GLP Ocular Toxicology & Safety

Safety assessment is the first major step to regulatory approval, so we offer a regulatory safety program that meets Good Laboratory Practice (GLP) standards.

Before initial administration into humans and prior to receiving regulatory approval, pharmaceutical and biotechnology companies must show evidence of a compound’s biological activity and provide data indicating that the drug is reasonably safe. 

Iris Pharma offers a safety assessment program that meets GLP standards, including acute local toxicity, chronic local toxicity, maximum tolerated dose (MTD)corneal anesthesia, and ocular histopathology assessment. Also, depending on the properties of the product, tests for measuring lacrimation and pupil reactivity can be included as well.

 

Acute Local Toxicity

Iris Pharma quantifies acute local toxicity using the following:

Guidelines: OECD 405: Acute Eye Irritation/Corrosion - adopted 12 May 1981, last updated 02 October 2012. European Commission Directive # 92/69/EC (July 31, 1992) - Offic. J. Eur. Commun. 1992; 35, L383: B5

Administration: Topical ocular administration: 1 x 100 µl

Animals: Albino rabbits: 3 per group

Evaluation: Draize test at 5 min, 60 min, 1, 2 and 3 days (4 and 7 days if necessary)

Groups: Test article, vehicle (when applicable), control substance

Chronic Local Toxicity

Iris Pharma quantifies chronic local toxicity using the following:

Guidelines: OECD 410: Repeated Dose Dermal Toxicity: 21/28-Day study, adopted 12 May 1981. European Commission Directive # 92/69/EC (July 31, 1992) - Offic. J. Eur. Commun. 1992; 35 L383: B9

Formulation (GMP): Eyedrop, gel, ointment, devices (insert, implant…), particles, patch, cream...

Administration: Topical ocular application, intravitreal injection (IVT), subconjunctival injection, subTenon injection (SBT), retrobulbar injection, periocular injection, intracameral injection, subretinal, intrascleral, transscleral, intrastromal, iontophoresis…

Animals: Albino rabbits: at least 5 males and 5 females per group

Dosage: Multiple daily administration for 28 days or more

Evaluation:

  • Daily: Draize scale, food and water consumptions
  • Weekly: McDonald-Shadduck scale and body weight, food and water consumptions
  • Autopsy, main organ weight and ocular histology
  • ERG, IOP, HRT, hematology, blood biochemistry, organ histology : customization according to the test substance

Groups: Test article, vehicle (when applicable), control substance, reference substance (when applicable).

 

Ocular toxicology

Corneal Anesthesia Tests

Corneal anesthesia

Iris Pharma performs corneal anesthesia tests, including: 

Guidelines: EMEA (CPMP) note for guidance on non-clinical local tolerance testing of medicinal products (adopted February 2001) CPMP/SWP/2145/00

Formulation: Eyedrop, gel, ointment, cream, …

Administration: Topical, iontophoresis…

Animals: Albino rabbits

Evaluation: Cochet Bonnet esthesiometer

Parameters: Number of mechanical stimuli necessary to induce a blinking reflex within 1 hour

Reference substances: Oxybuprocaine / tetracaine

 

 

 

Graph legend: Corneal anesthesia evaluated by the number of mechanical stimuli necessary to induced the blinking reflex

Ocular Histopathology

The performance of ocular histopathology is a true craft, requiring highly trained and specialized staff. The difference in density from one ocular structure to another may go unnoticed by those who have little experience in this field.

Iris Pharma’s team has been working for 25 years on detailing and analyzing every structure of the eye, even going so far as to observe inflammatory cells in the vitreous body and aqueous humor. Due to these skills, our pathologists are able to use several techniques and perform specialized evaluations, including: 

  • Biopsies
  • Histological sections
  • Ophthalmic specimen slide preparation
  • Microscopic examination of tissues
  • Staining by immunohistochemistry
  • Immunofluorescence

Eye section eosinophil

Lacrimation Tests

Guidelines: EMEA (CPMP) note for guidance on non-clinical local tolerance testing of medicinal products (adopted February 2001) CPMP/SWP/2145/00

Administration: Topical, iontophoresis...

Animals: Albino rabbits

Evaluation: Schirmer strips, microcapillaries

Parameters: Quantity of tears collected in 5 min

Reference substances: Pilocarpine

 

 

 

Graph legend: Changes in tear migration after one instillation

Pupillary Diameter

Guidelines: EMEA (CPMP) note for guidance on non-clinical local tolerance testing of medicinal products (adopted February 2001) CPMP/SWP/2145/00

Administration: Topical, iontophoresis…

Animals: Albino rabbits

Evaluation: Graduated rule

Parameters: Measurement in mm versus time

Reference substances: Pilocarpine or atropine

 

 

 

Graph legend: Changes in pupillary diameter after one instillation

Pupillary diameter