The Value of Expertise in Aseptic Fill Finish Manufacturing of Biologics
Aseptic fill finish manufacturing is one of the final but crucial steps between biopharmaceutical development and patient care. Using carefully managed liquid filling or lyophilization processes for vials and syringes, drugs are filled into a safe, convenient delivery form ready to administer to patients. This process is especially critical for highly valuable biologic drug substances since, with vast amounts of time and resources invested upstream, any errors resulting in loss of product at such a late stage have the potential to be catastrophic.
One way to mitigate the risk associated with aseptic fill finish manufacturing of biologics is to partner with a contract manufacturing organization (CMO) demonstrating proven expertise in all aspects of biologics production. An experienced service provider will not only have designed fill finish operations to consider the inherent lability of biologic drugs but will be capable of completing fill finish biologics manufacturing at a scale suitable to meet demand.
AbbVie operations has successfully developed and delivered drug products for more than 130 years. Over 14 million small volume parenterals (SVPs) are filled annually across AbbVie’s global network, with products distributed to over 175 countries worldwide. Benefiting from a fully integrated Science and Technology group supporting both biologics drug substance (DS) and drug product (DP) development, AbbVie also boasts a quality organization with an exemplary audit and regulatory track record of proven clinical and commercial success. Now, with a state-of-the-art line in Ireland dedicated to aseptic manufacturing of liquid and lyophilized biologic vials, and with the integration of Allergan’s SVP network, AbbVie has further expanded its capability and capacity to >40 million units annually.
Overcoming Manufacturing Challenges
In recent years, the production of biologic drugs has increased dramatically, with several monoclonal antibody products now ranked among the top-selling drugs in the world. However, manufacturing biologics remains extremely challenging, mainly due to the innate lability of these large and highly-complex molecules.
Unlike small molecules, biologics can readily aggregate or undergo conformational changes in response to various factors. Examples include high temperatures, varying pH, mechanical agitation, freeze-thaw cycles, and the presence of certain excipients, to name but a few. Biologics are also prone to adsorbing to surfaces and can easily become viscous at high concentrations.
Assuring product stability, quality and safety means implementing robust manufacturing control strategies that consider the unique properties inherent to biopharmaceuticals. Such measures should be designed to maintain essential product attributes during manufacture and storage and must align closely with analytical testing to ensure potential issues are detected and dealt with promptly.
AbbVie CMO employs multiple approaches to overcome the challenges of biologics manufacturing. These include using low-shear mixing methods to prevent protein aggregation and foaming; performing many activities within closed systems under tightly-controlled conditions to avoid fluctuating temperature or pH; and using peristaltic pumps with adjustable flow speeds for filling operations. As well as providing low-shear filling, peristaltic pumps benefit from single-use technology to enable a more efficient changeover and greatly reduce the risk of cross-contamination when compared to traditional piston pumps.
Transitioning biologics production to scale can be difficult due to scale-dependent behaviors. Consequently, studies must be planned with scale-up in mind and should focus on evaluating key process parameters for assuring drug safety and efficacy. Partnering with an experienced CMO offering these comprehensive capabilities is advantageous and helps mitigate risk to improve outcomes. Your CMO partner should be able to leverage a wealth of existing knowledge to help streamline your scale-up efforts and accelerate your time to market.
AbbVie is well-versed in lyophilization and formulation development, with facilities worldwide benefiting from best-in-class equipment operated by highly-experienced personnel. From lab-scale lyophilization, with manual or peristaltic vial filling, to dedicated equipment for lyophilization process optimization, scale-up and tech transfer, AbbVie’s expert team leverages state-of-the-art technologies across multiple global sites and has formulated numerous drug products over several decades.
Staying current on industry tools and technologies helps to define AbbVie’s success. Leading-edge capabilities include computer fluid dynamics (CFD) for modeling development, and state-of-the-art GMP equipment. Combined with other technologies, these are pivotal to AbbVie scientists’ continued demonstration of consistency and improved lyophilization cycle / lyophilization quality to minimize engineering runs at scale. With all fill finish manufacturing studies backed by significant analytical capability – including development and investigative testing; head space analysis, container closure integrity test development/validation; and HPLC and sub-vis particulate analysis – AbbVie is widely recognized as a global leader for operational excellence.
Integrating the development of drug substance and drug product
Successful biologic drug development can be generally defined in two categories. First is drug substance development, which includes generation of master and working cell banks, developing the manufacturing process, performing process characterization, and successfully implementing scale-up. Second is drug product development which, when performed as discussed above, results in accelerated delivery of a drug to market due to the close integration of DS and DP. It is this integration that provides the continuity necessary to reach set milestones more rapidly, yet only very few CMOs can effectively consider the dynamics and needs across the entire biologics spectrum.
By aligning quality systems and enterprise resource planning (ERP), AbbVie not only assures clinical and commercial supply but also adds overall value to biologics development and manufacturing through time reduction, risk mitigation and cost saving. Structured analytical testing from DS through DP makes managing product transfer straightforward, whereas comprehensive pharmaceutical clinical and commercial support is fundamental in helping AbbVie’s partners stay ahead of the competition.
Global expansion promises greater flexibility
A major advantage of working with AbbVie CMO is that partners are provided with access to a global network of resources encompassing many in-demand technologies and a broad up-to-date working knowledge of worldwide regulatory requirements. Our proven expertise in aseptic fill finish manufacturing comes from successfully developing, launching and marketing many of our own drug products, giving our partners confidence that we will deliver on this most critical step of bringing biopharmaceutical products to market.
Multiple AbbVie sites focus on small volume parenteral development and manufacturing. These include lyophilization development and optimization in our Ludwigshafen, Germany and Lake County, IL sites; our clinical fill/finish plant in Ludwigshafen, Germany that is capable of filling syringes, liquid and lyo vials; our Puerto Rico facility that produces biologic pre-filled syringes; and our Sligo, Ireland site with a new highly-engineered state-of-the-art aseptic filling line for liquid and lyo vials.
With an extensive and growing global network, we strive to offer more capabilities and even greater flexibility to support the various needs of our partners. Indeed, our newest line in Ireland is designed for both liquid and lyophilized biopharmaceutical vials and will be pivotal to increase the capacity available to third party markets, despite planned shortages across the rest of the industry due to COVID-19.
We treat your product exactly as our own, providing it with the full attention and support it deserves. Whatever the nature of your biologic drug, when it comes to aseptic fill finish manufacturing you can count on us to provide a safe, reliable product that is consistently filled and ready for patient use.
To learn more about how AbbVie CMO can support you with aseptic fill finish manufacturing of your biologic drug, contact us at 1-847-938-8524 or visit www.abbviecontractmfg.com
By: Jon Best, Director, Business Development
Jeff Tremain, Director Business Development
Ted Tharp, Associate Director, Parenteral S&T
Gene Wloch, Director, Parenteral Products, Operations