Development and Scale-up of a Microsphere Protein Delivery System

• Published in: Biotechnology progress Vol. 14; no. 1; pp. 108 - 115
• Main Author: Tracy, Mark A.
• Format: Journal Article
• Language: English
• Published: USA American Chemical Society 1998; American Institute of Chemical Engineers
• Subjects: Animals; Biological and medical sciences; Biotechnology; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Drug Delivery Systems; Drug Stability; Fundamental and applied biological sciences. Psychology; General pharmacology; Health. Pharmaceutical industry; Hormones; Human Growth Hormone - administration & dosage; Humans; Industrial applications and implications. Economical aspects; Medical sciences; Microspheres; Miscellaneous; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Proteins; Toxicity; Performance evaluation; Glycolic acid copolymer; Injectable form; Microsphere; Pharmaceutical technology; Controlled release form; Toxicity; Lactic acid copolymer; STH; Review; Dimensioning; Protein hormone; Preparation; Dosage form; Clinical trial; Recombinant protein
• ISSN: 8756-7938; 1520-6033
• DOI: 10.1021/bp9701271

This paper reviews the development path for the ProLease injectable microsphere delivery system for proteins using human growth hormone as an example. The process consists of four stages, the selection of a lead formulation for clinical testing, the preclinical evaluation of the lead formulation including toxicology and stability studies, the manufacture of phase I clinical supplies, and the scale‐up for phase II and phase III clinical trials. The approaches used to overcome obstacles during each stage are summarized including ways of stabilizing the protein, obtaining desirable release kinetics, and manufacturing sterile batches for clinical testing. Stability, release, toxicology, and scale‐up results for ProLease recombinant human growth hormone (rhGH) are given. The phase I clinical data show that bioactive rhGH was released for about 1 month in humans. This work shows that processes and procedures have been developed that enable the production of microsphere sustained release formulations for proteins suitable for clinical trails and commercialization.