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 secondary according to whether or not they
are intended to be in direct contact with the
product.

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1

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 FDA Container 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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2

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 components that 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 system is equivalent to a container
closure system

US FDA Container Closure Systems for Packaging Human Drugs and Biologics

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3

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 closure is 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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4

Containers (EP)

Single-dose container
Multidose container
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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5

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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6

Examples of Packaging Concerns for Common

Classes of Drug Products
Degree of Concern
Associated with the
Route of Administration
Highest

Likelihood of Packaging Component-Dosage Form Interaction

High
Inhalation Aerosols &
Solutions;
Injection & Injectable
Suspension

Medium

Low

Sterile Powders &

Powders for
Injection;
Inhalation Powders

High

Ophthalmic Solutions &

Suspension;
Transdermal Ointments &
Patches;
Nasal Aerosol & Sprays

Low

Topical Solutions &

Topical Powders;
Suspensions;
Oral Powder
Topical & Lingual Aerosols;
Oral Solutions & Suspension

Oral Tablets & Oral

(Hard & Soft
Gelatin) Capsules

General consideration of
container closure system
1. Suitability for Intended Use
a)
b)
c)
d)

Protection
Compatibility
Safety
Performance

2. Quality Control of Packaging Components

a)
b)

Physical Characteristic
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

Attributes

Protection

Compatibility

Safety

Performance

Concerns and Interaction

Proposed Methods

Exposure to light, moisture,

microbial ingress, and oxidation
from presence of oxygen

USP<661>Light Transmission and Water

Vapor Permeation, Container Integrity
(Microbial ingress, Dye Penetration, Helium
Leak)

Leachable induced degradation,

absorption or adsorption of drug,
precipitation, changes in pH,
discoloration, brittleness of
packaging materials

Leachability Study (Migration of chemicals

into drug product) using LC/MS, GC/MS,
ICP/AA, pH, appearance of drug and
container, Thermal analysis (DSC, TGA), IR

No leached harmful or
undesirable amounts of
substances to expose patients
treated with drug

Extraction study (USP Physicochemical

Tests-Plastics), USP Elastomeric Closures
for Injections, Toxicological Evaluation, USP
Biological Reactivity and complied with CFR
additives and purity

Container closure system

fuctionality,
drug delivery

Functionality (improved patient compliance

or use)
Delivery (transfer dose in right amount or
rate)

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Quality control of packaging components

a)

Physical Characteristics

b)

Dimensional criteria
Physical parameters critical to the consistent
manufacture of the packaging component
Performance characteristics

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 glass usually of soda-limesilica 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)
Calcium oxide (CaO)
Sodium oxide (Na2O)
Alumina (Al2O3)
Other oxide

59-75 %
5-12 %
12-17 %
0.5-3.0 %

Barium oxide (BaO)

Boric oxide (B2O2)
Potassium oxdie (K2O)
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
Coloured glass containers are tested for spectral
transmission.

Hydrolytic Resistance (EP)

Type of glass container

Test to be performed

Type I & Type II glass containers

( to distinguish from Type III glass container)

Test A
(surface test)

Type I glass containers

( to distinguish from Type II and type III glass
container)

Test B (glass grains

test) or Test C (etching
test)

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 A and B or
Test A and C

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13

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)
Maximum volume of 0.01 M HCl per 100 ml of test liquid (ml)
Glass containers

Filling volme (ml)

Type I and II

Type III

Up to 1

2.0

20.0

Above 1 and up to 2

1.8

17.6

Above 2 and up to 5

1.3

13.2

Above 5 and up to 10

1.0

10.2

Above 10 and up to 20

0.80

8.1

Above 20 and up to 50

0.60

6.1

Above 50 and up to 100

0.50

4.8

Above 100 and up to 200

0.40

3.8

Above 200 and up to 500

0.30

2.8

Above 500

0.20

2.2

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Limits for Glass Grains Test (Test B)

Glass Containers

ml of 0.02 M HCl

Type I

Not more than 1.0

Type II and Type III

Not more than 8.5

Chemical Resistance (USP 31)

Powdered Glass Test
Surface Glass Test
Water Attack at 121o

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15

Glass

Other factors to be considered in glass container

selection process are
Thermal expansion properties (:- freezedrying)
If a product is sensitive to particular ions :barium or calcium
If the glass is to be sterilized by radiation, a
special formulation containing cerium oxide
must be use.

Coloured Glass

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 Coloured Glass

Container

USP

<671> Container Performance Testing

Light Transmission Test

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Light resistant container

Limits

Coloured glass containers for

preparations that are not for parenteral
use does not exeed 10 % 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

Filling volume
(ml)

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

Max. percentage of spectral

transmission at any wavelength
between 290 nm and 450 nm
Flame-sealed
containers

Container with
closure

50
45
40
35
30
25

25
20
15
13
12
10

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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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20

Plastics
Factors responsible for plastics properties
Chemical structure
Molecular weight
Crystallinity and orientation
Cross-linking
Addition of other agents

Plastics

Chemical Structure

Linear polymer chain

Branched polymer chain

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21

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

Crystallinity and 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 so as 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
improving chemical 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
Polyvinylidene chloride
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 crystallinity and 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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28

HDPE bottles
HDPE bottle which provide
protection from light by using
Titanium dioxide as an
opacifying agent

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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29

POLYPROPYLENE PLASTIC JARS

Vinyl Plastics

Vinyl group (CH2=CH-)

Derivatives
Vinyl chloride (CH2=CHCl)
Vinylidene chloride (CH2=CCl2)
Vinyl acetate (CH2=COCOCH3)
Many polymers are made either as homopolymer of
themselves or as copolymers with other vinyl
derivatives or other monomer materials.

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30

Polyvinyl chloride (PVC)

Unplasticised PVC

Bottle made PVC are naturally clear, have extremely

good resistance to oils, and have very low oxygen
transmission.

Plasticised PVC

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
Catalylic residue

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31

UPVC Film
Suppositories package

Polyvinylidene chloride (PVdC)

Trade name Saran

Copolymer of vinyl chloride or vinyl acetate and
vinylidene chloride
Excellent resistance to permeation by moisture
and gas
Most widely used as a coating

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32

Polyethylene terephthalate (PET)

USP : Polyethylene terephthalate (PET) and Polyethylene

terephthalate (PETG) bottles that are interchangeably suitable for
packaging liquid oral dosage form.
PET resins are long-chain crystalline polymers prepared by the
condensation of ethylene glycol with dimethyl terephthalate or
terephthalic acid
PET copolymer resins are prepared in similar way, except that they
may contain a small amount of either isophthalic acid (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 terephthalate or terephthalic acid and 15 to 34
mole percent of 1,4-cyclohexanedimethanol. PETG
resins are clear, amorphous polymers.
PET and PETG resins do not contain any plasticizers ,
processing aids, or antioxidants. Colorants,if used in the
manuacture of PET and PETG bottles, do not migrate
into the contained liquid.

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PET bottles and jars

They offer a durable container with excellent gloss, and the

clarity and sparkle of glass.
PET plastic bottles and jars are resistant to breakage, have
excellent properties of carbonation retention, have high oxygen
barrier, are light to handle and transport,.
Choose PET jars for bath salts and bottles for lotions with
essential oils to keep in the aroma.

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
acrylonitrile and 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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35

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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36

Material Code System Symbols

PETE

PP

HDPE

PS

PVC

Others

LDPE

Comparison of Polymer Material

Material

Density

O2

CO2

Water
vapor

Clarity

Drop
impact

Chemica
l resist.

LDPE

0.92

300

2700

1.3

F/G

F/G

HDPE

0.98

185

580

0.3

F/G

F/G

PVC

1.32

17

27

3.0

F/G

PS

1.05

330

1160

8.5

F/G

PC

1.20

234

925

10

PP

0.91

135

390

0.3

F/G

OPP

0.91

68

195

0.3

G/E

F/G

OPET

1.36

4.4

31

1.85

PETE

1.33

12

77

F/G

PETG

1.27

24

105

4.5

E/G

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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. Preform design, mold
and machine maintenance, resin drying time and different
variations of resin can vary the properties drastically.

Density : G/CC
O2 : CC/100 SQ IN. 24 HR (lower = better)
CO2 : CC/100 SQ IN. 24 HR (lower = better)
RATING : P = Poor, F = Fair, G = Good, E = Excellent

Sterilization

Steam sterilization at temperature of 121o

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 2chloroethanol 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 dehydrochlorination lead to the
formation of conjugated double bonds, which impart
yellow discoloration.

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39

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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40

Tinplate

Mild or low-carbon steel sheet or strip

which is coated on both sides with pure tin

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41

BLISTER PACKAGE
2 basic packaging components
A. Forming film

Thermoformed

Cold formed
B. Lidding Material
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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42

BLISTER PACKAGE MATERIAL

Choice of film thickness affects 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

Unplasticized PVC

PVdC-coated PVC

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)
PVC applying a 25 to 50 m coating of PVdC can 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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43

BLISTER PACKAGE MATERIAL

PP

Water- vapor permeability of uncoated PP is lower than PVC,

and is comparable to PVdC coated 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 thermoformability and 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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44

BLISTER PACKAGE MATERIAL

Cold formed

Laminated of OPA / aluminium / PVC

OPA = biaxially oriented polyamide (nylon)

OPA is use primary for it forming capabilities

Enhance the forming process due to its elasticity

As it stretch, it bring the aluminium with it to create the cold form cavity.

Almost entirely eliminate water-vapor permeability.

The cost / m2 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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45

BLISTER PACKAGE MATERIAL

WVTR (mg/m2/day at 40oC, 80%RH)
Film structure
Sheet

Blister

% increase from
blister formation

PVC

3500

6500

86

PVC / PVdC

500

1000

100

PVC / Aclar

200

250

25

BLISTER PACKAGE MATERIAL

Lidding Material
Push through simple hard or soft aluminium
foil
Aluminium foil 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 / aluminium laminate

Child resistance paper /PET / Foil

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46

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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47

Solid Oral Dosage forms

Fillers, desiccants, and other 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.

Elastomeric Closures for Injection

Are produced from natural or synthetic substances.

Complex mixture of many ingredients

Basic polymer
Vulcanizing agent
Accelerators
Filler
Pigments

Safety USP Elastomeric Closure for Injections testing

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48

Elastomeric Closures 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
elastomeric closure for a specific use.

Drug
selection

Degradation
pathway

Preformulation

Drug
excipient
interaction

Drug
stability

Heat

Packaging

Formulation
Dosage
form
design
Dosage
form
selection

Light Moisture Oxygen

Cool

Amber

Heat

Light Moisture Oxygen

Tight

Sealed N2

Long term
stability

Production

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49

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)
Asean guideline 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

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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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