Glass Primary Packaging for Injectables: Selecting the Right Container
Glass Primary Packaging for Injectables: Selecting the Right Container Pharmapack 2017 – Alessio Bonati
Ompi Product Portfolio Ompi Fina: Optimized for Parenterals Ompi Nexa: Best in Class for Demanding Products Ompi Alba: Taking Drug Delivery to a New World Ompi EZ-fill®: Ready-to-Use Containers
The Ompi Product Portfolio in a Nutshell
Optimized for parenterals
Best in class for your most demanding products
Taking Drug Delivery to a New World
Ready-to-use containers
3
The Ompi Product Portfolio by Product Platforms Technological and Quality Solution Level
Breaktrough
State-of-the-art
High Quality Benefit/Value 4
Ompi Product Portfolio Ompi Fina: Optimized for Parenterals Ompi Nexa: Best in Class for Demanding Products Ompi Alba: Taking Drug Delivery to a New World Ompi EZ-fill®: Ready-to-Use Containers
Ompi Fina | Use, Features & Benefits Technological and Quality Solution Level
Optimized for Parenteral Drugs Intended Use • Vaccines • Diagnostics • Small Molecules • Anti-coagulants (i.e. Heparin) • Anesthetics • Veterinary • Insulin • GLP-1 • WFI/Diluents • Other Pharma applications • Cosmetics
High Quality
Main Features & Benefits • Suitable for a wide range of applications • Produced accordingly a high quality validated process • Customizable according to customer request
Benefit/Value 6
Ompi Fina | The Answer for Glass Delamination
•
Separation of thin glass layers (lamellae) that appear as shiny, needle shaped particles floating in the contact liquid
•
The formation of a silicarich layer poorly bonded to the substrate is the first stage of an extended delamination
•
Glass-liquid interactions are responsible for the formation of an altered layer
R.G. Iacocca et al., AAPS Pharm.Sci.Tech. (2010)
7
OMPI Fina – LDP Vials Option
Improved process on 6-Sigma approach
Thermal cycle optimization with low heat/energy forming process Low Delamination Propensity
Qualitative test method
Optimized vials manufacturing process with an higher quality product from chemical point of view
- 2017 | Strictly Confidential
8
Ompi Product Portfolio Ompi Fina: Optimized for Parenterals Ompi Nexa: Best in Class for Demanding Products Ompi Alba: Taking Drug Delivery to a New World Ompi EZ-fill®: Ready-to-Use Containers
Ompi Nexa | Use, Features & Benefits Technological and Quality Solution Level
Best in Class for your Most Demanding Products Intended Use • Biologics • Large Molecules • Sensitive Drugs • Insulin & GLP-1 • Hormones & Proteins • Adrenaline & Emergency • Auto-injectors • Drug Delivery Systems
State-of-the-art
Main Features & Benefits • High dimensional process capability • Higher Mechanical Resistance to minimize breakage issues • Very High Cosmetic Quality (No G2G Process, 100% Improved Camera Inspection) • Customizable according to customer request
Benefit/Value 10
Ompi Nexa | High dimensional process capability
COLLAR
NECK/MOUTH
SHOULDER
BOTTOM
Compatibility with caps and filling lines
Blowback repeatibility
Optimized for Inspection, to reduce false rejects
High stability of the vials on the transport belts Freeze-dryed drugs 11
OMPI Nexa – High dimensional process capability Cone Dimensions (Inside and Outside) Flange Dimensions Total Length
- 2017 | Strictly Confidential
12
Ompi Nexa – Higher Mechanical Resistance
Reduced breakage risk during the industrial life of your drug
Superior Mechanical Resistance • Limited Glass-to-Glass and Glass-toMetal contact along the entire process
13
Ompi Nexa | Higher Mechanical Resistance
Horizontal Compression (Body)
GTG process GTG process NGTG process
Vertical Compression (Shoulder) Up to 3x the current mechanical properties
Cone Test (Glazed Rim)
14
Ompi Nexa | Very High Cosmetic Quality
Unprecedented cosmetic performance reducing your cosmetic reject rates to the lowest level. PPM base for most critical defects (Vials) • Critical defects: PPM + AQL 0,025 – 0,1 • Major defects: 0,15-0,04 • Minor defects: 1,0-0,25
Argo Vision System for tight Cosmetic Inspection (Vials) • 100% full surface automatic inspection / 200μm • 9 cameras installed • No Glass2Glass - No Glass2Metal handling
15
Ompi Nexa | Very High Cosmetic Quality
Linear Scan - Shoulder Cone Inspection
Linear Scan - Body
Linear Scan
Area/Matrix Scan (Internal Channel)
Area/Matrix Scan Flange
16
Ompi Nexa | Syringe Features
Low Tungsten
Optimized siliconization
UV Curing
OMPI MAX LIM [ppb] Tungsten free
0
Low Tungsten
< 500
17
Ompi Nexa | Syringe Features In-line Siliconization Automatic Controls • Presence of silicone inside the barrel • Correct distribution inside the barrel
18
Ompi Product Portfolio Ompi Fina: Optimized for Parenterals Ompi Nexa: Best in Class for Demanding Products Ompi Alba: Taking Drug Delivery to a New World Ompi EZ-fill®: Ready-to-Use Containers
Ompi Alba | Pending issues raised by Biotech formulations
In 5-15% of cases, drug formulations have a high to very high sensitivity to one or more of the components of a primary container • Silicone oil emulsification: droplets/”particles” • Drug/surface interactions: protein aggregation, etc. • Extractable, etc. • Issue with Rubber formulation
Trend towards more concentrated drug formulations may reinforce this trend Technology improvement alone will find its limits in terms of capabilities and/or in terms of cost Biotech formulations must be understood in a more global manner, from conception to injection
20
Ompi Alba | Use, Features & Benefits Technological and Quality Solution Level
Breaktrough
Taking Drug Delivery to a New World Intended Use • Biologics with high sensitivity to primary packaging interaction • Ophthalmic Main Features & Benefits • Same NEXA Features & Benefits • ALBA Coating (Silicone Based) • Ultra Low Particle Level • Reduced Extractable & Lecheable • Limited pH Drift • No Delamination Propensity (Vials) • Highly Selected Rubber Components
Benefit/Value 21
Ompi Alba | Ultra Low Particle Level OmpiAlba | Syringes 2500 1-2 µm 2-5 µm
Fill the syringes with 1,3mL of filtered (0,22µm) and distilled water
120000
2.
Cap the syringes with aluminum foil
100000
3.
Put the syringes inside the autoclave (1h at 121°C)
4.
Analyze the extracts with the MFI 5200 series
5-10 µm 10-25 µm
Concentration (#/mL)
1.
140000
25-50 µm
80000
Concentration (#/mL)
MethodologyDescription*
1-2 µm
2243
2-5 µm 5-10 µm
2000
10-25 µm
1500
25-50 µm
1205
1000 500
60000 40000
0
122 26 5
Comments 20000
• All the three Types of syringes are inside the USP788 requirements • Significant particles reduction for the Alba syringes • Alba solution answers to the requirements of low particles
0 Std Syringes
HQ Syringes
ALBA syringes
*Test method development and analysis by SGlab
22
Ompi Alba | Reduced Extractable OmpiAlba | Vials
MethodologyDescription* Fill the vials with 3,6mL of distilled water cap the vials with aluminum foil
3.
Put the vials inside the autoclave (1h at 121°C)
4.
Analyze the extracts with the ICPOES
Comments •
•
The coating barrier characteristic leads to a significant inorganic extractable reduction for the Alba syringes and vials compared to other bulk market solutions as a vial Comparable inorganic extractable between Alba syringes and Alba vials
2,5
SiO2
Al2O3 Na2O tot
B2O3 Al2O3 SiO2 Na2O tot
11 10 9 8
1,5 1,0 0,5
7 ppm
2.
B2O3
2,0 ppm
1.
3,0
0,0
6 5 4 3 2 1 0 Typical bulk vial
Alba syringes
Alba vials
*Test method development and analysis by SGlab
23
Ompi Alba | Highly Selected Rubber Components
Vial System
Syringe System
Cartridge System
Key Point Ompi Alba is a system The rubber parts are key to the global performance: gliding of course but also particles, as plungers contribute to 50% of the particles in the assembled system in the best configuration.
=
=
The barrel performance are so good that not all plungers should be used.
Ompi R&D is performing a screening activity selecting the best closures adapt to the systems 24 21
Ompi Alba | Always the Same Interaction with the Drug
25 4
Ompi Alba | Always the Same Interaction with the Drug
MethodologyDescription* 1.
Fill the syringes with 3,6mL of filtered (0,22µm) and distilled water
2.
cap the vials with aluminum foil
3.
Put the vials inside the autoclave (1h at 121°C)
4.
Analyze the extracts with the MFI 5200 series
1-2 µm 2-5 µm 5-10 µm 10-25 µm 25-50 µm
2500
2000
1500
Comments •
•
Comparable particles release between Alba syringes and Alba vials Comparable particles release between Bulk and Alba vials
Concentration (#/mL)
1000
500
0 Alba Syringes
Alba Vials
*Test method development and analysis by SGlab
26 11
Sales Level
Ompi Alba | Risk Minimization in Drug Development
Reduced Time-to-Market
Traditional
Drug Design
Research
Phase I-II
Phase III
Market
Time
27
Ompi Product Portfolio Ompi Fina: Optimized for Parenterals Ompi Nexa: Best in Class for Demanding Products Ompi Alba: Taking Drug Delivery to a New World Ompi EZ-fill®: Ready-to-Use Containers
Ompi EZ-fill® | A Comprehensive Range of RTU Containers
Vials
Washing (Siliconization) Depyrogenation Nesting (no G2G) Final Sterilization
Cartridges
Nest & Tub
Syringes
Vials
Tray COMING SOON Cartridge Only Glass
29
Ompi EZ-fill® | PharmaCo Value
Pharmaceuticalneeds
Minimizing T.C.O.
Increasing Quality
Increasing Flexibility
Reducing Time-ToMarket
Value Chain: Roles & Responsabilities Packaging Industry:
Packaging
Capex
Packaging Industry:
Washing
Validation and Regulatory «non quality» Costs and issues
PharmaCo
Sterilization
Upstream Operations
Filling
More Resources Available
30
Minimizing T.C.O.
Reduction of initial investments on: • Equipment (washing, WFI system, tunnel) • Utilities (WFI, kWh,..) • Workforce • Validation • Maintenance
Increasing Quality
• •
No-glass-to-glass contact during transport Feeding, Washing, Depyrogenating Tunnel are very stressed phases for packaging
•
A unique fill&finish equipment for different packaging: Easy & fast change packaging/format in the same machine (combo line)
Increasing Flexibility
Reducing Time-ToMarket
•
•
Reduction of the time, using Ompi EZ-fill® from research to industrial scale
CostReductionforPharmaCo
Pharmaceuticalneeds
Ompi EZ-fill® | PharmaCo Value
31
OMPI EZ-fill® – Not only a Primary Packaging Primary Packaging
Filling Machinery
Closures & Components
Reduction of complexity for our Customer in each step of the process (from the collection of info to the manufacturingphase)
Engineering Companies
32
Ompi EZ-fill® | What are you Looking for?
High Productivity? Tray for dedicated filling line
Need of flexibility? Nest&Tub for combo line
33
Ompi EZ-fill® | Flexible Filling Machines
machines
machines
2013
2016
All the leading machine manufactuers have presented or are developing flexible machines for filling the full range of sterile containers based on Ompi EZ-fill® platform (from small batches to industrial capacity).
34
Thank You for Your Attention!
www.ompipharma.com
Ompi Product Portfolio Ompi Fina: Optimized for Parenterals Ompi Nexa: Best in Class for Demanding Products Ompi Alba: Taking Drug Delivery to a New World Ompi EZ-fill®: Ready-to-Use Containers
The Ompi Product Portfolio in a Nutshell
Optimized for parenterals
Best in class for your most demanding products
Taking Drug Delivery to a New World
Ready-to-use containers
3
The Ompi Product Portfolio by Product Platforms Technological and Quality Solution Level
Breaktrough
State-of-the-art
High Quality Benefit/Value 4
Ompi Product Portfolio Ompi Fina: Optimized for Parenterals Ompi Nexa: Best in Class for Demanding Products Ompi Alba: Taking Drug Delivery to a New World Ompi EZ-fill®: Ready-to-Use Containers
Ompi Fina | Use, Features & Benefits Technological and Quality Solution Level
Optimized for Parenteral Drugs Intended Use • Vaccines • Diagnostics • Small Molecules • Anti-coagulants (i.e. Heparin) • Anesthetics • Veterinary • Insulin • GLP-1 • WFI/Diluents • Other Pharma applications • Cosmetics
High Quality
Main Features & Benefits • Suitable for a wide range of applications • Produced accordingly a high quality validated process • Customizable according to customer request
Benefit/Value 6
Ompi Fina | The Answer for Glass Delamination
•
Separation of thin glass layers (lamellae) that appear as shiny, needle shaped particles floating in the contact liquid
•
The formation of a silicarich layer poorly bonded to the substrate is the first stage of an extended delamination
•
Glass-liquid interactions are responsible for the formation of an altered layer
R.G. Iacocca et al., AAPS Pharm.Sci.Tech. (2010)
7
OMPI Fina – LDP Vials Option
Improved process on 6-Sigma approach
Thermal cycle optimization with low heat/energy forming process Low Delamination Propensity
Qualitative test method
Optimized vials manufacturing process with an higher quality product from chemical point of view
- 2017 | Strictly Confidential
8
Ompi Product Portfolio Ompi Fina: Optimized for Parenterals Ompi Nexa: Best in Class for Demanding Products Ompi Alba: Taking Drug Delivery to a New World Ompi EZ-fill®: Ready-to-Use Containers
Ompi Nexa | Use, Features & Benefits Technological and Quality Solution Level
Best in Class for your Most Demanding Products Intended Use • Biologics • Large Molecules • Sensitive Drugs • Insulin & GLP-1 • Hormones & Proteins • Adrenaline & Emergency • Auto-injectors • Drug Delivery Systems
State-of-the-art
Main Features & Benefits • High dimensional process capability • Higher Mechanical Resistance to minimize breakage issues • Very High Cosmetic Quality (No G2G Process, 100% Improved Camera Inspection) • Customizable according to customer request
Benefit/Value 10
Ompi Nexa | High dimensional process capability
COLLAR
NECK/MOUTH
SHOULDER
BOTTOM
Compatibility with caps and filling lines
Blowback repeatibility
Optimized for Inspection, to reduce false rejects
High stability of the vials on the transport belts Freeze-dryed drugs 11
OMPI Nexa – High dimensional process capability Cone Dimensions (Inside and Outside) Flange Dimensions Total Length
- 2017 | Strictly Confidential
12
Ompi Nexa – Higher Mechanical Resistance
Reduced breakage risk during the industrial life of your drug
Superior Mechanical Resistance • Limited Glass-to-Glass and Glass-toMetal contact along the entire process
13
Ompi Nexa | Higher Mechanical Resistance
Horizontal Compression (Body)
GTG process GTG process NGTG process
Vertical Compression (Shoulder) Up to 3x the current mechanical properties
Cone Test (Glazed Rim)
14
Ompi Nexa | Very High Cosmetic Quality
Unprecedented cosmetic performance reducing your cosmetic reject rates to the lowest level. PPM base for most critical defects (Vials) • Critical defects: PPM + AQL 0,025 – 0,1 • Major defects: 0,15-0,04 • Minor defects: 1,0-0,25
Argo Vision System for tight Cosmetic Inspection (Vials) • 100% full surface automatic inspection / 200μm • 9 cameras installed • No Glass2Glass - No Glass2Metal handling
15
Ompi Nexa | Very High Cosmetic Quality
Linear Scan - Shoulder Cone Inspection
Linear Scan - Body
Linear Scan
Area/Matrix Scan (Internal Channel)
Area/Matrix Scan Flange
16
Ompi Nexa | Syringe Features
Low Tungsten
Optimized siliconization
UV Curing
OMPI MAX LIM [ppb] Tungsten free
0
Low Tungsten
< 500
17
Ompi Nexa | Syringe Features In-line Siliconization Automatic Controls • Presence of silicone inside the barrel • Correct distribution inside the barrel
18
Ompi Product Portfolio Ompi Fina: Optimized for Parenterals Ompi Nexa: Best in Class for Demanding Products Ompi Alba: Taking Drug Delivery to a New World Ompi EZ-fill®: Ready-to-Use Containers
Ompi Alba | Pending issues raised by Biotech formulations
In 5-15% of cases, drug formulations have a high to very high sensitivity to one or more of the components of a primary container • Silicone oil emulsification: droplets/”particles” • Drug/surface interactions: protein aggregation, etc. • Extractable, etc. • Issue with Rubber formulation
Trend towards more concentrated drug formulations may reinforce this trend Technology improvement alone will find its limits in terms of capabilities and/or in terms of cost Biotech formulations must be understood in a more global manner, from conception to injection
20
Ompi Alba | Use, Features & Benefits Technological and Quality Solution Level
Breaktrough
Taking Drug Delivery to a New World Intended Use • Biologics with high sensitivity to primary packaging interaction • Ophthalmic Main Features & Benefits • Same NEXA Features & Benefits • ALBA Coating (Silicone Based) • Ultra Low Particle Level • Reduced Extractable & Lecheable • Limited pH Drift • No Delamination Propensity (Vials) • Highly Selected Rubber Components
Benefit/Value 21
Ompi Alba | Ultra Low Particle Level OmpiAlba | Syringes 2500 1-2 µm 2-5 µm
Fill the syringes with 1,3mL of filtered (0,22µm) and distilled water
120000
2.
Cap the syringes with aluminum foil
100000
3.
Put the syringes inside the autoclave (1h at 121°C)
4.
Analyze the extracts with the MFI 5200 series
5-10 µm 10-25 µm
Concentration (#/mL)
1.
140000
25-50 µm
80000
Concentration (#/mL)
MethodologyDescription*
1-2 µm
2243
2-5 µm 5-10 µm
2000
10-25 µm
1500
25-50 µm
1205
1000 500
60000 40000
0
122 26 5
Comments 20000
• All the three Types of syringes are inside the USP788 requirements • Significant particles reduction for the Alba syringes • Alba solution answers to the requirements of low particles
0 Std Syringes
HQ Syringes
ALBA syringes
*Test method development and analysis by SGlab
22
Ompi Alba | Reduced Extractable OmpiAlba | Vials
MethodologyDescription* Fill the vials with 3,6mL of distilled water cap the vials with aluminum foil
3.
Put the vials inside the autoclave (1h at 121°C)
4.
Analyze the extracts with the ICPOES
Comments •
•
The coating barrier characteristic leads to a significant inorganic extractable reduction for the Alba syringes and vials compared to other bulk market solutions as a vial Comparable inorganic extractable between Alba syringes and Alba vials
2,5
SiO2
Al2O3 Na2O tot
B2O3 Al2O3 SiO2 Na2O tot
11 10 9 8
1,5 1,0 0,5
7 ppm
2.
B2O3
2,0 ppm
1.
3,0
0,0
6 5 4 3 2 1 0 Typical bulk vial
Alba syringes
Alba vials
*Test method development and analysis by SGlab
23
Ompi Alba | Highly Selected Rubber Components
Vial System
Syringe System
Cartridge System
Key Point Ompi Alba is a system The rubber parts are key to the global performance: gliding of course but also particles, as plungers contribute to 50% of the particles in the assembled system in the best configuration.
=
=
The barrel performance are so good that not all plungers should be used.
Ompi R&D is performing a screening activity selecting the best closures adapt to the systems 24 21
Ompi Alba | Always the Same Interaction with the Drug
25 4
Ompi Alba | Always the Same Interaction with the Drug
MethodologyDescription* 1.
Fill the syringes with 3,6mL of filtered (0,22µm) and distilled water
2.
cap the vials with aluminum foil
3.
Put the vials inside the autoclave (1h at 121°C)
4.
Analyze the extracts with the MFI 5200 series
1-2 µm 2-5 µm 5-10 µm 10-25 µm 25-50 µm
2500
2000
1500
Comments •
•
Comparable particles release between Alba syringes and Alba vials Comparable particles release between Bulk and Alba vials
Concentration (#/mL)
1000
500
0 Alba Syringes
Alba Vials
*Test method development and analysis by SGlab
26 11
Sales Level
Ompi Alba | Risk Minimization in Drug Development
Reduced Time-to-Market
Traditional
Drug Design
Research
Phase I-II
Phase III
Market
Time
27
Ompi Product Portfolio Ompi Fina: Optimized for Parenterals Ompi Nexa: Best in Class for Demanding Products Ompi Alba: Taking Drug Delivery to a New World Ompi EZ-fill®: Ready-to-Use Containers
Ompi EZ-fill® | A Comprehensive Range of RTU Containers
Vials
Washing (Siliconization) Depyrogenation Nesting (no G2G) Final Sterilization
Cartridges
Nest & Tub
Syringes
Vials
Tray COMING SOON Cartridge Only Glass
29
Ompi EZ-fill® | PharmaCo Value
Pharmaceuticalneeds
Minimizing T.C.O.
Increasing Quality
Increasing Flexibility
Reducing Time-ToMarket
Value Chain: Roles & Responsabilities Packaging Industry:
Packaging
Capex
Packaging Industry:
Washing
Validation and Regulatory «non quality» Costs and issues
PharmaCo
Sterilization
Upstream Operations
Filling
More Resources Available
30
Minimizing T.C.O.
Reduction of initial investments on: • Equipment (washing, WFI system, tunnel) • Utilities (WFI, kWh,..) • Workforce • Validation • Maintenance
Increasing Quality
• •
No-glass-to-glass contact during transport Feeding, Washing, Depyrogenating Tunnel are very stressed phases for packaging
•
A unique fill&finish equipment for different packaging: Easy & fast change packaging/format in the same machine (combo line)
Increasing Flexibility
Reducing Time-ToMarket
•
•
Reduction of the time, using Ompi EZ-fill® from research to industrial scale
CostReductionforPharmaCo
Pharmaceuticalneeds
Ompi EZ-fill® | PharmaCo Value
31
OMPI EZ-fill® – Not only a Primary Packaging Primary Packaging
Filling Machinery
Closures & Components
Reduction of complexity for our Customer in each step of the process (from the collection of info to the manufacturingphase)
Engineering Companies
32
Ompi EZ-fill® | What are you Looking for?
High Productivity? Tray for dedicated filling line
Need of flexibility? Nest&Tub for combo line
33
Ompi EZ-fill® | Flexible Filling Machines
machines
machines
2013
2016
All the leading machine manufactuers have presented or are developing flexible machines for filling the full range of sterile containers based on Ompi EZ-fill® platform (from small batches to industrial capacity).
34
Thank You for Your Attention!
www.ompipharma.com
