The outcome of a clinical research program depends, in no-small part, on the decisions made during the preclinical phases of development. As with virtually all fields of pharmaceutical research, the goal of the ophthalmic preclinical process is to identify and elevate a lead candidate to advance into the next phases of research, or to eliminate a candidate in the research stage as early as possible to optimize R&D resources and efforts.
Since animal models can reproduce important pathologic aspects of human ocular diseases, they’re used in preclinical research to determine the efficacy of the novel therapies.
Those developing such therapies, however, should be well aware of important limitations associated with animal models. While it’s possible to model some parts of a human disease in a non-human species, many ophthalmic conditions – particularly those affecting the posterior segment – could present challenges for researchers.
To meet these challenges, EyeKor’s EXCELSIOR™ Preclinical platform gives researchers more power to see valuable results from their preclinical data. To set the stage for how these new systems can help, let’s briefly step back and run through each phase of the ophthalmic preclinical process step-by-step.
1. Initial Discovery & Formulation
Discovery of potential candidate therapies is the first step toward developing them into novel drugs. With most ophthalmic diseases, this typically begins with target identification, or selecting the particular pathogenesis mechanism of the disease that affects the part of the eye one intends to treat.
Target identification for ophthalmic preclinical trials can be carried out a number of ways; but most studies use in vitro enzymatic assays or binding and cell-based studies. Common tools used for these initial preclinical stages include mass spectroscopy and liquid chromatography. After these studies are reviewed, researchers can confirm (or refute) an interaction and choose a lead compound based on their findings.
Compounds that perform well in preliminary tests move into in vivo pharmacokinetic and efficacy studies for further evaluation.
2. Drug Metabolism and Pharmacokinetics (DMPK)
Once a lead compound is identified, researchers must then develop a drug formulation and delivery route that is capable of been administered in vivo, as investigated through Drug Metabolism studies. In ophthalmic drug development, this is often a challenging task as it requires researchers and study teams to consider many factors that may influence the results of preclinical studies or clinical trials.
Pharmacokinetic studies of ophthalmic drugs provide developers with important data for determination of both optimal dose and frequency of administration. These studies also provide a number of other key data points, including:
- The maximum concentration of the drug inside specific ocular structures, like the retina (Cmax)
- When Cmax is reached (Tmax)
- How the body affects the characteristics of the drug
A strong PK study may facilitate “screening out” of many candidates that have made it to this level of testing. In today’s pharmaceutical landscape, therefore, researchers and study teams are conducting PK studies earlier and earlier to improve the selection process sooner.
3. Proof-of-Concept Studies
Proof-of-concept studies may have several goals, but among the most important is determining if the drug candidate exhibits expected results in a selected animal model, depending on known pathology and the drug’s mechanism of action. For ocular drug development, these studies involve testing animals in vivo and typically use multiple diagnostic imaging procedures. Imaging biomarkers, derived from the results of the imaging procedures through carefully planned imaging protocol and post-acquisition data analysis, are used to capture the treatment effects throughout the course of the studies.
Ultimately, the results of the preclinical study should reflect what will be tested in humans during the clinical trial.
Clinical success is never assured, no matter how well a study is designed or conducted, and translatability between animal models and human patients is complicated by numerous factors However, better decision-making early in the development process, can maximize the predictive value of of preclinical results if moving forward into clinical trials.
4. GLP Toxicity Studies
Before moving into the next phase of preclinical development, manufacturers must first carry out GLP toxicity studies to the satisfaction of the FDA’s regulatory guidelines. It’s important to note that GLP toxicity studies will need to adhere to Good Laboratory Practices (GLP). Conducting animal toxicity studies to this quality system ensures study data is collected correctly and enough animals are tested to ensure the drug is both reasonably safe and effective.
GLP toxicity studies from at least two different species need to be conducted. Using similar imaging biomarkers to those used in proof-of-concept studies, and ultimately those will be used during the clinical trial stage, these studies are done to evaluate the treatments effectiveness in animal models.
EyeKor’s EXCELSIOR™ Preclinical platform shines in the proof-of-concept and toxicology studies steps––allowing researchers to gather, manage and interpret imaging data in concordance with the information gathered at earlier stages.
5. CMC Efforts
CMC efforts (chemistry, manufacturing and control), represent the first phase of IND-enabling studies. When a final formulation for clinical use is prepared, these efforts ensure that the product is stable, and that the production process is both scalable and achievable within GMP standards.
6. Submitting IND Application
After compiling preclinical results, it’s time to present findings to the FDA in both pre-IND and subsequent IND meetings.
The ultimate goal of these meetings is to design the clinical trial protocols based on the data gathered during every step of the preclinical process as they relate to dosage, frequency of administration and safety.
Perhaps the most important takeaway to remember when planning and carrying out the preclinical investigation process is to keep the final result in mind at all times. Don’t make short-term decisions. Instead, consider the entire development process and put all necessary quality control measures in place well ahead of time.
Are you looking to bridge the gap between a preclinical and clinical program for your new treatment? EyeKor’s EXCELSIOR™ Preclinical platform is a first-of-its kind FDA 501(k)-cleared, cloud-based software platform revolutionizing the way ophthalmic imaging data in preclinical investigations is managed.
This customizable software is designed to help your team manage the full spectrum of preclinical study types and imaging modalities, harmonize findings with ophthalmic examination data, gather reports in real-time and receive seamless access to expert analysis. Contact our team today to learn how we can help you make more informed decisions during your preclinical research.