
==== Front
Bioanalysis
Bioanalysis
Bioanalysis
1757-6180
1757-6199
Taylor & Francis

39235075
10.1080/17576180.2024.2388939
2388939
Version of Record
Review Article
Bioanalytical Challenge
Patient-centric microsampling for abrocitinib pharmacokinetics: multiple-analytes assay bridging using Tasso device
https://orcid.org/0000-0002-5151-9983
Tripathy Sakambari a
https://orcid.org/0009-0007-9701-7771
Wan Katty X * b
Shahin Mohamed H a
Winton Jennifer A a
Malhotra Bimal K c
Kavetska Olga a
a Pfizer Inc., 445 Eastern Point Road, Groton, CT 06340, USA
b Pfizer Inc., 10555 Science Center Dr, San Diego, CA 92121, USA
c Pfizer Inc., New York, NY 10017, USA
* CONTACT: xia.wan@pfizer.com
5 9 2024
2024
5 9 2024
16 15 825834
Aptara04 8 2024
22 8 2024
24 6 2024
02 7 2024
© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group
2024
https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent.

Aim: The feasibility of using Tasso devices (Tasso-SST® and Tasso+) collecting capillary blood samples for measuring abrocitinib and its metabolites were evaluated, and assay concordance established between capillary and venous blood samplings.

Methods: Capillary serum and venous plasma concentrations were measured using their respective qualified and validated assays. Concentration and exposure comparisons were conducted for abrocitinib and its metabolites (M1, M2 and M4) to establish assay concordance.

Results: The correlation coefficient between capillary serum and venous plasma concentrations were >0.98 for all four analytes from three separate assays, and PK parameters (AUClast and Cmax) were compared and met bioequivalence criteria.

Conclusion: These results demonstrate the feasibility of patient-centric microsampling device, such as Tasso, in future abrocitinib pediatric study.

Article highlights

To evaluate feasibility, the Tasso serum collection microsampling devices were used parallel to venous plasma collection in abrocitinib clinical study.

The serum to plasma partial validations were conducted to ensure equivalence between serum and plasma methods.

Capillary serum to venous plasma concentration bridging were conducted for abrocitinib and three major metabolites (M1, M2 and M4) per currently available industry white paper.

The PK exposure comparison was conducted to demonstrate similarity in concentrations data generated using the two blood collection methods (Tasso vs. traditional venous phlebotomy).

Excellent concordance between the two sets of concentrations was demonstrated for all four analytes.

For abrocitinib and metabolites pharmacokinetic measurement, Tasso liquid blood microsampling device is less invasive, uses lower blood volume and can be easily implemented at clinical site in pediatric study without the complication of blood-to-plasma ratio determination.

Keywords: 

abrocitinib and its metabolites
concordance
concentration bridging
capillary serum
microsampling
Tasso-SST®
Tasso+
Pfizer 10.13039/100004319 This clinical study was funded by Pfizer Inc, no funding was received for manuscript development and submission.
==== Body
pmc1. Introduction

Patient-centric microsampling (PCS) has emerged as an innovative approach to improve blood sample collection by maximizing convenience and minimizing discomfort [1], allowing at-home sample collection, and enabling more flexible study design [2,3]. It has become a reality for pharmacokinetic (PK) sampling in recent years due to the innovative advances in collection devices as well as the analytical ability to accurately quantify concentrations of target analytes [4–8]. The miniature sample volume, lesser invasive collection method compared with conventional venipuncture collection method and the possibility of at-home collection makes it an attractive future sample collection method for PK and beyond in clinical trials. PCS can bring significant benefits to pediatric [9] and oncology patients [7], where small blood volumes are required both clinically and ethically and ambulation may be an issue. A main distinction between PCS and traditional blood sampling by venipuncture lies in prioritizing patients' needs and putting their preferences and comfort at the core of the process [10].

The improved analytical technology, such as more sensitive mass spectrometers and ultra-high performance liquid chromatography (UHPLC) coupled with tandem mass spectrometric (MS/MS) detections, is capable of analyzing small-volume PK samples with reliable results. Despite the advancement in highly sensitive quantitative methods and presence of several successful examples of using microsampling in clinical trials including data submitted to major regulatory agencies, the wide adoption of microsampling in drug development has been slow [11]. This is in part because of the conservative nature of the drug development process, questions about the sample stability and quality, comparability to standard sampling method and the perceived uncertainty of the acceptance of the technique by regulatory agencies. Large-volume samples are still being routinely used in clinical practice alongside their associated large volume bioanalytical methods [12]. More importantly, in vivo assay concordance evaluation (also known as bridging study) to compare the PCS approach with a conventional venous sampling technique is required as a regulatory expectation prior to any PCS implementation. The bridging study requires samples collected by both methods at the same time points from the same participants, so a direct correlation can be drawn [11]. Therefore, it may not be easy to find an appropriate opportunity late in the clinical development (such as after product approval) to conduct assay concordance evaluations. With a pediatric formulation study B7451061 (NCT04903093) planned in adult population, we decided to use the opportunity to conduct assay concordance evaluation for abrocitinib pediatric program in this study in order to bring these PCS benefits to the future pediatric study participants. It is acceptable to conduct the assay concordance evaluation in adult populations and continue to monitor assay concordance in the target population when feasible.

Currently multiple PCS devices are commercially available, either approved or in development as investigational use only (IUO) devices. We decided to partner with Tasso because their integrated devices do not require separate skin pricking, resulting in less stress and pain for participants. For device selection, liquid blood sampling format was selected because the future pediatric study is planned to be conducted at clinical sites. Therefore, liquid blood sample processing and storage at clinical site is not a concern, and the bridging is relatively easy compared to dried blood sampling format where blood-to-plasma (B/P) ratio has to be taken into account.

Once an appropriate device was identified based on program needs, bridging evaluation was incorporated into the study design as an exploratory end point. Time-matched PK samples were collected from the participants using selected PCS device along with traditional venous blood collections to generate data pairs from two sampling routes for concentration and subsequent PK parameters comparison.

2. Methods

2.1. Devices

PCS devices from Tasso Inc. offer both liquid blood and dried blood collection options. Bridging between concentrations measured from dried blood samples to gold standard venous plasma samples requires the application of B/P ratio [13]. Therefore, consistent B/P independent of subjects, time points and concentrations is the prerequisite to implement a dried blood assay if the intended bridging matrix is plasma. Alternatively, individual B/P ratio needs to be applied where the benefits of using PCS will be diminished due to the need to obtain B/P in individual subjects. In pediatric population, B/P ratio may be different from that obtained in adults. Moreover, it may vary in different age groups. This complexity requires additional sampling for B/P ratio determination, increasing burden in target population and leading to less benefits to patients. Because the future pediatric study will be conducted at clinical sites and liquid blood sample processing and storage at clinical site is not a concern, we decided to collect liquid blood samples at clinical site to take full advantage of small volume and less invasive sampling via Tasso device without the complications from B/P ratio measurements.

Serum tubes were selected due to potential clotting issues observed with plasma tube, which is specific to low flow rate of blood causing insufficient mixing with anticoagulant.

Due to the need for higher aliquot volume required to support three separate assays, the Tasso+ serum collection device was initially selected to allow higher blood volume collection. During the conduct of the clinical study, Tasso+ was discontinued from the study following observed unwanted tolerability issue and Tasso-SST® was used instead. Therefore, both devices were used in study B7451061 and this publication reports bridging results of both Tasso+ and Tasso-SST® devices.

Tasso-SST® can collect up to 300 μl of blood with approximately 100 μl of serum harvested. Tasso+ can collect up to 600 μl of blood with approximately 250 μl of serum harvested. The device was applied to the upper arm of the participant at protocol specific time points, following the IFUs (instruction for user) provided by Tasso Inc. The serum samples were allowed to clot at room temperature and processed according to the lab manual.

2.2. Sample collection

B7451061 was an open-label, randomized, single dose, crossover, three-treatment, six sequence, three-period study to evaluate a pediatric formulation in development. In brief, a total of 19 healthy participants were randomized to receive one of the following: ABRO 200 mg tablet (TRT A), ABRO 200 mg suspension (TRT B), or famotidine (40 mg tablet) + ABRO 200 mg tablet (TRT C). Serum microsamples were obtained using Tasso+ or Tasso-SST® device parallel to venous plasma samples for all participant in all periods at three selected time points (1, 8, 12 hrs). Capillary blood collection was timed as close as possible to the venous blood sample collection. Currently accepted industry white paper for guidance on microsampling was followed for sample size determination and data comparison [11].

2.3. Plasma method & plasma sample analysis

The validated plasma methods were used for samples collected through traditional venipuncture. There are four analytes (abrocitinib, Ml, M2 and M4) measured with three separate methods [14,15]. M2 is a chiral metabolite, and a validated chiral HPLC-MS/MS method was used for its quantitation. The chemical structures of all four analytes are presented in previously published article [15].

2.4. Serum method & serum sample analysis

The fit-for-purpose HPLC-MS/MS methods were qualified at Syneos Health Clinical Laboratories (Princeton, NJ) to confirm the suitability of using the validated plasma methods for the concentration determination of the same analytes in serum. This approach was used to enable a quick feasibility assessment without initially committing significant resources. For these method qualifications, quality control (QC) samples prepared in serum were analyzed against plasma calibration curve with plasma run validating QCs during assay accuracy and precision run. Selectivity and dilution linearity in serum were assessed in addition to primary precision and accuracy run in all three methods. The method qualifications met predefined acceptance criteria confirming the equivalency of serum vs. plasma samples for all four analytes across all three methods. The assay performance results of these qualifications are reported in Table 1.

Table 1. Inter-run precision and accuracy for Abrocitinib, M1, M2 and M4 in human serum.

Abrocitinib	QCLLOQ	QCL	QCML	QCMH	QCH	
Conc. (ng/ml)	1.00	3.00	60.0	1000	1600	
  Intra-run mean	1.03	3.15	64.7	1050	1690	
  %CV	4.07	2.84	1.99	1.70	1.52	
  %Bias	3.00	5.00	7.83	5.00	5.63	
  n	12	12	12	12	12	
M1	QCLLOQ	QCL	QCM	QCH	 	
Conc. (ng/ml)	1.00	3.00	50.0	750	 	
  Intra-run mean	0.964	3.04	52.7	738	 	
  %CV	4.04	3.32	1.99	2.72	 	
  %RE	-3.60	1.33	5.40	-1.60	 	
  n	6	6	6	6	 	
M2	QCLLOQ	QCL	QCML	QCMH	QCH	
Conc. (ng/ml)	5.00	15.0	75.0	250	3750	
  Intra-run Mean	4.37	13.2	67.1	229	3470	
  %CV	4.39	2.25	3.46	2.03	1.45	
  %RE	-12.6	-12.0	-10.5	-8.40	-7.47	
  n	6	6	6	6	6	
M4	QCLLOQ	QCL	QCM	QCH	 	
Conc. (ng/ml)	1.00	3.00	50.0	750	 	
  Intra-run mean	1.02	3.03	51.5	757	 	
  %CV	12.7	1.95	1.79	2.42	 	
  %RE	2.00	1.00	3.00	0.933	 	
  n	6	6	6	6	 	
Bold numbers indicate nominal concentrations

Subsequently, these qualified methods were utilized for the analysis of serum samples using the plasma calibration curves to generate PK concentrations. A dilution approach was applied to accommodate lower serum sample volume while avoiding over-dilution of low-concentration samples. In addition, the serum samples were strategically distributed across the three different methods to ensure sufficient serum volume was available for primary analysis and incurred sample reanalysis (ISR) in each of the three methods. The established plasma long term stability (LTS) and Freeze-Thaw (FT) stability were applied to the exploratory serum sample analysis.

A total of 162 samples were collected using Tasso+ (116) and Tasso-SST® (46) devices in this study. Dilution assisted sample analysis was conducted when volumes were insufficient. For abrocitinib, 140 samples analyzed for primary analysis and 33 samples for ISR. For M1 and M4, 129 samples analyzed for primary analysis and 33/31 for M1/M4 ISR respectively. For chiral M2 metabolite, 123 samples analyzed for primary and 22 samples for ISR. Incurred sample reanalysis was conducted for all the analytes and all analytes met ISR criteria (i.e. %Difference for 2/3 of the reanalysis were within ±20.0% of their mean values), confirming the qualified fit-for-purpose exploratory methods are robust and reproducible. The ISR results are reported in Table 2.

Table 2. ISR performance for Abrocitinib, M1, M2 and M4 in human serum from study B7451061.

Analyte	Number of samples evaluated	Passing rate %	
Abrocitinib	33	100	
M1	33	93.9	
M2	22	100	
M4	32	96.9	

2.5. Capillary serum & venous plasma concentration bridging

Venous plasma samples were analyzed using validated plasma methods. Capillary serum samples were analyzed using qualified serum methods. Agreement between the two blood collection methods was assessed using the following methods:

2.5.1. Concentration comparison between the two sampling methods

Concordance between the two methods was determined by computing the difference in concentrations for each data pair and expressing this difference relative to the average of the two results. For a small molecule analyte, like abrocitinib, the sampling methods are considered comparable if the relative percent differences for at least 2/3 (67%) of the samples are within ±20%.

2.5.2. Statistical correlation

Agreement between the two blood collection methods was assessed using a combination of two tests: Deming regression, and Bland-Altman (B-A) plots.

2.5.3. PK comparison between plasma & serum samples

PK parameters for abrocitinib and its metabolites (Ml, M2 and M4), from the capillary serum (Tasso) and venous plasma samples, were calculated for each subject using noncompartmental analysis of concentration-time data. Maximum observed concentration (Cmax), and area under the curve from time 0 to time of last quantifiable concentration (AUClast) were summarized descriptively by treatment. Actual sample collection times were used, and samples below the lower limit of quantitation (LLOQ) were set to 0, for the PK analysis. PK parameters were calculated using Pfizer-validated software, open noncompartmental analysis (oNCA, version 2.6.21). Natural log-transformed AUClast, and Cmax of abrocitinib and its metabolites were analyzed using a mixed-effects model with sequence, period and treatment as fixed effects and subject within sequence as a random effect. The adjusted mean differences and 90% confidence intervals (CIs) for the differences obtained from the model were exponentiated to provide estimates of the ratio of adjusted geometric means (GMR) (test: reference = serum: plasma)) and 90% CI for the ratio. For a small molecule analyte, like abrocitinib, the sampling methods are considered comparable if the AUC and Cmax ratios are within 0.80–1.25.

3. Results

3.1. Concentration comparison

The measured Tasso serum concentrations were compared with the plasma concentrations for each of the four analytes. Table 3 summarized concentration comparison data. For each data pair compared, it is considered as “passing” the pre-set criteria if the %Difference are within ±20%. For abrocitinib, %Difference ranged from -54.1% to 69.5%, with a passing rate of 71% (100 out of 140 data pairs). For M1, %Difference ranged from -49.4% to 42.1%, with a passing rate of 73% (94 out of 129 data pairs). For M2, %Difference ranged from -36.2% to 26.2%, with a passing rate of 82% (101 out of 123 data pairs). For M4, %Difference ranged from -46.8% to 49.6%, with a passing rate of 70% (90 out of 129 data pairs).

Table 3. Concentration comparison between venous plasma samples and capillary serum samples collected by Tasso.

Analyte	%Difference	Number of data pairs within ±20% of the mean value	%Passing Rate	
Abrocitinib	From -54.1% to 69.5%	100 out of 140	71	
M1	From -49.4% to 42.1%	94 out of 129	73	
M2	From -36.2% to 26.2%	101 out of 123	82	
M4	From -46.8% to 49.6%	90 out of 129	70	
%Difference ± [(Tasso Serum Conc – Plasma Conc)/Mean of the Two values] × 100%.

%Passing Rate ± (Number of data pairs within ±20% of the mean value)/total number of data pairs.

All analytes met pre-set concentration comparison criteria.

3.2. Statistical correlation

The capillary serum concentrations agreed well with the plasma concentrations for all four analytes. Figures 1–4 summarized the statistical analysis results. For abrocitinib, Bland-Altman bias was -2.95% with correlation coefficient of 0.9842 from 140 data pairs. For M1, Bland-Altman bias was -0.055% with correlation coefficient of 0.9880 from 129 data pairs. For M2 chiral metabolite, Bland-Altman bias was -7.76% with correlation coefficient of 0.9915 from 123 data pairs. For M4, Bland-Altman bias was -0.736% with correlation coefficient of 0.9824 from 129 data pairs.

Figure 1. Abrocitinib Deming regression and Bland-Altman plots between venous plasma concentrations and Tasso serum concentrations. (A) Deming regression and (B) Bland-Alman plot.

Figure 2. M1 Deming regression and Bland-Altman plots between venous plasma concentrations and Tasso serum concentration. (A) Deming regression and (B) Bland-Alman plot.

Figure 3. M2 Deming regression and Bland-Altman plots between venous plasma concentrations and Tasso serum concentrations. (A) Deming regression and (B) Bland-Alman plot.

Figure 4. M4 Deming regression and Bland-Altman Plots Between Venous Plasma Concentrations and Tasso Serum Concentrations. (A) Deming regression and (B) Bland-Alman plot.

3.3. PK comparison between plasma & serum samples

For abrocitinib and its three metabolites, the PK profiles with geometric mean across the three timepoints observed between plasma and serum samples overlapped well as shown in Supplementary Figure S1. Additionally, the comparison of key PK parameters (AUClast and Cmax) between the two sampling methods (Tasso serum as test and venous plasma as reference) showed good agreement with adjusted geometric mean ratio and 90% CI within the conventional bioequivalence (BE) acceptance range of 0.80 to 1.25. For abrocitinib, both AUClast and Cmax met BE criteria in 3 treatment groups (Table 4). For the metabolites, both AUClast and Cmax met BE criteria in all three treatment groups (Supplementary Table S1) except for M1. Although the 90% CI for Ml Cmax of participants treated with abrocitinib 200 mg tablet (121.70 [90.18–164.23]) and M1 Cmax of participants treated with abrocitinib 200 mg suspension (104.36 [80.86–134.70]) were the only results being outside the conventional BE acceptance range, the ratio and 90% CI of AUClast for these participants were contained within the BE acceptance range.

Table 4. Abrocitinib Exposure Comparison Between Venous Plasma Sampling and Capillary Serum Sampling by Tasso.

Treatment	Parameter (Units)	Venous Plasma (Geometric Mean)	Capillary Serum (Geometric Mean)	%Ratioa	90% CI for Ratio	
A (200 mg Abrocitinib Tablet)	AUClast (ng×hr/ml)	2851.53	2818.09	98.83	(94.16–103.72)	
 	Cmax (ng/ml)	780.03	809.59	103.79	(96.84–111.24)	
B (200 mg Abrocitinib Suspension)	AUClast (ng×hr/ml)	3196.99	3007.94	94.09	(91.03–97.25)	
 	Cmax (ng/ml)	869.07	854.59	98.33	(94.17–102.68)	
C (Famotidine 40 mg + Abrocitinib 200 mg Tablet)	AUClast (ng×hr/ml)	874.73	916.33	104.76	(101.09–108.55)	
 	Cmax (ng/ml)	120.73	128.14	106.14	(98.97–113.83)	
a Ratio = GM Derived from Capillary Serum Samples/GM Derived from Venous Plasma Samples × 100; GM=Geometric Mean.

The model is a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect.

The ratios (and 90% CIs) were expressed as percentages. The reference treatment is venous plasma.

Values are approximated to the nearest two decimal places.

4. Discussion

In the absence of any regulatory guideline, incurred sample reanalysis criteria (i.e. %difference in 2/3 of the data pairs must be within ±20.0% of their means) was used for the concentration comparison. It must be noted the incurred sample reanalysis criteria is intended for the same sample analyzed with the same method. For concentration bridging, different samples were analyzed with different analytical methods. For all four analytes the pre-set acceptance criteria was met. As shown in Table 3, concentration comparison passing rate ranged from 70% to 82%.

The observed ∼30% failure rate could be attributed to variability introduced by different samples and different methods during analysis. Due to limited volumes collected to cover 4 analytes from 3 different assays (including one chiral assay), dilution assisted analysis was utilized to make up the sample volume for analysis. These dilutions applied to all 3 assays have resulted in increased variability compared with historical assay performance without dilutions. However, the assay robustness of each for the four analytes is still deemed acceptable, supported by the incurred sample reproducibility result in each of the three separate assays established (Table 2).

4.1. Implementation considerations

In addition to assay feasibility, the application of microsampling to clinical PK studies requires further considerations when it comes to implementation. The decision for microsampling and type of microsampling devices to be used should be made based on various factors such as properties of the analytes to be quantitated (such as stability, nonspecific binding to sampling material), the location for sample collection (i.e. remote or at the clinic) and the type of patients expected in the clinical trial (i.e., healthy or diseased, adults or pediatric). The implementation strategy will need to be built early in the program [2]. Besides sample collection devices, procedures, technical, logistical and operational issues need to be addressed for the conduct of individual trials and sample bioanalysis. Regulatory requirements may relate to both the status of a given device for use in clinical trials, countries and the acceptability of the bioanalytical data generated for drug registration.

5. Conclusion

The evolution of PCS has marked a significant shift in the landscape of clinical care and clinical trials, fostering a more inclusive and personalized approach for patients and clinical trials participants. This study aimed to evaluate the feasibility of PCS using Tasso serum separator tubes for PK measurement vs. conventional plasma collection in healthy participants treated with abrocitinib. The comparison of the measured concentrations from the samples collected by the two different collection routes met acceptance criteria. Excellent correlation and agreement between capillary serum (collected by Tasso microsampling devices) and venous plasma (collected by traditional venipuncture) concentrations were demonstrated for abrocitinib, Ml, M2 and M4. The concentration comparison met pre-set criteria. Bland-Altman statistical correlation showed <-7.76% bias and r >0.9824 in all 3 assays. Additionally, exposure comparison shows similar concentration-time profiles between venous plasma and Tasso serum samples. Ratio (at 90% CI) of the PK parameters (AUClast and Cmax) for abrocitinib and its metabolites Ml, M2 and M4 being similar between the two sampling methods with abrocitinib meeting conventional BE acceptance range of 0.80 to 1.25. Thus, bridging between the two different collection routes was successfully established in healthy adults. In summary, we were able to bridge capillary serum concentration data against traditional venous plasma concentration data. We demonstrated that Tasso-SST® and/or Tasso+ can be successfully utilized to collect microsamples. Although widespread use of microsampling is yet to be seen, it is expected to increase with the progression of microsampling devices coupled with modern digitalization and artificial intelligence to enable real time and remote data collection.

Tasso serum microsampling device offers less invasive option for PK sampling by using much lower blood volume without venous puncture. It was noticed that the Tasso+ device that used a different lancet mechanism than Tasso-SST may cause excessive bleeding and prolonged wound healing time in some participants. The device use related Adverse Events (AEs) were reported back to manufacture. Tasso serum collection devices are FDA Class II Lancet 510(k)-cleared and available to customers in the United States. It has also obtained CE Marking recently and available to customers in the European market. Tasso-SST is no longer offered by the manufacture, even though we had zero AEs when using it. Advantages of Tasso device over other microsampling devices is that sampling site used is either upper arm or lower back which is less painful compared with finger pricks. Tasso is an integrated device: lancet, sampling (vacuum assisted bleeding) and sample storage are all integrated into one device, making it easy for patients/caregiver/medical staff to operate; thereby providing more consistent quality of samples. For implementation in future clinical studies, full validations in human serum will be established for all the analytes following regulatory guidelines prior to pediatric study samples analyses. To make microsampling the primary choice of sample collection, especially for pediatric population, more innovations in this field are needed. For example, to make widespread use of Tasso serum devices in neonates for blood collection vs. commonly used heel stick method, more data and experiments are desired which could be possible by close interaction between hospital neonate units, nurse practitioners, vendors and sponsors. Hemolysis is known for capillary sampling. Tasso's micro fluidics created slight vacuum to minimize hemolysis. Moreover, how can hemolysis in serum be evaluated? Plasma is preferred matrix for PK. However, current Tasso device needs three minutes or less for completion of blood collection to avoid clotting. This is very difficult for ped population. The slow blood drip into the microtubes (a few min) vs. quick blood turbulent flow (∼10 seconds) into the regular vacutainer has made the clotting a hurdle for the microsampling device manufacture to overcome. This is yet to evolve with further innovation in coming years. Lastly, to help bioanalysts, we would like to see more specific regulatory guidelines pertaining to microsampling to facilitate widespread use of these technologies in pharmaceutical drug development.

Overall, patient-centric microsampling can enhance recruitment, improve subject retention in clinical trials and generate more complete datasets that contribute to a better understanding of disease and drug effects. Small volume and less invasive blood collections are highly desired in pediatric populations. With most pediatric studies conducted within clinical sites, patient-centric liquid blood sampling platform makes the bridging easier without the need to measure blood-to-plasma ratio. As described in already published literature, microsampling is going to play an important role to minimize patient burden. The early investment in evaluating assay concordance can be paid off by later implementations. The regulatory guidance on conducting assay concordance evaluation and subsequent assay concordance monitoring in target population is still lacking specifics. Industry and regulators should come together to enable the broader adoption of the new technologies to bring benefits to patients.

Supplementary Material

Supplementary Figure S1 and Table S1

Acknowledgments

The authors thank Robert Horton for managing the plasma validation and Felicia Dunsmuir for conducting the plasma validation experiments at Syneos Health.

Supplemental material

Supplemental data for this article can be accessed at https://doi.org/10.1080/17576180.2024.2388939

Author contributions

Substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work. Drafting the work or revising it critically for important intellectual content. Final approval of the version to be published. Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Anyone unable to fulfill the criteria above may be acknowledged elsewhere in the manuscript, if appropriate, and with their agreement.

Financial disclosure

This clinical study was funded by Pfizer Inc, no funding was received for manuscript development and submission. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Competing interests disclosure

All Pfizer authors are employees of Pfizer and may hold stock/stock options. The authors have no other competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript apart from those disclosed.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The study was conducted in accordance with consensus ethical principles derived from international guidelines, including the Declaration of Helsinki, Council for International Organizations of Medical Sciences International Ethical Guidelines, applicable International Conference on Harmonisation Good Clinical Practice guidelines, and applicable laws and regulations. The final protocol and any amendments were reviewed and approved by the independent ethics committee or institutional review board for participating investigational center. The full name of the institutional review board which approved the study: Independent Ethics Committee or Institutional Review Board Address(es).
==== Refs
References

Papers of special note have been highlighted as: • of interest; •• of considerable interest

1. Lei BUW, Prow TW. A review of microsampling techniques and their social impact. Biomed Microdev. 2019;21 (4 ):81. doi:10.1007/s10544-019-0412-y
2. Maass KF, Barfield MD, Ito M, et al. Leveraging patient-centric sampling for clinical drug development and decentralized clinical trials: promise to reality. Clin Transl Sci. 2022;15 (12 ):2785–2795. doi:10.1111/cts.13411 36129129
• Explain the value of PCS to various stakeholders in clinical trials focusing on the most vulnerable patient population.

3. Chen Z, Goudarzi CC, Sikorski TW, et al. Enhancing drug development and clinical studies with patient-centric sampling using microsampling techniques: opportunities, challenges, and insights into liquid chromatography-mass spectrometry strategies. J Mass Spectrom. 2024;59 (5 ):e5023. doi:10.1002/jms.5023 38624283
4. Lee KC, Wan KX, Barricklow J, et al. Using Mitra sampling to support first-in-human pharmacokinetic evaluations for PF-07059013. Bioanalysis. 2023;15 (17 ):1083–1094. doi:10.4155/bio-2023-0066 37584365
5. Berm EJJ, Odigie B, Bijlsma MJ, et al. A clinical validation study for application of DBS in therapeutic drug monitoring of antidepressants. Bioanalysis. 2016;8 (5 ):413–424. doi:10.4155/bio.15.255 26893105
6. Wan KX, Potts D, Gonzalez P, et al. Bioanalytical method validation and sample analysis for nirmatrelvir in dried blood collected using the Tasso-M20 device. Bioanalysis. 2022;14 (20 ):1305–1315. doi:10.4155/bio-2022-0167 36541270
7. Narayanan S, Yuile A, Venkatesh B, et al. Therapeutic drug monitoring of osimertinib in EGFR mutant non-small cell lung cancer by dried blood spot and plasma collection: a pilot study. Br J Clin Pharmacol. 2024;90 (1 ):344–349.37815301
8. Wan K, Kavetska O, Damle B, et al. Patient centric microsampling to support paxlovid clinical development: bridging and implementation. Clin Pharmacol Ther. 2024;115 (1 ):42–51. doi:10.1002/cpt.3025 37597239
9. Wickremsinhe ER, Decker RL, Lee LB, et al. Microsampling in pediatric studies: pharmacokinetic sampling for baricitinib (Olumiant) in global pediatric studies. Bioanalysis. 2023;15 (11 ):621–636. doi:10.4155/bio-2023-0044 37293791
• These publications explain the value of PCS to various stakeholders in clinical trials focusing on the most vulnerable patient population.

10. Spooner N, Anderson M, Wickremsinhe ER. Patient-centric sampling special focus issue. Bioanalysis. 2020;12 (13 ):867–868. doi:10.4155/bio-2020-0176 32772899
11. Wickremsinhe ER, Ji QC, Gleason CR, et al. Land O'Lakes Workshop on Microsampling: Enabling Broader Adoption. AAPS J. 2020;22 (6 ):135. doi:10.1208/s12248-020-00524-2 33098040
•• The only guideline at the moment that provides detail on criteria to use.

12. Parker SL, Dorofaeff T, Lipman J, et al. Is there a role for microsampling in antibiotic pharmacokinetic studies? Expert Opin Drug Metab Toxicol. 2016;12 (6 ):601–614. doi:10.1080/17425255.2016.1178238 27087416
13. Barco S, Castagnola E, Moscatelli A, et al. Volumetric adsorptive microsampling-liquid chromatography tandem mass spectrometry assay for the simultaneous quantification of four antibiotics in human blood: method development, validation and comparison with dried blood spot. J Pharm Biomed Anal. 2017;145 :704–710. doi:10.1016/j.jpba.2017.07.033 28806566
14. Tripathy S, Wentzel D, Wan X, et al. Validation of enantioseparation and quantitation of an active metabolite of abrocitinib in human plasma. Bioanalysis. 2021;13 (19 ):1477–1486. doi:10.4155/bio-2021-0128 34601943
15. Wang EQ, Le V, O'Gorman M, et al. Effects of hepatic impairment on the pharmacokinetics of abrocitinib and its metabolites. J Clin Pharmacol. 2021;61 (10 ):1311–1323. doi:10.1002/jcph.1858 33749838
