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Lyo Lab R&D Analytical Services
Cutting edge contract R&D by internationally renowned freeze drying specialists. The expertise and experience of our dedicated lyophilization scientists in Winchester, UK has led to:
- our analytical lyo lab team becoming an industry leader in lyophilisation process analysis
- involvement in some major scientific breakthroughs and the development of high-performance lyophilization instrumentation. (LINK TO ANALYTICAL LYO INSTRUMENTS PAGE).
Industry, regulated industries and government agencies depend on BPS Crowthorne’s lyo analytical services in freeze drying – notably in the pharmaceutical, biotech, vaccines and diagnostic reagent sectors. Services include formulation and cycle development, scale up/optimisation, product and process reviews and much more.
World-Class Knowledge
Every product type, formulation and applications is different – requiring highly specialised knowledge and extensive experience. Our scientists work with companies and universities to help them:
- achieve critical enhancements in formulation quality
- generate significant efficiencies in product viability, time and costs.
Our team is led by Director of R&D, Dr Kevin Ward, renowned internationally for his pioneering work in the freeze drying of red blood cells.
Before joining the team, Dr Ward worked at Pfizer Central Research and as a Research Fellow in vaccine development at Aston University. He lectures on freeze drying extensively and is a member of the Academy of Pharmaceutical Sciences Parenterals Group.
He also chairs the PHSS Freeze Drying Special Interest Group, an international working group that produces monographs on practical aspects of freeze-drying technology. In addition, due to his excellent reputation in the field, Kevin has been involved in:
- co-authoring chapters such as The Principles of Freeze-Drying and Application of Analytical Technologies with Paul Matejtschuk in Cryopreservation & Freeze-Drying Protocols
- editing Lyophilization of Pharmaceuticals and Biologicals, published as part of the Springer Protocols series of books by Springer Science & Business Media and Humana Press.
Why BPS Crowthorne?
Clients and partners choose BPS Crowthorne for our expertise in R&D/process troubleshooting, cycle audit and regulatory support, new product development, variable and passed scale production, design and development of proprietary analytical technology.
They benefit from faster access to market and end-to-end process support. Applications include:
- Diagnostics – polymerase chain reaction (PCR) and loop-mediated isothermal amplification (LAMP) products, antibody tests, fluorescent probes, mastermixes
- Pharmaceuticals – small molecules, proteins, cytotoxic compounds, antibodies, antibiotics, conjugated compounds
- Biotech – collagen/ collagen scaffolding, hydrocolloids, liposomes/exosomes, human tissues, cells and bacteria.
- Food and nutraceuticals – fruit, vegetables, meat, fish, beverages, early life products and food supplements
Product Characterisation – Critical To Success
Product characterisation is central to all formulation and process development. It provides an early indication of any changes needed in formulations – and the detailed reporting is ideal for quality control and regulatory submissions.
BPS Crowthorne uses the following specific analyses to understand the behaviour of your product throughout the freeze drying process – and the impact of the different components on it:
Freeze Drying Microscopy (FDM)
FDM is a well-established lyophilization analysis technique developed in the 1960s for identifying critical formulation parameters. It is the only method for reliably determining collapse temperatures. Knowledge of critical temperatures saves precious time and budget – and is essential for cycle development on a quantitative scientific basis.
Previously FDM was used only to determine collapse/eutectic temperatures but the latest generation Lyostat FDM can also determine:
- crystallisation phenomena
- potential for skin/crust formation
- effects of annealing on ice crystal growth and solute structure.
Differential Thermal Analysis and Impedance Analysis
Differential Thermal Analysis and Impedance Analysis uses the unique Lyotherm frozen-state analyser to investigate changes within the frozen product:
- providing data such as glass transition (Tg’), eutectic (Teu) and melting (Tm) temperatures
- enabling determination of endothermic and exothermic events – such as crystallisations and eutectic melting – in the frozen sample (with major implications for the processing and stability of your product).
Post-Process Analyses
Moisture Analysis by Karl Fisher Coulometric Titration establishes the amount of moisture remaining in your product after processing (because no product is ever 100% dry). This analysis helps demonstrate the overall success and efficiency of the lyo process. Additionally, specialist analysis such as dynamic vapour sorption (DVS) is a gravimetric technique that measures how quickly a sample absorbs a solvent vapour, and how much solvent in total is absorbed. In most cases water vapour is used for DVS experiments, but this can also be performed using a variety of organic solvents if required.
Key Benefits Using of DVS
- Ultra-sensitive microbalance detects changes in mass smaller than one part in ten million, allowing very small samples to be used and minimising analysis time
- Allows determination of upper and lower humidity limits for storage of your product
- Reveals reversible and permanent changes in materials caused by increased humidity
- Used for quality control of foodstuff and chemical powders during production
- Can be used to evaluate suitability of packaging materials for storage of your dry product
- Allows calculation of surface area of samples – useful when studying porosity or reconstitution behaviour, and for batch comparison purposes
Modulated Differential Scanning Calorimetry (mDSC) identifies glass transitions, crystallisations and other significant events in freeze dried samples – verifying whether or not the freeze dried product will remain stable in long-term storage.
Other post-process R&D work includes analysis using MicroPress (to determines the robustness of the dried cake), mechanical testing, Scanning Electron Microscopy (SEM) and X-ray Diffraction Analysis (XRD).
Formulation Development – Improve Performance
Freeze drying can damage labile materials such as proteins or living organisms – so creating the right formulation requires precision. Damage can occur at various stages including freezing, drying and heating.
Every component can affect the outcome; selecting and combining the right excipients to protect the active ingredient requires experience and expertise.
Our scientists can improve the performance of existing formulations or create new ones, and provide assistance on pre-formulation studies. They have worked on more than 3,000 different products including small drug molecules, large and complex biomolecules, foods, tissues and cells.
Cycle Development – Create Robust, Repeatable, Efficient Processes
Freeze drying is a complex process because the risks are not constant. They can change – even if you don’t alter the temperatures involved.
Multiple freeze drying cycles may be needed for each product. All the processes must be optimised for maximum product performance and financial return.
Developing separate processes is also important for regulatory compliance. For example, the US Food & Drug Administration states: “A manufacturer that has one cycle for multiple strengths of the same product probably has done a poor job of developing the cycle and probably has not adequately validated their process. Investigators should review the reports and data that support the filed lyophilization cycle.”
Each stage – freezing, primary drying and secondary drying – can present challenges. Factors influencing cycle design include the:
- type and amount of product and its thermal characteristics
- capabilities of the processing equipment.
BPS Crowthorne’s Quality by Design (QbD) approach minimises risk by applying data and prior knowledge – it is more formal and structured than the traditional iterative R&D process. By looking at individual areas of the process, we can better understand where the risks are – and make the process more robust, minimising any potential issues during scale-up.
This enables our scientists to create robust, repeatable and efficient cycles – usually within three runs – saving time, product and money.
Our specialist team uses Lyostat freeze drying microscopes and unique Lyotherm instrumentation to provide key product data and draft an initial cycle. They then freeze dry a small amount of product in our pilot-scale equipment – monitoring product progression throughout the process. Other tests include Karl Fischer moisture determination, mDSC, DVS, SEM and XRD.
Specialist Analysis – For Superior Quality Control
Dynamic Vapour Sorption (DVS) is a gravimetric technique that measures how much solvent vapour a sample absorbs and how quickly it does so:
- enabling determination of upper and lower humidity limits for storage of your product
- revealing reversible and permanent changes caused by increased humidity
- minimising analysis time and sample size because the ultra-sensitive microbalance detects changes in mass smaller than one part in 10 million.
It can be used:
- for quality control of foodstuffs (and chemical powders) during production
- to evaluate the suitability of packaging materials for storage of your dry product
- to calculate the surface area of samples – useful when studying porosity or reconstitution behaviour, and for batch comparison.
Applications for DVS:
- Pharmaceutical – packaging (notably blister packs), material characterisation, pre-formulation and formulation, determining storage conditions
- Personal care – creams (moisturisation studies), effect of thermal or chemical hair treatment
- Food – caking of powders, visible changes with humidity, stability and shelf-life prediction.
Our standard procedure includes increasing the chamber’s relative humidity from 0% to 90% then down again in stepped increments of 10%. At each step, we hold the humidity until the sample weight stabilises, taking pictures throughout the process. It usually takes up to 72 hours but this can vary significantly depending on the sample’s hygroscopicity, porosity and other factors.
Differential scanning calorimetry (DSC) measures the temperature and heat flow associated with thermal transitions in a wide range of materials. It involves raising sample temperature at a constant rate. We log the heat flow against temperature to generate the DSC trace which, as a result, shows exothermic and endothermic events.
DSC is used to:
- characterise the thermal behaviour of solutions before freeze drying to determine critical process parameters
- determine the melting behaviour of complex organic materials
- determine the thermal stability of a material and predict ideal storage conditions
- quantify the amorphous and crystalline content of a material.
We measure the glass transitions, crystallisation and melting events – studying thermal transitions at low heating rates (or with small sample sizes) with no loss of sensitivity.
Visually observing and recording the physical changes enables quantitative reporting. This is of great benefit, especially for troubleshooting. Recorded images can be made into videos, exported easily with a data ribbon and annotated. An optically sealed crucible is also available for those wanting to conduct closed experiments.
Scale Up And Optimisation
Changing batch size, container size, fill depth or even simply equipment can affect the freeze drying process. Cycles optimised for the lab may not work on larger systems because production dryers may have different capacities to smaller R&D systems in terms of temperature, condenser load and process energy.
BPS Crowthorne uses Lyostat and Lyotherm freeze drying instrumentation to obtain key data about essential product characteristics. Our scientists:
- process small amounts of product in pilot-scale freeze dryers with sophisticated monitoring and data trending capabilities
- provide you with detailed reports and suggested alterations to your cycles.
Optimisation is important because overlong/ overcautious cycle parameters waste energy (and budget) and significantly reduce batch turnaround. Conversely, cycles that are too short or aggressive can compromise product stability to the point of failure.
Issues with unsuitable cycles waste time, delay production and may need operator intervention. Additionally, not all processing defects are immediately visible: they may show up only later during quality control or testing.
Outsource Your Production
Overcome your freeze drying capacity issues. Our production facilities are ideal for:
- start-ups or smaller organizations whose manufacturing runs are not yet large or consistent enough to justify investing in on-site production facilities
- manufacturers who need extra freeze drying capacity because of sudden large orders or technical issues with their existing equipment
- customers who have used our development facilities but not yet purchased equipment.
BPS Crowthorne offers pilot-scale freeze drying on a contract basis. Each unit has a shelf area of 0.5m² to 1.42m² and up to 35 litres condenser capacity – allowing 1,760 10ml DIN10 vials, 2,112 5ml DIN6 or 5,016 2ml DIN2 vials to be processed in one machine at a time. Stoppering and backfill is available where needed. PC control provides in-cycle monitoring and post-process analysis.
We can handle small molecules, nucleic acids, proteins, bacteria and biomaterials – and provide the necessary containment for genetically modified organisms (GMOs). Cytotoxic products are handled in a separate standalone facility with dedicated equipment.
Filling, labelling, post-process moisture analysis and validation are also available.
Collaborative Projects – Bid For Government Funding
Companies and universities have partnered with BPS Crowthorne/Biopharma Group to co-develop new products, bidding successfully for funding from Innovate UK (formerly the Technology Strategy Board).
We have a strong track record of successful bids for SME funding – and are keen to participate in more collaborative R&D projects involving freeze drying.
Together with our partners, we have addressed challenges including:
- Regenerative medicine – freeze drying human blood for long-term storage
- Regenerative medicine – freeze drying collagen scaffolds for regenerative repair of cartilage
- Industrial processing – freeze drying advanced formulations of probiotics
- Crop protection – developing novel formulations of innovative targeted pesticides.
BPS Crowthorne also collaborates with process equipment developers to test new machines and evaluate methods. These partnerships have included:
- Headspace Analysis – evaluating a novel method for non-destructible QA/QC applications
- Atmospheric Spray Freeze Dryer – prototyping.
Contact us to find out more about partnership opportunities.
Process Review – For Scale Up, Product Evolution, Regulatory Submissions
Even small adjustments to your freeze drying formulation or equipment can have a major impact after scale-up – affecting the cycle and your product quality.
The most serious processing failure is product collapse – affecting shelf life, stability and activity. However, you can’t always see it.
Reviewing the freeze drying process ensures that product and cycle remain in harmony. This is particularly important if you are:
- planning to scale up
- have changed your formulation or freeze drying equipment
- preparing for a regulatory submission.
Our scientists will use freeze drying microscopy to identify the most important thermal characteristics of a liquid sample, including the eutectic/collapse temperature. We will also test five dry samples using Karl Fischer Titration.
All data and conclusions will be outlined in a written report. The lead scientist will also schedule a phone call with you to discuss the findings.
Cytotoxic Handling – In Safe, Secure, Standalone Facilities
Specify freeze drying R&D analysis and processing of cytotoxic products in dedicated standalone lab facilities built to Class 7 standards.
BPS Crowthorne has expert knowledge of freeze drying cytotoxic products. Our dedicated facilities are developed specifically for this demanding area of R&D analysis.
Safe and responsible handling of cytotoxic drugs means:
- protecting staff with advanced safety measures significantly more stringent than those in normal labs
- avoiding cross-contamination of other products being developed or produced
- exacting operating procedures to avoid accidents and spillages
- appropriate precautions for handling and disposing of laboratory waste.
Your products will be processed in a safe and controlled working environment – providing ideal outsourcing for smaller developers and an outstanding product development service for more established enterprises.
Services include:
- product characterisation, formulation and cycle development
- concept and stability testing and trials
- optimised solutions for cost-efficient processing
- process scale-up and optimisation
- small-scale production.
Contact BPS Crowthorne – Access Our Expertise
Contact BPS Crowthorne for more information about contract lyo lab R&D analytical services for freeze drying applications. Ask us about partnerships and opportunities to bid for government funding.