overcoming the challenges in advancing manufacturing of biosimilars
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Overcoming The ChallengesIn Advancing Manufacturing
Of Biosimilars
SWAPNIL BALLAL
Head, Biopharma Mfg.Intas Biopharmaceuticals Ltd. Ahmedabad, Indiahttp:/ / ww w.intasbiopharma.co.in
swapnil.ballal@intasbiopharma.co.in
http://www.intasbiopharma.co.in/mailto:swapnil.ballal@intasbiopharma.co.inmailto:swapnil.ballal@intasbiopharma.co.inhttp://www.intasbiopharma.co.in/ -
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About Intas Biopharmaceuticalsp 1st and only EU-GMP approved Biotechnology
Facility in India
p Manufacturer of G-CSF, Interferon 2b,Erythropoietin and PEG-GCSF
p First PEG-GCSF in the World after innovator
p Part of the $250 Million Intas group
p Also offer services in Contract Research,Manufacturing and Analysis
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Biosimilars Business
Risky
Challenging
Troublesome
Variable Regulatory Demands
Commoditization
Substitution?
Pricing Pressure
Patent Litigation
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Expectations from Biosimilars..1p High Quality Equal or better than Innovator
n Purity
p Equal to or better than innovator
p Product Impurities : Same or lower than innovator. No newimpurity
n
Safety & Efficacyp Clinical, In vitro/ In Vivo Efficacy
p Toxicity
p Immunogenicity
p Viral Clearance
n Comparability
p Primary, Secondary, Glycan Structure,
p Mol. Wt., Isoform distribution
p Impurity Profiling
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Expectations from Biosimilars..2
General Expectation:
Cost of Goods 1/10th of the innovator selling price
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p Cost Effective
n Innovatorp Procrit (J&J) 2MIU = $35 (~1700 INR)
p Epogen (Amgen) 2MIU = $ 65 (~3000 INR)
p Mabthera(Roche) 100 mg=$ 400 (~20,000 INR)
n Biosimilarp Epofit (Intas) 2MIU = $ 15 (~750 INR)
p Epofit (Intas) 4MIU = $ 30 (~1480 INR)
p Reditux(Dr Reddys)100 mg = $ 200 (~10,000 INR)
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Other Challenges
p Limited Market
n Semi & Non Regulated Market Cost sensitive
n Competition
n ~ 90% of Product sales in Regulated Markets -
saturated
p Small Scale- Limited no. of batches
n 100 L fermenter @0.25 g/L yield- ~ 10% of AnnualWorld GCSF requirement
n Reduces the opportunities of processunderstanding
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Challenges in Biosimilar Production
The Ultimate Factor To Control Is
COSTwithout ever compromising
Safety & Efficacy
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Challenges in Biosimilar Production
The need to manage production efficiently
must be balanced with
the desire to adopt thestate of the art techniques
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Advancing Production-Facility Sizing
The Past
The Future
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Current State of Facility Sizing
p Indian companies are developing multiple biosimilarproducts
p Similar product basket
p Volume would not justify dedicated facilities
p Similar scenario in China, Brazil, Argentina
p Multi-use and flexible facilities needed
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p Lower Capital load and lower financing burden
p Catalog Process Equipment can be used lowering the start up costs
p Cooling and Air Handling contributes
significantly to the operating costp Leverage the controlled non classified (CNC)
concept to reduce classified cleanroom areas
p Segregate the process area in smaller modules-allows to overlap batch processing & maximize
facility utilization.
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Biogeneric Facility Sizing Smaller IS better
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Biogeneric Facility Sizing Smaller IS better
Consider Modular Approach
Replicate Vs Scale Up
n No changes in procedures, systems required
n Limited issues with validation of process, cleaning
n No training burden
n No Process & Product Comparability
n Minimal disruption to production
n Rapid Deployment Smaller units are catalog products short delivery time.
n Not so attractive for products with high QC testing cost
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Optimize Single Use Product Implementation
p Single use products have significantcost associated with them
p Yes, they are in vogue, but steel isstill fine
p As a thumb rule, consider bags if yourrequirement for a product is < 20batch/year
p Consider fixed tanks for non-productapplications
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Maximize advantages of Single Use Products
p Design completely closed systems-
n Tubing sealers, welders, sterile connectorsetc.
n Cleanroom Classification- 1-2 grade lower
p Lower Setup costp Lower Operational costs Power, Env.
monitoring
p Minimize Hard Process Piping
n Flexibility for diverse products
n Reduce significant capital cost
n Lower automation, maintenance cost
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Improving Operational Efficiencies2
p High end PAT applications (MS, FT-NIR)require significant development efforts
n More useful for high value/high riskapplications
p Use simpler PAT applications to improveprocess control- HPLCs/UPLC analysis asindicator of resin life
p Use faster analytical tools like UPLC to
reduce in-process analysis time.
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Improving Operational Efficiencies3
p Leverage Process Development Data to addressdeviations and process excursions
p Use Statistical Process Controls for process monitoringand as early warning system
p Make use of scale down models and mathematicalmodeling to understand the process, predict processbehavior, using limited process data
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Cost Optimization- Raw Material
p Develop Processes with production grade chemicals
p Low Bioburden, low endotoxin grade products maynot be required at early stages of processing
p Reduce multiple grades of water used- low volumeoperations can shift totally to WFI
p Use of common RM grades, vendor reducedlogistics, testing and QA costs & increased negotiationpower
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Operational Excellence in Multiproduct Setup
p The Key Word : Harmonize
p Harmonization of source of chemical reducedtesting, logistics
p Filters and membranes leachable studies,cleaning validation, regulatory documentation
p Avoid custom build products
p Similar/same model across modules/ platforms,
including R& D spares, service
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