Satish Singh, Ph.D., is research fellow at Pfizer, where his responsibilities include leading product development activities for biologics, vaccines, and oligonucleotides.
Glass packaging is ubiquitous in the pharmaceutical industry and most formulators take it for granted. “Make mine Type 1 please, and I will have a few hundred thousand of them to go.” However, glass is a complex material and the raw material, the glassmaking process, and the process of forming the vials and syringes each have a significant impact on the final quality of the material we use.
The glass we think of as strong has a chemical weakness. Under certain conditions, thin slivers (lamellae) of glass can flake off from the inside of the containers and contaminate the drug product solution—and they can be difficult to detect. This phenomenon of glass delamination has led to the recall of several products recently with the products representing a wide range of therapeutics (e.g., epoetin alfa, methotrexate, hyaluronidase recombinant, fluorouracil, sodium thiosulfate injections, potassium phosphates injection, bacteriostatic sodium chloride, acetylcysteine, phenylephrine HCl, etc.).
Although no adverse events have been reported or attributed to this phenomenon, it is clear that a severe risk exists in dosing parenterals that contain such particles. Apart from direct impact on the patient, glass particles carry the risk of functioning as an adjuvant and have the ability to potentiate immunogenicity against the biotherapeutic inadvertently injected along with such particles in the solution. There is also the financial cost of a product recall.
In order to prevent delamination from occurring, we need to understand the causes and contributing factors ranging from the glass-tubing-to-vial conversion process to vial processing at the drug product site to formulation of the product stored in it.
What have we learned from the recent episodes? Are our current inspection methods, especially on stability, capable of detecting the formation of lamellae? Is there greater incidence of delamination now, or are we simply better at detecting them? If the incidence is greater, what has changed? Can the susceptibility for a batch of glass vials to delamination be tested? Can the potential of a formulation to cause delamination, especially over time in storage, be studied? Do products in pre-filled syringes carry the same risk? What steps can be taken by the pharmaceutical manufacturer to prevent these incidences from happening and enhance control on the quality of the product? Can a risk assessment and mitigation strategy be created? These questions are slated for discussion at a hot topic session at the AAPS National Biotechnology Conference in San Diego.
I suspect that most formulation scientists do not give delamination a passing thought. Perhaps it is time that changed.