Guidelines on Good Distribution Practice of Medicinal Products

Quality Management

The organisation’s management is responsible for the quality system, which requires their leadership and active participation supported by staff commitment. The Responsible Person is to ensure that a Quality Management System is implemented and maintained. The Management is to ensure that all parts of the quality system are documented, defined and are adequately resourced with competent personnel, and suitable and sufficient premises, equipment and facilities.

The Quality System should also define the organisation’s:

• change control process
• management of their outsourced activities with a clear requirement to assess the suitability of the Contract Acceptor to perform the required activities
• the formal process for reviewing the quality management system on a periodic basis (Management Review).

All significant changes should be justified, validated and approved by relevant stakeholders via change control and risk management processes, using appropriate corrective actions and preventive actions (CAPA)

Personnel

This part defines the qualification requirements, tasks and responsibilities of all staff and the Responsible Person (RP).

Wholesalers are required to appoint a management representative to act in the role of responsible person (RP). The RP is considered to be the key member of staff accountable for ensuring that the quality, safety and traceability of medicinal products is maintained within the supply chain.

Wholesalers should have precise criteria for the selection of a suitable candidate(s) for undertaking the role of RP. This should take into account the complexity of the wholesale operation and the expertise and personal knowledge of the candidate. Key conditions in this regard are:

1. Sufficient pharmaceutical knowledge and experience to ensure full discharge of their responsibilities. Evidence of six months full-time direct GDP experience is considered a minimum requirement however all applications will be assessed on a case-by-case basis using a risk-based approach.
2. Knowledge, understanding and experience of:

• The conditions of the WDA for which they are nominated.
• The products wholesaled under the authorisation and the conditions necessary for their safe storage and distribution.
• Relevant provisions of the Directives, Acts and Regulations pertaining to the wholesaling
  of medicinal products.

RPs who are not employed on a full-time basis at the authorised site may be considered eligible if they can meet the key conditions outlined above and can demonstrate:

• They are continuously contactable and available to attend the site as required.
• They will be present at the authorised site for an adequate amount of time to effectively carry out their duties.
  This must be risk based and justified.
• They are able to maintain oversight of their responsibilities during the periods of absence from the site.

Training requirements for all staff including the RP are defined, there is a need for up to date training records, staff should receive training on tasks they perform, products they handle and the GDP guidelines.

The practical effectiveness of training should then be periodically assessed and documented for all staff.

Premises and Equipment

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

Access to medicinal product storage areas should be restricted and monitored with procedures in place to prevent unauthorised access at all times, this includes preventing unauthorised access to computerised systems and documentation.

Requirements have been set for products with specific handling instructions, to be followed as specified in national law. For example narcotics, radioactive materials and other hazardous products as well as products presenting special risks of fire or explosion.

the clear requirement for physical segregation has been emphasised for the following:

• recalled
• falsified
• expiredr
• ejected products
• products received from third countries and not intended for the Union markets

Initial temperature mapping of warehouses before use under representative conditions is required. After an initial mapping, temperature monitoring should be located according to the results of the mapping exercise.

Read also: Supply Chain Security Risks in Pharmaceutical Industry

Documentation

A good Quality Management System will be underlined by good documentation practice. Documentation comprises all written procedures, instructions, contracts, records and data, i.e. all information required to demonstrate the what, by who, when, how and why should be documented in the Quality Management System paying attention to compliance to Data Integrity, Data Management and Data Retention.

RP approval should be sought where required. All documentation whether current, superseded or withdrawn should be retained in line with national legislation but for a minimum of 5 years, document control logs should be made available for traceability and monitoring.

Read also: Vendor Audit in Pharmaceutical Industry

Operations

Qualification of Suppliers and Customers

All suppliers must be qualified in an adequate way, i.e. wholesale distributors must verify their

• supplier is authorised to supply medicinal products by way of wholesale
• dealing customers are authorised to purchase medicinal products either by way of wholesale dealing or as the authorised or entitled entity to receive and/or supply medicines to the public e.g. hospital, pharmacy, prison, university, research facility.

It is important that the qualification is performed prior to any procurement and any supply activities are authorised to take place. The selection, including qualification and approval of suppliers and customers should be defined in Standard Operating Procedures, SOPs, and the results should be documented and periodically evaluated.

Receipts of medicinal products, Storage and Destruction

Upon receipt, medicinal product should be visually inspected at Goods­In/Goods­Receipt area to ensure product is free from damage, tampering, contamination from other products and/or ingress of pests/dirt.

Products and documentation should be inspected for authenticity and accuracy on receipt. Anomalies should be documented and reported to the RP and Management according to written procedures. Products with special handling instructions should be processed first.

Medicinal product should be stored separately to other goods if the warehouse facility has multiple storage uses. Storage facilities should be clearly and adequately labeled to accurately identify stock. Stock should be stored according to the manufacturer’s instructions and following national legal requirements e.g. narcotics, psychotropics, substances liable to misuse and hazardous goods.

Batches/products should be appropriately segregated to prevent cross­contamination and prevent inadvertent supply. This includes medicinal product held in quarantine or held for destruction. In both instances stock should be physically segregated, appropriately identified and handled in accordance with written procedures.

Picking, Supply and Export to Third Countries

Procedures should be written in a clear and concise language to be understood by the operators to ensure the correct product is picked for supply and has an appropriate shelflife remaining.

A delivery document is required to be enclosed within all consignments containing complete product descriptions, quantities and information necessary to identify the supplier and consignee, along with any special handling and/or storage conditions.

Product intended for non­EEA countries falls under “Export” and as such the exporter must hold a wholesale distribution authrorisation or a manufacturing authorization permitting Export of medicinal products. The onus remains on the supplier to qualify their customer as entitled to receive the exported product.

Complaints, Returns, Suspected Medicinal Products and Medicinal product Recall

A complaints procedure should be in place which clearly defines the process steps for handling complaints received from customers. Complaints relating to distribution activities should be recorded, investigated to identify the root cause and where appropriate a corrective action to be identified. Product quality complaints should be forwarded to the manufacturer/MA holder for investigation.

Only the RP can authorise the final disposition of stock affected by a deviation, return, rejection or being suspected of being falsified or under a recall notice.

The major requirement in this section is to immediately inform the competent authority and the marketing authorisation holder of any medicinal products identified as falsified or suspected to be falsified. A procedure should be in place to cover this activity, including the recording of the relevant investigation.

Read also: Pharmaceutical Products Recall Guidelines and Procedures

Outsourced Activities

Clearly defines the roles and responsibilities of the Contract Giver and the Contract Acceptor and states the need for a detailed contract to cover the outsourced activity.

The Contract Giver is responsible for performing due diligence activities and, where required, to carry out an audit of the Contract Acceptor. Where a desk­top audit takes place full justification is required to be documented for not performing a physical audit.

Any work entrusted to the Contract Acceptor should not be outsourced to a third party without both an agreement from the Contract Giver and an audit of the third party. Outsourced activities include for example:

• Storage at third party facility
• Transportation
• Equipment Calibration and Maintenance
• Pest Control
• Alarms and/or Security
• Cleaning and Facility Maintenance and Site Management

Self Inspections

The RP is responsible to ensure this program is maintained and thus is responsible for keeping up to date with changes in legislation and regulations impacting the business with regards to GDP. Other departments may support the RP by performing local audits and/or participating in the organisation’s Self Inspection program.

Transportation

There is emphasis on the responsibility of the distributors to ensure that vehicles (and equipment) used to distribute and transport medicinal products are suitable for their use and do not affect the quality of the product nor the integrity of packaging. This requires the distributor to audit their transport providers and thus there is an onus on transport providers to ensure their vehicles and drivers meet the expectations of GDP for medicinal products. The transport provider should have written procedures in place, and a Contract should be in place with the wholesale distributor clearly defining responsibilities.

Other additions include

• The requirement for procedures to be in place for the operation and maintenance of all vehicles and equipment involved in the distribution process.
• Risk assessment of delivery routes should be used to determine where temperature controls are required. They can also be used to determine optimum delivery times e.g. late night transport in summer months or specific months to avoid risk of adverse weather conditions delaying deliveries and/or compromising the vehicle or product packaging.
• Deliveries should be made directly to the address stated on the delivery note and must be handed into the care of the consignee using dedicated vehicles where possible.
• Medicinal products should not be left on alternative premises.
• Transportation performed by third parties should be covered by a contract.
• Minimise the duration of temporary storage e.g. at hubs, while product awaits uplift or onward transshipment during delivery to the end customer.

Read also: Risk and Mitigation Strategies for Storage and Transportation of Finished Drug Products

Containers, packaging and labeling

The identity, integrity and quality of product should not be compromised by containers used to carry the goods, i.e. product should be appropriately packaged, clearly labeled and be protected from external influences and be free from risk of contamination.

Products requiring special conditions

The responsibility is on the wholesaler and transport/delivery provider to ensure a safe and secure supply chain is maintained for all medicinal products with special attention to products such as narcotics and psychotropic agents, in line with national legal requirements.

Products containing highly active and radioactive materials should be transported safely within secure containers using dedicated vehicles, in accordance with relevant national legislation and international agreements.

Specific Provisions for Brokers

It describes the requirements for Brokers to be registered by the local competent authority, to have a QMS in place supported by adequate documentation. Personnel working for Brokers should received adequate training on relevant sections of GDP. There is also a requirement for Brokers to follow and apply the principles of Good Documentation Practice, with all records made available according to national legislation but at least 5 years, the same as for wholesale distributors.

Read also:

• Data Quality Framework (DQF) for EU Medicines Regulation
• Guidelines on Packaging for Pharmaceutical Products

Reference: ECA Roadmap to Good Distribution Practice (GDP)