Guidelines on good distribution practices for pharmaceutical Products

GUIDELINES ON
GOOD DISTRIBUTION PRACTICES
FOR PHARMACEUTICAL
PRODUCTS

Document No: CDSCO/GDP.PP Ver.: 00




DRAFT GUIDANCE

This guidance document is for feedback purposes only. Comments
suggestions, if any, may please be submitted to the office of Drugs
Controller General India within thirty days


CENTRAL DRUGS STANDARD CONTROL ORGANIZATION
DIRECTORATE GENERAL OF HEALTH SERVICES
MINISTRY OF HEALTH & FAMILY WELFARE

GOVT. OF INDIA PREFACE
Distribution and storage are essential activity in the integrated supply-chain
management of pharmaceutical products. Various individuals and entities are
generally responsible for the handling, storage and distribution of such products. So
it is important to have adequate controls over the entire chain of distribution. To
maintain the original quality of pharmaceutical products, every party involved in the
distribution chain has to comply with the applicable requirement. Each activity in the
distribution of pharmaceutical products shall be carried out according to the principles
of Good Distribution Practices (GDP) as applicable.
The nature of the risks involved is likely to be similar to that for risks encountered in
the manufacturing environment, e.g. mix-ups, adulteration, contamination, cross-
contamination, spurious. The involvement of unauthorized entities in the distribution
and sale of pharmaceutical products is a particular concern. Only a joint approach of
all parties involved in the supply chain can be successful in the fight against
spurious/not of standard quality pharmaceutical products. Therefore, all parties in
supply chain shall take an active part in collaborative activities to protect the
pharmaceutical supply chain against the penetration of spurious/substandard
pharmaceutical products
Earlier, CDSCO had introduced guidelines on good distribution practices for biological
products vide Document No: CDSCO/GDP.BP Ver.: 00 Effective Date: 08/10/2012.
Later, the draft guidelines on Good Distribution Practices for Pharmaceutical products
was published / circulated on 25/09/2018 through Notice vide F. No. 15-14/2018-DC
seeking comments from stakeholders.
This document prepared in line with WHO TRS on Good Storage and Distribution
practices for Pharmaceutical products sets out steps to assist in fulfilling the
responsibilities involved in the different stages within the supply chain and to avoid the
introduction of spurious, adulterated, misbranded and not of standard quality products
into the market and is intended to be applicable to all entities involved in any aspect
of the storage and distribution of pharmaceutical products, from the premises of the
manufacturer of the medical product to his or her agent, or the person dispensing or
providing medical products directly to a patient.


TABLE OF CONTENTS

S.
No Topic Page No.
1.0 Objective
2.0 Scope
3.0 General Principles
4.0 Regulation of the Distribution of
Pharmaceutical products
5.0 Organization and Management
6.0 Personnel
7.0 Quality System
8.0 Premises Warehousing and Storage
9.0 Temperature, Environment and Storage
Control
10.0 Transportation
11.0 Shipment Containers and Labeling
12.0 Dispatch and Receipt
13.0 Documentation
14.0 Complaints
15.0 Recalls and Returns
16.0 Spurious Pharmaceutical Products
17.0 Importation
18.0 Contract Activities
19.0 Self-inspection
1.0 INTRODUCTION

This document sets out steps to assist in fulfilling the responsibilities involved
in the different stages within the supply chain and to avoid the introduction of not of
standard quality and spurious products into the market. The relevant sections
should be considered as particular roles that entities play in the storage and
distribution of medical products. Not of standard quality and spurious products are
a significant threat to public health and safety.
Consequently, it is essential to protect the supply chain against the
penetration of such products. This guideline is intended to be applicable to all
entities involved in any aspect of the storage and distribution of medical
products, from the premises of the manufacturer of the medical product to his
or her agent, or the person dispensing or providing medical products directly to
a patient.
This includes all entities involved in different stages of the supply chain
of medical products; manufacturers and wholesalers, as well as brokers,
suppliers, distributors, logistics providers, traders, transport companies and
forwarding agents and their employees.
This guideline can be used as a tool in the prevention of distribution of not
of standard quality and spurious products.


2.0 OBJECTIVE

The objective of these guidelines is to ensure the quality and identity of
pharmaceutical products during all aspects of the distribution process. These
aspects include, but are not limited to procurement, purchasing, storage,
distribution, transportation, documentation and record-keeping practices.

3.0 SCOPE

These guidelines are intended to be applicable to all persons and outlets
involved in any aspect of the storage and distribution of pharmaceutical
products from the premises of the manufacturer of the product to the person
dispensing or providing pharmaceutical products directly to a patient or his or
her agent. This includes all parties involved in trade and distribution of
pharmaceutical, including the manufacturers of bulk, finished products,
wholesalers, as well as others such as suppliers, distributors, Government
institutions, international procurement organization, donor agencies and
certifying bodies, logistics providers, traders, transport companies and
forwarding agents and their employees as well as health workers.
It also covers biological products in general. However, for specific purpose,
guidelines on Good Distribution Practices for Biological Products as published in
CDSCO website shall be referred.


4.0 GENERAL PRINCIPLES 4.1. According to Drugs & Cosmetics Act 1940 and Drugs & Cosmetic Rules 1945,
Rules 64 and 65 specify the conditions to be fulfilled to sell, stock, exhibit or
offer for sale or distribute the drugs.

4.2. It shall be the responsibility of all parties involved in the distribution of
pharmaceutical products to ensure that the quality of pharmaceutical products
and the integrity of the distribution chain are maintained throughout the
distribution process from the site of the manufacturer to the entity
responsible for dispensing or providing the product to the patient or his or
her agent.

4.3. The principles of GDP shall be applicable both to pharmaceutical products
moving forward in the distribution chain from the manufacturer to the
entity responsible for dispensing or providing pharmaceutical products to
the patient and to products which are moving backwards in the chain, for,
as a result of the return or recall thereof and shall be applicable for donated
pharmaceutical products.

4.4. There shall be collaboration between all parties including government,
custom agencies, law enforcement agencies, regulatory authorities,
manufacturers, distributors and entities responsible for the supply of
pharmaceutical products to patients to ensure the quality and safety of
pharmaceutical products, prevent the exposure of patients to spurious
pharmaceutical products and to ensure that the integrity of distribution
chain is maintained.

4.5. An agreement shall be in place with all the individual agencies involved in
the storage, transportation and distribution.

5.0 REGULATION OF THE DISTRIBUTION OF PHARMACEUTICAL
PRODUCTS

5.1. The activities of persons or entities involved in the distribution of products
shall be regulated by Drugs and Cosmetics Act 1940 and rules 1945 made
thereunder.

5.2. The distributor or the organization to which the distributor belongs shall be an
entity that is appropriately authorized by applicable legislation to perform
the function(s) that it intends to perform and the distributor or the organization
to which it belongs shall be held accountable for the activities that it performs
related to the distribution of products.

5.3. Only authorized persons or entities who hold the appropriate license shall
be entitled to import or export pharmaceutical products.

5.4. Distributors or their agents shall obtain their supplies of pharmaceutical
products from persons or entities authorized to sell or supply such products
to a distributor and shall supply pharmaceutical products only to persons
or entities which are themselves authorized to acquire such products either
in terms of an authorization to act as a distributor or to sell or supply
products directly to a patient or to his or her agent. 5.5. If the activity of a distributor or his or her agent is subcontracted to another
entity, the person or entity to which the activity is subcontracted shall be
appropriately authorized to perform the subcontracted activity and shall
uphold the same standards as the distributor.

5.6 The activity of distributor and retailer shall be taken under supervision of
qualified staff as specified in Drugs Rules 1945.

5. Quality management

5.1 Entities involved in the storage and distribution of pharmaceutical products
should shall have a comprehensively designed, documented and correctly
implemented quality system that incorporates GSP, GDP, principles of quality
risk management and management review.

5.2 Senior management has the ultimate responsibility to ensure that an
effective quality system is established, resourced, implemented and
maintained.

5.3 The quality system shall ensure that:
 GSP and GDP are adopted and implemented to ensure that the quality of
pharmaceutical products is maintained throughout their shelf life in the
supply chain; and pharmaceutical products are appropriately procured,
stored, distributed and delivered to the appropriate recipients,
 operations are clearly specified in written procedures;
 responsibilities are clearly specified in job descriptions;
 all risks are identified and necessary, effective controls are implemented;
 processes are in place to assure the management of outsourced activities;
 there is a procedure for self-inspection and quality audits;
 there is a system for quality risk management;
 there are systems for managing returns, complaints and recalls; and
 there are systems to manage changes, deviations and corrective an preventive
actions (CAPAs).

5.4 There shall be an authorized, written quality policy describing the overall
intentions and requirements regarding quality. This may be reflected in a
quality manual.

5.5 There shall be an appropriate organizational structure. This shall be
presented in an authorized organizational chart. The responsibility, authority
and interrelationships of personnel shall be clearly indicated.

5.6 Roles and responsibilities shall be clearly defined and understood by the
individuals concerned, and recorded as written job descriptions.

5.7 The quality system shall include appropriate procedures, processes and
resources.

6. Quality risk management 6.1 There shall be a system to assess, control, communicate and review risks
identified at all stages in the supply chain.

6.2 The evaluation of risk shall be based on scientific knowledge and experience
and ultimately be linked to the protection of the patient.

6.3 Appropriate controls shall be developed and implemented to address all risks.
The effectiveness of the controls implemented shall be evaluated at periodic
intervals.

7.0 ORGANIZATION AND MANAGEMENT

7.1. An adequate organizational structure for each entity in the chain of
distribution shall be defined with the aid of an organizational chart. The
responsibility, authority and interrelationships of all personnel shall be
clearly indicated. An organogram/ organizational chart shall be in place.

7.2. There shall be clearly defined duties and responsibilities for individuals and
shall be recorded as written job descriptions. At every level of the supply
chain, employees shall be fully informed and trained in their duties and
responsibilities.

7.3. There shall be designated person appointed within the organization, who
has defined authority and responsibility for ensuring that a quality system
is implemented and maintained.
7.4 Managerial and technical personnel shall have the authority and resources
needed to carry out their duties and to set up and maintain quality system,
as well as to identify and correct deviations from the established quality
system.

7.5. It shall be ensured that the responsibilities placed on any one individual
shall not be so extensive as to present any risk to product quality.

7.6. There shall be arrangements in place to ensure that management and
personnel are not subject to commercial, political, financial and other
pressures or conflict of interest that may have an adverse effect on the
quality of service provided or on the integrity of pharmaceutical products.

7.7. Safety procedures relating to all relevant aspects including the safety of
personnel and property, environmental protection and product integrity, shall
be in place.

8. Management review

8.1 There shall be a system for periodic management review. The review shall
include at least:
 senior management;
 review of the quality system and its effectiveness by using quality
metrics and key performance indicators;
identification of opportunities for continual improvement; and follow-up on recommendations from previous management review
meetings.

8.2 Minutes and related documentation from management review meetings
should be available.

9.0 PERSONNEL

9.1. All personnel involved in distribution activities shall be trained an qualified
in the requirements of GDP, as applicable. Training shall be based on written
standard operating procedures (SOPs), GSP and GDP. Personnel shall
receive initial and continuing training relevant to their tasks, and be
assessed as applicable, in accordance with a written training programme. In
addition, training of the personnel shall include the topic of product
handling, safety and security, as well as aspects of product identification, the
detection of spurious pharmaceutical product and the avoidance of spurious
pharmaceutical product entering the supply chain. A record of all training,
which includes details of subjects covered and participants trained, shall be
kept.

9.2 Personnel dealing with hazardous products (such as highly active materials,
radioactive materials, narcotics and other hazardous, environmentally
sensitive and/or dangerous pharmaceutical products, as well as products
presenting special risks of abuse, fire or explosion) should be given specific
training.

9.3. Key personnel involved in the distribution of pharmaceutical products shall
have the ability and experience for ensuring that the pharmaceutical
products are properly stored and distributed as per the requirement of the
product.

9.4. There shall be an adequate number of competent personnel involved in all
stages of the distribution of pharmaceutical products in order to ensure that
the quality of the product is maintained.

9.5. Personnel involved in the distribution of pharmaceutical products shall
wear garments and adopt other personnel protection measures suitable for
the activities that they perform. Protective garments as necessary shall be
provided to the personnel dealing with hazardous pharmaceutical products,
including products containing materials that are highly active, toxic,
infectious or sensitizing materials.

9.6. Procedures for personnel hygiene relevant to the activities to be carried out
shall be laid down and observed. Such procedures shall cover health, hygiene
and clothing of personnel.

9.7. Procedures and conditions of employment for employees, including
contract and temporary staff and other personnel having access to
pharmaceutical products shall be designed and administered to assist in
minimizing the possibility of such products coming into the possession of
unauthorized persons or entities. 10.0 QUALITY SYSTEM

10.1. All pharmaceutical product distributors shall establish and maintain Quality
System. There shall be documented quality policy describing the overall
intentions and requirements of distributors regarding quality, authorized
by the management.

10.2. There shall be an appropriate organizational structure with defined
responsibilities of the personnel recorded as job descriptions.

10.3. A responsible person shall be appointed by the management for each
distribution site, who shall have defined authority and responsibility for
ensuring that a quality system is implemented and maintained.

10.4. Senior management shall ensure that all parts of quality system are
adequately resourced with competent personnel and suitable and sufficient
premises, equipment’s and facilities.

10.5. There shall be written and approved procedure for all the activities.

10.6. Deviations from established procedures shall be documented and
investigated.

10.7. Appropriate corrective and preventive action (CAPA) shall be taken to correct
deviations and prevent them.

10.8. Procedures for procurement and release shall be in place to ensure that
appropriate pharmaceutical products are sourced only from approved
suppliers and distributed by approved entities.

10.9. Inspection, auditing and certification of compliance with a quality system
(such as the applicable International Standardization Organization (ISO)
series, or national or international guidelines) by external bodies are
recommended.

10.10. Procedures shall be in place to ensure safe, transparent and secure
distribution system which includes product traceability throughout the
supply chain.

10.11. There shall be procedures in place to ensure document traceability of
products received and distributed, to facilitate product recall.

10.12. All parties involved in the supply chain shall be identifiable depending
on type of product and in accordance with National Legislation.

10.13. Measures shall be in place to ensure that pharmaceutical products have
documentation that can be used to permit traceability of the products
throughout distribution channels from the manufacturer/imported to the
entity responsible for selling or supplying the product to the patient or his or her agent. Records including expiry dates and batch numbers shall be
part of a secure distribution documentation enabling traceability.

11.0 PREMISES, WAREHOUSING AND STORAGE

11.1. Storage areas shall be maintained or designed to ensure Good storage
practices (GSP).

11.2. Premises shall be suitably located, designed, constructed and maintained, to
ensure appropriate operations such as receiving, storage, picking, packing
and dispatch of pharmaceutical products. Storage areas shall be suitably
secured, structurally sound and of sufficient capacity to allow for the safe
storage and handling.

11.3. Storage areas shall be provided with adequate lighting to enable all operations
to be carried out accurately and safely.

11.4. Precautions shall be taken to prevent unauthorized persons from entering
storage areas.

11.5. Segregated areas shall be designated for storage of the pharmaceutical
products in quarantine and for storage of released, rejected, returned or
recalled products as well as those suspected to be spurious.

11.6. Storage areas shall be designed or adapted to ensure appropriate and good
storage conditions and shall be clean and dry and maintained within
acceptable temperature limits. Pharmaceutical products shall be stored off
the floor and suitably spaced to permit cleaning and inspection. Pallets shall
be kept in a good state of cleanliness and condition.

11.7. Premises and storage areas shall be cleaned regularly. Where possible,
receiving and dispatch bays shall be separate, to avoid mix-ups. Bays shall
protect products from weather conditions.

11.8 Activities relating to receiving and dispatch shall be done in accordance with
authorized procedures. Areas should be suitably equipped for the
operations.

11.9. There shall also be a written programme for pest control and the pest
control agents used shall be safe and there shall be no risk of contamination
of pharmaceutical products. There shall be appropriate procedures for the
clean-up of any spillage to ensure complete removal of any risk of
contamination.

11.10. If sampling is performed in the storage area, it shall be conducted in such
a way as to prevent contamination or cross-contamination. Adequate
cleaning procedures shall be in place for the sampling areas.

11.11. Receiving and dispatch bays shall protect pharmaceutical products from
the weather. Receiving areas shall be designed and equipped to allow
incoming containers of pharmaceutical products to be cleaned, if necessary, before storage. Handling and storage of pharmaceutical products
shall in such a manner as to prevent contamination, mix-ups and cross-
contamination.

11.12. There shall be a system in place to ensure that the pharmaceutical
products due to expire first are sold and/or distributed first (first expiry/
first out (FEFO)). Exceptions shall be permitted as appropriate, provided
that adequate controls are in place to prevent the distribution of expired
products.

11.13. Arrangement shall be made for withdrawing broken or damaged items from
unusable stock and storing separately.

11.14. There shall be appropriately identified areas with adequate segregation for
storage of quarantined, rejected, expired, recalled or returned products to
prevent unintentional or unauthorized use of such products.

11.15. Dedicated area(s) with appropriate additional safety and security
measures shall be provided for storage of radioactive materials, narcotics
and other hazardous, sensitive and/or dangerous pharmaceutical products
as well as products presenting special risks of abuse, fire or explosion (e.g
combustible or flammable liquids and solids and pressurized gases).

11.16 Toilets, washing, rest and canteen facilities should be separate from areas
where products are handled. Food, eating, drinking and smoking should be
prohibited in all areas where medical products are stored or handled.

12.0 TEMPERATURE, ENVIRONMENT AND STOCK CONTROL

12.1 Storage and handling conditions shall comply with applicable National
regulations.

12.2. Storage conditions for pharmaceutical products shall be in compliance with
the recommendations of the manufacturer. This is key to ensure quality of
all pharmaceutical products.

12.3. Facilities shall be available for the storage of all pharmaceutical products under
appropriate conditions (e.g environmentally controlled when necessary).

12.4. Records shall be maintained of storage conditions if they are critical for the
maintenance of the characteristics of the pharmaceutical products. Records
of temperature monitoring data shall be available for review. There shall be
defined intervals for checking temperature. The equipment used for
monitoring shall be checked at suitable predetermined intervals and the
results of such checks shall be recorded and retained. All monitoring records
shall be kept for at least the shelf-life of the stored product plus one year. 12.5. Storage areas shall be temperature mapped under representative conditions.
Temperature mapping shall show uniformity of the temperature across the
storage facility. It is recommended that temperature monitors be located in
areas that are most likely to show fluctuations.

12.6. Equipment used for monitoring of storage conditions shall also be
calibrated at defined intervals.

12.7 Records of stock levels for all pharmaceutical products in store shall be
maintained, in either paper or electronic format. These records should be
updated after each operation (e.g. entries, issues, losses, adjustments).
These records shall be kept for a suitable period of time and readily
available. Periodic stock reconciliation shall be performed at defined
intervals, by comparing the actual and recorded stock.

12.8. Stock discrepancies shall be investigated in accordance with a specified
procedure to check that there have been no inadvertent mix ups, incorrect
issues and receipts, thefts and/or misappropriations of pharmaceutical
products. Documentation relating to the investigation shall be kept for a
predetermined period.

12.9. The root cause for stock discrepancies shall be identified and appropriate
CAPAs taken to prevent recurrence.

12.10 When damaged containers are received, this shall be brought to the
attention of the person responsible for quality. Any action taken shall be
documented. (These containers shall not be issued unless the quality of the
pharmaceutical products has been shown to be unaffected.)

12.11. All stock shall be checked at regular intervals, to identify those items that
are close to their retest or expiry date. Appropriate action shall be taken, such
as removal of these items from useable stock.

13.0 TRANSPORTATION

13.1. Pharmaceutical products shall be transported in accordance with the
storage conditions indicated on the packaging information and on the label.

13.2. The individuals responsible for the transportation of pharmaceutical
products shall be informed about all relevant conditions for storage and
transportation. These requirements shall be adhered throughout
transportation and at any intermediate storage stages.

13.3. Pharmaceutical products shall be stored and transported in accordance
with procedures such that:

13.3.1. The identity of the product is not lost.
13.3.2. The product does not contaminate and is not contaminated by
other products. 13.3.3. Adequate precautions are taken against spillage, breakage,
misappropriation and theft. Spillage during transport shall be
handled as per type of vaccine (eg. live, killed, etc.) according to the
standard operating procedures of the manufacturer.
13.3.4. Appropriate environmental conditions are maintained, e.g. using
cold chain for thermo labile products.

13.4. A written agreement between the manufacturer, Government Institution,
agent and Transport Company shall be in place.

13.5. Appropriate transport methods shall be employed which may include
transport by air, road, sea, rail or a combination of the above. Regardless
of the chosen mode, it shall be demonstrated that the products have not
been subjected to conditions during transportation that may compromise
their quality. A risk based approach be utilized when planning
transportation routes.

13.6. The required storage conditions for pharmaceutical products shall be
maintained during transportation within the defined limits as described on
the packaging information.

13.7. Where special conditions are required during transportation that are different
from or limit the given environmental conditions (e.g temperature and
humidity), these shall be provided by the manufacturer on the labels, shall be
monitored and recorded.

13.8. If a deviation has occurred during transportation, this shall be reported to
the distributor and recipient of the affect