PHARMACEUTICAL INSPECTION CONVENTIONPHARMACEUTICAL INSPECTION CO-OPERATION SCHEME

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1 June 2014

PIC/S GUIDE TO GOOD DISTRIBUTION
PRACTICE
FOR MEDICINAL PRODUCTS© PIC/S June 2014
Reproduction prohibited for commercial purposes.
Reproduction for internal use is authorised,provided that the source is acknowledged.

Editor:PIC/S Secretariat

e-mail:web site:

info@picscheme.org
http://www.picscheme.org

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TABLE OF CONTENT
DOCUMENT HISTORY .............................................................................................................................. 4
INTRODUCTION ........................................................................................................................................ 4
PURPOSE.......................................................................................................................................... 5

SCOPE.......................................................................................................................................... 5

CHAPTER 1QUALITY MANAGEMENT ............................................................................................... 6

1.1

PRINCIPLE ................................................................................................................ 6

1.2

QUALITY SYSTEM .................................................................................................... 6

1.3

MANAGEMENT OF OUTSOURCED ACTIVITIES ...................................................... 6

1.4

MANAGEMENT REVIEW AND MONITORING ........................................................... 7

1.5

QUALITY RISK MANAGEMENT ................................................................................ 7

CHAPTER 2PERSONNEL ................................................................................................................... 8

2.1

PRINCIPLE ................................................................................................................ 8

2.2

GENERAL .................................................................................................................. 8

2.3

DESIGNATION OF RESPONSIBILITIES.................................................................... 8

2.4

TRAINING .................................................................................................................. 92.5

HYGIENE ................................................................................................................... 9

CHAPTER 3 PREMISES AND EQUIPMENT .......................................................................................... 10
3.1

PRINCIPLE ............................................................................................................... 10

3.2

PREMISES .............................................................................................................. 10

3.3

TEMPERATURE AND ENVIRONMENT CONTROL ........................................................ 11

3.4

EQUIPMENT ............................................................................................................ 11

3.5

COMPUTERISED SYSTEMS ................................................................................... 12

3.6

QUALIFICATION AND VALIDATION ...................................................................... 12

CHAPTER 4 DOCUMENTATION ........................................................................................................ 13
4.1

PRINCIPLE .............................................................................................................. 13

4.2

GENERAL ................................................................................................................ 13

CHAPTER 5

OPERATIONS ............................................................................................................... 14

5.1

PRINCIPLE .............................................................................................................. 14

5.2

QUALIFICATION OF SUPPLIERS ........................................................................... 14

5.3

QUALIFICATION OF CUSTOMERS ........................................................................ 14

5.4

RECEIPT OF MEDICINAL PRODUCTS .................................................................. 15

5.5

STORAGE ............................................................................................................... 15

5.6

DESTRUCTION OF OBSOLETE GOODS ............................................................ 15

5.7

PICKING .................................................................................................................. 16

5.8

SUPPLY ................................................................................................................... 16

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5.9

IMPORT AND EXPORT ........................................................................................... 16

CHAPTER 6 COMPLAINTS, RETURNS, SUSPECTED FALSIFIED MEDICINAL PRODUCTS AND
MEDICINAL PRODUCT RECALLS.................................................................................... 17
6.1

PRINCIPLE ............................................................................................................... 17

6.2

COMPLAINTS .......................................................................................................... 17

6.3

RETURNED MEDICINAL PRODUCTS .................................................................... 17

6.4

FALSIFIED MEDICINAL PRODUCTS ......................................................................... 18

6.5

MEDICINAL PRODUCT RECALLS ............................................................................. 18

CHAPTER 7

OUTSOURCED ACTIVITIES ........................................................................................ 20

7.1

PRINCIPLE ............................................................................................................... 20

7.2

CONTRACT GIVER ................................................................................................. 20

7.3

CONTRACT ACCEPTOR ........................................................................................ 20

CHAPTER 8

SELF-INSPECTIONS ...................................................................................................... 21

8.1

PRINCIPLE ............................................................................................................... 21

8.2

SELF-INSPECTIONS ............................................................................................... 21

CHAPTER 9

TRANSPORTATION ..................................................................................................... 22

9.1

PRINCIPLE .............................................................................................................. 22

9.2

TRANSPORTATION ................................................................................................ 22

9.3

CONTAINERS, PACKAGING AND LABELLING..................................................... 23

9.4

PRODUCTS REQUIRING CONTROLLED CONDITIONS......................................... 23

ANNEX 1

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DOCUMENT HISTORY
Adoption by the PIC/S Committee
Entry into force

15-16 May 2014
1 June 2014

INTRODUCTION
This Guide is based on the EU Guidelines on Good Distribution Practice (GDP) of
Medicinal Products for Human Use (2013/C 343/01). The EU Guidelines have been
adapted by the Expert Circle on GDP for PIC/S purposes. However, the EU specificreferences have been deleted in this Guide.
This Guide has been adopted by PIC/S as a guidance document. It is up to each PIC/S
Participating Authority to decide whether it should become a legally-binding standard.
The wholesale distribution of medicinal products is an important activity in integrated
supply chain management. Today’s distribution network for medicinal products isincreasingly complex and involves many players. These guidelines lay down appropriate
tools to assist wholesale distributors in conducting their activities and to prevent falsified
medicines from entering the legal supply chain. Compliance with these guidelines will
ensure control of the distribution chain and consequently maintain the quality and theintegrity of medicinal products.
Wholesale distribution of medicinal products is all activities consisting of procuring,holding, supplying, importing or exporting medicinal products, apart from supplying
medicinal products to the public. Such activities are carried out with manufacturers or
their depositories, importers, other wholesale distributors or with pharmacists andpersons authorized or entitled to supply medicinal products to the public. In the

territories of some PIC/S Participating Authorities importation may fall under GMP
and a manufacturer’s license may be required.
Any person acting as a wholesale distributor has to hold a wholesale distribution licencein accordance with national legislation.
Possession of a manufacturing licence includes authorisation to distribute the medicinal
products covered by the authorisation. Manufacturers performing any distribution
activities with their own products must therefore comply with GDP.
The definition of wholesale distribution does not depend on whether that distributor isestablished or operating in specific customs areas, such as in free zones or in free
warehouses. All obligations related to wholesale distribution activities (such as importing,exporting, holding or supplying) also apply to these distributors. Relevant sections ofthese guidelines should also be adhered to by other actors involved in the distribution of
medicinal products.
A glossary of some terms used in the Guide has been incorporated as Annex 1.

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PURPOSE
In order to ensure the maintaining of high standards of quality assurance and theintegrity of the distribution processes of medicinal products, to promote uniformity inlicensing of wholesaling of medicinal products and to further facilitate the removal of
barriers to trade in medicinal products, the following Guide to Good Distribution Practice(GDP) for Medicinal Products has been adopted.
Administrative measures of national health authorities should be directed towards theapplication of these standards in practice, and any new or amended national regulations
for good distribution practice should at least meet their level. These standards are also
intended to serve wholesale distributors as a basis for the elaboration of specific rules
adapted to their individual needs. It is recognised that there are acceptable methods,
other than those described in this Guide, which are capable of achieving the principles of
the Guide. This document provides guidance for preparation for inspections and may be
used for training purposes
SCOPE
The standards set out herein apply to medicines and similar products intended forhuman use. It is recommended, however, that the same kind of attention be given to the
distribution of veterinary medicinal products. This guideline can also be applicable forInvestigational Medicinal Products (IMP).
At the time of issue, this document reflected the current state of the art. It is not intended
to be a barrier to technical innovation or the pursuit of excellence or to place any
restraint upon the development of new concepts or new technologies, which have beenvalidated and provide a level of Quality Assurance and integrity of the distribution
processes at least equivalent to those set out in this Guide.

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CHAPTER 1QUALITY MANAGEMENT
1.1

PRINCIPLE
Wholesale distributors should maintain a quality system setting out responsibilities,
processes and risk management principles in relation to their activities. All distribution
activities should be clearly defined in procedures and systematically reviewed. All
critical steps of distribution processes and significant changes should be justified andwhere relevant validated. The quality system is the responsibility of the organisation’s
management and requires their leadership and active participation and should be
supported by staff commitment.

1.2

QUALITY SYSTEM

1.2.1

The system for managing quality should encompass the organisational structure,procedures, processes and resources, as well as activities necessary to ensure
confidence that the product delivered maintains its quality and integrity and remains
within the legal supply chain during storage and/or transportation.

1.2.2

The quality system should be fully documented and its effectiveness monitored. All
quality system related activities should be defined and documented. A quality manualor equivalent documentation approach should be established.

1.2.3

Designated responsible person(s) should be appointed by the management, whoshould have clearly specified authority and responsibility for ensuring that a quality
system is implemented and maintained.

1.2.4

The management of the distributor should ensure that all parts of the quality system
are adequately resourced with competent personnel, and suitable and sufficient
premises, equipment and facilities.

1.2.5

The size, structure and complexity of distributor’s activities should be taken into
consideration when developing or modifying the quality system.

1.2.6

A change control system should be in place. This system should incorporate quality
risk management principles, and be proportionate and effective.

1.2.7

The quality system should ensure that:i.

medicinal products are procured, held, supplied, imported or exported in a waythat is compliant with the requirements of GDP;ii. management responsibilities are clearly specified;iii. products are delivered to the right recipients within a satisfactory time period;
iv. records are made contemporaneously;
v. deviations from established procedures are documented and investigated;vi. appropriate corrective and preventive actions (commonly known as CAPA) aretaken to correct deviations and prevent them in line with the principles of quality
risk management.
1.3

MANAGEMENT OF OUTSOURCED ACTIVITIESThe quality system should extend to the control and review of any outsourced
activities related to the procurement, holding, supply, import or export of medicinal
products. These processes should incorporate quality risk management and include:

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i.

assessing the suitability and competence of the Contract Acceptor to carry out theactivity, preserving the integrity and security of the medicinal products, andrequesting, preserving documentation, and checking authorisation or marketing
status, if required;
ii. defining the responsibilities and communication processes for the quality-related
activities of the parties involved;
iii. monitoring and review of the performance of the Contract Acceptor, and theidentification and implementation of any required improvements on a regular basis.
1.4

MANAGEMENT REVIEW AND MONITORING

1.4.1

The management should have a formal process for reviewing the quality system on aperiodic basis. The review should include:
i. measurement of the achievement of quality system objectives;
ii. assessment of performance indicators that can be used to monitor theeffectiveness of processes within the quality system, such as complaints, recalls,
returns, deviations, CAPA, changes to processes; feedback on outsourced
activities; self-assessment processes including risk assessments and audits; andexternal assessments such as inspections, findings and customer audits;iii. emerging regulations, guidance and quality issues that can impact the quality
management system;
iv. innovations that might enhance the quality system;
v. changes in business environment and objectives.

1.4.2

The outcome of each management review of the quality system should be
documented in a timely manner and effectively communicated internally.

1.5

QUALITY RISK MANAGEMENT

1.5.1

Quality risk management is a systematic process for the assessment, control,
communication and review of risks to the quality of medicinal products. It can beapplied both proactively and retrospectively.

1.5.2

Quality risk management should ensure that the evaluation of the risk to quality isbased on scientific knowledge, experience with the process and ultimately links to theprotection of the patient. The level of effort, formality and documentation of theprocess should be commensurate with the level of risk. Examples of the processes
and applications of quality risk management can be found in guideline Q9 of theInternational Conference on Harmonisation (ICH).

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CHAPTER 2PERSONNEL
2.1

PRINCIPLE
The correct distribution of medicinal products relies upon people. For this reason,
there must be sufficient competent personnel to carry out all the tasks for which thewholesale distributor is responsible. Individual responsibilities should be clearly
understood by the staff and be recorded.

2.2

GENERAL

2.2.1

There should be an adequate number of competent personnel involved in all stagesof the wholesale distribution activities of medicinal products. The number of personnel
required will depend on the volume and scope of activities.

2.2.2

The organisational structure of the wholesale distributor should be set out in an
organisation chart. The role, responsibilities, and interrelationships of all personnel
should be clearly indicated.

2.2.3

The role and responsibilities of employees working in key positions should be set out
in written job descriptions, along with any arrangements for deputising.

2.3

DESIGNATION OF RESPONSIBILITIES

2.3.1

The wholesale distributor must designate personnel responsible for GDP compliance.
Relevant personnel should have appropriate competence and experience as well as
knowledge of and training in GDP.

2.3.2

Wholesale distributors should nominate personnel for out of hours contact (e.g.
emergencies and/or recall). Designated responsible person(s) may delegate duties
but not responsibilities.

2.3.3

Written job descriptions for designated responsible person(s) should define theirauthority to take decisions with regard to their responsibilities. The wholesale
distributor should give the designated responsible person(s) the defined authority,
adequate resources and responsibility needed to fulfil their duties.

2.3.4

Designated responsible person(s) should carry out their duties in such a way as toensure that the wholesale distributor can demonstrate GDP compliance and thatpublic service obligations are met.

2.3.5

The responsibilities of the designated responsible person(s) include but are notlimited to:i.
ii.

ensuring that a quality management system is implemented and maintained;focusing on the management of authorised activities and the accuracy and qualityof records;
iii. ensuring that initial and continuous training programmes are implemented andmaintained;
iv. coordinating and promptly performing any recall operations for medicinal
products;
v. ensuring that relevant customer complaints are dealt with effectively;
vi. ensuring that suppliers and customers are approved;vii. approving any subcontracted activities which may impact on GDP;viii. ensuring that self-inspections are performed at appropriate regular intervals
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following a prearranged programme and necessary corrective measures are put
in place;ix. keeping appropriate records of any delegated duties;
x. deciding on the final disposition of returned, rejected, recalled or falsified
products;
xi. approving any returns to saleable stock;xii. ensuring that any additional requirements imposed on certain products bynational legislation are adhered to.
2.4

TRAINING

2.4.1

All personnel involved in wholesale distribution activities should be trained on therequirements of GDP. They should have the appropriate competence and experience
prior to commencing their tasks.

2.4.2

Personnel should receive initial and continuing training relevant to their role, based on
written procedures and in accordance with a written training programme. Designatedresponsible person(s) should also maintain their competence in GDP through regulartraining.

2.4.3

In addition, training should include aspects of product identification and avoidance offalsified medicines entering the supply chain.

2.4.4

Personnel dealing with any products which require more stringent handling conditions
should receive specific training. Examples of such products include hazardous
products, radioactive materials, products presenting special risks of abuse (including
narcotic and psychotropic substances), and temperature-sensitive products.

2.4.5

A record of all training should be kept, and the effectiveness of training should beperiodically assessed and documented.

2.5

HYGIENE
Appropriate procedures relating to personnel hygiene, relevant to the activities being
carried out, should be established and observed. Such procedures should coverhealth, hygiene and clothing.

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CHAPTER 3
PREMISES AND EQUIPMENT
3.1

PRINCIPLE
Wholesale distributors must have suitable and adequate premises, installations andequipment, so as to ensure proper storage and distribution of medicinal products. In
particular, the premises should be clean, dry and maintained within acceptabletemperature limits.

3.2

PREMISES

3.2.1

The premises should be designed or adapted to ensure that the required storage
conditions are maintained. They should be suitably secure, structurally sound and of
sufficient capacity to allow safe storage and handling of the medicinal products.
Storage areas should be provided with adequate lighting and ventilation to enable all
operations to be carried out accurately and safely.

3.2.2

Where premises are not directly operated by the wholesale distributor, a written
contract should be in place. The contracted premises should be covered by aseparate wholesale distribution authorisation if required by national legislation.

3.2.3

Medicinal products should be stored in segregated areas which are clearly marked
and have access restricted to authorised personnel. Any system replacing physicalsegregation, such as electronic segregation based on a computerised system, should
provide equivalent security and should be validated.

3.2.4

Products pending a decision as to their disposition or products that have been
removed from saleable stock should be segregated either physically or through anequivalent electronic system. The requirement for physical segregation and storage ina dedicated area should be assessed using a risk based approach. At least, falsified
medicinal products, expired products, recalled products, rejected products andmedicinal products not authorised for the internal market must always be physicallysegregated. The appropriate degree of security should be applied in these areas toensure that such items remain separate from saleable stock. These areas should beclearly identified.

3.2.5

Special attention should be paid to the storage of products with specific handling
instructions as specified in national legislation. Special storage conditions (andspecial authorisations) may be required for such products (e.g. narcotics andpsychotropic substances).

3.2.6

Radioactive materials and other hazardous products, as well as products presenting
special safety risks of fire or explosion (e.g. medicinal gases, combustibles,
flammable liquids and solids), should be stored in one or more dedicated areas
subject to national legislation and appropriate safety and security measures.

3.2.7

Receiving and dispatch bays should protect products from prevailing weather
conditions. There should be adequate separation between the receipt and dispatch
and storage areas. Procedures should be in place to maintain control of
inbound/outbound goods. Reception areas where deliveries are examined following
receipt should be designated and suitably equipped.

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3.2.8

Unauthorised access to all areas of the authorised premises should be prevented.
Prevention measures would usually include a monitored intruder alarm system andappropriate access control. Visitors should be accompanied by authorised personnel.

3.2.9

Premises and storage facilities should be clean and free from litter and dust. Cleaning
programmes, instructions and records should be in place. Cleaning should be
conducted so as not to present a source of contamination.

3.2.10Premises should be designed and equipped so as to afford protection against theentry of insects, rodents or other animals. A preventive pest control programmeshould be in place. Appropriate pest control records should be maintained.

3.2.11

Rest, wash and refreshment rooms for employees should be adequately separated
from the storage areas. The presence of food, drink, smoking material or medicinal
products for personal use should be prohibited in the storage areas.

3.3

TEMPERATURE AND ENVIRONMENT CONTROL

3.3.1

Suitable equipment and procedures should be in place to check the environment
where medicinal products are stored. Environmental factors to be considered include
temperature, light, humidity and cleanliness of the premises.

3.3.2

An initial temperature mapping exercise should be carried out on the storage area
before use, under representative conditions. Temperature monitoring equipment
should be located according to the results of the mapping exercise, ensuring thatmonitoring devices are positioned in the areas that experience the extremes offluctuations. The mapping exercise should be repeated for significant changes
according to the results of a risk assessment exercise. For small premises of a few
square meters which are at room temperature, an assessment of potential risks (e.g.
heater / air-conditioner) should be conducted and temperature monitors placed
accordingly.

3.4

EQUIPMENT

3.4.1

All equipment impacting on storage and distribution of medicinal products should bedesigned, located, maintained and cleaned to a standard which suits its intended
purpose. Planned maintenance should be in place for key equipment vital to thefunctionality of the operation.

3.4.2

Equipment used to control or to monitor the environment where the medicinal
products are stored should be calibrated at defined intervals based on a risk andreliability assessment.

3.4.3

Calibration of equipment should be traceable to a national or international
measurement standard. Appropriate alarm systems should be in place to provide
alerts when there are excursions from predefined storage conditions. Alarm levels
should be appropriately set and alarms should be regularly tested to ensure adequate
functionality.

3.4.4

Equipment repair, maintenance and calibration operations should be carried out insuch a way that the quality and integrity of the medicinal products is notcompromised. Procedures should be in place to ensure the integrity of medicinal
products are maintained in the event of equipment failure.

3.4.5

Adequate records of repair, maintenance and calibration activities for key equipment
should be made and the results should be retained. Key equipment would include forexample cold stores, monitored intruder alarm and access control systems,

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refrigerators, thermo hygrometers, or other temperature and humidity recording
devices, air handling units and any equipment used in conjunction with the onward
supply chain.
3.5

COMPUTERISED SYSTEMS

3.5.1

Before a computerised system is brought into use, it should be demonstrated, throughappropriate validation or verification studies, that the system is capable of achieving
the desired results accurately, consistently and reproducibly.

3.5.2

A written, detailed description of the system should be available (including diagrams
where appropriate). This should be kept up to date. The document should describe
principles, objectives, security measures, system scope and main features, how thecomputerised system is used and the way it interacts with other systems.

3.5.3

Data should only be entered into the computerised system or amended by persons
authorised to do so.

3.5.4

Data should be secured by physical or electronic means and protected against
accidental or unauthorised modifications. Stored data should be checked periodicallyfor accessibility. Data should be protected by backing up at regular intervals. Backup
data should be retained for the period stated in national legislation but at least 5 years
at a separate and secure location.

3.5.5

Procedures to be followed if the system fails or breaks down should be defined. Thisshould include systems for the restoration of data.

3.6

QUALIFICATION AND VALIDATION

3.6.1

Wholesale distributors should identify what key equipment qualification and/or key
process validation is necessary to ensure correct installation and operation. The
scope and extent of such qualification and/or validation activities (such as storage,
pick and pack processes, transportation) should be determined using a documented
risk assessment approach.

3.6.2

Equipment and processes should be respectively qualified and/or validated before
commencing use and after any significant changes (e.g. repair or maintenance).

3.6.3

Validation and qualification reports should be prepared summarising the results
obtained and commenting on any observed deviations. Deviations from establishedprocedures should be documented and further actions decided to correct deviations
and avoid their reoccurrence (corrective and preventive actions). The principles of
CAPA should be applied where necessary. Evidence of satisfactory validation andacceptance of a process or piece of equipment should be produced and approved byappropriate personnel.

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CHAPTER 4
DOCUMENTATION
4.1

PRINCIPLE
Good documentation constitutes an essential part of the quality system. Written
documentation should prevent errors from spoken communication and permits the
tracking of relevant operations during the distribution of medicinal products. Records
should be made at the time each operation is undertaken.

4.2

GENERAL

4.2.1

Documentation comprises all written procedures, instructions, contracts, records anddata, in paper or in electronic form. Documentation should be readily
available/retrievable.

4.2.2

With regard to the processing of personal data of employees, complainants or any
other natural person, national legislation on the protection of individuals applies to theprocessing of personal data and to the free movement of such data.

4.2.3

Documentation should be sufficiently comprehensive with respect to the scope of thewholesale distributor’s activities and in a language understood by personnel. It should
be written in clear, unambiguous language and be free from errors.

4.2.4

Documentation should be approved, signed and dated by designated persons, as
required. It should not be handwritten; although, where it is necessary, sufficientspace should be provided for such entries.

4.2.5

Any alteration made in the documentation should be signed and dated; the alteration
should permit the reading of the original information. Where appropriate, the reason
for the alteration should be recorded.

4.2.6

Documents should be retained for the period stated in national legislation but at least
5 years. Personal data should be deleted or anonymised as soon as their storage is
no longer necessary for the purpose of distribution activities.

4.2.7

Each employee should have ready access to all necessary documentation for thetasks executed.

4.2.8

Attention should be paid to using valid and approved procedures. Documents shouldhave unambiguous content; title, nature and purpose should be clearly stated.
Documents should be reviewed regularly and kept up to date. Version control should
be applied to procedures. After revision of a document a system should exist to
prevent inadvertent use of the superseded version. Superseded or obsolete
procedures should be removed from workstations and archived.

4.2.9

Records must be kept either in the form of purchase/sales invoices, delivery slips, oron computer or any other form, for any transaction in medicinal products received or
supplied. Records must include at least the following information: date; name of the
medicinal product; quantity received, supplied; name and address of the supplier,customer, or consignee, as appropriate; and batch number , expiry date, as requiredby national legislation . Records are made contemporaneously and if handwritten, inclear, legible and indelible handwriting.

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CHAPTER 5
OPERATIONS
5.1

PRINCIPLE
All actions taken by wholesale distributors should ensure that the identity of the
medicinal product is not lost and that the wholesale distribution of medicinal products
is performed according to the information on the outer packaging. The wholesale
distributor should use all means available to minimise the risk of falsified medicinal
products entering the legal supply chain. All medicinal products distributed in theintended market by a wholesale distributor must be appropriately authorised by thenational authorities. All key operations described below should be fully described in
the quality system in appropriate documentation.

5.2

QUALIFICATION OF SUPPLIERS

5.2.1

Wholesale distributors must obtain their supplies of medicinal products only frompersons who are themselves in possession of a wholesale distribution authorisation,or who are in possession of a manufacturing authorisation which covers the productin question.

5.2.2

Where medicinal products are obtained from another wholesale distributor thereceiving wholesale distributor must verify that the supplier complies with theprinciples and guidelines of good distribution practices and that they hold a licence.

5.2.3

Appropriate qualification and approval of suppliers should be performed prior to
procurement of any medicinal products. This should be controlled by a procedure andthe results documented and periodically rechecked using a risk based approach.

5.2.4

When entering into a new contract with new suppliers the wholesale distributor should
carry out ‘due diligence’ checks in order to assess the suitability, competence andreliability of the other party. Attention should be paid to:i. the reputation or reliability of the supplier;ii. offers of medicinal products more likely to be falsified;iii. large offers of medicinal products which are generally only available in limited
quantities;
iv. diversity of products handled by supplier;v. and out-of-range prices.

5.3

QUALIFICATION OF CUSTOMERS

5.3.1

Wholesale distributors must ensure they supply medicinal products only to persons
who are themselves in possession of a wholesale distribution authorisation or who
are authorised or entitled to supply medicinal products to the public or otherwise
authorised to procure medicinal products from a distributor (for example medicinal
products intended for clinical trials).

5.3.2

Checks and periodic rechecks may include: requesting copies of customer’s
authorisations, verifying status on an authority website, requesting evidence ofqualifications or entitlement according to national legislation.

5.3.3

Wholesale distributors should monitor their transactions and investigate any
irregularity in the sales patterns of medicinal products at risk of diversion (e.g.
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diversion or misuse of medicinal product should be investigated and reported tocompetent authorities where necessary. Steps should be taken to ensure fulfilment ofany public service obligation imposed upon them.
5.4

RECEIPT OF MEDICINAL PRODUCTS

5.4.1

The purpose of the receiving function is to ensure that the arriving consignment iscorrect, that the medicinal products originate from approved suppliers and that they
have not been visibly damaged during transport.

5.4.2

Medicinal products requiring special handling, storage or security measures should
be prioritised and once appropriate checks have been conducted they should be
immediately transferred to appropriate storage facilities.

5.4.3

Batches of medicinal products should not be transferred to saleable stock before
assurance has been obtained in accordance with written procedures, that they areauthorised for sale.

5.4.4

If a falsified product is suspected, the batch should be segregated and reported tocompetent authorities as required by national legislation.

5.5

STORAGE

5.5.1

Medicinal products and, if necessary, healthcare products should be stored
separately from other products likely to alter them and should be protected from theharmful effects of light, temperature, moisture and other external factors. Particularattention should be paid to products requiring specific storage conditions.

5.5.2

Incoming containers of medicinal products should be cleaned, if necessary, before
storage. Any activities performed on the incoming goods (e.g. fumigation) should not
impact on the quality of the medicinal products.

5.5.3

Warehousing operations must ensure appropriate storage conditions are maintained
and allow for appropriate security of stocks.

5.5.4

Stock should be rotated according to the first expiry, first out (FEFO) principle.
Exceptions should be documented.

5.5.5

Medicinal products should be handled and stored in such a manner as to prevent
spillage, breakage, contamination and mix-ups. Medicinal products should not be
stored directly on the floor unless the package is designed to allow such storage(such as for some medicinal gas cylinders).

5.5.6

Medicinal products that are nearing their expiry date/shelf life should be withdrawn
immediately from saleable stock.

5.5.7

Stock inventories should be performed regularly taking into account national
legislation requirements. Stock irregularities should be investigated,documented andreported to the competent authorities when needed.

5.6

DESTRUCTION OF OBSOLETE GOODS

5.6.1

Medicinal products intended for destruction should be appropriately identified, held
separately and handled in accordance with a written procedure.

5.6.2

Destruction of medicinal products should be in accordance with national orinternational requirements for handling, transport and disposal of such products.

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5.6.3

Records of all destroyed medicinal products should be retained for a defined period.

5.7

PICKING
Controls should be in place to ensure the correct product is picked. The productshould have an appropriate remaining shelf life when it is picked.

5.8

SUPPLYFor all supplies, a document (e.g. delivery note/packing list) must be enclosed stating
the date; name and pharmaceutical dosage form of the medicinal product, batch
number, expiry date, as required by national legislation; quantity supplied; name andaddress of the supplier, name and delivery address of the consignee (actual physicalstorage premises, if different) and applicable transport and storage conditions.
Records should be kept so that the actual location of the product can be known.

5.9

IMPORT AND EXPORT

5.9.1

Import and export activities should be conducted in accordance with national
legislation and with international guidelines or standards when appropriate. This isalso the case if the wholesale distributor is holding medicinal product in a free zone.
Wholesalers should take the appropriate measures in order to prevent medicinal
products not authorised for the internal market and intended for export from reaching
the internal market.

5.9.2

Where wholesale distributors obtain/supply medicinal products from/to othercountries, they must ensure that entities are authorised or entitled to supply/receive
medicinal products in accordance with the applicable legal and administrative
provisions of the countries concerned.

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CHAPTER 6COMPLAINTS, RETURNS, SUSPECTED FALSIFIED MEDICINAL PRODUCTS AND
MEDICINAL PRODUCT RECALLS
6.1

PRINCIPLE
All complaints, returns, suspected falsified medicinal products and recalls must berecorded and handled carefully according to written procedures. Records should bemade available to the competent authorities. An assessment of returned medicinal
products should be performed by designated personnel before any approval for
resale. A consistent approach by all partners in the supply chain is required in order
to be successful in the fight against falsified medicinal products.

6.2

COMPLAINTS

6.2.1

Complaints should be recorded with all the original details. A distinction should bemade between complaints related to the quality of a medicinal product and thoserelated to distribution. In the event of a complaint about the quality of a medicinal
product and a potential product defect, the manufacturer and/or marketing
authorisation holder should be informed without delay. Any product distribution
complaint should be thoroughly investigated to identify the origin of or reason for thecomplaint.

6.2.2

If a defect relating to a medicinal product is discovered or suspected, consideration
should be given to whether other batches of the product should also be investigated.

6.2.3

A person should be appointed to handle complaints.

6.2.4

If necessary, appropriate follow-up actions (including CAPA) should be taken afterinvestigation and evaluation of the complaint, including where required notification to
the national competent authorities.

6.3

RETURNED MEDICINAL PRODUCTS

6.3.1

Returned products must be handled according to a written, risk based process taking
into account the product concerned, any specific storage requirements and the time
elapsed since the medicinal product was originally dispatched. Returns should be
conducted in accordance with national legislation, and contractual arrangements
between the parties. A record/ list of returned goods must be maintained.

6.3.2

Medicinal products which have left the premises of the distributor should only be
returned to saleable stock if all of the following are confirmed:i.

the medicinal products are in their unopened and undamaged secondary
packaging and are in good condition; have not expired and have not beenrecalled;
ii. medicinal products returned from a customer not holding a wholesale distribution
authorisation or from pharmacies authorised to supply medicinal products to the
public should only be returned to saleable stock if they are returned within an
acceptable time limit, for example 10 days;iii. it has been demonstrated by the customer that the medicinal products have beentransported, stored and handled in compliance with the specific storage
requirements;
iv. they have been examined and assessed by a sufficiently trained and competentperson authorised to do so;the distributor has reasonable evidence that the
product was supplied to that customer (via copies of the original delivery note orby referencing invoice numbers/batch numbers, expiry date etc., as required by
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national legislation), and that there is no reason to believe that the product has
been falsified.
6.3.3

Moreover, for medicinal products requiring specific temperature storage conditions,
returns to saleable stock can only be made if there is documented evidence that the
product has been stored under the authorised storage conditions throughout theentire time. If any deviation has occurred a risk assessment has to be performed, on
which basis the integrity of the product can be demonstrated. The evidence should
cover:
i.
ii.
iii.
iv.
v.
vi.
vii.

delivery to customer;
examination of the product;
opening of the transport packaging;return of the product to the packaging;collection and return to the distributor;
record of temperature readings during transportation;
return to the distribution site refrigerator.

6.3.4

Products returned to saleable stock should be placed such that the ‘first expired firstout’ (FEFO) system operates effectively.

6.3.5

Stolen products that have been recovered cannot be returned to saleable stock andsold to customers.

6.4

FALSIFIED MEDICINAL PRODUCTS

6.4.1

The sale and distribution of a suspected falsified medicinal product should besuspended immediately.

6.4.2

Wholesale distributors must immediately inform the competent authority and themarketing authorisation holder of any medicinal products they identify as falsified orsuspect to be falsified and act on the instructions as specified by the competentauthority. A procedure should be in place to this effect. It should be recorded with all
the original details and investigated.

6.4.3

Any falsified medicinal products found in the supply chain should immediately bephysically segregated and stored in a dedicated area away from all other medicinal
products and be appropriately labelled. All relevant activities in relation to suchproducts should be documented and records retained.

6.4.4

Upon confirmation as a falsified medicinal product, a formal decision should be taken
on removal of such product from the market, ensuring that it does not re-enter the
supply chain, including retention of any samples necessary for public health,regulatory, or legal needs and arrangements for its disposal. All related decisions
should be appropriately documented.

6.5

MEDICINAL PRODUCT RECALLS

6.5.1

There should be documentation and procedures in place to ensure traceability of
products received and distributed, to facilitate product recall.

6.5.2

In the event of a product recall, all customers to whom the product has been
distributed shall be informed with the appropriate degree of urgency and clear
actionable instructions.

6.5.3

The national regulatory authority should be informed of all product recalls. If the
product is exported, the overseas counterparts and/or regulatory authorities must be

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informed of the recall as required by national legislation.
6.5.4

The effectiveness of the arrangements for product recall should be evaluatedregularly (at least annually).

6.5.5

Recall operations should be capable of being initiated promptly and at any time.

6.5.6

The distributor must follow the instructions of a recall message, which should beapproved, if required, by the competent authorities.

6.5.7

Any recall operation should be recorded at the time it is carried out. Records should
be made readily available to the competent authorities.

6.5.8

The distribution records should be readily accessible to the person(s) responsible forthe recall, and should contain sufficient information on distributors and directly
supplied customers (with addresses, phone and/or fax numbers inside and outside
working hours, batch numbers as required by national legislation and quantities
delivered), including those for exported products and medicinal product samples (ifpermitted by national legislation).

6.5.9

The progress of the recall process should be recorded for a final report includingreconciliation of the recalled product.

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CHAPTER 7OUTSOURCED ACTIVITIES
7.1

PRINCIPLE
Any activity covered by the GDP Guide that is outsourced should be correctly defined,
agreed and controlled in order to avoid misunderstandings which could affect the
integrity of the product. There must be a written Contract between the Contract Giverand the Contract Acceptor which clearly establishes the duties of each party.

7.2

CONTRACT GIVER

7.2.1

The Contract Giver is responsible for the activities contracted out.

7.2.2

The Contract Giver is responsible for assessing the competence of the Contract
Acceptor to successfully carry out the work required and for ensuring by means of thecontract and through audits that the principles and guidelines of GDP are followed. An
audit of the Contract Acceptor should be performed before commencement of, andwhenever there has been a change to, the outsourced activities. The requirement foraudit and frequency should be defined based on risk depending on the nature of theoutsourced activities. Audits should be permitted at any time.

7.2.3

The Contract Giver should provide the Contract Acceptor with all the informationnecessary to carry out the contracted operations in accordance with the specificproduct requirements and any other relevant requirements.

7.3

CONTRACT ACCEPTOR

7.3.1

The Contract Acceptor is responsible for the activities covered by GDP and delegatedby the Contract Giver.

7.3.2

The Contract Acceptor should have adequate premises and equipment, procedures,
knowledge and experience, and competent personnel to carry out the work orderedby the Contract Giver.

7.3.3

The Contract Acceptor should not pass to a third party any of the work entrusted tohim under the contract without the Contract Giver’s prior evaluation and approval of
the arrangements and an audit of the third party by the Contract Giver or the Contract
Acceptor. Arrangements made between the Contract Acceptor and any third party
should ensure that the wholesale distribution information is made available in thesame way as between the original Contract Giver and Contract Acceptor.

7.3.4

The Contract Acceptor should refrain from any activity which may adversely affect thequality of the product(s) handled for the Contract Giver.

7.3.5

The Contract Acceptor must forward any information that can influence the quality ofthe product(s) to the Contract Giver in accordance with the requirement of thecontract.

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CHAPTER 8
SELF-INSPECTIONS

8.1

PRINCIPLE
Self-inspections should be conducted in order to monitor implementation andcompliance with GDP principles and to propose necessary corrective measures.

8.2

SELF-INSPECTIONS

8.2.1

A self-inspection programme should be implemented covering all aspects of GDP andcompliance with the regulations, guidelines and procedures within a defined timeframe. Self-inspections may be divided into several individual self-inspections oflimited scope.

8.2.2

Self-inspections should be conducted in an impartial and detailed way by designatedcompetent company personnel. Audits by independent external experts may also be
useful but may not be used as a substitute for self-inspection.

8.2.3

All self-inspections should be recorded. Reports should contain all the observations
made during the inspection. A copy of the report should be provided to the
management and other relevant persons. In the event that irregularities and/or
deficiencies are observed, their cause should be determined and the corrective andpreventive actions (CAPA) should be documented and followed up.

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CHAPTER 9
TRANSPORTATION
9.1

PRINCIPLE

9.1.1

It is the responsibility of the supplying wholesale distributor to protect medicinal
products against breakage, adulteration, theft and to ensure that temperature
conditions are maintained within acceptable limits during transport.

9.1.2

Regardless of the mode of transport, it should be possible to demonstrate that the
medicines have not been exposed to conditions that may compromise their quality
and integrity. A risk-based approach should be utilised when planning transportation.

9.2

TRANSPORTATION

9.2.1

The required storage conditions for medicinal products should be maintained duringtransportation within the defined limits as described on the outer packaging and/or
relevant packaging information.

9.2.2

If a deviation such as temperature excursion or product damage has occurred duringtransportation, this should be reported to the distributor and recipient of the affected
medicinal products. A procedure should also be in place for investigating andhandling temperature excursions.

9.2.3

It is the responsibility of the wholesale distributor to ensure that vehicles andequipment used to distribute, store or handle medicinal products are suitable for theiruse and appropriately equipped to prevent exposure of the products to conditions that
could affect their quality and packaging integrity.

9.2.4

There should be written procedures in place for the operation and maintenance of all
vehicles and equipment involved in the distribution process, including cleaning andsafety precautions.

9.2.5

Risk assessment of delivery routes should be used to determine where temperature
controls are required. Equipment used for temperature monitoring during transport
within vehicles and/or containers, should be maintained and calibrated at regularintervals.

9.2.6

Dedicated vehicles and equipment should be used, where possible, when handling
medicinal products. Where non-dedicated vehicles and equipment are used
procedures should be in place to ensure that the quality and integrity of the medicinal
product will not be compromised.

9.2.7

Deliveries should be made to the address stated on the delivery note and into thecare or the premises of the consignee. Medicinal products should not be left onalternative premises.

9.2.8

For emergency deliveries outside normal business hours, persons should bedesignated and written procedures should be available.

9.2.9

Where transportation is performed by a third party, the contract in place should
encompass the requirements of Chapter 7. Transportation providers should be madeaware by the wholesale distributor of the relevant transport conditions applicable tothe consignment. Where the transportation route includes unloading and reloading ortransit storage at a transportation hub, particular attention should be paid totemperature monitoring, cleanliness and the security of any intermediate storage

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facilities.
9.2.10

Provision should be made to minimise the duration of temporary storage while
awaiting the next stage of the transportation route.

9.3

CONTAINERS, PACKAGING AND LABELLING

9.3.1

Medicinal products should be transported in containers that have no adverse effect on
the quality of the products, and that offer adequate protection from external
influences, including contamination.

9.3.2

Selection of a container and packaging should be based on the storage andtransportation requirements of the medicinal products; the space required for theamount of medicines; the anticipated external temperature extremes; the estimatedmaximum time for transportation including transit storage at customs; the qualification
status of the packaging and the validation status of the shipping containers.

9.3.3

Containers should bear labels providing sufficient information on handling andstorage requirements and precautions to ensure that the products are properly
handled and secured at all times. The containers should enable identification of thecontents of the containers and the source.

9.4

PRODUCTS REQUIRING CONTROLLED CONDITIONS

9.4.1

In relation to deliveries containing medicinal products requiring special conditions
such as narcotics or psychotropic substances, the wholesale distributor should
maintain a safe and secure supply chain for these products in accordance withrequirements laid down in national legislation. There should be additional control
systems in place for delivery of these products. There should be a protocol to address
the occurrence of any theft.

9.4.2

Medicinal products comprising highly active and radioactive materials should betransported in safe, dedicated and secure containers and vehicles. The relevant
safety measures should be in accordance with international agreements and national
legislation.

9.4.3

For temperature-sensitive products, qualified equipment (e.g. thermal packaging,temperature-controlled containers or temperature controlled vehicles) should be used
to ensure correct transport conditions are maintained between the manufacturer,
wholesale distributor and customer.

9.4.4

If temperature-controlled vehicles are used, the temperature monitoring equipmentused during transport should be maintained and calibrated at regular intervals.
Temperature mapping under representative conditions should be carried out andshould take into account seasonal variations, if applicable.

9.4.5

If requested, customers should be provided with information to demonstrate that
products have complied with the temperature storage conditions.

9.4.6

If cool packs are used in insulated boxes, they need to be located such that the
product does not come in direct contact with the cool pack. Staff must be trained on
the procedures for assembly of the insulated boxes (seasonal configurations) and on
the reuse of cool packs.

9.4.7

There should be a system in place to control the reuse of cool packs to ensure that
incompletely cooled packs are not used in error. There should be adequate physicalsegregation between frozen and chilled ice packs.

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9.4.8PE 011-1

The process for delivery of sensitive products and control of seasonal temperature
variations should be described in a written procedure.

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ANNEX 1
Glossary of Terms
Term
Competent
Authority

Definition
Organisation that has the legally delegated or invested authority,
capacity or power over wholesaling of medicinal products in thejurisdiction in which it is located.

Contract Acceptor

The company who is contracted to conduct an activity covered by GDP
by the contract giver.

Contract Giver

The company who is contracting out any activity covered by GDP toanother legal entity.

Due diligenceThis is a term used for a number of concepts, involving either aninvestigation of a business or persons prior to signing a contract, or an
act with a certain standard of care.

ExportAllow goods to leave the customs territory of the country or economic
area.

Falsified(counterfeit)
medicinal productWithin the EEA:
“Any medicinal product with a false representation of:a) its identity, including its packaging and labelling, its name or its
composition as regards any of the ingredients including
excipients and the strength of those ingredients;b) its source, including its manufacturer, its country of
manufacturing, its country of origin or its marketing authorisation
holder; orc) its history, including the records and documents relating to the
distribution channels used.”
Source: 2013/C 343/01
Outside the EEA:
Any medicinal product “which is deliberately and fraudulently
mislabelled with respect to identity and/or source. Counterfeiting canapply to both branded and generic products and counterfeit products
may include products with the correct ingredients or with the wrong
ingredients, without active ingredients, with insufficient (inadequate
quantities of) active ingredient(s) or with fake packaging.”
Source: WHO Technical Report Series, No. 957, 2010

Free zones and free Free zones and free warehouses are parts of the customs territory of
warehouses
the country or economic area or premises situated in that territory andseparated from the rest of it in accordance with national customs
regulations.
Good Distribution
Practice (GDP)PE 011-1

GDP is that part of quality assurance which ensures that the quality of
medicinal products is maintained throughout all stages of the supply
chain from the site of manufacturer to the pharmacy or person
authorised or entitled to supply medicinal products to the public.

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Term
Holding

Definition
Storing medicinal products.

ImportAllow goods to enter the customs territory of the country or economic
area.

Manufacturing
Licence

A written authorisation from the national regulatory authority to
manufacture (& distribute) those medicinal products covered under the
licence.

Procuring

Obtaining, acquiring, purchasing or buying medicinal products frommanufacturers, importers or other wholesale distributors.

Public Service
Obligations

The authorisation/licence holder shall, in respect of a medicinal productthat has actually been placed on the market in its jurisdiction and within
the limits of his or her responsibility, ensure appropriate and continued
supplies of that product so that the needs of patientsin its jurisdiction in respect of such medicinal product are covered.

Qualification

Action of proving that any equipment works correctly and actually leads
to the expected results.
The word validation is sometimes widened to incorporate the concept ofqualification.

Quality Risk
Management

A systematic process for the assessment, control, communication andreview of risks to the quality of the drug (medicinal) product across the
product life cycle.

Quality System

The sum of all aspects of a system that implements quality policy andensures that quality objectives are met. (International Conference on
Harmonisation of Technical Requirements for Registration of
Pharmaceuticals for Human Use, Q9).

Supplying

All activities of providing, selling, donating medicinal products towholesalers, pharmacists, or persons authorised or entitled to supply
medicinal products to the public.

Suspected falsified Any medicinal product suspected to have a false representation of:(counterfeit)
medicinal producta) its identity, including its packaging and labelling, its name or its
composition as regards any of the ingredients including
excipients and the strength of those ingredients;b) its source, including its manufacturer, its country of
manufacturing, its country of origin or its marketing authorisation
holder; orc) its history, including the records and documents relating to the
distribution channels used.

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Term
Temperature

Definition
Deep freeze : Below -15 °C
In a refrigerator : +2 to +8 °C
Cold or Cool: +8 to + 15 °C
Room Temperature: +15 to + 25 °C
Ambient: The required storage temperature of non refrigerated
medicinal product; usually stated on the product as ‘store
below 25 °C’ or ‘store below 30 °C’.

Transport

Moving medicinal products between two locations without storing themfor unjustified periods of time.

Validation

Action of proving that any procedure, process, equipment, material,
activity or system actually leads to the expected results (see also
Qualification).

Wholesale
distribution

Wholesale distribution of medicinal products is all activities consisting ofprocuring, holding, supplying, importing or exporting medicinal
products, apart from supplying medicinal products to the public.

Wholesale
distributor

Operator who conducts wholesale distribution activities.

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