photo courtesy of texwipe nextpharma technologies geneviève motte, phd vp sterile product...
TRANSCRIPT
![Page 1: Photo courtesy of Texwipe NextPharma Technologies Geneviève Motte, PhD VP Sterile Product Development Advanced Aseptic Manufacturing Solutions for Clinical](https://reader035.vdocuments.mx/reader035/viewer/2022062421/56649db15503460f94aa0996/html5/thumbnails/1.jpg)
Photo courtesy of Texwipe
NextPharma TechnologiesGeneviève Motte, PhDVP Sterile Product Development
Advanced Aseptic Manufacturing Advanced Aseptic Manufacturing Solutions for Clinical Trial Solutions for Clinical Trial
MaterialMaterial
Paris, 26 – 27 January 2010
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Introduction
Market and Clinical Pipeline
Challenges of NCEs
Manufacturing Solutions
NextPharma Technologies
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Market outlook World pharmaceutical market forecast is $750bn in 2009
Expected growth rate: 3 – 6% per year through 2013
Weight of biomedicines: $127bn by 2012 (more than 15%)Expected growth rate: 12% per year
Anticancer drugs: $80bn by 2012Expected growth rate: 12% per year
Injectables: $147bn (20% of the entire market)Expected to grow at 11% per year through 2012 (26% of market)
NextPharma Technologies
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Clinical pipeline
Over the last 4 years, 30% of NCE were biomedicines
The number of biologics in Phase I has been multiplied by 6, in contrast to only 2 for small molecules
Top targeted disease area is cancer which represents 30% of the global pipeline and 35% of biologics
More than half of the drugs in development are for parenteral administration of which 75% of all biologics
NextPharma Technologies
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Traditional Drugs and Biologics by Clinical Phase
0
500
1000
1500
2000
2500
3000
3500
Total Phase I Phase II Phase III
Biologics
Small Molecules
NextPharma Technologies
Source : Leem Biotech Bioproduction 2008
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Biologics by Therapeutic Class
18027%
18427%
7211%
17326%
599%
Mabs
Vaccines
Oligonucleotides
Therapeutic Proteins
Gene and cell therapies
NextPharma Technologies
Source: Leem Biotech Bioproduction 2008
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Anticancer Drugs by Therapeutic Class
32
6
40
27
18
67
on the market in development
%
Targeted
Cytotoxic
Hormonal
NextPharma Technologies
Source: Availability of medicines and supporting therapies in pediatric oncology -- Warsaw – Oct. 14, 2009
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Challenges - Biologics
Minimal quantities of API available (g vs kg)
Unknown toxicity
Stability issue
Solubility issue
Controlled-release formulations to extend half-life and to reduce dose-related side-effects
NextPharma Technologies
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Challenges - Anticancer drugs
Extremely high potency levels and/or toxicity
Tumor-targeting formulations
Fast-track development programs and high failure rates
Small batch size
NextPharma Technologies
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How to address these challenges?
Facility Design
Highly flexible manufacturing from Formulation Development to Clinical Trial Material and Commercial Supply
Innovative drug delivery systems
NextPharma Technologies
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Solubilization and stabilization
Targeted and sustained drug delivery systems
Lyo cycle development
Process parameters
Formulation labs at NextPharma
NextPharma Technologies
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Manufacturing and supply of Phase I to Phase III Clinical Trial Material
Cytotoxic and biologics/conventional drugs in segregated units (Toxicity 4)
Clinical Trial Packaging, labeling and storage
Scaling-up, validation, registration and commercialization
Development Center and Commercial Manufacturing
NextPharma Technologies
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Flexibility
2-100ml glass and plastic vials handled on standard trays
Washing machineOvenFilling lineFreeze-dryerCapping
Automatic tool-free filling and stoppering machine ( 14.25 – 52 mm)
NextPharma Technologies
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Flexibility
Temperature control through the manufacturing process
Oxygen control in solution + head space
Light control in RABS
Compatibility with material stainless steel or glass vessels, flex bags EVA et PE PES, PVDF, Nylon® filters Pt silicone, Teflon® tubings
NextPharma Technologies
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Innovative Drug Delivery Systems
Solvent-based formulations
Controlled release matrix
Nanoscale drug carriers
Conjugated APIs
NextPharma Technologies
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Case study 1 - Oxygen control
Filling machine: Head space in the vials:Current process
N2 N2Filling
Stoppering
NextPharma Technologies
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Filling machine: Head space in the vialsImprovement
N2 N2Filling Stoppering
Case study 1 - Oxygen control
NextPharma Technologies
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Case study 2 - Quantity of API
Lyo cycle development and Phase I clinical trial material 800mg API available for lyo cycle development
Determination of freeze-drying parameters on small vials (2R)o Freezingo Sublimationo Secondary drying
Transposition to the final dosage form (10R vials) - adjustment of phases length only, with same pressure and t° parameters
NextPharma Technologies
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Case study 3 – Fast to Clinic
Freeze-dried drug product for First In Humans Fast to clinic
Aseptic manufacturing and IPC Clinical trial packaging and labeling Final release testing QP release 3 weeks after manufacturing date
NextPharma Technologies
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Sterile depot formulation in PFS for intra-articular administration
Rheumatoid arthritis
Semi-automatic filling of syringes with peristaltic pump Stopper placement unit under vacuum 0.5-20ml PFS
Case study 4 - Prefilled syringes
NextPharma Technologies
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Allow clients to use a new technology Minimize investment costs Offer key advantages for patient quality and ease of use to
pharmaceutical companies
Create partnership with Aseptic Technologies Leverage both EMEA approved / FDA registered facility
and preliminary R&D setting
Case study 5 – Closed Vial Technology
NextPharma Technologies
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New concept of Crystal®
Sterilization
(Gamma irradiation)Molding & Closing
(Class ISO 5)Assembly
(Class ISO 8)
Capping Laser re-sealing Filling
Filling line under barrier (Class ISO 5)
MOLDING SITE IRRADIATION UNIT
PHARMACEUTICAL SITE
Clean & Sterile ready-to-fill vial
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EMEA approved2 DMF filed at FDA
Approved for recombinant viruses
Clinical line in Class ISO8 at Aseptic Technologies
Offer in-house ad-hoc contract manufacturing for small quantities of GMP material (e.g., stability batches), especially to client interested to test the concept
Authority approved filling facility
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Clinical line and lyo unit in Class ISO8 at Aseptic Technologies
Offer in-house ad-hoc contract manufacturing for small non-GMP quantities to perform R&D investigation
Preliminary R&D filling facility
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Filling of GMP batches:
– Filling of 3000 vials for stability tests with two vaccines
– Filling of 3 recombinant viruses for stability tests
Ad-hoc R&D projects:
– Filling of 4 x 10 vials (2ml) with a protein to investigate reasons for lack of stability in glass vials
– Filling of 2 x 400 vials (1ml) of an antibody to investigate stability in oxygen free condition and in presence of oxygen
– Filling of 300 vials (1ml) to investigate stability of a recombinant virus in accelerated conditions
– Filling of 500 vials to investigate stability on 2 year basis with a recombinant protein
Examples of filling performed
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Case study 6 - Controlled release matrix
Injectable depot formulation for Phase I clinical trial Lipid-based sterile solution Cyclic peptide 800 vials – 1,4ml fill volume
High sensitivity to water =>o Anhydrous formulationo Ethanol rinse of equipments and pipeso Nitrogen flush
High viscosity of excipients =>o Compounding with viscosity-controlled stirringo Larger tubing for dispensing
NextPharma Technologies
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Case study 7 - Nanoparticles
Injectable nanoscale drug carrier of a cytotoxic drug for Phase II clinical trial
API entrapped in nanoparticles Freeze-dried sterile formulation
Dissolution of API and sterile filtration of the solution Aseptic addition of monomer => emulsion (isolator) In situ polymerization – control of particle size! Aseptic filling and freeze-drying
NextPharma Technologies
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Conclusions
Facility Design and equipments adapted to highly sensitive and highly potent drugs
Cost and Time efficiency
Advanced manufacturing solutions
NextPharma Technologies