blood microsampling and the drug development process
by Fiona Mahjoor | 4 min read
Animal research has been a polarizing topic in our society for a number of years now. However, when we weigh our own health and wellness and that of our loved ones against the cost of animal lives, the practice, for many, comes into perspective as an unfortunate necessity. But is there something we can do to ease the burden on the creatures sacrificing for us, without compromising the efficacy of the drug development process? Blood Microsampling could be the answer.
A Little Background on Microsampling
Blood microsampling is a process by which a small sample of blood -often just a few drops- is applied to a given matrix (DBS cards are most common, but other options are appearing), dried, and then extracted using various solvents, and analyzed. Even though traditional wet blood sampling usually takes a much larger volume, for many tests, those few drops of blood are all that is needed for a result.
Microsampling and the Discovery Phase
In the Discovery Phase of the Pre-Clinical process, the prospective drug is first introduced into mice and rats, where it is tested both for its effects on the malady it is engineered to combat, as well as for its efficacy- namely, its clearance from the rodent’s system. Mice are the preferred subject, both because they breed so quickly and because they are the most well-understood animal model.
However, using small mammals poses a critical problem. Think about the amount of blood drawn at your annual check-up. Now compare that to the body mass of a mouse. See the issue?
Quite often, an entire mouse is sacrificed for the testing of one (drug) at one time-point. This is not only a sad reality for test animals, but it is also costly for testing labs and may not even be the best way of obtaining good data and results.
The cost of a rodent life adds up practically to the expense of its housing, cleaning, feeding, handling, and disposal of the animal (bio waste disposal is not cheap!) That cost is compounded when it comes to testing on animals that have been genetically engineered for the purposes of the study.
Those animals, as you know, are extremely expensive to sacrifice.
Furthermore, results of drug discovery can potentially become more valuable if we are able to sample from the same subject at multiple time points. This provides far better data and insight into how the drug is interacting with and moving through the system of the same animal (because although little white lab mice may look all the same to us, they aren’t!).
Given these benefits, one would wonder why not simply use less blood? The answer is that most labs work with plasma, which is derived from spinning down larger volumes of whole blood. The results from whole blood can be different than those from plasma, and correlations to the widely accepted plasma results require a bridging study.
The time and expense of carrying out the bridging studies can cause reluctance to adopt the microsampling method. Despite this hurdle, the myriad of microsampling benefits has created significant interest in the use of microsampling for pre-clinical applications.
Microsampling in the Toxicology Phase
At this point in the drug development process, the inclination towards using blood microsampling nose-dives for the very obvious reason that the animals used at the toxicology stage are larger, and therefore have greater blood volumes to sample from.
The cost-saving advantages of conserving more animal lives all but disappear at this point, and the cost of doing a bridging study is no longer seen as worthwhile.
However, there is an argument to be made that the direction that our society is taking with respect to the humane treatment of animals warrants a better standard of care for test subjects even with if it comes at a slightly higher cost.
Perhaps even many consumers would be glad to have those costs shared between them at market if they knew that the animals sacrificing for their health were fewer and more comfortable. Themes of restraint and conservation are also beginning to pervade the actions of individuals and companies, who are becoming aware of the harmful impact on the world.
Unchecked taking without questioning the necessity is no longer the norm. Large blood draws create stress in the test subjects, which is not only a harm in and of itself, but which can actually convolute test results. Given this, if we don’t actually need copious amounts of blood from these animals, perhaps using restraint is worth the cost.
Microsampling in Clinical Trials
Microsampling is garnering attention at the clinical trial level for a different sort of reason, and that reason stems from its comfort and convenience to humans. At the clinical trial stage, pharmaceutical companies are more likely to spend on the cost of the bridging study to whole blood since the total investment by this time has been a large one.
There is considerable motivation to do so, and the keyword here is ‘adherence’. One of the greatest threats to clinical trial success and accuracy is the simple fact that participants don’t always adhere to their regimen of medication and blood testing.
Commitments, inconvenience, discomfort, or forgetfulness can stop them from coming into the clinic for their blood draws. This almost inevitably causes unreliable data in the study. The advantage of blood microsampling is that it offers trial participants the freedom to take their own samples any time from the comfort of home, with only the minimal pain of a finger prick. This matters to trial coordinators because they care greatly about improving adherence and getting better results, but they also care about the people and their comfort.
Given the many advantages blood microsampling has to offer at different stages of the drug development process, maybe more thought should be given to spreading its benefits of accuracy, restraint, and comfort to all living participants in the process.
Where do you think blood microsampling offers the most benefit in the drug development process?