R e v i s e d

GUIDELINES FOR

GOOD ST OR A GE P R A C T I C E S IN M EDIC A L ST ORES A ND H OSP IT A LS

Central Administration of Pharmaceutical Affairs, M inistry of H ealth And Pop ulation

F aculty of Pharmacy , Cairo U niv ersity W orld H ealth O rg aniz ation

Cairo - E g y p t 2 0 0 4

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Cont r i b u t e r s - R e v i s e d E d i t i on F r o m C e n t r a l A d m i n i s t r a t i o n o f P h a r m a c e u t i c a l A f f a i r s : • D r. Zeinab Ebied, G eneral Manager, Technical Research

and Training • D r. M o u s t af a I br ah im , G eneral Manager of

Pharmaceutical Inspection P h a r m a c e u t i c a l I n d u s t r y E x p e r t s : • D r. R eda S h o u k r y • D r. O s am a El -G h af f ar y • D r. A bdel A z iz A bdel R eh iem U n d e r S e c r e t a r y o f S t a t e f o r P h a r m a c e u t i c a l A f f a i r s • D r. O s am a El -K h o l y

C o n t r i b u t e r s - F i r s t E d i t i o n , 1 9 9 7 From Faculty of Pharmacy. Cairo University: • P r o f . D r . A hm e d A b d E l -B a r y , D e a n, p r o f e s s o r o f p ha r m a ce u t i cs a nd i ndu s t r i a l

p ha r m a cy . • P r o f . D r . A l i a A . B a da w y , p r o f e s s o r o f p ha r m a ce u t i cs a nd i ndu s t r i a l p ha r m a cy . • D r . M o ha m e d S . E l -S a m a l i g y , p r o f e s s o r o f p ha r m a ce u t i cs a nd i ndu s t r i a l

p ha r m a cy . From M inistry of H ealth and Pop ulation: • D r . A b d E l -H a m i d A b d E l -A z i z , f o r m e r u nde r s e cr e t a r y o f s t a t e f o r

p ha r m a ce u t i ca l a f f a i r s . • D r . A l y M . E l -S ha r k a w y , he a d o f t he E g y p t i a n ho l di ng dr u g co m p a ny . • D r . G a m i l a M . M o s a , di r e ct o r o f dr u g co nt r o l de p a r t m e nt .

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TABLE OF CONTENTS I . D E F I N I T I O N S A N D C O N C E P T S . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 I I . P R E M I SE S A N D F A C I L I T I E S . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 1

B a s i c R e q u i r e m e n t s .............................................................................................................. 1 1 S a n i t a t i o n .............................................................................................................................. 1 4 H o u s e k e e p i n g ........................................................................................................................ 1 5 F i r e P r e v e n t i o n ..................................................................................................................... 1 5 W a r e h o u s e S i z e ..................................................................................................................... 1 6 W a r e h o u s e S i t e S e l e c t i o n ..................................................................................................... 1 6 W a r e h o u s e D e s i g n ................................................................................................................ 1 7

I I I . P E R SO N N E L . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 9 I V . SE C U R I T Y A N D SA F E T Y . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 1 V . ST O R A GE P R O C E D U R E S A N D I N ST R U C T I O N S . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 4

G e n e r a l P r i n c i p l e s ................................................................................................................24 R e c e i p t o f I n c o m i n g M a t e r i a l s ............................................................................................26 S t o r a g e o f A p p r o v e d P r o d u c t s ............................................................................................29 S t o r a g e a t C l i n i c a l F a c i l i t i e s ................................................................................................30 S p e c i a l S t o r a g e C o n d i t i o n s ..................................................................................................31

V I . ST O C K A R R A N GE M E N T R O T A T I O N A N D C O N T R O L . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 2 S t o c k R o t a t i o n a n d C o n t r o l .................................................................................................32 A r r a n g e m e n t o f S t o c k ..........................................................................................................33 C o n t r o l o f O b s o l e s c e n t a n d O u t d a t e d S t o c k ......................................................................33

V I I . D I SP A T C H A N D I SSU I N G . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 4 V I I I . ST A B I L I T Y F O L L O W -U P T H R O U GH C U R R E N T C H E C K -U P A N D I N SP E C T I O N O F P H A R M A C E U T I C A L P R O D U C T S . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 6 I X . M A T E R I A L S A N D D R U GS R E Q U I R I N G SP E C I A L ST O R A GE C O N D I T I O N S . . . . . . . . . . . . 41

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I. DE F IN IT IO N S A N D C O N C E P T S

Storage: The 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 materials and drug products in drug stores, pharmacies, hospitals, etc., under the specified conditions.

Storage C on d i ti on s: The conditions specified for storing the product e.g. temperature, humidity, container, etc.

Q u al i ty : The ability of a drug product to satisfy the users need. Q u al i ty C on trol U n i t: Means any person or organizational element

designated to be responsible for the duties relating to quality control.

M ateri al : A term used to cover stating materials, intermediate products, packaging materials and components and finished products.

Starti n g M ateri al : Any substance used in the manufacture of a medicinal product ex cluding packaging materials.

I n term ed i ate P rod u c t: A partly processed material which must undergo further processing before it becomes a finished product.

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D osage F orm : Refers to the gross physical form in which a drug is administered to or used by a patient.

D ru g P rod u c t: A dosage form containing one or more active therapeutic ingredients along with other substances included during the manufacturing process.

P ac k agi n g M ateri al : 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.

a) Primary Packaging Material: A packaging material which is in direct contact with medicinal product.

b) Printed Packaging Material: A packaging material which is imprinted with a tex t.

F i n i sh ed P rod u c t: A medicinal product which has completed all stages of manufacture, including packaging.

B atc h : A specific quantity of a drug and/ or other material that is intended to have uniform character and quality, within specified limits, and is produced according to a single manufacturing order during the same cycle of manufacture.

L ot: A batch, or a specific identified portion of a batch, having uniform character and quality within specified limits, or, in the case of a drug product produced by continuous process. It is a specific identified amount produced in a unit of time or quantity in a manner that assures its

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having uniform character and quality within specified limits.

L ot N u m b er (C ontrol N umber or Batch N umber): Any distinctive combination of letters, numbers, or symbols, or any combination of them, from which the complete history of the manufacture, processing, packing, holding, and distribution of a batch or lot of drug product or other material can be determined

M an u f ac tu re, P roc essi n g, P ac k i n g or H ol d i n g of a D ru g P rod u c t: includes packaging and labeling operations, testing, and quality control of drug products.

C om p on en t: Any ingredient intended for use in the manufacture of a drug product.

A c ti v e I n gred i en t: Any component that is intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease, or to affect the structure of function of the body of man or other animals.

I n ac ti v e I n gred i en t: Any component other than an " active ingredient" .

I n -P roc ess M ateri al : Any material fabricated, compounded, blended, or derived by chemical reaction that is produced for, and used in the preparation of the drug product.

Stren gth :

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i. The concentration of the drug substance (for ex ample weight/ weight, weight/ volume, or unit dose/ volume basis) and/ or

ii. The potency, that is, the therapeutic activity of the drug product as indicated by appropriate laboratory tests or by adequately developed and controlled clinical data (ex pressed, for ex ample, in terms of units by reference to a standard).

Stab i l i ty : 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 ex piration.

a) C h emical S tab ility: The components making up the preparation should remain chemically unchanged, that is, their change should be within the specified limits.

b) Ph ys ical s tab ility: 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) Micro b io lo gical S tab ility: Sterility or resistance to the growth of microorganisms should remain unchanged. D uring storage, the efficacy of preservatives should change only within the specified limits.

d) T h erap eu tic S tab ility: The therapeutic effect of the pharmaceutical preparation should remain unchanged.

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e) T o x ico lo gical S tab ility: There must be no significant change in the tox icity of the pharmaceutical preparation.

E x p i rati on D ate: The date placed on the immediate container label of a drug product that designates the date through which the product is ex pected to remain within specifications. If the ex piration date includes only a month and a year, it is ex pected that the product will meet specifications through the last day of the month. K inetically it is the time required for 10 % of the material to disappear.

E x p i rati on D ati n g P eri od : The interval of time that a drug product is ex pected to remain within specifications as detonated from stability studies on a limited number of batches of the product. The ex piration dating period is used to establish the ex piration date of individual batches.

A c c el erated T esti n g: (Stress Testing): Studies designed to increase the rate of chemical or physical degradation of a drug substance or drug product by using ex aggerated storage conditions. The purpose is to determine kinetic parameters, if possible, and/ or to predict the tentative ex piration dating period.

Stab i l i ty I n d i c ati n g A ssay : The assay which is sensitive and selective to determine quantitatively the active ingredient in the presence of its decomposition products.

Sh el f -Stab i l i ty : The stability of the drug or drug product at ambient room temperature (15 - 35° C )

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O v erage: The ex cess quantity of drug that must be added to the preparation to maintain at least 10 0 % of the labeled amount during the ex pected shelf-life of the drug.

T em p eratu re C on trol : All following temperatures in D egrees C elsius.

C ol d P l ac e: The temperature does not ex ceed 8° C . R ef ri gerator: The temperature is thermostatically controlled

between 2° and 8° C . F reez er: The temperature is thermostatically controlled to no higher

than -10 ° C . C ool P l ac e: The temperature is between 8° and 15° C . W arm P l ac e: Any temperature between 30 ° and 40 ° C . R oom T em p eratu re: The temperature is between 15° and 30 ° C . E x c essi v e H eat: Any temperature above 40 ° C . E x trem e T em p eratu re F l u c tu ati on s: The packaged drug product

should be cycled through temperature conditions that simulate the changes that may be encountered once the drug product is in distribution.

Storage T em p eratu res: The actual storage temperatures (numerical) used during stability studies should be specified.

E x trem es of T em p eratu re an d H u m i d i ty i n P h arm ac y : Temperature above 40 ° and RH above 70 % are

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considered to be the ex tremes of temperature and humidity respectively.

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II. P R E M IS E S A N D F A C IL IT IE S

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 ex plosive materials).

5. The storage of temperature-sensitive materials as appropriate in deep freezes, cold rooms or air conditioned areas.

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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 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 G ood Manufacturing Practice (G MP). 14. Max imum 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. O nly electric powered (or hand operated) trucks should be used in enclosed spaces. D iesel powered Trucks should be avoided to decrease contamination

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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. M a i n S t o r a g e A r e a . 2. R e p a c k a g i n g . 3. C o l d R o o m . 4. W a r e h o u s e D i r e c t o r . 5. P r o c u r e m e n t O f f i c e . 6. D i r e c t o r o f S u p p l y ( L o g i s t i c s ) . 7. F l a m m a b l e S u b s t a n c e s . 8. S h i p p i n g a n d R e c e i v i n g . 9. R e c e p t i o n A r e a . 10 . R e c o r d s a n d I n v e n t o r y C o n t r o l . 11. S t e n o g r a p h y C l e r k s . 12. C o f f e e R o o m . 13. T o i l e t s . 14. C o n t r o l l e d S u b s t a n c e s . 15. M a i n E n t r a n c e a n d L o a d i n g D o c k s .

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S anitatio n G MP 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.

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H o usek eep ing 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. C ontrol 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 ex terior of the building.

3. Precautions must be taken to minimize the contamination of the store by dirty, damaged or unsuitable containers.

4. W aste 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.

F ire P rev entio n Accumulation of flammable trash, such as cartons and box es, must not occur. Smokes alarms are inex pensive to install and provide warning in case fire does break out. For fire ex tinguishing, 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 ex tinguishers suitable for chemical

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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.

W areh o use S iz e 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 20 0 clinical facilities consume a total of 1,0 0 0 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 1,0 0 0 m3 plus safety stock.

W areh o use S ite S el ectio n In selecting the site of the warehouse, the following points should be considered:

1. Accessibility: Road is open the year round. 2. U tilities: Site served by water and electricity. 3. C ommunications: Reliable telephone service. 4. D rainage: N either site nor surrounding area subject to

flooding due to direct runoff or high water table. 5. Size: U nimpaired entry and ex it for large vehicles. 6. Security: Area not likely to invite intrusion or vandalism. 7. Prox imity: G ood access to transport links, railways,

highways.

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W areh o use D esig n C ertain points should be considered in designing warehouse (Fig. 1.), the most important are the following:

1. Easy Movement: U se one-floor layouts. Interior partitioning limits stock arrangement; if partitions are used, position walls and doors to promote easy movement.

2. Air C irculation: U se 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. C old C hain Maintained: V accines require special cold storage arrangements. C old rooms, refrigerators, and freezers should be protected from power cuts by backup generators.

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7. Secure Storage Area for C ontrolled Substances: N arcotics 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. O therwise the storage room should seal tightly, be well ventilated and be insulated with fireproof material.

9. Fire Prevention Measures: D o not allow trash to accumulate; provide smoke alarms, fire ex tinguishers and a night watchman.

Fig. (2) T e m p e r a t u r e R e q u ir e m e n t s f o r v a c c in e s t o r a ge

L e v e l : C e n t r a l R e g i o n a l L o c a l V A C C I N E S t o r a g e T i m e : 6-1 8 m o n t h s 3 m o n t h s 1 m o n t h M e a s l e s O r a l P o l i o -1 5 ° C t o -2 5 ° C D P T * T e t a n u s * B C G

+ 4 ° C t o + 8 ° C

* N e v e r F r e e z e D P T o r T e t a n u s

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III. P E R S O N N E L

1. Personnel who carry out supervision and/ or controlling functions should possess the necessary integrity, knowledge, ex perience and qualification.

2. Each store should employ sufficient staff of a quality and ex perience 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 ex amined 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. W here staff have to work under ex tremes of temperature (e.g. cold room) appropriate clothing should be provided.

7. D rinking, eating and smoking must not be permitted in any part of the premises ex cept those designated for that purpose and adequately separated from storage areas.

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8. Staff must maintain high standards of personal hygiene and cleanliness. D irect contact between raw materials or products and operators hands must be avoided whenever possible.

9. The personnel should have the basic knowledge concerning.

a. Types of materials and dosage forms to be handled.

b. Materials that require specific storage conditions. c. Types of storage conditions. d. Types of stability (physical, chemical,

microbiological, tox icological and therapeutic). e. Ex piration date. f. Stress storage conditions. g. Sampling. h. Q uality control and quality assurance

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IV . S E C U R IT Y A N D S A F E T Y

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. W here 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, tox ic and corrosive materials, must comply with the appropriate guide to be safe working.

6. Fire fighting precautions must include:

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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 ex its, 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. W alk-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.

Saf ety c on trol s f or f l am m ab l e storage areas i n c l u d e:

a. Electrically conductive floor. b. Raised door sill. c. Ex plosion-proof light fix tures. d. Blow-out wall. e. Forced draft vapor take-off.

i. At floor level. ii. N ear the ceiling.

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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. H eavy safe for storage of nitro compounds and other

ex plosives. O perations 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.

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V . S T O R A G E P R O C E DU R E S A N D IN S T R U C T IO N S

G eneral P rincip l es 1. Factors to be taken in consideration for proper storage

a. Sanitation. b. Temperature. c. L ight. d. Moisture. e. V entilation. f. Segregation.

2. 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.

3. Appropriate temperatures are: a. For materials labeled " s to re in ref rigerato r" , they should

be stored at temperature between 2° and 8° C .

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b. For materials labeled " s to re in a co o l p lace" , they should be stored at a temperature between 8° and 15° C .

c. For materials labeled " s to re in f reez er" , they should be stored at a temperature not higher than -10 ° C .

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 max imum usually below 30 ° C and above 4° C . Materials should be protected from direct sunlight.

4. 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.

5. 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 ex treme conditions.

6. 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

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decision that for a special reason an alternative priority has to be applied.

7. 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.

Receip t o f I nco ming M aterial s See figure 3

1. U pon 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 ex amined 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.

5. Samples should be taken only by appropriately trained and qualified personnel strictly in accordance with written

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sampling instructions. The samples should be representative of the batch from which they were taken.

6. The recommended product related storage conditions, for ex ample, 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 form other materials.

8. W hen 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.

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Fig. (3 ) I n s p e c t io n C h e c k l is t f o r D r u g R e c e ip t s

A L L S H I P M E N T S - C o m p a r e p h y s i ca l s t o ck w i t h s up p l i e r ' s i n v o i ce a n d o r i g i n a l p ur ch a s e o r d e r / co n t r a ct . N o t e d i s cr e p a n ci e s o n t h e R e ce i v i n g R e p o r t − N um b e r o f co n t a i n e r s d e l i v e r e d − N um b e r o f p a ck a g e s i n e a ch co n t a i n e r − V i s i b l e e v i d e n ce o f d a m a g e s ( d e s cr i b e ) − q ua n t i t y i n e a ch p a ck a g e − C o r r e ct d r ug ( d o n ' t co n f us e g e n e r i c n a m e s a n d b r a n d n a m e ), d o s a g e f o r m

( t a b l e t , l i q ui d , e t c.), d o s e ( m i l l i g r a m s , % , co n ce n t r a t i o n , e t c.) − T a k e a s a m p l e f o r t e s t i n g − P r e s e n ce o f un i q ue i d e n t i f i e r s i f r e q ui r e d ( M i n i s t r y o f H e a l t h s t a m p , e t c.) T A B L E T S - F o r e a ch s h i p m e n t , t a b l e t s o f t h e s a m e d r ug a n d d o s e s h o ul d b e co n s i s t e n t . T h e f o l l o w i n g ch a r a ct e r i s t i cs s h o ul d b e ch e ck e d − Id e n t i ca l s i z e , s h a p e , co l o r ( s h a d e o f co l o r m a y v a r y f r o m b a t ch t o b a t ch ) − M a r k i n g s ( s co r i n g , l e t t e r i n g , e t c.) s h o ul d b e i d e n t i ca l o n a l l t a b l e t s − N o e v i d e n ce o f s p o t s , p i t s , ch i p s , b r e a k s , un e v e n e d g e s , cr a ck s ,

e m b e d d e d o r a d h e r e n t f o r e i g n m a t t e r , s t i ck i n e s s . − N o o d o r up o n o p e n i n g a s e a l e d b o t t l e ( e x ce p t f l a v o r e d t a b l e t s a n d t h o s e

w i t h a ct i v e i n g r e d i e n t s n o r m a l l y h a v i n g a ch a r a ct e r i s t i c o d o r ) a n d n o o d o r a f t e r b e i n g e x p o s e d t o r o o m a i r f o r 2 0 -3 0 m i n ut e s .

C A P S U L E S - C a p s ul e s s h o ul d b e i n s p e ct e d f o r t h e s a m e ch a r a ct e r i s t i cs a s t a b l e t s . In a d d i t i o n , t h e f o l l o w i n g s h o ul d b e ch e ck e d : − N o e v i d e n ce o f h o l e s i n t h e ca p s ul e − N o e m p t y ca p s ul e s − N o o p e n o r b r o k e n ca p s ul e s P A R E N T E R A L S ( I n j e c t a b l e s ) - A l l p r o d uct s f o r i n j e ct i o n ( IV l i q ui d s , a m p o ul e s , d r y s o l i d s f o r r e co n s t i t ut i o n , s us p e n s i o n s f o r i n j e ct i o n , e t c.) s h o ul d b e ch e ck e d f o r t h e f o l l o w i n g : − C l a r i t y o f s o l ut i o n ( s o l ut i o n s s h o ul d b e f r e e f r o m un d i s s o l v e d p a r t i cl e s ,

w i t h i n p e r m i t t e d l i m i t s ). − Dr y s o l i d s i n t e n d e d f o r us e i n i n j e ct a b l e s o l ut i o n s s h o ul d b e e n t i r e l y f r e e

f r o m v i s i b l e f o r e i g n p a r t i cl e s − E v i d e n ce o f l e a k a g e f r o m t h e i m m e d i a t e co n t a i n e r ( b o t t l e , a m p o ul e , e t c.)

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S to rag e o f A p p ro v ed P ro d ucts 1. All stored products should be accurately documented

particularly with respect to product name, batch number, ex piry date and quantity.

2. C omprehensive records should be maintained of the receipt and issue of all products.

3. Products should be protected from ex cessive 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 ex ceptional 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. H andling 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.

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

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S to rag e at C l inical F acil ities 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. L arge labels placed on the shelves with each product facilitate recognition. The Storekeeper and assistant storekeeper alone have access to the storeroom. A " D u tch D o o r" 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 aux iliaries 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 � U se of stock control forms including requisitions, stock

records, and prescriptions � C old chain procedures, including the use and preventive

maintenance of refrigerators.

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S p ecial S to rag e C o nd itio ns Some categories of supplies require special storage conditions. These include vaccines, narcotics, and combustibles. V accines require both refrigerators and freezers. N arcotics and other controlled substances should be kept in secure locking rooms with only one entrance. The keys should be kept in a secure place, preferably a safe. O nly the warehouse director and one other person should have access to them. C ombustibles 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.

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V I. S T O C K A R R A N G E M E N T R O T A T IO N A N D C O N T R O L

S to ck Ro tatio n and C o ntro l 1. C omprehensive 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 ex piry dated materials are concerned.

5. Partly used containers of materials should be securely re-closed to prevent spoilage and/ or contamination during subsequent storage. D amaged containers should not be issued but should be brought to the attention of the organization responsible for quality control.

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A rrang ement o f S to ck W ithin 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. W ithin 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. L evel-of-use can be combined with this approach by using preprinted Requisition/ Issue Tickets for each type of facility. W ith this system, drugs are arranged in the warehouse by their classes in the same order as they appear on the Requisition/ Issue Ticket. W orkers move along the rows of 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 box es assures that aux iliaries have not requested unauthorized drugs (e.g., morphine for backaches).

C o ntro l o f O b so l escent and O utd ated S to ck All stocks should be checked regularly for obsolescent and degraded materials. Materials with an ex pired shelf life should be destroyed unless an ex tension of shelf life is granted following the satisfactory results or re-analysis. All due precautions should be observed to preclude issue of outdated materials.

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V II. DIS P A T C H A N D IS S U IN G

1. The allocation and shipping of products should be made only after the receipt of a written sale order.

2. 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. The shipping container should offer adequate protection from all ex ternal influences, and should be indelibly and clearly labeled.

3. D ispatch documents should be retained indicating: • D ate of dispatch. • C ustomer name and address. • Product name and quantity sent.

All documentary records should be readily accessible and be kept in a secure place. In Medical Stores:

1. W hen requisition/ issue tickets (R/ I) 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 and send the R/ I to the Inventory C ontrol U nit. There, stock clerks review the availability of the supplies requested. They note any

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low inventory levels and send the R/ I to the D irector. The D irector reviews the document, taking into account the stock clerks’ notations. H e may delete items, modify quantities, or approve the R/ I as it is. H e then returns the document to the Inventory C ontrol U nit. There, the clerks post the Stock Record C ards and send all copies of the R/ I to the Pharmaceutical Store Room. Eventually, when Shipping and Receiving provides a signed copy of the R/ I verifying that the shipment has been made the stock clerks change the pencil entries to ink.

2. The C hief Storekeeper supervises preparation of shipments. As a clinical pharmacist, he is the only person authorized to make substitutions. W ithin the store room, supplies are arranged in the order that they appear on the Requisition/ Issue. Ticket. The store men loose-pack supplies in cartons. W hen issuing drugs, an important principle is to issue those drugs with the nearest ex piration date first. The Assistant Storekeeper is responsible for this and for posting the Bin C ard.

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VIII. STABILITY FOLLOW-U P TH R OU G H C U R R E N T C H E C K -U P AN D IN SP E C TION OF P H AR M AC E U TIC AL

P R OD U C TS

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 tox icological 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 ex hibits a dual protection role. The protection function of packaging provided the major vehicle for optimization of the elements of storage and security. The cG MP include two acts controlling drug stability and G ood Storage Practice (G SP).

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A ct 5 . 5 3 :

D rug storage should be regularly checked for cleanliness and good order, and for misplaced, deteriorated, or out-dated stock. A ct 5 . 5 4 :

D rug products should be stored under conditions which minimize deterioration, contamination, spillage, or breakage.

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 Zone II: Mediterranean-like and subtropical climate Zone III: H ot, dry climate, dry regions Zone IV : H ot, humid climate, tropics. In Egypt the climate, varies with season and place, roughly corresponding to climates of zones II, and IV round the year.

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Both temperature and relative humidity (RH ) determine the ex act climate for drug storage.

2. C urrent 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 ex piration. 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 ox idized rapidly by

frequent container opening H ence, inspection should include frequent product ex amination to detect signs of product deterioration which differ according to the dosage form, where deterioration may be physically detected as follows: I- P a r ent er a l S ol u t i ons a nd O r a l S ol u t i ons : a. Slight gradual discoloration. b. Swirly precipitation. c. W hiskering: pinhole at ampoule tip that leaks solution which precipitates or crystallizes solid matter. d. C louding

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e. Fading of color II- D i s p er s e S y s t em s : a. C ake sedimentation (suspension). b. C reaming and cracking (emulsions) c. D iscoloration. III. S em i -S ol i d s (O intments, creams, gels and suppositories) a. C hange in consistency and feel to touch b. Syneresis. c. Phase-separation. d. D iscoloration. e. Surface crystal growth. f. H ardness. IV S ol i d D os a g e F or m s : a. Surface chipping or pitting (plain tablets). b. D eformation (C apsules). c. Increased hardness. d. D iscoloration. e. C olor fading (colored tablets). f. C hipping of coat.

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4. In this respect the trained pharmacist, should be aware (during inspection) that drugs mostly susceptible to hydrolytic, ox idative, or photolytic decomposition should be carefully ex amined for deterioration. D rugs susceptible to hydrolysis are those containing, -C O O -C O N H -, lactone or lactame group. Most vitamins, hormones, enzymes are highly sensitive to ox idation 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.

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IX . M A T E R I A L S A N D DR U G S R E Q U IR IN G S P E C IA L S T O R A G E

C O N DIT IO N S

1. M e d i c a l G a s e s G as cylinders should be stored under cover, and not subjected to ex tremes 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 ox ygen and other ox idizing gases. Storage arrangement for gas-mix ture should be such as to avoid separation of the mix ture into its component gases.

2. A e r o s o l s

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 ex piration dating period. For contents under pressure, the label should carry out do not ex pose to heat or store at a temperature above 49° C . K eep out of children reach.

3. C r e a m s

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C reams can be destroyed under ex treme temperature fluctuations; hence they should be stored at temperature above 10 ° C and not ex ceeding 30 ° C . If the creams are opened and diluted, they should not be kept more than 14 days to avoid microbial contamination.

4 . O p h t h a l m i c S o l u t i o n s a n d D r o p s 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. C a p s u l e s Ex tremes of humidity and temperature should be avoided. H igh 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. H igh 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 ex ceed 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. Ex posure to either heat or moisture ex tremes can distort empty capsules to the ex tent that they can not be handled by automatic filling machines.

6. S u p p o s i t o r i e s

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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 body temperature. G lycerinated gelatin suppositories should be protected from heat, moisture, and dry air by packaging in well sealed containers and stored in a cold place.

7 . E m u l s i o n s a n d S u s p e n s i o n s Emulsions and suspensions should be stored at a temperature between 15° C and 30 ° C . H igh and low temperature may destroy the system and cause separation.

8. V a c c i n e s

D PT and Tetanus should not be stored in a freezer .They should be stored at cold place (3-8° C ). Also BC G 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. R a d i o p h a r m a c e u t i c a l s

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 ex ample, 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 ex posure.

10 . D r u g s R e q u i r i n g S p e c i a l S t o r a g e C o n d i t i o n

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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. Idox uridine Solution: Protected from light, in completely filled containers.

e. Ergometrine and Ergotamine Solutions: Filled containers with minimum headspace, protected from light.

f. G lyceryl Trinitrate Tablets: In water proof non-plastic containers.

g. H eparin Injections: At temp not ex ceeding 25° C , in refrigerators (2-8° C ), freezing is avoided.

h. Insulin Injections: In refrigerators (2-8° C ), freezing should be avoided.

i. C arbamazipine 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. N ystatin Preparations: In dark cool place, in tightly closed containers.

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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. O x ytocin Injections: In amber colored containers with minimum headspace in refrigerator (2-8° C ).

o. N oradrenaline Injections: In dark filled containers, if color change to brown the preparation is not to be used.

p. V egetable and Animal D rugs: Protected from insect infestations or microbiological contaminations by means of suitable agents or processes that leave no harmful residues. Mycotox in detection such as aflatox ins B1 and B2 should be performed on crude drugs before use, because of the carcinogenicity of these mycotox ins.

q. Mannitol Injections: Should be stored at a temperature not less than 20 ° C . If crystallization occur, heat to dissolve before use.