Biomedical Engineering Reference
In-Depth Information
Sustained-Release Ocular Drug Delivery Systems:
Bench to Bedside Development
Susan S. Lee, Michael R. Robinson, and Scott M. Whitcup
Abstract
The process of bringing a drug through early development and on through a successful clinical trials
campaign is long and complex. This chapter provides an overview of the drug development process and
some of the challenges and pitfalls that can be encountered on the path to marketing approval for a
sustained-release intraocular drug delivery system. In general, the drug development process proceeds
from exploratory analyses of new compounds, through preclinical and clinical testing of promising drug
candidates, to application for marketing approval in one or more markets. Although the application for
marketing approval is the final step, success depends on taking the requirements for obtaining marketing
approval into consideration early in the process and initiating communication with the relevant regulatory
agency(s) while the candidate drug is still in preclinical testing. A successful preclinical development
program should be designed to provide all the information needed to determine if the drug is appropriate
for further testing in human subjects. Approval to begin human testing (phase I trials) is only granted if
there is sufficient evidence of drug safety, if the pharmacologic profile of the drug is appropriate for the
condition it is proposed to treat, and the clinical trial design submitted is sufficient to ensure the safety of
the human subjects. Clinical testing, if approved, proceeds through phase I (to evaluate safety and dosing
considerations), to phase II (early investigations of efficacy and further exploration of dose-response), and
finally to phase III (definitive investigations of safety and efficacy in the intended patient population). If the
results of the clinical trials demonstrate sufficient safety and efficacy, the drug developer can apply for
marketing approval in the United States (US) through the Food and Drug Administration (FDA) or in the
European Union (EU) through one of three separate pathways to approval—the centralized, decentralized,
or mutual recognition procedures. In all cases, the success of an application will depend not only on
the merits of the drug itself but also on how well the drug development program was designed to meet the
concerns and requirements of the appropriate regulatory agency(s). The single most effective way to ensure
that a drug application meets these requirements and concerns is through early and frequent consultation
with the appropriate regulatory agency contacts.
Key words
Clinical trials, Ocular drug delivery, Regulatory, FDA, EMA, Sustained-release, Marketing
approval, Drug approval
1
Introduction
As our understanding of normal physiology and pathophysiological
processes improves, new targets for therapeutic intervention
become apparent and begin to be investigated by drug developers.
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