Considerations In Development & Manufacturing Of Complex Injectables For Early Phase Studies

By Jim Huang, PhD, Founder & CEO, Ascendia Pharmaceuticals

A complex injectable is a product that has a complex active ingredient, complex formulation, complex route of delivery, or complex drug device combinations. Complex parenteral products include delivery systems, such as sterile suspensions, liposomes, lipid nanoparticles, emulsions, polymeric microspheres, pellet implants, etc, for administration of drug via the injection, ophthalmic, subcutaneous, implant route, etc. Complex injectables have gained increasing attention due to their advantage in applications in both acute and chronic diseases treatments. Particularly, suspensions and lipid-based nanoparticles are being increasingly utilized due to their ability to increase drug loading to improve bioavailability/stability and to enable long-acting injectable of poorly soluble drugs and biologicals.

However, the development and manufacturing of those injectables is extremely complex, requiring careful design of formulation and process, in-depth characterization of products, confirmation of safety and efficacy per FDA regulation, and high-quality standards in manufacturing, packaging, distribution, and storage. Production of the first clinical trial materials for a new pharmaceutical dosage form is a significant milestone event in the development of a pharmaceutical product. As a product transitions from pre-clinical development to the clinical development phase, the manufacturing process takes on a much greater role in the overall success of the project. This transition is particularly difficult for emerging pharmaceutical companies whose expertise typically lies in the biology and chemistry, and less on the engineering, regulatory, and quality aspects of manufacturing the drug product. This critical milestone is made even more challenging when the drug product is intended to be a sterile injectable dosage form.