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.

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

A responsible person should be appointed by the management, who should have clearly specified authority and responsibility for ensuring that a quality system is implemented and maintained.

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.

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

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

The quality system should ensure that:

(i) medicinal products are procured, held, supplied or exported in a way that 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’) are taken to correct deviations and prevent them in line with the principles of quality risk management.

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

(i) assessing the suitability and competence of the contract acceptor to carry out the activity and checking authorisation 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 the identification and implementation of any required improvements on a regular basis.

The management should have a formal process for reviewing the quality system on a periodic 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 the effectiveness of processes within the quality system, such as complaints, deviations, CAPA, changes to processes; feedback on outsourced activities; self-assessment processes including risk assessments and audits; and external 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.

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

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

Quality risk management should ensure that the evaluation of the risk to quality is based on scientific knowledge, experience with the process and ultimately links to the protection of the patient. The level of effort, formality and documentation of the process 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 the International Conference on Harmonisation (‘ICH’).

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 the wholesale distributor is responsible. Individual responsibilities should be clearly understood by the staff and be recorded.

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

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.

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

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

Personnel should receive initial and continuing training relevant to their role, based on written procedures and in accordance with a written training programme. The responsible person should also maintain their competence in GDP through regular training.

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

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.

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

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

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 to enable all operations to be carried out accurately and safely.

Where premises are not directly operated by the wholesale distributor, a contract should be in place. The contracted premises should be covered by a separate wholesale distribution authorisation.

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

Products pending a decision as to their disposition or products that have been removed from saleable stock should be segregated either physically or through an equivalent electronic system. This includes, for example, any product suspected of falsification and returned products. Medicinal products received from a third country but not intended for the Union market should also be physically segregated. Any falsified medicinal products, expired products, recalled products and rejected products found in the supply chain should be immediately physically segregated and stored in a dedicated area away from all other medicinal products. The appropriate degree of security should be applied in these areas to ensure that such items remain separate from saleable stock. These areas should be clearly identified.

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

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 local legislation and appropriate safety and security measures.

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.

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

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

Premises should be designed and equipped so as to afford protection against the entry of insects, rodents or other animals. A preventive pest control programme should be in place.

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.

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.

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 that monitoring devices are positioned in the areas that experience the extremes of fluctuations. The mapping exercise should be repeated according to the results of a risk assessment exercise or whenever significant modifications are made to the facility or the temperature controlling equipment. For small premises of a few square meters which are at room temperature, an assessment of potential risks (e.g. heaters) should be conducted and temperature monitors placed accordingly.

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

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 and reliability assessment.

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 pre-defined storage conditions. Alarm levels should be appropriately set and alarms should be regularly tested to ensure adequate functionality.

Equipment repair, maintenance and calibration operations should be carried out in such a way that the integrity of the medicinal products is not compromised.

Adequate records of repair, maintenance and calibration activities for key equipment should be made and the results should be retained. Key equipment would include for example cold stores, monitored intruder alarm and access control systems, refrigerators, thermo hygrometers, or other temperature and humidity recording devices, air handling units and any equipment used in conjunction with the onward supply chain.