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Leo Trevino, Michael Hunter, Sanjib Das, Tyler Pegoraro, Tyler Massey, Andres Garcia, Janet Tully, Kristie Hamby, Tomas Navratil, Benjamin Yerxa; The Aseptic Fabrication of ENV515 (Travoprost) Intracameral Implants. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4158. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
The ENV515 (travoprost) Intracameral Implant is a biodegradable, rod shaped implant using an extended release formulation of travoprost. These dosage forms do not lend themselves to typical sterilization techniques used for liquid dosage forms, such as filtration, and the drug substance travoprost is prone to degradation via ionizing radiation utilized during terminal gamma sterilization. Therefore, alternate approaches must be utilized to produce a sterile product. We describe a method for producing sterile ENV515 implants using an aseptic cGMP process and evaluate ENV515 implants produced in this process for sterility and other key attributes to support further clinical development.
ENV515 implants were produced utilizing PRINT microparticle engineering technology. An aseptic manufacturing process was developed, utilizing a combination of sterile filtration, aseptic processing, and gamma sterilization of consumables, including the mold used to form the implants. The aseptic process was validated using three consecutive process simulations (3 batches, 2,300 implants/batch) and testing 100% of each batch for sterility. The validated aseptic cGMP process was used to fabricate clinical trial material for use in first-time-in-human Phase 2a clinical study. Batch samples were also tested for assay, dose content uniformity, and in vitro drug release.
Three consecutive process simulation batches (2,300 implants/batch) were tested for microbial growth and were found to be 100% sterile in a 14 day sterility test. ENV515 clinical trial material was manufactured in this aseptic cGMP process for the initial Phase 2a study, with dose, dose content uniformity, and sterility meeting specifications generally acceptable for US commercial product (90.0 to 110.0% of label claim, content uniformity per USP905).
An aseptic cGMP manufacturing process was developed and validated for ENV515 (travoprost) Intracameral Implants. ENV515 clinical trial material was manufactured and tested in support of planned Phase 2a clinical study in glaucoma patients.
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