On this episode of Molecular Moments, Dr. Jim McNally chats with DMPK Senior Director Dr. David Johnson, Ph.D., from BioAgilytix
Premier Preclinical and Clinical Support for PK/PD Assay Development and Validation
BioAgilytix understands that when it comes to PK assays, PD assessments, and DMPK assays, it is of the highest priority that the applied bioanalytical method is well characterized, fully validated, and documented in order to yield reliable results. We offer high-quality PK/PD assay procedures and results strictly in compliance with GLP / GMP regulations and in accordance with international regulatory standards (FDA, EMEA, ICH).
Pharmacokinetics (PK) describes what the human body does to a given pharmaceutical, from the time of administration to absorption, distribution, metabolism, and excretion from the body. By assessing PK of a biological drug in different samples, including serum, plasma, urine, and saliva, we can understand a drug’s interaction with the body, as well as the intensity and duration of its efficacy.
Pharmacodynamics (PD) studies the biochemical, physiologic, and molecular effects of drugs on the body and involves receptor binding, postreceptor effects, and chemical interactions. Together PK/PD data explain the dose-response relationship of a drug and are integral in designing the dose, route, and schedule of administration to maximize effectiveness while reducing adverse effects.
Understanding the pharmacokinetic and pharmacodynamic behavior of a given therapeutic drug is an essential element of understanding its effectiveness and safety, as well as identifying the proper dosage and distribution. PK assay bioanalytical testing methods are used to determine concentration time profiles of the drug and metabolites in biological sample fluids, providing information necessary for PK analysis. PK assays are a vital component of the drug development process, and the data derived is used to help select dosage for preclinical and clinical studies. The Federal Drug Administration (FDA) has also issued extensive industry guidance on measuring Population Pharmacokinetics (PK).
See recommendations from the AAPS Biosimilars Action Program Committee (APC) for the development and validation of LBAs to support PK assessments for biosimilar drug development.
Our scientists are experienced in supporting PK assessments in a variety of species including rodents, humans, and non-human primates, and in multiple matrices such as serum, plasma, urine, and saliva. We are well-versed in the factors that could influence the validity of the data generated by these assays, and take those complexities into account during method validation to ensure optimal results. Our team has a clear understanding of the ability of the assay to detect the drug in the sample matrix.
In addition to their use for the detection of monoclonal antibodies using anti-idiotypic antibodies, BioAgilytix establishes and validates PK assays for therapeutic proteins with endogenous counterparts. PK assays are also required for comparative analysis of originator and biosimilar products, which our team is well-versed in performing.
We conduct our high-quality PK assay procedures and results strictly in compliance with GLP / GMP regulations and in accordance with international regulatory standards (FDA, EMEA, ICH).
For pharmacodynamic studies, our team brings extensive experience in developing receptor occupancy assays in soluble proteins, such as Bruton’s tyrosine kinase (Btk). Btk regulates the proliferation and survival of cancer cells in various B-cell lymphoid malignancies, and we have successfully developed, optimized, and validated various ELISA-based, GLP-compliant assays to determine the Btk occupancy in PBMC lysates.
In fact, our Boston lab is capable of acting as a central laboratory for Phase I/II studies, from sample collection kit preparation to whole blood PBMC isolation and processing and lysate sample preparation to receptor occupancy testing.
There are several analytical technologies that can be used for PK analysis and to assess PD profiles. BioAgilytix will help you select the best-fit platform for your project, based on both sensitivity and regulatory requirements. We have extensive experience developing and validating assays to evaluate pharmacokinetic and pharmacodynamic behavior throughout the phases of the drug development process using the platforms listed below.
Download the white paper “Serum pharmacokinetics and cerebrospinal fluid concentration analysis of the new IgG4 monoclonal antibody GNbAC1 to treat multiple sclerosis: A Phase 1 study”, contributed to by our Global Chief Scientific Officer, Dr. Arno Kromminga.
BioAgilytix combines a diverse range of platform offerings with a team of tenured scientists who are experts in the complexities of PK assays. The result is scientific excellence, delivered on a global scale to customers at any phase of the drug development process. We have proven our expert ability to interpret PK assay data to gain an accurate understanding of the absorption, distribution, metabolism, and excretion characteristics of the product. We also offer these services under GLP, GMP, and GCP to meet your regulatory requirements.
High performance liquid chromatography (HPLC) is one of our additional technologies that can be leveraged to support your needs. Let our specialized scientists help you identify the optimal method and platform for your PK/PD assay needs today.
Calibration Curves in Quantitative Ligand Binding Assays: Recommendations and Best Practices for Preparation, Design, and Editing of Calibration Curves.
Mitra Azadeh, Boris Gorovits, John Kamerud, Stephen MacMannis, Afshin Safavi, Jeffrey Sailstad, Perceval Sondag. AAPS J 2018 Jan; 20:22- Open Access White Paper.
Serum pharmacokinetics and cerebrospinal fluid concentration analysis of the new IgG4 monoclonal antibody GNbAC1 to treat multiple sclerosis: A Phase 1 study.
Curtin F, Vidal V, Bernard C, Kromminga A, Lang AB, Porchet H. MAbs. 2016 Jul;8(5):854-60.
eBook: Bioanalysis for Biosimilars Development
D. Gouty, 2015. Bioanalysis Zone.
Preclinical and early clinical development of GNbAC1, a humanized IgG4 monoclonal antibody targeting endogenous retroviral MSRV-Env protein.
Curtin F, Perron H, Kromminga A, Porchet H, Lang AB. MAbs. 2015;7(1):265-75.
Recommendations on incurred sample stability (ISS) by GCC.
Lowes S, Gouty D, et al. Bioanalysis. 2014 Sep;6(18):2385-90. doi: 10.4155/bio.14.155.
Systematic verification of bioanalytical similarity between a biosimilar and a reference biotherapeutic: committee recommendations for the development and validation of a single ligand-binding assay to support pharmacokinetic assessments.
Marini JC, Anderson M, Cai XY, Chappell J, Coffey T, Gouty D, Kasinath A, Koppenburg V, Oldfield P, Rebarchak S, Bowsher RR. AAPS J. 2014 Nov; 16(6):1149-58. doi: 10.1208/s12248-014-9669-5. Epub 2014 Oct 3.