Development cycle Unither Pharmaceuticals, a Contract Development and Manufacturing Organization (CDMO), offers a comprehensive range of services for the development of ophthalmic products. This article delves into Unither’s approach to the preformulation, formulation, analytical, sterilization, container/contents interactions, scale-up, and industrialization stages of ophthalmic product development. Unither initiates the development process with a thorough preformulation study, encompassing API characterization through various techniques such as optical microscopy, assays, DRX, PSD, Log P, Log D, and membrane permeability assessments. The study includes a compatibility study, solubility study, early conservation study, and the manufacturing of preclinical batches. Analytical methods are developed to ensure accurate API assay, impurities assay, and forced degradation studies. Additionally, preservative and antioxidant assays are conducted as needed. Unither explores various formulations, including solutions, gels, emulsions, micellar solutions, micro and nanoemulsions, and nanosuspensions. Formulation development follows Quality by Design (QBD) principles, integrating risk analysis and Design of Experiments (DoE) on Jmp software. Rheological properties, bioadhesion, particle size distribution (PSD), and packaging choices are meticulously assessed, ensuring the finished product meets critical criteria such as appearance, pH, osmolality, density, drop size, and viscosity. The impact of steam sterilization, filtration, and filterability are evaluated to ensure the efficacy of the sterilization process. Unither meticulously examines container/contents interactions through stressed studies and works closely with packaging suppliers to assess extractables and leachables. Unither employs a systematic approach to scale-up studies, evaluating process robustness, conducting preliminary stability studies, manufacturing technical batches, validating analytical methods, and verifying cleaning procedures with LOQ method validation and recovery efficiency assessments. This stage culminates in the production of clinical batches, paving the way for further development. The transition to industrialization involves the production of small commercial batches, process validation, sterilization validation, ICH stability studies, and ongoing stability studies. Unither places a strong emphasis on compliance with ICHQ3D guidelines and conducts studies on nitrosamines to ensure product safety and quality. Unither’s commitment to excellence in ophthalmic product development is evident through its systematic and thorough approach across various stages. From preformulation studies to industrialization, Unither prioritizes quality, safety, and efficacy. By integrating cutting-edge technologies and adhering to rigorous standards, Unither stands as a reliable partner for pharmaceutical companies seeking CDMO services in the development of innovative and high-quality ophthalmic products. Preformulation study • API characterization: Optical microscopy, assays, DRX, PSD, Log P, Log D, membrane permeability… • Compatibility study • Solubility study: o Solubility at saturation in different media o Solubility improvement: Cyclodextrin complexation, co-solvent, surfactants, micronization… o Modelization (software) o Early conservation study • Preclinical batches manufacturing Analytical methods development • API assay • Impurities assay and forced degradation study • Preservative and antioxidant assays if necessary • Sterility and microbiological controls Formulation study • Different forms: Solution, Gel, Emulsion, Micellar solution, Micro and nanoemulsion, Nanosuspension • Formulation development by QBD (risk analysis and DoE on Jmp software) • Rheology (viscoelastic behavior, gelation assessment, resistance under simulated eye blinking, viscosity behavior after tear contact…) • Bioadhesion (mucoadhesive force) • PSD by laser diffraction and DLS, Zeta potential if necessary • Packaging choice: single or multiple use, glass or plastic • Finished product characterization: Appearance, pH, Osmolality, Density, Drop size, Viscosity Sterilization study • Steam sterilization impact • Filtration study • Filterability study Container/contents interactions • Stressed studies • Extractables and leachables (support of packaging supplier) Scale-up study • Process robustness evaluation by QBD (risk analysis and DoE on Jmp software) • Preliminary stability study • Technical batches • Analytical methods validation • Cleaning verification (product cleanability) with LOQ method validation and recovery efficiency • Clinical batches manufacturing Industrialization • Small commercial batches • Process validation • Sterilization validation • ICH stability studies and ongoing stability studies • ICHQ3D and nitrosamines studies
