pharmaceutical storage practises, ways, according to dosage form

1. Good storage practices
Part 2

2. Definitions and concepts
• Storage : a term used to describe the safe
keeping of starting materials, packaging
materials, components received semi-finished,
in-process and finished products awaiting
dispatch.
• The term is also applied for safe keeping of
drug products in drug stores, pharmacies,
hospitals… etc

3. Definitions and concepts
• Storage conditions : the conditions specified
for storing the product e.g. temperature,
humidity, container… etc
• Quality: the ability of drug product to satisfy
the user needs.
• Quality control unit : any person or
organization element designed to be
responsible for the duties related to quality
control.

4. Definitions and concepts
• Material: a term to cover stating material,
intermediate products, packaging material
and components and finished products.
• Starting material : any substance used in the
manufacture of a medical product excluding
packaging material.

5. Definitions and concepts
• Intermediate product : a partly proceeded
material which must undergo further
processing before it become a finished
product.
• Dosage form: refers to the gross physical form
in which a drug is administered to or used by
patient.

6. Definitions and concepts
• 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.

7. Definitions and concepts
• Finished product: a medicine product which
has completed all stages of manufacture,
including packaging.
• A batch: a specific quantity of a drug or other
material that is intended to have uniform
character of quality, within specific limits and
produced according to single manufacturing
order during the same cycle of manufacture.

8. Definitions and concepts
• Lot : a batch, or specific identified portion of a
batch, having a uniform character and quality
within specified limits, or in case of a drug
product produced by continuous process.

9. Definitions and concepts
• Manufacturing, processing, packing, or
holding of the drug: include packaging and
labeling operations, testing, and quality
control of drug products.
• Active ingredient : any component that
intended for a pharmaceutical activity (direct
action, diagnosis, cure, treatment, or
prevention of a disease.

10. Definitions and concepts
• In-active ingredients: any components other
than the active ingredient.
• In-process material: any material fabricated,
compounded, blended, or derived by chemical
reaction that is produced for, and used in
preparation of the drug product.

11. Definitions and concepts
• Strength :
• i. the concentration of the drug substance ( for
example weight/weight, weight/volume, or
unit dose/volume basis)
• ii. The potency (the therapeutic activity of the
drug product).

12. Definitions and concepts
• Shelf stability: the stability of the drug
product at ambient room temperature (15-
35°C)
• Cold place doesn’t exceed 8°C.
• Refrigerated  between 2-8 °C.
• Freezer not more than -10°C.
• Cool place 8-15°C.
• Warm place 30-40°C.
• Room temperature  15-30°C.

13. Definitions and concepts
• Extremes of temperature and humidity in the
pharmacy  40°C ,, 70% RH.

14. Sanitation
• Any building used in the manufacture,
processing, packing, or holding of a drug
product shall be maintained in clean and
sanitary conditions.
• Any such building shall be free infestation by
rodents, birds, insects or other vermin.
• Trash and organic waste matter shall be held
disposed in a timely and sanitary manner.

15. Sanitation
• There shall be written procedure assigning
responsibility for sanitation and in describing
in sufficient detail and cleaning schedules,
methods, equipments, and materials to be
used in cleaning the building and facilities.

16. Sanitation
• There shall be written schedules and
procedures for the used of a suitable
rodenticides, insecticide, fungicides and other
cleaning products.

17. Housekeeping
• 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 of accumulation of waste.
• Precautions must be taken to minimize the
contaminations of the store by dirty, damaged
or unsuitable containers.

18. Housekeeping
• Waste materials should be collected in a
suitable receptacles for removal to collection
points outside the building and disposed of at
regular and frequent intervals.

19. Fire prevention
• Make sure to never accumulate flammable
trash such as cartons and boxes.
• Smoke alarms should be placed in every room
possible in case fire does break out.
• Sprinkler system is the must effective.

20. Fire prevention
• The drawback is that if accidently set off they
may ruin some stock.
• A cheaper alternative is to place “fire
extinguishers” suitable for chemical fires, but
their with no use if there is no one around to
use them in case of fire.

21. Warehouse site selection
• 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
exit high-water table.

22. Warehouse site selection
5. Size: unimpaired entry and exit for large
vehicles.
6. Security: area not likely to invite intrusion and
vandalism.
7. Proximity: good access to transport links,
railways, highways.
8. Secure storage area for controlled substances:
Narcotics, must be stored in areas with
restricted access.

23. Warehouse site selection
9. Protected storage area from flammable
substance: ether, alcohol and fuels are best
stored in out-buildings. Other wise rooms
should be seal tightly, be well ventilated and
isolated with fireproof material.
10.Fire prevention measures: do not allow trash
to accumulate: provide smoke alarms, fire
extinguishers and night watchman.

24. Temperature requirements for vaccine
storage
• Measles : -15°C to -25°C ‫الحصبة‬ ‫لقاح‬
• Oral polio: -15°C to -25°C
‫الفم‬ ‫طريق‬ ‫عن‬ ‫األطفال‬ ‫شلل‬ ‫لقاح‬
• DPT: 4-8 °C (don’t freeze)*
DPT ( = diphtheria - pertussis - tetanus vaccine
) ‫الثالثي‬ ‫اللقاح‬
• Tetanus : 4-8 °C (don’t freeze)* ُ‫ح‬‫قا‬ِ‫ل‬‫زاز‬ُ‫ك‬‫ال‬
• BGC : 4-8 °C ‫السل‬ ‫لقاح‬

25. Others
• Staff must maintain high standard personal
hygiene and cleanliness.
• Direct contact between raw materials or
products or operator hands must be avoided
whenever possible.

26. Security and safety
• Security precautions should be related to the
social environment in which the facility is suited.
• A tight security measures is necessary in places
where significant quantities or valuable materials
are held or where theft is prevalent.
• Good security arrangements where poisons and
habit-forming drugs should be considered.

27. Security and safety
• Arrival and departure of visitors to warehouse
should be controlled.
• Safty and security measures should include
procedures of handling, transportation, usage
and disposal of highly flammable liquids, toxic
and corrosive material.

28. Security and safety
• Fire exit, corridors, walk-ways, doorways and
other points must be clearly defined and kept
free from obstructions.
• Walk-in refrigerators and similar facilities must be
equipped with safety operator devices and must
not be fitted with self locking doors which cannot
be open from within.
• The internal light must be manually operated
from within refrigerator.

29. Security and safety
• Safety controls for flammable storage areas:
1. Electricity conductive floor.
2. Raised door sill.
3. Explosion proof light fixtures.
4. Blow-out wall.
5. Forced draft vapour take-off (at floor level
and near the ceiling).

30. Security and safety
6. rate-of temperature rise fire alarm.
7.Fire alarms linked to fire stations,
8.Switches for the vapor take-off fans should be
placed out side the room as well as inside.

31. Storage procedures and instructions
• General principle:
1. Factors to be taken in safety storage:
a. sanitations
b. temperature
c. light and moisture.
d. ventilation (air supply).
e. segregation

32. Storage procedures and instructions
• 2. materials should be stored in conditions
which minimize deteriorations,
contaminations, or damage.
• 4. temperature and humidity controlled
environments must be equipped with suitable
indicators, recorders and failure warnings.
• 6. the stock control procedure should ensure
the materials with the shortest life used first.

33. Storage procedures and instructions
• 7. materials and products should be inspected
at specified intervals to ensure that containers
are properly closed, labeled, and there is no
evidence of serious damage in the container
or the material inside it.

34. Receipt of incoming materials
• Each incoming delivery should be checked
against the relevant documentation and
physically verified by label description, type
and quantity, against the relevant purchase
order form.
• The consignments should be examined for
uniformity and divided according to supplier’s
lot number.

35. Receipt of incoming materials
• All containers should be carefully inspected
for contaminations and damage and if
necessary they should be cleaned.
• Records should be retained for each delivery.
they should include the description of the
goods, quality, quantity, supplier, supplier
patch number, the date of receipt.

36. Receipt of incoming materials
• Samples should be taken only by appropriately
trained and qualified personnel strictly in
accordance with written sampling
instructions.
• The recommanded product storage conditions
should be maintained throughout storage
periods.

37. Receipt of incoming materials
• Secure measures should be taken to ensure
that rejected materials cannot be used and
they should be stored separately from other
materials.
• When necessary to minimize contaminations
of the storage area, incoming material must
be cleaned, repacked or over wrapped.

38. Receipt of incoming materials
• If its not possible to clean and repack the
materials should be held in a segregated area

39. Inspection check-list
(all shipments)- compare physical stock with
supplier’s invoice and original purchase
order/contact. Note discrepancies on the
receiving report:
• Number of containers delivered.
• Number of packages in each container.
• Visible evidence of damage (describe)
• Quantity on each package.
• Correct drug, dosage form, dose.
• Presence of unique identifiers required (ministry
of health stamp … etc)

40. Inspection check-list
(Tablets)- for each shipment, tablets of the
same drug and dose should be consistent. The
following should be checked:
• Identical size, shape, color (shade of color may
vary from batch to batch).
• Marking (scoring, lettering, etc.) should be
identical on all tablets.
• No evidence of spots, pits, chips, breaks,
uneven edges, cracks, embedded or adherent
foreign material, stickiness.

41. Inspection check-list
Continue on tablets:
• 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

42. Inspection check-list
(Capsules)- same as tablets in additional to the
following:
• No evidence of holes in the capsule.
• No empty capsule.
• No open or broken capsule.

43. Inspection check-list
(Parenterals / injections)- all products for
injections (I.V liquids, ampoules, dry solids for
reconstitutions, suspension for injection , etc.)
should be checked like the following:
• Clarity of the solution (solutions should be free
from the un-dissolved particles, within permitted
limits)
• Dry solids should be free entirely from visible
foreign particles.
• Evidence of leakage from the immediate
container (bottle, ampoules.. Etc.)

44. Storage of approved products
• All stored products should be accurately
documented particularly with respect to
product name, batch number, expiry date and
quantity.
• Comprehensive records should be maintained
of the recipient and issue of all products.

45. Storage of approved products
• Products should be protected from excessive
climatic conditions during storage, and transit,
such as heat, frost, moisture and direct
sunlight.
• Picking stock should be stored to facilitate
stock security rotation, order assembly and
dispatch.

46. Storage of approved products
• 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.
• Handling of goods should be kept to
minimum, in large facilities the provision of
mechanized order assembly system should be
considered.

47. Storage of approved products
• There should be laid down procedure for
checking of assembled orders.

48. Stock arrangement rotation and
control

49. Stock rotation and control
• Comprehensive records should be maintained
showing all receipts and issues of materials
and according to batch number.
• Periodic stock reconciliations should be
performed comparing the actual and recorded
stocks. In any event this should be performed
when each batch totally used up.

50. Stock rotation and control
• All significant stock discrepancies should be
subjected to investigation as a check against
inadvertent mix-ups and wrong issues.
• Issues should normally observe the principle
of stock rotation (first-in first-out) especially
where expiry dated materials are concerned.

51. Stock rotation and control
• Partly used containers of materials should be
securely closed to prevent spoilage and
contamination.

52. Arrangement of stock
• Drugs arranged according to:
1. Therapeutic/pharmacological class
2. Clinical indication
3. Alphabetic order
4. Level-of use
(most common categories)

53. Arrangement of stock
• Using the therapeutic/pharmacological
classification is the best in warehouse storage
because it provide a frame of reference within
which workers can easily recognize products.
• Level-of-use can be combined with this
approach by using preprinted
requisition/issue ticket for each type of
facility.

54. Arrangement of stock
• In the previous system, drugs 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 pallets
packing only the type and quantity of the
drugs shown on the tickets.
• Greater range of the tickets for hospitals and
the lesser ranger for dispensaries.

57. Control of obsolescent and out dated
stock
• Materials with an expired shelf life should be
destroyed .
• Unless an extension of date is granted
following the satisfactory result or re-analysis.

58. Dispatch and issuing

59. Dispatch and issuing
• The allocation and shipping of the products
should be made only after the receipt of a
written sale order.
• Results for dispatch procedures should be
established depending on the nature of the
product and after taking into account any
special precautions to be observed.

60. Dispatch and issuing
• The shipping container should be protected
from external influences, and be indelibly and
clearly labeled.
• Dispatch document should be retained
indicating : (Date of dispatch, customer name
and address, product name and quantity sent)

61. In medical stores
• When requisition/issue (R/I) ticket arrive,
shipping clerks review them to see that the
types and quantities of supplies correspond to
the needs of the warehouse or clinical facility
requesting them.
• The clerks initial approval send the R/I to the
inventory control unit.
• In the IC unit the stock clerks review the
availability of supplies request.

62. In medical stores
• They note the low inventory levels and send
the Director who reviews the document.
• The director may delete items, add items,
modify quantities or approve the R/I as it is.
• The Director returns the document to the IC
unit.
• Then all copies and approval sent to the
pharmaceutical store room.

63. In medical stores
• After this step all copies are changed from
pencil entries to ink.
• Chief store storekeeper (a clinical pharmacist)
supervises preparation of shipments.
• Store men loose-pack supplies in cartons.
• When issuing drugs the nearest date is first to
consume, the Assistant storekeeper is
responsible for this and posting the bin card.

64. Stability follow-up

65. Stability follow-up in current check-up
and inspection of pharmaceutical
products.
• Protection of the pharmaceutical products may
be viewed from two perspectives:
• 1- it is necessary to provide protection for dosage
form from the environment, by controlling
product storage and distribution conditions.
• 2- products should be well packed to protect the
end user from the product itself. Security
packaging or temperature resistant packaging
(dual packaging)

66. • 3- the protection function of packaging
provided the major vehicle for optimizing of
the element of storage and security.
• 4- the cGMP include two acts controlling drug
security and good storage practice (GSP).

67. Current inspection at appropriate time
intervals
• Should be done to verify:
1. Proper selection of storage conditions
according to the state of product label.
following word-wide climate zone
zone I : cold temperature climate
zone II : Mediterranean-like and subtropical
zone III: hot dry climate, dry regions.
zone IV: Hot humid climates, tropics.

68. Current inspection at appropriate time
intervals
• In Egypt the climate vary from season to
season, roughly corresponding to climate of
zones II and IV round the year.
2. Current recording and occasionally validation
of monitoring equipment (thermometers,
hygrometers, etc.) to ensure proper climate
adjustment.

69. Current inspection at appropriate time
intervals
3. Pharmacist should be aware of deterioration
of products may occur before expiration date,
due to improper storage or some storage
critical that not mentioned on the label.
Examples:
a. Sorbitol discolored rapidly when stored into
metal containers.
b. Sodium metabisulfite gets oxidized rapidly by
frequent container opening.

70. Current inspection at appropriate time
intervals
• Inspection should include frequent product
examination, where deterioration should be
detected as the following
1-Parentral and oral solutions:
a. slightly gradual discoloration
b. swirly precipitation
c. whiskering (pinholes and leaking which lead to
crystallization of solid matter)
d. clouding
e. fading of color.

71. Current inspection at appropriate time
intervals
2- Disperse systems:
a. cake sedimentation (suspension)
b. creaming and cracking (emulsions)
c. discoloration.
3- Semi-solids (ointments, creams, gels, supp):
a. change in consistancy
b. synersis, phase separation, discoloration
c. hardness, crystal growth

72. Current inspection at appropriate time
intervals
4- solid dosage forms:
a. surface chipping and pitting (plain tablets)
b. Deformation (capsules)
c. increase hardness
d. discoloration
e. color fading (tablets)
f. chipping of coat

73. Current inspection at appropriate time
intervals
• 4- pharmacist should be aware that drugs can
undergo hydrolytic, oxidative, photolytic
decomposition should be carefully examined
for deterioration.
- drugs susceptible to hydrolysis should
contain –COO or CONH- , lactone or lactame
groups.
- most vitamins, hormones, enzymes are highly
sensitive to oxidation and photolysis.

74. Current inspection at appropriate time
intervals
• 5. after inspections , products showing any
signs of instability should be subjected to
sample analysis to ensure product activity.

75. Materials and drugs require
special storage conditions

76. Medical gases
• Gas cylinder should be stored under cover and
not subjected to extreme temp.
• Areas where they are stored should be clean,
dry, well ventilated and free of combustible
materials.
• They should be stored vertical and secured to
prevent falling.
• Flammable gases should be segregated from
oxygen source and other oxidizing agents.

77. Medical gases
• Storage arrangements for gas mixture should
be such as avoid separation of the mixture
into its component gases.

78. Aerosols
• Stored in clean separate area, away from heat
and sunlight.
• Because the container content are under
pressure, filled containers must be checked for
weight loss over the expiration date period.
• For contents under pressure, label should
carry out “do not expose to heat” or “do not
store at temperature above 49” and “ keep
out of reach of children”

79. Creams
• Creams can be destroyed under extreme
temperature fluctuations.
• They should be stored at temperature above
10°C and don’t exceed 30°C.
• If creams are opened and diluted they should
not be kept more than 14 days to avoid
contaminations.

80. Ophthalmic solutions and drops
• Stored according to conditions specified at
their label.
• After opening they should not be used after
one month at home and not more than 15
days at hospitals.

81. Capsules.
• Extreme humidity and temp should be
avoided.
• High humidity >60% at 21-24°C produce more
lasting effects to the capsule shell, capsule
become softer, tackier and more bloated
(moisture absorbed).

82. Capsules.
• If temp increased above 40°C capsule shell
may melt and fuse together.
• High temp and a Dry place may cause cracking
in a capsule shell.
• Capsules should be stored in air-conditioning
area where humidity doesn't exceed 45% and
21-24° C temp.

83. Capsules.
• Empty hard gelatin capsule generally range in
moisture between 12%-15%.
• Less than 10% moisture content they become
brittle and shrink to the point where they no
longer fit their filling.
• Above 16% loss of mechanical strength and
become hard to fill and stay sturdy .

84. Suppositories
• Should be protected from heat, preferably
stored in the refrigerator.
• Polyethylene glycol suppositories and
suppositories enclosed within in a solid shell
are less prone distortion at temp above body
temp.
• Glycerinated gelatin supp should be protected
from heat, moisture, dry air.
• In well sealed containers and stored in cold
place.

85. Emulsions and Suspensions
• Stored at temp between 15-30 °C .
• High temperature may destroy their system.

86. Vaccines
• DPT and tetanus should not be stored in a
freezer stored at cold place (refrigerated)
• BCG stored in a cold place 3-8 °C.
• Measles and oral polio stored in a freezer (-25
to -15) °C.

87. Radiopharmaceutics
• Gaseous or volatile Radiopharmaceutics
should kept in special vented area.
• Other materials may keep refrigerated.
• Storage conditions depends on the label
inserts.
• In addition, appropriate shielding must be
used in the storage to minimize personnel
exposure.

88. Drugs required special storage
conditions
• Aminophylline injection: protected from light,
discolored product should never be used.
• Aspirin tablets: in moisture proof containers,
avoid moist conditions.
• Epinephrine solution: protected from light,
ophthalmic solutions should be in small volumes,
dicolored products shouldn’t be used.

89. Drugs required special storage
conditions
• idoxuridine solutions: protected from light, in
completely filled containers.
• Ergometrine and ergotamine solutions: filled
containers with minimum headspace,
protected from light.

92. Drugs required special storage
conditions
• Glyceryl-Trinnitrate Tablets: in water proof
non-plastic containers.
• Heparin injections: freezing avoided,
refrigeration required (2-8°C).
• Insulin injections: freezing avoided,
refrigeration required (2-8°C).

93. Drugs required special storage
conditions
• Carebamazipine tablets: in cool dry place,
tight enclosed containers, tablets rapidly loss
at least one third of their content when stored
in humid environment , tablets become
harder and dissolution impaired.
• Nystatin preparations: in dark cool place,
tightly close containers.
• Riboflavin tablets: protected from light, tight
containers

94. Drugs required special storage
conditions
• Phenothizaine preparations: protected from
light.
• Sulfacetamide tablets: dark tight containers,
minimum headspace.
• Oxytocin injections: amber containers with
minimum headspace in refrigerator.
• Noreadrinaline injections: dark filled
containers, if color changed to brown don’t
use the preparation.

95. Drugs required special storage
conditions
• Vegetable and animal drugs: protected from
insect infestation or microbial contaminations.
Mycotoxin detection such as aflatoxin B1 and
B2 should be performed.
• Mannitol injections: should be stored at temp
not less than 20°C, if crystallization occur use
heat to dissolve before use.