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Application of blood microsampling in cynomolgus monkey and demonstration of equivalent monoclonal antibody PK parameters compared to conventional sampling

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Abstract

Purpose

The purpose of this study was to evaluate the suitability of whole blood microsampling procedures in non-human primate (NHP) to support toxicokinetic assessments of biotherapeutics in non-human primates.

Method

A one-month single dose intravenous pharmacokinetic (PK) study was performed in male cynomolgus monkeys with a human IgG1 control monoclonal antibody (mAb) as a surrogate monoclonal antibody biotherapeutic. In this study, both serum samples (conventional sample collection) and microsampling samples were collected. Microsampling samples were collected from two sites on cynomolgus monkey, with each site using two different devices for the whole blood collection. The drug concentrations from all sample types were determined using a quantitative ligand binding assay (LBA). The PK parameters obtained from microsampling samples and serum samples were examined using a standard PK analysis method. The comparability of key PK parameters from both sample types were analyzed statistically.

Results

Similar profiles of drug concentrations versus timepoints from all sampling procedures were observed. The correlations of PK concentration data obtained from serum and microsampling samples were ≥ 0.97 using Brand Alman Plot analysis. The key PK parameters obtained from microsampling samples were comparable to those obtained from serum samples (the % differences of mean PK parameters obtained from both sample types were within ±25%).

Conclusion

This study confirmed that PK parameters obtained from samples using microsampling were comparable to that of serum samples in cynomolgus monkeys. Therefore, the microsampling procedure described can be used as a substitute for conventional sampling procedure to support PK/TK studies of biotherapeutics in non-clinical product developments.

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Abbreviations

AUC:

Area Under the Concentration-Time Curve

CL:

Clearance

Cmax:

Maximum Drug Concentration

CMS:

Capillary Microsampling

DBS:

Dried Blood Spot

DQC:

Dilution Quality Control

GLP:

Good Laboratory Practices

HQC:

High Quality Control

IND:

Investigational New Drug

LBA:

Ligand Binding Assay

LC-MS:

Liquid Chromatography-Mass Spectrometry

LIMS:

Laboratory Information Management System

LLOQ:

Lower Limit of Quantitation

LMS:

Liquid Microsampling

LQC:

Low Quality Control

LTS:

Long-Term Stability

mAb:

Monoclonal Antibody

MQC:

Middle Level Quality Control

MRD:

Minimum Required Dilution

MSD:

Mesoscale Discovery

PD:

Pharmacodynamic

PK:

Pharmacokinetic

POCT:

Point of Care Test

QC:

Quality Control

RE:

Relative Error

RPM:

Revolutions Per Minute

RT:

Room Temperature

T 1/2:

Half-life

TK:

Toxicokinetic

ULOQ:

Upper Limit of Quantitation

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Authors and Affiliations

  1. BioMedicine Design (BMD), Pfizer Inc., 1 Burtt Road, Andover, Massachusetts, 01810, USA

    Ying Wang, Alison Joyce & Lisa Dyleski

  2. Drug Safety Research and Development (DSRD), Pfizer, Inc., 445 Eastern Point Road, Groton, Connecticut, 06340, USA

    Sarah J. Crowell, Jennifer Cargill, Sarah Murphy & Meghan Gomes

  3. BioMedicine Design (BMD), Pfizer Inc., 610 Main St, Cambridge, Massachusetts, 02139, USA

    Dean Messing

  4. Early Clinical Development (ECD), Pfizer, Inc., 610 Main St, Cambridge, Massachusetts, 02139, USA

    Zhiping You

  5. Sana Biotechnology, 100 Technology Square, Cambridge, Massachusetts, 02139, USA

    Boris Gorovits

Authors
  1. Ying Wang
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  2. Sarah J. Crowell
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  3. Alison Joyce
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  4. Lisa Dyleski
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  5. Dean Messing
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  6. Jennifer Cargill
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  7. Zhiping You
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  8. Sarah Murphy
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  9. Meghan Gomes
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  10. Boris Gorovits
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Corresponding author

Correspondence to Ying Wang.

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Co-author worked on manuscript while employed with Pfizer, Inc.

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Wang, Y., Crowell, S.J., Joyce, A. et al. Application of blood microsampling in cynomolgus monkey and demonstration of equivalent monoclonal antibody PK parameters compared to conventional sampling. Pharm Res 38, 819–830 (2021). https://doi.org/10.1007/s11095-021-03044-6

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  • DOI: https://doi.org/10.1007/s11095-021-03044-6

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