screening Methods Three Parameters to Keep in Mind: 1. Visual and chemical profile of inner surface layer - DIC/EM and SIMS 2. Amount of elements in solution - pH testing/ICP-MS/ICP-OES 3. Number of sub-visible and visible particles present in solution - Particle Size Analyzer/SEM-EDS Gateway Proprietary Information ©Gateway Analytical, LLC 2016. All Rights Reserved. Gateway Products and Services are protected by U.S. and International issued patents and pending patent applications.
  28. 28. Accelerated Testing • Examples of models that can be used to accelerate delamination – Specific % of KCl (pH 8.0), Citric Acid (pH 8.0), and Glycine (pH 10.0) – These are tested at specific temperatures for specific amount of time • For a typical drug stored at 25C, every 30 days at 60C is roughly equivalent to a full year of storage at 25C Gateway Proprietary Information ©Gateway Analytical, LLC 2016. All Rights Reserved. Gateway Products and Services are protected by U.S. and International issued patents and pending patent applications.
  29. 29. Product Specific Model Source: USP <1660>, usp.org Gateway Proprietary Information ©Gateway Analytical, LLC 2016. All Rights Reserved. Gateway Products and Services are protected by U.S. and International issued patents and pending patent applications.
  30. 30. Poll Question #2 • Do you currently perform glass delamination testing in-house or do you outsource this work? In-house Subcontract Neither Both Gateway Proprietary Information ©Gateway Analytical, LLC 2016. All Rights Reserved. Gateway Products and Services are protected by U.S. and International issued patents and pending patent applications.
  31. 31. Analysis Methods for Glass Delamination What analyses do we perform? . Gateway Proprietary Information ©Gateway Analytical, LLC 2016. All Rights Reserved. Gateway Products and Services are protected by U.S. and International issued patents and pending patent applications.
  32. 32. • “Twinkling” – Light reflected off lamellae • Signs of extensive glass breakdown • Can be difficult to detect Initial Stereomicroscopic Examination Gateway Proprietary Information ©Gateway Analytical, LLC 2016. All Rights Reserved. Gateway Products and Services are protected by U.S. and International issued patents and pending patent applications.
  33. 33. Filtration of Vial Contents • The liquid vial contents are filtered onto polycarbonate filter membranes for further analysis • Polycarbonate filters allow for the visualization of lamellae in subsequent steps – Thin, smooth surface to the filter membrane Gateway Proprietary Information ©Gateway Analytical, LLC 2016. All Rights Reserved. Gateway Products and Services are protected by U.S. and International issued patents and pending patent applications.
  34. 34. Stereoscopic Evaluation • Analysis of filter for the presence of lamellae – Co-axial lighting recommended – Distinctive, thin, colorful or reflective flakes indicate glass lamellae – Thin, smooth, flat; can have straight/angular edges Gateway Proprietary Information ©Gateway Analytical, LLC 2016. All Rights Reserved. Gateway Products and Services are protected by U.S. and International issued patents and pending patent applications.
  35. 35. Stereoscopic Evaluation • Analysis of filter for the presence of lamellae – Variability in appearance of lamellae between samples – Due to thickness of the lamellae Gateway Proprietary Information ©Gateway Analytical, LLC 2016. All Rights Reserved. Gateway Products and Services are protected by U.S. and International issued patents and pending patent applications.
  36. 36. SEM-EDS of Lamellae 500 µm 200 µm keV 1086420 Counts 2,000 1,500 1,000 500 0 C O Al Si filename=100515_Lamellae3.TIF Manual SEM-EDS of glass lamellae • SEM-EDS: Scanning Electron Microscopy – Energy Dispersive Spectroscopy – Determine elemental composition of a sample • Filter surface evaluated using SEM- EDS to detect elements consistent with glass in the lamellae • Lamellae are so thin, large contributions from substrate Gateway Proprietary Information ©Gateway Analytical, LLC 2016. All Rights Reserved. Gateway Products and Services are protected by U.S. and International issued patents and pending patent applications.
  37. 37. Stereomicroscopy and SEM-EDS • Stereomicroscopy with a coaxial light source and SEM-EDS are used in conjunction to confirm that the particles identified are both morphologically and elementally consistent with glass lamellae • Addresses the USP<1660> test parameter “visible and sub-visible glass particles” Gateway Proprietary Information ©Gateway Analytical, LLC 2016. All Rights Reserved. Gateway Products and Services are protected by U.S. and International issued patents and pending patent applications.
  38. 38. Particle Number and Size • Quantity/Size of lamellae in solution • Particle Size Analyzer – Difficulty in detecting lamellae – Not chemical specific • CCSEM – limitations in detecting glass lamellae due to thin nature of lamellae • Manual counting/sizing using stereomicroscope and software is best current option – Image shown above Manual counting and sizing of glass lamellae using LAS software. Gateway Proprietary Information ©Gateway Analytical, LLC 2016. All Rights Reserved. Gateway Products and Services are protected by U.S. and International issued patents and pending patent applications.
  39. 39. Limitations of CCSEM of Lamellae 500 µm 200 µm keV 1086420 Counts 2,000 1,500 1,000 500 0 C O Al Si filename=100515_Lamellae3.TIF Manual SEM-EDS of glass lamellae Attempt to set automated thresholds for the detection of glass lamellae on polycarbonate filter. • Even thick/overlapping lamellae could not be flagged by the automated system’s thresholds • Overwhelming background signal Gateway Proprietary Information ©Gateway Analytical, LLC 2016. All Rights Reserved. Gateway Products and Services are protected by U.S. and International issued patents and pending patent applications.
  40. 40. EM of Vial Interiors • Secondary Electron Detector of EM • Minute changes in surface topology detected • Pitting, delamination, corrosion, manufacture defects • Magnifications of 2500x – 10,000x or more Gateway Proprietary Information ©Gateway Analytical, LLC 2016. All Rights Reserved. Gateway Products and Services are protected by U.S. and International issued patents and pending patent applications.
  41. 41. EM of Vial Interiors • Pitting, delamination, manufacture defects • Addresses the USP<1660> test parameter “glass surface” Gateway Proprietary Information ©Gateway Analytical, LLC 2016. All Rights Reserved. Gateway Products and Services are protected by U.S. and International issued patents and pending patent applications.
  42. 42. Analyses Sent for Subcontract • pH testing – Changes in the pH of the solution • ICP-OES – Extracted elements in solution from the glass • These two analyses address the USP<1660> parameter of “extracted elements in solution” Gateway Proprietary Information ©Gateway Analytical, LLC 2016. All Rights Reserved. Gateway Products and Services are protected by U.S. and International issued patents and pending patent applications.
  43. 43. Gateway Proprietary Information ©Gateway Analytical, LLC 2016. All Rights Reserved. Gateway Products and Services are protected by U.S. and International issued patents and pending patent applications.
  44. 44. Analyses We Don’t Perform • DIC – SED allows us higher resolution and magnification – More detail obtained using SED • SIMS – Little-used method – Few laboratories with this capability operate under the FDA Good Manufacturing Practices Gateway Proprietary Information ©Gateway Analytical, LLC 2016. All Rights Reserved. Gateway Products and Services are protected by U.S. and International issued patents and pending patent applications.
  45. 45. Proactive vs. Reactive Analytical Approaches What’s the difference? . Gateway Proprietary Information ©Gateway Analytical, LLC 2016. All Rights Reserved. Gateway Products and Services are protected by U.S. and International issued patents and pending patent applications.
  46. 46. Proactive vs. Reactive They are addressing different questions: • Proactive: Will THIS drug cause THIS vial/container to delaminate? – This is performed as part of drug formulation testing, and prior to manufacturing or distribution – Finding the best vial/container for a particular drug of interest • Least likely to delaminate Gateway Proprietary Information ©Gateway Analytical, LLC 2016. All Rights Reserved. Gateway Products and Services are protected by U.S. and International issued patents and pending patent applications.
  47. 47. Proactive Testing • Durability testing • Aggressive investigation to determine suitability of a specific drug in a specific container • Most extreme circumstances it will face • Over life of the vial • Accelerated testing methods are often employed Gateway Proprietary Information ©Gateway Analytical, LLC 2016. All Rights Reserved. Gateway Products and Services are protected by U.S. and International issued patents and pending patent applications.
  48. 48. So many factors… • A good idea is to take a proactive approach – Stability Studies – So many variables, it is hard to state that one particular vial has better overall durability than another – Each situation is unique Gateway Proprietary Information ©Gateway Analytical, LLC 2016. All Rights Reserved. Gateway Products and Services are protected by U.S. and International issued patents and pending patent applications.
  49. 49. Proactive Testing • USP<1660> specifically addresses proactive testing methods • We utilize all available test methods for proactive testing – Twinkling – Stereomicroscopy of Filters – SEM-EDS of Filters – SED of Vial Interiors – pH/ICP-OES of Solution Gateway Proprietary Information ©Gateway Analytical, LLC 2016. All Rights Reserved. Gateway Products and Services are protected by U.S. and International issued patents and pending patent applications.
  50. 50. Proactive Testing • Recommendations: – At least three lots of drug product – At least two different vial types – Several time points • From time of fill to expected expiration date – All temperature ranges it may be subjected to – Changes in pH may also be evaluated Gateway Proprietary Information ©Gateway Analytical, LLC 2016. All Rights Reserved. Gateway Products and Services are protected by U.S. and International issued patents and pending patent applications.
  51. 51. Proactive vs. Reactive They are addressing different questions: • Reactive: Is delamination already present in this vial? – This is performed typically as a spot check or part of a recall or customer complaint – Vials that have been in circulation for a given amount of time are sent for analysis to determine the presence/absence of glass lamellae Gateway Proprietary Information ©Gateway Analytical, LLC 2016. All Rights Reserved. Gateway Products and Services are protected by U.S. and International issued patents and pending patent applications.
  52. 52. Reactive Testing • Testing for presence of lamellae or surface breakdown after it has been manufactured and put into circulation • A less-extensive analysis is needed when delamination is already suspected – Twinkling – Stereomicroscopy of Filters – SEM-EDS of Filters – SED of Vial Interiors • Three samples are typically sufficient to confirm or reject the presence of active delamination Gateway Proprietary Information ©Gateway Analytical, LLC 2016. All Rights Reserved. Gateway Products and Services are protected by U.S. and International issued patents and pending patent applications.
  53. 53. Reactive Testing • Drug product has already been manufactured – The “study” phase is over • Therefore, no need for: – Extracted elements in solution – Temperature Changes – pH Changes Gateway Proprietary Information ©Gateway Analytical, LLC 2016. All Rights Reserved. Gateway Products and Services are protected by U.S. and International issued patents and pending patent applications.
  54. 54. Poll Question #3 • Has your lab ever performed a stability study for glass delamination? YES NO Gateway Proprietary Information ©Gateway Analytical, LLC 2016. All Rights Reserved. Gateway Products and Services are protected by U.S. and International issued patents and pending patent applications.
  55. 55. FDA Requirements . Gateway Proprietary Information ©Gateway Analytical, LLC 2016. All Rights Reserved. Gateway Products and Services are protected by U.S. and International issued patents and pending patent applications.
  56. 56. FDA Requirements • Unfortunately the FDA has not issued requirements for glass delamination testing • UPS<1660> is a guidance document – Does not address a “reactive” approach • No cut and dry guidelines or protocols Gateway Proprietary Information ©Gateway Analytical, LLC 2016. All Rights Reserved. Gateway Products and Services are protected by U.S. and International issued patents and pending patent applications.
  57. 57. Q&A Session Please submit any questions using the chat box in the lower left of your screen Gateway Proprietary Information ©Gateway Analytical, LLC 2016. All Rights Reserved. Gateway Products and Services are protected by U.S. and International issued patents and pending patent applications.
  58. 58. Contact Us & Follow-up For more information about our analytical services, please visit: www.gatewayanalytical.com Connect with us on social media: Contact Information Emily Landsperger Scientist landsperger@gatewayanalytical.com Tel: 724-443-1900 x107 Patrick Lehr Global Marketing Manager lehrp@gatewayanalytical.com Tel: 724-443-1900 x132 Gateway Proprietary Information ©Gateway Analytical, LLC 2016. All Rights Reserved. Gateway Products and Services are protected by U.S. and International issued patents and pending patent applications.
  59. 59. For Attending Today’s Presentation! Please remember to complete the short survey following this slide Gateway Proprietary Information ©Gateway Analytical, LLC 2016. All Rights Reserved. Gateway Products and Services are protected by U.S. and International issued patents and pending patent applications.

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Join Gateway Analytical Scientists as they discuss UPS &lt;1660> recommendations and Gateway’s approach to different types of glass delamination investigations.

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