Maintaining product stability during the various drug product process unit operations is paramount to our ability to supply safe and efficacious biotech products to patients. New technologies are helping us ensure that we meet these challenges successfully and are able to embrace the Quality by Design paradigm. This article presents best practices to meet three of the significant technical challenges experienced in drug product manufacturing, namely, maintaining product stability during frozen storage, performing visual inspection of drug product vials, and controlling protein particulates.
Freezing and thawing large volumes of bulk protein solutions has become an important step in biopharmaceutical manufacturing because the flexibility it affords makes it possible to maximize productivity and align drug product logistics with market demands.4 The stability of therapeutic proteins during long-term storage has been highlighted as a key issue for product safety and efficacy.1 Storing drug substance for periods of time in the frozen state enables a decoupling of drug substance manufacturing from drug product manufacturing. A successful operation, therefore, requires an understanding of the fundamental aspects of freezing and thawing proteins as well as the impact of the practical aspects of heat and mass transfer, along with knowledge of the technology available.
Manufacturing sterile biotech products requires visual inspection of the final drug product filled in sealed containers to ensure there is no contamination from foreign particulates.5 Such inspection can be performed by humans or through an automated inspection machine (AIM). Compared to manual inspection, automated visual inspection (AVI) offers more consistency, higher speed, and improved quality of inspection. It also is cost efficient over a longer period and for higher production volumes.