Utah Life Science Summit

State of the Industry - Growth and Success

through Outsourcing/Partnering

Regulated Bioanalysis
for the Pharmaceutical
Industry
Scott A. Reuschel, M.S.F.S
Tandem Labs Salt Lake City, UT
A Labcorp Company

Who are we?

Who or what is Tandem Labs and what do

we do?

Company Overview

Our 33rd year of operation

1981 Northwest Toxicology established in SLC, UT (clinical toxicology)
1985 Certified drugs-of-abuse testing lab (NIDA, DoD, SAMSHA) GC/MS
1994 Established bioanalytical division, SLC, UT GLP bioanalytical, GC/MS,
LC/MS
1998 Established 2nd site in NJ Discovery PK/GLP bioanalytical, LC/MS
2004 Divested drug testing division Renamed company to Tandem Labs
2008 Acquired by Laboratory Corporation of America Holdings
2009 Established 3rd site in San Diego, CA GLP Immunoanalytical
2010 Acquired BA division of Enthalpy Analytical - RTP, NC (4 th Tandem site)
GLP
bioanalytical, LC/MS
200+ scientific/support staff; ~50 mass spectrometers across all sites
Contract Research Organization (CRO) Regulated Bioanalysis

Tandem Labs Locations

Regulated Bioanalysis
What regulatory agencies have
authority over the work performed
at Tandem Labs?
Not regulated by Clinical Laboratory
Improvement Amendments(CLIA)

Regulated Bioanalysis
What regulatory agencies have
authority over the work performed
at Tandem Labs?
Not regulated by Clinical Laboratory
Improvement Amendments(CLIA)
Are regulated by the Food and Drug
Administration (FDA)

Regulated Bioanalysis
What regulatory agencies have authority
over the work performed at Tandem
Labs?
Not regulated by Clinical Laboratory Improvement
Amendments(CLIA)
Are regulated by the Food and Drug Administration
(FDA)
Are subject to the Code of Federal Regulations
(CFR)
21 CFR Part 58 Good Laboratory Practice for NonClinical Laboratory Studies
21 CFR Part 11 Electronic Records, Electronic
Signatures

Regulated Bioanalysis
What regulatory agencies have
authority over the work performed at
Tandem Labs?
Not regulated by Clinical Laboratory Improvement
Amendments(CLIA)
Are regulated by the Food and Drug Administration
(FDA)
Are subject to the Code of Federal Regulations (CFR)
21 CFR Part 58 Good Laboratory Practice for Non-Clinical
Laboratory Studies
21 CFR Part 11 Electronic Records, Electronic Signatures

Also subject to:

ICH (International Conference on Harmonization)
- Guideline for Good Clinical Practice (GCP)
informed consent, patient confidentiality, blinding

Regulated Bioanalysis
What regulatory agencies have
authority over the work performed
at Tandem Labs?
Are subject to additional regulations and
guidelines from various international
regulatory authorities, including:

Regulated Bioanalysis
What regulatory agencies have
authority over the work performed
at Tandem Labs?
Are subject to additional regulations and
guidelines from various international regulatory
authorities, including:
US FDA Guidance for Industry:
Bioanalytical Method Validation

Regulated Bioanalysis
What regulatory agencies have
authority over the work performed
at Tandem Labs?
Are subject to additional regulations and
guidelines from various international regulatory
authorities, including:
US FDA Guidance for Industry: Bioanalytical
Method Validation
European Medicines Agency (EMA):
Guideline on Bioanalytical Method Validation

Regulated Bioanalysis
What regulatory agencies have
authority over the work performed
at Tandem Labs?
Are subject to additional regulations and
guidelines from various international regulatory
authorities, including:
US FDA Guidance for Industry: Bioanalytical
Method Validation
European Medicines Agency (EMA): Guideline on
Bioanalytical Method Validation
Brazilian Health Surveillance Agency
(ANVISA): Bioanalytical Guidance RDC
27/2012

Regulated Bioanalysis
What regulatory agencies have
authority over the work performed at
Tandem Labs?
Are subject to additional regulations and guidelines
from various international regulatory authorities,
including:
US FDA Guidance for Industry: Bioanalytical Method
Validation
European Medicines Agency (EMA): Guideline on
Bioanalytical Method Validation
Brazilian Health Surveillance Agency (ANVISA):
Bioanalytical Guidance RDC 27/2012
Japanese Ministry of Health, Labour and Welfare
(MHLW): Draft Guideline on Bioanalytical Method
Validation in Pharmaceutical Development

Regulated Bioanalysis

What is the purpose of all this regulated

bioanalysis?

Pharmacodynamics (PD) and

Pharmacokinetics (PK)
Tandem Labs helps pharmaceutical companies obtain the
necessary information to make assessments regarding PD/PK
of new drugs that are being developed.
Pharmacodynamics (PD) is the study of the biochemical and
physiological effects of drugs on the body (i.e. what the drug
does to a body).
Pharmacokinetics (PK) describes the drug
concentration/time course in body fluids resulting from
administration of a certain drug dose (i.e. what the body does
to a drug).
Tandem Labs use mass spectrometry to provide both
qualitative and quantitative information to our pharmaceutical
partners during all phases of the drug development process.

Drug Discovery and

Development Timeline

Drug Discovery and Development

Timeline
1 - 5+ yrs

2-3 yrs

Discovery Preclinical

1 yr

Phase I

IND to FDA

2 yrs

Phase II

3 yrs

1-2 yrs

Phase III

Review

NDA to FDA

Phase IV

Discovery
Drug Development
Qualitative Analysis (by Mass Spectrometry)
In Vitro
High-throughput screening (lead generation, identification,
and optimization)
Metabolite Identification (cytochrome P450 enzymes)

Quantitative Analysis (by Mass Spectrometry)

In Vitro
Solubility, plasma protein binding, permeability, plasma
stability, metabolic stability
In Vivo (preliminary animal studies)
Determine basic PK parameters (e.g. half-life, oral
bioavailability , clearance and tissue distribution)
Qualified Assays / Fit for Purpose; less stringent
acceptance criteria, quick and dirty

Preclinical
Drug Development
Quantitative Analysis (by Mass Spectrometry)

Exploratory Toxicology (non-GLP)

Dose range finding studies
Different species and methods of administration
Multiple dosing regimens

Definitive Toxicology (GLP) validated assays

General toxicology studies
Different species and methods of administration
Immunogenicity studies with non-human primates
(NHPs)
Dose formulation analysis
Safety is the key focus

Clinical Drug Development

Clinical (Phases I-IV)

Quantitative Analysis (by Mass
Spectrometry)
Validated Assays not GLP; however, conducted
under the principles of GLP
First in Human
Single Ascending Dose (SAD)
Multiple Ascending Dose (MAD)
Food Effects (fed vs. fasted)
Special Populations
Elderly, renal impaired, hepatic impaired
Drug-Drug Interaction (DDI)
Bioequivalence (BE)

Quantitative Analysis
by LC/MS
Method Development
Extraction conditions, chromatography conditions, MS parameters
Very challenging; dictated by the chemistry of the analytes, maximum
sensitivity often required, instability, non-specific binding, tight time
pressures.

Method Validation
Highly regulated; A/P, stability, robustness, selectivity, matrix effects,
etc.
Constantly evolving requirements; additional tests

Sample Analysis
Tight time pressures, sample dilution, sample discrepancies with
clinics, ISR

PK/PD Parameters
ADME (Absorption, Distribution, Metabolism,
Excretion)
Dose
Concentration
Area under the curve (AUC)
Accumulation
Bioavailability
Clearance (CL)
Half life (t )
Cmax

PK/PD Parameters

PK/PD Parameters

Mass Spectrometry
in Drug Development
Why is Mass Spectrometry such a good tool for these
applications?
Selective
Allows the discrimination of a target analyte to the exclusion of
other interferences.

Sensitive
Can routinely detect analytes at ng/mL, pg/mL and sub pg/mL levels.

Compatible with other separation techniques

hyphenated methods
GC-MS, LC-MS, UPLC-MS, CE-MS, etc.

Robust / High throughput

Versatile

Mass Spectrometry
in Drug Development
Why is Mass Spectrometry such a good tool for these
applications?
Selectivity
Biological samples are first extracted (PPE, SPE, LLE, SLE)
Chromatographic Separation (GC, HPLC, UPLC, Microflow
LC)
Multiple MS Techniques
Full Scan
SIM
MS/MS (SRM, Product Ion, Precursor Ion, Neutral Loss)
TOF/MS
HRAM

Mass Spectrometry
in Drug Development
MS/MS (tandem MS, triple-quadrupole MS) and
Selected Reaction Monitoring (SRM) is by far the most
commonly used technique for quantitative bioanalysis
for PK/PD testing.

Mass Spectrometry
in Drug Development

LC ionization techniques have also

revolutionized quantitative MS bioanalysis for
PK/PD testing.
Ionization is required for mass spectrometry (charged
species; m/z)
GC/MS applications were limited to volatile, thermally
stable compounds for ionization.
Atmospheric ionization techniques (ESI, APCI) removed
these limitations, allowing for LC/MS applications to
expand to a wider variety of compounds.

Mass Spectrometry
in Drug Development

Mass Spectrometry
in Drug Development

Types of compounds analyzed with LC/MS

techniques:
Small Molecules (MW < 800 amu)
Traditional drugs, NCEs
Large Molecules (MW > 800 amu; up to 10-40,000
Da)
Biologics
Peptides
Oligonuclieotides
SiRNA
Lipids
Biomarkers
Proteins

Mass Spectrometry
in Drug Development

Mass Spectrometry
in Drug Development

Acknowledgements

Tandem Labs - Salt Lake City, UT

Laixin Wang, PhD

Min Meng, PhD
Troy Voelker, PhD
Juan Rogness, MS

Life Science Cluster, Utah Governor's

Office of
Economic Development

Kevin Jessing

Q&A