Moving from lab-scale production to clinical trial manufacturing marks a major leap in the drug development pathway. Scale-up manufacturing for clinical trials requires translating small-batch formulations into dependable, reproducible processes while preserving safety, quality, and regulatory compliance.
UPM Pharmaceuticals has deep experience supporting such transitions through its technology transfer & scale-up support services. Below, we explore the steps of the scale-up process in the pharmaceutical industry, common obstacles and how to overcome them, best practices to ensure success, and criteria for selecting the right CDMO partner for scale-up.
Article Contents
What Is the Scale-Up Process in the Pharmaceutical Industry?
The scale-up process in the pharmaceutical industry involves several distinct phases, each with its own objectives and regulatory requirements. Understanding these stages helps teams plan effectively and avoid costly missteps.
Pre-scale / Pilot Stage
Small-batch or pilot-scale development establishes proof of concept. Critical process parameters (CPPs) are identified, and dosage forms are refined (e.g., tablets, capsules, semi-solids). Analytical methods are developed to assess content uniformity, dissolution, stability, and other key attributes. UPM’s formulation development capabilities support these stages with labs that conduct method development, stability studies, and formulation testing.
Technology Transfer & Scale-Up Support
Moving from pilot batches to clinical-scale (IND / Phase I-III) involves tech transfer, scale-up of process equipment, qualification of manufacturing lines, validating analytical assays, and adjusting process parameters so that scale-dependent effects are managed. UPM’s tech transfer & scale-up team works cross-functionally (R&D, manufacturing, quality, regulatory) to minimize risk and ensure consistency.
Clinical Trial Manufacturing / Regulatory Support
Clinical phase manufacturing demands cGMP compliance, batch records, stability data, and documentation suitable for regulatory submissions. Scale-up must preserve efficacy, purity, and safety attributes, even when production volumes increase. Quality by Design (QbD) and risk assessments play a role. UPM provides full regulatory filing support and stability studies.
Challenges in Scale-Up Manufacturing for Clinical Trials
While scale-up is an exciting milestone, it introduces complexities that can derail timelines and budgets if unaddressed. Below are the most common scale-up manufacturing challenges pharmaceutical companies face when preparing for clinical trials.
- Scale-Dependent Process Variables: Mixing, heat transfer, granulation, drying times, compression forces—all change when moving from bench to pilot and pilot to clinical scale. Effects that are negligible at small scale can lead to batch failures if not properly addressed.
- Analytical Method Translation: Small-scale analytical assays might behave differently when sample matrices or batch sizes change. Inadequate analytical method development services risk inaccurate measurements of impurities, content uniformity, dissolution, or stability.
- Regulatory & Compliance Hurdles: The process must comply with cGMP, ICH guidances, DEA rules (if controlled substances are involved), and other regional regulatory requirements. Documentation must be detailed and robust.
- Supply Chain & Material Consistency: Sourcing excipients or raw materials that are consistent lot to lot becomes more difficult as scale increases. Changes to materials may trigger requalification or validation work.
- Equipment Limitations: Not all pilot or clinical batches use the same equipment type or scale, which can lead to challenges in equivalence, maintenance, and process reproducibility.
- Time & Cost Pressures: Scaling up is expensive and time-consuming. Delays, rework, or batch failures can consume resources and affect clinical timelines. Efficiencies in planning and execution are critical.
Best Practices for Successful Scale-Up in Clinical Phase Manufacturing
Applying proven practices can dramatically reduce risk during clinical phase manufacturing scale-up. Below are the most effective strategies to ensure a smooth transition from lab to clinic.
Start with Robust Process Development & Design of Experiments (DOE)
Use statistical design to map key variables, define ranges, and identify critical quality attributes early. UPM uses DOE and QbD approaches to anticipate scale effects and reduce surprises.
Conduct a Thorough Gap / Risk Analysis
Compare lab-scale vs pilot-scale requirements, regulatory expectations, equipment differences, and analytical assay performance. UPM’s tech transfer & scale-up support includes a risk gap analysis as part of every scale-up project.
Secure Raw Material & Excipient Supply Early
Ensure that materials used at small scale are available at larger scale, or have alternates qualified. Consistency in material quality mitigates risk of variability in drug product.
Validate Analytical Methods Early & Monitor Continuously
Method validation (LOD/LOQ, linearity, specificity, accuracy) should be done under conditions expected at the larger scale. Continuous process verification helps with consistency.
Maintain Close Communication Between Teams
R&D, manufacturing, quality assurance, regulatory affairs, and project management must align. Clear documentation, shared data, and stage-gate reviews help avoid misalignment.
Implement Strong Quality & Regulatory Oversight
Follow cGMP from pilot through clinical manufacturing. Document everything, prepare for regulatory filings, stability studies, audits. Choose CDMO partners with proven regulatory compliance.
Pilot Lots & Bridging Studies
Producing pilot or clinical lots before full scale helps detect unexpected issues, confirms stability, and enables bridging if formulation or process changes are needed.
How to Choose a CDMO Partner for Scale-Up
Selecting the right CDMO partner for scale-up is one of the most important decisions in clinical phase manufacturing. The following criteria can help you evaluate potential partners and ensure they have the expertise, facilities, and systems you need.
| Factor | Key Questions | Why It Matters |
|---|---|---|
| Experience with Clinical Scale-Up | Has the CDMO successfully transferred tech from lab to clinical stage? How many products scaled in oral solids, semi-solids? | Minimizes risk of process failures and delays. UPM has brought 80+ compounds to commercialization and handles both solid and semi-solid dosage forms. |
| Analytical & Regulatory Capabilities | Does the CDMO have in-house analytical labs, stability programs, and the ability to support regulatory filings? Can they handle controlled substances if needed? | Ensures you can submit credible data to regulators; avoids delays. UPM’s facility supports analytical, microbial, and stability testing, with DEA licensing. |
| Facility & Scale Flexibility | What batch sizes are possible? Are there pilot and scale equipment; can they scale volumes efficiently? | Different scales bring different challenges; a facility that supports pilot to clinical to late stage is essential. UPM’s facility is 475,000 sq ft, able to support millions of units and large-volume semi-solids. |
| Quality & Risk Management Systems | How strong is their QbD and risk assessment practice? Track record for process validation, GMP audits, compliance? | Scale-up without risk management can lead to costly failures. UPM emphasizes a cross-functional tech transfer team and risk gap analysis. |
| Transparency & Collaboration | Will the CDMO share project status, provide access to stakeholders, permit site tours, and allow you to engage leadership early on? | Better visibility and collaboration reduces surprises, helps you stay on schedule. UPM invites clients to engage with leadership and offers full transparency during scale-up projects. |
| Cost, Timelines, & Flexibility | What are cost estimates, what buffers are built into timeline, how is change managed if unexpected issues arise? Can they adapt? | Unexpected delays or cost overruns can delay clinical trials. Choosing a CDMO that plans for them is essential. |
UPM’s Role & Strengths in Scale-Up and Clinical Phase Manufacturing
UPM Pharmaceuticals stands out as a CDMO partner for scale-up manufacturing for clinical trials because of its integrated services and experience. This combination allows clients to move seamlessly from formulation development through scale-up to commercial manufacturing with a single trusted partner.
- Proven ability to move products through formulation, technology transfer, scale-up support, and commercial manufacturing.
- Extensive facility capacity in Bristol, Tennessee: capable of producing large volumes (tablets, capsules, semi-solids), with DEA-licensed vaults, full analytical, microbial, and stability testing labs under one roof to support clinical and late-stage work.
- Cross-functional project teams that manage tech transfer, regulatory compliance, analytical method development, and risk assessment as integrated parts of scale-up.
FAQs About Scale-Up Manufacturing
Below are some of the most common questions pharmaceutical professionals have about scaling up manufacturing for clinical trials.
Can changes made during scale-up affect the clinical trial material’s stability or efficacy?
Yes. Changes in scale can influence factors such as mixing, heat transfer, moisture, and particle size, all of which may impact stability or efficacy. That is why analytical method development, stability studies, and bridging lots are essential during the scale-up process.
Is it possible to use the same CDMO for both clinical and commercial manufacturing?
Absolutely. Selecting a CDMO with capacity for both clinical phase manufacturing and commercial manufacturing ensures consistency, minimizes the risk of transfer errors, and can speed time to market. UPM supports this through its commercial manufacturing services and scale-up support.
How early should I engage a CDMO partner when planning for clinical trial scale-up?
Ideally, engagement should begin during the early formulation development or pre-scale phase so that process constraints, raw material sourcing, regulatory needs, and equipment limitations are all taken into account. Early collaboration reduces risk and lays the foundation for smoother scale-up.
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Partner with UPM Pharmaceuticals to Navigate Your Scale-Up Path
Scaling up manufacturing for clinical trials is full of technical, regulatory, and operational challenges—but with the right planning, best practices, and partner, the transition can be efficient and successful. CDMO partner selection becomes a critical decision. UPM Pharmaceuticals offers the experience, facility, and integrated service capabilities to support clients through the scale-up process, from the earliest stages through clinical manufacturing and beyond.
If you are preparing for clinical-phase scale-up, talk to our team to understand how our tech transfer and scale-up support, commercial manufacturing services, and regulatory expertise can help you stay on track and deliver quality trial material on time. Contact UPM Pharmaceuticals today to learn how we can support your scale-up goals.
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