Upload
hangoc
View
235
Download
0
Embed Size (px)
Citation preview
1 | P HA RMA & B IOT E CH | P ROT E IN T HE RA P E UT ICS MA NUFA CT URING | MAY 20 – 22 , 2015
Container Closure Integrity Testing Practical Aspects and Approaches in the Pharmaceutical IndustryIndustry considerations related to draft USP <1207>
Hanns-Christian Mahler
AAPS NBC
Boston | 16.05.2016
Pharma&Biotech
2 | P HA RMA & B IOT E CH | P ROT E IN T HE RA P E UT ICS MA NUFA CT URING | MAY 20 – 22 , 2015
Forward-Looking Statements
Certain matters discussed in this presentation may constitute forward-looking
statements. These statements are based on current expectations and estimates
of Lonza Group Ltd, although Lonza Group Ltd can give no assurance that these
expectations and estimates will be achieved. Investors are cautioned that all
forward-looking statements involve risks and uncertainty and are qualified in their
entirety. The actual results may differ materially in the future from the forward-
looking statements included in this presentation due to various factors.
Furthermore, except as otherwise required by law, Lonza Group Ltd disclaims any
intention or obligation to update the statements contained in this presentation.
3 | P HA RMA & B IOT E CH | P ROT E IN T HE RA P E UT ICS MA NUFA CT URING | MAY 20 – 22 , 2015
Container Closure Integrity of Parenteral Products
All products labeled as sterile are required to be
free of microbial contamination throughout their
shelf life (obligatory CQA).
Sterility testing alone does not provide assurance
of product sterility.
Container closure integrity (CCI) addresses the
maintenance of integrity to prevent
microbiological ingress in sterile product
packaging until the time of use (product opening).
4 | P HA RMA & B IOT E CH | P ROT E IN T HE RA P E UT ICS MA NUFA CT URING | MAY 20 – 22 , 2015
USP <1207>, Package Integrity Evaluation - Sterile Products. First supplement to USP 39-NF34.
ICH Harmonised Triplicate Guideline Pharmaceutical Development Q8(R2). Current Step 4 version.
ICH Q 5 C: Quality of Biotechnological Products: Stability Testing of Biotechnological/Biological
Products. Part 5.
Annex 1, EU-GMP
Section 11. Media Fill test. Japanese Pharmacopoeia, JPXV.
Section 5.1.1. Methods of Preparation of Sterile Products. European Pharmacopoeia, 8th Edition.
USP<671> Containers – Performance Testing.
FDA Guidance for Industry. Container Closure Systems for Packaging Human Drugs and Biologics,
(Chemistry, Manufacturing, and Controls Documentation). 1999.
FDA Guidance for Industry, Container and Closure System Integrity Testing in Lieu of Sterility Testing
as a Component of the Stability Protocol for Sterile Products. 2008.
Commision Directive 2003/94/EC. Official Journal of the European Union 2003.
Directive 2001/83/EC. Official Journal of the European Union 2001.
Directive 93/42/EEC. Official Journal of the European Union 1993.
World Health Organization, Annex 9: Guidelines on packaging for pharmaceutical products. WHO
Technical Report Series 2002, (902), 121-122.
(Some) Regulatory requirements
5 | P HA RMA & B IOT E CH | P ROT E IN T HE RA P E UT ICS MA NUFA CT URING | MAY 20 – 22 , 2015
Problem statements
There is currently no universally accepted test method nor gold
standard for conducting CCIT.
Worldwide and local regulatory requirements offer no clear
distinction as to what is required for microbiological quality (sterility)
shall be maintained until the end of product shelf life.
Artificial leaks do not necessarily simulate actual defects due to, for
example, irregular shapes and pathways in a CCS. There is also
high variability depending on the method used to create such holes.
Artificial leaks also cannot be easily related to a leak size.
There is a need to correlate microbial contamination and the
physical CCI (pCCI) test method.
Different CCIT methods can serve the same purpose when
appropriately validated.
Local regulations may differ and should be considered as well as
experience within an organization.
Challenges related to CCI, pCCI and CCIT
6 | P HA RMA & B IOT E CH | P ROT E IN T HE RA P E UT ICS MA NUFA CT URING | MAY 20 – 22 , 2015
Main Purpose of the paper
Address common understanding of the application of
container closure integrity testing (CCIT)
Raise awareness throughout the industry of the
complexity of topics when evaluating leaks in
container closure systems (CCS)
Reflect the experiences of the contributing companies
and is not regarded to be exhaustive of the industry
Primary Goal of CCI Industry Expert Paper
7 | P HA RMA & B IOT E CH | P ROT E IN T HE RA P E UT ICS MA NUFA CT URING | MAY 20 – 22 , 2015
The new draft USP <1207>
1207.1 Package Integrity and Test Method Selection.
Package integrity and testing during product life cycle
Package development and validation
Product manufacturing
Commercial Product stability
Test method selection criteria, incl Package Integrity Test Method Leak & Leak Detection Index
Probabilistic vs Determinstic Methods
Test instrument qualification, method development and method validation
1207.2 Package Integrity Leak Test Technologies.
Deterministic and probabilistic method descriptions
1207.3 Package Seal Quality Test Methods
Closure application and removal torque
Package burst test
Package seal strength (Peel test)
Residual seal force
Airborne ultrasound
8 | P HA RMA & B IOT E CH | P ROT E IN T HE RA P E UT ICS MA NUFA CT URING | MAY 20 – 22 , 2015
USP <1207> Package Integrity Test Method Leak Detection Index
Detectable Leaks Expressed in Two Different
Units of Measure
Limit of Detection
Index Classification
Air Leakage
Ratea (stdcm3/s) Orifice Leak Sizeb (µm)
1 <10 6 <0.1
2 10 6 to 10 4 0.1 to 1
3 6 × 10 4 to 4 × 10 3 2 to 5
4 5.0 × 10 3 to 1.6 × 10 2 6 to 10
5 0.017 to 0.360 11 to 50
6 >0.36 >50
?
9 | P HA RMA & B IOT E CH | P ROT E IN T HE RA P E UT ICS MA NUFA CT URING | MAY 20 – 22 , 2015
Container Closure Integrity needs to be ensured and
evaluated across a product lifecycle
Container closure system (CCS) qualification (prior first human use):
Evaluation and transportation and storage conditions
During drug product manufacturing / processing characterization and
validation
Routine drug product manufacture
For Quality Control purposes (release and stability)
… from clinical to commercial
When to test / evaluate CCI ?
10 | P HA RMA & B IOT E CH | P ROT E IN T HE RA P E UT ICS MA NUFA CT URIN G | MAY 20 – 22 , 2015
Deterministic method: A method in which the leakage event being detected, or
measured, is based on phenomena that follow a predictable chain of events. In
addition, the measurement of leak detection is based on physicochemical
technologies that are readily controlled and monitored, yielding objective
quantitative data.
High voltage leak detection (electrical conductivity and capacitance
Laser-based headspace analysis
Helium leak test
Mass extraction, mass flow
Pressure decay
Vacuum decay
Corona discharge testing
Probabilistic method: A method which is the converse of a deterministic leak test
method, being stochastic in nature. Probabilistic tests rely on a series of sequential
and/or simultaneous events, each associated with random outcomes described by
probability distributions. Thus, the findings are associated with uncertainties that
necessitate sufficiently large sample sizes and rigorous test-condition controls to
obtain meaningful results.
Dye ingress (liquid tracer test)
Bubble emission
Microbial immersion or aerosol challenge (mCCI)
CCIT methods – determinstic vs probabilisticaccording USP <1207> and CCIT method examples
11 | P HA RMA & B IOT E CH | P ROT E IN T HE RA P E UT ICS MA NUFA CT URING | MAY 20 – 22 , 2015
Comparison CCIT methodsWuchner et al., PDA J Pharm Sci Technol, in submission
Technique Measuring Principle Advantages (literature, instrument
manufacturer)
Disadvantages (literature,
instrument manufacturer)
Author Experience and Area of Application
High voltage leak
detection
(electrical
conductivity and
capacitance
Deterministic. Based on a quantitative electrical conductance measurements. The
presence of a leak path in the proximity of electrically conductive liquid results in a drop in
test sample electrical resistance, shown as a spike in current above a predetermined
pass/fail threshold.
Non-destructive
Feasible for 100% online testing
Rapid
No sample preparation required
Accuracy not dependent on operator skill
Testing performed under normal atmospheric pressure
Pass/fail result, no quantitative result
Product must be more conductive than the package
Potential for damage to the product (e.g. protein degradation)
The formulation must not be flammable
Ozone generation
Special fixtures are required for a specific CCS
Electrodes must be within a certain distance of leak for detection
Product liquid needs to be in contact or close to the leak
Product clogging could lead to incorrect results
Does not work for lyophilized products
High throughput on commercial production line
Need to assess product quality after exposure to voltage
Limitations for use in long term stability testing due to clogging (drying out) of liquid residues in the voids during prolongedstorage
Risk that conductivity of the drug product is not sufficient to detect a defective syringe
A 100% online module can be integrated with the automated visual inspection
Has limited sensitivity in 100% online testing because only larger leak sizes, i.e. visually leaking cracks, are detected
Limited applicability for cracks in the vial head region under the crimp cap given lack of product liquid contact
Laser-based
headspace
analysis (17-18)
Deterministic. Assessment of package headspace via laser-based analysis techniques
provides a quantitative, non-destructive measure of oxygen, nitrogen, carbon dioxide,
water vapor, or internal pressure in a non-porous, rigid or non-rigid package’s headspace.
A near-infrared diode laser light is passed through the gas headspace region of the
sealed package. Light absorption, measured using frequency-modulated spectroscopy,
is indicative of gas concentration and pressure.
Non-destructive
Quantitative
Feasible for 100% online testing
Rapid measurement
The container must be transparent
Requires modified atmosphere in the headspace
Requires a certain minimum volume of headspace with a certain size window for
detection
Will take an extended period of time to detect small leak size the longer
Change parts need to cover different container sizes and types
Could take weeks of gas exchange to detect micron-sized leaks
Easy to use
Can be used to evaluate transient leaks (e.g. for products stored under cryogenic conditions)
Risk of false results, particularly during stability testing due to gas permeation or absorption of the tracer gas into the l iquid product
phase
Large leaks may not be detectable (e.g. for studies under cryogenic conditions) because of fast equilibration with ambient ai r
Difficult to discriminate between different leak sizes
Difficulties resp inability in detecting leaks located in the liquid solution area, thus, limited applicability for filled syringes or cartridges
Potential for clogging in lyophilisate products
Partial pressure is temperature-dependent
Helium leak test
(14, 19)
Deterministic. Helium-filled or flushed samples are placed in a test chamber, where a
vacuum is created by the instrument’s internal pumps. Fixtures may be required to
isolate particular package areas of interest. Leaking samples allow helium to escape,
enter the test system, and be detected by an analyzer cell. The stream of helium ions
hitting the analyzer cell target is proportional to the partial pressure inside a sample.
Quantitative
Short measurement time needed
Wide range of CCS sizes can be analyzed
A specific leak rate can be calculated
Accurate and reproducible results.
Very sensitive (if flow rate is determined by a mass spectrometer)
American Standard for Materials Testing (ASTM) available
Destructive
Low throughput
Off line use only
Product clogging could lead to incorrect results
Reproducible and easy to use once tooling has been qualified
Cannot be performed on intact product containing packages unless under artificial helium atmosphere (e.g. via bombing), i.e. destructive test
Detection sensitivity to 2 micrometers and possibly below considerable
Can be used for testing samples for frozen drug products/at low temperatures (20-22)
Mass extraction,
mass flow (20-21)
Deterministic. A vacuum is drawn on a sample enclosed in a chamber. Once a vacuum is
established, the instrument monitors the amount of airflow required to sustain a specific
vacuum level. The amount of flow required to keep the vacuum steady is proportional to
the amount of flow escaping from leaks in the sample under test.
Non-destructive
Quantitative
100% testing feasible
Flexible, can be used on liquid and lyophilized samples and plastic
bottles/intravenous (IV) bags
Sensitive
Product clogging could lead to incorrect results Detection sensitivity to two micronmeter leak size is possible
It has long cycle times with large packages
Good repeatability for testing the same packages multiple times
Labeled packaging can induce false positives due to off-gassing; testing unlabeled samples mitigates this potential issue
Pressure decay
(20, 23)
Deterministic. A test package is placed into a custom-designed test chamber that is
subsequently exposed to overpressure. Sensitive pressure transducers monitor changes
in chamber pressure. A pressure drop indicates a leak.
Non-destructive
Feasible for 100% online testing
ASTM method available
Typically only a pass/fail result
Product clogging could lead to incorrect results
Less sensitive than vacuum decay test
High throughput on commercial production line
Vacuum decay (14,
20, 24-25)
Deterministic. A test package is placed into a custom-designed test chamber that is
subsequently exposed to vacuum. Sensitive pressure transducers monitor changes in
chamber pressure. A pressure increase indicates a leak.
Non-destructive
Feasible for 100% online testing
Rapid
No time lapse between manufacture and testing necessary
ASTM method available
Can be used on liquid and lyophilized samples
Can be used on colored CCS’s and labeled samples
Expensive equipment which requires specific instrumentation / tailored test
chambers for each CCS
Product clogging could lead to incorrect results
Vacuum chamber preparation is critical (humidity can impact on measurement
results)
Versatile and can be used on primary and secondary packaging in support of development, manufacturing and stability testing
Suitable for liquid and lyophilized products
Can be used for device testing and for products with labels; however, test sensitivity is reduced compared to unlabeled primary
packaging
Limitations for on-line use, generation of false positive results (e.g. due to potential for air entrapment within a crimped cap or
humidity fluctuations)
Development studies have shown equivalent sensitivity for lyophilized product and liquid filled syringes and vials
Rapid clogging observed for positive controls which contained laser drilled holes in contact with the liquid product (viscosi ty
limitations) or clogging by proteins or silicone oil in pre-filled syringes
Magnitude of pressure change can be correlated with size of leak or leakage rate, however, no distinction between multiple small
leaks or single breach or gap in CCS can be made
Corona discharge
testing (16)
Deterministic. A high voltage frequency electrode is applied to the outside of the sample.
Gas molecules in the sample’s headspace are ionized followed by a Corona discharge
(glow) measured as a current/ discharge pattern.
Non-destructive
100% testing feasible
Rapid
No sample preparation required
Accuracy is not dependent on operators skill
Testing is conducted under ambient atmospheric pressure
Headspace required
CCS has to be closed under a vacuum
There is a threshold for minimum detectable vacuum level
Potential ozone creation, thus potential for damage to the product
Does not work for a CCS closed under atmospheric pressure
Reliable detectable vacuum range is limited
Currently not widely used and a lack of published data specific to CCIT
Bubble emission
(26)
Probabilistic. The test package is submerged into an immersion fluid and inflated by
applying a defined vacuum or an overpressure. Evidence of bubble emission through the
package is considered a failure.
Widely used for decades
ASTM method available
Inexpensive
Convenient and easy to use
Good for flexible packaging
Leak location can be confirmed
Destructive
Pass/fail result, no quantitative result
100% testing is not possible
Easy to train the operator and perform the test. However, the results can depend on operator technique and can take several
minutes per sample.
Limit of detection (LOD) may be too high to assess microbial contamination risk.
Dye ingress (liquid
tracer test) (14, 27-
30)
Probabilistic. In its most common form, a package is placed in a bath of water with a dye
and perhaps surfactant within a test chamber and a set vacuum is drawn on the
package. The method attempts to draw air out of the package cavity. The vacuum is then
released from the test chamber. If the package cavity leaks air the package cavity will
have a reduced pressure drawing dye into the package cavity. Subsequent exposure to
increased pressure can enhance dye penetration if leak is present. An operator (or
instrument) will then inspect the package for any degree of coloration, i.e. dye ingress.
Widely used for decades
ASTM and ISO methods available (31-35)
Industry and regulatory familiarity
Basic and efficient
Flexible, can be used for several different CCS’s (types and size and products)
in same run
The leak location can be specified
The leak can be in the liquid phase
Pass/fail result, no quantitative result
Destructive
100% testing is not possible
The test samples need to be transparent, for visual assessment
In larger volume products ingress of small amounts of tracer liquid may be more
challenging to detect
Detection is probabilistic particularly for small size defects
Versatile and can be used on primary and secondary packaging in support of development, manufacturing and stability testing
Detects directly relevant leaks of concern
Different dyes can be used to tailor the method
Improved sensitivity when optimized vacuum/pressure cycles are used. LOD varies depending on the leak size, materials, dye
concentration and challenge conditions
The tracer liquid must be miscible and not chemically reactive with the product
Correlation to microbial ingress can be established using the same challenge conditions
Has been seen to work well for liquids but depending on the dye it may not be suitable for lyophilized products
Microbial
immersion or
aerosol challenge
(mCCI) (20, 27, 31)
Probabilistic. The sample is filled with sterile nutritive media, then the outside of the
container is challenged with an actively growing motile micro-organism in order to assess
container closure integrity. Any microbes detected in the sample after a defined period of
storage time are classed as a failure.
Widely used for decades
Industry and regulatory familiarity
Readily incorporated into media fill runs
Direct assessment of relevant property (i.e. maintenance of integrity with
respect to microbial contamination)
Destructive
Pass/fail result, no quantitative result
100% testing is not possible
Can take weeks
Labor intensive
Media filled CCS only
Potential for false positives and false negatives; the level of detection is partly
related to operator technique
Detection is probabilistic for small size defects
No harmonization on media and organisms and method specifics
Can be used for offline testing
The LOD varies with leak size, materials, organisms, media and challenge conditions
Historically used to establish a critical leak (rate or size)
The submersion method is more common and easier to set up and more reproducible than the aerosol method
Long term checks over a period of weeks without using vacuum or overpressure can be more representative of actual storage
conditions
Short term checks over a period of hours with applying vacuum and/or overpressure can be more representative of transport
conditions and reduces test time
12 | P HA RMA & B IOT E CH | P ROT E IN T HE RA P E UT ICS MA NUFA CT URIN G | MAY 20 – 22 , 2015
CCIT methods – Some Selection CriteriaWuchner et al., PDA J Pharm Sci Technol, in submission
The intended purpose, e.g. CCS development and qualification,
manufacturing process control or validation, or release or stability testing
Prior knowledge of the CCS, e.g. initial product development with a CCS
vs. further development of a CCS for a new product
The CCS format, e.g. vial, syringe, drug/device combination product, IV bag
The CCS material, e.g. flexible, glass, polymer
The type of product, e.g. liquid vs. lyophilisate, small vs. large molecule,
water-based formulation vs. solvent or oily, conductivity, viscosity, ambient
pressure or vacuum/overpressure
Test duration
The required sensitivity
The type and availability of samples with artificial leaks
The sample size required for a specific study
Teed for sample preparation and potential risks associated with the
sample preparation (e.g. label removal, vials to be emptied and cleaned)
Other (eg in-line, on-line, off-line, test efficacy, costs, test output)
13 | P HA RMA & B IOT E CH | P ROT E IN T HE RA P E UT ICS MA NUFA CT URIN G | MAY 20 – 22 , 2015
Unit container with artificial leaks are required in order to
assess a CCIT method capability to detect a leak and also act
as positive controls
Different methods for artificial leaks considerable, e.g.
• laser drilling into the body of the container
• laser drilling into a metal plate or tubing that is integrated to a CCS
• micron wires inserted at the interface between the closure and
container
• micropipettes (glass) inserted into the stopper or glued into an artificial
hole of the container
• capillaries (fused silica, nickel, glass) inserted into the stopper or glued
into an artificial hole of the container
No gold standard
Each approach has advantages and disadvantages
It cannot be assumed that the Artifical Leaks are somewhat
representive to actual product defects
Artifical Leaks
14 | P HA RMA & B IOT E CH | P ROT E IN T HE RA P E UT ICS MA NUFA CT URIN G | MAY 20 – 22 , 2015
Experience with Artificial LeaksWuchner et al., PDA J Pharm Sci Technol, in submission
Leak Type Advantages Disadvantages Author Experience Micro-pipettes,
0.4 to 5µm (e.g.
glass)
Easy sample preparation Fragile and broken tips may not be easily
detected
Difficult to determine “hole size”
Difficult to handle
Too fragile for routine use
High risk of false sensitivity after preparation of a
positive control
Complete seal around micropipette is required
Silicone oil can cause clogging
Laser-drilled
holes
Nominal leak size >1µm orifice size
Better resembles natural defects in
glass (cracks) and polymer
(pinholes)
State of the art laser drilling
processes result in defined holes
(e.g. holes are drilled with the cold
ablation process, showing fewer
cracked pathways). This new
technique is, however, more
expensive.
Cost
The size of laser-drilled void needs to be
calibrated and represent a defined path
Small holes can clog easily, e.g. silicone oil
or highly viscous liquids, or even lengthen
Holes can increase size in glass materials
from a crack under tension or when
exposed to large temperature changes in a
short period of time
Can get wide a variability in hole size. May
differ according to material and wall
thickness
Holes can be irregular shape
Positive controls cannot be prepared
directly on the product (e.g. for stability
testing purposes)
Non-negligible risk of alteration of void post
manufacture and/or calibration
Requires a specialized external supplier with
shipment or prepared and calibrated units
A small hole (≤ 5 to 10 microns) may not show
product leakage when laser drilled on filled
containers
Holes typically do not increase significantly over
time due to lab-based controls of temperature
May re-use positive control samples, but this
must be verified
Can get wide variability in hole size and may
differ according to material and wall thickness
Drilling and shipment may not be in a clean
environment, so dirt or particulates could impact
the quality of the holes created
The service is offered by few companies
Capillaries (e.g.
Fused silica
capillaries)
Robust
Easy preparation directly at the
testing location
Possibility to prepare positive
controls in a specific packaging
format and for multiple products
(e.g. syringes and lyophilized vial
products)
Can be prepared in a flexible way
(e.g. may contact liquid and
headspace)
The length of the microtube defects is
usually longer than that of typical real life
defects, which may affect the flow pattern
Typically nominal diameters >2µm
available and high uncertainty with respect
to the actual diameter
In regard to flow rate, capillary diameter
and hole diameter are not comparable
Care should be taken if glue is present as
blockage can occur
Dye ingress works well with liquid-filled products
but not so well with lyophilized products
Injection needles are not an adequate substitute
because inner diameter is too wide
Micron wires (e.g.
uncoated copper)
Low cost
Robust
Handling of the micron wires can be
difficult and the size of the void needs to
be calibrated and represent an undefined
path
The holes can close up over time
depending on the relaxation of the
materials (e.g. stopper)
No direct measurement of hole size exists
(37)
Reproducible leak size with defined capping
parameters and wire diameter (37)
Leak size only defined when measured relative to
a physical phenomenon
Need to consider actual copper wire diameter and
elastomer behavior for repeatability
15 | P HA RMA & B IOT E CH | P ROT E IN T HE RA P E UT ICS MA NUFA CT URIN G | MAY 20 – 22 , 2015
Justification is required for the rationale to set acceptance
criteria based on a predictable leak rate and microbial
contamination
Reference and Acceptance Criteria setting of pCCITWuchner et al., PDA J Pharm Sci Technol, in submission
Unit container with artificial leaks are required to assess a CCIT
method capability to detect a leak and also act as positive controls
Different methods for artificial leaks considerable
mCCIT is one way of supporting the establishment of acceptance
criteria for a pCCIT based on experimental data during initial
evaluation of a CCS (correlation of mCCI and pCCI output data)
Or establish the acceptance criteria for a pCCIT is to reference
established literature or company-based studies with comparable
CCSs if a suitable justification is provided
There is no universal way for setting acceptance criteria based on the
probability of microbial ingress
e.g. some companies declare “positive” when 1% and some when 100% of the
samples show ingress in the study.
16 | P HA RMA & B IOT E CH | P ROT E IN T HE RA P E UT ICS MA NUFA CT URIN G | MAY 20 – 22 , 2015
Example: mCCI and pCCI correlationMathaes et al., Impact of Vial Capping on Residual Seal Force and Container Closure Integirty, PDA J, 2016
17 | P HA RMA & B IOT E CH | P ROT E IN T HE RA P E UT ICS MA NUFA CT URIN G | MAY 20 – 22 , 2015
Summary & Conclusions
Ensuring sterility of a parenteral drug product -to the
end of its shelf-life and prior to any human use- is a
regulatory requirement and warrants product safety.
For container closure system (CCS) qualification
During manufacturing
For Quality Control purposes
During storage and shipment up to the end of shelf life.
Current regulatory guidance, which is country specific, provides limited
detail on how to assess CCI.
USP draft <1207> aims to provide extensive and detailed guidance for
CCI assessments
CCI industry experts concluded that there is currently no gold standard
for CCI test methods or generation of artificial leaks, flexibility towards
CCI approaches is required.
Any CCI approach must consider the intended use, product design and phase of
development.
18 | P HA RMA & B IOT E CH | P ROT E IN T HE RA P E UT ICS MA NUFA CT URIN G | MAY 20 – 22 , 2015
Authors & Contributors from CCI industry discussion group
Klaus Wuchner, Rene Spycher, Johnson and Johnson, Schaffhausen, CH
Helen Brown, Alejandra Nieto, Markus Hemminger, Sascha Dreher, Holger Roehl, IngeborgKraemer Pittrof, F. Hoffmann-LaRoche , Basel, CH & Nathalie Yanze, Genentech, SSF, USA
Franz Schmitting, Abbvie, Ludwigshafen, D
James Mellman, Juergen Kossinna , Matthias Schaar, Novartis, Basel & Stein, CH &Lisa Blackwell,
Alcon, USA
Daniel Wagner, Sanofi, Frankfurt, D
Roman Mathaes, Hanns-Christian Mahler, Lonza, Basel, CH
Jörg Zürcher, Bayer, Wuppertal, D
Pierre Guiswe, Boehringer Ingelheim, Biberach, D
Jacques Maring, CSL Behring, CH
Valeria Delia, Merck Serono, Rome, I
Acknowledgments
19 | P HA RMA & B IOT E CH | P ROT E IN T HE RA P E UT ICS MA NUFA CT URIN G | MAY 20 – 22 , 2015
Lonza - Drug Product ServicesSupporting the Development & Manufacture of Your Parenteral Drug Product
Customer Patient
Formulation Development
Analytics & QC
Drug Product
Primary Packaging
Drug Product
Manufacturing
& Processing
Container Closure Integrity
Seal Quality
Extractables/
Leachables
Particles Identification
& Characterization
URL www.lonza.com/DrugProduct | Email [email protected]