XBL * A subsidiary of Lab Testing Division, WuXi AppTec Inc. WuXi AppTec XBL * A subsidiary of Lab Testing Division, WuXi AppTec Inc. WuXi AppTec
Friday, December 15, 2017

DMPK and TOX "IND Enabling" Study Services

During a new drug's early preclinical development, the Sponsor's primary goal is to determine if the product is reasonably safe for initial use in humans, and if the compound exhibits pharmacological activity that justifies commercial development. In preparation for submission of an Investigational New Drug (IND) Application (21CFR312), a series of non-clinical DMPK and Toxicology "IND Enabling" studies are conducted that become an integral part of the Investigator's brochure and IND application.

DMPK and TOX IND Enabling Packages:

DMPK Studies:
Prior to or in conjunction with Toxicology studies, several in vitro and in vivo drug metabolism and pharmacokinetic (DMPK) studies are conducted to characterize the compound's ADME (absorption, distribution, metabolism and excretion) properties.

DMPK Studies May Include:

  • In vitro studies
    • Chemical and metabolic stability
    • Metabolic profiling and metabolite identification
    • CYP inhibition, induction and phenotyping
    • Transporter substrate and inhibition
    • Plasma protein binding
    • Cross species comparisons
  • In vivo PK studies (rodent and large animal)
    • Bioavailability - absolute and relative for formulation selection
    • Selection of salt form
    • Dose linearity
    • Multi-dose administration
    • Metabolic profiling and metabolite identification

WuXi/XBL conducts these DMPK studies in-house its facilities located in New Jersey and China.

Toxicology Studies:
IND enabling Toxicology studies conducted to GLP regulations include general tox, genetic tox and safety pharmacology.

GLP TOX Studies May Include:

  • In vitro TOX studies(Suzhou, China):
    • Bacterial reverse mutation assay (AMES)
    • Mammalian cell chromosome aberration assay
    • Effects of hERG current in stably transfected HEK-293 cells
  • In vivo TOX studies (rodent and large animal)
    • Acute single and 5 to 7-day dose range finding (non-GLP)
    • 28-day chronic repeat dose
    • Safety pharmacology – Cardiovascular, CNS (Irwin), Respiratory
    • Mammalian erythrocyte micronucleus assay (rodent)

WuXi/XBL works with its Suzhou Tox facility or your preferred partner in the US to provide and manage a comprehensive toxicology package. WuXi/XBL supports these studies with dose formulation and plasma concentration assays and toxicokinetic analysis.

Bioanalytical Support Services
WuXi/XBL provides a full array of bioanalytical support (GLP and non-GLP) for the DMPK and TOX studies listed above, using the latest and most sophisticated LC-MS/MS instrumentation.

Bioanalytical Support May Include:

  • Non-GLP
    • Metabolite profiling and ID
    • Qualified LC-MS/MS method for drug/metabolite concentration assay in plasma or other matrices
  • GLP
    • Validated LC-MS/MS method for drug/metabolite concentration assay in plasma or other matrices
    • Validated HPLC/UV method for dose formulation concentration assay
    • Certificate of Analysis for reference compounds
    • Toxicokinetic Evaluation

Effective Project Management and Consulting Services:
WuXi/XBL has established a network of highly knowledgeable consultants who, along with WuXi/XBL project managers, enable us to provide comprehensive support for your IND Enabling package.

Support Services May Include:

  • Toxicologist review
  • Clinical protocol design
  • IND application preparation and submission

Allow WuXi/XBL to integrate a cost effective and time efficient package of IND Enabling studies and services.

Benefits Include:

  • Single point of contact for effective project management and timeline control
  • A cost effective solution due to lower overhead and efficient program execution
  • US based toxicology studies and consultants

WuXi/XBL stands ready to assist with individual projects, or coordinate complex multi-disciplinary IND Enabling DMPK and TOX packages. Let WuXi/XBL become an extension of your drug development program.

 

 

 

“XBL will work with you to assess your drug development needs and provide a custom fit solution.”