Glass Delamination Risks Reality and Regulatories
Glass Delamination Risks Reality and Regulatories
Glass Delamination Risks Reality and Regulatories
Regulatories.
PDA: A Global
Association
Daniele Zuccato
R&D Project Management
Nuova OMPI Stevanato Group
AGENDA
GLASS DELAMINATION
WFI or
Acid
Leaching
H+
Cracking
Glass
Detachment of scales
OH
Glass
flakes
sulfur treatment
siliconization
coating
speed of the transformation process
burners flame temperature
improper annealing stage, tensile stresses
type of glass
Surface
treatments
Conversion
process
Drug
formulation &
posttreatments
ORGANICS ACIDS
OPEN QUESTIONS
AGENDA
SG DELAMINATION STUDY
Investigation of:
Two different Exp 51 glasses provided by different suppliers
Exp 33 (pyrex) glass
Exp 51 sulfur treated glass
Filled with:
0.9% KCl pH 6
0.9% KCl pH 8
Citric and Glutaric acid
Autoclave
Treat.
1h+1h@121C
Exp 33
Glass
Type
E.P. titration
values
Exp 33
0.93
Exp 51/b
Exp 51/b
0.92
Pyrex
Exp 51/a
0.63
Exp 51 Sulfur
treated
0.51
60
50
40
SIO2 ppm
30
Exp 51/a
Sulphur treated
20
10
Exp 51
0
0
2
Extraction number
Glass
Type
E.P.
titration values
Exp51/b
0.92
Exp51/a
0.63
Exp 51 Sulfur
treated
0.51
Exp 51
Treatment
Exp 51/A
Exp 51/B
SiO2
pH
SiO2
pH
1 h121C
16.78 F
8.14
36.36 F
8.54
2 h121C
28.15 F
8.31
49.20 F
8.68
8.56
43.85 F
8.79
8.86
47.06 F
8.71
1 h121C
2 h121C
Sulf. treated
Exp 33
17.20 F
26.76 F
1 h121C
10.56 F
8.54
47.70 F
8.51
2 h121C
19.42 F
8.91
31.87 F
7.97
1 h121C
65.21 F
7.94
140.11 F
8.24
2 h121C
148.76 F
8.11
198.93 F
8.42
CONCLUSIONS
EP titration values are not always reliable indicators of
delamination risk
RESULTS
AGENDA
SG DELAMINATION STUDY
Objective
TEST PROTOCOL
Vial As received
Colorimetric test
Colorimetric test
Colorimetric test
Methylene Blue
Cup as received
COLORIMETRIC TESTING
Exp 51 vial, standard process, sample as received
COLORIMETRIC TESTING
Exp 51 vial, standard process, sample after autoclaving
COLORIMETRIC TESTING
Exp 51 vial, stressed process, sample as received
COLORIMETRIC TESTING
Exp 51 vial, stressed process, samples after autoclaving
Flakes+
SiO2 17.9 ppm
COLORIMETRIC TESTING
Sulfur treated Exp 33 vial , sample as received
COLORIMETRIC TESTING
Sulfur treated Exp 33 vial,after autoclaving
Flakes +++
SiO2 49.6 ppm
CONCLUSIONS
1. Product
development
4.Shelf
life
Freezed
production
conditions +
colorimetric
testing
Raw material
selection and
design
optimization
3.Serial
Production
2.
Sampling
Tuning of
production
parameters +
testing
AGENDA
SYRINGES vs VIALS
DELAMINATION RISK
12 recalls (2010-today)
NO recalls
SYRINGES vs VIALS
Previous studies on a similar transformation process (cartridges)
showed that the contribution of the forming process has a low
impact
Glass Technol.: Eur. J. Glass Sci. Technol. A, December 2011, 52 (6), 203209
SYRINGES vs VIALS
Silica extraction results with 0.9% KCl pH 6.3
Significantly
different SiO2
release from vials
and syringes with
comparable S/V
ratio after multiple
autoclave cycles
SYRINGES vs VIALS
Methylene blue testing
No coloration and
absence of visible
flakes
AGENDA
U.S.P. Guidance
41
Screening Strategies
42
August, 2012
Comment period ended September 31, 2012
Comments received from glass industry and pharmaceutical
companies
USPs Packaging Storage & Distribution Expert Committee is
revising the chapter taking into account the comments received
It is estimated that the revised chapter will be published in the
USP36-NF31 Second Supplement
43
Questions?