As increasingly bespoke and expensive biologics continue to permeate the pharmaceutical space, the need for fill/finish applications that ensure valuable drug substance is safeguarded from contamination and loss has become a critical consideration for biopharmaceutical companies.
Newer technologies that minimize line losses are crucial to optimizing 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 drug substance in its manufacturing.
AbbVie, a global leader in contract pharmaceutical production, has recently expanded its facilities in Sligo, Ireland to prioritize this utilization and mini mize line loss. This investment, which affords greater flexibility and reduces both contamination risk and weight check losses, will allow AbbVie to provide state-of-the-art fill/finish services to companies with valuable drug substance.
Mitigating Loss Through Non-Destructive Weight Checks
There are a number of practical considerations that, when given the appropri ate attention from operators, can serve to greatly reduce the 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 whether the system utilizes a RABS or an isolator can make a big difference, for instance, 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 trial and error that often results in the loss of vials. This can prove particularly damaging to operators whose drug substance is otherwise difficult or costly to produce – cell and gene therapies, as well as many other advanced ther apeutics, may have tens or hundreds of thousands of dollars wrapped up in a single dose. For newer equipment like AbbVie’s Sligo line, this issue is circumvented through 100 percent non-destructive weight checks. These checks, performed offline during setup, 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 pre-filling, weighed again post-filling, and any deviations are recorded and the pumps recalibrated accordingly in real time, so that any process drifts are corrected to bring the vials 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 operator 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 operators to forfeit every vial filled between the last weight check and the current one.
The Advantages of SUTs in Minimizing Drug Substance Loss
Another potential cause of line loss is contamination; for operators working with traditional stainless-steel lines, the cleaning and changeover between products can represent a source of potential compromise that can result in contaminated vials. To address this, many operators have shifted to single use technologies (SUTs), which often afford them added flexibility by greatly reducing the time required to change over products. For some traditional filling lines, the issues around stainless-steel equipment are further compli cated 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, the pipe in between, and the autoclave above the surge vessel. Additionally, this paradigm creates holdup of product in the pipe, which often cannot be completely emptied prior to cleaning.
These advantages exist alongside the changeover flexibility inherent to AbbVie’s Sligo line. Its Grade A isolator provides unparalleled product protec tion, and additional features related to vaporized hydrogen peroxide (VHP) decontamination and inline monitoring help to ensure optimal sterility. 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 on the fly. These filling heads can also identify isolated issues and adjust accordingly – if one needle malfunctions, the filling head in ques tion is flagged and shut down independent of the other five, which remain operational.
While the line was designed for high potency products, it can be adjusted to perform fill/finish for a wide range of products under a number of scenarios. Importantly, its design focuses on a sort of dual defense, protecting both the product from the operator and the operator from the product. This, combined with a design that simplifies the number of parts that are interchanged between fill/finish runs and the ease with which operators are able to switch out vials of various sizes, greatly streamlines timelines and reduces complex ity for these applications.
AbbVie as a Partner for Drug Substance Utilization
Ultimately, AbbVie’s track record of quality and quality assurance, combined with the sea-change improvements represented by its new fill/finish line, make it an ideal partner for companies with high-value drug substance. As part of its focus on comprehensive facility upgrades, the Sligo line can afford customers the latitude to bring an established product online or to scale up with support from AbbVie. With the capability of producing batch sizes from 50 liters to as much as 500 liters, this line represents the latest in drug substance utilization for fill/finish applications.
With manufacturing and R&D facilities in more than 20 countries, as well as products that serve patients in more than 175 countries, AbbVie possesses the expertise and experience to help customers achieve their goals. AbbVie is dedicated to developing and delivering innovative new medications across a wide range of indications, continually working to create high-quality therapeu tic solutions for complex conditions, all while working to ensure their safety, efficacy, and accessibility.
Contact us today for fill/finish applications that ensure your valuable drug substance is safeguarded from contamination and loss.