importance of partnerships in the biopharmaceutical industry · gives regulators the confidence...
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© 2015 Waters Corporation 1
Importance of Partnerships in the
Biopharmaceutical Industry
Ken Fountain
Biopharmaceutical Business
November 17, 2015
Seoul
© 2015 Waters Corporation 2
Requires
– Physical/chemical
characterization
– Process/Quality control
– Comparability
Challenges
– Scientific
o Complexity
o Expertise
o Process understanding
– Business
o Cost
o Time to market
Impact of Biopharmaceuticals
http://www.dailymail.co.uk/health/article-2567455/Cancer-patients-lethal-70-tumours-disappear-just-two-WEEKS-thanks-pioneering-treatment.html
© 2015 Waters Corporation 3
Importance of Partnerships
Industry Trends
Regulatory Technology
© 2015 Waters Corporation 4
Importance of Partnerships
Industry-Industry
Industry-Regulatory
Industry-Technology
Technology-Regulatory
Industry Trends
Regulatory Technology
© 2015 Waters Corporation 5
Industry Trends
Biotherapeutics the leading driver of growth in Pharma industry
– 50% of top 100 drugs are now bio-molecules - up from 28% in 2008
Global regulatory harmonization/standardization
Increasing price pressure on drugs
– Biosimilars (first in US in 2015)
Increased outsourcing – use of CRO’s and CMO’s
Expanding production in emerging markets (India, Asia, Latin America)
mAbs (70% of late stage development pipeline)
MS in late development and QC
© 2015 Waters Corporation 6
Future of MS in Biopharma Development and QC
Improve productivity and product certainty in the biotherapeutic
production through the use of routine mass detection.
– Reduce number of assays
– Direct monitoring of product quality attributes (vs. indirect methods)
– Potential for real-time control of process (true QbD approach)
Barriers for MS
– Cost, complexity
o Prevents scalability and redundancy
– Expertise required
– Compliance
– Spec setting
Industry Trends
© 2015 Waters Corporation 7
Technology
Glycans
Antibody-Drug Conjugates (ADCs)
Hydrogen Deuterium Exchange (HDX)
Host cell proteins (HCP)
Bioanalysis of peptides and proteins
© 2015 Waters Corporation 8
US FDA Emphasis on New Technologies
http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm386366.pdf
Over the life cycle of a product, new information (e.g., a better understanding of product CQAs or awareness of a new impurity) may warrant the development and validation of a new or alternative analytical method. “New technologies may allow for greater understanding and/or confidence when ensuring product quality. Applicants should periodically evaluate the appropriateness of a product’s analytical methods and consider new or alternative methods.”
VIII. LIFE CYCLE MANAGEMENT OF ANALYTICAL PROCEDURES
© 2015 Waters Corporation 9
Life Cycle Management of Analytical Procedures with New Technologies
New technologies allows for greater understanding when ensuring product quality.
– Reduces exposure to unnecessary compliance risk
– Reduces validation costs
– Patients get quicker and safer access to drugs
Gives regulators the confidence that industry can be responsible for greater self-management of improvements and changes
– Companies with good quality management systems
– Well controlled processes and products
– Appropriate technologies are being used for product safety
Increases ROI by decreasing equipment down time, overheads, solvent usage etc.
Proper management of the analytical equipment lifecycle is
required to meet business and regulatory requirements
© 2015 Waters Corporation 10
Regulatory View on Biosimilars: FDA Totality of Evidence
“Characterization of Filgrastim using Intact and Top-down MS”, Mass Spec 2015 conference, Johann Holzmann, Sandoz Biopharmaceuticals
© 2015 Waters Corporation 11
Definition of Similarity
Not similar- “biodifferent”
Similar- additional analytical data and other studies
needed (i.e., glycosylation differences)
Highly similar- meets standard for analytical
similarity; targeted animal/clinical studies to address
residual uncertainty
Highly similar with fingerprint-like similarity- meets
standards for analytical similarity based on multi-
parameter approaches that are extremely sensitive
in identifying analytical differences
“The outcome of the comparative analytical characterization should inform the next steps in the demonstration of biosimilarity.”
Regulatory
© 2015 Waters Corporation 12
Structural Analysis of a Biosimilar and the Reference Product – Scientific Considerations
Primary structures, such as amino acid sequence
Higher order structures, including secondary,
tertiary, and quaternary structure (including
aggregation)
Enzymatic post-translational modifications, such
as glycosylation and phosphorylation
Other potential variants, such as protein
deamidation and oxidation
Intentional chemical modifications, such as
PEGylation sites and characteristics
Regulatory
© 2015 Waters Corporation 13
Antibody Drug Conjugates (ADCs): FDA Suggestions
Can do today
Conjugated Antibody (DAR)
Total Antibody (Ab with and without drug)
In progress
Change in DAR (Biotransformation)
Antibody-Conjugated Drug (Total small molecule drug conjugated to the Ab)
Unconjugated Drug (Small molecule drug not conjugated to antibody, free drug)
Total Drug (Total unconjugated and conjugate drug; above 2 added together)
Regulatory
© 2015 Waters Corporation 14
Customer Success is Our Mission
Purposeful Innovation
Pioneering valuable and sustainable breakthroughs
Keen Understanding
Unparalleled insight into customer
laboratory operations
True and Enduring Partnership A collaborative and symbiotic working style that enables
positive advancements to science and humanity
Resulting in
Meaningful Impact
Fundamental, systemic contributions to our customers’
success around the world
Facilitate the interaction between the biopharma industry, regulators, and technology providers
© 2015 Waters Corporation 15
2005
2006
2007
2008
2009
2010
2011
2012
Purposeful Innovation for Biopharmaceutical Characterization
2014
Amino Acid Analysis
Ion mobility MS (SYNAPT) BioPharmaLynx 1.0
Peptide separation technology
Protein separation technology Oligonucleotide separation technology
BioPharmaLynx 1.1
1st UPLC glycan column BioPharmaLynx 1.2
UNIFI Biopharmaceutical Solution UPLC Bio (H-Class)
1st UPLC SEC columns IEX columns
BioPharmaLynx 1.3
2013
2015
1st commercial HDX solution
HDX (2nd generation) DynamX 3.0
Rapid glycan tagging (GlycoWorks RFMS) Glycoprotein separation technology
HPLC SEC columns
DynamX 1.0 (HDX)
DynamX 2.0 (HDX)
Glycan database (2-AB)
UPLC nano (M-Class)
Peptide separation technology (CSH)
2016?
© 2015 Waters Corporation 16
Biopharmaceutical Platform Solutions and Technologies
Routine Monitoring
1. Raw materials
2. Critical quality attributes (CQAs)
Routine Characterization
1. Primary structure
2. PTMs
3. Aggregates & Heterogeneity
4. Intentional modifications (PEG)
Advanced Characterization
1. Higher order structure
2. Impurities (HCPs)
3.0
21 CFR Part 11 Compliant
© 2015 Waters Corporation 17
Monitoring Variants in Herceptin® (Breast Cancer Drug)
T21-Oxidized T21
5.5%
94.5%
QDa
UV
© 2015 Waters Corporation 18
Rapid Screening: Process Development E
U
0
20
40
FLR
Inte
nsity
0
1x10 6
2x10 6
Minutes 1 2 3 4 5 6
QDa
Trastuzumab N-Glycan Analysis RapiFluor-MS labeled glycans- 10 minute method In
tensity
0
50000
Inte
nsity
0
200000
Inte
nsity
0
1x10 6
2x10 6
Inte
nsity
0
50000
100000
Inte
nsity
0
1x10 6
Inte
nsity
0
200000
400000
Inte
nsity
0
20000
Minutes
1 2 3 4 5 6
A2G(4)1 895.9 m/z
F(6)A2 887.9 m/z
F(6)A2G(4)1 968.9 m/z
F(6)A2G(4)2 1049.9 m/z
A2 814.8 m/z
F(6)A2G(4)2S1 1195.5 m/z
M5 774.1 m/z
© 2015 Waters Corporation 19
Waters Biopharmaceutical Portfolio- 2015
© 2015 Waters Corporation 20
Waters Biopharmaceutical Portfolio- 2016
© 2015 Waters Corporation 22
Global Biopharm Customers
© 2015 Waters Corporation 23
협력 을 통해 성공
Waters is a key partner and innovator for the biopharmaceutical industry
– Customer feedback drives our innovations in analytical science
10 year record of purposeful innovation in biopharm analytics
Platform technologies for routine and advanced analysis
– Methods, reports, chemistries, analytical standards…
Ability to take high resolution MS and routine mass detection into regulated biopharma development and QC
Challenges
– Scientific
o Complexity
o Expertise
o Process understanding
– Business
o Cost
o Time to market