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Temperature Stability Testing

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The detection of soluble aggregates is a crucial step for a wide range of bio-pharmaceutical products.The content of soluble aggregates is one of the most crucial quality attributes of pharmaceutical drug products. Their quantification is necessary for all drug products independent of the type of API. ZentriForce Pharma offers a wide range of analytical techniques for the detection of soluble aggregates.  If you need further information please follow the link. 

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Dynamic light scattering is known as a fast and efficient screening method for aggregate / particle detection. Therefore, it is widely used within biopharmaceutical development. It is used to close the gap between results gained in the range of small soluble aggregates via size exclusion chromatography (SEC) and particle methods such as light obscuration (LO) or micro flow imaging (MFI). Due to the high sensitivity toward large species, even small impurities can be detected within the measurement range (0.5 nm – 1 µm). For more information please follow the link.

µ-DSC is a well-stablished method for thermodynamic analysis of biomolecules, due to combined high data reproducibility and method sensitivity, and the “structural fingerprint” character of thermograms that is unique for each biomolecule. In addition, µ-DSC provides a direct and label-free measurement of thermal stability without the same solvents restrictions that apply to spectroscopic methods. For more information, please follow the link.


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Temperature Stability Testing 

Temperature stability is a critical parameter in drug product development, especially during formulation development or within biosimilarity studies. The aggregation temperature (Tagg) and melting temperature (Tm) may be determined by application of a heat ramp. Stress studies at isothermal temperatures are applied to monitor time-dependent structural changes.

Our scientists have worked on a wide range of biopharmaceutical products, offering expertise in dynamic and static light scattering as well as differential scanning calorimetry that helps to keep the expenses of method development as low as possible. We provide highest quality results while maintaining high throughput. We can therefore assure to keep the cost per sample measurement low.

ZentriForce Pharma Instrumentation

ZentriForce Pharma laboratories are equipped with instrumentation for temperature stability testing via dynamic light scattering (DLS) as well as static light scattering (SLS), and differential scanning calorimetry (DSC).

Light scattering

Zentriforce Pharma uses the DynaPro®Plate Reader III for temperature stability testing. We offer highest quality dynamic light scattering (DLS), as well as static light scattering (SLS) measurements. The combination of both allows us to simultaneously monitor, the formation of large particles as well as changes in the active pharmaceutical ingredient (API), such as dimer formation, and its soluble aggregates.

The DynaPro®Plate Reader III  can perform measurements at small sample volumes (down to 4 µl).  At the same time, the instrument offers highest available sensitivity and allows us to measure at low concentrations.

The use of a well-plate-based approach provides the opportunity to screen a large number of samples in parallel. This reduces the cost per measured sample. Another benefit that comes with this setup is the elimination of contamination risk of the instrument by previously measured samples. Furthermore, comparability of results increases by simultaneous measurement of multiple samples.  We also offer to implement a system suitability check and/or a reference standard into your sample set.

For a more detailed description of dynamic and static light scattering theory please follow the link.

Differential scanning calorimetry

ZentriForce Pharma uses the Malvern automated MicroCal PEAQ-DSC for temperature stability testing. We offer this highly sensitive technique to study thermally induced transitions, such as protein unfolding. MicroCal differential scanning calorimetry (µ-DSC) is considered the gold standard for thermal stability analysis of biomolecules in protein engineering and formulation development, emphasized by a wide range of applicable solvents and no requirements for markers.

During the heating of a biomolecule or mixture, several thermal events may occur simultaneously or sequentially, indicating the unfolding or melting temperatures of different domains of the same molecule. The µ-DSC thermograms register the respective midpoints (Tm) by measuring the heat capacity change as a function of temperature, and the enthalpy can be derived. Tm indicates the protein’s thermal stability. In addition to stability, binding and drug delivery systems fall within µ-DSC applications. Upon binding of ligands and drug uptake, intra and intermolecular interactions change, as well as the dynamic of the components, and can be investigated by monitoring the phase transition temperatures and enthalpies from the thermograms.

Our µ-DSC system is equipped with an autosampler for hands-free operation and samples are loaded in standard 96-well plate format (minimum volume of 325 µL / well).

For a more detailed description of differential scanning calorimetry theory, please visit here.

Interested in Temperature Stability Testing  ?

We are more than happy to assist you with Temperature Stability Testing services.
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Accessible Parameters

Our techniques to assess temperature stability yield melting temperature (Tm), aggregation temperature (Tagg), onset temperatures (Tonset). µ-DSC additionally provides information about change in heat capacity (∆Cp) and change in enthalpy (∆H). This information can help to understand both the temperature dependence of the colloidal and conformational stability at the same time. 

Additionally, we offer to set up isothermal stress studies with a high number of samples simultaneously. We are thus able to assess the temperature stability of different samples, e.g. within a formulation development. 

Temperature Stability Testing Specifications

Light scattering

Main OutputTemperature stability (Tonset, Tm, Tagg)
Size range0.5 – 1000 nm; 1 kDa to 1 Mda
Aditional Outputstime/temperature dependent Size distribution (rH or dH); molecular weight (Mw)
Sample Volume4 µL to 150 µL
Measurement typewell plate (96, 384 or 1536)
Temperature range 4°C to 85°C

Differential scanning calorimetry

Main OutputMelting temperature (Tm); heat capacity change (∆Cp); enthalpy change (∆H)
concentration0.01 – 10 mg/ml
Aditional Outputsbinding constants up to 1020M-1; Tonset
Sample Volume325 µl (minimum / well)
Measurement typewell plate (96 wells)
Temperature range 2°C to 130°C
ZentriForce Quality System
ZentriForce Pharma has established a laboratory quality system that closely follows the extensive and detailed guidelines provided by the WHO and the principle of “writing what you do and doing what you write”. ZentriForce implements procedural, equipment and analytical SOPs. To date, close to 30 SOPs are in place.
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Gene Therapy
For gene therapy product development, traditional quality attributes (e.g. purity) as well as new quality attributes (e.g. the ratio of particles that carry nucleic acids to empty particles) must be addressed. The diversity of approaches for gene therapy API analysis adds a further challenge to product characterization. Our scientists have worked with a wide range of different gene therapy products, ranging from small DNA / RNA complexes over lyposome-based carrier systems and adeno-associated viruses (AAV) to viruses that are several hundred nanometers in size.
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Biosimilarity
Within biosimilarity studies attention is on the collection of evidence that proves that no differences (larger than method variability) in structure and purity exist between a proposed biosimilar and the reference product. Evidence is collected through extensive analytical testing. The different focus between development and biosimilarity testing require an adjusted mindset and a customized study design for the respective task. ZentriForce Pharma can be a valuable partner on your way to release a biosimilar
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Peptides
Despite being far less complex than full proteins, analytical handling of peptides is challenging. Species as small as peptide-based APIs require analytical instrumentation to be run at its physical limits. Expertise and extensive experience in working with such materials is imperative for successful method development. Our scientists have worked with a large number of peptide-based APIs, with sizes down to 1 kDa. They will be valuable assets where expertise and consultation in analytical method development are concerned.
Click here for more information
ZentriForce Quality System
ZentriForce Pharma has established a laboratory quality system that closely follows the extensive and detailed guidelines provided by the WHO and the principle of “writing what you do and doing what you write”. ZentriForce implements procedural, equipment and analytical SOPs. To date, close to 30 SOPs are in place.
Click here for more information
Gene Therapy
For gene therapy product development, traditional quality attributes as well as new quality attributes must be addressed. Our scientists have worked with a wide range of different gene therapy products, ranging from small DNA / RNA complexes over lyposome-based carrier systems and adeno-associated viruses (AAV) to viruses that are several hundred nanometers in size.
Click here for more information
Biosimilarity
Within biosimilarity studies attention is on the collection of evidence that proves that no differences (larger than method variability) in structure and purity exist between a proposed biosimilar and the reference product. Evidence is collected through extensive analytical testing.
Click here for more information
Peptides
Despite being far less complex than full proteins, analytical handling of peptides is challenging. Species as small as peptide-based APIs require analytical instrumentation to be run at its physical limits. Expertise and extensive experience in working with such materials is imperative for successful method development. Our scientists have worked with a large number of peptide-based APIs, with sizes down to 1 kDa.
Click here for more information

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