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Breakage during fill-finish pharmaceutical manufacturing

Updated: Jun 7, 2020

Fill-finish operations are generally the most capital-intensive stage of the drug manufacturing process — heavy asset utilization is therefore critical to profitability. Product that has reached the fill-finish stage of manufacturing has the greatest value. Process changes that have the potential to negatively impact yield are generally avoided to mitigate risk. As a result, adoption of new technologies within fill-finish operations has historically been conservative and incremental. These manufacturing innovations can also be limited by the glass vial used on the filling line.

Glass vial performance in fill-finish operations is evaluated by multiple metrics. Glass particulate contamination is one type of defect that occurs during filling operations. If particulates are detected during post-filling inspection, the resulting root cause investigations can lead to significant downtime. Other glass-related factors that impact yield include tip overs and broken vials that require operator intervention and/or line stoppage in addition to loss of product.

Low coefficient of friction (COF) coatings provide additional benefits that improve manufacturing throughput. The ability of coated vials to smoothly flow on a line reduces tip overs and jams. Coatings also provide protection against the creation of strength-limiting surface flaws that render a vial more susceptible to breakage. The benefits of damage resistance extend to the inspection stage — less damage during filling leads to fewer cosmetic defect rejects.

Additional features can be designed into a glass vial to augment breakage resistance. One solution is to chemically strengthen the glass surface using an ion exchange process. The resulting compressive stress layer imparts additional breakage resistance to a vial by closing surface flaws and resisting applied tensile stresses encountered on a filling line.

The cumulative benefits of using new vial technology with low COF coatings and chemical strengthening have shown an average throughput improvement of >20 percent for filling lines operating at the same set speed used for conventional vials. As a result, pharmaceutical companies can realize an immediate boost in capacity without investing in expensive fixed assets or increasing their manufacturing footprint.

Contract manufacturing organizations that are frequently engaged to fill the additional demand of pharmaceutical companies can also benefit from the increased efficiency and improved yield of quality product that is enabled by innovative glass packaging.

Capacity can also be hypothetically increased by operating filling lines at faster speeds. The efficiency of current high-speed filling lines is typically 60-70 percent with extensive breakage throughout the process, and the efficiency continues to decline significantly when using conventional glass packaging. The improved machinability and breakage resistance of enhanced glass packaging enables a new, previously unattainable trajectory in efficiency and throughput relative to conventional packaging.

Glass Delamination

Delamination is a response primarily observed in converted tubing glass vials in which thin flakes release from the interior surface of the vial into the liquid formulation. The propensity for delamination is dependent on multiple factors, although its origin is the surface chemical heterogeneity that is created during conversion of glass tubing to vials. Potential risks of delamination flakes include inflammatory responses that injure tissue, stimulation of undesirable immune responses, and/or tissue injury through occlusion of vasculature. As a result of these potential risks, drug lots affected by glass delamination are recalled, thereby impacting supply. Subsequent work on new glass formulations has led to solutions that address the root cause of delamination. In particular, boron-free aluminosilicate glasses eliminate the volatilization-prone component leading to chemical heterogeneity and subsequent delamination. These aluminosilicate glasses also meet the hydrolytic performance requirements used for parenteral packaging as outlined by the United States Pharmacopeia (USP).

Glass particulate contamination

The presence of glass particulates is another frequent source of recalls. Frictive contact between vials and vial impact events during filling can generate particulates. Complete breakage of a vial can also generate glass particulates. In either case, the resultant particles can lead to contamination, loss of product, and expensive recalls that jeopardize the supply chain. Potential health risks of glass particulate contamination of a parenteral product are similar to those related to delamination events.

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