stability testing services for biologics - sgs.com · generating a stable environment for...
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Stability teSting for biologicS
caring for yoUr biologicS DeVeloPMent
Generating a stable environment for biopharmaceutical drug products is a critical step in the drug develop-ment 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 screen-ing and subsequently monitored through long term stability studies to ensure product shelf life. SGS pro-vides full analytical support through all phases of drug development.
oVerVieW of bioPHarMaceUtical DrUg DeVeloPMent actiVitieS
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PRODUCT SELECTION, CELL LINE SELECTION
Pre-clinical
coMMercialDrUg ProDUct
clinicalPHaSe
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MARKETED DRUG PRODUCT
• DS & DP stability studies • Commercial reference standard stability • Extractables & leachables
PPQ SERIES (PV)
GMP BATCHES
• DS & DP stability studies (3 batches) • Product specifi c method validations • Forced degradation studies • Shipment support studies • Batch release/QC • Biosafety testing
• Commercial reference standard stability • Specifi cation for commercial product determined • DS & DP stability studies • In-use Studies • Extractables & leachables
PROCESS DEVELOPMENT, PROCESS SCALE-UP
PILOT SCALE
GMP BATCHES
• Method development with forced degradation • Preformulation screening • Extractables testing
• Quality specifi cation & stability assays • Pilot stability studies • Lead candidate formulation screening
• Stability studies • Extractables & leachables
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 compo-nents 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 purpose- built, state-of-the-art, fully cGMP-qualified and FDA/MHRA regulatory inspected laboratories.
integrateD SerViceS froM r&D to ProDUction
Pre/forMUlation DeVeloPMent
Ensuring a stable environment for bio-pharmaceutical 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 comprehen-sive 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 & opti-mization available at SGS
■ Extensive characterization experi-ence ensures lead candidates can also be fully characterized, giving confidence in the final, selected formulation
■ Conformational and structural chang-es can be evaluated using an array of higher order structure biophysical techniques
BiologicProduct
Protein Characterization
Pre/Formulation
Stability Studies
Forced Degradation
Biosafety
Extractables & Leachables
forceD DegraDation
ICH, EMA and FDA guidelines require stress testing of drug substances and drug products to establish potential forced degradation pathways and al-low 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
Stability StUDieS
ICH, EMA and FDA guidelines require manufacturers to monitor drug sub-stances 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 tempera-ture, 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 in-cluding long term and accelerated stabil-ity / shelf life assessment, in use studies, short term temperature excursion stud-ies, and forced degradation assessments according to ICH Q5C and ICH Q1B.
facilitieS
cGMP-qualified, FDA/MHRA regulatory inspected laboratoy facilities:
■ Validated, 24h/7day monitoring system
■ Ultralow freezers (≤-65°C), freezers (-20°C), refrigerators (+5°C) and en-vironmental cabinets (at 25°C/60% relative humidity [RH], 30°C/65% RH and 40°C/75% RH)
■ Access-controlled stability stor-age 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 photostabil-
ity cabinet with Option 2 ICH Q1B light conditions
SerViceS
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 cus-tomer updates for the duration of each study. Range of pharmacopeia and high throughput analytical methods are avail-able for routine analysis of protein stabil-ity, as well complex analytical testing.
In addition to pharmacopeial methods the following analytical services are also available:
■ 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 Spectros-
copy (FTIR) ■ Extrinsic and Intrinsic Fluorescence ■ Bioassays / BIAcore ■ Glycan Profiling (Neutral Glycans &
Sialic Acids)
eXtractableS & leacHableS
SGS designs and performs Extractables and Leachables (E&L) studies for the successful human health risk assess-ment 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 compli-ant laboratories using technologies that detect ultra trace levels. SGS also per-
forms other compatibility studies such as container characterization (USP, EP, JP, ISO) and adsorption studies.
bioSafety
Health Authorities, including the US FDA and the EMA, require companies to undergo safety testing to demon-strate 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 (pro-cess 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
SGS Life Science Services is a leading contract service organization providing clinical research, pharmaceutical develop-ment, biologics characterization, bio-safety, 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.
aboUt SgS
Protein cHaracteriZation
SGS pioneered physicochemical charac-terization using high-end mass spectrom-etry 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 pro-tein aggregation services. This step en-sures an excellent understanding of the tested product profile and will save time for tuning and explaining the stability.
contact inforMationbioPHarMaceUtical laboratory contactS
eUroPe
SWitZerlanD (geneVa)
+41 22 794 8374
UK (glaSgoW)
+44 141 952 0022
UK (lonDon)
+44 118 912 1190
nortH aMerica
canaDa (toronto)
+ 1 905 364 3757
USa (PHilaDelPHia)
+ 1 610 696 8210
aSia
cHina (SHangHai)
+86 21 6107 2718
WWW.SgS.coM/bioPHarMa
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