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.

Barrier properties and hydrothermal aging of amorphous alumina coatings applied on pharmaceutical vials

“…Such molecules are often accompanied by excipient solutions that protect them from degradation induced from changes in pH, oxidation and other processes [2]. However, even though pharmaceutical glass vials, the primary packaging of choice, appear chemically inert towards an aqueous phase, reactive excipient solutions can still affect the glass surface, sometimes leading to the flaking through delamination [3]. Such degradation of the functionality of the primary packaging is a longstanding problem and can result in product failures that force numerous recalls.…”

Minimizing Oxidation of Freeze-Dried Monoclonal Antibodies in Polymeric Vials Using a Smart Packaging Approach

“…Vials made of glass are the most common primary packaging for freeze-dried pharmaceuticals [ 7 ] due to the materials’ inertness, transparency and excellent barrier properties against moisture and gases [ 8 , 9 ]. Nevertheless, concerns with glass like ion leaching, delamination and its susceptibility regarding breakage can affect safety and efficacy [ 7 , 10 ] and thus may lead to recalls [ 11 ]. More recently, vials made of cyclic olefin polymers and copolymers (COP and COC) have attracted attention as they have overcome the major drawbacks of glass by showing excellent chemical resistance [ 9 ] and low adsorption [ 7 , 12 , 13 ], while likewise providing a translucent and inert surface [ 7 ].…”

“…More recently, vials made of cyclic olefin polymers and copolymers (COP and COC) have attracted attention as they have overcome the major drawbacks of glass by showing excellent chemical resistance [ 9 ] and low adsorption [ 7 , 12 , 13 ], while likewise providing a translucent and inert surface [ 7 ]. Moreover, an obvious benefit over glass is the great break resistance of the polymers, which therefore makes them favorable for recent cell and gene therapies as well [ 10 , 14 , 15 , 16 ]. Moreover, an environmental benefit using polymer over glass vials was found [ 17 ].…”

Influence of Protein Adsorption on Aggregation in Prefilled Syringes

“…[9][10][11] Although there are concerns with using COP containers, including the high water and CO 2 /O 2 permeability and the unknown extractability and leachability properties of the material, mitigation of protein aggregation has been achieved for antibody drugs using silicone oil-free COP syringes and such syringes have been recently marketed. 3,5,12,13 However, the mechanism underlying protein aggregation remains unclear, which limits the ability to enhance the stability of protein-based drugs, and the development of methods for minimizing protein aggregation.…”