Module232025

Takeda Pediatric CMC Considerations

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FCT: film-coated tablet

Initial Material Characterization ▪ Dosing/Extrapolation ▪ Tablet dimensions ▪ Taste Assessment / Patient Compliance ▪ Manufacturability: Powder Flow; Compressibity, Tabletability and Compactibility (CTC) Analysis

Formulation ▪

Not recommended to reconstitute API in water Spray dried dispersion (SDD) formulation needed

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Powder/granules

Mini-tablets

Chewable tablet

Formulation strategy

Roller compacted granules

Roller compaction + compression

Roller compaction + compression

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Used components of adult tablet as base components

Used components of adult tablet as base components

Used components of adult tablet as base components

20% API SDD loading

2.5 mm tablets

20% API SDD loading

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Incorporation of sweeteners and taste modifiers to assess compatibility

60-70% API SDD loading to minimize tablet size Initial assessments of potential challenges with powder flowability, disintegration, and dissolution Acceptable processability at lab-scale Very slow disintegration and dissolution (40-60% after 45 min) performance

• Incorporation of sweeteners and taste modifiers to assess compatibility • Initial assessments for potential challenges with friability, disintegration, and dissolution

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Key findings

Acceptable processability at lab-scale De-prioritized after observing crystallization after reconstituting tablet in water

Acceptable processability at lab-scale

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• Acceptable friability, disintegration, and dissolution performance

Quality (CMC) Development Considerations

The Organisation for Professionals in Regulatory Affairs