The FDA published a draft guidance that discusses quality considerations for ophthalmic drug products (i.e., solutions, suspensions, emulsions, gels, ointments, and creams) intended for topical delivery in and around the eye. In particular, the guidance discusses:
Approaches to evaluating visible particulate matter, extractables & leachables (including safety thresholds), and impurities and degradation products.
Use of in vitro drug release/dissolution testing as an optional quality control strategy for certain ophthalmic dosage forms.
Recommendations for design, delivery, and dispensing features of container closure systems (CCSs).
Recommendations for stability studies, including in-use stability studies and freeze/thaw studies for emulsions and suspensions.
Container Closure System (CCS) Design
The CCS section of the document describes recommendations regarding design elements and delivery / dispensing characteristics that applicants and over-the-counter (OTC) manufacturers should consider. When the CCS that holds or contains an ophthalmic drug also delivers it, it may also be a device-constituent part and, together with the drug contained within, a combination product. The following quality attributes are recommended for the CCS:
All containers of ophthalmic drugs must be sterile at the time of filling and closing and sealed to prevent product use without destruction of the seal (i.e., tamper-evident packaging).
Unit Dose Containers: The agency recommends that the maximum fill volume of a unit dose container (nonpreserved) be no more than 0.5 mL for solutions, emulsions, and suspensions. It is also recommended that the maximum fill for a unit dose ointment or gel be no more than 1 gram. Unit dose containers should not be able to be recapped.
Multidose Containers: - Drop size: The FDA recommends that the drop size in a multidose CCS be between 20 and 70 microliters. - Dose uniformity of suspension drug products: As recommended in USP General Chapter <771> Ophthalmic Products—Quality Tests, a resuspendability/redispersibility test should be performed. For multidose containers, data for a one-time dose-uniformity study (from top, middle, and bottom of the container) should be provided from at least three pilot or exhibit batches to demonstrate that the drug substance is uniformly dispersed and the labeled dose can be consistently delivered throughout the shelf life. Alternatively, applicants may consider providing data from development batches (such as IMP batches) that represent the to-be-marketed formulation to demonstrate dose uniformity.