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© SCHOTT AG, Dr. Folker Steden, Technical Glass Symposium Rio de Janeiro
1st Technical Glass Symposium
9th/10th April 2019, Rio De Janeiro
Agenda
© SCHOTT AG, Dr. Folker Steden, Technical Glass Symposium Rio de Janeiro
1. Glass Basics – A fascinating material
2. Not every Type I glass is the same – How minor differences can impact
3. Dimensional accuracy and cosmetic quality – How a zero-defect philosophy
can support superior container properties
2
Quartz crystall Quartz glass
Glass Composition and Structure
© SCHOTT AG, Dr. Folker Steden, Technical Glass Symposium Rio de Janeiro3
Glass Composition and Structure
Amorphous silica Borosilicate glass Soda lime glass
- 0,24 nm -
Oxygen
Silicon
Boron
Network
formersSodium
Calcium
Network
modifiers
Alkali metals
e.g. Na, K
Alkaline earth metals:
e.g. Ca, Ba, Mg
chemical resistance
- 0,28 nm -
H2O
© SCHOTT AG, Dr. Folker Steden, Technical Glass Symposium Rio de Janeiro4
© SCHOTT AG, Dr. Folker Steden, Technical Glass Symposium Rio de Janeiro
Glass Properties: Viscosity
5
Glass Properties: Thermal ExpansionThe coefficient of thermal expansion (CTE or ) describes how much a material expands when it is
heated.
The smaller the CTE the less it expands
© SCHOTT AG, Dr. Folker Steden, Technical Glass Symposium Rio de Janeiro6
Different types of Type I glasses
© SCHOTT AG, Dr. Folker Steden, Technical Glass Symposium Rio de Janeiro7
Different types of Type I glasses
© SCHOTT AG, Dr. Folker Steden, Technical Glass Symposium Rio de Janeiro8
Glass Properties: Thermal Shock resistanceTemperature resistance depends on both the CTE and the wall thickness.
© SCHOTT AG, Dr. Folker Steden, Technical Glass Symposium Rio de Janeiro
The smaller the CTE the higher the
thermal shock resistance.
The thinner the wall the higher the
thermal shock resistance.
9
Glass Properties: Chemical stabilityChemical stability is the resistance of the glass to chemical attack by defined agents
Water and acid attack cause an ion exchange
Water
+
Acid
OH-
H+ Cl-
Na+
Na+
H+
+
© SCHOTT AG, Dr. Folker Steden, Technical Glass Symposium Rio de Janeiro10
Glass Properties: Chemical stabilityChemical stability is the resistance of the glass to chemical attack by defined agents
Alkali attack causes a dissolution of the network
© SCHOTT AG, Dr. Folker Steden, Technical Glass Symposium Rio de Janeiro11
Hydrolytic ResistanceTwo methods to determine the glass quality – principle
Type III
Type I
© SCHOTT AG, Dr. Folker Steden, Technical Glass Symposium Rio de Janeiro
Depending on the
composition
Performed by Tubing
Also depending on the
converting process
Performed by
converter
Type III
Type I
12
Hydrolytic ResistanceConstant resistance of glass grains due to constant composition
© SCHOTT AG, Dr. Folker Steden, Technical Glass Symposium Rio de Janeiro13
Hydrolytic ResistanceType I and III classification
Type I Type III
Amount of released ions Low High
Hydrolytic Resistance of glass grains High Low
Hydrolytic Resistance of inner surface High Low
Application All, especially parenteral packagingOnly recommended for non-
parenteralia (tablets, sprays, etc.)
Glass Type Borosilicate Glass Soda-Lime Glass
Glass Type SCHOTTFIOLAX®,
BORO-8330TMAR-GLAS®, ILLAX®
© SCHOTT AG, Dr. Folker Steden, Technical Glass Symposium Rio de Janeiro14
Hydrolytic ResistanceType II classification – Ammonium sulfate treatment
Na
Na
Na Ammonium
sulfate
NH4
SO4Na
SO4
Na
NH4
Increasing the hydrolytic resistance of the surface
BUT: compromising the surface integrity and increasing the risk of flake creation
© SCHOTT AG, Dr. Folker Steden, Technical Glass Symposium Rio de Janeiro15
Movie Pharma Glass
© SCHOTT AG, Dr. Folker Steden, Technical Glass Symposium Rio de Janeiro16
Agenda
© SCHOTT AG, Dr. Folker Steden, Technical Glass Symposium Rio de Janeiro
1. Glass Basics – A fascinating material
2. Not every Type I glass is the same – How minor differences can impact
3. Dimensional accuracy and cosmetic quality – How a zero-defect philosophy
can support superior container properties
17
Every Tubing Manufacturer has its own composition
© SCHOTT AG, Dr. Folker Steden, Technical Glass Symposium Rio de Janeiro
SCHOTT
FIOLAX®Corning
51-V
Corning
51-D
Nipro NEG
SiO2 75 72.0 73.0 75 72
B2O3 10.5 11.5 11.2 11.5 11
Al2O3 5 6.8 6.8 6 7
Na2O/K2O 7 8.9 8.0 8 8
MgO/CaO 1.5 0.7 1.0 0.5 1
BaO - - 0.02 1
A change of the tubing supplier automatically implies a change in the glass composition
Small Differences in the composition can have a huge impact
Worst Case: New Elements which are not present in the former glass (e.g. Barium, which is known to
cause precipitation in combination with. E.g. sulfate containing solutions)
18
A change in the glass composition requires prior approval by
FDA
© SCHOTT AG, Dr. Folker Steden, Technical Glass Symposium Rio de Janeiro
A change of the tubing supplier and thus a change in the glass composition is rated as a major change
Thus it requires additional stability studies and approval by FDA prior to the change
Source: FDA Code of Federal Regulations, 21 CFR 314.70
19
Small Differences in Glass Composition can have a Huge
Impact on the Impurity Profile
Comparison of different 5.0 Type I borosilicate glasses
Despite only small differences in compositions multiple levels of extractables
© SCHOTT AG, Dr. Folker Steden, Technical Glass Symposium Rio de Janeiro20
Surface Alkalinitydepends on the converting process
© SCHOTT AG, Dr. Folker Steden, Technical Glass Symposium Rio de Janeiro21
Surface Alkalinitydepends on the converting process
© SCHOTT AG, Dr. Folker Steden, Technical Glass Symposium Rio de Janeiro22
Surface AlkalinityNot every Type I tubing becomes a Type I container
© SCHOTT AG, Dr. Folker Steden, Technical Glass Symposium Rio de Janeiro23
pH shift
© SCHOTT AG, Dr. Folker Steden, Technical Glass Symposium Rio de Janeiro24
pH shift
© SCHOTT AG, Dr. Folker Steden, Technical Glass Symposium Rio de Janeiro
‚high alkalinity converting‘ ´‘low alkalinity converting‘
25
pH shiftWhat can influence the pH value of WFI in e.g. an ampoule?
© SCHOTT AG, Dr. Folker Steden, Technical Glass Symposium Rio de Janeiro26
Extractables & Leachables
Extractables are components of the packaging
material that are released into the solution during a
certain stress procedure (e.g. autoclaving at 121 °C)
Leachables are coming out of the glass under realistic
storage conditions
The composition of a glass gives evidence for
potential extractables
The level of extractables may change during
converting and possible treatments
© SCHOTT AG, Dr. Folker Steden, Technical Glass Symposium Rio de Janeiro27
Extractables & LeachablesInfluencing factors
Glass composition: Type I 5.0 borosilicate glass
Converting process: smooth with low alkalinity
Container size/volume ratio: use container capacity
Rubber components
Drug product: pH value, complexing agents
Storage conditions: the colder the better
© SCHOTT AG, Dr. Folker Steden, Technical Glass Symposium Rio de Janeiro28
Different 10 ml Tubing Vials Type I
60 minutes Autoclaving,
Extraction with water
Different pH values
S.J.Borchert, M.M.Ryan, R.L.Davison, W.Speed;
Journal of Parenteral Science & Technology
1989; 43 (2); 67 - 79:
Accelerated Extractable Studies of Borosilicate
Glass Containers
Extractables & LeachablesInfluence of pH value
© SCHOTT AG, Dr. Folker Steden, Technical Glass Symposium Rio de Janeiro29
Extractables & LeachablesConstant glass composition globally ensures a stable and low extractables profile
Extractables study with FIOLAX® and
converted vials from other tubing suppliers:
2 ml vials were stored at 40°C with WFI,
pH 5.5
Sum of all Extractables was measured by
ICP-OES and ICP-MS
© SCHOTT AG, Dr. Folker Steden, Technical Glass Symposium Rio de Janeiro30
Extractables & LeachablesConstant glass composition globally ensures a stable and low extractables profile
Extractables study with FIOLAX® and
converted vials from other tubing suppliers:
2 ml vials were stored at 40°C with Citric
acid, pH 6.0
Sum of all Extractables was measured by
ICP-OES and ICP-MS
© SCHOTT AG, Dr. Folker Steden, Technical Glass Symposium Rio de Janeiro31
Extractables & LeachablesComparison of 5.0 and 7.0 glass types
0
2
4
6
8
10
12
14
16
18
20
Sum
of
Extr
acta
ble
s m
g/l
FIOLAX® Supplier C Supplier D
1h 121°C WFI
Extractables study with 2 ml vials from two different 7.0 – CTE glasses from the market
© SCHOTT AG, Dr. Folker Steden, Technical Glass Symposium Rio de Janeiro32
0
0,02
0,04
0,06
0,08
0,1
0,12
0,14
7.0 tubingChina
7.0 tubingChina
7.0 tubingChina
FIOLAX® clear5.0 tubing
Usa
ge m
L 0
.01
M H
Cl/
g g
lass
Hydrolytic Resistance acc. to ISO 719
0
0,02
0,04
0,06
0,08
0,1
0,12
7.0 tubingChina
7.0 tubingChina
7.0 tubingChina
FIOLAX® clear5.0 tubing
Usa
ge m
L 0
.02
M H
Cl/
g g
lass
Hydrolytic Resistance acc. to Ph. Eur. / USP
© SCHOTT AG, Dr. Folker Steden, Technical Glass Symposium Rio de Janeiro
Extractables & LeachablesComparison of 5.0 and 7.0 glass types
33
Extractables & LeachablesComparison of 5.0 glass with 7.0 glass
Acc. Leachables study with 2 ml vials from two different 7.0 – CTE glasses from the market
0
10
20
30
40
50
WFI, pH 5.5 Citrate, pH 6 Phosphate, pH 7 Carbonate, pH 8Su
m o
f al
l Ext
ract
able
s [m
g/L]
6 months, 40°C
FIOLAX® Supplier X Supplier Y
© SCHOTT AG, Dr. Folker Steden, Technical Glass Symposium Rio de Janeiro34
Agenda
© SCHOTT AG, Dr. Folker Steden, Technical Glass Symposium Rio de Janeiro
1. Glass Basics – A fascinating material
2. Not every Type I glass is the same – How minor differences can impact
3. Dimensional accuracy and cosmetic quality – How a zero-defect philosophy
can support superior container properties
35
What have been your requirements?
Determined by chemical glass composition
Better hydrolytic resistance of container surface
Delamination free containers
Improved Extractables & Leachables Profile
Determined by Tubing production and therewith
a perfeXionTM topic!
Tighter tolerances for improved container performance
„Zero cosmetical defects“
No inner surface open airlines (CCI)
Tube End Quality
36
Na+
Na+
OH-
OH-
Extractables
Leachables
© SCHOTT AG, Dr. Folker Steden, Technical Glass Symposium Rio de Janeiro36
A Focus on Patient SafetyFrom AQL to Zero Defect
Patient Safety is the most important direction in the pharmaceutical industry
Patient Safety is established by uncompromised quality standards
Uncompromised quality standards are directly connected to 100% controlled
stability and transparency of a production process
Therefore the future standard will be to change from a statistical quality control
concept (AQL) towards a single piece control concept (Zero defect) as it is
established already at the converter and pharma companies
Sand Tubing Convert Filling
AQL
Quality based on
statistical sampling
Zero Defect
ppm
Quality based on
100% measurement
© SCHOTT AG, Dr. Folker Steden, Technical Glass Symposium Rio de Janeiro37
Data Management
Geometry
Glass Defects
Tubing Defects
Outside Diameter, Wall Thickness
Circularity and Straightness
Airlines-, Knot- Stone- Detector
Tube End Inspection
Historical and Quality Database
Tube End Quality
Cross Section Control
perfeXionTMThe Components
© SCHOTT AG, Dr. Folker Steden, Technical Glass Symposium Rio de Janeiro38
© SCHOTT AG, Dr. Folker Steden, Technical Glass Symposium Rio de Janeiro
Glass Tubing Production: Raw Materials
39
© SCHOTT AG, Dr. Folker Steden, Technical Glass Symposium Rio de Janeiro
Glass Tubing Production: Melting
40
© SCHOTT AG, Dr. Folker Steden, Technical Glass Symposium Rio de Janeiro
Glass Tubing Production: Tube Drawing
41
© SCHOTT AG, Dr. Folker Steden, Technical Glass Symposium Rio de Janeiro
Glass Tubing Production: perfeXion®
42
Tube Drawing Single Tube processing Data Processing
dimensional cosmetic dimensional cosmetic
Before
perfeXionTM
100% control of
• Outer diameter
100% control of
• Airlines
• Stones / knots
Statistical measurement of
• Straightness
• Circularity
• Outside diameter
• Square cut
Statistical control of
quality relevant
parameters
Data stored in
disconnected data
management
systems
With
perfeXionTM
100% control of
• Outer diameter
• Inner diameter
• Wall Thickness
• Siding
100% control of
• Airlines –
differentiation
between open and
closed
• Stones / knots
Measurement of each single
tube for
• Straightness
• Circularity
• Outside diameter
• Square cut
Measurement of
each single tube for
• Tube ends
• Particles
• Contamination
Integrated PI
database
collecting all data
from melting to
pallet
Glass Tubing Production: perfeXion®
© SCHOTT AG, Dr. Folker Steden, Technical Glass Symposium Rio de Janeiro43
Benefits at a glance
perfeXionTM is based on figures,
data and facts
perfeXionTM facilitates superior
cosmetic quality
perfeXionTM enables more
precise geometry
Glass Tubing Production: perfeXion®
© SCHOTT AG, Dr. Folker Steden, Technical Glass Symposium Rio de Janeiro44
Customizable inside
diameter tolerances
down to ± 0.05 mm
support dosage
accuracy
Customized perfeXion® Tubing Quality
Zero defect on inside
open airlines enable
high security on
container closure
integrity
Customizable wall
thickness tolerance
down to ± 0.03 mm
support accurate bottom
and neck forming
Narrowed
dimensional
specification supports
consistant opening
break forces
Glass Tubing Production: perfeXion®
© SCHOTT AG, Dr. Folker Steden, Technical Glass Symposium Rio de Janeiro45
0,05mm (50µm) ID API Production (10.60/9.70), 4h production
With perfeXionTM Process Standard
© SCHOTT AG, Dr. Folker Steden, Technical Glass Symposium Rio de Janeiro
Customized perfeXionTM Tubing Quality 100% inside diameter measurement
46
© SCHOTT AG, Dr. Folker Steden, Technical Glass Symposium Rio de Janeiro
Customized perfeXionTM Tubing Quality Cross-Section Measurement and Control
47
© SCHOTT AG, Dr. Folker Steden, Technical Glass Symposium Rio de Janeiro
Customized perfeXionTM videoCross-Section Measurement and Control
48
Timing: The perfeXion™ based tighter tubing quality
specification was made available with publication of the new
SCHOTT Technical Performance Specification (TLB) 2017
Customizing: perfeXion™ in addition to the tightened quality
standard offers the customizing of critical quality parameters
Data Management: SCHOTT has started the dialog with its
industry partners to identify opportunities to materialize the
holistic quality data of the perfeXion™ process. There is more
to come…
49
perfeXionTMTake away Messages
© SCHOTT AG, Dr. Folker Steden, Technical Glass Symposium Rio de Janeiro49
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