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GMP 6 (11 2551)

Packaging material
PIC/S GMP
Any material employed in the packaging of a
medicinal products, excluding any outer
packaging used for transportation or shipment.
Packaging materials are referred to as primary
or secondaryaccording to whether or not they
are intended to be in direct contact with the
product.
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. .
Packaging component
Any single part of a container closure system.
Typical components are
Containers , Container liners
Closures, Closure liners
Stopper overseals, Container inner seals
Administration ports
overwraps
Administration accessories
Container labels
US FDAContainer Closure Systems for Packaging Human Drugs and Biologics
Primary packaging component
Packaging component that is or
may be in direct contact with the
dosage form.
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. .
Secondary packaging component
Packaging component that is not and
will not be in direct contact with the
dosage form.
Container closure system
The sum of packaging componentsthat together
contain and protect the dosage form.
This includes primary packaging components &
secondary packaging components, if the latter are
intended to provide additional protection to the drug
product.
Packaging systemis equivalent to a container
closure system
US FDA Container Closure Systems for Packaging Human Drugs and Biologics
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. .
Containers
A containers for Pharmaceutical use is an article
which holds or is intended to contain and protect
a drug and is or may be in direct contact with it .
The closureis a part of the container.
The container and its closure must not interact
physically or chemically with the substance
within in any way that would alter its quality.
WHO Guidelines on packaging for pharmaceutical products, TRS, No.902, 2002
Containers
General requirements for the permeability of
containers
Well-closed containers
Tightly closed containers
Hermetically closed containers
Light-resistant container
WHO Guidelines on packaging for pharmaceutical products, TRS, No.902, 2002
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. .
Containers (EP)
Single-dose container
Multidosecontainer
Well-closed container
Airtight container
Sealed container
Tamper-proof container
Child-proof container
Containers ( USP31)
Tamper-Evident Packaging
Light-Resistant Container
Well-Closed Container
Tight Container
Hermetic Container
Single-Unit Container
Single-Dose Container
Unit-Dose Containers
Unit-of-Use Containers
Multiple-Unit Containers
Multiple-dose Containers
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Tamper-evident packaging
Having an indicator or barrier to entry which, if
breached or missing, can reasonably be
expected to provide visible evidence to
consumers that tampering has occurred.
Packaging concerns
Depend on
Dosage form
Route of administration
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Examples of Packaging Concerns for Common
Classes of Drug Products
Oral Tablets & Oral
(Hard & Soft
Gelatin) Capsules
Topical Powders;
Oral Powder
Topical Solutions &
Suspensions;
Topical & Lingual Aerosols;
Oral Solutions & Suspension
Low
Ophthalmic Solutions &
Suspension;
Transdermal Ointments &
Patches;
Nasal Aerosol & Sprays
High
Sterile Powders &
Powders for
Injection;
Inhalation Powders
Inhalation Aerosols &
Solutions;
Injection & Injectable
Suspension
Highest
Low Medium High
Likelihood of Packaging Component-Dosage FormInteraction
Degree of Concern
Associated with the
Route of Administration
General consideration of
container closure system
1. Suitability for Intended Use
a) Protection
b) Compatibility
c) Safety
d) Performance
2. Quality Control of Packaging Components
a) Physical Characteristic
b) Chemical Composition
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. .
General consideration of
container closure system
Suitability tests and studies and accepted for
the initial qualification of a component or a
container closure system for its intend use.
Quality control tests typically used and
accepted to established that the components
and container closure system continue to posses
the characteristics established in the suitability
studies
Functionality (improved patient compliance
or use)
Delivery (transfer dose in right amount or
rate)
Container closure system
fuctionality,
drug delivery
Performance
Extraction study (USP Physicochemical
Tests-Plastics), USP ElastomericClosures
for Injections, Toxicological Evaluation, USP
Biological Reactivity and complied with CFR
additives and purity
No leached harmful or
undesirable amounts of
substances to expose patients
treated with drug
Safety
LeachabilityStudy (Migration of chemicals
into drug product) using LC/MS, GC/MS,
ICP/AA, pH, appearance of drug and
container, Thermal analysis (DSC, TGA), IR
Leachableinduced degradation,
absorption or adsorption of drug,
precipitation, changes in pH,
discoloration, brittleness of
packaging materials
Compatibility
USP<661>Light Transmission and Water
Vapor Permeation, Container Integrity
(Microbial ingress, Dye Penetration, Helium
Leak)
Exposure to light, moisture,
microbial ingress, and oxidation
from presence of oxygen
Protection
Proposed Methods Concerns and Interaction Attributes
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Quality control of packaging components
a) Physical Characteristics
Dimensional criteria
Physical parameters critical to the consistent
manufacture of the packaging component
Performance characteristics
b) Chemical Composition
May affect the safety, compatibility,
functional characteristics or protective
properties of a packaging components.
PACKAGING MATERIALS
Glass
Plastics
Metal
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PACKAGING MATERIALS
The choice of primary and/or secondary
packaging materials will depend on
Degree of protection required
Compatibility with the contents
Filling method
Cost
Presentation for OTC drug
Convenience of packaging for user
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GLASS used for pharmaceutical
containers (EP)
Glass containers are classified according to their hydrolytic
resistance
Type I Glass: Neutral glass, with a high hydrolytic
resistant due to the chemical composition of the glass
itself.
Type II Glass: usually of soda-lime-silica glass with a
high hydrolytic resistance resulting from suitable treatment
of the surface.
Type III Glass: Soda-lime glassusually of soda-lime-
silica glass with only moderate hydrolytic resistance.
Glass type & recommendation for used
Type I glass: suitable for most preparations whether
or not for parenteral use.
Type II glass: suitable for most acidic & neutral,
aqueous preparations whether or not for parenteral
use.
Type III glass: general suitable for non-aqueous
preparations for parenteral use, for powders for
parenteral use (except for freeze-dried preparations)
and for preparations not for parenteral use.
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GLASS
Composition
Silica (SiO2) 59-75 %
Calcium oxide (CaO) 5-12 %
Sodium oxide (Na
2
O) 12-17 %
Alumina (Al
2
O
3
) 0.5-3.0 %
Other oxide
Barium oxide (BaO)
Boric oxide (B
2
O
2
)
Potassium oxdie(K
2
O)
Magnesium oxide (MgO)
Glass type & recommendation for used
Except for type I glass containers, glass
containers for pharmaceutical preparation are
not to be re-used
Containers for human blood and blood
components must not be re-used.
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Quality of glass container
Test for hydrolytic resistance
To define the glass type (I, II or III)
To control its hydrolytic resistance
Containers for aqueous parenteral preparations
are tested for arsenic release
Colouredglass containers are tested for spectral
transmission.
Hydrolytic Resistance (EP)
Test A and B or
Test A and C
Type I & Type II glass containers where it is
necessary to determine whether the high
hydrolytic resistance is due to the chemical
composition or to the surface treatment
Test B (glass grains
test) or Test C (etching
test)
Type I glass containers
( to distinguish from Type II and type III glass
container)
Test A
(surface test)
Type I & Type II glass containers
( to distinguish from Type III glass container)
Test to be performed Type of glass container
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Hydrolytic Resistance (EP)
By titration of the extract solutions obtained under
the conditions described for test A, B and C
TEST A : SURFACE TEST(hydrolytic resistance of
the inner surfaces of glass container)
TEST B : GLASS GRAINS TEST(hydrolytic
resistance of glass grains)
TEST C : ETCHING TEST( To determine whether
the containers have been surface-treated)
Limit values in the test for Surface Glass Test
(Test A)
2.2 0.20 Above 500
2.8 0.30 Above 200 and up to 500
3.8 0.40 Above 100 and up to 200
4.8 0.50 Above 50 and up to 100
6.1 0.60 Above 20 and up to 50
8.1 0.80 Above 10 and up to 20
10.2 1.0 Above 5 and up to 10
13.2 1.3 Above 2 and up to 5
17.6 1.8 Above 1 and up to 2
20.0 2.0 Up to 1
Type III Type I and II
Glass containers
Maximum volume of 0.01 M HCl per 100 ml of test liquid (ml)
Filling volme(ml)
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Limits for Glass Grains Test (Test B)
Not more than 8.5 Type II and Type III
Not more than 1.0 Type I
ml of 0.02 MHCl Glass Containers
Chemical Resistance (USP 31)
Powdered Glass Test
Surface Glass Test
Water Attack at 121
o
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Glass
Other factors to be considered in glass container
selection process are
Thermal expansion properties (:- freeze-
drying)
If a product is sensitive to particular ions :-
bariumor calcium
If the glass is to be sterilized by radiation, a
special formulation containing cerium oxide
must be use.
ColouredGlass
Is obtained by the addition of small amounts of
metal oxides, chosen according to the desired
spectral absorbance
Iron and manganese dioxide
Iron oxide, manganese dioxide, chromium dioxide
Cobalt oxide
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Light Transmission
Light resistant container
EP
3.2 Container
Glass Container for Pharmaceutical Test
Spectral Transmission for ColouredGlass
Container
USP
<671> Container Performance Testing
Light Transmission Test
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Light resistant container
Limits
Colouredglass containers for
preparations that are not for parenteral
use does not exeed10 %at any
wavelength in the range of 290 nm to
450 nm, irrespective of the type and the
capacity of the glass container
Limit of spectral transmission for coloured
glass containers for parenteral preparations
25
20
15
13
12
10
50
45
40
35
30
25
Up to 1
Above 1 and up to 2
Above 2 and up to 5
Above 5 and up to 10
Above 10 and up to 20
Above 20
Container with
closure
Flame-sealed
containers
Max. percentage of spectral
transmission at any wavelength
between 290 nm and 450 nm
Filling volume
(ml)
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PLASTICS
A plastic is a material that contains an
essential ingredient one or more
polymeric organic substances of large
molecular weight.
Classification of polymer types
1. Thermosets(Thermosetting plastics)
2. Thermoplastics
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PLASTICS
1. Thermosets(Thermosetting plastics)
Consist of those plastics that, when subjected to
heat, normally will become infusible or insoluble,
and as such cannot be remelted.
2. Thermoplastics
Consist of those plastics that normally are rigid
at operating temperatures but can be remelted
and reprocessed
POLYMER
Homopolymer :
involve one type of monomer
Copolymer :
involve 2 or more monomers of different
chemical substance
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. .
Plastics
Factors responsible for plastics properties
Chemical structure
Molecular weight
Crystallinityand orientation
Cross-linking
Addition of other agents
Plastics
Chemical Structure
Linear polymer chain
Branchedpolymer chain
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Plastics
Molecular weight
Melt flow index (MFI)
Useful factor for characterization of polyolefins
High melt (flow) indicate lower molecular weights & low
melt (flow) indicate high molecular weights.
Increase in MFI is related to :
Ease of moulding
Impact strength (decreases)
Stress cracking resistance (decreaes)
Plastics
Crystallinityand orientation
Crystallinity
Orderly compact structure
of the molecular chain
Polymer chain may
twisted and tangled
formation given an
amorphous type polymer
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Plastics
Orientation
The alignment of crystalline structure in polymeric materials soas to
produce a highly aligned molecular structure.
Materials are stretched just below or above their softening point .
Depending on the degree of orientation, significant changes can
occur in both the physical & chemical properties.
Improving clarity
Reducing to moisture & gas permeation
improvingchemical resistant
Plastics
Cross-linking
Joints between chains which occur in three
dimensions.
Reflected in physical properties, increasing,
for example, polymer rigidity.
Thermoset are cross-link.
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Plastics
Addition of other agents
Antioxidants
Stablizers
Plasticizers
UV absorbers
Antistatics
Dyes or pigments
Lubricants
Etc.
Plastics
Important problems
1. Sorption
2. Desorption(Leaching)
3. Permeation
4. Photodegradation
5. Polymer Modification
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Thermosets
Phenol Formaldehyde
Urea Formaldehyde
Melamine Formaldehyde
Thermosets
These plastics are used when good dimensional
and temperature stability are required.
The formaldehyde plastics have been found the
most used in the pharmaceutical industry as
closures for glass and /or plastics containers.
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Thermosets
Melamine Formaldehyde
Good-to-excellent dimensional stability
When used in the manufacture of closures, high
torque strength and good impact strength.
Good resistance to oils, grease, and many organic
solvent
Phenol Formaldehyde
Good scratch-resistant parts.
Very low shrinkage and low water-absorption
properties
Thermosets
Urea Formaldehyde
Good dimensional stability as well as good strength
properties
Highly rigid and provide good resistance to alcohols,
oils, grease, and some weak acids.
Use for injection-molded heads for collapsible tubes
used to contai liquid-based topical product.
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Thermoplastics
Polyethylene
Polypropylene
Polyethylene Terephthalate(PET)
Polyvinyl chloride
Polyvinylidenechloride
Polystyrene
Polycarbonate
Polyethylene (PE)
Properties vary according to molecular weight and type.
Low density polyethylene (LDPE) branched chain
High density polyethylene(HDPE) linear chain
Linear type is more crystalline, more heat resistant, and
stiffer
As crystallinityand density increase, opacity, stiffness,
tensile strength, surface hardness, and chemical
resistance increase.
Both have low water absorption, high resistant to most
solvents and chemicals and are tasteless and odorless.
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High Density Polyethylene (HDPE)
Is the most crystalline material (~ 95%)
Naturally translucent
HDPE has better moisture- barrier properties and
better tensile strength than LDPE.
HDPE is used widely for bottles of solid dosage form
product.
HDPE is NOT suitable for use with essential oils.
Low Density Polyethylene (LDPE)
Has branched chains and limit crystallinity(60-65%
crystallinity)
More translucent than HDPE
LDPE is used when flexibility is required, for
squeeze bottles of spray and drops, as well as
drum liner for bulk solid drugs.
LDPE is significantly more expensive than HDPE
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HDPE bottles
HDPE bottle which provide
protection from light by using
Titanium dioxide as an
opacifyingagent
Polypropylene (PP)
Lighter, much stiffer and more heat resistant
than HDPE
Same chemical resistance properties as HDPE
Can be sterilized with steam and ethylene oxide,
but not radiation, unless modified PP are used.
Biaxial orientation PP (BOPP) will improve its
clarity.
Used wildly for solid dosage products.
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POLYPROPYLENEPLASTICJARS
Vinyl Plastics
Vinyl group (CH
2
=CH-)
Derivatives
Vinyl chloride (CH
2
=CHCl)
Vinylidenechloride (CH
2
=CCl
2
)
Vinyl acetate (CH
2
=COCOCH
3
)
Many polymers are made either as homopolymer of
themselves or as copolymers with other vinyl
derivatives or other monomer materials.
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Polyvinyl chloride(PVC)
UnplasticisedPVC
Bottle made PVC are naturally clear, have extremely
good resistance to oils, and have very low oxygen
transmission.
PlasticisedPVC
Plasticizer - DEHP (di(2-ethylhexyl)phthalate) is
used most often.
Plasticization also reduces chemical resistant and
increases gas and moisture permeation
Polyvinyl chloride(PVC)
Factors to consider when PVC is uses for
pharmaceutical
Stablizers
Plasticizer
Monomer residue
Modifiers
Lubricants
Catalylicresidue
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UPVC Film
Suppositories package
Polyvinylidenechloride (PVdC)
Trade name Saran
Copolymer of vinyl chloride or vinyl acetate and
vinylidenechloride
Excellent resistance to permeation by moisture
and gas
Most widely used as a coating
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. .
Polyethylene terephthalate(PET)
USP: Polyethylene terephthalate(PET) and Polyethylene
terephthalate(PETG) bottles that are interchangeably suitable for
packaging liquid oral dosage form.
PET resinsare long-chain crystalline polymers prepared by the
condensation of ethylene glycol with dimethyl terephthalateor
terephthalicacid
PET copolymer resinsare prepared in similar way, except that they
may contain a small amount of either isophthalicacid (NMT 3 mole
percent) or 1,4-cyclohexanedimethanol (NMT 5 mole percent)
PET copolymer resins have physical and spectral properties similar
to PET
Polyethylene terephthalate(PET)
PETG resin are high molecular weight polymers
prepared by the condensation of ethylene glycol with
dimethyl terephthalateor terephthalicacid and 15 to 34
mole percent of 1,4-cyclohexanedimethanol. PETG
resins are clear, amorphous polymers.
PET and PETG resinsdo not contain any plasticizers ,
processing aids, or antioxidants. Colorants,if used in the
manuactureof PET and PETG bottles, do not migrate
into the contained liquid.
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PETbottlesandjars
Theyoffera durablecontainerwithexcellentgloss, andthe
clarityandsparkleofglass.
PETplasticbottlesandjarsareresistanttobreakage, have
excellentpropertiesofcarbonationretention, havehighoxygen
barrier, arelighttohandleandtransport,.
ChoosePETjarsforbathsaltsandbottlesforlotionswith
essential oilstokeepinthearoma.
Polystyrene (PS)
PS has relative low heat resistance and is
attacked by a number of chemical agents.
Conventional grade clear
crystal grade, lack of impact
strength.
Impact-modified graded copolymerized with
acrylonitrileand butadiene, poor optical
properties.
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Polycarbonates
PC are formed by condensation of polyphenols
such as bisphenol-A with phosgene.
PC are transparent thermoplastics with high
strength and high temperatures resistance.
Because they are expensive, their use is imited
to specialty application.
Ionomer(Surlyn

)
Are sodium or zinc salts of ethylene/ methacrylic
acid copplymers.
Is used as an inner ply in laminates, offering god
heat sealing (even when the seal area is
contaminated by liquid or powder) over a wide
temperature range.
Are clear , semiflexible, tough materials with good
abrasion resistance.
Valued in sachet and pouch packs.
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Polymonochlorotrifluoroethylene(PCTFE)
Aclar film
Has extremely low transmission of moisture.
Transparent, and can be heat sealed, laminated,
printed, thermoformed, metallized.
Because it is the most expensive plastic used in the
pharmaceutical industry, it is employed only where the
most demanding barrier properties are required.
Laminated Aclar/PVC sheet is used widely in
thermoformed blister pack for moisture-sensitive solid
dosage form.
Polyurethane Foams
Are formed by polymerization in the presence of
a foaming agent.
Used as a replacement for cotton wool in tablet
containers.
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Material Code SystemSymbols
PETE
HDPE
PVC
LDPE
PP
PS
Others
1
2
3
4
5
6
7
Comparison of Polymer Material
G F/G E 4 77 12 1.33 PETE
F F E/G 4.5 105 24 1.27 PETG
E E E 1.85 31 4.4 1.36 OPET
F/G F G/E 0.3 195 68 0.91 OPP
F/G F P 0.3 390 135 0.91 PP
F F E 10 925 234 1.20 PC
F/G F E 8.5 1160 330 1.05 PS
F/G G G 3.0 27 17 1.32 PVC
F/G F/G P 0.3 580 185 0.98 HDPE
F/G F/G P 1.3 2700 300 0.92 LDPE
Chemica
l resist.
Drop
impact
Clarity Water
vapor
CO
2
O
2
Density Material
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. .
DISCLAIMER : This matrix may only be used as an
indication of how different materials relate to each other.
Testing and manufacturing conditions can influence the
properties of the materials and bottles. Preformdesign, mold
and machine maintenance, resin drying time and different
variations of resin can vary the properties drastically.
Density : G/CC
O
2
: CC/100 SQ IN. 24 HR (lower = better)
CO
2
: CC/100 SQ IN. 24 HR (lower = better)
RATING : P = Poor, F = Fair, G = Good, E = Excellent
Sterilization
Steam sterilization at temperature of 121
o
Polypropylene
High density polyehthylene
Polycarbonate
PVC for certain application
All thermosets
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. .
Sterilization
Gas sterilization (Ethylene Oxide)
Cannot be used for containers of aqueous product because
side-reaction products such as ethylene glycol and 2-
chloroethanol are formed.
Ethylene oxide itself is carcinogenic.
Regulatory permissible limit have been established for
residual levels of ethylene oxide. Packaged products are
degassed prior to shipping or use.
Degassing properties depend upon geometry, heat history,
storage conditions, contact with other plastics, and type of
secondary packages used. Because of this complexity,
degassing hold times must be determined for each product.
Sterilization
Irradiation
Can cause degradation or cross-linking of certain
polymers.
Particularly serious for polyprolylene. Although a
radiation stable form of PP has been developed, it
may not suitable for multiple sterilizations.
PVC loses hydrochloric acid upon radiation,
decomposing into unstable fragments, which may
then cross-link. This dehydrochlorinationlead to the
formation of conjugated double bonds, which impart
yellow discoloration.
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Aluminium
Tin
Tinplate
Aluminium
Density of 2.7
Odourless, tasteles, non-toxic and sterilizable
Corrosion
Direct chemical attack
Strong acid and alkaline
Mercurrial compound
Galvanic corrosion
Electrolytes
Halogen : chloride
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Tinplate
Mild or low-carbon steel sheet or strip
which is coated on both sides with pure tin
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BLISTER PACKAGE
2 basic packaging components
A. Forming film
Thermoformed
Cold formed
B. LiddingMaterial
Push-through
Peelable
BLISTER PACKAGE MATERIAL
Main consideration in selecting suitable
material
Degree to which the product needs to be
protected from light, moisture & gas
permeation
Differing cost implication
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. .
BLISTER PACKAGE MATERIAL
Choice of film thicknessaffects both material
cost and barrier properties
Other considerations are
Machineability
production rate
Depth of the blister
Wall thickness and uniformity of the thickness
Sealing properties
BLISTER PACKAGE MATERIAL
Thermoformed Materials
UnplasticizedPVC
Most common material because it is thermoformed easily and
has barrier properties that are adequate for many drugs.
Typical film thickness of 250 m (10 mil)
PVdC-coated PVC
PVC applying a 25 to 50 m coating of PVdCcan increase
the water vapor barrier properties 5- to 10 fold.
Aclar / PVC
15 fold less permeable to moisture than is PVC of
comparable thickness.
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. .
BLISTER PACKAGE MATERIAL
PP
Water- vapor permeability of uncoated PP is lower than PVC,
and is comparable to PVdCcoated PVC
One problem posed by PP processing is thermoforming.The
temperature required for thermoforming PP and the
temperature of subsequent cooling process must be precisely
controlled.
Another problem is warping of package often resulting in
the requirement for PP formed packages to be straightened
before cartoning.
BLISTER PACKAGE MATERIAL
Cyclic Olefin Copolymer (COC)
New high barrier thermoforming film.
Excellent thermoformabilityand moisture barrier properties.
Its tends to be brittle on its own, so it is usually laminates to
PP to withstand forming.
30 PP / 190 COC / 30 PP
30 PP / 300 COC / 30 PP
Can be thermoformed on existing blister lines for PVC,
PVC/PVdC, and ACLAR/PVC
COC is a candidate for a lamination to cold-form foil as a
sealant side because of its ease of forming.
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. .
BLISTER PACKAGE MATERIAL
Cold formed
Laminated of OPA / aluminium/ PVC
OPA = biaxiallyoriented polyamide (nylon)
OPA is use primary for it forming capabilities
Enhance the forming process due to its elasticity
As it stretch, it bring the aluminiumwith it to create the cold form cavity.
Almost entirely eliminate water-vapor permeability.
The cost / m
2
is equivalent to PVdC- coated PVC.
Required more packaging material than thermoformed plastics
for packaging the same number and the same size of tablets or
capsules.
BLISTER PACKAGE MATERIAL
Cold formed
Thermoformed
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. .
BLISTER PACKAGE MATERIAL
25 250 200 PVC / Aclar
100 1000 500 PVC / PVdC
86 6500 3500 PVC
% increase from
blister formation
Blister Sheet
WVTR (mg/m
2
/day at 40
o
C, 80%RH)
Film structure
BLISTER PACKAGE MATERIAL
LiddingMaterial
Push through simple hard or soft aluminium
foil
Aluminiumfoil usually has thickness varies from 18
to 25 m
Heat sealing lacquer must comply with FDA
standard and must precisely match the
respectively forming film.
Peeling off paper / aluminiumlaminate
Child resistance paper /PET / Foil
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. .
Strip Packaging
Produced at lower speeds and occupy greater volume than
blister
Pocket area is critical to
diameter, shape and
thickness of the product
If the pocket is too tight, tearing,
perforation of the pocket periphery
or wrinkling of the seal area may occur.
Strip Packaging Materials
the choice of laminate structure
Technical requirements
Cost of base materials
Cost of lamination processes
Amount of laminate required (quantity)
Yield from which the cost per area of laminate is
derived
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. .
Solid Oral Dosage forms
Fillers, desiccants, andother absorbent material are
considered primary packaging components.
USP monographs for Purified Cotton and Purified
Rayon sufficient standards to established the safety of
these materials
Cotton need not meet the monograph requirements for
sterility, fiber length or absorbency
Rayon need not meet the monograph requirements for fiber
length or absorbency
Rayon has been found to be a potential source of dissolution
problem for gelatin capsules and gelatin-coated tablets.
ElastomericClosures for Injection
Are produced from natural or synthetic substances.
Complex mixture of many ingredients
Basic polymer
Vulcanizing agent
Accelerators
Filler
Pigments
Safety USP ElastomericClosure for Injections testing
49
. .
ElastomericClosures for Injection
Properties are dependent not only upon
those ingredients, but also on processing
procedure:-mixing, milling, dusting agent
used, molding and curing.
Factor such as cleansing procedure,
contacting media, and conditions of storage
may also affect the suitability of an
elastomericclosure for a specific use.
Drug
selection
Preformulation
Drug
stability
Formulation
Dosage
form
design
Dosage
form
selection
Production
Heat Light Moisture Oxygen
Heat Light Moisture Oxygen
Long term
stability
Packaging
Degradation
pathway
Drug
excipient
interaction
Cool Amber Tight Sealed N
2

50
. .
Stability testing
Should be conducted on the dosage form
packaged in the container closure system
proposed for marketing( including, as
appropriate, any secondary packaging and
container label)
Aseanguideline on stability study of drug product
Stability Studies
Ultimate proof of suitability of the
container closure system and the
packaging processes established by
full shelf life stability studies
51
. .
Sampling plan for packaging material
Should take account of at least the following
Quantity received
Quality required
Nature of material (:- primary packaging
materials and/or printed packaging materials)
Production methods
Knowledge of Quality Assurance system of the
packaging materials manufacturer based on
audits.
PIC/GMP ANNEX 8
Sampling plan for packaging material
Efficient inspection does not mean large sample sizes,
and it therefore cost effective (as well as logical) for
sample sizes to be as low as possible, but compatible
with the risk level.
Examples of the factors that quantify sample size are:
Machine performance
New suppliers
Sterile / clean components
Reel fed laminates
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