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When the pharmaceutical industry started research in spring 2020 on vaccines to fight COVID-19, the issue of manufacturing and packaging capacities arose almost at the same time. For Thermo Fisher Scientific , it meant upgrading its contract development and manufacturing business to support production of therapies and vaccines. Requests for suppliers like Optima to provide new sterile fill finish lines with isolators were scheduled to start immediately as emergency drug approvals were granted. New ultra-high speed fill/finish lines from Optima enabled by new technology vials from Corning now offer the possibility to further increase filling capacities within a very short period as is discussed in this joint in-depth evaluation.
Since the outbreak of the pandemic, Optima Pharma has been making great efforts to adapt existing filling systems for vaccine filling and to build new filling systems with isolators as quickly as possible. "Our employees have been extremely challenged and are delivering top performance worldwide," says Juergen Rothbauer, Managing Director of OPTIMA pharma GmbH. One example for a successful collaboration during the pandemic is with Thermo Fisher, headquartered in Waltham, Massachusetts.
The company’s Pharma Services business provides contract development and manufacturing services, which includes sterile fill operations for COVID-19 vaccines and other critical care medications for pharma companies globally. As a strategic partner with the necessary technological know-how, and end to end drug substance and drug product development and manufacturing capabilities, Optima is helping the company increase capacity for vaccine filling at several of its sites as quickly as possible.
Optima Pharma makes every effort to keep delivery times as tight as possible: "This is about nothing less than saving lives by expanding global vaccine filling. In this light, we have pulled out all the stops to expedite the completion and delivery of the filling lines for Thermo Fisher,” Rothbauer reports. Besides the employees' high level of commitment, a whole package of measures contributed to the extremely rapid starts of production. These include the CSPE approach (Comprehensive Scientific Process Engineering), rapid modifications to machines that were already under construction, and the simultaneous development of vaccines and filling lines.
The digitalization of engineering as part of CSPE has been a time saver. High levels of precision were already achieved in the 3D models and simulations, and this was carried over into installation, with high efficiency/high quality lines being created right from the start. A significant amount of time was also saved by assembling the isolator and the entire filling line together in the CSPE Center at Optima in Schwaebisch Hall before delivery as well as extensive testing of the complex technology.
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In addition to fast project processes, selecting the right primary packaging materials offers great potential for increasing filling capacities. As is the case for filling lines, the global demand for primary packaging materials has risen in response to the COVID-19 pandemic. Global supply chain leaders have identified vials as a supply chain vulnerability for both COVID-19 and non-COVID-19 products
[1].
Recent US Food and Drug Administration guidance highlights this concern and helps to address it by outlining pathways to facilitate vial and stopper changes
[2].
FDA points to Comparability Protocols (CPs) as well-suited for glass vial changes (such as shifts to Corning’s Valor® Glass), as CPs can support vial changes broadly including across multiple products that use the same container (e.g., group supplements, trans-BLAs). In recent guidance, manufacturers are encouraged to contact the FDA to discuss specific cases that might warrant modified post-approval reporting categories and other risk-based approaches.
“Corning has tested its coated vial technology on numerous customer lines and has repeatedly demonstrated that line efficiency is improved by 20 to 50 percent relative to conventional vials”, says Brendan Mosher, General Manager at Corning. Corning, headquartered in Corning, NY, and employing more than 50,000 worldwide.
This was also confirmed in a recent collaboration between Thermo Fisher, Corning and Optima Pharma. Corning Valor Glass was tested at Optima Pharma, Germany to evaluate two situations. On the one hand, retrofitting of existing Optima filling lines to reach higher speeds by use of Corning Valor Glass vials. On the other hand, building new lines that operate at even higher speeds without compromising established quality features such as 100 % in-process controls or product saving technologies such as re-dosing, re-stoppering and re-capping functions.
During the testing of Valor® Glass vials, no breakage occurred at any time, even though worst-case conditions were provoked, Tobias Dombrowski, Project Engineering Manager at Optima Pharma, reports. “The low friction of the vials surface combined with its very high strength are excellent properties”, he says. Regarding the challenging situations for vial filling under the highest speeds, this results in an avoidance of negative cosmetic effects to the vial, breakage of the vial, static charge and less wear of the machinery equipment such as guidings and star wheels. Due to fewer interventions and a better processability in comparison with traditional borosilicate glass, line efficiency is increased.
“Simply substituting Valor vials for conventional vials under typical operating conditions can provide an immediate operational benefit,” Mosher explains. This is illustrated by the difference between points 1 and 2 in Figure 3. “We have also observed that line efficiency tends to rapidly decrease when using conventional vials because of increased downtime,” he adds. In contrast, the improved flow behavior, damage resistance, and other characteristics of Valor vials enable efficient operation at speeds up to 750 vials per minute as shown by point 3 on Figure 3.
To apply these findings to Thermo Fisher the joint team of experts from Corning, Thermo Fisher and Optima Pharma undertook more in-depth evaluation and further developed the concept onto a project to boost Thermo Fisher sterile fill/finish production with highest speed and quality.
As not only investment costs, but also operating costs are very relevant for pharmaceutical companies, the estimation of required cleanroom and isolator space proved to be a major consideration during this project. While raising the speed by almost 70 % from 450 vials to 750 vials per minute, space requirements increased by only 25 % without compromising accessibility of the line. The results expected by Corning could be achieved in the in-depth investigations as shown in Figure 4.
Luca Andretta, Sr. Director within the Pharma Services Technical Operations team at Thermo Fisher said this about his observations during technical assessments: “With Corning glass evaluation and trials we have seen improved quality through reduced risks of glass defects usually seen in normal operation due to Corning’s lower coefficient of friction coating, higher yields as a result of reduced AVI rejects, all of which can allow us to operate our fill/finish lines at higher speeds, resulting in improved overall line outputs. In our experience with Corning glass options, we have concluded that substantial operational and quality improvements may be achieved, with minor qualification and regulatory impact,” Andretta explains [2].
Existing sterile fill/finish lines at Thermo Fisher plants were analyzed and requirements for retrofitting were defined. Downtime due to retrofitting had to be kept at the lowest level possible. An extension of complete stations or machine parts is not justifiable and causes further consequences, such as a revalidation of the isolator’s decontamination cycle. With minimal well-thought interventions in the existing machine design, performance increases of 10 to 20 % can be achieved, depending on the current system. “The combination of a higher efficiency of up to 50 % at increased operating speeds ultimately provides a step change improvement in pharmaceutical manufacturing capacity,” Mosher summarizes.
“In a time when the pharmaceutical industry and our customers need us to ramp up sterile fill/finish capacity to meet the growing needs of patients both for COVID-19 pandemic and emergency healthcare medications, as well as many livesaving mRNA and other treatments, we see the increased quality, output, and capacity potential of using Corning Valor® vials in combination with ultra-high speed fill/finish solutions by Optima as a game changer in our ability to serve patients in need of these products,” Stephen Closs, Vice President within the Pharma Services Technical Operations team at Thermo Fisher, emphasizes.
[1] Landscape of Current COVID-19 Supply Chain and Manufacturing Capacity, Potential Challenges, Initial Responses, and Possible “Solution Space,” March 2021,
https://www.ifpma.org/wp-content/uploads/2021/03/Summit_Landscape_Discussion_Document.pdf
[2] COVID-19 Container Closure System and Component Changes: Glass Vials and Stoppers, Guidance for Industry, March 2021,
https://www.fda.gov/media/146428/download
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