Microsampling
We have launched a survey to gather information on the current use of microsampling. If you use a microsampling technique within any research or safety study for new drugs and (agro)chemicals, we are interested to learn the 3Rs impacts you have achieved. If you do not use microsampling, please let us know your concerns and any barriers you may have experienced to help guide our future strategy.
Please download the survey (.XLSX format) and return it to helen.prior@nc3rs.org.uk by Wednesday 24 February. It should take no more than 15 minutes. |
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Advances in bioanalytical techniques have opened up the potential to use smaller sample volumes (microsamples) to assess drug and chemical exposure in blood, plasma and/or serum. It is now possible to assess drug levels and blood biochemistry parameters from samples of 5-20µl.
A microsample generally refers to a sample of ≤50µl. The small sample volume required enables samples to be taken from the main study animals which reduces or avoids the use of satellite animals. The sampling procedure provides a refinement because microsampling is quicker and less stressful, for example, warming of animals can be reduced or avoided.
Microsampling is used by many companies in early studies, such as those in discovery and for dose range finding. However there are scientific, business and animal welfare incentives to implement microsampling more widely within other toxicology and non-clinical studies where blood sampling is performed. Uptake for GLP toxicology studies was slower due to perceived regulatory hurdles and concerns that sampling from main study animals will compromise key endpoints. Many of these concerns have been addressed in recent studies, as described in Powles-Glover et al1 and Powles-Glover et al2 and microsampling is now also routinely included in many regulatory studies. Additionally, updates to international regulatory guidance in 2017 (ICH S3a Q&A, The assessment of systemic exposure in toxicity studies: Focus on microsampling) support and promote microsampling.
The aim of this web resource is to guide strategy and encourage adoption of microsampling techniques within academia and the pharmaceutical and chemical industries.
- Working Group
- Benefits of microsampling
- Can you use microsampling in your toxicology study?
- Resources
- Bibliography
Working group
To further increase uptake of microsampling, we lead an international microsampling user group which includes 27 companies and regulators. We act as an honest broker for data sharing - the evidence that we collated fed into the updates to regulatory guidelines (ICH S3A Q&A document) and is published within peer-reviewed journals.
Benefits of microsampling
There are multiple advantages associated with microsampling including scientific, resource related and animal welfare benefits, which are summarised in the diagram above.
- Ability to relate toxicity directly to exposure in the same animal
- All animals are sampled in the same way
- Multiple endpoints can be assessed in one animal
- Better toxicokinetic profiles
- Possibility of sampling from alternative routes
- Blood loss from the animal is reduced
- The procedure is less invasive
- Reduced restraint time or alternative restraining methods can be used
- Warming time is reduced
- Removing smaller volumes takes less time and is less stressful to animals
- No satellite animals or smaller satellite groups means fewer animals are required
- Less test material is required
- Fewer animal-related resources, such as housing and care, is required
Can you use microsampling in your toxicology study?
There are many considerations that need to be taken into account to implement microsampling within your organisation and for a specific compound.
This decision tree can help to determine if your study is amenable to microsampling, and which is the most relevant approach (for example microsampling from a group of satellite animals or from main study animals).
For more information on sampling techniques in general, refer to our blood sampling pages.
Resources
Example study designs and videos (with accompanying protocols) for microsampling can be found by following the links below.
Bibliography
We have collated a selection of key papers relevant to microsampling, the bibliography can be downloaded below.
Follow this link to submit a paper for inclusion in our bibliography.
We have also collated posters containing exciting or unpublished data relating to microsampling. These can be downloaded below.
- Effect of capillary microsampling on toxicological endpoints in juvenile rats at PND4, 10 and 17
- Microsampling-coupled bioanalysis in the neonatal and juvenile Göttingen minipig and beagle dog
- Further progress on steps to reduce animal numbers used on regulatory toxicology studies utilising microsampling and sample-sparing techniques
- How big is a microsample?
The following posters were presented at the NC3Rs workshop on “Using microsampling to refine blood sampling procedures in industry and academia” on July 5 2016.
- Use of Microsampling in Oncology Projects: Reduction & Refinement
- Checklist for the use of capillary microsampling in regulatory studies
- DM-MAP: Designing a Drug and Metabolite Microanalytical Platform for Detection and Quantification of Molecules in Pre-Clinical Studies: Initial Studies with Lamotrigine
- Practical capillary microsampling – avoiding the pitfalls
- Supporting Tests for Non-capillary Microsampling of plasma in rat and mice in-vivo studies: small volumes, containers - it all matters!
- Effect of capillary microsampling on toxicological endpoints in juvenile rats at PND4, 10 and 17
- Using continuous intravenous microdialysis sampling as an alternative to free fraction pharmacokinetics determination in plasma
If you have a relevant poster to share, please follow this link to submit a poster for inclusion on our website.