Drug Safety Evaluation Services

Ocular Irritation and Corrosion Safety Evaluation

We can provide comprehensive ocular irritation and corrosion testing for topical ophthalmic formulations, including eye drops, ointments, gels, and contact lens solutions. Services include in vitro assays using corneal epithelial cell cultures, 3D corneal organoids, and ex vivo corneal models to evaluate cytotoxicity, barrier function disruption, and inflammatory response. In vivo testing using validated rabbit models is available to assess clinical signs of irritation—such as conjunctival hyperemia, edema, discharge, and corneal opacity—per OECD and FDA guidelines. We also conduct histopathological analysis of ocular surface tissues (cornea, conjunctiva, eyelid) to evaluate structural damage, and measure tear film break-up time and corneal staining to assess functional impairment. These evaluations help clients determine the local tolerability of formulations and identify potential irritants that may require formulation optimization.

Retinal and Posterior Segment Toxicity Evaluation

Our team can conduct specialized safety evaluations for drugs targeting the posterior segment, including the retina, choroid, and optic nerve—critical for therapies addressing age-related macular degeneration (AMD), diabetic retinopathy (DR), and inherited retinal diseases (IRDs). Services include in vivo toxicity testing using rodent, zebrafish, and non-human primate models, with assessments of retinal structure via OCT, fundus autofluorescence, and histopathology; retinal function via ERG and visual evoked potential (VEP); and optic nerve integrity via nerve fiber layer thickness measurement and axonal counting. In vitro assays using iPSC-derived retinal organoids, RPE cells, and retinal ganglion cell cultures enable mechanistic analysis of toxicity mechanisms, such as oxidative stress, apoptosis, and mitochondrial dysfunction. For gene therapies, we can evaluate off-target effects, insertional mutagenesis, and immunogenicity in retinal tissues to ensure long-term safety.

Anterior Segment Toxicity Evaluation

We offer tailored safety evaluation services for drugs targeting the anterior segment, including the cornea, iris, ciliary body, and lens. Services cover assessments of IOP fluctuations—critical for glaucoma therapies—using tonometry and gonioscopy; lens opacity and cataract formation via slit-lamp photography and histopathology; and uveal inflammation via clinical scoring and inflammatory marker analysis (e.g., cytokines, chemokines). In vivo models for anterior segment toxicity include rodents, rabbits, and pigs, with specialized protocols for intravitreal, subconjunctival, and topical drug administration. In vitro models, such as corneal endothelial cell cultures and ciliary body epithelial cell lines, enable evaluation of cell viability, morphology, and functional integrity. These evaluations help clients identify potential toxicities such as corneal endothelial dysfunction, iritis, and cataractogenesis that may limit clinical utility.

Systemic Toxicity Evaluation for Ophthalmic Drugs

We can assess systemic toxicities associated with ophthalmic drug absorption, even for topical formulations, which may penetrate the ocular surface or enter the systemic circulation via nasolacrimal drainage. Services include acute, subacute, and subchronic toxicity testing using rodent and non-rodent models, with evaluations of body weight, food and water consumption, clinical signs of distress, hematological and biochemical parameters (e.g., liver and kidney function, electrolyte balance), and organ weight and histopathology. We also conduct genotoxicity testing (Ames test, micronucleus assay, chromosome aberration test) to assess potential DNA damage, and immunotoxicity testing to evaluate effects on the immune system—critical for biologics and gene therapies. These assessments ensure that ophthalmic drugs do not induce unintended systemic adverse effects that could compromise patient safety.

Reproductive and Developmental Ocular Toxicity Evaluation

For ophthalmic drugs intended for use in reproductive-age populations, we can provide specialized reproductive and developmental toxicity evaluations. Services include assessment of fertility and early embryonic development, embryonic-fetal development, and pre- and postnatal development using validated rodent and non-rodent models. Ocular-specific endpoints include fetal ocular structure and function (via histopathology and ERG), postnatal retinal maturation, and long-term ocular sequelae in offspring. These evaluations help clients determine whether a drug poses risks to fetal or neonatal ocular development, enabling appropriate labeling and risk mitigation strategies for clinical use.

Biologic and Gene Therapy Ocular Safety Evaluation

We can deliver specialized safety evaluation services for biologic and gene therapies, which present unique safety challenges such as immunogenicity, off-target effects, and long-term persistence. For biologics (e.g., monoclonal antibodies, cytokines), services include immunogenicity testing via antibody detection assays (ELISA, Western blot) and evaluation of immune-mediated ocular inflammation; pharmacokinetic (PK) and pharmacodynamic (PD) profiling to assess drug distribution and accumulation in ocular tissues; and toxicity testing to evaluate tissue-specific damage. For gene therapies (e.g., AAV vectors, lentiviral vectors), we can assess vector biodistribution, insertional mutagenesis via next-generation sequencing, immune response to the vector, and long-term ocular safety via extended in vivo studies. These services are critical for advancing biologic and gene therapies, which are increasingly being developed for previously untreatable ocular disorders.

Toxicokinetic and Pharmacokinetic (TK/PK) Integration

To enhance the translational relevance of safety data, we can integrate toxicokinetic (TK) and pharmacokinetic (PK) analyses into ophthalmic drug safety evaluations. Services include quantification of drug concentrations in ocular tissues (cornea, retina, vitreous humor, aqueous humor) and systemic fluids (plasma, serum) via liquid chromatography-mass spectrometry (LC-MS/MS) and other sensitive analytical techniques. TK/PK profiling enables correlation of drug exposure with toxicity endpoints, identification of dose-dependent effects, and determination of safety margins. Protheragen's team can design TK/PK studies tailored to the drug's administration route and modality, providing critical data to optimize dosing regimens and inform clinical trial design.

Regulatory-Compliant Safety Reporting

We can generate comprehensive, regulatory-compliant safety evaluation reports aligned with GLP standards and guidelines from the FDA, EMA, NMPA, and OECD. Reports include detailed study design, methodology, raw data, statistical analysis, and conclusions, with clear documentation of ocular and systemic safety endpoints. Our team works closely with clients to address regulatory feedback, ensure data integrity, and prepare submission-ready documents that support investigational new drug (IND) and new drug application (NDA) filings. Protheragen's regulatory expertise ensures that safety evaluation data meets global requirements, facilitating the smooth advancement of ophthalmic drugs through the development pipeline.