Many contract organizations promise to “accelerate” testing and, by implication, a biotherapeutic’s progress, but what does the term “accelerate” really mean in practice?
Acceleration in biologics testing means more than simple speed. It’s about making decisions early that won’t create friction later, as much removing future impediments as pushing forward. Biologics programs rarely fail because a single test runs slowly. More often, they slow down because rushed and/or uninformed decisions create regulatory issues later, operational bottlenecks, or unnecessary rework.
Assays that lack lifecycle foresight, release strategies that don’t align with product realities, and operational structures that introduce unnecessary variability are high level decisions that, only as they play out later, end up quietly eroding timelines.
Because of the time lag between decision and outcome, these may seem like hidden failure points. They’re not. Here are four specific examples based on our experience, along with how to address them and thereby accelerate testing for your biotherapeutic.
1. The Potency Assay You Start with Is Rarely the One You Finish With
One of the trickiest areas in early development is how to approach the potency assay.
In early development, teams may identify an assay that generates consistent data and appears biologically relevant. Some may begin refining it immediately. SOPs are drafted. Acceptance criteria are set. The data package grows around that method.
Later, however, the difficult question arises: does the assay truly represent how the product works in patients?
One of the leaders in our analytical sciences team with significant experience developing GMP potency assays described two recurring patterns. “Some teams wait too long to build a meaningful potency method. Others narrow too quickly and invest heavily in one format before they’re certain it reflects the mechanism.”
Both approaches create downstream pressure.
In cell therapy programs, this dynamic is common. Early assays may measure surrogate indicators such as CAR expression by flow cytometry or cytokine release after bead stimulation. These methods can confirm transduction and activation. They support manufacturing development and help establish process control.
As programs mature, regulators may expect a more representative functional readout. That may involve a more direct measurement of therapeutic activity, such as a co-culture cytotoxicity assay demonstrating antigen-specific tumor cell killing. The shift reflects a deeper understanding of mechanism and clinical intent.
The challenge arises when that evolution occurs late. If significant time has already been invested in validating an earlier surrogate method, transitioning to a more representative assay can require additional validation work, bridging studies, and revised regulatory justification.
The strategic balance to strike is best described as deliberate exploration early, followed by disciplined convergence.
Teams benefit from evaluating multiple assay formats in parallel long enough to understand their limitations. Surrogate markers, functional assays, and alternative detection platforms each provide insight. The objective is not to run multiple assays indefinitely. It is to avoid committing prematurely to a method that may not withstand regulatory scrutiny.
Such an approach may seem counterintuitive, even wasteful of precious resources, yet in our experience it often represents the most efficient path in potency assay development.
2. Regulators Review Your Methods as Closely as Your Molecule
Testing is often treated as a supporting function. In regulatory review, it is not secondary.
At the IND stage, regulators begin examining how you define and measure quality. That includes whether your potency assay reflects the product’s mechanism of action and whether your validation strategy supports consistent, reproducible performance.
A scientific advisor on the Minaris Advanced Testing team who is involved in multiple programs summarized it this way: “We’ve seen promising programs slow down because their assays weren’t positioned to meet regulatory expectations. It’s not always limited to a discussion of safety. Sometimes it’s about whether the method can stand up to scrutiny.”
What does that scrutiny look like in practice?
It often centers on questions such as:
- What evidence links this readout to clinical effect?
- How were acceptance criteria established?
- How was assay variability characterized?
- Is the method robust across operators, lots, and time?
When these elements are not clearly defined, friction follows.
A “poorly defined” assay is rarely nonfunctional. More often, it lacks documented rationale. The link between the readout and the intended biological effect may be assumed rather than demonstrated. Acceptance criteria may be based on limited early data rather than statistical characterization. Variability may not be fully explored across different manufacturing runs.
At IND, those gaps surface.
Regulatory durability means that an assay remains defensible when those questions are asked. It means the justification for the method, the statistical basis for its specifications, and the validation data are coherent and aligned with the product’s clinical intent.
Experience plays a role here. Organizations that have supported multiple programs know how to collaborate with regulators and as a result, prepare sufficient documentation that minimizes rework at later stages.
As a biologic moves into late phase development and commercial production, analytical methods must shift from flexible, development focused tools to fully validated, highly controlled, and inspection ready procedures.
Methods that were previously “fit-for-purpose” and allowed to evolve must become locked, robust, and reproducible, with defined operating ranges, system suitability criteria, and statistically justified acceptance limits.
Specifications narrow and are clinically and process capability supported; validation expands to include full accuracy, precision, robustness, and stability indicating capability; and documentation becomes submission quality.
In addition, formal method transfer, reference standard qualification, lifecycle management, data integrity controls, and ongoing trending are required to ensure the method can reliably support commercial release and withstand regulatory scrutiny for the long term.
3. Operational Complexity Creates Unnecessary Failure Points
Testing rarely collapses because of a single dramatic mistake. More often, complexity accumulates in ways that increase risk of delay and variability.
Operational design decisions matter.
Several leaders described the same pattern: samples move more than sponsors realize. A sterility test may be run in one location, viral clearance in another, and specialized analytics elsewhere. Material is packaged, shipped, received, logged, queued, and reassigned.
Each transfer introduces additional variables:
- Shipping windows
- Temperature control during transit
- Customs clearance for international movement
- Chain-of-custody documentation
- Scheduling alignment between sites
Temperature excursions are a practical example. Samples are often shipped under controlled conditions, with data loggers monitoring temperature throughout transit. Most shipments arrive within range. But when a shipment goes out of specification, even briefly, questions follow:
- Is the excursion within acceptable limits?
- Does it affect test validity?
- Does the sample need to be rejected?
- Does manufacturing need to repeat the batch?
Even when no excursion occurs, the risks increase at every transfer point. Biologics manufacturers conduct shipping studies to prove that their product remains within quality specifications under realistic and worst-case transportation conditions, but as the operational complexity and number of transfers increases, those studies become more complex and harder to design and defend.
One CMC leader emphasized the danger of increased complexity in testing operations this way: “Testing is a relatively small part of the program, but it’s high risk. If something goes wrong here, it affects everything downstream.”
Complexity also appears inside the laboratory. Delays in getting material on test can add hours or days if intake processes are not aligned with manufacturing schedules. QA review cycles can become rate-limiting, particularly for long-running assays. Manual documentation steps increase the possibility of transcription errors or rework.
These events are not constant. In well-run organizations, most samples move without incident, and most tests perform as expected. The issue is cumulative exposure. As complexity increases, the number of potential breakpoints increases with it.
Acceleration depends on reducing that exposure.
Sponsors should examine:
- How many locations handle their material before results are issued
- How quickly are samples placed on test upon receipt
- Where QA review sits in the release sequence
- How much manual intervention is required between assay execution and certificate of analysis
Operational simplicity does not eliminate risk. It reduces the number of variables that must be managed simultaneously. Likewise, operational complexity is not dramatic. It is structural. And when left unexamined, it may itself become a failure point.
4. When Release Strategy and Product Reality Diverge
Cell and gene therapy programs make one constraint unavoidable: some products must be released in less than 72 hours. Traditional sterility testing under USP <71> requires 14 days. Conventional culture-based mycoplasma methods can take up to 28 days.
Faster methods promise to address the gap. Rapid sterility platforms, PCR-based mycoplasma detection, automation, and multi-attribute methods are all part of the current landscape. Many teams are evaluating how these tools can support compressed release timelines.
Regulators are also evolving. As one leader noted, agencies are showing increasing flexibility with novel approaches, particularly in advanced therapies. Yet that flexibility does not remove uncertainty. New technologies must still be validated within a GMP framework and justified for lot release.
Another technical lead summarized the hesitation succinctly: “Who wants to be first?” Integrating newer platforms can feel exposed. The technical capability may exist. The question becomes whether it can be implemented, documented, and defended with confidence.
Compressed timelines make the tension visible. The integration of new testing technologies requires deliberate coordination between technical, quality, and regulatory teams.
Redefine “Acceleration” in Your Testing Strategy
Acceleration in biologics testing is often framed as speed. In practice, it is design. It is the discipline of making early decisions that reduce friction later: selecting assays that will withstand regulatory scrutiny, simplifying operational pathways, and aligning release strategy with product reality. Programs move faster when fewer structural barriers stand in the way.
If you are evaluating your testing strategy in light of compressed timelines, evolving modalities, or upcoming regulatory milestones, we welcome the opportunity to discuss how these principles apply to your program. Please reach out at minaris.com/contact to connect with our experts.