The cost of biopharma drug product reaches far beyond the costs for aseptic filling operations placing Drug Substance (DS) into a vial or prefilled syringe. As increasingly bespoke and expensive biologics continue to permeate the pharmaceutical space, the need for fill/finish applications that ensure valuable drug substance is protected from contamination and loss has become a primary consideration for biopharmaceutical companies.
Newly available technologies that minimize line losses are crucial to optimizing the full scope of a company’s drug substance production, creating compounding efficiencies for a process as it scales. Maximizing drug substance utilization hinges on identifying a contract development and manufacturing organization (CDMO) with the equipment, facilities, and expertise to prioritize high value biopharmaceutical DS within its manufacturing.
AbbVie, a global leader in pharmaceutical operations, has recently expanded its facilities in Sligo, Ireland to prioritize quality throughout, while minimize line loss of valuable biopharmaceutical DS. This recent investment was carefully designed and built using a joint team of engineers at Syntegon and AbbVie to afford greater flexibility, accuracy and reduced contamination risk to provide cutting edge fill/finish services to companies developing high value drug product.
Mitigating Loss Through Non-Destructive Weight Checks
There are a number of practical considerations that, when given the appropriate attention from technicians, can serve to reduce drug substance loss that occurs during the fill/finish process. The first is experience and how it relates to setup and operation of the line; this, coupled with the features of the line itself, form the core process improvements that drive optimization. Factors such as RABS vs. isolators and unique features like non-destructive weight checks may serve to set a system apart when compared to similar systems.
For many existing fill/finish lines, achieving filling accuracy requires periodic sampling and trial and error, which often leads to product loss and sometimes batch failure. This can prove particularly costly to advanced therapeutics that may have hundreds of thousands of dollars wrapped up in a single dose. For fill lines like AbbVie’s, specifically engineered for high value products, this issue is circumvented through 100 percent non-destructive weight checks. These checks, performed offline during qualification, help eliminate losses resulting from traditional weight calibration runs. Subsequent weight checks are performed inline, with weigh systems integrated into the vial transfer system that weigh vials as they move through the line. Empty vials are weighed prior to filling, and weighed again post-filling, with any deviations recorded, and pumps recalibrated accordingly in real time, so that any process drifts are corrected to maintain fill volumes within three decimal points of accuracy.
This approach exists in contrast to many traditional weight checks, which typically use a percent of the vials to extrapolate a rate of accuracy for an entire batch. This can create confusion if the sample or samples collected fail to meet weight requirements – for example, an technician may choose to weigh one in every 100 vials to get a representative sample of the weight of a much larger run, but if the selected vial falls outside the chosen weight parameters, it can force technicians to forfeit every vial filled between the last weight check and the current one.
Advantages in Single Use Technology to Minimize Drug Substance Loss
Another potential cause of Product loss is from batch contamination; for technicians working in traditional stainless-steel, cleaning and changeover between production can represent a source of potential compromise that can result in contaminated vials. To address this, many companies have shifted to single-use technologies (SUTs), which often afford them added flexibility by greatly reducing the time required to change over products. For traditional filling lines, the issues around stainless-steel equipment are further complicated by their configuration – the line may have a fixed stainless-steel vessel performing piping in one room, then transferring to a filling line and a smaller vessel. This creates the need for Clean-in-Place (CIP) and Sterilize-in-Place (SIP) of the larger vessel and surrounding equipment train. Moreover, this configuration results in a certain amount of product withheld in the transfer system and cannot be used for final drug product.
AbbVie has carefully engineered the Sligo Ireland fill finish line to capitalize on these product and efficiency advantages, in addition to changeover flexibility inherent within the aseptic fill finish line. AbbVie’s Grade A isolator provides unparalleled product protection, and additional features related to vaporized hydrogen peroxide (VHP) decontamination and inline monitoring help to ensure optimal aseptic manufacturing and quality. One of the more unique components of AbbVie’s new line is its six filling heads, each of which is capable of operating independent of the others to adjust weights inline, during production. These filling heads use automation to adjust during the run to maintain fill accuracy and prevent line downtime.
While originally designed for highly potent products, AbbVie’s newest fill/finish line can manage a wide range of biopharmaceuticals and vaccines with an isolator design protecting both the product from the technician and the technician from the product. This design simplifies the number of parts interchanged between fill/finish runs which streamlines timelines and reduces complexity for various applications.
AbbVie as a Partner for Drug Substance Efficiency
AbbVie’s commercial track-record and quality assurance, combined with one of the industry’s most advanced fill/finish lines, make it an ideal clinical and commercial partner for companies with high-value biopharmaceuticals. As part of its focus on comprehensive facility engineering and expansion, the Sligo line can easily manage client products from clinical to commercial launch and ongoing supply. With the capability of producing batch sizes from 20 to 500 liters, this line represents the latest in fill and finish technology and carefully protecting and maximizing drug substance utilization.
AbbVie manufactures and distributes commercial biopharmaceuticals from four global Bio sites within its global network serving patients in more than 175 countries. AbbVie is dedicated to helping its partners develop and deliver innovative new medicines across a wide range of indications, while working to ensure safety, efficacy, and accessibility.