Technical paper
Prioritize scalability
for an efficientbiopharmaceuticalproduct development
lifecycle
By standardizing on the right
instrumentation, biopharmaceuticalmanufacturers can ensure seamlessscale up from research in the lab all theway to full-scale production.
Authors
Maryann Cuellar and Michael Weiß, Industry Managers Life Sciences - Endress+Hauser

2Prioritize scalability for an efficient biopharmaceutical product development lifecycle

ProcessLaboratory

Creating trust throughcomparable measured values

In the fast-paced world of biopharmaceutical development,speed, efficiency, quality, and cost-effectiveness areparamount. Scalability, the ability to seamlessly transitiona bioprocess from small-scale laboratory experiments tolarge-scale commercial manufacturing, is a critical factor
driving success in this competitive landscape.
However, scalability is not just about increasing the size ofequipment; it is a holistic balancing strategy for operational
workflows, processing equipment and instrumentation,
software, data handling, and supply chain partnerships.
For biopharmaceutical manufacturers, specifying scalable
solutions from small-scale experiments to full-scale
production can significantly bolster success by acceleratingtime-to-market, minimizing risks, easing qualification,
ensuring process safety, and maximizing yield.

Scaling from the lab to production
The drug development lifecycle begins on the micro-scalewith discovery research, including identification, screening,and sample measurements. As promising findings emerge,
researchers advance to lab-scale product development,
which includes activities such as defining primary processtargets and classifying analytical and safety methods.
When a new drug shows efficacy during development in
the lab, the next step is process development at a pilotscale, where manufacturers begin establishing automatedproduction procedures. Analytical measurement technology
helps ensure success during this transitional phase,comprised of requirements and design limit definition,
process validation, and analytic method qualification.

Once these production baselines are established,
manufacturers then pivot their operations and sponsor therequired projects and initiatives to increase production toprofitable levels for filling order demands. At this stage,
inline monitoring becomes vital to achieve high production
volume, maintain required product quality levels, andensure process safety.

Holistic approach to scalability
Scalable bioprocesses hinge on several key elements. The
first of these factors is a deep understanding of the processitself, which requires identifying the critical variables that
influence performance, and understanding how to optimize
them during each stage of product development.
Once this foundation is laid, biopharmaceuticalmanufacturers can focus on equipment scalability.
As production increases, equipment of all types—frombioreactors to utility purification systems—must be
considered to ensure smooth accommodation for larger
batches and higher volumes, without compromisingperformance or creating bottlenecks.
And finally, reliable measurement can make or break ascale-up effort. Consistent and accurate data are essential
for making informed decisions regarding operational
efficiency, production throughput, and quality throughout
the project.

Challenges, success, and advantages

Challenges and risks

Inline sensing advantages

The journey from lab to production poses several
challenges. To begin with, biopharmaceuticalmanufacturing operates under stringent regulatorycompliance, demanding rigorous quality assurance
and product safety protocols. With so many variables,
measurement discrepancies often arise during scale up,
potentially undermining quality assurance and decreasing
yield as a result of time-consuming manual sampling andtesting.

Inline analysis reduces the risk of process issues andincreases production capacity by continuously measuring
product characteristics, and by reporting scaled process
values to a host control system in real time. This eliminates
the need for personnel to take manual samples, which inaddition to being inefficient, presents the risk of detecting
issues retroactive to production.

Adding to the complexity, different stages of productdevelopment often occur at separate locations, potentiallyusing equipment from multiple manufacturers that are
not set up to share data natively, further amplifying risk.
Even similar instruments from different suppliers canexhibit measurement or performance inconsistencies
due to variations in design, materials, or compensation
algorithms.
Furthermore, transferring calibration protocols, methods,and models across separate facilities and stages of scale
up can introduce issues, requiring substantial rework andexpertise if not mindfully designed for scalability from theoutset. When these threats materialize, they necessitate
costly and time-consuming equipment qualification
procedures at each stage of scale up for mitigation.

Success at scale
To reduce the risk of encountering these undesirable
conditions, biopharmaceutical manufacturers canimplement strategies for promoting efficient and consistentprocesses. Seamless technology transfer between processdevelopment in the lab and production at scale is critical tominimize batch variability and enable efficient, continuous,and methodical workflows. When sufficiently planned,
scale-up progresses more quickly and robustly, and quality
is increased as a result at every stage, contributing to longterm manufacturing viability.
To achieve this success at scale, standardizing on processequipment and instrumentation with native support forscaling is essential. This can drastically reduce the risk ofincompatible measurement or data sharing technology,
while significantly spurring workflows for calibration,
configuration, and validation—primarily because staff must
learn and retain fewer technical procedures.
Endress+Hauser’s scalable bioprocessing portfolio provides
manufacturers with substantial advantages by applying thesame measurement technologies in both lab sampling andinline production instruments. Particularly, manufacturers
are achieving success by combining real-time Raman
spectroscopy and Memosens digital sensor technology
for monitoring in their facilities, each of which minimize
configuration complexity, reduce the risk of measurementinconsistencies, and improve overall process efficiency.

Instrumentation for inline analysis typically consists of asensor or probe directly inserted in the process, which sends
information to a transmitter or analyzer for processing. The
instrument then makes process values available for a hostcontrol system for near-real-time monitoring, operational
decision-making, and process optimization. For example,manufacturers can gain comprehensive insights into almost
any biopharmaceutical process by combining inline Raman
spectroscopy with liquid analysis technologies, such as
potentiometric, conductive, fluorescence quenching, UV,and visible light measurement.
Endress+Hauser instrumentation shares commontechnology and materials of construction, simplifying
protocol transition from research and development tomanufacturing. By adopting scalable Raman technology
and digital sensors, biopharmaceutical manufacturers
can minimize equipment complexity and the risk ofmeasurement inconsistency. Endress+Hauser bioprocessing
offerings—including spectrometers, sensors, optics, andcalibration tools—cover a wide range of upstream anddownstream applications for measuring composition, pH,dissolved oxygen, conductivity, concentration, and othercharacteristics.

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4Prioritize scalability for an efficient biopharmaceutical product development lifecycle

Endress+Hauser Raman portfolio for bioprocessing
High-throughput

Flow paths

Single use

Development

cGMP

One Raman probe technology for many real-time bioprocess measurements at all scales
Figure 1: Optimized for both fine-tuned measurement in a lab environment and real-time results in high-volume production,
Endress+Hauser Raman systems help biopharmaceutical manufacturers accelerate the transition from lab to process.

The right instrumentation products enablebiomanufacturers to use many of the same devices in
the lab and in the process to ensure a smooth transition
during scale up. For example, Endress+Hauser’s
Raman systems—measuring chemical composition andconcentration via optical methods—provide continuous
monitoring of critical process parameters, such as glucose
concentration and viable cell density, along with realtime insights for process optimization. The same Raman
instruments used for small-scale experiments can beseamlessly integrated into larger-scale bioreactors,
providing consistent and reliable data throughout theentire production process (Figure 1).
Similarly, Memosens digital sensors provide unparalleledmeasurement accuracy and minimal maintenancerequirements with their reliable non-contact signaltransmission technology. These plug-and-play, precalibrated sensors help minimize downtime and ensure
consistent performance from the lab to production.
Digital data transmission eliminates signal interference
and enables predictive maintenance, further enhancing
process reliability (Figure 2).

Benefits
Endress+Hauser provides:• Single-source solution: An extensive portfolio ofindustry-conforming products and services lengthen
lifecycles.
• Simplified equipment: The same devices can be utilized
in the lab, pilot plant, and production line, streamlining
qualification procedures and minimizing the need forpersonnel retraining.
• Faster time-to-market: Smoothly transition from smallscale experiments to full-scale production.
• Reduced risk: Minimize quality risks and simplify
compliance efforts.
• Decreased costs: Achieve cost savings with less waste
and maximized yield.

Agility wins the day
As the biopharmaceutical industry shifts towards newmodalities, single-use technologies, and increasing relianceon continuous manufacturing, the importance of scalability
is growing quickly and is evidenced widely. Manufacturers
must be nimble to continue meeting the demands of thisdynamic sector.
By leveraging instrumentation technologies designed withscalability front and center, manufacturers are progressing
drugs through the product development lifecycle quickly
and safely, delivering life-changing therapies to patients
faster and more efficiently.
Endress+Hauser is committed to providing innovative
solutions that empower biopharmaceutical companies tonavigate this evolving landscape and achieve sustainablesuccess.

Figure 2: The cycle of Memosens sensor operation, cleaning,and calibration.

PU01584C/66/EN/01.24

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