. Author manuscript; available in PMC: 2022 Nov 1.

Published in final edited form as: Adv Drug Deliv Rev. 2021 Sep 13;178:113971. doi: 10.1016/j.addr.2021.113971

Table 7.

Key obstacles in the clinical translation of local delivery strategies.

Obstacle	Description of Challenges	Ref(s)
Formulation Development
Scale-up	Complex formulations challenging to scale	[254]
Scale-up	Specifications needed to limit batch-to-batch variability	[254,257]
Sterilization	Aseptic vs. terminal sterilization decision	[258]
	Can damage polymeric chains	[257]
	Can damage biologic-based cargo	[256]
Preclinical Evaluation
Dose scaling	Pre-existing dose scaling guidance based on systemic exposure	[259,260]
Dose scaling	Biologics distribute differently than small molecules	[259,260]
In vitro to In vivo models	Need more emphasis on pharmacokinetic (i.e., absorption) and pharmacodynamic (i.e., toxicity) studies	[254]
In vitro to In vivo models	In vitro to in vivo models do not always correlate	[256,262]
Cost
Overall Cost	Between $161 million to $2 billion USD	[261]
Clinical Trials (average cost)	Phase I: $6.6 million USD; Phase II: $16 million USD; Phase III: $11.9 million USD	[261]