09:03:56 From Bruno Hancock (Pfizer) to Everyone : Welcome. We will be using the chat function for questions today. 09:04:58 From Bruno Hancock (Pfizer) to Everyone : Feel free to type questions into chat as we go. I will call on people in the order the questions are received. 09:06:58 From Bastiaan Dickhoff - DFE Pharma to Everyone : Bas v Laarhoven will present for DFE Pharma 09:12:53 From Zukowski, Samual (Corteva) to Everyone : Could we also discuss how to handle the R&D approach to specs vs. the practicality of measuring them in a production setting? 09:18:27 From Kumar_Rohit to Everyone : Sometimes the particle size spec has to be set based on small scale studies, which can be controlled very tightly. However, when we go for the commercial scale, now the particle size is harder to control and it is falling out of spec affecting the final yield. Is there a good way to set such spec? 09:20:47 From Paul Mort, Purdue Univ. to Everyone : Thoughts or experience with using PSD specs in patent filings? 09:24:01 From Navin Venugopal (Corning) to Everyone : What roles do gauge-based studies such as MSA or Gauge R&R play in establishing specifications? Can’t spec what you can’t consistently measure 09:26:13 From Jim Michaels - IFPRI to Everyone : I believe that Gauge R&R is underused - at least in Pharma! I've seen too many examples of setting specs too narrow for the measurement... 09:31:58 From Bastiaan Dickhoff - DFE Pharma to Everyone : Flow function, which apparatus is golden stndard , we would say rst-xs with limestone 316 calibration? 09:33:10 From Bastiaan Dickhoff - DFE Pharma to Everyone : Also, like to hear the presenters view on 'd' vs 'x' nomenclature for particle size by lsd. (both are iso approved) 09:33:20 From Jim Michaels - IFPRI to Everyone : Years ago, Derrick Geldart did a shear cell study for IFPRI. Result showed there was no gold standard - even labs using the same shear cell got a different result! 09:34:19 From Bastiaan Dickhoff - DFE Pharma to Everyone : with the astm certifications of methods this has significantly improved, but depend on the equipment 09:38:18 From Jim Michaels - IFPRI to Everyone : Schulze cell requires a lot of material, doesn't it? Too much for pharmaceutical materials? 09:38:27 From Leo Manley - Abbvie to Everyone : was the Freeman FT4 included in the 'gold standard' study for flowability? 09:40:06 From Mike Gentzle (Merck) to Everyone : Do you ever set specs on flowability or control though PSD (e.g. d10)? 09:42:01 From Paul Mort, Purdue Univ. to Everyone : To your point on multimodal, to what extent do you use fitting models, lognormal, Weibull, etc, using a breathe parameter in a spec? 09:43:01 From Navin Venugopal (Corning) to Everyone : Does the type of distribution matter for the sake of specification? (E.g. number vs volume) 09:45:57 From Jim Michaels - IFPRI to Everyone : Bas - can you speak to the problem of providing a certificate of analysis for multiple drums of material produced in a continuous process? 09:50:12 From Bastiaan Dickhoff - DFE Pharma to Everyone : Jim - Good question - we are aligned to IPEC EU/USA/etc meaning the parameter on a CoFa is determined on a risk based profile - thus most parameters have a different sampling regime and cofa data represents the pooled sample. However each individual sample taken in a process have to fit the specifications. 09:50:23 From Jeff Bodycomb (Horiba) to Everyone : You mention full distributions by laser diffraction. Do you ever evaluate/compare the entire distribution (say by earth mover algorithm)? 09:51:27 From Bastiaan Dickhoff - DFE Pharma to Everyone : DFE Pharma does this via MVA approaches 09:52:31 From Johannes Walter, FAU Erlangen to Everyone : Beyond the issue of distribution weighting (e.g. number vs mass/volume), different measurement methods will track different equivalent size properties (e.g. volume, surface, scattering equivalent, hydrodynamic diameter, sedimentation equivalent,...). How can comparability between different measurment methods (e.g. sieving vs LD) be guaranteed? 09:56:30 From Mike Gentzle (Merck) to Everyone : To Navin: for Merck / pharma, weight-based PSD (sieve or LS) is most relevant to key product performance such as assay and dissolutiony but Number is relevant for contamination in injectable solution products. 10:06:07 From Paul Mort, Purdue Univ. to Everyone : To what extent do you adjust optical models (absorption, refraction) to achieve correlation? Material dependent? 10:06:13 From Poom Bunchatheeravate (Vertex) to Everyone : Can you speak to different PSD obtain from the same type of equipment (same model but different unit and location)? 10:08:58 From Pete Bergstrom- Sila Nanotechnologies to Everyone : Relating to offsets between laser diffraction instrumentation, is it best practice to use 10, 20, 30+ batch samples to correlate and assess “offsets”? Should certified reference materials also be a part of the instrument correlation, and if so to what level? 10:14:33 From Conny- AbbVie to Everyone : Coming back to moisture detection, what is the presenter’s opinion on water activity vs LOD? 10:17:31 From Stefan Bellinghausen - PSE to Everyone : What method to collect representative samples do you use/recommend? 10:18:44 From Edgar Chavez (Nestlé) to Everyone : When PSD, solubility, density measurements are done, do you normally control and report at which environmental conditions (T° and RH%) ? 10:19:41 From Mike Gentzler (Merck) to Everyone : For pharma, the inter-model inconsistency [e.g. dispersing power] and inherent uncertainty of LS [Mie fitting model] can be very expensive for registered PSD methods for active powders. A world-wide filing update can cost > $1million if an 'equivalent' method is not obtainable on a 'difficult' sample; risk factors = PSD extending below 5 um, multiple PSD metrics specified, and/or, sensitivity to dispersion[ e.g. strongly flocculated, attrition prone]. This is under-appreciated by vendors--even on their own models. Accuracy standards are woefully inadequate and inconsistent. 10:21:39 From Chris Rueb - AVEKA to Everyone : Ninna, How are your customers using the info and SPEC you tabulate on the electrostatic measurements ? Is that becoming a more common request or more common QC type measurement you are doing? 10:27:10 From Bastiaan Dickhoff - DFE Pharma to Everyone : paper on lod vs aw 10:28:20 From Jim Michaels - IFPRI to Everyone : Bastiaan - thanks! Can you type in the reference? Zoom won't save the file with chat. 10:29:51 From Bastiaan Dickhoff - DFE Pharma to Everyone : Watwer activity and moisture: the complexity and interrelationships explained by PHM Janssen, in Sept 2020 Tablets and Capsules 10:30:17 From Bastiaan Dickhoff - DFE Pharma to Everyone : watwer=water 10:30:58 From Massih Pasha (Chemours) to Everyone : To All Presenters: assuming you have a "representative" sample, how do you take into account the sample (stress) history? e.g. a sample sent from a manufacturing site to a R&D department and its effects on measurements such as loose bulk density , flowability, etc. 10:33:47 From Massih Pasha (Chemours) to Everyone : another example is samples taken from top of a package vs. the bottom 10:36:25 From Paul Mort, Purdue Univ. to Everyone : To what extent do you use in or at line measures of incoming raw materials to adjust your process? 10:40:42 From Matt Russell (Corteva) to Everyone : technique, technique, technique. 10:41:12 From Andrei to Everyone : I believe GranuTools is trying to address the variability in sample preparation for bulk density measurements 10:42:26 From Hugh Stitt [JM] to Everyone : Was I that made the comment on BD being an easy measurement. I dd not comment on its reliability. Point well made 10:43:20 From Bas van Laarhoven- DFE pharma to Everyone : For sampling challenges please I would refer to Terence Allen his "Golden Rules of Sampling". 10:48:25 From Jeff Bodycomb (Horiba) to Everyone : Where does porosity matter? What size pores are important? 10:49:31 From Hugh Stitt [JM] to Everyone : In catalysis - pore volume is the critical term in effective diffusivity,, small pores (BET) are vital to getting catalyst activity 10:50:02 From Navin Venugopal (Corning) to Everyone : Catalyst storage capacity too (carriers) 10:51:17 From Kevin Lewis - Ecolab to Everyone : Porosity is critial for surfactant loading on solids for Ecolab products. Also for compaction processes. 10:53:18 From Kumar_Rohit to Everyone : micropores in extended release particles, specially used in long acting injectables, can impact the final release profile 10:54:19 From Jeff Bodycomb (Horiba) to Everyone : Thank you 10:54:45 From Mike Gentzler (Merck) to Everyone : closed porosity in spray-dried powders is a practical concern and characterization challenge if you want to get quantititative 10:56:55 From Jim Michaels - IFPRI to Everyone : I think there's an opportunity for a Round Table on item 2... 10:57:24 From Mike Gentzler (Merck) to Everyone : Yes. SD analyzer / method inconsistencies is a solvable problem with industry cooperation 10:57:26 From Mark Strohmeier to Everyone : Agree - 10:58:29 From Chuck Cravens, Lincoln Electric to Everyone : Yes, we study this 10:58:32 From Jeremy Lechman to Everyone : It's important to us 10:58:40 From Matt Russell (Corteva) to Everyone : This is important in Ag Chem also. 10:58:55 From Edgar Chavez (Nestlé) to Everyone : It is quite important for Foods 10:58:55 From Kevin Lewis - Ecolab to Everyone : It's important in regards to porosity and density. 10:59:09 From Andrei to Everyone : agreed, formulations for Ag Chem are very sensitive to phase stability and quality 10:59:09 From Matt Maille-Keurig Dr Pepper to Everyone : Agreed 10:59:09 From Chuck Cravens, Lincoln Electric to Everyone : Outstanding discussion, must leave, thank you 10:59:44 From Chris Rueb - AVEKA to Everyone : most interesting. thanks all 11:00:10 From Varsha Paida (Albemarle) to Everyone : Very interesting virtual discussion! Thanks a lot! 11:00:16 From Pete Bergstrom- Sila Nanotechnologies to Everyone : Thanks so much to you all, fascinating conversation! 11:00:34 From Weili Yu (Pfizer) to Everyone : Excellent discussions, thank you! 11:00:36 From Kumar_Rohit to Everyone : Thanks everyone, very fruitful and insightful discussion! 11:00:39 From Jeff Bodycomb (Horiba) to Everyone : Yes, thank you all. 11:00:54 From Bastiaan Dickhoff - DFE Pharma to Everyone : thanks for organizing 11:01:05 From Mark Strohmeier to Everyone : Thank you 11:01:06 From Poom Bunchatheeravate (Vertex) to Everyone : thank you this is very interesting 11:01:09 From Zukowski, Samual (Corteva) to Everyone : Great discussion, thanks! 11:01:23 From Corwin Miller Lincoln Electric to Everyone : Very good thank you