Development of syringes and vials for delivery of biologics: current challenges and innovative solutions

ABSTRACT

Introduction

Several new biopharmaceutical dosage forms have developed over time, such as lyophilized vial, liquid vial, and liquid prefilled syringe formulations. This review summarizes major pharmaceutical dosage forms and their advantages, disadvantages, and countermeasures against the shortcomings of each formulation. The appropriate combination of active pharmaceutical ingredients, excipients, and containers should be selected for the safe and less burdensome administration to the patients. Finally, we note certain opinions on the future development of not only therapeutic proteins but also gene therapeutics.

Areas covered

This review is to discuss the challenges of the development of dosage forms to improve pharmaceutical stability and how they can be overcome.

Expert opinion

Silicone oil-free syringes are highly preferable for minimizing subvisible particles in the drug. It can be proposed that materials with less protein adsorption property are preferable for the suppression of protein aggregation. It is required to minimize adverse effects of biopharmaceuticals through proper quality control of the drug in a container, based on the understating of physicochemical stability of the protein in solution, the physicochemical properties of the container, and their combinations.

KEYWORDS:

• Biopharmaceuticals
• antibody drug
• syringe
• vial
• container
• formulation
• immunogenicity

Acknowledgments

The authors would like to thank Terumo Corporation, Gerresheimer AG, and DAICEL Corporation for providing images of syringes and Enago (www.enago.jp) for the English language review.

Article highlights

• Containers affect the stability and safety of the drug product.

• Several new technologies for container closure systems were developed and contributed to improve quality of biopharmaceuticals.

• Container closure system-related challenges are still present, including protein adsorption, aggregation, and excipients degradation.

• Thorough investigations into not only the physicochemical stability of the protein under formulation conditions but also the physicochemical properties of containers are required for effective developments of biopharmaceuticals.

• It is recommended to employ a combination of experiments and a molecular dynamics approach to understand stability of therapeutic proteins in containers.

• From the viewpoint of quality control, in-line monitoring of protein aggregates after the fill and finish process will be beneficial.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.