By Tatiana Nanda, VP, Technical Development and Analytical Services, SK pharmteco; Christopher Nieder, Senior Director, Head of Technical Development, SK pharmteco; Mardhani Aparajithan, Director, MSAT, SK pharmteco; and Robert Brousseau, Senior Content Manager, SK pharmteco
An adenoviral process that works for one construct can fail with the next. A harvest step optimized in development can erode yield at scale, and an early analytical method can stall a program at validation. These are the predictable costs of forcing adenoviral vectors into a rigid, one-size-fits-all platform.
A platform should provide speed, structure, knowledge, and a clearer path from development to GMP. For adenoviral vectors, it delivers that value only when it standardizes what can be standardized, applies prior knowledge, and tailors the process where product biology demands it.
Adenoviral vectors have a long history in vaccines, oncolytic viruses, and gene therapy research, but their manufacturing and CMC strategies often require more flexibility than other modalities. Compared with AAV or lentiviral vectors, adenoviral programs can be especially sensitive to construct design, cell line behavior, harvest conditions, purification, formulation, and analytics. They need an adaptive, adenovirus-specific framework built around process understanding, modular tools, analytical rigor, and GMP readiness. Flexibility is what makes the platform work, and knowing when a standard approach is not enough is itself a mark of platform maturity.
Where to Standardize, Where to Tailor
The question is not whether to use a platform, but how to apply it. An adaptive platform standardizes the elements that reliably accelerate development and preserves program-specific judgment where biology decides the outcome. The table below shows how that line is drawn.
Upstream Development
Harvest conditions for adenovirus are not always straightforward. Salt adjustment can influence stability, recovery, and downstream clarification pH, and the timing of endonuclease addition, lysis buffer addition, and salt quench can affect recovery and stability. A harvest approach that works for one construct or cell line may not transfer cleanly to another, so early optimization is critical.
Cell line selection also carries long-term consequences. A highly productive cell line may increase host cell protein (HCP) burden or other residuals, and replication-competent adenovirus (RCA) risk must be addressed. Candidates should be assessed for both upstream output and broader process performance, including early downstream evaluation.
Downstream Purification and Residual Clearance
Adenovirus manufacturing does not benefit from a universally accepted dedicated affinity chromatography solution. Teams may need to evaluate multiple purification pathways, chromatography modes, tangential flow filtration steps, and residual-clearance strategies. A well-designed platform does not assume every product follows the same path; it provides a structured basis for selecting and optimizing downstream strategies while balancing recovery, purity, impurity clearance, scalability, and GMP readiness. HCP clearance can be especially challenging, and cumulative losses across downstream operations can significantly affect final yield.
Formulation and Stability
There is no single broadly accepted formulation buffer for early- and late-phase adenoviral vectors. Complex buffers can add characterization requirements, while simpler formulations may not adequately protect the product. An adaptive platform selects buffers and excipients based on stability, route of administration, storage requirements, and target product profile. Stability should be understood early, because formulation decisions affect manufacturing timelines, clinical supply, commercial readiness, and regulatory expectations.
Analytics and Critical Quality Attributes
The ratio of infectious to physical particles is often important for adenoviral vectors, yet expectations vary by indication, product type, and program, with no universal consensus. Teams should define the quality target product profile early, then connect analytical strategy, process development, and release testing to the clinical and regulatory path. Analytical development belongs with process development from the outset. OD260 may serve early work, but methods such as anion exchange-based assays may be needed to support validation. Genomic titer assays must show accuracy and precision, and teams need early insight into replication propensity and product specifications.
Viral Banking, Clearance, and GMP Readiness
Adenovirus manufacturing depends on viral banks with dedicated processes relevant to drug substance manufacturing. Banks need fit-for-purpose analytics, stability programs, and multiplicity of infection testing, and should connect to upstream development, downstream expectations, analytical readiness, and the GMP plan.
Viral clearance should also be considered early. Demonstrating it is difficult because adenovirus is large, non-enveloped, lacks a proven affinity-based purification solution, and can be hard to distinguish from potential adventitious agents in clearance and safety testing. Clearance planning intersects directly with RCA testing and should be built into process design rather than deferred.
Choosing a CDMO Partner
The regulatory environment raises the stakes. Compared with AAV and lentiviral vectors, adenoviral vectors have limited recent commercialization precedents, so process understanding, analytical robustness, and documentation discipline matter more. Adenoviral manufacturing should not be run as a rigid platform exercise. It should be managed through an adaptive platform that links cell line selection, harvest, purification, formulation, analytics, viral clearance, and banking from the beginning. The most important question is not whether a CDMO has an adenoviral platform, but whether it knows when a standard approach is not enough.
From Platform Promise to Program Success
That is the principle behind SKyvec Adeno. Backed by years of adenoviral manufacturing, it is an adaptive platform built for adenoviral vector development: structured enough to accelerate progress, flexible enough for program-specific complexity, and grounded in the process and analytical experience clinical advancement requires.
Adenoviral manufacturing rewards early insight. The sooner developers understand product behavior, process vulnerability, and the decisions that matter later, the better positioned they are to move with confidence from development to GMP. That is the conversation SK pharmteco welcomes.