Overcoming the challenges in advancing manufacturing of biosimilars

8/14/2019 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

[email protected]
http://www.intasbiopharma.co.in/mailto:[email protected]:[email protected]://www.intasbiopharma.co.in/


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3 Dec 09 Swapnil Ballal 2 of 22

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


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.


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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Documents

Overcoming the challenges in advancing manufacturing of biosimilars