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

• EU GMP Annex 1 | Contamination Control Strategy (CCS)

  → A core reference for microbial and particulate control across aseptic manufacturing. Defines lifecycle expectations for raw materials, components, utilities, filling operations, and batch release. Aligning contamination control with a risk-based, particle-aware strategy.

• 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.

Raw Materials, Root Cause & Lifecycle Particle Control

• Identification of Particles in Parenteral Drug Raw Materials

  Kathryn Lee, Markus Lankers and Oliver Valet 🔗 https://doi.org/10.5731/pdajpst.2017.008185

  Demonstrates how Raman/CSPS detects low-level foreign particulate matter in incoming excipients, polymers, and buffers with chemical specificity. Supports raw material release testing and QbD/QRM principles defined in FDA’s QbD framework

• Raman, Infrared, and Laser-Induced Breakdown Spectroscopy Identification of Particles in Raw Materials

  Kathryn Lee, Markus Lankers and Oliver Valet 🔗 https://doi.org/10.1177/0003702817742791

  Visual inspection effectively isolates contaminated units, but revealing the particle's chemistry requires subsequent filtration and spectroscopic analysis (Raman, LIBS, FTIR) to catalog the specific material and pinpoint its origin within the manufacturing process.

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.