Working document QAS/04.

068
RESTRICTED

WORLD HEALTH ORGANIZATION

ORGANISATION MONDIALE DE LA SANTE

GOOD DISTRIBUTION PRACTICES (GDP)

FOR PHARMACEUTICAL PRODUCTS

This document has been prepared by Ms S.J. Putter of Walmer, Port Elizabeth, South Africa.

Please address any comments and/or corrections you may have on thereon to
Dr S. Kopp, Quality Assurance and Safety: Medicines, Essential Drugs and Medicines Policy,
World Health Organization, 1211 Geneva 27, Switzerland, fax: (+41 22) 791 4730
or e-mail: kopps@who.int, with a copy to bonnyw@who.int, by 31 March 2004.

© World Health Organization 2004

All rights reserved.
This draft is intended for a restricted audience only, i.e. the individuals and organizations having received this
draft. The draft may not be reviewed, abstracted, quoted, reproduced, transmitted, distributed, translated or
adapted, in part or in whole, in any form or by any means outside these individuals and organizations (including
the organizations’ concerned staff and member organizations) without the permission of WHO. The draft should
not be displayed on any website.
Please send any request for permission to:
Dr Sabine Kopp, Quality Assurance & Safety: Medicines (QSM), Department of Essential Drugs and Medicines
Policy (EDM), World Health Organization, CH-1211 Geneva 27, Switzerland.
Fax: (41-22) 791 4730; e-mails: kopps@who.int; bonnyw@who.int
The designations employed and the presentation of the material in this draft do not imply the expression of any
opinion whatsoever on the part of the World Health Organization concerning the legal status of any country,
territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines
on maps represent approximate border lines for which there may not yet be full agreement.
The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or
recommended by the World Health Organization in preference to others of a similar nature that are not mentioned.
Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters.

The World Health Organization does not warrant that the information contained in this draft is complete and
correct and shall not be liable for any damages incurred as a result of its use.
Working document QAS/04.068
page 2

TENTATIVE SCHEDULE FOR THE ADOPTION PROCESS OF DOCUMENT

QAS/04.068: GOOD DISTRIBUTION PRACTICES (GDP) FOR
PHARMACEUTICAL PRODUCTS1

Deadline
First draft prepared and mailed for comments January 2004
Deadline for receipt of comments 31 March 2004
Collation of comments April 2004
Revision of draft document May-June 2004
Mailing of draft for second round of June 2004
comments

Deadline for receipt of comments end August 2004

Collation of comments September 2004
Presentation to Thirty-ninth WHO Expert Autumn 2004
Committee on Specifications for
Pharmaceutical Preparations

1
This text is complementary to the WHO guide on Good trade and distribution practices for pharmaceutical
starting materials (WHO Expert Committee on Specifications for Pharmaceutical Preparations. Thirty-eighth
Report. Geneva, World Health Organization, 2004 (WHO Technical Report Series, No. 917, Annex 2).
 Working document QAS/04.068
page 3

GOOD DISTRIBUTION PRACTICES (GDP) FOR PHARMACEUTICAL

PRODUCTS

CONTENTS

page
1. Introduction ………………………………………………………… 4
2. Scope of document ………………………………………………… 5
3. Definitions ………………………………………………………… 5
4. Organization and management ……………………………………. 9
5. Personnel ………………………………………………………….. 9
6. Quality management ……………………………………………… 10
7. Premises, warehousing and storage ………………………………. 11
8. Vehicles and equipment ………………………………………….. 12
9. Containers and container labelling ……………………………….. 13
10. Dispatch …………………………………………………………… 14
11. Transportation and products in transit ……………………………. 15
12. Documentation …………………………………………………… 17
13. Repackaging and relabelling ……………………………………… 18
14. Complaints ………………………………………………………… 19
15. Recalls ……………………………………………………………... 20
16. Rejected and returned products ……………………………………. 21
17. Importation ………………………………………………………… 21
18. Contract activities …………………………………………………. 22
19. Self inspection …………………………………………………….. 22
20. Bibliography ………………………………………………………. 22
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1. INTRODUCTION

Distribution forms part of the supply chain of pharmaceutical products. Distributors are often
responsible for the effective, efficient and safe handling, storage and distribution of such
products. In some cases, however, a person or entity involved in the distribution of
pharmaceutical products is only involved in and is responsible for certain elements of the
distribution process. This document sets out appropriate steps to assist in meeting the
responsibilities involved in the different aspects of the distribution process. The guidelines are
intended to apply to all steps in the entire distribution/supply chain, and the relevant sections
should be considered by various role players as applicable to their role in distribution.

The storage, trade and distribution of pharmaceutical products are activities that are carried out
by various companies, institutions and individuals. The nature of the risks involved may
generally, however, be the same as those in the manufacturing environment, e.g. mix-ups,
contamination and cross-contamination. There are thus aspects in distribution to which the
principles of Good Manufacturing Practice (GMP) should be applied. These include, but are
not limited to, storage, distribution, transportation, documentation and record-keeping
practices, packaging, repackaging, labelling and relabelling.

The quality of pharmaceutical products can be affected by a lack of adequate control over
numerous activities which occur during the distribution process. Furthermore, the distribution
process has generally been rather neglected with regard to the establishment, development,
maintenance and control over the activities involved. Experience has also shown that, in
particular, activities such as repackaging and relabelling can pose an increased risk of
contamination, cross-contamination, mix-ups, degradation and changes in the properties of
products. The objective of these guidelines is to assist in ensuring the quality and integrity of
pharmaceutical products during all aspects of the distribution process.

In order to maintain the original quality, every activity in the distribution of pharmaceutical
products should be carried out according to the principles of GMP, Good Storage Practice
(GSP) and Good Distribution Practice (GDP). Although this guideline is intended to be a stand-
alone text, it does not deal with standards for the storage of pharmaceuticals which is covered
in the “WHO Guide to good storage practices for pharmaceuticals” (WHO Expert Committee
on Specifications for Pharmaceutical Preparations. Thirty-seventh Report. Geneva, World
Health Organization, 2003 (WHO Technical Report Series, No. 908, Annex 9)). It should also
be read in conjunction with other guidelines such as “WHO Good Manufacturing Practices:
main principles” (WHO Expert Committee on Specifications for Pharmaceutical Preparations.
Thirty-seventh Report. Geneva, World Health Organization, 2003 (WHO Technical Report
Series, No. 908, Annex 4)); “Guidelines for implementation of the WHO Certification Scheme
on the Quality of Pharmaceutical Products Moving in International Commerce (WHO Expert
Committee on Specifications for Pharmaceutical Preparations. Thirty-fourth Report. Geneva,
World Health Organization, 1996 (WHO Technical Report Series, No. 863, Annex 10)); WHO
pharmaceutical starting materials certification scheme (SMACS) (WHO Expert Committee on
Specifications for Pharmaceutical Preparations. Thirty-eighth Report. Geneva, World Health
Organization, 2004 (WHO Technical Report Series, No. 917, Annex 3)); and the Guidelines
 Working document QAS/04.068
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on import procedures for pharmaceutical products (WHO Expert Committee on Specifications

for Pharmaceutical Preparations. Thirty-fourth Report. Geneva, World Health Organization,
1996 (WHO Technical Report Series, No. 863, Annex 12)).

2. SCOPE OF THE DOCUMENT

These guidelines are intended to be applicable to all persons and companies involved in any
aspect of the distribution of pharmaceutical products. This includes all parties involved in trade
and distribution, pharmaceutical manufacturers, including the manufacturers of intermediate
and/or finished products, brokers, suppliers, distributors, wholesalers, traders, transport
companies, forwarding agents, processors, etc. The relevant sections of the guidelines should
also be considered and implemented by inter alia governments, regulatory bodies, international
organizations and donor agencies, certifying bodies, as well as all parties including health care
workers involved in any aspect of the trade and distribution of pharmaceutical products. The
guidelines can also be used as one tool in the prevention of the distribution of counterfeit and
substandard medicines.

3. DEFINITIONS

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 so used, becomes an active ingredient of that
pharmaceutical dosage form. 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.

Agreement
Arrangement undertaken by and legally binding on parties.

Batch
A defined quantity of starting material, packaging material or product processed in a single
process or series of processes so that it can be expected to be homogeneous. It may sometimes
be necessary to divide a batch into a number of sub-batches which are later brought together to
form a final homogeneous batch.

Batch number
A distinctive combination of numbers and/or letters which uniquely identifies a batch on the
labels, the batch records, the certificates of analysis, etc.

Calibration
The set of operations that establish, under specified conditions, the relationship between values
indicated by an instrument or system for measuring (especially weighing), recording and
controlling, or the values represented by a material measure and the corresponding known
values of a reference standard. Limits for acceptance of the results of measuring should be
established.
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Certificate of analysis (COA)

A document listing the results of testing a representative sample drawn from the batch to be
delivered. A COA should be equivalent to the WHO Model COA (WHO Expert Committee on
Specifications for Pharmaceutical Preparations. Thirty-sixth Report. Geneva, World Health
Organization, 2002 (WHO Technical Report Series, No. 902, Annex 10)).

Consignment
The quantity of a pharmaceutical starting material made by one manufacturer and supplied at
one time in response to a particular request or order. A consignment may comprise one or more
packages or containers and may include material belonging to more than one batch.

Container labelling
All information that appears on any part of a container, including that on any outer packaging
such as a carton.

Contamination
The undesired introduction of impurities of a chemical or microbiological nature, or of foreign
matter, into or onto a starting material, intermediate or finished product during production,
sampling, packaging or repackaging, storage or transport.

Cross-contamination
Contamination of a starting material, intermediate product or finished pharmaceutical product
with another starting material or product.

Contract
Business agreement for the supply of goods or performance of work at a specified price.

Distribution
The division and movement of pharmaceutical products from the premises of the manufacturer
of such products, or another central point, to the end user thereof, or to an intermediate point by
means of various transport methods, via various storage and/or user facilities.

Distributor
A person or entity that distributes or oversees the distribution of pharmaceutical products
through the distribution system.

Excipient
A substance, other than the active ingredient, that is intended or designated to be used in the
manufacture of a pharmaceutical product.

Expiry date
The date placed on the container of a pharmaceutical product or starting material which
designates the date up to and including which the pharmaceutical product is expected to remain
within specification if stored correctly. It is established for each batch by adding the shelf-life
period to the date of manufacture.
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FEFO (First Expiry/First Out principle concept)

A distribution procedure that ensures the stock with the earliest expiry date is distributed and/or
used before an identical stock item with a later expiry date is distributed and/or used.

FIFO (First In/First Out principle concept)

A distribution procedure that ensures that the oldest stock is distributed and/or used before a
newer and identical stock item is distributed and/or used.

Good manufacturing practices (GMP)

Good manufacturing practices are that part of quality assurance which ensure that products are
consistently produced and controlled to the quality standards appropriate to their intended use
and as required by the marketing authorization.

Labelling
The action involving the selection of the correct label, with the required information, followed
by line clearance and application of the label to the container.

Manufacture
All operations of purchase of materials and products, production, quality control, release,
storage and distribution of pharmaceutical products, and the related controls.

Material
A general term used to denote starting materials (active pharmaceutical ingredients (API) and
excipients), reagents, solvents, process aids, intermediates, packaging materials and labelling
materials.

Pharmaceutical product
Any product intended for human or veterinary use presented in its finished dosage form that is
intended to modify or explore physiological systems or pathological states to the benefit of the
recipient.

Pharmaceutical starting material

A pharmaceutical starting material is an API or excipient intended or designated for use in the
production of a pharmaceutical product.

Product recall
Product recall is a process of withdrawing or removing a pharmaceutical product from the
pharmaceutical distribution chain because of defects in the product, or complaints of serious
reactions to the product. The recall might be initiated by the manufacturer/importer/distributor
or a responsible agency.

Quality assurance
Quality assurance is a wide-ranging concept covering all matters that individually or
collectively influence the quality of a product. It is the totality of the arrangements made with
the object of ensuring that pharmaceutical products are of the quality required for their intended
use.
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Quality control
Quality control covers all measures taken, including the setting of specifications, sampling,
testing and analytical clearance, to ensure that starting materials, intermediates, packaging
materials and finished pharmaceutical products conform to established specifications for
identity, strength, purity and other characteristics.

Quarantine
The status of pharmaceutical products isolated physically or by other effective means (e.g.
electronically) pending a decision on their subsequent approval or rejection.

Relabelling
Process of putting a new label on the product (see also labelling).

Repackaging
Action of changing the packaging of the product.

Retest date
The date when a product should be re-examined to ensure that it is still suitable for use.

Sampling
Operations designed to obtain a representative portion of a pharmaceutical product, based on an
appropriate statistical procedure, for a defined purpose, e.g. acceptance of consignments, batch
release, etc.

Skip lot testing

Periodic or skip testing is the performance of specified tests at release on preselected batches
and/or at predetermined intervals, rather than on a batch-to-batch basis, with the understanding
that those batches not being tested must still meet all acceptance criteria established for that
product.

Standard operating procedure (SOP)

An authorized written procedure giving instructions for performing operations not necessarily
specific to a given product but of a more general nature (e.g. equipment operation, maintenance
and cleaning, validation, cleaning of premises and environmental control, sampling and
inspection).

Storage
The storage of pharmaceutical products up to their point of use.

Validation
The documented act of proving that any procedure, process, equipment, product, activity or
system actually leads to the expected results.

Vehicle
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Vehicle refers to trucks, vans, buses, minibuses, cars, trailers, aircraft, railway carriages, boats
and other means which are used to convey pharmaceutical products.
4. ORGANIZATION AND MANAGEMENT

4.1 The distributor or the organization, of which the distributor is part, must be an entity
that is appropriately authorized in terms of the applicable legislation, and which can be held
liable for its activities.

4.2 There should be an adequate organizational structure defined with the aid of an
organizational chart. The responsibility, authority and interrelationships of all personnel should
be clearly defined.

4.3 There must be sufficient personnel to carry out all the tasks for which the distributor is
responsible.

4.4 Managerial and technical personnel must have the authority and resources needed to
carry out their duties and to identify and correct departures from the quality management
system.

4.5 The responsibilities placed on any one individual should not be so extensive as to
present any risk to quality standards.

4.6 There should be arrangements in place to ensure that management and personnel are not
subject to commercial, political, financial and other pressures or conflicts of interest that may
have an adverse effect on the quality of service provided.

4.7 Individual responsibilities should be clearly defined and understood by the individuals
concerned and recorded as written job descriptions. Certain activities may require special
attention such as the supervision of performance of activities, in accordance with local
legislation.

4.8 In the event of a distributor having a limited number of personnel some duties may be
delegated or contracted out to suitably designated persons or entities. There should, however,
be no gaps or unexplained overlaps with regard to the application of GDP.

4.9 Safety procedures should be in place.

5. PERSONNEL

5.1 All personnel should be aware of and motivated to support the establishment and
maintenance of standards of GDP.

5.2 Key personnel involved in the distribution of pharmaceutical products should have the
ability and experience appropriate to their responsibility of ensuring that pharmaceutical
products are distributed properly.
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5.3 There should be an adequate number of competent personnel involved in all stages of
the distribution of pharmaceutical products in order to achieve pharmaceutical quality
assurance objectives.

5.4 National regulations with regard to qualifications and experience of personnel should be
followed.

5.5 Personnel should receive initial and continued training relevant to their tasks, in
accordance with a written training programme. Personnel dealing with hazardous
pharmaceutical products (such as highly active, toxic, infectious or sensitizing products) should
be given specific training. Training records should be kept.

5.6 Personnel involved in the distribution of pharmaceutical products should wear

protective or working garments suitable to the activities that they perform. Personnel dealing
with hazardous pharmaceutical products (such as highly active, toxic, infectious or sensitizing
products) should be provided with the necessary protective garments.

5.7 Procedures relating to personnel hygiene relevant to the activities to be carried out
should be established and observed. Such procedures should relate to health, hygiene and
clothing of personnel.

5.8 First-aid procedures and equipment for dealing with emergencies involving personnel
should be available.

5.9 Procedures and conditions of work for employees and other personnel having access to
pharmaceutical products must be designed and administered to assist in minimizing the
possibility of such products coming into unauthorized possession.

6. QUALITY MANAGEMENT

6.1 Within an organization quality assurance serves as a management tool. In contractual

situations quality assurance also serves to generate confidence in the supplier. There should be
a documented quality policy describing the overall intentions and policies of the distributor
regarding quality, as formally expressed and authorized by management.

6.2 Quality management should include:

- an appropriate infrastructure or “quality system”, encompassing the

organizational structure, procedures, processes and resources; and

- systematic actions necessary to ensure adequate confidence that a

product (or service) and documentation will satisfy given requirements for
quality. The totality of these actions is termed “quality assurance”.

6.3 The system should at least cover the principles of quality assurance as embodied in the
WHO guidelines on GMP for pharmaceutical products: main principles.
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6.4 All parties involved in the manufacture and distribution of pharmaceutical products
must share responsibility for the quality and safety of products to ensure that they are fit for
their intended use.

6.5 Where electronic commerce (e-commerce) is used, defined procedures and adequate
systems should be in place to ensure traceability and confidence in the quality of
pharmaceutical products.

6.6 Where applicable, authorized procurement and release procedures should be in place,
ensuring that appropriate pharmaceutical products are sourced from approved suppliers and
distributed.

6.7 The original manufacturer of pharmaceutical products and intermediaries should always
be traceable and the information available to authorities and end-users, downstream and
upstream.

6.8 Inspection and certification of compliance with a quality system (such as the applicable
International Standardizations Organization (ISO) series or national or international guidelines)
by external bodies is recommended. Such certification should not, however, be seen as a
substitute for compliance with this guideline and the applicable principles of GMP relating to
pharmaceutical products.

6.9 A system should be in place to perform self audits at regular intervals with the aim of
continuous improvement. Audit findings and corrective actions should be documented and
brought to the attention of management.

6.10 Authorized SOPs for all administrative and technical operations performed should be in
place.

6.11 Pharmaceutical products should be sampled randomly at the end of the distribution
process and sent for independent analysis to ensure that the products retain their quality
throughout the distribution process.

7. PREMISES, WAREHOUSING AND STORAGE

7.1 Good Storage Practice (GSP) is applicable in all circumstances where pharmaceutical
products are stored throughout the distribution process. For guidance relating to premises,
warehousing and the general principles of storage of pharmaceutical products including storage
areas, receipt and dispatch bays, sampling areas, storage conditions and requirements, receipt of
products, stock rotation and control of obsolete pharmaceutical products refer to the WHO
guideline on Good Storage Practices (WHO Expert Committee on Specifications for
Pharmaceutical Preparations. Thirty-seventh Report. Geneva, World Health Organization,
2003 (WHO Technical Report Series, No. 908, Annex 9)).

7.2 A system should be in place to ensure that products due to expire first are sold and/or
distributed first (FEFO). Where no expiry dates exist for the products, the FIFO principle
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should be applied. Deviations should, however, be permitted in exceptional cases where such a
deviation is temporary and appropriate.

8. VEHICLES AND EQUIPMENT

8.1 Where applicable, vehicles and equipment must be selected, located, designed,
constructed, adapted, used and maintained to suit the operations to be carried out. Suitable
policies and procedures should be in place with regard to the above-mentioned activities.

8.2 The design and use of vehicles and equipment must aim to minimize the risk of errors
and permit effective cleaning and/or maintenance, in order to avoid contamination, build-up of
dust or dirt and/or any adverse effect on the quality of pharmaceutical products being
distributed.

8.3 Dedicated vehicles and equipment should be used, where possible, when handling
pharmaceutical products. Where non-dedicated vehicles and equipment are used, cleaning
validation should be performed.

8.4 Defective vehicles and equipment should not be used, and should either be removed or
labelled as such.

8.5 There should be procedures in place for the operation and maintenance of all vehicles
and equipment involved in the distribution process.

8.6 Vehicles and containers should be kept clean and dry and free from accumulated waste.
A written sanitation programme should be available, indicating the frequency of cleaning and
the methods to be used.

8.7 Vehicles and containers should be kept free from rodents, vermin, birds and other pests.
There should also be written programmes for such control.

8.8 Apparatus used for the cleaning of vehicles and equipment should be chosen and used
as such that it is not a source of contamination.

8.9 Special attention should be given to the design, use, cleaning and maintenance of all
equipment used for bulk handling of pharmaceutical products.

8.10 Where special storage conditions (e.g. temperature and relative humidity) are required
during transit these should be provided, checked, monitored and recorded. All monitoring
records should be kept for a minimum of the shelf-life of the product distributed plus one year,
or as required by national legislation. Temperature mapping of vehicles (where applicable)
should support uniformity of the temperature across the vehicle. Recorded temperature
monitoring data should be available for review.

8.11 Equipment used for monitoring conditions within vehicles and containers, e.g.
temperature and humidity, should be calibrated at predetermined intervals.
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8.12 Vehicles and containers should be of sufficient capacity to allow orderly storage of the
various categories of pharmaceutical products during transportation.

8.13 Mechanisms to allow for the segregation of rejected, recalled and returned
pharmaceutical products during transit should be available.

8.14 Measures should be in place to prevent unauthorized persons from entering and/or
tampering with vehicles and/or equipment.

9. CONTAINERS AND CONTAINER LABELLING

9.1 All pharmaceutical products should be stored and distributed in containers which do not
have an adverse effect on the quality of the products, and which offer adequate protection from
external influences, including bacterial contamination.

9.2 Labels applied to containers should be clear, unambiguous, permanently fixed to the
container and be indelible. Information on the label should comply with applicable national
legislation with regard to the labelling of containers.

9.3 Each container should be identified by labelling bearing at least the following
information:

(a) the name of the pharmaceutical product, including grade and reference to
pharmacopoeias, where relevant;

(b) if applicable, the International Nonproprietary Name(s) (INN);

(c) the amount, weight or volume (as applicable);

(d) the batch number assigned by the original manufacturer or the batch number assigned
by the repacker, where the product has been repacked and relabelled (this requirement is not
applicable to medical gases);

(e) the expiry date;

(f) any specified storage conditions;

(g) any necessary handling precautions;

(h) identification of the original manufacturing site; and

(i) name and contact details of the supplier.

9.4 Special transport and/or storage conditions should be stated on the label. If a
pharmaceutical product is intended for transfer outside the control of the manufacturer’s
products management system, the name and address of the manufacturer, quality of contents,
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special transport conditions and any special legal requirements should also be included on the
label.

9.5 Unauthorized abbreviations, names or codes should not be used in the labelling of
containers.

9.6 The outside container should offer adequate protection from all external influences to
the pharmaceutical products contained therein.

9.7 Special care should be used when using dry ice in containers. In addition to safety
issues it must be ensured that the pharmaceutical product does not come into contact with the
dry ice, as it may have an adverse effect on the quality of the product.

10. DISPATCH

10.1 Pharmaceutical products should only be sold and/or distributed to persons or entities
that are entitled to acquire such products in terms of applicable national legislation.

10.2 For each batch of pharmaceutical product there should be proof of appropriate
laboratory determination of satisfactory conformity to specifications prior to the supply of such
product for use or consumption. Note that this requirement should not preclude the
transportation of pharmaceutical products prior to such confirmation being provided.

10.3 The supplier of pharmaceutical products should, prior to the dispatch of such products,
ensure that the person or entity, e.g. the contract acceptor for transportation of the
pharmaceutical products, is aware of and follows the appropriate storage and transport
conditions.

10.4 The dispatch and transport of pharmaceutical products should be commenced only after
the receipt of a valid delivery order which should be documented.

10.5 Written procedures for the dispatch of pharmaceutical products should be established.
Such procedures should take into account the nature of the pharmaceutical products, as well as
any special precautions to be observed.

10.6 Records for the dispatch of pharmaceutical products should be prepared and should
include at least the following information:

- date of dispatch;

- name and address of the addressee;

- a description of the products including, for example name, dosage form and
strength (if applicable);

- quantity and quality of the products;

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- assigned batch number and expiry date; and

- applicable transport and storage conditions.

10.7 Records of dispatch should contain enough information to enable traceability of the
pharmaceutical product from the point of supply to the end-user thereof. Such records should
facilitate the recall of a batch of a product as necessary.

10.8 Methods of transportation, including vehicles to be used, should be selected with care,
taking into consideration local conditions including the climate of the region and any seasonal
variations experienced. Delivery of products requiring controlled temperatures should be
carried out by the fastest practical means.

10.9 Delivery schedules should be established and route planning performed where needed,
taking local needs and conditions into account. Such schedules and plans should be realistic
and systematic. Care should be taken that the volume of pharmaceutical products delivered
does not exceed the capacity of storage facilities at destination.

10.10 Where applicable vehicles and containers should be loaded carefully and systematically
on a first-out/last-in basis in order to save time when unloading and prevent physical damage.

10.11 Products should not be received or supplied after their expiry date, or so close to the
expiry date that this date is likely to occur before the products are used by the consumer.

11. TRANSPORTATION AND PRODUCTS IN TRANSIT

11.1 Pharmaceutical products should be transported and handled whilst in transit, in

accordance with the principles of GMP. Products should be transported in such a way
that:
(a) the identity of the product is not lost;
(b) the product does not contaminate and is not contaminated by other
products;
(c) adequate precautions are taken against spillage or breakage; and
(d) thermolabile pharmaceutical products are transported in such a
way that the cold chain is maintained.

11.2 The required storage conditions for the pharmaceutical product should be maintained
within acceptable limits during transportation. The specific storage conditions of the product
should thus not be grossly exceeded, or exceeded for an unacceptable period of time during the
transit period.

11.3 Where special storage conditions are required (e.g. temperature, humidity) these should
be provided, monitored and recorded.
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11.4 The transport process should not have a negative effect on the integrity and quality of
pharmaceutical products.

11.5 Written procedures should be in place to deal with violations of specified storage
conditions, e.g. temperature violations.

11.6 Highly active and radioactive materials, other dangerous drugs and substances
presenting special risks of abuse, fire or explosion (e.g. combustible liquids, solids and
pressurized gases) should be stored and transported in safe, dedicated and secure areas,
containers and vehicles. In addition, applicable international agreements and national
legislation should be applied.

11.7 Products containing narcotics and other dependence-producing substances should be

stored and transported in safe, dedicated and secure areas, containers and vehicles. In addition,
applicable international agreements and national legislation should be applied.

11.8 Spillages should be cleaned as soon as possible to prevent possible contamination,

cross-contamination and hazards. Written procedures should be in place for the handling of
such occurrences.

11.9 Physical or other equivalent (e.g. electronic) segregation should be provided for the
storage and distribution of rejected, expired, recalled or returned pharmaceutical products
during transit. The products should be appropriately identified.

11.10 Provision should be made for the proper and safe storage and transportation of waste
materials awaiting disposal. Toxic substances and flammable materials should be stored and
transported in suitably designed, separate and closed containers, taking into account national
legislation and international agreements.

11.11 Vehicles and containers should be kept clean and dry whilst pharmaceutical products
are in transit.

11.12 Bulk transport of pharmaceutical products requires numerous precautions to avoid

contamination and cross-contamination. Dedicated equipment, tanks or containers should be
used. Procedures should be in place to ensure proper cleaning and prevention of cross-
contamination when liquids and bulk or packed materials are transported.

11.13 For bulk transport of pharmaceutical products validated cleaning procedures should be
used between loadings, and a list of restricted prior cargoes must be communicated to the
transport company (as applicable).

11.14 Packaging materials and transportation containers should be suitable to prevent damage
of pharmaceutical products during transport.
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11.15 Sufficient security should be provided to prevent theft and other misappropriation of
products. Steps should be taken to prevent unauthorized access to pharmaceutical products
being transported.

11.16 General international requirements regarding safety aspects (e.g. explosion,

contamination of the environment, etc.) should be observed.

11.17 Damage to containers and any other event or problem which occurs during transit must
be recorded and reported to the relevant department, entity or authority and investigated.

11.18 A batch tracking system should, as far as possible, be used which enables specific
batches transported to be traced during the distribution process.

12. DOCUMENTATION

12.1 Written instructions and records should be available which document all activities
relating to the distribution of pharmaceutical products, including all applicable receipts and
issues of pharmaceutical products.

12.2 Procedures must be established and maintained for the development, control and review
of all documents relating to the distribution process. Procedures must be in place for both
internally generated documents and documents from external sources.

12.3 Documents, in particular instructions and procedures relating to any activity that could
have an impact on the quality of pharmaceutical products, should be designed, completed,
reviewed and distributed with care.

12.4 The title, nature and purpose of each document should be stated clearly. The contents of
documents should be clear and unambiguous. Documents should be laid out in an orderly
fashion and be easy to check.

12.5 All documents should be completed, approved, signed and dated by an appropriate
authorized person(s) and should not be changed without the necessary authorization.

12.6 There should be compliance with national legislative requirements with regard to the
nature, content and retention of documentation, relating to the distribution of pharmaceutical
products. Where such requirements are not in place the documents should be retained for a
period equal to the shelf life of the products where applicable, plus one year.

12.7 The distributor must establish and maintain procedures for the identification, collection,
indexing, retrieval, storage, maintenance, disposal of and access to all applicable
documentation.

12.8 All records must be readily retrievable, stored and retained using facilities that provide a
suitable environment to prevent modification, damage, deterioration and/or loss of
documentation.
Working document QAS/04.068
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12.9 Documents should be reviewed regularly and kept up to date. When a document has
been revised a system should exist to prevent inadvertent use of the superseded version.

12.10 Mechanisms should exist to allow for transfer of information, including quality or
regulatory information between a manufacturer and a customer, as well as the transfer of
information to the relevant regulatory authority as required.

12.11 Records relating to storage of pharmaceutical products should be kept and be readily
available upon request in accordance with Good Storage Practices (WHO Expert Committee on
Specifications for Pharmaceutical Preparations. Thirty-seventh Report. Geneva, World Health
Organization, 2003 (WHO Technical Report Series, No. 908, Annex 9)).

13. REPACKAGING AND RELABELLING

13.1 Repackaging (including relabelling) of pharmaceutical products should only be

performed by distributors appropriately licensed to do so, and in accordance with GMP
principles. The guidelines provided below must be read in conjunction with other applicable
national and international guidelines relating to repackaging and relabelling of pharmaceutical
products.

13.2 Operations such as combining into a homogeneous batch, repackaging and/or

relabelling, are manufacturing processes and should, therefore, follow GMP when performed.
Special attention should be given to the following aspects:
(a) prevention of contamination, cross-contamination and mix-ups;
(b) security of stocks of labels, line clearance checks, on-line inspections,
destruction of excess batch-printed labels;
(c) good sanitation and hygiene practices;
(d) maintaining batch integrity;
(e) all labels which were removed from the original container during operations,
and a sample of the new label, should be kept as part of batch records;
(f) if more than one batch of label is used in one operation samples of each batch
should be kept; and
(g) maintaining product identity and integrity.

13.3 When different batches of a pharmaceutical product from the same original
manufacturing site are received by a distributor and combined into a homogenous batch, the
conformity of each batch with its specification should be confirmed before it is added.

13.4 Only products from the same manufacturing site received by a distributor and
conforming to the same specifications can be combined. If different batches of the same
products are combined to form a homogeneous batch, it should be defined as a new batch,
tested and supplied with a batch COA. In such cases the customer should be informed that the
 Working document QAS/04.068
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product supplied is a mixture of the manufacturer’s batches. The product may only be supplied
with a certificate of conformity to a specification identified by date of supply.

13.5 In all cases the original COA of the original manufacturer should be provided. If
retesting is done both the original and the new COA should be provided. The batch referred to
on the new COA should be traceable to the original COA.

13.6 Repackaging of products should be carried out with primary packaging materials, where
the quality and suitability of such packaging materials is equal to or better than the original
container.

13.7 Reuse of containers should be discouraged unless they have been cleaned using a
validated procedure. Recycled containers should not be used unless there is evidence that the
quality of the product packed will not be negatively affected.

13.8 Repackaging of products should only be performed if efficient environmental control

exists to ensure that there is no possibility of contamination, cross-contamination, degradation,
physicochemical changes and/or mix-ups. The quality of air supplied to the area should be
suitable for the activities performed.

13.9 Procedures should be followed to ensure proper label control.

13.10 Containers of repackaged products and relabelled containers should bear the name of
the original manufacturing site, in addition to the name of the distributor/repacker.

13.11 Procedures should be in place to ensure maintenance of the identity and quality of
pharmaceutical products, by appropriate means before and after repackaging operations.

13.12 Batch release procedures should be in place in accordance with GMP.

13.13 The repacker and relabeller should ensure that stability of repackaged pharmaceutical
products is not adversely affected. Stability studies to justify assigned expiry dates should be
conducted if the product is repackaged in a different container to that used by the original
manufacturer. Only official pharmacopoeial methods or validated analytical test methods
should be used for analysis.

14. COMPLAINTS

14.1 There should be a written procedure in place for the handling of complaints. Distinction
should be made between complaints about a product or its packaging and those relating to
distribution.

14.2 All complaints and other information concerning potentially defective pharmaceutical
products must be reviewed carefully according to written procedures describing the action to be
taken, including the need to consider a recall where appropriate.
Working document QAS/04.068
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14.3 Any complaint concerning a material defect should be recorded and thoroughly
investigated to identify the origin or reason for the complaint (e.g. repackaging procedure,
original manufacturing process, etc.).

14.4 If a defect relating to a pharmaceutical product is discovered or suspected consideration

should be given as to whether other batches of the product should also be checked.

14.5 Where necessary appropriate follow-up action should be taken after investigation and
evaluation of the complaint.

15. RECALLS

15.1 There should be a system which includes a written procedure to recall promptly and
effectively pharmaceutical products known or suspected to be defective, with a designated
person(s) responsible for recalls.

15.2 Such procedures should be checked regularly and updated.

15.3 The original manufacturer should be informed in the event of a recall.

15.4 The effectiveness of the arrangements for recalls should be evaluated at regular
intervals.

15.5 All recalled pharmaceutical products should be stored in a secure, segregated area
pending appropriate action.

15.6 Recalled pharmaceutical products should be segregated during transit and clearly
labelled as recalled products.

15.7 The storage conditions applicable to a pharmaceutical product which is subject to recall
should be maintained during storage and transit until such time as a decision has been made.

15.8 All customers and competent authorities of all countries to which a given
pharmaceutical product may have been distributed should be informed promptly of any
intention to recall the product because it is, or is suspected to be, defective.

15.9 All records should be readily available to a designated person(s) responsible for recalls.
These records should contain sufficient information on pharmaceutical products supplied to
customers (including exported products).

15.10 The progress of a recall process should be recorded and a final report issued, which
includes a reconciliation between delivered and recovered quantities of products.
 Working document QAS/04.068
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16. REJECTED AND RETURNED PRODUCTS

16.1 Rejected products and those returned to a distributor should be appropriately identified
and handled in accordance with a procedure which involves at least the keeping of such
pharmaceutical products in quarantine in a dedicated area, in order to avoid confusion and
prevent distribution until a decision has been taken with regard to their disposition.

16.2 The necessary assessment and decision regarding the disposition of such products must
be taken by a designated person. The nature of the product returned to the distributor, any
special storage conditions required, its condition and history and the time elapsed since it was
issued should all be taken into account in this assessment. Where any doubt arises over the
quality of a pharmaceutical product it should not be considered suitable for reissue or reuse.

16.3 Provision should be made for the proper and safe transport of returned products in
accordance with the relevant storage and other requirements.

16.4 Provision should be made for the proper and safe transport of rejected and waste
materials prior to their disposal.

16.5 Pharmaceutical products should be destroyed where necessary in accordance with

international, national and local requirements regarding disposal of such products, and with due
consideration to protection of the environment.

16.6 Records of all returned products and/or destroyed pharmaceutical products should be
kept.

17. IMPORTATION

17.1 Consideration should be given to the guidelines on import procedures for

pharmaceutical products (WHO Expert Committee on Specifications for Pharmaceutical
Preparations. Thirty-fourth Report. Geneva, World Health Organization, 1996 (WHO
Technical Report Series, No. 863, Annex 12)). The following aspects should be given
particular attention.

17.2 The number of ports of entry in a country for the handling of imports of pharmaceutical
products should be limited.

17.3 The most appropriately located and best equipped to handle imports of pharmaceutical
products should be chosen as the point(s) of entry when such products are imported into a
country.

17.4 Imported medicines should be in original packs except for those imported in bulk for
repackaging and/or manufacturing drug formulations.

17.5 At the port of entry consignments of pharmaceutical products should be stored under
suitable conditions for as short a time as possible.
Working document QAS/04.068
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17.6 All reasonable steps should be taken by importers to ensure that products are not
mishandled or exposed to adverse storage conditions at wharves or airports.

17.7 Where necessary persons with pharmaceutical training should be involved with the
customs procedures.

17.8 The WHO Certification Scheme on the Quality of Pharmaceutical Products Moving in
International Commerce should be used to provide data regarding quality assessment of
imported pharmaceutical products.

18. CONTRACT ACTIVITIES

18.1 Any activity relating to the distribution of a pharmaceutical product which is delegated
to another person or entity should be performed in terms of a written contract which is agreed
upon by the contract giver and the contract accepter.

18.2 The contract should define the responsibilities of each party including observance of the
principles of GDP.

18.3 All contract accepters should comply with the requirements in this guideline.

18.4 Subcontracting may be permissible under certain conditions subject to the written
approval of the contract giver, particularly for activities such as sampling, analysis, repacking
and relabelling.

19. SELF INSPECTION

19.1 Self inspections should be conducted in order to monitor the implementation and
compliance with the principles of GDP and to propose necessary corrective measures.

19.2 Self inspections should be conducted in an independent and detailed way by a

designated, competent person.

19.3 All self inspections should be recorded. Reports should contain all observations made
during the inspection and where applicable, proposals for corrective measures. Actions taken
should also be recorded.

20. BIBLIOGRAPHY

WHO Expert Committee on Specifications for Pharmaceutical Preparations. Thirty-fourth

Report. Geneva, World Health Organization, 1996 (WHO Technical Report Series, No 863).

WHO Expert Committee on Specifications for Pharmaceutical Preparations. Thirty-sixth

Report. Geneva, World Health Organization, 2002 (Technical Report Series, No. 902).
 Working document QAS/04.068
page 23

WHO Expert Committee on Specifications for Pharmaceutical Preparations. Thirty-seventh

Report. Geneva, World Health Organization, 2003 (Technical Report Series, No. 908).

WHO Expert Committee on Specifications for Pharmaceutical Preparations. Thirty-eighth

Report. Geneva, World Health Organization, 2004 (Technical Report Series, No. 917).

Quality Assurance of Pharmaceuticals. A compendium of guidelines and related materials,

Volume 1. Geneva, World Health Organization, 1997.

Quality Assurance of Pharmaceuticals. A compendium of guidelines and related materials.

Good manufacturing practices and inspection, Volume 2 (updated version). Geneva, World
Health Organization, 2004.

Marketing Authorization of Pharmaceutical Products with Special Reference to Multisource

(Generic) Products – A Manual for a Drug Regulatory Authority. Geneva, World Health
Organization, 1999 (Regulatory Support Series, No. 5, WHO/DMP/RGS/98.5).

A Model Quality Assurance System for Prequalification, Procurement, Storage and

Distribution of Pharmaceutical Products. Geneva, World Health Organization, 2003
(unpublished draft).

Australian Code of Good Wholesaling Practice for Therapeutic Goods for Human Use.
Therapeutic Goods Administration, Australia. November 1991.

Current Good Manufacturing Practice in Manufacturing, Processing, Packing or Holding of

drugs and Current Good Manufacturing Practice for Finished Pharmaceuticals. Code of
Federal Regulations Parts 210 and 211. Food and Drug Administration, USA.

Principles and Guidelines of Good Manufacturing Practice for Medicinal Products for Human
Use. Commission Directive 91/356/EEC, 13 June 1991. European Agency for Evaluation of
Medicinal Products.

Guidance Document: Good Manufacturing Practice for Medicine in South Africa. Medicines
Control Council, South Africa, 2003.

Guide to Good Manufacturing Practices for Medicinal Products. Pharmaceutical Inspection

Convention, Pharmaceutical Inspection Co-operation Scheme, January 2002.

Managing Medicine Supply. The selection, procurement, distribution, and use of

pharmaceuticals. Management Sciences for Health in collaboration with World Health
Organization. 2nd Ed. Connecticut, USA. Kumarian Press, Inc., 1997.

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