WHO Good distribution practices for pharmaceutical Products
Distribution is an important activity in the integrated supply-chain management of pharmaceutical products. Various people and entities are generally responsible for the handling, storage, and distribution of such products. In some cases, however, a person or entity is only involved in and responsible for certain elements of the distribution process. The objective of these guidelines is to assist in ensuring 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, repackaging, relabelling, documentation, and record-keeping practices. The storage, sale, and distribution of pharmaceutical products are often carried out by various companies, institutions, and individuals. This document sets out appropriate steps to assist in fulfilling the responsibilities involved in the different aspects of the distribution process within the supply chain and to avoid the introduction of counterfeits into the marketplace via the distribution chain. The relevant sections should be considered by various participants as applicable to the particular role that they play in the distribution of pharmaceutical products. The nature of the risks involved is likely to be similar to that of risks encountered in the manufacturing environment, e.g. mix-ups, adulteration, contamination, and cross-contamination. When the distribution chain is interrupted by manufacturing steps such as repackaging and relabelling, the principles of good manufacturing practices (GMP) should be applied to these processes. Counterfeit pharmaceutical products are a real threat to public health and safety. Consequently, it is essential to protect the pharmaceutical supply chain against the penetration of such products. Weak points in the distribution processes of pharmaceutical products provide an avenue for counterfeit as well as illegally imported, stolen, and substandard medicines to enter the supply chain. This is a concern in both developed and developing countries. The methods by which such products enter the supply chain have become increasingly complex and have resulted in the development of thriving secondary and grey markets throughout the world. The involvement of unauthorized entities in the distribution and sale of pharmaceutical products is a particular concern. Only a joint approach including all parties involved in the supply chain can be successful in the fight against counterfeit pharmaceutical products and, therefore, all parties active in the market should take an active part in collaborative activities.
Different models for the distribution of pharmaceutical products are used in different countries and sometimes within the same country, for example, TRS957.indd 236 21.04.10 11:04 237 in the public and the private sector. These guidelines are intended to be applicable to all persons and outlets involved in any aspect of the 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 the trade and distribution of medicines, pharmaceutical manufacturers, including the manufacturers dist of finished products and pharmaceutical wholesalers as well as other parties such as brokers, suppliers, distributors, logistics providers, traders, transport companies, and forwarding agents and their employees. To maintain the original quality of pharmaceutical products, every party active in the distribution chain has to comply with the applicable legislation and regulations. 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) as applicable. These guidelines do not deal with all aspects of the standards for the storage of pharmaceuticals which are covered in the WHO guide to I storage practices for pharmaceuticals. The dispensing to patients is addressed in the. WHO good pharmacy practice (GPP) guide. These guidelines should also be read in good conjunction with other WHO guidelines. Although medical devices are not included in the definition of pharmaceutical products for the purposes of this document, the main principles established in this document may also be used where applicable for medical devices…
Definition of GDP
That part of quality assurance ensures that the quality of a pharmaceutical product is maintained by means of adequate control of the numerous activities which occur during the distribution process as well as providing a tool to secure the distribution system from counterfeits, unapproved, illegally imported, stolen, counterfeit, substandard, adulterated, and/or misbranded pharmaceutical products.
The principles of GDP are 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 that are moving backward in the chain, for example, as a result of the return or recall thereof. There should be a collaboration between all parties including governments, customs 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 and prevent the exposure of patients to counterfeit pharmaceutical products.
Organization and management
There should be an adequate organizational structure for each entity defined with the aid of an organizational chart. The responsibility, authority, and interrelationships of all personnel should be clearly indicated. At every level of the supply chain, employees should be fully informed and trained in their duties and responsibilities. A designated person should be appointed within the organization, who has defined authority and responsibility for ensuring that a quality system is implemented and maintained. The responsibilities placed on any one individual should not be so extensive as to present any risk to product quality
All personnel involved in distribution activities should be trained and qualified in the requirements of GDP, as applicable. Training should be based on written standard operating procedures (SOPs). There should 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. Personnel involved in the distribution of pharmaceutical products should wear garments suitable for the activities that they perform. Procedures and conditions of employment for employees, including contract and temporary staff, and other personnel having access to pharmaceutical products must be designed and administered to assist in minimizing the possibility of such products coming into the possession of unauthorized persons or entities. Codes of practice and punitive procedures should be in place to prevent and address situations.
Within an organization, quality assurance serves as a management tool. There should be a documented quality policy describing the overall intentions and requirements of the distributor regarding quality, as formally expressed and authorized by management. Where electronic commerce (e-commerce) is used, i.e. electronic means are used for any of the distribution steps, defined procedures and adequate systems should be in place to ensure traceability and confidence in the quality of the pharmaceutical products concerned. Electronic transactions ( including those conducted via the Internet), relating to the distribution of pharmaceutical products, should be performed only by authorized persons or entities. 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. Such certification should not, however, be seen as a substitute for compliance with these GDP guidelines and the applicable principles of GMP relating to pharmaceutical products. Distributors should from time to time conduct risk assessments to assess potential risks to the quality and integrity of pharmaceutical products.
Premises, Warehousing, and Storage
Precautions must be taken to prevent unauthorized persons from entering storage areas. Employees should comply with the company policies to maintain a safe, secure, and efficient working environment. Storage areas should be of sufficient capacity to allow the orderly storage of the various categories of pharmaceutical products, namely commercial and non-commercial products in quarantine, and released, rejected, returned, or recalled products as well as those suspected to be counterfeited. Storage areas should be clean and free from accumulated waste and vermin. If sampling is performed in the storage area, it should be conducted in such a way as to prevent contamination or cross-contamination. Adequate cleaning procedures should be in place for the sampling areas. Radioactive materials, narcotics, and other hazardous, sensitive, and/ or dangerous pharmaceutical products/s well as products presenting special risks of abuse, fire, or explosion (eg: combustible or flammable liquids and solids pressurized gases) should be stored in a dedicated area(s) that is subject to appropriate additional safety and security measures. A system should be in place to ensure that the pharmaceutical products due to expire first are sold and/or distributed first (first expiry/ first-out (FEFO)). Exceptions may be permitted as appropriate, provided that adequate controls are in place to prevent the distribution of expired products Storage conditions for pharmaceutical products should be in compliance with the recommendations of the manufacturer. Equipment used for monitoring storage conditions should also be calibrated at defined intervals. Stock discrepancies should be investigated E accordance with a specified procedure to check that there have been no inadvertent mixups, incorrect issues and receipts, thefts, and/or misappropriations of pharmaceutical products. Documentation relating to the investigation should be kept for a predetermined period.
Vehicles and Equipment
Vehicles and equipment used to distribute, store or handle pharmaceutical products should be suitable for their purpose and appropriately equipped to prevent exposure of the products to conditions that could affect their stability and packaging integrity and to prevent contamination of any kind. Where feasible, consideration should be given to adding technology, such as global positioning system (GPS) electronic tracking devices and engine kill buttons to vehicles, which would enhance the security of pharmaceutical products while in the vehicle. Where special storage conditions (e.g. temperature and/or relative humidity), different from, or limiting, the expected environmental conditions are required during transportation, 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.
Shipment container and Container labeling
Shipping containers should bear labels providing sufficient information on handling and storage conditions and precautions to ensure that the products are properly handled and secure at all times. The shipment container should enable the identification of the container’s contents and source. Normally, internationally and/or nationally accepted abbreviations, names, or codes should be used in the labeling of shipment containers. Special care should be taken when using dry ice in shipment 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.
Dispatch and receipt
Prior to the dispatch of the pharmaceutical products, the supplier should ensure that the person or entity, e.g. the contract acceptor for transportation of the pharmaceutical products, Is aware of the pharmaceutical products to be distributed and complies with the appropriate storage and transport conditions. Records for the dispatch of pharmaceutical products should be prepared and should include at least the following information:
- date of dispatch;
- complete business name and address (no acronyms), type of entity responsible for the transportation, telephone number, and names of contact persons; complete business name, address (no acronyms), and status of the addressee (e.g. retail pharmacy, hospital, or community clinic);
- a description of the products including, eg. name, dosage form, and strength (if applicable);
- quantity of the products, ie. number of containers and quantity per container (if applicable);
- applicable transport and storage conditions; a unique number to allow identification of the delivery order; and assigned batch number and expiry date (where not possible at dispatch, this information should at least be kept at receipt to facilitate traceability).
Care should be taken to ensure that the volume of pharmaceutical products ordered does not exceed the capacity of storage facilities at the destination. Incoming shipments should be examined to verify the integrity of the container/closure system, ensure that tamper-evident packaging features are intact and that labeling appears intact.
Transportation and product in transit
Products and shipment containers should be secured to prevent or provide evidence of unauthorized access. Vehicles and operators should be provided with additional security, as appropriate, to prevent theft and other misappropriation of products during transportation. Pharmaceutical products should be stored and transported in accordance with procedures such that:
- The identity of the product is not lost.
- The product does not contaminate and is not contaminated by other products.
- Adequate precautions are taken against spillage, breakage, misappropriation, and theft.
- Appropriate environmental conditions are maintained, e.g. using a cold chain, for thermolabile products.
- Spillages should be cleaned up as soon as possible to prevent possible contamination, cross-contamination, and hazards. Written procedures should be in place for the handling of such occurrences.
Written instructions and records which document all activities relating to the distribution of available. Records should be kept for seven years unless otherwise specified in national or regional regulations. Distributors should keep records of all pharmaceutical products received. Records should contain at least the following information:-date;-name of the pharmaceutical product, — quantity received, or supplied; and — name and address of the supplier.
The nature, content, and retention of documentation relating to the distribution of pharmaceutical products and any investigations conducted and action taken, should comply with national legislative requirements. Where such requirements are not in place, the documents should be retained for at least one year after the expiry date of the product concerned. Procedures should be in place for temperature mapping, security services to prevent theft or tampering with goods at the storage facilities, destruction of unsaleable or. unusable stocks and on retention of the records.
Repacking and Relabelling
Repackaging and relabelling of pharmaceutical products should be limited, as these practices may represent a risk to the safety and security of the supply chain. Where they do occur, they should only be performed by entities appropriately authorized to do so and in compliance with the applicable national, regional, and international guidelines, ie. in accordance with GMP principles. In the event of repackaging by companies other than the original manufacturer, these operations should result in at least equivalent means of identification and authentication of the products. Procedures should be in place for the secure disposal of the original packaging.
There should be a written procedure in place for the handling of complaints. A distinction should be made between complaints about a product or its packaging and those relating to distribution. In the case of a complaint about the quality of a product or its packaging, the original manufacturer and/ or marketing authorization holder should be informed as soon. as possible. Where necessary, appropriate follow-up action should be taken after investigation and evaluation of the complaint. There should be a system in place to ensure that the complaint, the response received from the original product manufacturer, or the results of the investigation of the complaint, are shared with all the relevant parties.
There should be a system, which includes a written procedure, to effectively and promptly recall pharmaceutical products known or suspected to be defective or counterfeit, with a designated person(s) responsible for recalls. The system should comply with the guidance issued by the national or regional regulatory authority. This procedure should be checked regularly and updated as necessary. The original manufacturer and/or marketing authorization holder should be informed in the event of a recall. Where a recall is instituted by an entity other than the original manufacturer and/or marketing authorization holder, consultation with the original manufacturer and/or marketing authorization holder should, where possible, take place before the recall is instituted. Recalled pharmaceutical products should be segregated during transit and clearly labeled as recalled products. Where segregation in transit is not possible, such goods must be securely packaged, clearly labeled, and be accompanied by appropriate documentation.”
A distributor should receive pharmaceutical product returns or exchanges pursuant to the terms and conditions of the agreement between the distributor and the recipient. Both distributors and recipients should be accountable for administering their returns process and ensuring that the aspects of this operation are secure and do not permit the entry of counterfeit products.
Counterfeit pharmaceutical products. Provision should be made for the appropriate and safe transport of returned products in accordance with the relevant storage and other requirements. Rejected pharmaceutical products and those returned to a distributor should be appropriately identified and handled in accordance with a procedure that involves at least the segregation of such pharmaceutical products in quarantine in a dedicated area, or other equivalents (e.g. electronic) segregation.
Counterfeit pharmaceutical products
Counterfeit pharmaceutical products found in the distribution chain should be kept apart from other pharmaceutical products to avoid any confusion. They should be clearly labeled as not for sale and national regulatory authorities and the holder of the marketing. authorization for the original product should be informed immediately. Upon confirmation of the product being counterfeit a formal decision should be taken on its disposal, ensuring that it does not re-enter the market, and the decision recorded.
The number of ports of entry in a country for the handling of imports of pharmaceutical products should be limited by appropriate legislation. Such ports could be designated by the state. The chosen port(s) of entry should be those most appropriately located and best equipped to handle imports of pharmaceutical products. At the port of entry, consignments of pharmaceutical products should be stored under suitable conditions for as short a time as possible. 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.
Contract and Activities
Any activity relating to the distribution of a pharmaceutical product that is delegated to another person or entity should be performed by parties appropriately authorized for that function and in accordance with the terms of a written contract. The contract should define the responsibilities of each party including observance of the principles of GDP and relevant warranty clauses. It should also include the responsibilities of the contractor for measures to avoid the entry of counterfeit medicines into the distribution chain, such as through suitable training programs. Contract accepters should be audited periodically.
The quality system should include self-inspections. These should be conducted to monitor implementation and compliance with the principles of GDP and, if necessary, to trigger corrective and preventive measures. Self-inspections should be conducted in an independent and detailed way by a designated, competent person. The results of all self-inspections should be recorded. Reports should contain all observations made during the inspection and, where applicable, proposals for corrective measures. There should be an effective follow-up program. Management should evaluate the inspection report and the records of any corrective actions taken.
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