Biologics

Novel process development | safe, pure, potent, stable | AAV vectors, lentivirus, adenovirus | key manufacturability gaps | transfer to constrained manufacturing suites | game changer for cell and gene therapy

Cell and gene therapies require novel process development and manufacturing strategies to deliver on their revolutionary promise. These advanced therapeutics require you to develop processes that deliver a safe, pure, potent, and stable medicine, as guided by the FDA, with a manufacturing control strategy that can ensure high-quality delivery to patients over the product lifecycle. 

We deploy our upstream, downstream, and analytical expertise across AAV vectors, lentivirus, and adenovirus systems on various host cell platforms, to baseline, optimize and then transfer processes to cell and gene manufacturing suites. We identify key manufacturability gaps early in our collaborations and define and execute a development program that will improve processes and deliver the critical quality attributes required.

We also leverage our 500L pilot plant facility to conduct training runs that build process understanding at scale and support effective and on-time tech transfer into constrained cell and gene manufacturing slots. Our collaborative approach, where we share every data point with you, is a game-changer helping you to take control of your cell and gene therapy development and manufacturing programs.

High yield and purity | ÄKTA^™ technology | ion exchange and affinity | purification and isolation | impurity removal and polishing | ChromX modeling | upstream integration 

Chromatography is the cornerstone of our downstream process development approach where we strive to isolate and purify your product in a manner that delivers high yields and purity. 

We build design spaces around ion exchange and affinity chromatography platforms and we use our ÄKTA™ technology infrastructure to screen resins and run powerful DOEs that gather the most information, using the least material, in the shortest space of time. Throughout downstream development, we constantly evaluate the best approach to capture, concentrate and stabilize products before removing impurities and polishing the final product.

We also leverage chromatography modeling packages, like ChromX, to obtain process understanding earlier in development, and to minimize the number of experiments we run in the lab. This approach, combined with our downstream expertise and smart experimental strategies, ensure that downstream development can keep up with upstream breakthroughs.

Predict heat and mass transfer | run virtual experiments | design equipment sets faster | shorter, smarter experiments | predictive labs models | solve manufacturing issues

Computational Fluid Dynamics (CFD) is a turnkey solution that we use to deliver key process development breakthroughs across all our synthetic and biologics programs. As a modeling tool, CFD helps predict heat and mass transfer across any kind of equipment set – but more fundamentally CFD enables our teams to run 100's of virtual experiments before we hit the lab. 

These virtual, in silico, experiments, adjusting impeller types, feed locations, vessel geometries and fill levels, help us build a library of process knowledge that we pore over before running short and smart experiments. In the hands of our experts, this tool helps us design and select the equipment sets rapidly, build predictable scale-up/down models quickly and identify probable root causes for manufacturing issues before conducting a single experiment. 

The use of CFD for process development goes to the heart of what we do at APC – which is to fundamentally understand processes, from first principles, before quickly charting the fastest process development path forward. We believe that as a platform approach to process development CFD is a game-changer that can slash development time, reduce laboratory effort and identify engineering scale-up and manufacturing strategies that would never be considered using brute force, experiment-centric approaches.

Process yield and impurities | production bottlenecks | cassette, TFF, hollow fibre | inline particle sizing and Raman | solve aggregation challenges

We believe the selection and optimization of the right separation and filtration technology is often overlooked during process development, impacting process yields and impurity removal, while also often introducing challenging production bottlenecks. 

We couple process simulations with experimental screens across cassettes, TFF and hollow fibre systems to help you select and then optimize the right filtration and separation platform for your process. We also work to ensure that the selected platform works seamlessly with your upstream process. Our downstream engineering teams bring breakthroughs in scale-up science and modeling to quickly build representative scale-down separation and filtration models and we apply computational fluid dynamics and PAT tools including inline particle sizing and Raman spectroscopy, to solve difficult separation challenges including protein aggregation. 

We treat the selection and optimization of filtration and separation bioprocess operations as integral to the overall development plan for every biologic we work on and we collaborate closely with clients to ensure focused process development effort translates to high yielding processes with no manufacturing bottlenecks.

Identity, strength, quality, purity | 97% in house samples | deep technology infrastructure | process development focus | confident decision-making

The development of reliable analytical methods to monitor the quality attributes of a biologic or synthetic molecule is critical for guiding process and product development activities. Reliable analytical methods are also required to monitor the drug substance (DS) and drug product (DP) to ensure that applicable standards of identity, strength, quality, and purity are met.

We have deep analytical expertise and an in-house analytical infrastructure that allows us to characterize 97% of the samples we take within minutes of being extracted from the process. Our methods development experience has been applied to a variety of molecules including classic synthetics as well as recombinant proteins, mAb’s, vaccines, gene therapy products, and antibody-drug conjugates and our capabilities include HPLC, capillary electrophoresis, laser diffraction, DSC, SEM, TGA, qPCR, and TCDI50. 

Methods development, optimization, and validation, as well as process development support for our fast-moving scientists, is the daily business of our analytical group and our goal with every sample is to generate high-quality information that provides clarity for you and helps us make critical process development decisions with confidence.

Close collaboration | many sample types | compliant protocols | documentation packages | fast turnaround | flexible collaborative style

Transferring your analytical methods to us is a step in the externalization process where we invest time and attention. As a team that relies on data to make decisions, we want the methods we run to run to help us make real scientific breakthroughs at a fast pace. To accomplish this, we treat every method you transfer to us carefully and collaborate with you closely to ensure we can rely on those methods together on the process development journey

We have experience executing methods transfer for finished product, API, bulk drug, drug substance (DS), drug product (DP), intermediates and many other sample types.  We generate compliant protocols and highly detailed documentation packages in accordance with your quality guidelines to ensure a successful method transfer. Our experience encompasses all available types of equipment sets and procedures for both biological and synthetic products.

We provide quick turnaround on feasibility assessment of analytical methods, protocol execution and preparation of final reports. The degree of success for a method transfer is often proportionate on how close we can work together and we strive for a flexible and collaborative working style that helps develop the most appropriate strategy to ensure an efficient, timely method transfer.

High productivity, high titer | attachment and spreading | batch or perfusion mode | reduced media cost and contamination | avoid roller bottles and cell factories 

Microcarrier-based cell culture systems deliver high productivity and high titer processes for adherent cell lines in robust and scale-friendly bioreactors. Microcarrier based processes, reduce the volume to cell density ratio compared to roller bottles and help you reduce media cost, avoid contamination, and minimize manual steps during production. 

We combine our upstream and bioengineering expertise to develop and scale-up microcarrier based processes from flasks to bioreactors in record time. We evaluate microcarrier systems in terms of their attachment and spreading efficiency, and choose critical process parameters, such as pH, feed profile and mixing regime, that help you deliver high titers at low volumes across various scales. 

Collaborating with us on a microcarrier system process development can mean the difference between using non-reproducible and difficult-to-approve cell factories instead of deploying standard bioreactors for fast, predictable scale-up and clinical delivery. Evaluating microcarriers as an option for adherent cell lines, early in development, is a process development strategy we believe can truly accelerate the delivery of medicines to the people that need them.

Complex interrelated datasets | actionable insights | CPP vs. CQA | manufacturing troubleshooting | process characterization | DoEs | find breakthroughs faster

Today’s process development and manufacturing operations produce massive amounts of information that require new tools, like multivariate data analysis, to extract relevant information from complex and interrelated datasets.  

We use MVDA to unearth actionable insights from the datasets we create during process development and we also use it to review historical production information when we tackle a challenging manufacturing issue. By more clearly understanding the interactions between process variables and critical quality attributes across our datasets, we find optimization breakthroughs faster and solve technical challenges without running experiments. 

We also use MVDAs during process characterization activities and on the DoEs that we run, ensuring that a full statistical analysis is deployed against the precious data we collect, helping us make better process development decisions that facilitate speed through your pipeline.

Large-scale demonstration | tech transfer strategy | 250L SUBs | avoid manufacturing delays | scale-up sciences | confidence and clarity | right-first-time manufacturing

Large-scale demonstration of process performance is a key component of our tech transfer strategy. With the ability to run bioprocesses in single-use systems at up to 250L scales we can test process performance before transfer to GMP manufacturing suites.

The information we gather at these scales helps us lock in process parameters and identify potential bottlenecks or manufacturing gaps before they start to impact manufacturing timelines. These large-scale runs also inform our total scale-up strategy confirming that the parameters we choose to go from lab to pilot plant will also serve the final commercial introduction at even larger scales.

Combined with our PAT and bioanalytical infrastructure we can support right-first-time tech transfers with confidence and provide you with the clarity you need to confidently introduce ground-breaking processes into manufacturing.

Thousands of datasets | CMC strategy | NDA and BLA | process development evidence | eliminate experimental rework | fast creation of regulatory control documents

During process development, you will collect thousands of datasets, across many unit operations, which must be collated into a cohesive development report that will serve your CMC strategy and ultimate NDA or BLA filing.

Working externally across a process development and manufacturing network of partners often feels like you are losing control of these critical datasets, not having them at your fingerprints when you need them. We believe this slows you down so we built a first-in-class digital data management platform, called iACHIEVE®, which our technical and project management teams use every day, to capture and share every datapoint directly with as it is collected. 

This digital-first approach to process development makes tech transfer easier. By having development reports and raw data to hand as we collaborate on the tech transfer strategy for your asset, we can base scale-up decisions, equipment selection and batch record creation on sound process development evidence. This approach eliminates experimental rework late in development and enables faster creation of regulatory control documents.

Kinetic and statistical | computational fluid dynamics | virtual experiments | smarter DoEs | self-optimizing processes | slash development time | better processes | smarter lab work

We believe modeling is a game-changer for process development. We use kinetic, statistical, and state-of-the-art computational fluid dynamic process modeling platforms to run virtual experiments, predict how processes will behave at scale and reduce the experimental burden across your process development programs. 

We combine off-the-shelf modeling packages such as Fluent, DynoChem, Aspen and JMP with our own purpose-built models, typically developed in MATLAB, to power up your process development activities, delivering scientific breakthroughs with real speed. 

We leverage modeling to define smaller and smarter DoEs, design bioreactors from first principles and to predict solubility and particle morphology during crystallization development. We also combine our models with bespoke control architectures to run self-optimizing processes that leverage the kinetics and thermodynamics of the system itself to define the recipe that will deliver the critical quality attributes required.

We have seen our platform approach to modeling slash development time and deliver better processes compared to brute force, experiment-centric approaches. We also believe it offers us the opportunity to make our lab work more effective reducing the total cost of development and making every valuable experiment count.

Raman and mid-IR spectroscopy | particle imaging and sizing | automated sampling | at line analysis | PAT experts | calibration and verification | careful analysis | total process understanding

We are proud to be a technology powerhouse having standardized on the most advanced process development platforms in the world, using PAT, automation, and data management software to transform productivity in the laboratory and deliver scientific insights never thought possible. 

Our PAT infrastructure combines in-line particle size analysis and microscopy with Raman and mid-infrared spectroscopy to monitor liquid and solid phase behaviour for every process we develop. Coupled with automated sampling to support rapid offline analysis, at process conditions, we build a data-rich kinetic profile for every experiment we run. We also bring key offline characterization tools closer to our process, developing at line or flow-based methods to deliver real-time information for transient mechanisms or difficult to sample components. Critically our process development experts are steeped in PAT experience and use it every day for every experiment as a standard way of working. They know how to calibrate instruments, capture the right data, and analyse it carefully to deliver the insights our clients need. 

We believe that process understanding is the raw material from which medicines are made and our best-in-class PAT infrastructure is a foundation from which we strive to accelerate the delivery of medicines to patients.

Right first time | vast equipment infrastructure | FMEA risk assessments | CPP classification | model support DoEs | PARs | design space builds | source documentation | data transfer in real-time

The closer a process gets to the patient the harder we work together to ensure that your life-changing medicine can be introduced to manufacturing right first time. We combine a vast equipment infrastructure, with tools to characterize processes completely and a team who understand how processes run in real manufacturing scenarios. 

Together we conduct FMEA risk assessments, CPP classification, model supported design of PARs and DoEs to fully characterize late-stage processes as they are prepared for commercial introduction. The depth of knowledge collected and collated across process, analytical, modeling and scale-up sciences becomes the platform for manufacturing introduction and is essential for lab model development, design space builds and the provision of source document to the regulators for demonstrating knowledge of your manufacturing control strategy.

Our clients are never kept in the dark when they work with us and we return every data point in real-time so that you can lock in process parameters quickly and conduct tech transfer transparently. We seek to provide clarity when you most need it, as you take your medicine to the market. 

Fit for purpose | CMC collaboration | flexible manufacturing options | bioanalytical infrastructure | return data in real-time | dynamic early phase collaboration

We take your most promising clinical candidates, wrap world-class processes around them in a fit for purpose manner, and collaborate with you on every step of your CMC journey. 

We strive to understand your clinical landscape and the technical work needed to advance your programs with speed. We optimize challenging steps, solve key technical challenges related to process and product performance and we provide you with flexible manufacturing options that never lock you into a single manufacturing approach or vendor. 

We also use our state-of-the-art analytical infrastructure to obtain process understanding from every experiment and we return every single data point to you, in real-time, to support the dynamic nature of your early phase process definition work.

Technical challenges | manufacturability gaps | QbD approaches | modeling and PAT | glassware, bioreactors, wave bags, SUBs | equipment design and selection | partner network

After thorough process baselining has identified the key technical challenges and associated manufacturability gaps for your process, we collaborate with you to define and then execute a development program that takes CMC off the critical path. 

We screen process conditions identifying the key process parameters requiring optimization and define strategies to ensure the critical quality attributes for your product can be delivered consistently across scales and manufacturing platforms. We deploy QbD approaches as standard, obtaining deep kinetic and thermodynamic understanding for your processes, leveraging real-time analytics and modelling platforms to accelerate development decisions. 

Throughout development, we evaluate strategies for scale-up, to standard or bespoke manufacturing equipment sets, with processes that are well understood and behave robustly across defined design spaces.

Predictive and representative | optimal manufacturing | GMP experience | FDA and ICH guidance | lab model build and transfer | MSAT lab options 

Developing a bioprocess scale-down model is at the core of your development and validation activities. A non-predictive scale-down model has severe consequences including unexpected changes to quality attributes during scale-up and suboptimal manufacturing performance.

We use our deep engineering and modeling expertise to develop, optimize and characterize bioprocesses in the lab that accurately predict performance at scale. Our process development experts, steeped in GMP manufacturing experience, follow the relevant FDA and ICH guidelines for developing scale-down models, and collaborate closely with you and your equipment suppliers to ensure better models are developed faster.

We partner with you to build one-off scale-down models but also have the expertise to run complete MSAT operations for your organization at a single location running multiple scale-down models simultaneously and supporting GMP production, troubleshooting and optimization across the lifecycle of your product. 

Process understanding | 3L, 7L, 15L | CPPs and CQAs | modeling mixing | virtual experiments | pilot plant test runs | unique manufacturing strategies

Scale-up design is at the heart of what our bioengineering team do to support your medicines journey to manufacturing. From the earliest stages of upstream and downstream processes development, we strive to select cell lines, develop media, select separation technology, and choose chromatography resins that will make the mass production of your medicine possible. 

We work in glassware to critically understand your process, leveraging a vast bioanalytical suite of technologies, before determining a scale-up strategy that gets your bioprocess into a bioreactor at the 3L, 7L and 15L scales. From here we assess the process for scalability, evaluating the relevant CPPs and developing the analytical methods to deliver the information needed to target the relevant quality attributes. We model mixing regimes at feed locations and determine shear rates that may impact the product yield. We also deploy PAT tools, upstream and downstream, that can monitor the metabolic flux or reveal protein aggregation. 

From this position of deep process knowledge, we prepare to move to larger scales, ultimately targeting test runs at the 250L scale in our single-use pilot plant. These runs confirm performance and help make optimizations that will support a fast and effective transfer to commercial manufacturing. For many bioprocesses, the ultimate manufacturing strategy involves non-standard equipment sets that must be designed and built from the ground up. We support this effort running virtual experiments on SUBs and wave bags so challenging manufacturing introductions can happen right first time under challenging timelines.

Vials, bioreactors, wave bags, SUBs | target titers and product profiles | QbD approaches | modeling and analytics | metabolic flux, turnover, pathway | fast efficient CMC work 

We treat your biologics platforms with the care they deserve, working across vials and shaker flasks, into multiscale bioreactors, wave bags and single use platforms in our state-of-the-art process development labs and pilot plant. Our experts conduct phase appropriate design on standard and advanced therapeutics including mAbs, vaccines, ADCs, cell and gene therapies. 

We collaborate with you closely to define target titer ranges and product quality profiles and keep bioreactor design and control strategies in mind during early-stage upstream process design. We use QbD approaches from first principles, modeling processes before entering the lab and using offline, at-line and inline analytics, to better understand metabolic flux, turnover and pathway. 

The result is fast and efficient CMC outcomes and a high performing upstream process, that can be scaled-up and manufactured easily, helping you hit timelines and address your patients’ needs.