Curated Insights

While we prepare our own whitepapers, we’re sharing a curated selection of key resources and recent regulatory materials shaping the future of in-vitro bioequivalence testing for complex generics.

These sources highlight the scientific and regulatory trends that define our work at SizeID.bio.

Regulatory Guidance & Agency Resources

• FDA Product-Specific Guidances (PSGs)
  → Includes the new in-vitro–only option for nasal suspensions and detailed expectations for OINDPs.

• EMA Draft Guideline on Quality and Equivalence of Topical Products (2022)
  → Key reference for establishing equivalence of creams, gels, and suspensions.

• FDA Guidance on Topical Dermatologic Drug Products
  → Outlines comparative assessment and in-vitro release test (IVRT) expectations.

• USP-NF Addressing Subvisible Silicone Oil Droplets – Proposal for a New General Informational Chapter

  → Outlines analytical limitations, safety and immunogenicity considerations, regulatory perspectives, and lifecycle risk management strategies relevant to subvisible particle control.

Scientific Reading | OINDP Bioequivalence

• Raman Chemical Imaging for Ingredient-Specific Particle Size Characterization of Aqueous Suspension Nasal Spray Formulations: A Progress Report
  Doub, Adams, Spencer, Buhse, Vogel, Poon et al. (2007)
  🔗 https://link.springer.com/article/10.1007/s11095-006-9211-2
  🔒 Peer-reviewed | Login required
  → Early foundation for Raman/MDRS-style ingredient-specific PSD in nasal sprays.

• Characterizing a Nasal Spray Formulation from Droplet to API Particle Size
  Kippax, Huck, Levoguer, Virden, Suman (2011)
  🔗 PharmTech article (open)
  📘 Open access trade article
  → Bridges spray droplet metrics to API particle sizing and Raman imaging.

• Scientific Considerations for the Review and Approval of First Generic Mometasone Furoate Nasal Suspension Spray in the United States from the Bioequivalence Perspective
  Liu, Absar, Saluja, Guo, Chowdhury (2018)
  🔗 SpringerLink – The AAPS Journal
  🔒 Peer-reviewed | Login required
  → FDA case explaining the weight-of-evidence logic where MDRS supports BE.

• Investigating Orthogonal In Vitro Analytical Approaches to Demonstrate Bioequivalence of Nasal Suspension Formulations
  Farias, Huck-Jones (2018)
  🔗 https://www.materials-talks.com/wp-content/uploads/2017/12/82.-Farias-Nasal-UoB-Poster-2017-A0.pdf
  📘 Open access conference paper
  → MDRS paired with orthogonal assays to strengthen BE.

• Challenging the Bioequivalence Hurdles for OINDPs: Achieving Q3 Structural Equivalence
  Price, Farias, Ganley, Shur (2018)
  🔗 https://nanopharm.co.uk/wp-content/uploads/2023/11/Publication-Challenges-in-OINDPs-Achieving-Q3-Equivalence.pdf
  📘 Open access conference paper
  → Q3 structural equivalence framing that underpins current OINDP strategies.

• The Application of Morphological Filters in Automated Imaging for Nasal Formulations: A Design of Experiment Approach
  Serra, Hall, Rossi, Shur (2022)
  🔗 https://ddl-conference.com/ddl2021/conference-papers/the-application-of-morphological-filters-in-automated-imaging-for-nasal-formulations-a-design-of-experiment-approach/
  📘 Open access conference paper
  → DoE-driven optimization of morphology filters to enhance MDRS classification.

• A Systematic Approach in the Development of the Morphologically-Directed Raman Spectroscopy Methodology for Characterizing Nasal Suspension Drug Products
  Farias, Shur, Price, Bielski, Newman (2021)
  🔗 https://link.springer.com/article/10.1208/s12248-021-00605-w
  📘 Peer-reviewed | Open access
  → Full MDRS method development & validation workflow for nasal suspensions.

• Analytical Method Development for Characterizing Ingredient-Specific Particle Size Distributions of Nasal Spray Suspension Products
  Thomas, Absar, Delvadia, Conti, Saluja, Lee (2021)
  🔗 https://jpharmsci.org/article/S0022-3549(21)00152-0/abstract

🔒 Peer-reviewed | Subscription
→ Defines analytical parameters for MDRS ingredient-specific PSDs; supports Q3 work.

• Recent Advances in Orthogonal Analytical Techniques for Microstructural Understanding of Inhalable Particles: Present Status and Future Perspective
  Jadhav, Patil, Bhagwat, Gaikwad, Chaudhari (2022)
  🔗 https://www.sciencedirect.com/science/article/abs/pii/S1773224721007693
  🔒 Peer-reviewed | Subscription
  → Review of orthogonal tools (MDRS, X-ray, MS, etc.) for microstructural insight.

• O-PTIR Spectroscopy for Characterizing Active Pharmaceutical Ingredient-Specific Particle Size Distributions of Nasal Spray Suspension Products
  Khanal, Cao, Tai, Chan (2024)
  🔗 https://www.sciencedirect.com/science/article/abs/pii/S0378517324008871
  🔒 Peer-reviewed | Subscription
  → O-PTIR as a next-gen orthogonal complement to MDRS for API-specific PSD.

Stability | Polysorbate and Silicone Oil Droplets

• Differentiation between foreign particulate matter and silicone oil induced protein aggregation in drug solutions by automated Raman spectroscopy
  Lankers, M., Munhall, J., Valet, O. (2008) 🔗 https://doi.org/10.1017/S1431927608086807

  🔒 Peer-reviewed | Conference
  → Automated Raman proof-of-concept distinguishing silicone oil droplets from protein aggregates in liquid drug formulations — foundation for modern in-situ MDRS.

• Subvisible particle identification in protein-based formulations by Raman spectroscopy
  Lankers, M., Valet, O., Laskina, O. (2017) 🔗 https://www.europeanpharmaceuticalreview.com/article/22945/subvisible-particle-identification-in-protein-based-formulations-by-raman-spectroscopy/

  🌐 Open access
  → Introduces wet-cell Raman microscopy for in-situ identification of protein aggregates and silicone oil droplets in monoclonal antibody formulations — preserving their native liquid state.

• Characterization of protein aggregates in suspension and on a filter membrane by Morphologically-Directed Raman Spectroscopy 🔗 https://www.technologynetworks.com/analysis/application-notes/characterization-of-protein-aggregates-in-suspension-and-on-a-filter-membrane-by-morphologicallydirected-raman-spectroscopy-228607
  ( The Analytical Scientist / Malvern Panalytical )

  🌐 Application note
  → Compares “wet-cell” vs. traditional “dry” MDRS — showing that filtration crystallizes aggregates while in-situ Raman captures their true diffuse morphology.