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 in toxicology studies. Uptake for GLP toxicology studies is 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.

The aim of this web resource is to guide strategy and encourage adoption of microsampling techniques within 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 are acting as an honest broker for data sharing and the evidence that we are collating is feeding into the ICH S3A (Q&A document).

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

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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.

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Resources

Example study designs and videos (with accompanying protocols) for microsampling can be found by following the links below.

Bibliography