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Transcript of Photo courtesy of Texwipe NextPharma Technologies Geneviève Motte, PhD VP Sterile Product...
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
Introduction
Market and Clinical Pipeline
Challenges of NCEs
Manufacturing Solutions
NextPharma Technologies
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
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
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
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
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
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
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
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
Solubilization and stabilization
Targeted and sustained drug delivery systems
Lyo cycle development
Process parameters
Formulation labs at NextPharma
NextPharma Technologies
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
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
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
Innovative Drug Delivery Systems
Solvent-based formulations
Controlled release matrix
Nanoscale drug carriers
Conjugated APIs
NextPharma Technologies
Case study 1 - Oxygen control
Filling machine: Head space in the vials:Current process
N2 N2Filling
Stoppering
NextPharma Technologies
Filling machine: Head space in the vialsImprovement
N2 N2Filling Stoppering
Case study 1 - Oxygen control
NextPharma Technologies
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
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
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
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
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
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
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
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
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
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
Conclusions
Facility Design and equipments adapted to highly sensitive and highly potent drugs
Cost and Time efficiency
Advanced manufacturing solutions
NextPharma Technologies