Packaging & Storage

of Pharmaceutical
Products
By
Dr. Alaa Zaky Dr. Asmaa Elbakry
Professor of Pharmaceutics Ass. Professor of Pharmaceutics
and Industrial Pharmacy and Industrial Pharmacy
Faculty of Pharmacy Faculty of Pharmacy
Al-Azhar University Al-Azhar University

Second Year
2018-2019
Acknowledgments

This two-year curriculum was developed through a participatory and collaborative approach
between the Academic faculty staff affiliated to Egyptian Universities as Alexandria University, Ain
Shams University, Cairo University , Mansoura University, Al-Azhar University, Tanta University,
Beni Souef University , Port Said University, Suez Canal University and MTI University and the
Ministry of Health and Population(General Directorate of Technical Health Education (THE). The
design of this course draws on rich discussions through workshops. The outcome of the workshop
was course specification with Indented learning outcomes and the course contents, which served as
a guide to the initial design.

We would like to thank Prof.Sabah Al- Sharkawi the General Coordinator of General Directorate
of Technical Health Education, Dr. Azza Dosoky the Head of Central Administration of HR
Development, Dr. Seada Farghly the General Director of THE and all share persons working at
General Administration of the THE for their time and critical feedback during the development of this
course.

Special thanks to the Minister of Health and Population Dr. Hala Zayed and Former Minister
of Health Prof. Ahmed Emad Edin Rady for their decision to recognize and professionalize health
education by issuing a decree to develop and strengthen the technical health education curriculum
for pre-service training within the technical health institutes.
Contents

Course Description V

I. General Introduction of Pharmaceutical Packaging 1

Materials.

II. Types of Packaging Materials 6

III. Quality Assurance of Packaging 18

IV. Good Storage Practice (GSP) 27

V. Practical Part 49

References and Recommended Readings 88

‫حقوق النشر والتأليف لوزارة الصحة والسكان ويحذر بيعه‬

Course Description

Course Specifications

‫ بيانات المقرر‬-1

‫الثانية‬:‫الفرقة‬ ‫التخزين والتغليف‬: ‫اسم المقرر‬ : ‫الرمز الكودى‬

Packaging and storage

‫عملى‬ ‫نظرى‬ : ‫عدد الوحدات الدراسية‬ : ‫التخصص‬

6 3 ‫التصنيع الدوائي‬

The prime objective of this course is to provide

students with the basic information of different
2- Overall Aim of
packaging materials used in pharmaceutical industry.
Course:
This course focuses on aspects of knowledge, skills and
abilities of packaging and storing of different
:‫ هدف المقرر‬-2 pharmaceutical dosage forms according to good storage
practice

3- Intended learning outcomes of the course (ILOs):

‫المستهدف من تدريس المقرر‬- 3

i. Knowledge and By the end of this course, students should be able to:
Understanding:
1. Identify the different Pharmaceutical packaging
materials.
‫ المعلومات‬.‫ا‬ 2. Recognize quality control testing of packaging
materials.
: ‫والمفاهيم‬
3. Understand the basic requirement for good storage
practice.
4. classify different parts in storage area

ii. Intellectual By the end of this course, students should be able to:
Skills:
1. Evaluate Packaging material is regarding as an
‫ المهارات‬-‫ب‬ economical means of providing protection,
presentation, identification, information and
: ‫الذهنية‬
convenience for a pharmaceutical product from
the moment of production until it is used or
administrated.
2. Distinguish between the different parts and
requirement for GSP

V
III. Professional By the end of this course, students should be able to:
Skills:
1. Differentiate between primary, secondary and
‫ المهارات المهنية‬-‫ج‬ tertiary packaging material.
:‫الخاصة بالمقرر‬ 2. Apply GSP in the factories.
3. Practice pharmaceutical terms for different plants
used in unit packaging operation.
4. Use the appropriate machines safely and
effectively.

IV. General and By the end of this course, students should be able to:
Transferable
1. Assess problems.
Skills:
2. Work coherently and successfully as a part of a
‫ المهارات‬-‫د‬
team in pharmaceutical factories.
: ‫العامة‬
3. Practice independent learning by using information
technology tools.

4- Course content 1. General introduction of pharmaceutical packaging

materials
:‫ محتوى المقرر‬-4
2. Packaging testing, Types of packaging materials
(glass, metal and rubbers).
3. Types of packaging materials (plastic , fibrous
material, films, foils and laminates)
4. Foils for Blister Packing, closures types, types of
symbole for package labeling
5. Quality Assurance Aspects of Packaging, Sampling
and testing of packaging materials and Package
validation
6. Quality control tests for packaging materials.
7. General introduction of good storage practices
(GSP)
8. GSP concept and basic requirements.
9. GSP premises and facilities
10. GSP security and safety, Storage procedures and
instructions
11. Stock Rotation and Control, Stock arrangement and
stability of a pharmaceutical product
12. Materials and drugs requiring special storage
conditions

5- Teaching and 1. Lectures.

Learning Methods:
2. Group discussions
‫ أساايب التعليم والتعلم‬-5
3. Practical cessions

VI
6- Teaching and
learning methods for
students with limited
abilities
‫ أساليب التعليم والتعلم‬-6
‫للطالب ذوى القدرات‬
‫المحدودة‬

7- Student Assessment:
: ‫ تقويم الطالب‬-7

a- Assessment methods: a. Class work:

‫ األساليب المستخدمة‬-‫أ‬ 1. Quizzes
2. Midterm theoretical
3. Practical exam
4. Assignments
5. Participation

b. Final exam:
Written theoretical

b- Assessment schedule: a. Class work:

‫ التوقيت‬-‫ب‬ 1. Quizzes:
Quiz I (4th week)
Quiz II (11th week)
2. Midterm theoretical (7th week)
3. Assignments
4. Participation

b. Final exam
Practical exam (13th week)
written theoretical exam (15th week)

C-Weight Of 1. Quizzes and class work (20%), 30 marks

Assessments:
2. Practical (20%), 30 marks.
‫ توزيع الدرجات‬-‫ج‬
3. Final written theoretical exam (60%), 90 marks.
Total percentage 100%

7- List of References:
: ‫ قائمة الكتب الدراسية والمراجع‬-8

VII
a- Course notes: Lecture and practical notes for package and storage
in pharmaceutical industries
‫ مذكرات‬-‫أ‬

b- Essential books (text 1. Ansel, H.C., Popovich, N.G. and Allen, L.V.,
books) editors. Pharmaceutical Dosage Forms and Drug
Delivery Systems, 10th edition. Philadelphia:
‫ كتب ملزمة‬-‫ب‬ Williams & Wilkins. (2014).
2. Aulton's Pharmaceutics: The design and
manufacture of medicine, Micheal Aulton, 4th
Edition, 2013.
3. Packaging of Pharmaceuticals And Healthcare
Products, H. Lockhart and F.A. Paine, Blackie
Academic & Professional, 1996.

c- Recommended books 1. Remington: the science and practice of

pharmacy. London; Philadelphia:
‫ كتب مقترحة‬-‫ج‬ Pharmaceutical Press, 22nd edition (2013).
2. Pharmaceutical production facilities. Design
and applications. Graham C. Cole 2nd edition
(2006)
3. Handbook of pharmaceutical technology.
L.K.Ghosh. CBS Publishers and distributors.
(2006)

d- Periodicals, web  www.pharmamanufacturing.com

sites, ,,,,,
 www.pharmaceutical-technology.com
‫ دوريات علمية أو‬-‫د‬
 www.google.com
‫ الخ‬...... ‫نشرات‬
 www.pubmed.com
 www.biomed.net

VIII
General Introduction

General Introduction of Pharmaceutical

Packaging Materials
Objectives

After reading this chapter, the student will be able to:

1. Know different terms related to the packaging, packaging material, storage
and stability of pharmaceutical product and other related terms.

2. Know the selection criteria for packaging material

3. Recognize the Uses of packaging material

1. Definitions
Packaging
Is the science, art, and technology of enclosing or protecting products for
distribution, storage, sale, and use. Packaging also refers to the process of
design, evaluation, and production of packages.
Packaging may also be defined as the collection of different components
(e.g. bottle, vial, closure, capsules, ampoule, and blister) which surround the
pharmaceutical product from the time of production until its use.
Packaging Material:
Any material used in the packaging of a product. It does not normally include the
outer packaging or transit cases used for departmental transportation or
shipment of orders.
o Primary Packaging Material: A packaging material which is in direct
contact with medicinal product.
o Printed Packaging Material: A packaging material which is imprinted with a
text.
o Finished Product: A medicinal product which has completed all stages of
manufacture, including packaging.
Storage:
The term used to describe the safe keeping of starting materials, packaging
materials, components received semi-finished, in-process and finished products

1
General Introduction

awaiting dispatch. The term is also applied for safe keeping of materials and drug
products in drug stores, pharmacies, hospitals, etc., under the specified
conditions.
Storage Conditions:
The conditions specified for storing the product e.g. temperature, humidity,
container, etc.
Stability:
Stability is the degree of resistance to chemical and physical changes. The
efficacy of the preparation must remain constant (or change only within the
limits specified by legal provisions) until the date of expiration.
a. Chemical Stability: The components making up the preparation should
remain chemically unchanged, that is, their change should be within the
specified limits.
b. Physical stability: The initial physical properties (shape, taste, solubility,
crystalline form, disintegration time, dissolution, colloidal properties, etc.) of
the pharmaceutical preparation should remain unchanged, that is, their
changes should be within the specified limits.
c. Microbiological Stability: Sterility or resistance to the growth of
microorganisms should remain unchanged. During storage, the efficacy of
preservatives should change only within the specified limits.
d. Therapeutic Stability: The therapeutic effect of the pharmaceutical
preparation should remain unchanged.
e. Toxicological Stability: There must be no significant change in the toxicity
of the pharmaceutical preparation.
Expiration Date:
The date placed on the immediate container label of a drug product that
designates the date through which the product is expected to remain within
specifications. If the expiration date includes only a month and a year, it is
expected that the product will meet specifications through the last day of the
month. Kinetically it is the time required for 10% of the material to disappear.
Expiration Dating Period:
The interval of time that a drug product is expected to remain within
specifications as detonated from stability studies on a limited number of batches

2
General Introduction

of the product. The expiration dating period is used to establish the expiration
date of individual batches.
Accelerated Testing:
(Stress Testing): Studies designed to increase the rate of chemical or physical
degradation of a drug substance or drug product by using exaggerated storage
conditions. The purpose is to determine kinetic parameters, if possible, and/or to
predict the tentative expiration dating period.
Shelf-Stability:
The stability of the drug or drug product at ambient room temperature (15 - 35°
C)
Cold Place:
The temperature does not exceed 8° C.
Refrigerator:
The temperature is thermostatically controlled between 2° and 8° C.
Freezer:
The temperature is thermostatically controlled to no higher than -10° C.
Cool Place:
The temperature is between 8° and 15° C.
Warm Place:
Any temperature between 30°and 40°C.
Room Temperature:
The temperature is between 15°and 30°C.

2.Selection criteria for packaging material

There are many factors which need to consider when selecting a suitable type
of pack for the product:
 The product or pack contents
 The application of the product
 Content stability, and the need of protection form any environmental
factors
 Content reactivity (with relevant to the packaging material)
 Acceptability of the pack to the consumer or user
 The packaging process
 Regulatory, legal and quality issues
3
General Introduction

3. Characteristics of packaging material

The material selected must have the following characteristics:
 Must meet tamper-resistance requirements
 Must be FDA approved
 Must be non-toxic
 Must not impart odor/taste to the product
 Must not reactive with the product
They must protect the preparation from environmental conditions

4. Barrier properties of packaging material

Pack barrier capabilities may be critical to the viability of a medicine:
 Moisture ingress can lead to hydrolytic degradation or physical instability;
high humidity territories may warrant extra precautions
 Air ingress can lead to oxidative degradation
 Some products are photolabile and need protection from light
 Bacteria must be excluded from sterile/ sterilized products
 Other biological challenges need to be denied ingress, e.g. insects
 Leaking of liquid products from their pack must be avoided
 The egress of any volatile excipients must be prevented to maintain
integrity of the product

5. Uses of packaging material

a. Physical protection: It protects from, among other things, mechanical
shock, vibration, electrostatic discharge, compression, temperature, etc.
b. Information transmission: Packages and labels communicate how to use,
transport, recycle, or dispose of the package or product. With
pharmaceuticals, food, medical, and chemical products, some types of
information are required by governments.
c. Marketing: The packaging and labels can be used by marketers to encourage
potential buyers to purchase the product.

4
General Introduction

d. Convenience: Packages can have features that add convenience in

distribution, handling, stacking, display, sale, opening, re-closing, use,
dispensing, reuse, recycling, and ease of disposal.
e. Barrier protection: A barrier from oxygen, water vapor, dust, etc., is often
required. Permeation is a critical factor in design. Some packages contain
desiccants or oxygen absorbency to help extend shelf life. Keeping the
contents clean, fresh, sterile and safe for the intended shelf life is a
primary function.
f. Security: Packaging can play an important role in reducing the security risks
of shipment. Packages can be made with improved tamper resistance to
deter tampering and also can have tamper-evident features to help indicate
tampering. Packages can be engineered to help reduce the risks of package
pilferage.

5
Types of Packaging Materials

Types of Packaging Materials

Objectives

After reading this chapter, the student will be able to:

1. Differentiate between primary, secondary and tertiary packaging.

2. Know different types of packaging materials.

3. Recognize the advantage and disadvantages of different type of packaging
materials and its uses.

4. Know different symbols used on packages and labels

Types of packaging
a. Primary packaging is the material that first envelops the product and
holds it. This usually is the smallest unit of distribution or use and is the
package which is in direct contact with the contents. Examples: Ampoules,
Vials, Containers , Dosing dropper, Closures (plastic, metal) Syringe ,Strip
package, Blister packaging.
b. Secondary packaging is outside the primary packaging – perhaps used to
group primary packages together. Example: Paper and boards, Cartons,
Corrugated fibers ,Box
c. Tertiary packaging is used for bulk handling, warehouse storage and
transport shipping. The most common form is a palletized unit load that
packs tightly into containers., Apart from primary and secondary
packaging, two types of special packaging are currently in use, as follows:
Unit-dose packaging: This packaging guarantees safer medication by
reducing medication errors; it is also more practical for the patient. It may
be very useful in improving compliance with treatment and may also be
useful for less stable products.
“Device” packaging: Packaging with the aid of an administration device is
user-friendly and also improves compliance. This type of packaging permits
easier administration by means of devices such as prefilled syringes,
droppers, transdermal delivery systems, pumps and aerosol sprays. Such

6
Types of Packaging Materials

devices ensure that the medicinal product is administered correctly and in

the right amount two types of special

Types of packaging materials

A. Glass
o Glass has been widely used as a drug packaging material.
o Glass is composed of sand, soda ash, limestone, and cullet.
o Si, Al, Na, K, Ca, Mg, Zn & Ba are generally used into preparation of glass
Advantages
o They are hygienic and suitable for sterilization
o They are relatively non-reactive ( depending on the grade chosen)
o It can accept a variety of closures
o They can be used on high speed packaging lines
o They are transparent.
o They have good protection power.
o They can be easily labeled.
Disadvantages
o It is relatively heavy
o Glass is fragile so easily broken.
o Release alkali to aqueous preparation
Types of glasses

Type I (Neutral or Borosilicate Glass)

o Least reactive.
o Higher ingredients and processing cost therefore used for more sensitive
pharmaceutical products such as parenteral or blood products.
o Mostly ampoules and vials are made up of TypeI glass.
Type II (Treated Soda lime glass)
o Higher chemical resistance but not as much as type I.
o Cheaper than Type I.
o Acceptable for most products accept blood products
Type III ( Soda lime glass) and Type IV ( General purpose soda lime glass)
o Have similar composition and are distinguished from each other on the basis
of their hydraulic resistance

7
Types of Packaging Materials

o Type III has average or slight better than average resistance and is suitable
for non- aqueous parenteral and non-parenteral products. Type III glass
containers are normally dry sterilized before being filled.
o Type IV has lowest hydraulic resistance and is suitable for solid products,
some liquids and semisolids and not for parenteral.

Type of formulation can be packed Minimum quality of glass

Package Type that can be used

Ampoule Aqueous Injectables Of Any pH Type I

Aqueous Injectables Of pH Less Than Type II
7

Non-Aqueous Injectable Type III

Vial Aqueous Injectable Of Any pH Type I

Aqueous Injectable Of pH Less Than 7 Type II

Non-Aqueous Injectable Type III

Dry Powders For Parenteral Use (Need
To Be Reconstituted Before Use) Type IV

Bottles and Jars Tablets, Capsules, Oral Solids & Other

Solids For Reconstitution Type IV
Oral Liquids (Solutions, Suspensions,
Emulsions) Type IV
Nasal & Ear Drops Type IV
Certain Types Of External Semisolids
(Rubeficients, Local Irritants) Type IV

Blood & Related Products Type I

Dropper Auxiliary Packaging Device With Type IV
Certain Kind Of Products

Aerosol container Aerosol product (solution, suspension, Type I

emulsion or semisolid type)

8
Types of Packaging Materials

B. METALS
Metal containers are used solely for medicinal products for non-parenteral
administration. Metal is strong, opaque, impermeable to moisture, gases, odors,
light,
bacteria, and shatterproof, it is the ideal packaging material for pressurized
containers.
o It is resistant to high and low temperatures
o They include tubes, packs made from foil or blisters, cans, and aerosol and
gas cylinders.
o Aluminum and stainless steel are the metals of choice for both primary and
secondary packaging for medicinal products.
o Form an excellent tamper evident container.

C. ALUMINIUM
o It is relatively light yet strong
o Barrier to light and chemicals
o Impermeable and easy to work into a variety of formats, depending on its
thickness.
o Thickest aluminum is used for rigid containers such as aerosol cans and
tubes for effervescent tablets.
o Intermediate thickness is when mechanical integrity is still important but
the pack should be capable of being reformed under a reasonable force. E.g.
Collapsible tubes for semi solid preparations or roll on screw caps.
o Thinnest aluminum is used in flexible foil that is usually a component of
laminated packaging material.
Disadvantages and their overcome solution
a. Major disadvantage is its reactivity in raw state, although it rapidly forms a
protective film of aluminum oxide it is still liable to corrosion (when exposed
to some liquids and semi-solid formulations, particularly at extreme pH or if
the product contains electrolytes.
b. To overcome this problem, Aluminum is lined with epoxide, vinyl or phenolic
resins.
c. They are work hardening like collapsible tubes are made by impact extrusion
which tends to make aluminium less flexible.

9
Types of Packaging Materials

d. To overcome, flexibility has to restore by an annealing stage.

D. RUBBERS (Elastomers):
Excellent material for forming seals, used to form closures such as bungs for
vials or in similar applications such as gaskets in aerosol cans.
Categories of Rubbers:
1. Natural rubbers;
Suitable for multiple use closures for injectable products as rubber reseals
after multiple insertion of needle.
Disadvantages are;
a. It doesn't well tolerate multiple autoclaving becoming brittle and leads to
relative degree of extractable material in presence of additives.
b. Risk of product absorbing on or in to a rubber.
c. It has certain degree of moisture & gas permeation.
2. Synthetic rubber:
Have fewer additives and thus fewer extractable and tends to experience less
sorption of product ingredients.
o Are less suitable for repeated insertions of needle because they tend to
fragment or core pushing small particles of the rubber in to the product.
e.g. Silicone, butyl, bromobutyl, chlorobutyl etc.
o Silicone is least reactive but it does experience permeability to moisture
and gas.
o Softer rubbers experience less coring and reseal better, harder rubbers are
easier to process on high speed packaging lines.

E. PLASTICS
According to British standards institutes plastics represents;
a. A wide range of solid composite materials which are largely organic, usually
based upon
b. Synthetic resins or upon modified polymers of natural origin and possessing
appreciable mechanical strength. At a suitable stage in their manufacturing,
most plastics can be cast, molded or polymerized directly into shape‖.

10
Types of Packaging Materials

Classes of plastics:

There are two classes of plastics, reflecting the behavior with respect to
individual or repeated exposure to heating and cooling.
1. Thermoplastics
Capable of being shaped after initial heating and solidifying by cooling.
Resistant to breakage and cheap to produce and providing the right plastics are
chosen will provide the necessary protection of the product in an attractive
containers. E.g. Polystyrene, polyethylene and polyvinyl chloride.
2. Thermosets
They need heat for processing into a permanent shape. During heating such
materials form permanent crosslinks between the linear chains, resulting in
solidification and loss of plastic flow. E.g. Phenolic, urea and melamine are
representative of thermosets.
Uses
Used for many types of pack including; rigid bottles for tablets and capsules,
squeezable bottles for eye drops and nasal sprays, jars, flexible tubes and strip
and blister packs.
Advantages
o Least expensive than glasses
o Ease of transportation
o No risk of breakage
o Flexible
o Light in weight
Disadvantages
o They are not as chemically inert as Type -I glass.
o They are not as impermeable to gas and vapour as glass.
o They may possess an electrostatic charge which will attract particles.

TYPES OF PLASTICS

1. POLYETHYLENE
This is used as high and low density polyethylene.
o Low density polyethylene (LDPE) is preferred plastic for squeeze bottles.

11
Types of Packaging Materials

o Ease of processing, barrier to moisture, strength /toughness, flexibility,

ease of sealing.
o High density poly ethylene (HDPE) is less permeable to gases and more
resistant to oils, chemicals and solvents.
o Properties: Stiffness, strength / toughness, resistance to chemicals. It is
widely used in bottles for solid dosage forms.
o Drawback: prone to stress cracking in the presence of surfactants or
vegetable or mineral oils.
2. POLYPROPYLENE
o It has good resistance to cracking when flexed.
o Good resistance to heat sterilization.
o It is colorless, odorless thermoplastic material with excellent tensile
properties even at high temperature.
o Excellent resistance to strong acids and alkalis.
o Low permeability to water vapour
o Permeability to gases is intermediate between polyethylene HD and un-
plasticized PVC
o Suitable for use in closures, tablet containers and intravenous bottles.
3. POLYSTYRENE
o Versatility, insulation, clarity, easily foamed (―Styrofoam‖).
o It is also used for jars for ointments and creams with low water content.
Drawback: Chemicals like isopropyl myristate produce crazing (a fine network
of surface cracks) followed by weakening and eventually collapsible of the
container.
4. POLYVINYL CHLORIDE
o Versatility, ease of blending, strength / toughness, resistance to grease/oil,
resistance to chemicals, clarity.
o Used as rigid packaging material and main component of intravenous bags.
Drawback: Poor impact resistance which can be improved by adding elastomers
to the plastics but it will increase its permeability.

5. POLY VINYLEDENE CHLORIDE:

o Excellent barrier properties against: moisture, water vapour, UV light,

aroma, inorganic acids, alkalies, aqueous salt solutions, organic water

12
Types of Packaging Materials

soluble acids, aliphatic hydrocarbons , esters of long chain fatty acids,

detergent base materials, emulsifying agents and wetting agents.
o Good thermoform ability.
o PVDC is very cost-effective, as coating weight can be customized depending
on the requirements of the barrier properties.
o Medical grade and non-toxic.
o High levels of transparency which improves the aesthetics of the product.
Examples of plastics

Plastic bottles made from PP, HDPE and Plastic pouches of

HDPE

F. FIBROUS MATERIALS
o The fibrous materials are the important part of pharmaceutical packaging.
o Fibrous materials include: Papers, Labels, Cartons, Bags, Outers, Trays for
Shrink Wraps, Layer Boards On Pallets, etc.
The Applications as well as Advantages of Cartons include:
o Increases display area Provides better stacking for display of stock items
o Assembles leaflets
o Provides physical protection especially to items like metal collapsible tubes
o Fiberboard outers either as solid or corrugated board also find substantial
application for bulk shipments.
o Regenerated cellulose film, trade names Cellophane and Rayophane, is use
for either individual cartons or to assemble a number of cartons.

13
Types of Packaging Materials

Paper Corrugated Fiber board

G. FILMS, FOILS and LAMINATES

Regenerated cellulose film based on viscose ( chemical used for

manufacturing of rayon) and laminating two or more types of films, cellulose
coatings, foil and paper play diff roles such as supportive, barrier, heat seal &
decorative.
For Example: Aluminum foil even in the thinnest gauges offers the best barrier
properties, which are not approached even by the most impermeable plastics.
o „Metallization‟: A relatively new process whereby particles of metal are
laid down onto a surface under vacuum, can significantly improve the
barrier properties of a material but these do not approach the properties of
a pure foil.
o In the newer technology „Co-Extrusion‟, a number of plastic plies are
extruded in combination to produce cheaper laminations.
Uses of films, foils, laminations:
o Strip packs
o Blister packs
o Sachets
o Diaphragm seals for bottles
o Liners for boxes either attached or loose bag-in-box systems & bags.
a. Foil blisters:
When sealed with a metal foil-cover, the blister can provide a hermetic pack
i.e. an isolated system, which excludes any exchange of gases between the
product & surrounding atmosphere.
b. Alu-alu foil
The best pharmaceutical packaging film used for tablets, capsules, which is
taking place of PVC film.

14
Types of Packaging Materials

Characteristics:
o Applicable to tablets, capsules, pills, etc.
o It's a good substitute for PVC sheet.
o No cracking, delamination or pinholes
o It has the quite good blocking properties effectively protecting drugs from
water vapor, oxygen and ultraviolet.
o It can extend the storage period of drugs.
o It is particularly suitable for packing moisture-sensitive drugs or those sold in
the hot and humid areas.
o Taking out a part of the drugs from the drug boards without any impact on
other well-packaged drugs.
o It is used by cold-molding packaging machines.
o It is shaped easily by changing the mold.
o Nice appearance can upgrade drug's image
c. BLISTER PACK
Blister packs are commonly used as unit dose packaging for pharmaceutical
tablets, capsules or lozenges
o Blister packs consist of two principal components : 1) a formed base web
creating the cavity inside which the product fits and 2) the lidding foil for
dispensing the product out of the pack.
o There are two types of forming the cavity into a base web sheet:
thermoforming and cold forming.
Thermoforming
o In the case of thermoforming, a plastic film or sheet is unwound from the
reel and guided though a pre-heating station on the blister line
o The temperature of the pre-heating plates (upper and lower plates) is such
that the plastic will soften and become moldable.

Cold forming
o In the case of cold forming, an aluminum-based laminate film is simply
pressed into a mold by means of a stamp.

15
Types of Packaging Materials

o The aluminum will be elongated and maintain the formed shape.

Advantage of cold form foil blisters is that the use of aluminum is offering a
near complete barrier for water and oxygen, allowing an extended product
expiry date.
Disadvantages of cold form foil blisters are the slower speed of production
compared to thermoforming and the lack of transparency of the package and
the larger size of the blister card

d. Aluminium Foils for Blister Packing

Aluminium Foil suitable for blister packing of Pharmaceutical Products such as
Tablet, Capsules, etc.

H. STRIP PACKING

o It is commonly used for the packaging of tablets and capsules. A strip

package is formed by feeding two webs of a heat sealable flexible film
through a heated crimping roller .The product is dropped into the pocket
formed before forming the final set of seals. A continuous strip of packets
is formed which is cut to the desired number of packets in length.
o The materials used for strip package are cellophane, polyester,
polyethylene, polypropylene, polyvinylchloride.

I. CLOSURES

16
Types of Packaging Materials

Closures are the devices by means of which containers can be opened and
closed.
Proper closing of the container is necessary because
o It prevents loss of material by spilling or volatilization.
o It avoids contamination of the product from dirt, microorganisms or insects.
o It prevents deterioration of the product from the effect of the environment
such as moisture, oxygen or carbon dioxide.

Material used for closures are;

The closures for containers meant for storage of pharmaceutical products are
generally made from the following basic materials.
1. Cork
2. Glass
3. Plastic
4. Metal
5. Rubber

SYMBOLS USED ON PACKAGES AND LABELS

Many types of symbols for package labeling are nationally and internationally
standardized. For product certifications, trademarks, proof of purchase, etc.
identification code.

Fragile This way up Keep away from

sunlight

17
Quality Assurance of Packaging

Quality Assurance of Packaging

Objectives

After reading this chapter, the student will be able to:

1. Recognize the aspect of quality assurance for packaging.

2. Know different quality control tests for glasses.

3. Know different tests for plastics containers.

Quality Assurance Aspects of Packaging

To ensure that patients and consumers receive high-quality drugs, the quality
management system must take the following considerations into account if the
required quality of packaging is to be obtained:
a. The requirements of the national authorities and the relevant legislation
b. The product
c. The production process
d. The manufacturers’ internal policies (safety, marketing, etc.).
Bad packaging which is the result of deficiencies in the quality assurance system
for packaging can have serious consequences, and packaging defects can create
problems that may result in drug recalls. Such defects may include breakage, and
problems relating to printing or inks, or errors on labels and package inserts
(patient information leaflets). The use of GMP and quality control will prevent
the release of a defective medicinal product.
Packaging processes and equipment need validation/qualification in the same
way as any other part of processing within a pharmaceutical facility.
Sampling and testing of packaging materials
Sampling
Sampling is used;
o To check the correctness of the label, packaging material or container
reference, as well as in the acceptance of consignments,

18
Quality Assurance of Packaging

o Detecting adulteration of the medicinal product, obtaining a sample for

retention, etc.
o The sampling procedure must take into account the homogeneity and
uniformity of the material so as to ensure that the sample is representative of
the entire batch.
o The sampling procedure should be described in a written protocol.
Testing program

Quality control tests are intended to check the identity of the material
concerned. Complete pharmacopoeial or analogous testing may also be carried
out, as may special tests, where necessary. All written specifications for
packaging materials and containers should include the nature, extent and
frequency of routine tests. Routine tests vary according to the type of material
and its immediate packaging, the use of the product, and the route of
administration. Nevertheless, such tests usually include the following:
o visual inspection (cleanliness, defects)
o tests to identify the material
o dimensional tests
o physical tests
o chemical tests
o microbiological tests

QUALITY CONTROL AND TESTING STANDARDS

It is to first determine which batch is for testing purposes.

o The basic testing system is the same for both the components, primary and
secondary.
o Although component compatibility and chemical testing are required, in
addition for primary components.

SETTING THE STANDARDS

1. Appearance
o Critical: Unacceptable at any level, eg; rogue printed items in a delivery ,
incorrect printing of data such as the product name or concentration , insects
in the bottles, etc.
19
Quality Assurance of Packaging

o Major: Acceptable at low level; standard is decided by the pharmaceutical

company. Very easy to ask for perfection if not possible so a reasonable
compromise has to be reached. Two type standards will result in a supplier
not supplying because the standard cannot be met or a 100% inspection of
each consignment received by the pharmaceutical company. Too low standard
– excessive complaint from market loss of company image and orders.
o Minor: acceptable at higher level than the major appearance defect this will
detract from perfection and include marked components, slight color
variation, etc.
2. Dimensions
o Critical: requiring close control to insure that the components functions
correctly and can be used satisfactorily by the packaging equipment.
o Non critical: necessary to maintain the component shape but not requiring
close control e.g a vial containing injectable product. Components are
brought together by filling machine to give sterility to seal, rubber plug and
aluminium overseal Compatibility and Customer usability.
o Measuring component :
It is possible to accurately measure component without trained staff and
variety of measuring equipment such as callipers, micrometer etc. the
variety and types of equipment used are determined by materials to be
measured.
a. Measuring techniques: Even when measuring something simple with a
micrometer, such as thickness of a sheet of metal, it is possible to
measure it incorrectly due either to not using the ratchet or using the
ratchet incorrectly.
b. Precision and accuracy: Firstly a set of recently calibrated gauging blocks
are required, together with a certificate of calibration. The gauging blocks
must cover the full measuring range of the equipment and must be
periodically recalibrated at a frequency to be determined by the
frequency of use.
3. Compatibility and customer usability
This involves checking that each component forming a pack fits together
and functions correctly.
o Consider an eye dropper pack as an example.

20
Quality Assurance of Packaging

o The nozzle must have a interference fit in the bottle and allow 1 drop at
a time delivery through the hole in the nozzle when inverted, but not
leak from the fitted position.
o The cap must screw into position and leakage must not occur when the
bottle is squeezed in the inveted position.

4. Chemical testing
The majority of chemical testing is required on primary component.
The type of testing required depends on the type of component used.
a. Glass vials and ampules: The USPXXII requirements for glass containers are
chemical resistance and light transmission. The requirements vary from
country to country.
b. Plastic primary components: The testing is more extensive with plastic
components, requiring both biological and physicochemical test. This is
because the plastic components contain other substance such as
plasticizers , stabilizers, antioxidants, pigment, lubricants ,etc.
c. water attack Test
This test is used only with containers that have been exposed to sulphur
dioxide fumes under controlled humidity conditions. Such a treatment
neutralizes the surface alkali. Now the glass becomes chemically more
resistant. The principle involved in the water attack test is to determine
whether the alkali leached form the surface of a container is within the
specified limits or not. Since the inner surface is under test entire
container (ampoule) has to be used. The amount of acid that is necessary
to neutralize the released alkali from the surface is estimated, the
leaching of alkali is accelerated using elevated temperature for a specified
time. Methyl red indicator is used to determine the end point. The basic is
acid-base titration.

21
Quality Assurance of Packaging

QUALITY CONTROL TESTS FOR GLASSES

1. CHEMICAL RESISTANT OF GLASS CONTAINERS
a. Powdered Glass Test:
It is done to estimate the amount of alkali leached from the powdered glass
which
Usually happens at the elevated temperatures. When the glass is powdered,
leaching of alkali is enhanced, which can be titrated with 0.02N sulphuric acid
using methyl red as an indicator
Step-1: Preparation of glass specimen: Few containers are rinsed thoroughly
with purified water and dried with stream of clean air. Grind the containers in
a mortar to a fine powder and pass through sieve no.20 and 50.
Step-2: Washing the specimen:
10gm of the above specimen is taken into 250 ml conical flask and wash it
with 30
Ml acetone. Repeat the washing, decant the acetone and dried after which it
is used within 48hr.
Procedure:
10gm sample is added with 50ml of high purity water in a 250ml flask. Place it
in an autoclave at 121⁰C±2⁰C for 30min.Cool it under running water. Decant
the solution into another flask, wash again with 15ml high purity water and
again decant.Titrate immediately with 0.02N sulphuric acid using methyl red
as an indicator and record the volume
b. Water Attack Test:
This is only for treated soda lime glass containers under the controlled
humidity conditions which neutralize the surface alkali and glass will become
chemically more resistant. Principle involved is whether the alkali leached or
not from the surface of the container.
Procedure:
o Rinse thoroughly with high purity water.
o Fill each container to 90% of its overflow capacity with water and is
autoclaved at 121⁰C for 30min then it is cooled and the liquid is decanted
which is titrated with 0.02N sulphuric acid using methyl red as an
indicator.

22
Quality Assurance of Packaging

o The volume of sulfuric acid consumed is the measure of the amount of

alkaline oxides present in the glass containers.

TESTS CONTAINER VOL.OF 0.02N

H2SO4
Powdered glass test Type I 1.0
Type II 8.5
Type III 15.0
Water attack test Type II (100ml or below) 0.7
Type II (above 100ml) 0.2

2. Hydrolytic Resistance of Glass Containers:

Rinse each container at least 3times with distilled water and fill with the
same to their filling volume. Heat to 100⁰C for 10min and allow the steam to
issue from the vent cork. Rise the temp from 100⁰C to 121⁰C over 20min.
Maintain the temp at 121⁰C to 122⁰C for 60min. Lower the temp from 121⁰C
to 100C over 40min venting to prevent vacuum.
Remove the container from autoclave, cool and combine the liquids being
examined. Measure the volume of test solution into a conical flask and titrate
with 0.01M HCl using methyl red as an indicator. Perform blank with water
and the difference between the titration represents the volume of HCl
consumed by the test solution.

Nominal Number of Volume of test

Capacity Of containers solution to be
container (ml) to be used used for titration
(ml)
5 or less at least 10 50
6 to 30 at least 5 50.0
More than 30 at least at least 3 100.0

3. Thermal Shock Test:

Place the samples in upright position in a tray. Immerse the tray into a hot
water for a given time and transfers to cold water bath, temp of both are
closely controlled. Examine cracks or breaks before and after the test. The
amount of thermal shock a bottle can withstand depends on its size and
design. Small bottles withstand a temp differential of 60 to 80⁰C and large

23
Quality Assurance of Packaging

bottle 30 to 40⁰C. A typical test uses 45C temp difference between hot and
cold water.
4. Leakage Test:
Fill 10 containers with water, fit with intended closures and keep them
inverted at room temperature for 24hr.The test is said to be passed if there
is no signs of leakage from any container.

5. Internal bursting pressure test

The most common instrument used is American glass research increment
pressure tester .The test bottle is filled with water and placed inside the test
chamber. A scaling head is applied and the internal pressure automatically
raised by a series of increments each of which is held for a set of time. The
bottle can be checked to a preselected pressure level and the test continues
until the container finally bursts.

Test for plastics containers

1. For non-injectable preparations
Collapsibility test:
Applicable to containers which are to be squeezed in order to remove
contents. yield 90%of its contents at required rate of flow at ambient
temperature.
Clarity of aqueous extract:
Clarity of aqueous extract Select unlabeled portion from a suitable containers
Cut these portions into strips Wash it with extraneous matter by shaking with
two separate portions of distilled water Transfer to flask – previously washed
with chromic acid Rinse with distilled water add 250ml d.w. Cover the flask
autoclave at 121Ċ, 30min Colorless , free from turbidity
Non-volatile residue
Evaporate 100 ml of the extract obtained in the test for Clarity of aqueous
extract to dryness and dry to constant weight at 105º. The residue weighs not
more than 12.5 mg.
2. For injectable preparations
o Leakage test, Collapsibility test Same As Describe in Non- Injectable

24
Quality Assurance of Packaging

o Clarity and colour of solution

o Acidity or alkalinity
o Light absorption
o Reducing substances
o Transparency
Solution Test
Fill a container to its nominal capacity with water and close it, if possible using
the usual means of closure; otherwise close using a sheet of pure aluminium.
Heat in an autoclave so that a temperature of 121 ± 2º is reached within 20 to
30 minutes and maintain at this temperature for 30 minutes. If heating at 121º
leads to deterioration of the container, heat at 100º for 2 hours.
1. Blank.
Prepare a blank by heating water in a borosilicate glass flask closed by a sheet
of pure aluminum at the temperature and for the time used for the
preparation of solution S.
2. Clarity and color of solution S. Solution S is clear and is colorless.
3. Acidity or alkalinity. To a volume of solution S corresponding to 4 per cent
of the nominal capacity of the container add 0.1 ml of phenolphthalein
solution. The solution is colorless. Add 0.4 ml of 0.01M sodium hydroxide.
The solution is pink. Add 0.8 ml of 0.01M hydrochloric acid and 0.1 ml of
methyl red solution. The solution is
4. Light absorption.
The light absorption in the range 230 nm to 360 nm of solution S using a
blank prepared as described under Solution S is not more than 0.20.
5. Reducing substances.
To 20.0 ml of solution S add 1 ml of dilute sulphuric acid and 20.0 ml of
0.002M potassium permanganate. Boil for 3 minutes. Cool immediately. Add
1 g of potassium iodide and titrate immediately with 0.01M sodium
thiosulphate, using 0.25ml of starch solution as indicator. Carry out a
titration using 20.0 ml of the blank prepared as described under Solution S.
The difference between the titration volumes is not more than 1.5 ml.
6. Transparency
Fill the container previously used for the preparation of solution S to its
nominal capacity with a 1 in 200 dilution of the standard suspension for a

25
Quality Assurance of Packaging

container made from polyethylene or polypropylene. For containers of

other materials, use a 1 in 400 dilution. The cloudiness of the suspension is
perceptible when viewed through the container and compared with a
similar container filled with water orange-red or red.
7. Water vapor permeability
o Fill 5 containers with nominal volume of water and heat seal the bottles
with aluminum foil.
o Weigh accurately each container and allow to stand for 14 days humidity-
60±5%
Temperature. 20 0Ċ and 25 0Ċ.
o Reweigh the containers.
o Loss in weight in each container is NMT 0.2%

26
Good Storage Practice

Good Storage Practice (GSP)

Objectives

After reading this chapter, the student will be able to:

1. Know the concept and basic requirements of GSP.

2. Know the basic requirement for facilities and premises utilized for storage
purposes

3. Recognize the importance of security and safety in different storage areas.

4. Know the storage procedures and instructions required for storage of

different pharmaceutical products.

5. Know stock arrangement rotation and control.

General introduction of good storage practice (GSP)

This GSP is intended for those involved in the storage, transportation and
distribution of pharmaceuticals. It is closely linked to other existing guides
recommended by the WHO Expert Committee on Specifications for
Pharmaceutical Preparations, such as:
o Good trade and distribution practice (GTDP) of pharmaceutical starting
materials
o The stability testing of pharmaceutical products containing well-established
drug substances in conventional dosage forms (information given in
connection with regulation for marketing authorization)
o Good manufacturing practices (GMP)
o The cold chain, especially for vaccines and biologicals;
The objective of the GSP is to describing the special measures considered
appropriate for the storage and transportation of pharmaceuticals. However,
they may be adapted to meet individual needs where necessary, provided that

27
Good Storage Practice

the desired standards of quality are still achieved. The GSP are applicable not
only to manufacturers of medicinal products but also to pharmaceutical
importers, contractors and wholesalers, and community and hospital pharmacies.
They should be adjusted in line with the type of activity where the storage of
pharmaceuticals is taking place. National or regional regulations should be
followed for all related activities.

I. GLOSSARY
The definitions given below of some of the terms used in this chapter take into
account the terminology of current regulations and recommendations.
Active pharmaceutical ingredient (API)
Any substance or mixture of substances intended to be used in the manufacture
of a pharmaceutical dosage form and that, when used in the production of a
drug, becomes an active ingredient of that drug. Such substances are intended to
furnish pharmacological activity or other direct effect in the diagnosis, cure,
mitigation, treatment or prevention of disease, or to affect the structure and
function of the body.
Contamination
The undesired introduction of impurities of a chemical or microbiological nature,
or of foreign matter, into or onto a starting material, or intermediate or finished
product during production, sampling, packaging or repackaging, storage or
transport.
Cross-contamination
Contamination of a starting material, intermediate product or finished product
with another starting material or product during production.
Excipient
A substance, other than the active ingredient, which has been appropriately
evaluated for safety and is included in a drug delivery system to:
 aid in the processing of the drug delivery system during its manufacture;
 protect, support or enhance stability, bioavailability, or patient
acceptability;
 assist in product identification; or
 enhance any other attribute of the overall safety and effectiveness of the
drug during storage or use.

28
Good Storage Practice

Expiry date
The date given on the individual container (usually on the label) of a drug
product up to and including which the product is expected to remain within
specifications, if stored correctly. It is established for each batch by adding the
shelf-life to the date of manufacture.
Labeling
Labeling is the action involving the selection of the correct label, with the
required information, followed by line clearance and application of the label.
Manufacture
All operations of purchase of materials and products, production, quality control,
release, storage and distribution of finished products, and the related controls
are called manufacture.
Material
A general term used to denote starting materials (active pharmaceutical
ingredients and excipients), reagents, solvents, process aids, intermediates,
packaging materials and labelling materials.
Packaging material
Any material, including printed material, employed in the packaging of a
pharmaceutical product, but 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.
Pharmaceutical product
Any medicine intended for human use or veterinary product administered to
food-producing animals, presented in its finished dosage form or as a starting
material for use in such a dosage form, that is subject to control by
pharmaceutical legislation in both the exporting state and the importing state.
Production
All operations involved in the preparation of a pharmaceutical product, from
receipt of materials, through processing, packaging and repackaging, labeling and
relabeling, to completion of the finished product.
Retest date

29
Good Storage Practice

The date when a material should be re-examined to ensure that it is still suitable
for use.
Storage
Storage is the storing of pharmaceutical products and materials up to their point
of use.
Supplier
A person providing pharmaceutical products and materials on request is termed
supplier. Suppliers may be agents, brokers, distributors, manufacturers or
traders. Where possible, suppliers should be authorized by a competent
authority.

II. PREMISES AND FACILITIES

Premises and other areas to be utilized for storage purposes should comply with
the prescribed minimum standards. They should be located, constructed,
serviced and maintained so as to protect the stored materials, from all
potentially harmful influences such as undue variations of temperature and
humidity; dust and odor; entry of animals vermin and insects.
A. Basic Requirements
a. Facilities must be provided for:
1. The safe and orderly receipt or dispatch of all materials, products or
components.
2. The safe sampling and cleaning of any incoming materials to prevent
contaminating the areas of other material.
3. Sufficient separation or segregation of pharmaceuticals, veterinary, food
products, chemicals, disinfectants and cleaning materials to eliminate the risk
of unacceptable chemical or organoleptic cross contamination.
4. The safe storage of hazardous materials (pressurized gases, flammable
solvents and explosive materials).
5. The storage of temperature-sensitive materials as appropriate in deep
freezes, cold rooms or air conditioned areas.
6. The storage of cleaning equipment and materials
7. Appropriate personnel service facilities such as toilets, etc.
8. The safe charging of powered forklifts and trucks
9. Secure storage of any controlled drugs (e.g. drugs of addictions, narcotics)

30
Good Storage Practice

10. The separation or segregation of reception and dispatch facilities

11. Effective lighting permitting all operations to be carried out accurately and
safely.
12. The safe storage of materials requiring dry or humidity controlled conditions.
13. Racking and shelving must conform to the requirements of the Good
Manufacturing Practice (GMP).
14. Maximum safe working loads should be displayed.
15. To allow access for cleaning and to avoid harboring pests, racking should be
positioned at least 0.5 m form the walls of the warehouse and the bottom
layer of pallets should be supported at least 0.3 m above the floor.
16. Forklift trucks should be provided with overhead protection against falling
objects, and if used frequently in the open, weather protection and lighting.
17. Only electric powered (or hand operated) trucks should be used in enclosed
spaces. Diesel powered Trucks should be avoided to decrease contamination
18. Adequate washing facilities should be provided, including hot and cold water,
soap or detergent, air driers or single service towels, and clean toilet
facilities easily accessible to working areas.
1. Main Storage Area.
2. Repackaging.
3. Cold Room.
4. Warehouse Director.
5. Procurement Office.
6. Director of Supply (Logistics).
7. Flammable Substances.
8. Shipping and Receiving.
9. Reception Area.
10. Records and Inventory Control.
11. Stenography Clerks.
12. Coffee Room.
13. Toilets.
14. Controlled Substances.
15. Main Entrance and Loading Docks.

b. Sanitation

31
Good Storage Practice

GMP Regulations require:

1. Any building used in the manufacture, processing, packing, or holding of a
drug product shall be maintained in a clean and sanitary condition. Any such
building shall be free of infestation by rodents, birds, insects, and other
vermin. Trash and organic waste matter shall be held and disposed in a
timely and sanitary manner.
2. There shall be written procedures assigning responsibility for sanitation and
describing in sufficient detail the cleaning schedules, methods, equipment,
and materials to be used in cleaning the buildings and facilities. Such written
procedures shall be followed.
3. There shall be written procedures for use of suitable rodenticides,
insecticides, fungicides, fumigating agents, and cleaning and sanitizing
agents. Such written procedures shall be designed to prevent the
contamination of equipment, components, drug product containers, closures,
packaging, labeling materials, or drug products, and shall be followed.
4. Sanitation procedures shall apply to work performed by contractors or
temporary employees as well as work performed by full-rime employees
during the ordinary course of operations.

c. Housekeeping
1. Premises and surrounding areas should be in a good appearance, be well
maintained and must be kept in an orderly, clean and hygienic conditions
free from accumulated waste.
2. Buildings must be kept free of vermin, insects, birds and other pests. Control
treatments should be carried out according to written procedures by trained
personnel using proven effective and safe procedures which do not
contaminate the goods being held and should cover both the interior and
exterior of the building.
3. Precautions must be taken to minimize the contamination of the store by
dirty, damaged or unsuitable containers.
4. Waste materials should be collected in suitable receptacles for removal to
collection points outside the building and disposed of at regular and frequent
intervals.

32
Good Storage Practice

5. Floor surface should be sealed to minimize the generation of dust and to

facilitate cleaning.
d. Fire Prevention
Accumulation of flammable trash, such as cartons and boxes, must not occur.
Smokes alarms are inexpensive to install and provide warning in case fire does
break out. For fire extinguishing, sprinkler systems are most effective. Their
principal drawback is that if accidentally set off they may ruin some stock. A
cheaper alternative is to place extinguishers suitable for chemical
fires at frequent intervals throughout storage areas, although they offer no
protection unless someone is around to use them. Employing night watchmen
serves the dual purpose of responding to fire alarms and protecting against theft.

e. Warehouse Size
The average takeoff of all clinical facilities for a given delivery interval will
determine the volume to be delivered down through the system. Assume that 200
clinical facilities consume a total of 1,000 m3 during a three months interval, and
that they are served by few district warehouses, each of these must be capable
of holding an average of 250 m3 a piece plus room for safety stock; the central
warehouse must hold at least 1,000 m3 plus safety stock.

f. Warehouse Site Selection

In selecting the site of the warehouse, the following points should be considered:
1. Accessibility: Road is open the year round.
2. Utilities: Site served by water and electricity.
3. Communications: Reliable telephone service.
4. Drainage: Neither site nor surrounding area subject to flooding due to direct
runoff or high water table.
5. Size: Unimpaired entry and exit for large vehicles.
6. Security: Area not likely to invite intrusion or vandalism.
7. Proximity: Good access to transport links, railways, highways.

g. Warehouse Design

33
Good Storage Practice

Certain points should be considered in designing warehouse (Fig. 1.), the most
important are the following:
1. Easy Movement: Use one-floor layouts. Interior partitioning limits stock
arrangement; if partitions are used, position walls and doors to promote easy
movement.
2. Air Circulation: Use of fans and forced ventilation prolongs shelf-life and
improves working conditions.
3. Bulk Storage on Pallets: This improves efficiency of stock handling; pallets
are cheaper to construct than shelves and hold more stock for the amount of
space they occupy; they facilitate air circulation and allow easier access to
stock for cleaning.
4. Easy Maintenance: Floors should be graded and drains placed to catch runoff;
provide well-spaced faucets.
5. Systematic Arrangement of Stock: Frequently used arrangements are by
therapeutic/pharmacological class, clinical indications, level of service, and
alphabetic sequence. Array stock in the same order that products appear on
standard requisitions
6. Cold Chain Maintained: Vaccines require special cold storage arrangements.
Cold rooms, refrigerators, and freezers should be protected from power cuts
by backup generators.
7. Secure Storage Area for Controlled Substances: Narcotics must be stored in
areas with restricted access.
8. Protected Storage Area for Flammable Substances: Ether, alcohol, and fuels
are best stored in out-buildings. Otherwise the storage room should seal
tightly, be well ventilated and be insulated with fireproof material.
9. Fire Prevention Measures: Do not allow trash to accumulate; provide smoke
alarms, fire extinguishers and a night watchman.
10. VACCINE Level: Central Regional Local
11. Storage Time: 6-18 months 3 months 1 month
12. Measles
13. Oral Polio -15 °C to -25 °C
14. DPT *
15. Tetanus * BCG +4 °C to +8 °C

34
Good Storage Practice

III. PERSONNEL
1. Personnel who carry out supervision and/or controlling functions should
possess the necessary integrity, knowledge, experience and qualification.
2. Each store should employ sufficient staff of a quality and experience
appropriate with their individual responsibilities and the operations carried
out.
3. Staff must be given specific authority, facilities and training to discharge
their responsibilities effectively.
4. Staff should be medically examined before being employed and at such
subsequent times as may be required by national authorities.
5. Before being employed an applicant's background should be investigated.
Staff with convictions for theft or drug abuse should not be employed.
6. Protective clothing must be worn by persons working in warehousing areas.
Safety-hats must be provided for people working within racking areas. Where
staff have to work under extremes of temperature (e.g. cold room)
appropriate clothing should be provided.
7. Drinking, eating and smoking must not be permitted in any part of the
premises except those designated for that purpose and adequately separated
from storage areas.
8. Staff must maintain high standards of personal hygiene and cleanliness.
Direct contact between raw materials or products and operators hands must
be avoided whenever possible.
9. The personnel should have the basic knowledge concerning.
i. Types of materials and dosage forms to be handled.
ii. Materials that require specific storage conditions.
o Types of storage conditions.
o Types of stability (physical, chemical, microbiological,
toxicological and therapeutic).
o Expiration date.

IV. SECURITY AND SAFETY

35
Good Storage Practice

1. The cost of security precautions should be related to the social environment

in which the facility is situated and the value and nature of the goods used.
Where large or significant quantities of valuable materials are held or where
theft is prevalent, 24 hour security coverage should be provided.
2. Security arrangements with respect of poisons and habit- forming drugs
should at least meet the standards laid down in the relevant legislation.
3. Stock control procedures should be sufficiently tight to ensure that
significant loss by theft can be detected.
4. Arrival and departure of visitors to the warehouse must be controlled. The
right to inspect all persons including employees, contractor staff and visitors
entering or leaving the site should be reserved and random searches should
be cashed out.
5. Safety and risk reduction measures, which must include procedures for the
handling, transportation, usage and disposal of highly flammable liquids,
toxic and corrosive materials, must comply with the appropriate guide to be
safe working.
6. Firefighting precautions must include:
a. The training of selected staff to form a fire fighting team capable of using
effectively the equipment available in the site.
b. The routine maintenance and testing of fire fighting alarms, detection
systems, and sprinkler alarms.
7. Fire exits, corridors, walk-ways, doorways and other points requiring
immediate access must be clearly defined and kept free from obstruction and
litter. Regular fire evacuation drills must be carried out.
8. Walk-in refrigerators and similar facilities must be equipped with safety
devices for operators and must not be fitted with self locking doors which
cannot be opened from within. The internal light must be manually operated
from within the refrigerator.
Safety controls for flammable storage areas include:

a. Electrically conductive floor.

b. Raised door sill.
c. Explosion-proof light fixtures.
d. Blow-out wall.
e. Forced draft vapor take-off.

36
Good Storage Practice

i. At floor level.
ii. Near the ceiling.
f. Rate-of-temperature-rise fire alarm.
g. Fire alarm monitored at fire station or continuously manned control board.
h. Switches for lights and vapor take-off fans located outside the room.
i. Supply of safety cans for dispensing fluids.
j. Alcohol storage located in this area meets Treasury regulations.
k. Heavy safe for storage of nitro compounds and other explosives.
l. Operations relating to the manufacture, processing, and packing of
penicillin shall be performed in facilities separate from those used for
other drug products for human use.

V. STORAGE PROCEDURES AND INSTRUCTIONS

General Principles
Factors to be taken in consideration for proper storage
a. Sanitation.
b. Temperature.
c. Light.
d. Moisture.
e. Ventilation.
f. Segregation.
Materials must be stored under conditions which minimize deterioration,
contamination, or damage. They must be stored under conditions compatible
with their recommended storage requirements of temperature and/or humidity
and where necessary, to comply with legal requirements, under secure or
segregated conditions.
Appropriate temperatures are:
a. For materials labeled "store in refrigerator", they should be stored at
temperature between 2° and 8° C.
b. For materials labeled "store in a cool place", they should be stored at a
temperature between 8° and 15° C.
c. For materials labeled "store in freezer", they should be stored at a
temperature not higher than -10° C.

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Good Storage Practice

d. In the absence of more stringent storage requirements pharmaceutical

products and raw materials should be stored at an average over any month
of below 25° C with the maximum usually below 30° C and above 4°
C. Materials should be protected from direct sunlight.
Temperature or humidity controlled environments must be equipped with
suitable indicators, recorders and/or failure warning devices which must be
checked at appropriate intervals and the results recorded. Recording
thermometers should be used. Temperature in uncontrolled storage areas holding
raw materials or products should also be monitored.
Temperatures should be measured at different levels in the warehouse and if
necessary storage of sensitive materials should be restricted to locations in the
warehouse where they will be protected from extreme conditions.
There must be an appropriate formal stock control system which record the
receipt, location and issue of materials and facilitate proper stock rotation and
reconciliation. The stock control procedure should ensure that materials with the
shortest life are used first unless there is a conscious. decision that for a special
reason an alternative priority has to be applied.
Materials and products should be inspected at specified intervals to ensure that
containers are properly closed, labeled, and that there is no evidence of serious
damage or deterioration in the containers or their contents and that the stock
rotation system is functioning correctly.

Receipt of Incoming Materials

1. Upon receipt, each incoming delivery should be checked against the relevant
documentation and physically verified by label description, type and
quantity, against the relevant purchase order information.
2. The consignment should be examined for uniformity and if necessary should
be subdivided according to supplier’s lot numbers especially if the delivery
comprise more than one batch.
3. All containers should be carefully inspected for contamination and damage
and if necessary they should be cleaned or set aside for further investigation.
4. Records should be retained for each delivery. They should include the
description of the goods, quality, quantity, supplier, supplier’s batch
number, the date of receipt.

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Good Storage Practice

5. Samples should be taken only by appropriately trained and qualified

personnel strictly in accordance with written sampling instructions.
The samples should be representative of the batch from which they
were taken.
6. The recommended product related storage conditions, for example, type of
container, temperature, humidity, protection from light etc., should be
maintained throughout the period of storage.
7. Secure measures should be taken to ensure that rejected materials cannot be
used and they should be stored separately from other materials.
8. When necessary, to minimize contamination of the storage area, incoming
materials must be cleaned, repacked or over wrapped where large quantities
of materials in poor quality containers have to be handled. If it is neither
possible to have the material supplied in more suitable containers nor
practical to repack the material, it should be held in segregated area.

ALL SHIPMENTS - Compare physical stock with supplier's invoice and original
purchase order/contract. Note discrepancies on the Receiving Report
 Number of containers delivered
 Number of packages in each container
 Visible evidence of damages (describe)
 quantity in each package
 Correct drug (don't confuse generic names and brand name), dosage form
(tablet, liquid, etc.), dose (milligrams, %, concentration, etc.)
 Take a sample for testing
 Presence of unique identifiers if required (Ministry of Health stamp, etc.)
TABLETS - For each shipment, tablets of the same drug and dose should be
consistent. The following characteristics should be checked
 Identical size, shape, color (shade of color may vary from batch to batch)
 Markings (scoring, lettering, etc.) should be identical on all tablets
 No evidence of spots, pits, chips, breaks, uneven edges, cracks, embedded
or adherent foreign matter, stickiness.
 No odor upon opening a sealed bottle (except flavored tablets and those
with active ingredients normally having a characteristic odor) and no odor
after being exposed to room air for 20-30 minutes.

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Good Storage Practice

CAPSULES - Capsules should be inspected for the same characteristics as tablets.

In addition, the following should be checked:
 No evidence of holes in the capsule
 No empty capsules
 No open or broken capsules
PARENTERALS (Injectable) - All products for injection (IV liquids, ampoules, dry
solids for reconstitution, suspensions for injection, etc.) should be checked for
the following:
 Clarity of solution (solutions should be free from undissolved particles,
within permitted limits).
 Dry solids intended for use in injectable solutions should be entirely free
from visible foreign particles
 Evidence of leakage from the immediate container (bottle, ampoule, etc.)

Storage of Approved Products

1. All stored products should be accurately documented particularly with

respect to product name, batch number, expiry date and quantity.
2. Comprehensive records should be maintained of the receipt and issue of all
products.
3. Products should be protected from excessive climatic conditions during
storage and transit, such as heat, frost, moisture and direct sunlight.
4. Products should not be distributed if they are approaching the end of their
life. There must be a written policy laying down the remaining shelf-life
after which products must not be distributed other than under exceptional
circumstances.
5. Picking stock should be stored to facilitate stock security, rotation, order
assembly and dispatch.
6. The picking and assembly areas should be organized to minimize the
distance traveled by operators. The general environment should be of a high
standard and well lit.
7. Handling of goods should be kept to a minimum on grounds of high efficiency
and safety. In large facilities the provision of mechanized order assembly
system should be considered.

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Good Storage Practice

8. There should be a laid down procedure for the checking of assembled

orders.

Storage at Clinical Facilities

The basic characteristics of good storage space at clinical facilities are the same
as for warehouses. Storerooms require ready access, good circulation, dryness,
and security. In most cases, the smaller quantities of drugs stored will permit use
of shelving. Products are arranged in convenient manner and in the order they
appear on requisitions. Large labels placed on the shelves with each product
facilitate recognition.

The Storekeeper and assistant storekeeper alone have access to the storeroom. A
"Dutch Door" arrangement, in which the top half of the door opens, while the
bottom remains closed, keeps out unauthorized persons and permits easy
communication.
At lower level facilities such as rural health posts, clinical personnel frequently
perform all supply management activities. It is seldom the case, however, that
medical auxiliaries or community- based workers receive specific training for
this. The result is that the quality of supply handling and storage conditions
deteriorates as one move to the periphery of the delivery system.
Training programs for clinical personnel who will handle supplies should include
specific courses of instruction in the following subjects:
 Setting up a storeroom and good storage practices
 Use of stock control forms including requisitions, stock records, and
prescriptions
 Cold chain procedures, including the use and preventive maintenance of
refrigerators.

Special Storage Conditions

Some categories of supplies require special storage conditions. These include
vaccines, narcotics, and combustibles. Vaccines require both refrigerators and
freezers. Narcotics and other controlled substances should be kept in secure
locking rooms with only one entrance. The keys should be kept in a secure place,

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Good Storage Practice

preferably a safe. Only the warehouse director and one other person should have
access to them.
Combustibles such as alcohol, ether, and fuels must be stored in special rooms. A
small, separate out-building is preferable since it virtually guarantees that fire
will not spread throughout the warehouse. If a special building is not available,
the room used to store these supplies must be fireproof and well-ventilated.

VI. STOCK ARRANGEMENT ROTTION AND CONTROL

Stock Rotation and Control

1. Comprehensive records should be maintained showing all receipts and issues

of materials according to batch number.
2. Periodic stock reconciliations should be performed comparing the actual and
recorded socks. In any event this should be performed when each batch is
totally used up.
3. All significant stock discrepancies should be subjected to investigation as a
check against inadvertent mix-ups and wrong issues.
4. Issues should normally observe the principle of stock rotation (first-in first-
out) especially where expiry dated materials are concerned.
5. Partly used containers of materials should be securely re- closed to prevent
spoilage and/or contamination during subsequent storage. Damaged
containers should not be issued but should be brought to the attention of the
organization responsible for quality control.
Arrangement of Stock
Within warehouses and storerooms, drugs are arranged according to a specified
organizational principle. Therapeutic/pharmacological class, clinical
indication, alphabetic order, and level-of-use are commonly used. Within the
warehouse itself as well as in clinical facilities, use of the
therapeutic/pharmacological classification produces good results, perhaps
because it provides a frame of reference within which workers can easily
recognize individual products. Level-of-use can be combined with this approach
by using preprinted Requisition/Issue Tickets for each type of facility. With this
system, drugs are arranged in the warehouse by their classes in the same order
as they appear on the Requisition/Issue Ticket. Workers move along the rows of

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Good Storage Practice

pallets packing only the type and quantity of drugs shown on the Ticket - a
greater range of products for hospitals, a lesser range for dispensaries. A final
check before sealing the boxes assures that auxiliaries have not requested
unauthorized drugs (e.g., morphine for backaches).
Control of Obsolescent and Outdated Stock
All stocks should be checked regularly for obsolescent and degraded
materials. Materials with an expired shelf life should be destroyed unless an
extension of shelf life is granted following the satisfactory results or re-
analysis. All due precautions should be observed to preclude issue of outdated
materials.

VII. STABILITY FOLLOW-UP THROUGH CURRENT CHECK-UP AND

INSPECTION OF PHARMACEUTICAL
PRODUCTS
The stability of a pharmaceutical product can be defined as the ability of its
formulation, in a specific container-closure system, to remain within the defined
physical, chemical, microbiological, therapeutic, and toxicological specifications
till the end of the stated dating, under defined storage conditions. Protection of
a pharmaceutical product may be viewed from two perspectives:
1. It is necessary to provide protection for the dosage form from the
environment, by controlling product’s storage and distribution conditions.
2. Products should be well packaged to protect the end user from the product
itself. In this sense security packaging or temperature resistant packaging
exhibits a dual protection role. The protection function of packaging
provided the major vehicle for optimization of the elements of storage and
security. The cGMP include two acts controlling drug stability and Good
Storage Practice (GSP).
Accordingly, current inspection at appropriate time intervals should be done
to verify:

1. Proper selection of storage conditions according to that stated on products

label.
The following world-wide climatic zones are assigned.
Zone 1: Temperate climate

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Good Storage Practice

Zone II: Mediterranean-like and subtropical climate

Zone III: Hot, dry climate, dry regions
Zone IV: Hot, humid climate, tropics.
In Egypt the climate, varies with season and place, roughly corresponding to
climates of zones II, and IV round the year.
Both temperature and relative humidity (RH) determine the exact climate for
drug storage.
2. Current recording and occasionally validation of monitoring equipment
(thermometers, hygrometers, etc.) to insure proper climate adjustment.
3. Pharmacist should be aware that deterioration of drug products may happen
even before their expiration. This may occur perhaps due to improper storage
or the fact that the product may require critical storage conditions not stated
on the label e.g.:
 Sorbitol discolors rapidly when stored in metal containers.
 Sodium metabisulfite gets oxidized rapidly by frequent container opening
 Hence, inspection should include frequent product examination to detect
signs of product deterioration which differ according to the dosage form,
where deterioration may be physically detected as follows:
A. Parenteral Solutions and Oral Solutions:
a. Slight gradual discoloration.
b. Swirly precipitation.
c. Whickering: pinhole at ampoule tip that leaks solution which precipitates
or crystallizes solid matter.
d. Clouding
e. Fading of color
B. Disperse Systems:
a. Cake sedimentation (suspension).
b. Creaming and cracking (emulsions)
c. Discoloration.
C. Semi-Solids (Ointments, creams, gels and suppositories)
a. Change in consistency and feel to touch
b. Syneresis.
c. Phase-separation.
d. Discoloration.

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Good Storage Practice

e. Surface crystal growth.

f.Hardness.
D. Solid Dosage Forms:
a. Surface chipping or pitting (plain tablets).
b. Deformation (Capsules).
c. Increased hardness.
d. Discoloration.
e. Color fading (colored tablets).
f.Chipping of coat.
4. In this respect the trained pharmacist, should be aware (during inspection)
that drugs mostly susceptible to hydrolytic, oxidative, or photolytic
decomposition should be carefully examined for deterioration. Drugs
susceptible to hydrolysis are those containing, -COO-CONH-, lactone or
lactame group. Most vitamins, hormones, enzymes are highly sensitive to
oxidation and photodecomposition.
5. The integrity of packing and packaging of dosage form is one of the important
tacks of inspection pharmacist as these protect the drug in a tailored fashion.
6. After each inspection, products showing any signs of instability should be
subjected to sample analysis to insure product activity.

VIII. MATERIALS AND DRUGS REQUIRING SPECIAL STORAGE

CONDITIONS
1. Medical Gases
Gas cylinders should be stored under cover, and not subjected to extremes
of temperature. Areas where they are stored should be clean, dry, well
ventilated and free of combustible materials. They should be stored
vertically and secured to prevent falling. Storage arrangements should
permit segregation of different gases and of full/empty cylinders and
permit rotation of the stock. Flammable gases should be segregated from
oxygen and other oxidizing gases. Storage arrangement for gas-mixture
should be such as to avoid separation of the mixture into its component
gases.
2. Aerosols

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Good Storage Practice

Aerosols should be stored in a clean separate area away from heat and
sunlight. Because the container contents are under pressure, filled
containers must be checked for weight loss over the expiration dating
period. For contents under pressure, the label should carry out do not
expose to heat or store at a temperature above 49° C. Keep out of
children reach.
3. Creams
Creams can be destroyed under extreme temperature fluctuations; hence
they should be stored at temperature above 10° C and not exceeding 30°
C. If the creams are opened and diluted, they should not be kept more
than 14 days to avoid microbial contamination.
4. Ophthalmic Solutions and Drops
They should be stored according to the conditions specified on the label.
After opening they should not be used for more than one month at home
and not more than 15 days in hospitals.
5. Capsules
Extremes of humidity and temperature should be avoided. High humidity
(>60% RH at 21° C to 24° C) produce more lasting effects on the capsule
shell, since as moisture is absorbed, the capsules become softer, tackier
and bloated. If temperature is increased the capsule shells may melt and
fuse together. High temp > 40° in a dry place may cause cracking of the
capsule shell. Therefore, capsules should be stored in an air-conditioned
area in which the humidity does not exceed 45% RH at 21° C to 24° C.
Empty hard gelatin capsules, generally range in moisture content between
12 to 15%. Below 10% moisture content, they become brittle and may
shrink to the point of not fitting in the filling equipment. Above 16%, size
problems in the filling equipment, plus a loss of mechanical strength, may
be encountered. Exposure to either heat or moisture extremes can distort
empty capsules to the extent that they cannot be handled by automatic
filling machines.
6. Suppositories
Suppositories should be protected from heat, preferably stored in the
refrigerator. Polyethylene glycol suppositories and suppositories enclosed
in a solid shell are less prone to distortion at temperature slightly above

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Good Storage Practice

body temperature. Glycerinated gelatin suppositories should be protected

from heat, moisture, and dry air by packaging in well-sealed containers
and stored in a cold place.

7. Emulsions and Suspensions

Emulsions and suspensions should be stored at a temperature between 15°
C and 30° C. High and low temperature may destroy the system and cause
separation.
8. Vaccines
DPT and Tetanus should not be stored in a freezer .They should be stored
at cold place (3-8° C). Also BCG should be stored in a cold place (3-8° C).
Measles and oral polio should be stored in a freezer (-25° C to -15° C).
9. Radiopharmaceuticals
Storage of radiopharmaceuticals must take into consideration the chemical
state of the radioactive drug, the quantity and type of radiation involved,
and any special storage and stability requirements. For example, gaseous
or volatile radiopharmaceutical should be kept in specially vented areas,
whereas certain other radioactive drugs require refrigeration. Storage
conditions are normally specified in product package inserts. In addition,
appropriate shielding must be used for storage areas to minimize personnel
exposure.
10. Drugs Requiring Special Storage Condition
a. Aminophyline Injection: Protected from light, discolored product not to
be used.
b. Aspirin Tablets: In moisture proof containers, avoid moist conditions.
c. Epinephrine Solution: Protected from light, ophthalmic solutions should
be in small volumes, discolored products not used.
d. Idoxuridine Solution: Protected from light, in completely filled containers.
e. Ergometrine and Ergotamine Solutions: Filled containers with minimum
headspace, protected from light.
f. Glyceryl Trinitrate Tablets: In water proof non-plastic containers.
g. Heparin Injections: At temp not exceeding 25° C, in refrigerators (2-8°
C), freezing is avoided.
h. Insulin Injections: In refrigerators (2-8° C), freezing should be avoided.

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Good Storage Practice

i. Carbamazipine Tablets: In cool dry place in tightly closed containers.

Tablets readily lose as much one third of their activity when stored in
humid environment and the tablet become harder and dissolution is
impaired.
j. Nystatin Preparations: In dark cool place, in tightly closed containers.
k. Phenothiazine Preparations: Protected from light in tightly closed
containers.
l. Riboflavin Tablets: Protected from light in tightly closed containers.
m. Sulfacetamide Solution: In dark tight containers with minimum
headspace.
n. Oxytocin Injections: In amber colored containers with minimum
headspace in refrigerator (2-8°C).
o. Noradrenaline Injections: In dark filled containers, if color change to
brown the preparation is not to be used.
p. Vegetable and Animal Drugs: Protected from insect infestations or
microbiological contaminations by means of suitable agents or processes
that leave no harmful residues. Mycotoxin detection such as aflatoxins B1
and B2 should be performed on crude drugs before use, because of the
carcinogenicity of these mycotoxins.
q. Mannitol Injections: Should be stored at a temperature not less than 20°
C. If crystallization occurs, heat to dissolve before use.

Practical Part

PRACTICAL PART

INTRODUCTION
A Pharmaceutical Package container is an article or device which contains the
Pharmaceutical Product and the container may or may not in direct contact with the
product. The container which is designed for pharmaceutical purpose must be stable.

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Practical Part

Ideal characteristics of a Pharmaceutical Package

1. It should have sufficient mechanical strength so as to withstand handling, filling,

closing and transportation.

2. It should not react with the contents stored in it.

3. It should be of such shape that can be elegant and also the contents can be easily
drawn from it.

4. It should not leach alkali in the contents.

5. The container should not support mold growth.

6. The container must bear the heat when it is to be sterilized.

7. The contents of container should not be absorbed by the container.

8. The material used for making the container should be neutral or inert.

9. Any part of the container or closure should not react with each other.

10. Must meet tamper-resistance requirements

11. Must be FDA approved
12. Must be non-toxic
13. Must not impart odor/taste to the product
14. Must not reactive with the product
Closure should be of non-toxic nature and chemically stable with container contents

Types of packaging

a. Primary packaging is the material that first envelops the product and holds it. This
usually is the smallest unit of distribution or use and is the package which is in direct
contact with the contents. Examples: Ampoules, Vials, Containers , Dosing dropper,
Closures (plastic, metal) Syringe ,Strip package, Blister packaging.

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Practical Part

b. Secondary packaging is outside the primary packaging – perhaps used to group

primary packages together. Example: Paper and boards, Cartons, Corrugated fibers
and Box.

c. Tertiary packaging is used for bulk handling, warehouse storage and transport
shipping. The most common form is a palletized unit load that packs tightly into
containers., Apart from primary and secondary packaging, two types of special
packaging are currently in use, as follows:

Aspects of packaging
1. General considerations
Packaging may be defined as the collection of different components (e.g. bottle, vial,
closure, cap, ampoule, blister) which surround the pharmaceutical product from the time
of production until its use.
The aspects of packaging to be considered which include:
o The functions of packaging;

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Practical Part

o The selection of a packaging material;

o The testing of the material selected;
o Filling and assembling;
o Sterilization;
o Storage and stability.
Packaging materials include printed material employed in the packaging of a
pharmaceutical product, but not any outer packaging used for transportation or shipment.
Examples of the types of materials used are shown in Table 1. A distinction must be made
between primary and secondary packaging components. The primary packaging
components (e.g. bottles, vials, closures, blisters) are in direct physical contact with the
product, whereas the secondary components are not (e.g. aluminium caps, cardboard
boxes). The choice of primary and/or secondary packaging materials will depend on the
degree of protection required, compatibility with the contents, and the filling method and
cost. Both single-dose and multi-dose containers exist.
Table 1; Types of raw materials used in packaging

Types of materials Uses

Cardboard Boxes Display units
Paper Labels Leaflets
Glass Ampoules Bottles Vials Syringes Cartridges
Plastic Closures Bottles Bags Tubes Laminates with paper or foil
Metal, e.g. aluminium Collapsible tubes Rigid cans Foils Needles Gas cylinders
Pressurized containers
Rubber Closures
Containers may be well-closed, tightly closed, hermetically closed or light-resistant, as
defined in the glossary.
The packaging process, as defined in the glossary, is the process that a bulk material must
undergo to become a finished product. The properties and attributes of the product should
be as specified by the manufacturer and required by the user. The packaging process
consists of the following stages:
, including plungers
 filling and assembling;
 sterilization in the final container, if applicable;
 placing labels on the container;
 Storage at the manufacturing and shipping sites.

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Practical Part

Packaging documentation which includes aspects related to:

 specifications and quality control, including batch records;
 labels, inks and adhesive materials (e.g. glue);
 Package inserts for patients.
Apart from primary and secondary packaging, two types of special packaging are currently
in use, as follows:
2. Functions of packaging
a. Containment
The containment of the product is the most fundamental function of packaging for
medicinal products. The design of high-quality packaging must take into account both the
needs of the product and of the manufacturing and distribution system. This requires the
packaging:
 not to leak, nor allow diffusion and permeation of the product;
 to be strong enough to hold the contents when subjected to normal handling;
 Not to be altered by the ingredients of the formulation in its final dosage form.
b. Protection
The packaging must protect the product against all adverse external
influences that may affect its quality or potency, such as:
 light
 moisture
 oxygen
 biological contamination
 mechanical damage.

c. Stability. Information on stability is given in the guidelines for stability testing of

pharmaceutical products containing well-established drug substances in conventional
dosage forms. For primary packaging, it is necessary to know the possible interactions
between the container and the contents. Normally, product/component stability and
compatibility are confirmed during the primary research and development stage. While
excluding the effect of external factors on the product, the packaging itself should not
interact with it so as to introduce unacceptable changes. There are numerous possibilities
of interactions between (primary) packaging materials and pharmaceutical products, such
as:
 the release of chemicals from components of the packaging materials;
 the release of visible and/or subvisible particles;

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Practical Part

 the absorption or adsorption of pharmaceutical components by the packaging

materials;
 chemical reactions between the pharmaceutical product and the packaging
materials;
 the degradation of packaging components in contact with the pharmaceutical
products;
 The influence of the manufacturing process (e.g. sterilization) on the container.
3. Presentation and information
Packaging is also an essential source of information on medicinal products. Such
information is provided by labels and package inserts for patients.
The information provided to the patient may include the following:
 the name of the patient;
 the identification number for dispensing records;
 the name, strength, quantity and physical description or identification of the
medicinal product;
 directions for use and cautionary statements, if applicable;
 the storage instructions;
 the date of dispensing and period of use (related to the expiry date);
 The name and address of the dispenser.

4. Labels
Throughout manufacturing, a succession of specific outer labels are
applied to the container of the medicinal product. The level of processing
is indicated by the following words:
 quarantine
 storage
 Distribution.
Written labels on the packaging:
• Permit the identification of each active ingredient by means of its INN, and also give the
dosage form and the trade name/trademark. All information concerning the medicinal
product, as required by national legislation, must be stated on the packaging.
After the stability of the product has been evaluated, one of the following
recommendations as to storage conditions can be prominently indicated on
the label:
 store under normal storage conditions;

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Practical Part

 store between 2 and 8 °C (under refrigeration, no freezing);

 store below 8 °C (under refrigeration);
 store between -5 and -20 °C (in a freezer);
 store below -18 °C (in a deep freezer).
• Permit the follow-up of a specific medicinal product by means of the batch number on
the labels.

Repacking, relabeling and dispensing

In some countries, it is common practice not to dispense drugs in the original packaging,
but rather in a personalized manner to each patient. This applies especially to solid oral
dosage forms, and involves the “repacking” and “relabelling” of drugs in small quantities.
Different drugs may even be included in “customized” medication packages, also referred
to as “patient med packs”.
Where repacking and relabelling are necessary, the WHO guidelines on GMP for
pharmaceutical products should be followed to avoid any mix-up or contamination of the
product, which could place the patients’ safety at risk.

Package inserts for patients (patient information leaflets)

Product information must help patients and other users to understand the medication. The
patient package insert, together with the label, provides the patient with key information
concerning the proper use of the product, potential adverse drug reactions and
interactions, storage conditions and the expiry date.
Compliance
Packaging and labeling may help to reinforce the instructions given by the physician or the
pharmacist, and improve compliance with drug therapy. In this respect, packaging
becomes a compliance aid. The design of pharmaceutical packaging should be such that
the product can easily be administered in a safe manner to the patient. If the patient feels
at ease with the packaging and route of administration, the design of the packaging may
become a key factor in increasing compliance. This is also an important factor in clinical
trials.

Protection of patients
Packaging must not only increase compliance through its design, but must also protect the
patient and indicate the integrity of the product.

Packaging materials and closures

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Practical Part

Closures
Closures used for the purpose of covering drug containers after the filling process should
be as inert as possible. They should not give rise to undesired interactions between the
contents and the outside environment, and should provide a complete seal. Besides their
protective function, closures must also allow the easy and safe administration of the drug.
Depending on the application, closures may have to be pierced with a needle for
intravenous sets. Such closures are made from elastomeric materials (rubbers), while those
that cannot be pierced are generally made from plastics such as polyethylene or
polypropylene. Depending on the type of container, closures may have different shapes
and sizes, e.g. stoppers for infusion or injection bottles or plungers for prefilled syringes. A
special design of stopper may also be required for some pharmaceutical production
processes such as lyophilization. Closures, as primary packaging components, are of critical
importance and must be carefully selected. They are an essential component of the
container and, as such, an integral part of the drug preparation.
A container type which does not require a removable closure at the time of administration
is usually preferred since such a container/ closure system avoids, or at least minimizes,
the risk of biological and other contamination as well as tampering. For parenteral
preparations, the combination of glass containers and elastomeric closures, usually
secured by an aluminium cap, is widely used.
Typical examples are infusion bottles, injection vials and prefilled syringes. The rubber
closures used within such a system must be carefully selected in accordance with the
intended purpose. Most often, improper rubber closures are the cause of incompatibility
between the packaging and the drug.
Rubber closures
Rubber consists of several ingredients, one of which is elastomer. Modern rubber
compounds used in packaging pharmaceuticals contain only a limited number of
ingredients, which are very difficult to extract. Closures made from such materials
generally do not pose any problems, and can be used in contact with a large number of
drug preparations. Rubber closures for pharmaceutical use must meet the relevant
requirements of the most important pharmacopoeias (the European, Japanese and United
States pharmacopoeias). International standards have also been established (ISO 8871). It
should be emphasized that the requirements of pharmacopoeias and standards must be
seen as minimal requirements. The suitability of a rubber closure for a given application
can only be established by means of stability studies.

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Caps or overseals
Caps or overseals are used to secure the rubber closure to the container in order to
maintain the integrity of the seal under normal conditions of transport, handling and
storage during the intended shelf-life of the product. Such caps are usually made of
aluminium and can be equipped with a plastic top to facilitate opening. Caps also provide
evidence of tampering: once opened or removed they cannot be repositioned. This is
especially true for caps with aplastic top.

Types of packaging materials

The following materials are used for the construction of containers and closures.
1. Glass

Preparation of glass: Glass is composed principally of sand, soda-ash and lime stone. Glass
made from pure silica consists of a three dimentional network of silicon atoms each of
which is surrounded by 4 oxygen atoms in tetrahedral way to produce the network.
Properties
1. It is very hard

2. Chemically resistant

3. Structure is less rigid so low m.p.

4. Glass made of pure silica.

Types of glass

Type-1: Borocilicate glass

 e.g: pyrex, borosil

 Main constituents: Sio2-80%, Al203-2%, Na2O, CaO-6%

 Properties: Resistant to chemical substances, Reduced leaching action.

 Uses: Laboratory glass apparatus, for water for injection.

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Type-2: Treated soda lime glass

 Main constituents: Made of soda lime glass. The surface of which is treated with
acidic glass like so2 at Elevated temperature and moisture.

 Uses: For alkali sensitive products, Infusion fluids, blood, & plasma, large volume
container.

 Properties: The surface of glass is resistant to attack by water for a period of time.

Type-3: Regular soda lime glass

 Main constituents: Sio2, Na2O, Cao.

 Properties: Flakes separate easily, many crack due to sudden change of

temperature.

 Uses: Topical use, For oral use, Not for ampoules.

Type-4 NP (Non Parenteral glass or general purpose soda lime glass).

 Uses: Topical use, for oral use, not for ampoules.

Neutral glass
 Main constituents: Sio2 -72 to 75%, B2o3 -7to 10, Na2o -6 to 8%, K2o - 0.5 to 2%, Bao
-2 to 4%.

 Properties: Lower cost than borosilicate, they are softer & can easily be moulded.

 Uses: Small vials (25 ml), Large transfusion bottles.

Colored bottles
 Main constituents: Glass + iron oxide.

 Properties: Produce amber color glass, Can resist Uv visible radiation from 290-400-
450nm

 Use: for photosensitive products.

2. METALS

 Advantages

a. Metal containers are strong, relatively unbreakable opaque.

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b. Resistance to chemical attack.

c. Impervious to water vapor, bacteria

d. Readily coats a number of metals

 Disadvantages

This is the most expensive metal among tin, lead, aluminium, & iron. b. Currently some
eye ointments still package in pure tin ointment tubes.

a. Aluminum

 Advantages

1. Aluminium is a light metal hence the shipment cost of the product is less.

2. They provide attractiveness of tin at somewhat lower cost.

 Disadvantages

1. As a result of corrosion process H2 may evolve

2. Any substances that react with the oxide coating can cause corrosion.
 Uses: Aluminum ointment tubes, Screw capes
b. Iron

 Advantages

Iron as such is not used for pharmaceutical packaging, large quantities of tin combines the
strength of steel with corrosion resistance of tin.
 Use: fabrication of milk containers, screw caps and aerosol cans.

c. Lead

 Advantages

Lowest cost of all metals used in pharmaceutical containers, Soft metal.

 Disadvantages

Lead when taken internally there is risk of lead poisioning. So lead containers and tubes
should always have internal lining of inert metal or polymer.
 Use: with lining lead tubes are used for products such as fluoride tooth paste.

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3. Plastics

General properties of plastics:

 Robust, strong, light, aesthetic.

 Plastics are synthetic polymers of high molecular weight.

 Easy to handle.

 They are poor conductor of heat, a disadvantage, if the content is to be autoclaved.

 Very few types of plastics completely prevent the entry of water vapor and some are
permeable to gases like O2, CO2.

Types of plastics

Plastics are classified in to 2 groups according to their behavior when heated.

 Thermoplastic type: On heating, they soften to a viscous fluids which hardens
again on cooling. Eg: Polyetyline, Polypropylene, PVC, Polystyrene, Nylon etc.

 Thermosetting type: When heated, they may become flexible but they do not
become liquid, usually hard and brittle at room temperature. Eg: Phenol,
Formaldehyde, Urea etc.

4. Rubber

Natural rubber consists of long chain polymers of isoprene units linked together in the cis
portion. Its most important source is the tree Hevea braziliensis from which latex,
containing 30 to 40% of rubber in colloidal suspension, exudes when shallow cuts are made
in the bark.
a. Butyl rubber: These are co polymer of isobutylene with 1-3% of butadiene.

Advantages
1. Permeability to water vapor and air is very low.

2. Water absorption is very low

3. They are relatively cheaper compared to other synthetic rubbers.

4. Slow decomposition takes place above 130°c

5. Oil and solvent resistance is not very good.

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b. Nitrile rubber

 Advantages: Oil resistant due to polar nitrile group, heat resistant.

 Disadvantage: Absorption of bactericide and leaching of extractives are

considerable.

c. Chloroprene rubber

These are polymers of 1:4 choprene.

Advantages
 Due to the presence of cl group close to the double bond so the bond is resistant to
oxidation hence these rubbers age well.

 This rubber is more polar hence oil resistant.

 Heat stability is good (up to 1500c).

d. Silicon rubbers Advantages

 Heat resistance (up to 2500c)

 Extreamly low absorption and permeability of water.

 Poor tensile strength.

Disadvantage: They are very expensive.

5. Labeling
Definition: Labeling is the term used in the pharmaceutical industry. It is the information
that appears on a bottle or package. It gives the best information about a drugs quality,
efficacy and safety. The term labeling designates all labels and other written, printed or
graphic matter upon or in any package or wraper in which it is enclosed. The label states
that a name of the preparation, percentage content of drug of a liquid preparation, the
volume of liquid to be added to prepare an injection or suspension from a dry
preparation, the route of administration, a statement of storage condition and expiry
date. Also indicate the name of manufacturer or distribution.

Types of labels

Various materials are used for labelling such as paper, foil and fabric. It is also possible

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to print directly on a bottle or other containers by means of silk screen or hot transfer
process. Choice will depend on need and economy.
1. Paper labeling

Most labels are printed on paper, since it is the most economical method, whether the
quantities are large or small. There is limit to the colours and techniques that can be
used in case of paper label.
2. Foil labels

It is nearly always necessary to liminate foil with paper so that the label will work properly
in the labeling machines. The foil and paper together should measure 0.0025 to 0.003 inch
for best results.
3. Transfer Labels

There are several processes for transferring heat sensitive inks from a pre-printed strip to
the container that is to be decorated. These are known by the trade names.
a. Therimage

b. Electoral

4. Sleeve Labels

There are the two types of sleeve labels

1. Stretch band and

2. Shrink tubing

Packaging Testing of Containers

Quality Control and Testing Standards

It is to first determine which batch is for testing purposes.

o The basic testing system is the same for both the components, primary and secondary.
o Although component compatibility and chemical testing are required, in addition for
primary components.
5. Compatibility and customer usability
This involves checking that each component forming a pack fits together and functions
correctly.
o Consider an eye dropper pack as an example.

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o The nozzle must have a interference fit in the bottle and allow 1 drop at a time
delivery through the hole in the nozzle when inverted, but not leak from the fitted
position.
o The cap must screw into position and leakage must not occur when the bottle is
squeezed in the invited position.
6. Chemical testing
The majority of chemical testing is required on primary component.
The type of testing required depends on the type of component used.
d. Glass vials and ampules: The USPXXII requirements for glass containers are chemical
resistance and light transmission. The requirements vary from country to country.
e. Plastic primary components: The testing is more extensive with plastic components,
requiring both biological and physicochemical test. This is because the plastic
components contain other substance such as plasticizers , stabilizers, antioxidants,
pigment, lubricants ,etc.
f. water attack Test
This test is used only with containers that have been exposed to sulphur dioxide fumes
under controlled humidity conditions. Such a treatment neutralizes the surface alkali. Now
the glass becomes chemically more resistant. The principle involved in the water attack
test is to determine whether the alkali leached form the surface of a container is within
the specified limits or not. Since the inner surface is under test entire container (ampoule)
has to be used. The amount of acid that is necessary to neutralize the released alkali from
the surface is estimated, the leaching of alkali is accelerated using elevated temperature
for a specified time. Methyl red indicator is used to determine the end point. The basic is
acid-base titration.

PHARMACEUTICAL PACKAGING AREA

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The quality control of parts begins at the end stage. Once the parts are viewed as worthy
by the bundling material research facility, the control of parts quality must be kept up
through every phase of taking care of and use.
A. Area standard
Depending on the sort of item and bundling operation, the standard requirement of the
bundling range will differ, in spite of the fact that the fundamental norms required are:
1. Every bundling line should be in discrete room.
2. There should be secured floors for simple cleaning.
3. The bundling administrators should wear non –fiber shedding overalls that have a tight
fit around the neck and sleeves.
4. The filling part of the bundling operation ought to be encased and supplied with
sifted air.
5. Crucial safety measures before filling can be controlled, for example, blowing the
holder with
6. Separated air promptly before filling. Washing of holders is not essential .
Product quality and security

Item quality and security must be kept up all through the bundling stage. It should be
possible in taking after ways:
1. Critical gadgets - a basic gadget is any gadget that is working effectively, could
influence item quality. Every gadget must be recognized and adjusted or test to
guarantee that it is working inside indicated limits.
1. Bar coding – all the printed things ought to be bar coded, with the ampules and vials,
a ring coding framework or a comparative strategy ought to be utilized.

Packaging Material Specifications

The specifications of packaging materials are :
Printed strip rolls:
Common name, Code number, Description, Color plan and outline, Quality of printed
matter, Seal quality, Effect of warmth, Name of endorsed supplier, Frequency of re-
investigation of put away material, Precaution, and Date of issue of determination
Containers:
name of the medication and quality, Code number, Description, Dimensions (length, width,
stature), Color plan, Quality of printed matter, Printed matter, Gram per square meter,
Suitability, Name of affirmed supplier, Frequency of re-assessment of put away material,
and Date of issue of specification

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Bottles:
Common name, Code number, Description, Total tallness, Neck tallness, Body distance
across, Type of glass, Overflow limit, Suitability, Name of affirmed supplier, and Date of
issue of Particular
Evidence tops:
Common name, Code number, Description( including configuration and monograph),
Uniformity of weight, Thickness of top, Sealing quality, and Date of issue of determination
Completed item determination:
Generic name of the item, Trade name, Dosage structure and quality, Description
(shading, shape, measurement, taste, and so on.), Physical properties (pH, disintegration
time, breaking down time and so on.), Name of pharmacopeia, date of expiry, safeguards
and wellbeing angles, date of issue of detail.

Inspection and audit

1. Rules
It is extremely important to control the security and quality of packaging. The
requirements to be met by packaging for pharmaceutical products are more stringent than
those for the packaging of food products, although many similarities exist. The goal of
inspection is to ascertain the quality of the products, and especially the quality of the
packaging. Items for self-inspection include documentation, storage of starting materials
and finished products, validation of programs, production and in-process controls,
calibration of instruments or measurement systems, control of labels, sanitation and
hygiene, recall procedures, premises (including personnel facilities), and maintenance of
buildings and equipment. Labels play an important part in the quality of packaging.
Packaging and labelling errors in the manufacture of pharmaceutical products are often
reported.

2. Audits of suppliers
Pharmaceutical manufacturers are usually audited or inspected by national or international
licensing authorities; the same applies to suppliers of starting materials, active
pharmaceutical ingredients, excipients and packaging materials. All suppliers of
pharmaceuticals and packaging materials play an important role in the chain of quality
assurance of the final medicinal product.
3. Protection of the environment

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The protection of the environment has become increasingly important in many countries in
recent years. Greater attention has been paid to the disposal and recycling of waste and
legislation has been introduced in many countries.
4. Packaging waste
Pharmaceutical packaging represents a very small percentage of waste, but its disposal can
cause problems for the environment. For this reason, the Committee, at its thirty-second
meeting (1), decided
that:
o Provisions should be made for the proper and safe storage of waste materials awaiting
disposal. Toxic substances and flammable materials should be stored in suitably
designed, separated, enclosed cupboards, as required by national legislation.
o Waste material should not be allowed to accumulate. It should be collected in suitable
receptacles for removal to collection points outside the buildings and disposed of safely
and in a sanitary manner at regular and frequent intervals.
5. Waste policies
Waste is created at all stages in the production, supply and use of a pharmaceutical
product. At each step, care therefore needs to be taken, either by the manufacturer or
the end-user, to protect the environment. Environmental concerns in the international
community have led to certain changes in the conditions for the licensing of medicines.
Thus an environmental risk assessment may have to be carried out in some cases in order
to identify potential risks to the environment arising from the storage, use and disposal of
medicinal products. The medicinal product as a whole may become the subject of the
environmental risk assessment so that consideration has to be given not only to the active
ingredient but also to the adjuvants/excipients in the formulation, and the primary and
secondary packaging. Another major environmental issue affecting certain types of
pharmaceutical products concerns the chlorofluorocarbon (CFC) propellants, and the
threat that they represent to the ozone layer. A

Reducing packaging. Efforts should be made to reduce the volume and weight of
packaging materials, and to eliminate packaging which is not essential for the protection
of the contents of medicinal
products.

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Salvaging and recycling packaging. The use of environmental friendly packaging needs to
be considered, i.e. recyclable or degradable packaging. (Valuable packaging materials,
such as

Methods of disposal of uncontaminated packaging

Material Recycling Landfill Incineration
Paper, cardboard +++ ++ ++
Plastics ++ + +++
Glass +++ ++ NA
Rubber + ++ +++
Metal +++ + NA
+++: Highly recommended;
++: recommended;
+: acceptable;
NA: not applicable.
aluminium, have been extensively recycled for many years. Recently, paper, glass and
plastic materials have joined the list of recyclable packaging materials.) However,
materials that have been in contact with toxic or highly potent drugs require special
consideration.
Eliminating and incinerating packaging. Some plastic materials cannot be recycled and
are therefore incinerated. The burning of polyvinyl chloride (PVC) is controversial since, if
combustion is not complete, it causes a potential increase in the levels of dioxin in the
environment. Incineration can be recommended if the combustion heat produced by it can
also be used for other purposes. Developing countries are often short of incinerators.

MACHINERY FOR PACKAGING

The machinery is an important technique for packing the any medicines or other materials.
1. Strip packing machine

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Figure 1: Strip packing machine.

Application

This model is applied for the packing of tablets, candy and pills in medicine, healthcare,
chemical, and foodstuff industry etc with automatic double-aluminum foil hot sealing.
Meeting the requirement of sealing for avoiding light, and also it is for double plastic hot
sealing packing.

2. Blister Packing Machine

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Figure 2: Blister Packing Machine.

It is high quality machine, which are suitable for handling automatic loading, filling or
none stop feeding. Blister packaging machines are used by pharmaceutical industry to
pack capsules and tablets. The packing process initiates with the capsules or tablets
being loaded in to a hopper and then in to a feeder which in turn can either be linear
feeder or a brush box feeder depending on the shape of the product and also the
material to be used.
Applications
 Unit dose hospital packs.

 Ampoule& vial tray packs

 Multi product and child resistant blister packs.

3. Cartoning Machine

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Figure 3: Cartooning machine

Description

This machine is applied to automatically box packing for medicine board, medicine
bottle, soft box with palletized granule and ointment. Such as automatically boxing
package of medicine, cosmetics. This machine features stable performance, compact
structure and beautiful appearance. And it can automatically print stainless steel
stamp. It has multi-function identification system. Automatically stopping or elimination
when no tablets or vials are available. Cartoners have an output ranging 30 to 300 cartons
per minute depending on whether the machine is vertical loading, intermittent
cartooning or a continuous motion model. These machines can handle blister stripes &
other pharmaceutical packing.

4. Ampoule Filling Line

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Figure 4: Ampoule filling machine

Figure 4: Ampoule filling machine

Description

These high precision machines completely encase the product in the inert glass don not
have a rubber stopper or any other material in direct contact with the drug. The line can
be applied to fill 1-20ML ampoule with automatic procedures as follows: Ultrasonic
washing, three times water washing (twice circulating water washing, plus one time fresh
water washing), three times air spraying, drying and sterilizing, cooling, liquid filling and
protection gaseous filling (compressed air filling and nitrogen filling).

5. Liquid Filling Machine

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Figure 5: Liquid filling machine

Description

It features advanced control system, accurate filling, stable performance, excellent

appearance.
1. Ideal equipment for filling liquid injection and lyophilization injection.

2. Imported peristaltic pump system has high filling accuracy.

3. Completely 100c purifying laminar flow protection.

4. With function of stop filling without vial.

5. It can automatic count the filled vials.

6. Syringe Filling Machine

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Figure 6: Syringe filling machine

These machines are high precision reliable machines used to fill syringes, cartridges and
other related containers. Filling is done with the help of rotary piston pumps. The
machines format spectrum can range from
0.2 to 29ml.
1. Semi-automatic syringe filling machine: These machines require manual operators
for loading the syringes in to the machine which are then filled & capped
automatically. Applications include oral dosage syringe& dental gels.

2. Fully automatic syringe filling machine: These high speed and compact machines
automatically fill and are used for saline flush syringes, dental gels and oral dose
syringe.

6. Automatic Labelling / Gumming / Stickering Machine

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Figure 7: Automatic labeling machine

Description

 Fully Automatic Labeling machine is useful to place label accurately on round shape
of product.

 Full /partial wrap labeling can be possible. A unique feature of machine is if the
body diameters changes, than also machine operates without change part.

 Labeling speed is automatically synchronized with conveyor speed to ensure quality.

Pharmaceutical Printing Machine

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Figure 8: Pharmaceutical Printing Machine

Description

This machine is suitable for printing labels, batch number, validity time and series
numbers on the surface of cartons, tissue paper, non-ferrous plastic film and aluminum
film. No matter with the dry-ink roller or instant liquid ink, it has the features of instant
printing and instant drying, and strong adhesion.

Good Storage Practices

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Introduction
Drug storage is among the pharmacist’s most important responsibilities. Therefore,
adequate methods to assure that these responsibilities are met must be developed and
implemented. The pharmaceutical are to be stored under conditions that prevent
contamination and, as far as possible, deterioration. The stability of product retain within
the specified limit, throughout it period of storage and use1. Precautions that should be
taken in relation to the effects of the atmosphere, moisture, heat and light are indicated.
During storage of the pharmaceutical products is one of the fundamental concerns in
patient care. The conditions under which pharmaceutical products are manufactured and
stored can have a major impact on their quality. High temperature and relative humidity
(RH) are the most important factors involved in drug degradation. Factors such as
temperature, humidity, air quality, time and production process characteristics can all
have a significant impact on the final quality, and therefore the saleability, of a product or
batch of products. For many products requiring storage in cool conditions, refrigeration
plant is widely used, which needs to be carefully monitored to ensure that the correct
temperatures are maintained. Stock must be stored in appropriate and auditable
environmental conditions. Appropriate conditions of light, humidity, ventilation,
temperature and security should be ensured. All medicinal products must be stored in
accordance with the manufacturer’s directions and within the terms of product
authorizations. The following factors to be taken in consideration for proper storage:
1. Sanitation
2. Temperature
3. Light
4. Moisture
5. Ventilation
6. Segregation
Different pharmaceutical product storage temperature on the basis of stability studies as
given below:
Freezer: A place in which the temperature is maintained thermostatically between -25ºC
and – 10ºC (-13 ºF and -14 ºF).
Cold: Any temperature not exceeding 8ºC (46 ºF). A refrigerator is a cold place in which
the temperature is maintained thermostatically between 2ºC and 8ºC.

Storage Condition on label

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Storage conditions for pharmaceutical products and materials should be in compliance with
the labeling, which is based on the results of stability testing Storage conditions should be
defined and described on the label of the product. All drugs should be stored according to
the conditions described on the label. When specified on the label, controls for humidity,
light, etc., should be in place. Storage areas should be designed or adapted to ensure good
storage conditions. The label should specify any special storage conditions required for the
product. Written procedures should be available describing the actions to be taken in the
event of temperature excursions outside the labeled storage conditions. All excursions
outside the labeled storage conditions must be appropriately investigated and the
disposition of the stock in question must be evidence-based (for example, stability data
and technical justification). Stability testing thus evaluates the effect of environmental
factors on the quality of the a drug substance or a formulated product which is utilized for
prediction of its shelf life, determine proper storage conditions and suggest labeling
instructions.
Storage of Tablet
Storage on label:
 Store in a cool, protected from light and moisture.
 Store in a cool and dark place, protected from light and moisture.
 Keep in a dry dark place.
 Store in cool dry and dark place.
Storage of Capsule
Storage on label:
 Store in a cool and dry place, protected from light.
Storage of Emulsion
An emulsion should be stored in air tight container, protected from light, high temperature
or freezing. The emulsions are required to be in cool place.

Storage of Suspension
Suspension should be stored in a cool place but not be kept in a refrigerator. Freezing at a
very low temperature should be avoided which may lead to aggregation of the suspended
particles.
 Storage on label:
 Store in cool and dry place, protect from heat and light.

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 Store in a cool and dark place, protect from direct sun light.
 Keep in dry place at a temperature not exceeding 30 ºC. Keep the bottle tightly
closed.
 Store below 25 ºC, protected from moisture.
 Store at temperature not exceeding 30 ºC, protect from light.
Storage of Ointment
Ointment should be stored in well closed container so as to prevent the loss of volatile
constituents. The ointment should be protected from high temperature or direct sunlight.
 Storage on label:
 Keep in a cool place.
Storage of Paste
The paste should be stored in well closed container and in a cool place so as to prevent
evaporation of moisture present.
Storage of syrup
The syrup should be stored in well closed and stopper bottle in a cool dark place. The
syrup should be stored at a temperature not exceeding 25 ºC.
Storage on label:
 Store in cool, dry and dark place.
 Store in a cool and dry place, protected from light.
 Store in a cool place, protected from direct sunlight.

Storage of Oral Drop

Storage on label:
 Store at temperature not exceeding 30 ºC.
 Store in cool, dry place and protected from light.
 Store at temperature not exceeding 30 ºC, protect from direct sunlight.
 Keep in a dry place, dark place.
 Store in a dry place, away from light.
Storage of injection
Storage on label:
 Store below 30 ºC, protected from light.
 Store below 25 ºC, protected from light.
 Drugs products that must be stored under defined conditions require appropriate
storage instructions. Unless otherwise specified stated deviation may be tolerated

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only during short term interruptions. Improper storage of insulin decreases the
potency and hence the pharmacological action of insulin. Patients should be
educated on the proper methods of storage. Insulin is one such labile drug, sensitive
to extreme temperatures and sunlight and hence needs to be stored under
refrigeration between 2- 8°C9.

Storage area
1. Storage areas should be of sufficient capacity to allow the orderly storage of the
various categories products, namely bulk and finished products, products in quarantine,
and released, rejected, returned or recalled products.
2. Storage areas should be designed or adapted to ensure good storage conditions. In
Particular, they should be clean and dry and maintained within acceptable temperature
limits. Where special storage conditions are required on the label (e.g. temperature,
relative humidity), these should be provided, checked.
3. Pharmaceutical products should be stored off the floor and suitably spaced to permit
cleaning and inspection.
4. A written sanitation programme should be available indicating the frequency of
cleaning and the methods to be used to clean the premises and storage areas.
5. Pharmaceutical products should be handled and stored in such a manner as to prevent
contamination, mix-ups and cross-contamination.
6. Narcotic drugs should be stored in compliance with international conventions, and
national laws and regulations on narcotics.
7. Radioactive materials, dangerous drugs, psychotropic substances, and cytotoxic drugs
should be stored in dedicated areas that are subject to appropriate additional safety
and security measures.
Temperature-controlled storage
Pharmaceutical manufacturers have long realized the importance of a robust and efficient,
temperature controlled supply chain. In some areas, notably in the storage of
pharmaceutical products, it has been necessary for the regulatory authorities to introduce
guidelines or legislation to ensure compliance to temperature limits. The storage
environment needs to be temperature-mapped and have relevant controls in place to avoid
extremes of temperature. Probes monitoring the environmental conditions need to be
calibrated to a certified internal standard and be regularly checked and maintained to
ensure continued accuracy of data recorded. Time- and temperature-sensitive
pharmaceutical product (TTSPP) which, when not stored or transported within predefined

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environmental conditions and/or within predefined time limits, is degraded to the extent
that it no longer performs as originally intended.

1- Routine Warehouse or Storeroom Management Tasks

A. Daily/Weekly
o Monitor storage conditions
o Clean receiving, storage, packing, and shipping areas
o Sweep or scrub floors
o Remove garbage
o Clean bins, shelves, and cupboards, if needed
o Ensure that aisles are clear
o Ensure adequate ventilation and cooling
o Ensure that products are protected from direct sunlight
o Monitor store security and safety
o Check the store roof for leaks, especially during the rainy season and during or after
a storm
o Monitor product quality (visually inspect commodities and check expiration dates)
o Ensure that products are stacked correctly (are the lower cartons being crushed?)
o Update stock records and maintain files
o If cycle counting, conduct physical inventory and update stock-keeping
Records
o Monitor stock levels, stock quantities, and safety stocks
o Submit emergency order (as needed, using local guidelines)
o Update back-up file for computerized inventory control records

B. Monthly
o Conduct physical inventory or cycle count, and update stock keeping records
o Run generator to ensure the system is working correctly; check the level of fuel
and add fuel, if needed
o Check for signs of rodents, insects, or roof leaks

o Inspect the storage structure for damage, including the walls, floors, roof,
windows, and doors

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C. Every 3 Monthly
o Conduct physical inventory or cycle count, and update stock keeping records

o Use established procedures to dispose of expired or damaged products

o Visually inspect fire extinguishers to ensure that pressures are maintained and
extinguishers are ready for use

D. Tasks According to Reorder Interval & Reporting Schedule (Usually Monthly or

Quarterly)
o Assess stock situation

o Complete and submit requisition form (indent or “pull” systems)

o Determine issue quantity and issue products (“push” systems)

o Receive products

o Store products using correct procedures; rearrange commodities to facilitate the

first-to-expire, first-out (FEFO) policy

o Complete required reporting and documentation

E. Every 6 Months
o Conduct fire drills and review fire safety procedures
o Inspect trees near the medical store and cut down or trim any trees with weak
branches
F. Every 12 Months
o Service fire extinguishersand smoke detectors

o Conduct complete physical inventory and update stock keeping records

o Reassess maximum/minimum stock levels, and adjust if needed

Receiving and arranging commodities

o Ensure there is sufficient storage space
o Prepare and clean the areas used for receiving and storing the products
o Inspect packages for damaged or expired products
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If Products are Damaged or Expired

o Separate the damaged or expired stock from the usable stock
o If damage or expiry is discovered while the delivery truck is still at your site,
refuse to accept the products and note the problem(s) on the delivery note

o If damage or expiry is discovered after the delivery truck has departed, follow
your facility’s procedures for handling damaged or expired stock

If Products are not damaged or expired

o Count the number of units for each product received and compare to issue
voucher

o Ensure the expiry date is visibly marked on every package or unit

o Arrange products in the storage area to facilitate the first-to- expire, first-out
(FEFO) procedure.

Arranging Commodities
A. Arrange the Storeroom and Shelves as follows: If using pallets, stack cartons on
pallets….
o At least10 cm(4inches) off the floor
o At least 30 cm (1 foot) away from the walls and other stacks
o No more than 2.5m (8feet) high (general rule)

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o Follow the manufacturer or shipper’s directions when stacking, and follow

o labels for storage conditions

o Place liquid products on the lower shelves or on bottom of stacks
o Store products that require cold storage in appropriate temperature controlled
zones
o Store high security/high value products in appropriate security zones
o Separate damaged or expired products from the usable stock without delay, and
dispose of using established disposal procedures

o Always store all commodities in a manner that facilitates FEFO policy for stock
management

o Arrange cartons so arrows point up and identification labels, expiry dates, and
manufacturing dates are visible

o If this is not possible, write the product name and expiry date clearly on the
visible side

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Orderly Arrangement of Essential Medicines

Medical stores must have a system for classifying or organizing medicines, and must
ensure that all employees know the system being used
o Alpha betical orderby generic name
o Therapeutic or pharmacologiccategory
o Dosage form
o System level
o Frequency of use
o Random bin
o Commodity coding

Special storage conditions

o Some products need storage in an access-controlled environment
o It is important to identify products that are at risk of theft or abuse or have the
potential for addiction, and to provide increased security for those items

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o This includes products that are in high demand or have the potential for resale
(black market value)
o Usually, National Essential Medicines Lists (NEML) include several narcotics and
psychotropic medicines; one or two will be on facility lists
Typical examples are
o Narcotics
o Other opioid and strong analgesics
o Psychotropic drugs

PREMISES AND FACILITIES

Premises and other areas to be utilized for storage purposes should comply with the
prescribed minimum standards. They should be located, constructed, serviced and
maintained so as to protect the stored materials, from all potentially harmful influences
such as undue variations of temperature and humidity; dust and odor; entry of animals
vermin and insects.

Basic requirements

facilities must be provided for:

1. The safe and orderly receipt or dispatch of all materials, products or components.
2. The safe sampling and cleaning of any incoming materials to prevent contaminating
the areas of other material.
3. Sufficient separation or segregation of pharmaceuticals, veterinary, food products,
chemicals, disinfectants and cleaning materials to eliminate the risk of unacceptable
chemical or organoleptic cross contamination.
4. The safe storage of hazardous materials (pressurized gases, flammable solvents and
explosive materials).
5. The storage of temperature-sensitive materials as appropriate in deep freezes, cold
rooms or air conditioned areas.
6. The storage of cleaning equipment and materials
7. Appropriate personnel service facilities such as toilets, etc.
8. The safe charging of powered forklifts and trucks
9. Secure storage of any controlled drugs (e.g. drugs of addictions, narcotics)
10. The separation or segregation of reception and dispatch facilities

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11. Effective lighting permitting all operations to be carried out accurately and safely.
12. The safe storage of materials requiring dry or humidity controlled conditions.
13. Racking and shelving must conform to the requirements of the Good Manufacturing
Practice (GMP).
14. Maximum safe working loads should be displayed.
15. To allow access for cleaning and to avoid harboring pests, racking should be
positioned at least 0.5 m form the walls of the warehouse and the bottom layer of
pallets should be supported at least 0.3 m above the floor.
16. Forklift trucks should be provided with overhead protection against falling objects,
and if used frequently in the open, weather protection and lighting.
17. Only electric powered (or hand operated) trucks should be used in enclosed spaces.
Diesel powered Trucks should be avoided to decrease contamination
18. Adequate washing facilities should be provided, including hot and cold water, soap or
detergent, air driers or single service towels, and clean toilet facilities easily
accessible to working areas.
16. Main Storage Area.
17. Repackaging.
18. Cold Room.
19. Warehouse Director.
20. Procurement Office.
21. Director of Supply (Logistics).
22. Flammable Substances.
23. Shipping and Receiving.
24. Reception Area.
25. Records and Inventory Control.
26. Stenography Clerks.
27. Coffee Room.
28. Toilets.
29. Controlled Substances.
30. Main Entrance and Loading Docks.

Sanitation

GMP Regulations require:

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1. Any building used in the manufacture, processing, packing, or holding of a drug

product shall be maintained in a clean and sanitary condition. Any such building shall
be free of infestation by rodents, birds, insects, and other vermin. Trash and organic
waste matter shall be held and disposed in a timely and sanitary manner.
2. There shall be written procedures assigning responsibility for sanitation and describing
in sufficient detail the cleaning schedules, methods, equipment, and materials to be
used in cleaning the buildings and facilities. Such written procedures shall be
followed.
3. There shall be written procedures for use of suitable rodenticides, insecticides,
fungicides, fumigating agents, and cleaning and sanitizing agents. Such written
procedures shall be designed to prevent the contamination of equipment, components,
drug product containers, closures, packaging, labeling materials, or drug products, and
shall be followed.
4. Sanitation procedures shall apply to work performed by contractors or temporary
employees as well as work performed by full-rime employees during the ordinary
course of operations.

Housekeeping

1. Premises and surrounding areas should be in a good appearance, be well maintained

and must be kept in an orderly, clean and hygienic conditions free from accumulated
waste.
2. Buildings must be kept free of vermin, insects, birds and other pests. Control
treatments should be carried out according to written procedures by trained personnel
using proven effective and safe procedures which do not contaminate the goods being
held and should cover both the interior and exterior of the building.
3. Precautions must be taken to minimize the contamination of the store by dirty,
damaged or unsuitable containers.
4. Waste materials should be collected in suitable receptacles for removal to collection
points outside the building and disposed of at regular and frequent intervals.
5. Floor surface should be sealed to minimize the generation of dust and to facilitate
cleaning.

Fire Prevention

Accumulation of flammable trash, such as cartons and boxes, must not occur. Smokes
alarms are inexpensive to install and provide warning in case fire does break out. For fire
extinguishing, sprinkler systems are most effective. Their principal drawback is that if

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accidentally set off they may ruin some stock. A cheaper alternative is to place
extinguishers suitable for chemical
fires at frequent intervals throughout storage areas, although they offer no protection
unless someone is around to use them. Employing night watchmen serves the dual purpose
of responding to fire alarms and protecting against theft.

Warehouse Size

The average takeoff of all clinical facilities for a given delivery interval will determine the
volume to be delivered down through the system. Assume that 200 clinical facilities
consume a total of 1,000 m3 during a three months interval, and that they are served by
few district warehouses, each of these must be capable of holding an average of 250 m3 a
piece plus room for safety stock; the central warehouse must hold at least 1,000 m3 plus
safety stock.

Warehouse Site Selection

In selecting the site of the warehouse, the following points should be considered:
1. Accessibility: Road is open the year round.
2. Utilities: Site served by water and electricity.
3. Communications: Reliable telephone service.
4. Drainage: Neither site nor surrounding area subject to flooding due to direct runoff or
high water table.
5. Size: Unimpaired entry and exit for large vehicles.
6. Security: Area not likely to invite intrusion or vandalism.
7. Proximity: Good access to transport links, railways, highways.

Warehouse Design

Certain points should be considered in designing warehouse (Fig. 1.), the most important
are the following:
1. Easy Movement: Use one-floor layouts. Interior partitioning limits stock arrangement; if
partitions are used, position walls and doors to promote easy movement.
2. Air Circulation: Use of fans and forced ventilation prolongs shelf-life and improves
working conditions.
3. Bulk Storage on Pallets: This improves efficiency of stock handling; pallets are cheaper
to construct than shelves and hold more stock for the amount of space they occupy;
they facilitate air circulation and allow easier access to stock for cleaning.

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4. Easy Maintenance: Floors should be graded and drains placed to catch runoff; provide
well-spaced faucets.
5. Systematic Arrangement of Stock: Frequently used arrangements are by
therapeutic/pharmacological class, clinical indications, level of service, and alphabetic
sequence. Array stock in the same order that products appear on standard requisitions
6. Cold Chain Maintained: Vaccines require special cold storage arrangements. Cold
rooms, refrigerators, and freezers should be protected from power cuts by backup
generators.
7. Secure Storage Area for Controlled Substances: Narcotics must be stored in areas with
restricted access.
8. Protected Storage Area for Flammable Substances: Ether, alcohol, and fuels are best
stored in out-buildings. Otherwise the storage room should seal tightly, be well
ventilated and be insulated with fireproof material.
9. Fire Prevention Measures: Do not allow trash to accumulate; provide smoke alarms, fire
extinguishers and a night watchman.

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References

References and Recommended books

1. Pharmaceutical packaging technology. D.A.Dean, E.R.Evans and I.H.Hall (2000)

2. Packaging of Pharmaceuticals and Healthcare Products, H. Lockhart and F.A. Paine,
Blackie Academic & Professional, 1996.
3. Pharmaceutical Packaging Handbook, Edward Bauer, 1st Edition, 2009
4. Pharmaceutical production facilities. Design and applications. Graham C.Cole 2nd
edition (2006)
5. Handbook of pharmaceutical technology. L.K.Ghosh. CBS Publishers and distributors.
(2006).
6. Lachman L., Lieberman H.A., Kanig J.L., editors.The Theory and Practice of Industrial
Pharmacy 4th Edition, Philadelphia: Lea & Febiger 2013
7. Aulton's Pharmaceutics: The design and manufacture of medicine, Micheal Aulton, 4th
Edition, 2013.

8. Book Coordinator ; Mostafa Fathallah

9. General Directorate of Technical Education for Health

‫حقوق النشر والتأليف لوزارة الصحة والسكان ويحذر بيعه‬

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