Stability Testing for
Biologics
CARING FOR YOUR BIOLOGICS DEVELOPMENT
Generating a stable environment for biopharmaceutical drug products is a critical step in the drug development process for ensuring a long product shelf life. Development of the optimal protein environment to
maintain product integrity is initiated early on in the development process through pre/formulation screening and subsequently monitored through long term stability studies to ensure product shelf life. SGS provides full analytical support through all phases of drug development.
oVerVieW of bioPHarMaceUtical DrUg DeVeloPMent actiVitieS
PRODUCT SELECTION,
CELL LINE SELECTION
PROCESS DEVELOPMENT,
PROCESS SCALE-UP
Pre-clinical
PILOT SCALE
• Quality specification & stability assays
• Pilot stability studies
• Lead candidate formulation screening
GMP BATCHES
• Stability studies
• Extractables & leachables
GMP BATCHES
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DS & DP stability studies (3 batches)
Product specific method validations
Forced degradation studies
Shipment support studies
Batch release/QC
Biosafety testing
PPQ SERIES (PV)
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Commercial reference standard stability
Specification for commercial product determined
DS & DP stability studies
In-use Studies
Extractables & leachables
inD / iMPD
i
ii
clinical
PHaSe
bla / Maa
iii
coMMercial
DrUg ProDUct
• Method development with forced degradation
• Preformulation screening
• Extractables testing
MARKETED DRUG
PRODUCT
• DS & DP stability studies
• Commercial reference standard stability
• Extractables & leachables
INTEGRATED SERVICES FROM R&D TO PRODUCTION
A good understanding of your product’s
characteristics and degradation profile is
an essential step in designing the right
pre/formulation study approach in order
to utilize the optimal formulation components to reduce expected degradation
events and a safe stability. This is why
SGS offers integrated services from R&D
to production.
For custom analysis of your products,
SGS employs 40 years of experience in
biologics characterization with purposebuilt, state-of-the-art, fully cGMP-qualified
and FDA/MHRA regulatory inspected
laboratories.
Biologic
Product
Protein
characterization
Extractables &
Leachables
Biosafety
Pre/Formulation
Forced
degradation
Stability
studies
PRE/FORMULATION DEVELOPMENT
Ensuring a stable environment for biopharmaceutical drug products enables
a long product shelf life and appropriate
formulation for route of administration.
Forced degradation studies are designed
to identify stability indicating methods
and evaluate potential degradation
pathways
SGS’s offerings include fully comprehensive studies and, if required, risk-based
pilot scale studies.
■■ Stability-indicating methods can be
transferred or developed to evaluate
critical quality attributes (CQAs),
including conformational changes
■■ Formulations are developed with
regulatory approved excipients,
which target specific degradation
pathways and protect CQAs
■■ Lyophilization development & optimization available at SGS
■■ Extensive characterization experience ensures lead candidates can
also be fully characterized, giving
confidence in the final, selected
formulation
■■ Conformational and structural changes can be evaluated using an array
of higher order structure biophysical
techniques
STABILITY STUDIES
ICH, EMA and FDA guidelines require
manufacturers to monitor drug substances and drug products “to provide
evidence on how the quality of a drug
substance or drug product varies with
time under the influence of a variety of
environmental factors such as temperature, humidity, and light, and to establish
a re-test period for the drug substance
or a shelf life for the drug product and
recommended storage conditions”.
All stability aspects of drug substances
and drug products can be monitored including long term and accelerated stability / shelf life assessment, in use studies,
short term temperature excursion studies, and forced degradation assessments
according to ICH Q5C and ICH Q1B.
FACILITIES
services
cGMP-qualified, FDA/MHRA regulatory
inspected laboratoy facilities:
Customer-tailored reporting where
full data interpretation by experienced
personnel or standard results data tables
can be provided. Live data trending
will be performed with routine customer updates for the duration of each
study. Range of pharmacopeia and high
throughput analytical methods are available for routine analysis of protein stability, as well complex analytical testing.
■■ Validated, 24h/7day monitoring
system
■■ Ultralow freezers (≤-65°C), freezers
(-20°C), refrigerators (+5°C) and environmental cabinets (at 25°C/60%
relative humidity [RH], 30°C/65%
RH and 40°C/75% RH)
■■ Access-controlled stability storage unit for samples and reference
standards
■■ Dedicated thermal cycling unit
for freeze-thaw and short term
temperature excursion studies with
relative humidity control
■■ Shipment support studies
■■ Temperature-controlled photostability cabinet with Option 2 ICH Q1B
light conditions
In addition to pharmacopeial methods
the following analytical services are also
available:
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Visible particles
Degree of coloration and clarity
Sub-Vis particle counting
pH
Osmolality
Imaged Capillary IEF (icIEF) and
Agarose Gel IEF
SDS-PAGE
UPLC & HPLC (SEC/RP/IEX/HIC)
SEC-MALS
Protein concentration
Peptide mapping with UV, MS and/
or MS/MS and/or MS analysis
Intact mass MS (MALDI-TOF and
ESI-MS)
Analytical Ultracentrifugation (AUC)
Dynamic Light Scattering (DLS)
Circular Dichroism (CD)
Differential Scanning Calorimetry
(DSC)
Fourier Transform Infrared Spectroscopy (FTIR)
Extrinsic and Intrinsic Fluorescence
Bioassays / BIAcore
Glycan Profiling (Neutral Glycans &
Sialic Acids)
FORCED DEGRADATION
ICH, EMA and FDA guidelines require
stress testing of drug substances and
drug products to establish potential
forced degradation pathways and allow characterisation of product-related
impurities. “Stress testing of the drug
substance can help identify the likely
degradation products, which can in turn
help establish the degradation pathways
and the intrinsic stability of the molecule
and validate the stability indicating power
of the analytical procedures used.”
SGS has state-of-the-art laboratories and
expert methodologies available for forced
degradation studies during early product
development and studies performed
according to ICH Q5C and ICH Q1B to
support licence application in a cGMP
compliant laboratory.
A range of stressing conditions and ICH
storage conditions are available:
■■ Forced Degradation Studies used to
assess effects of:
• Agitation
• Exposure to ICH light conditions
• High and low pH
• Temperature excursions
• Freeze/Thaw
• Sheer stress
• Oxidative and deamidative
conditions
BIOSAFETY
Health Authorities, including the US
FDA and the EMA, require companies
to undergo safety testing to demonstrate that all cell banks, viral banks, raw
materials of animal origin, bulk harvests,
and batches of clinical drug are free of
bacteria, fungi, mycoplasma, viruses and
other potential contaminants. SGS helps
clients by ensuring product safety in
satisfying these regulatory requirements.
■■ GMP Cell Bank & Virus Seeds
Characterisation (Vaccines & Gene
Therapies)
■■ GMP Bulk Harvest Release Testing
(Sterility, in vitro assays, RVLPs
quantification, (EM), qPCR)
■■ Host Cell DNA for Non - GLP (process development) & GMP testing
by qPCR
■■ GMP Final Product Batch Release
Testing (HCD & HCP – Endotoxin Ab.Toxicity - other process related
impurity testing)
■■ Regulatory Consultancy, Expert
Report - Custom Assay
development & validation
EXTRACTABLES & LEACHABLES
SGS designs and performs Extractables
and Leachables (E&L) studies for the
successful human health risk assessment of these substances in order to
satisfy regulatory authorities such as the
US-FDA, CN-FDA and EMA, as well as
adhere to PQRI, BPOG, BPSA and ISO
10993 recommendations.
Testing is performed in cGMP compliant laboratories using technologies that
detect ultra trace levels. SGS also per-
Protein CHARACTERIZATION
SGS pioneered physicochemical characterization using high-end mass spectrometry and ancillary techniques to analyze
the primary and higher-order structure of
(glyco) proteins. These services include
protein and peptide, glycosylation, and
oligonucle otide analyses, as well as protein aggregation services. This step ensures an excellent understanding of the
tested product profile and will save time
for tuning and explaining the stability.
ABOUT SGS
SGS Life Science Services is a leading
contract service organization providing
clinical research, pharmaceutical development, biologics characterization, biosafety, and quality control testing. With
a strong focus on biologics & biosimilars
and vaccines, operating 25 facilities in 13
countries across the Americas, Europe
and Asia, SGS represents the broadest
wholly owned global network of contract
analytical laboratories.
forms other compatibility studies such
as container characterization (USP, EP, JP,
ISO) and adsorption studies.
CONTACT INFORMATION
BIOPHARMACEUTICAL LABORATORY cONTACTS
EUROPE
North America
ASIA
SWITZERLAND (GENEVA)
CANADA (Toronto)
CHINA (SHANGHAI)
+41 22 794 8374
+ 1 905 364 3757
+86 21 6107 2718
ch.biopharma@sgs.com
ca.pharmaqc@sgs.com
cn.pharmaqc@sgs.com
UK (GLASGOW)
USA (Philadelphia)
+44 141 952 0022
+ 1 610 696 8210
biosafety@sgs.com
us.biopharma@sgs.com
UK (London)
+44 118 912 1190
uk.biopharma@sgs.com
WWW.sgs.com/BIOpharma
© SGS Group Management SA – 2015 – All rights reserved - SGS is a registered trademark of SGS Group Management SA
www.sgs.com