Webinar: Case Studies in Foreign Particulate Analysis
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The document outlines a webinar by Gateway Analytical focusing on foreign particulate analysis in pharmaceutical manufacturing. It covers the characteristics, sources, and analysis methods of foreign particulate matter, while also providing case studies on contamination issues, such as hair and embedded materials in vials. Attendees will receive a replay link, presentation slides, and a digital certificate upon completion of the webinar.
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Particle Size and Identification Using SPE™
Automated Raman System
© Gateway Analytical, LLC, 2015
Spectra # Material
Size Distribution [µm]
2 - 10 10 - 25 25 - 50 50 - 100 100-1000 Totals
1 Amorphous Carbon 7 0 0 0 0 7
2 beta-Carotene 1 0 0 0 0 1
3 Blue Pigment 28 3 2 4 2 39
4 Boot cover 0 0 0 1 0 1
5 Boron Carbide 1 1 1 6 3 12
6 Calcium Chloride 1 0 0 0 0 1
7 Cellulose 1 0 0 1 0 2
10 storage bag 0 0 1 1 0 2
11 Filling suite, Ext 12 2 0 3 0 17
12 Filter from air line 0 0 0 0 1 1
13 Fluorescence 175 24 26 74 28 327
17 Gowning material 1 0 0 3 0 4
18 Plunger 0 1 6 26 10 43
20 Laurylsulfate Sodium, SDS 0 0 0 1 0 1
21 Nitrate Sodium 0 0 0 2 0 2
25 Plastic bags 0 0 0 1 0 1
26 Poly(acrylonitrile) 4 2 0 1 1 8
28 Polycarbonate 2 0 0 0 0 2
30 Polysulfone 1 0 0 0 0 1
31 Porous Particle Production Air 7 0 0 0 0 7
32 Sample 1 1 0 0 0 0 1
33 Sample 5 0 0 0 1 0 1
37 Smalt 1 0 0 0 0 1
38 Starch 1 0 0 1 0 2
40 Talcum 8 3 0 1 0 12
41 Titanium(IV)oxide, Anatase 2 0 0 1 0 3
42 gasket 0 0 1 0 0 1
All Particles 10,260 1548 460 128 45 12,441](https://image.slidesharecdn.com/webinar-casestudiesinforeignparticulateanalysis-150727164115-lva1-app6891/85/Webinar-Case-Studies-in-Foreign-Particulate-Analysis-33-320.jpg)
Webinar: Case Studies in Foreign Particulate Analysis
- 1. @GatewayTweets #gatewaywebinars @GatewayTweets #gatewaywebinars Case Studies in Foreign Particulate Analysis © Gateway Analytical, LLC, 2015 Welcome to Today's Webinar Presented by Gateway Analytical How to Listen & Participate in Todays Webinar: Streaming audio is available through your computer speakers. Questions can be asked at anytime though the chat function interface. Start Time: 2 pm am EDT (U.S & Canada) Duration: 45 min. including Q&A time Join Gateway Analytical scientists as they dive into best practice methods for characterizing and identifying foreign particulate
- 2. @GatewayTweets #gatewaywebinars @GatewayTweets #gatewaywebinars How to Interact 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. After the webinar you will be ask to take a short survey. #gatewaywebinars Join the conversation at: © Gateway Analytical, LLC, 2015
- 3. @GatewayTweets #gatewaywebinars What You Will Receive via Email after the Webinar Link to the Webinar Replay Link to the Presentation Slides A Digital E-Certificate of Attendance Q&A at the end of the webinar
- 4. @GatewayTweets #gatewaywebinars About Gateway Analytical Located in Gibsonia, Pennsylvania, USA Particulate Identification Services Detailed Report Characterizing and Identifying particulate Customer Support to help identity the source of contaminates. cGMP-compliant | FDA Registered & Inspected | ISO 17025 & ISO 9001
- 5. @GatewayTweets #gatewaywebinars About Gateway Analytical Located in Gibsonia, Pennsylvania, USA Particulate happens, but that shouldn't stop your progress. Our focus is to remove the hurdles involved with identifying foreign particulate and guide our customers to fast remediation.
- 6. @GatewayTweets #gatewaywebinars Meet the Presenters © Gateway Analytical, LLC, 2015 David Exline Vice President Gateway Analytical exlined@gatewayanalytical.com Julia Patterson Scientist Gateway Analytical pattersonj@gatewayanalytical.com Marina Parra Scientist Gateway Analytical parram@gatewayanalytical.com
- 7. @GatewayTweets #gatewaywebinars @GatewayTweets #gatewaywebinars Outline • What is foreign particulate matter? • Commonly found sources of particulate contamination • How manual analysis compares to automated technologies • Sample preparation • Specialized foreign particulate testing methods • Foreign particulate analysis methods and case study examples © Gateway Analytical, LLC, 2015
- 8. @GatewayTweets #gatewaywebinars Common Characteristics of Foreign Particulate Matter • Visible and sub-visible particles • Stains and discoloration • Often charred from sterilization processes • Precipitated materials • Typical in all process related manufacturing equipment – Cleaning system – CIP – Protective Clothing – Stainless steel tanks – Filter systems – Storage containment © Gateway Analytical, LLC, 2015
- 9. @GatewayTweets #gatewaywebinars Why is Foreign Particulate Matter So Common? • Product constantly in contact with process • Process of manufacturing has so many stages • Chemical breakdown and aging • Process precipitation • Raw material contamination • Containers and packaging • Washing and storage process • Customer site contamination • Environment • Sterile does not mean “particle free” © Gateway Analytical, LLC, 2015
- 10. @GatewayTweets #gatewaywebinars Common Types of Foreign Particulate Contaminations in Pharmaceutical Manufacturing Stainless Steel Human/Animal Hairs Paint Glass Rubber (stoppers) Polymers Insects Silicone Products © Gateway Analytical, LLC, 2015 Teflon Synthetic Fibers Natural Fibers Labels Burned Material Paper products Metals Environment • Often found during 100% inspection process • Mechanical Failure Investigation • Customer Return Samples • Contamination studies of processes • Evaluation of raw materials • Foreign particulate can be detected at any stage in the manufacturing process
- 11. @GatewayTweets #gatewaywebinars Pharmaceutical Forensics • Application of forensic testing & problem solving methods • Answer specific questions like: – How, why and when did it break? – What is this foreign material? – Where did it come from? • Typical Applications: – Particle contamination / Source Determination – Deviations from in process methods – Product returns – Foreign particulate matter identification – Tablet non-conformance investigation – Parenteral particulate characterization • Visible and sub-visible • 100% Particle inspection approach © Gateway Analytical, LLC, 2015
- 12. @GatewayTweets #gatewaywebinars Overall Sample Flow for Manual or Automated Analysis © Gateway Analytical, LLC, 2015 Non- Conformance Issue Sample Collection/ Evaluation Manual Analysis SEM-EDS FTIR Raman Optical/ PLM Glass Delamination Automated Analysis CCSEM SPE
- 13. @GatewayTweets #gatewaywebinars Manual vs. Automated Manual Analysis • Typically longer analysis time per sample • Better suited for a smaller number of samples • Can determine the size, shape, and color of each individual particle. • Can determine both the elemental composition of the sample and spectral data © Gateway Analytical, LLC, 2015 Automated Analysis • Faster analysis • Better suited for a larger number of samples • Can provide information on the size bins of the particles in a population • Sometimes you will not obtain as much data from each individual particle: Elemental composition OR spectral data
- 14. @GatewayTweets #gatewaywebinars Typical Sample Flow for Manual Analysis © Gateway Analytical, LLC, 2015 Sample Collection / Evaluation Physical Properties Color, shape, texture Optical Evaluation Fiber, glass, paint, metal, organic, inorganic Sample Isolation Non-conformance Issue Organic Analysis FT-IR, Raman, Chemistry, Chromatography Inorganic Analysis SEM/EDS, XRD, Inorganic Chemistry Identification of Foreign Material Comparison Foreign material with known Evaluation Source Determination
- 15. @GatewayTweets #gatewaywebinars Isolation of Particulate Manual Analysis • Initial collection – Filtration of parenteral product – Manual isolation • Washing/ rinsing of samples • Preparation for Analysis – Microscopy preparations – FTIR preparations – SEM/EDS preparations – Raman preparations © Gateway Analytical, LLC, 2015
- 16. @GatewayTweets #gatewaywebinars © Gateway Analytical, LLC, 2015 Preparation of Filter Manual Analysis
- 17. @GatewayTweets #gatewaywebinars Sample Collection / Isolation Manual Analysis © Gateway Analytical, LLC, 2015 • Isolation / cleaning of sample critical step • Understand substrate conditions
- 18. @GatewayTweets #gatewaywebinars Particle Isolation – Analysis Substrates Manual Analysis © Gateway Analytical, LLC, 2015 Microscopy – Temporary mount with glass slides FTIR – Low-e slide Raman – Al Slide SEM – Stub with carbon tape
- 19. @GatewayTweets #gatewaywebinars Preparation of Filter – Automated Raman Automated Analysis Gold Coated Polycarbonate Filter Filtration Preparation • Low blanks • Cleanroom manufactured • System integrated • High sensitivity • No background signal for ID © Gateway Analytical, LLC, 2015
- 20. @GatewayTweets #gatewaywebinars Microscopy – Key Techniques Manual Analysis © Gateway Analytical, LLC, 2015 • Size • Morphology • Consistency • Color • Documentation • Unique features • Organic vs. inorganic • Comparison • Optical properties • Fluorescence properties
- 21. @GatewayTweets #gatewaywebinars Optical Microscopy Manual Analysis • Efficient method of particle characterization • Cost effective • Critical evaluation for particle comparison and differentiation © Gateway Analytical, LLC, 2015 Optical and Polarized Light Microscopy Fluorescence Microscopy
- 22. @GatewayTweets #gatewaywebinars Fourier Transform Infrared Spectrometry (FTIR) Manual Analysis © Gateway Analytical, LLC, 2015 • A microscope attachment is usually required for precise analysis • Light can be passed through the sample (transmission) or reflected through the sample (reflectance) • The interaction of the light with the sample is interpreted as an FTIR spectrum 100015002000250030003500 Wavenumber cm-1 0.20.40.60.81.01.21.41.6 AbsorbanceUnits Polyethylene
- 23. @GatewayTweets #gatewaywebinars Raman Spectroscopy Manual Analysis • Generally a surface analysis method • Useful for: – Embedded materials – Pigments – Oxides – Amorphous Carbon • Is a complementary technique to FTIR analysis © Gateway Analytical, LLC, 2015
- 24. @GatewayTweets #gatewaywebinars Manual SEM-EDS Manual Analysis • The analyst manually drives the instrument to perform the analysis. • Useful for determining: – Surface features of a sample – Elemental composition of the sample • Can visualize and analyze different areas of a heterogeneous sample © Gateway Analytical, LLC, 2015 500 µm 100 µm keV 14121086420 Counts 2,500 2,000 1,500 1,000 500 0 CO Fe Fe Fe
- 25. @GatewayTweets #gatewaywebinars Automated CCSEM Automated Analysis • The analyst inputs an area and analysis criteria for the instrument to scan and analyze. • Useful for determining: – Elemental composition – Size for a population of particles © Gateway Analytical, LLC, 2015
- 26. @GatewayTweets #gatewaywebinars Glass Delamination Specialized Analysis What is Glass Delamination? • Small, thin, glass fragments, termed “glass lamellae”, which are shed from the interior portion of glass containers and vials • Glass lamellae are shed into, and suspended in the liquid drug contained in the glass vial • Detection of glass lamellae can be very difficult during visual product inspections © Gateway Analytical, LLC, 2015 High resolution SEM imaging analysis identifying regions on the interior vial surface which show indications of pitting and delamination
- 27. @GatewayTweets #gatewaywebinars Why Does Glass Delamination Occur? Specialized Analysis • Glass delamination is an effect of glass corrosion • Glass corrosion can occur in silicate glasses through three types of chemical reactions: – Acidic (H3O+) – Basic (OH-) – Neutral (H2O) © Gateway Analytical, LLC, 2015 keV 109876543210 Counts 6,000 4,000 2,000 0 C O Na Al Si Automated SEM- EDS analysis identifying Si-rich particles which are elementally and morphologically consistent with delamination
- 28. @GatewayTweets #gatewaywebinars Screening Studies per USP General Chapter <1660> PARAMETER TEST PARAMETER ANALYTICAL METHODS Glass surface • Degree of surface pitting • Chemical composition as a function of depth • DIC Microscopy or EM • SIMS Extracted elements in solution • Conductivity/pH • Individual and total extractables • SiO2 concentration • SiO2/B2O3 or Si/Al ratio • Conductivity/ pH meter • ICP-MS or ICP-OES Visible/ Subvisible glass particles • Particle number and size • Particle morphology and composition • Particle size analyzer • SEM-EDS © Gateway Analytical, LLC, 2015
- 29. @GatewayTweets #gatewaywebinars Specialized Analysis - Automated Raman Spectroscopy Overview © Gateway Analytical, LLC, 2015
- 30. @GatewayTweets #gatewaywebinars How Does Combined Raman/LIBS Compare to Other Technologies? Method Sizing and counting Elemental Chemical Automation Specific Level of expertise Cost Speed Optical Microscopy Yes No No Possible No High Low Slow HIAC Yes No No Yes No Low Low Fast Manual Raman No No Yes Possible Yes High Middle Fast Automated Raman Yes No Yes Yes Yes High Middle Fast FTIR No No Yes Possible Yes High Middle Fast SEM-EDS Yes Yes No Possible Yes Middle High Fast Automated LIBS YEs Yes Yes Yes Moderate High High Fast © Gateway Analytical, LLC, 2015
- 31. @GatewayTweets #gatewaywebinars Overall Filter Montage Automated Raman Spectroscopy © Gateway Analytical, LLC, 2015
- 32. @GatewayTweets #gatewaywebinars Database Search of Selected Particles Automated Raman Spectroscopy © Gateway Analytical, LLC, 2015 Raman Database Search Consistent with Plunger Material
- 33. @GatewayTweets #gatewaywebinars Particle Size and Identification Using SPE™ Automated Raman System © Gateway Analytical, LLC, 2015 Spectra # Material Size Distribution [µm] 2 - 10 10 - 25 25 - 50 50 - 100 100-1000 Totals 1 Amorphous Carbon 7 0 0 0 0 7 2 beta-Carotene 1 0 0 0 0 1 3 Blue Pigment 28 3 2 4 2 39 4 Boot cover 0 0 0 1 0 1 5 Boron Carbide 1 1 1 6 3 12 6 Calcium Chloride 1 0 0 0 0 1 7 Cellulose 1 0 0 1 0 2 10 storage bag 0 0 1 1 0 2 11 Filling suite, Ext 12 2 0 3 0 17 12 Filter from air line 0 0 0 0 1 1 13 Fluorescence 175 24 26 74 28 327 17 Gowning material 1 0 0 3 0 4 18 Plunger 0 1 6 26 10 43 20 Laurylsulfate Sodium, SDS 0 0 0 1 0 1 21 Nitrate Sodium 0 0 0 2 0 2 25 Plastic bags 0 0 0 1 0 1 26 Poly(acrylonitrile) 4 2 0 1 1 8 28 Polycarbonate 2 0 0 0 0 2 30 Polysulfone 1 0 0 0 0 1 31 Porous Particle Production Air 7 0 0 0 0 7 32 Sample 1 1 0 0 0 0 1 33 Sample 5 0 0 0 1 0 1 37 Smalt 1 0 0 0 0 1 38 Starch 1 0 0 1 0 2 40 Talcum 8 3 0 1 0 12 41 Titanium(IV)oxide, Anatase 2 0 0 1 0 3 42 gasket 0 0 1 0 0 1 All Particles 10,260 1548 460 128 45 12,441
- 34. @GatewayTweets #gatewaywebinars @GatewayTweets #gatewaywebinars Looking at Unknown Clear Particles Internal Case Study © Gateway Analytical, LLC, 2015
- 35. @GatewayTweets #gatewaywebinars A Common Problem • Clear particles are a common form of particulate contamination • They can be anything from glass to polymers, to cellulose, or crystalized drug product • Optical analysis can give you some idea of what the particle is however, further analysis is often required • Additional analysis can include: – SEM – PLM – FTIR – Raman © Gateway Analytical, LLC, 2015
- 36. @GatewayTweets #gatewaywebinars Unknown Particle - Optical Image Unknown particle recovered from membrane filter © Gateway Analytical, LLC, 2015 Optical Image
- 37. @GatewayTweets #gatewaywebinars 500 µm keV 109876543210 Counts 12,000 10,000 8,000 6,000 4,000 2,000 0 C O Al 1000 µm filename=040215_CI-1111_A_mp_01.tif SEM/EDS & FTIR of Clear Particulate © Gateway Analytical, LLC, 2015 SEM / EDS Spectra Y:Project_FoldersPractice ProjectsLS-15-0101FTIR040215_CI-1111_A_mp_01.1 040215_CI-1111_A_mp_01 4/2/2015 100015002000250030003500 Wavenumber cm-1 0.20.40.60.81.01.21.4 AbsorbanceUnits Page 1/1 You can tell its not glass because it is carbon rich instead of silicon rich FTIR Infrared Spectra
- 38. @GatewayTweets #gatewaywebinars @GatewayTweets #gatewaywebinars Imbedded Foreign Particulate in Vial Case Study © Gateway Analytical, LLC, 2015
- 39. @GatewayTweets #gatewaywebinars Case Study: The Problem • A drug developer had an issue with vials that were flagged during a visual inspection. • They identified several vials with a black and brown material visible on the side of the glass wall. • The unknown contaminate could not be reach for extraction due to its location in the vial. © Gateway Analytical, LLC, 2015
- 40. @GatewayTweets #gatewaywebinars Case Study: The Solution • Vials were sent to Gateway Analytical for extraction and analysis • Vial was broken to expose the unknown material • Material was found to be embedded in the vial wall • Preformed SEM and Raman on the material as it could not be isolated from the glass vial wall. © Gateway Analytical, LLC, 2015
- 41. @GatewayTweets #gatewaywebinars Case Study: Iron Oxide Embedded in Glass Vial © Gateway Analytical, LLC, 2015
- 42. @GatewayTweets #gatewaywebinars Case Study: Iron Oxides (i.e. Rust) © Gateway Analytical, LLC, 2015 Iron oxide particulates may be present in glass vial mold materials 50 µm keV 109876543210 Counts 7,000 6,000 5,000 4,000 3,000 2,000 1,000 0 C O Na Al Si Fe Fe Fe 200 µm filename = 062215_CI-8167_amf_01.TIF Y:Project_FoldersLS-15-0416Raman062215_CI-8167_amf_01.0 062215_CI-8167_AMF_01 UNDEFINED 6/22/2015 200 400 600 800 1000 1200 1400 Wavenumber cm-1 1000200030004000 RamanIntensity Page 1/1
- 43. @GatewayTweets #gatewaywebinars @GatewayTweets #gatewaywebinars Hair Discovered in Manufacturing Process Case Study © Gateway Analytical, LLC, 2015
- 44. @GatewayTweets #gatewaywebinars © Gateway Analytical, LLC, 2015 Hair Examination – Value High resistance to degradation Each species has characteristic color, length, shape, root appearance, and internal characteristics Human Hair Racial Origin Body area Disease Natural Vs. Forcibly Removed Cosmetic Treatment Environmental Factors Comparison mtDNA or nuclear DNA Animal Hair Species of Origin Dyeing Methods Possible Sources Forensic Hair Comparisons required to associate source
- 45. @GatewayTweets #gatewaywebinars Case Study: The Problem • Customer found a hair in their manufacturing process • They were able to isolate it with forceps and package it between two glass slides in order to send it out for analysis. © Gateway Analytical, LLC, 2015
- 46. @GatewayTweets #gatewaywebinars Case Study: The Solution • Gateway Analytical utilized PLM analysis to – Confirm that the sample was a hair – Determine the species of the hair (human or animal) © Gateway Analytical, LLC, 2015
- 47. @GatewayTweets #gatewaywebinars Case Study: PLM Analysis – Canine Hair © Gateway Analytical, LLC, 2015 1. Spade shaped root 2. Wide, amorphous medulla 3. Physical damage – splitting 4. Narrow, tapered distal end
- 48. @GatewayTweets #gatewaywebinars @GatewayTweets #gatewaywebinars It’s Time for the Q&A Session. Please Submit Your Questions! © Gateway Analytical, LLC, 2015
- 49. @GatewayTweets #gatewaywebinars Contact Us & Follow-up Get Insights from our Blog: www.gatewayanalytical.com/blog Contact Information David Exline Vice President Gateway Analytical exlined@gatewaya nalytical.com Julia Patterson Scientist Gateway Analytical pattersonj@gatew ayanalytical.com Marina Parra Scientist Gateway Analytical parram@gatewaya nalytical.com Brittney Norris Marketing & Creative Director Gateway Analytical norrisb@gatewaya nalytical.com @GatewayTweets © Gateway Analytical, LLC, 2015
- 50. @GatewayTweets #gatewaywebinars For Attending Today’s Webinar! @GatewayTweets © Gateway Analytical, LLC, 2015