As biologics steadily grow in pipeline development and commercialisation, inherently they require precise support to ensure effective delivery to the patient. In this article, Justin Schroeder, vice president for global programme management at PCI Pharma Services, looks at how to support the delivery of biologics through automated inspection systems.
Automation
Predominantly these medicines are delivered parenterally, and most commonly through injection. This may leverage traditional sterile vials, or increasingly methods such as prefilled syringes, or injectible systems leveraging a platform built out on prefilled syringe or cartridge as the sterile housing. Safety syringes, autoinjectors and pens, as well as more complex mechanisms for metered infusion, all leverage complex assemblies that work effectively and reliably due to extreme precision. These systems require this advanced precision in the moulding and fabrication of the various parts of the assembly, as well as utmost precision in both the subassemblies and final assemblies. In many instances this heightened level of sophistication is supporting a delivery mechanism that may be intended for only a single use. Conversely, multi-use pens inherently are designed to be used repeatedly or even refilled, and some applications such as diabetes may allow the user to customise their dosing in the delivery.
There is an impressive amount of intricacy and engineering architecture to make complex dosing systems effective and intuitive for the average patient. Many biologics and sterile injectable non-biologics still rely on traditional vials for patient administration. While we naturally infer that a complex autoinjector requires sophisticated automation and multilayered inspection, we do not necessarily infer that a traditional sterile vial in a kit may warrant the same.
Take, for example, a kit containing the following: one sterile vial of lypholised drug product, one prefilled syringe of sterile water for injection (WFI), one alaris cap for vial extraction, one 20-gauge needle, one 22-gauge needle, one leaflet for regulatory information, and one set of instructions for use (IFU). While the vial and water for extraction may be a well-established delivery mechanism, it is abundantly apparent that without the needles, alaris cap, or other critical components, the entirety of the system fails. In short, this expensive drug is rendered ineffective if the kit is not complete in its entirety, and we have failed the patient.
Often in the manufacturing environment, kitting is thought of as a manual process, achieved by workers hand-placing and loading individual components. Some companies may also rely on those same workers for the quality assurance responsibilities to verify and assure both the presence and correctness of these components. Unfortunately, the practical realities are that using human inspection as the primary means of verification leads to error.
Working in close collaboration with our client, PCI was tasked with the challenge of developing a system for a particular application. The complex kit required a fool-proof system to provide automated machine inspection of the kit, while balancing the cost considerations since the overall product demand did not warrant a highly automated line with robotic placement. We were challenged therefore to blend the human elements with the automated inspections.
The key to automated inspection systems is to provide inspection criteria that can be validated to assure robustness and reliability. These inspection systems are beholden to certain criteria and are built out with these. For the partnership, we needed to identify those critical elements that would allow us to successfully inspect a system that had many elements of variability.
The components utilised in the kit were, for the most part, ‘off the shelf’ stock items providing little opportunity to add key identifiers such as barcodes, by which items could be scanned in the packaging assembly process. We were challenged to find other key characteristics of the existing packaging that would allow us to both verify the presence and correctness of the component’s location, as well as its correctness for use.
One of the most challenging parts of the project was ‘creating a solution that identified the features of each individual component without slowing down the process,’ according to PCI’s Ray Hook, director, global serialisation.
And while this did present variability challenges at the beginning of the project, Hook notes that PCI found an ‘optimal solution to address that real- world variability,’ settling on a solution ‘that is very robust’.
Through considerable time spent in engineering analysis and proof-of-concept challenge testing, we were able to leverage combinations of critical text and colour to establish a basis of validated parameters by which the system could ensure the presence of each component. Variability, however, continued to provide an ever present challenge in establishing parameters. Green and yellow were two key distinguishing features for identifying the 20- and 22-gauge needles. Due to printing variability from the sourced components, the distinction between yellow and green was found to be particularly difficult. In the end, using colour with other key attributes allowed the system to deliver a robust solution.
Once the key elements of the vision systems were fool-proofed, the remaining architecture of the line engineering elements needed to be established. With modest product volume requirements, full automation was not the optimal solution. The line ultimately blended human activities with automated elements, all governed by inline automated inspections at each critical milestone of the build. This included fully automated WFI syringe assembly, beginning with sterile glass barrels and adding components such as finger flange, syringe labels, plunger rods and protective packaging. The WFI is paired with the labelled active drug product lyophilised vial, and the kit is then fitted out with the remaining components. At every step of this complex build, the vision system ensures the proper fit, placement, and correctness of each critical component.
Once a kit is complete in its contents, anti-counterfeiting tamper stickers are added to provide additional security. Kits are then serialised with market specific requirements, vision inspected, and further aggregated to the case and pallet.
Marc Luebbing, PCI business unit manager, added: “Working closely with our customer ‘at the table’ meant we could develop a package design that was elegant and intuitive for the care-giver delivering the medicine, but also incorporated all the key elements for our packaging system to deliver with a high degree of confidence. The project called on resources across many functional groups and teams and yielded a great solution for everyone concerned.”