Good Distribution Practice in Pharmaceuticals

Good Distribution Practice (GDP) and Falsified Medicines Directive (FMD)

• GDP is a part of quality assurance that maintains pharmaceutical product quality throughout distribution. It controls various activities during distribution, preventing counterfeits, unapproved, illegally imported, stolen, substandard, adulterated, or misbranded products.
• The Falsified Medicines Directive (FMD) aims to reduce the incidence of falsified medicines entering the legitimate supply chain. It contains four delegated acts: Good Distribution Practice, safety features, internet sales, and API traceability.
• Distribution is a complex process involving multiple stakeholders (companies, contractors, re-packers, re-labelers, agents, brokers, traders, distributors, warehousing, pharmacy, and patients). Each stage has specific requirements.
• A reliable supply chain ensures uninterrupted drug supply, maintains drug conditions, minimizes wastage, optimizes drug storage, uses efficient transport, manages inventory accurately, and provides information for management decisions. A good supply chain considers the right products, quantity, condition, place, time, and cost.
• GDP guidelines aim to maintain product quality from manufacturing to patient use. They ensure authorized products, proper storage conditions, prevention of contamination, appropriate stock rotation (expiry dates), and safe storage in transit. They also require full traceability, a robust recall system, and compliance with EU legislation.
• A secure distribution network requires personnel, products, infrastructure and delivery means, SOPs, and GDPs; Quality control must comply with regulatory requirements, ensure licensed medicines, maintain records, and correct storage and transport conditions.

Principles of GDP

• GDP guidelines maintain quality throughout distribution. Products shouldn't change quality from factory to patient.
• Distribution companies must have quality systems in place.
• Products must comply with EU legislation. Suppliers must be fully trusted.
• Storage conditions maintained during storage and transport.
• Prevent contamination during storage and transport.
• A system for proper stock rotation is needed.
• Adequate control over product and people handling it is essential.
• Traceability of all units is maintained throughout distribution, a key requirement for a recall system.
• Ensure full distributor participation in any product recall.

Quality Management

• Wholesale distributors must have a quality system that covers responsibilities, processes, and risk management principles for all distribution activities.
• All activities must be clearly defined, regularly reviewed.
• Justification and validation of critical steps and significant changes in distribution processes.
• Quality systems should encompass organizational structure, procedures, processes, and resources required for product quality and integrity.
• Includes storage, transportation.
• Full documentation, procedures, change control, and clear authority and responsibility for the quality management system.
• Adequately resourced; considering complexity of the process.
• Incorporate QRM principles.

Personnel

• Correct distribution relies on qualified personnel.
• Adequate competent personnel are needed in all stages of wholesale distribution for medicinal products.
• All personnel performing distribution activities must undergo initial and ongoing training according to the GDP requirements.
• Records of the training should be maintained and training must follow written procedures, relevant to the role and training programme.
• Training is needed for handling sensitive or hazardous materials.
• Responsible person must ensure proper implementation, and maintenance of the quality system. They should also ensure that conditions of WDA (wholesale distribution authorisation) are met and followed.
• They should oversee that all GDP guidelines are being followed. Delegated tasks must be reviewed for compliance.
• A degree in pharmacy is desired; HPRA assesses suitability.
• Personnel involved must fulfil their responsibilities personally, be continuously contactable, and appropriate experience and training in GDP.

Premises and Equipment

• Premises must be suitable, specifically designed to maintain storage conditions for required medicinal products.
• Protect from weather, unauthorised access must be restricted.
• Segregate products pending disposal, clearly mark and restrict access to areas.
• Ensure premises are clean.
• Prevent pest entry.
• Use proper equipment, properly maintained and calibrated.
• Records of maintenance and calibration must be maintained.
• Computerized systems need validation and verification.
• Full documentation of the system is essential, including principles, objectives, security measures, system scope, and how the system is used, along with its integration with other systems, including data security and integrity.

Documentation

• Well-maintained documentation is integral to a quality system.
• Adequate documentation prevents errors from poorly communicated directions.
• Relevant operations are tracked.
• All documents must comply and meet principles of GDP.
• All written procedures, instructions, contracts, records and data are used, whether physical or electronic.
• Docs should be readily accessible and comprehensively cover all activities.
• Every procedure must be approved, signed, and dated by a responsible person.
• Any changes to documentation must be approved and dated.
• All documents must be legible. Procedures for documentation are essential and are kept for at least five years.

Operations

• All distributor actions should preserve medicinal product identity.
• Distributors should avoid distributing falsified products.
• All EU medicinal products distributed needs marketing authorisation (from EU or member state).
• Distributors that are not the marketing authorisation holder must notify the competent authority of intent to import.
• All key operations must be fully documented.

Qualification of Suppliers and Customers

• Supplier qualifications include verifying compliance with GMP and GDP principles and having a GMP certificate.
• Due diligence on reputable and reliable suppliers.
• Customers must be authorized to hold the product, with regular verification.
• Monitor transactions, ensuring they are compliant.

Receipt, Storage, and Supply

• Ensure correct consignment from approved suppliers.
• Products with special storage needs and security measures are prioritized.
• Proper storage conditions protected from light, temperature, moisture.
• Suitable storage conditions and security.
• Appropriate storage management, e.g., FIFO system. - Control for inventory, expiries and rejections.

Complaints, Returns, Suspected Falsified Medicinal Products and Recalls

• Careful recording and handling of complaints, returns, product suspicion, and recall procedures is mandated.
• Assess and evaluate returned products before their resale.
• Maintaining a consistent standard across all parties in related complaints.
• Separate complaints from quality issues and distribution issues.
• Documentation, investigation, review, and action (including corrective actions or CAPAs) for all complaints.
• Returned products handled according to written, risk-based process.

Outsourced Activities and Self-Inspections

• Outsourced activities related to GDP must be carefully defined, agreed upon, and controlled to ensure product integrity.
• Written contract outlining responsibilities of both contract giver and receiver.
• Self-inspections monitor GDP implementation and compliance, identify needed corrections, follow regulations, guidelines, and procedures.
• Conduct thorough and impartial checks.
• Document all observations, and implement corrective and preventive actions (CAPAs) for identified issues.

Transportation

• Wholesale distributors are responsible for protecting medicinal products during transport, maintaining temperature conditions, and preventing theft, breakage, and adulteration.
• Proper transport conditions and appropriate containers and packaging.
• A risk-based approach to transportation planning.
• Maintaining data logs for temperature and transport conditions using data loggers.

Internet Supply

• Only non-prescription medicines can be sold online in Ireland.
• Registered pharmacies that adhere to relevant guidelines are the primary online suppliers.
• There's a common logo that authenticates authorized online suppliers.
• Websites will have requirements and adherence from EU member states for legitimacy.
• Lists maintained by the Pharmaceutical Society of Ireland.

EU Falsified Medicines Directive

• Aim to reduce falsified medicines entering the EU legal supply chain.
• It contains four delegated acts that describe Good Distribution Practice (GDP), safety features, internet sales, and API Traceability.

Safety Features

• All safety features are mandatory for prescription medicines but not OTC medicines.
• The medicine pack includes anti-tampering devices (e.g., foil seal, breakable cap) and unique identifiers (product codes, serial numbers, batch numbers, expiry dates.)
• The unique identifiers are documented in a database for verification purposes.

Medicines Verification - EMVO/EMVS

• EU-wide collaboration for implementation and management of unique identifier requirements, covering manufacturers, distributors, wholesalers, and pharmacies.
• EMVO (the European Medicines Verification Organisation) serves as a central point.
• EMVS (the European Medicines Verification System) is a cloud-based system.

Irish Medicines Verification Organisation (IMVO)

• Manufacturers add unique identifiers (via barcodes) to medicinal products that are sent to IMVO and then to the EU Hub database.
• Pharmacies, hospitals and wholesalers can check authenticity.
• Pharmacist/wholesaler checks medicine using the barcode.
• Alert generated for suspicious products not present in the database (potential verification issues or fake products).

Medicines Authentication

• The process of authenticating medicines by including unique identifiers, verification checks, and decommissioning features
• The pharmaceutical manufacturer, distributor, pharmacist, and patient are linked.