- First Expiration, First out (FEFO) – Inventory control methodology that assures material/product with the shortest remaining shelf life will be distributed/used first.
- Logistic Service Providers (LSP/3PLs) – Freight forwarders and brokers that assist product transportation but may not physically touch the product.
- Mean Kinetic Temperature (MKT) – A single derived temperature , which if maintained over a defined period, would afford the same thermal challenge to a pharmaceutical product as would have been experienced over the range of both higher and lower temperatures for an equivalent defined period (ICH, Q1A).
- Transportation service provider – Company that physically transport the product.
- Validation Master Plan (VMP) – Approved plan that documents rational for the approach to validation, defines the validation scope and lists all systems and their validation status.
- Verified Accredited Wholesale Distributors (VAWD) – An accreditation governed by the U.S national Association of Boards of Pharmacy for pharmaceutical wholesale distribution facilities indicating they are in compliance with state and federal laws.
According to PDA technical report No. 52, Good Distribution Practice includes seven different categories:
Stability studies data will be collected, analyzed and used in order to determine the required conditions for safe storage, transportation and distribution of the product.
In case specific storage conditions for the Pharmaceutical/Medical product are required, it should be defined on the product label. Storage or cargo areas should be designed and equipped properly in order to maintain these conditions within the defined limits. These areas should be validated and relevant storage parameters should be mapped through the entire storage area. Moreover, conditions should be constantly monitored using an appropriate calibrated instrumentation. Specifically for temperature monitoring, the calibrated temperature data logger should indicate and record when, for how long and what was the temperature at the exact time period it was out of the defined allowable temperature limits. The effect of deviation on product quality will be using product stability data and characteristics/parameters such as MKT. Storage conditions should be monitored and controlled in the entire storage area/warehouse volume and not only in adjacent to the floor level. Data loggers and other monitoring devices should be located in the worst case locations identified in the Validation stage (warmest, high humidity etc.). Data loggers should technically allow continuous monitoring as well as alarms generation in cases of the monitored parameter deviations (outside the limits) were monitored.
As part of Computerized System Validation, data loggers and other monitoring, alarm systems and software should be Qualified / Validated and comply the GAMP, Annex 11 and 21CFR part 11 standards.
In cases of out of range storage and/or transportation conditions, a deviation should be reported to the manufacturer immediately and until deviation closure, the product should be kept in “hold” and should not released to the market. The deviation should be investigated for root cause, corrective actions implementation and the potential product impact should be assessed. Moreover, as part of CAPA process, preventive actions should be considered as well.
Pharmaceutical and Biological products should be transported in such a way that will maintain and control the environmental conditions that the product is subjected to as well as other conditions that may affect product quality and safety. Shipping conditions should be monitored continuously through all shipping routes, unless it was validated under supply chain Validation. The shipping conditions may differ from the product long term recommended storage conditions, for a limited time periods during shipment, based on excursion, forced degradation, freeze-thaw, accelerated and long term stability studies results and other challenging studies in order to assure no impact on product quality during shipment. Product impact should be assessed for shipping conditions (single as well as cumulative excursion) during the storage, shipment and distribution process.
- Stability testing to support distribution
Primary and secondary Pharmaceutical/Biological/Medical product packaging should be designed in such a way that will protect the product from mechanical and environmental conditions impact in addition to product identification and other relevant information that suppose to be printed/labeled on product packaging. Product packaging type and material should be designed considering several issues including transportation mode, conditions, routes and destination (for example: for cold chain it is recommended to use non-paper labels). In case specific storage conditions are required, the packaging type and design should support maintaining the required conditions through the whole supply chain including during product handling, storage, transportation and distribution activities. In addition, the Pharmaceutical/Biological/Medical product packaging should be validated after Risk Assessment completion. Allowable time period for product handling, storage, transportation, repackaging and distribution exposure outside the storage conditions specified on product label will be based on the product stability data. These ‘out of range’ time periods and conditions should be monitored, controlled, documented, investigated and justified.
- Distribution control management
Distribution control management purpose is to define the required process and controls in order to assure product safety, identity, quality, integrity and tractability through the entire supply chain life cycle. “Track & Trace” methodology should be implemented as part of supply chain control. Every packaging configuration of the product, from primary package to the shipment pallet should be aggregated and identified using bar-codes (visible and non-visible).
- Qualification and training of personnel
Employees, logistics service providers and contractors who were hired for Pharmaceutical, Medical and Biological product supply chain, need to be trained and qualified for their job in addition to background check. Controlled documents such as policies and SOPs should be written and trained for all supply chain functions and relevant personnel in the manufacturer company and related companies, service providers and contractors. In cases of narcotic and hazardous products/material handling, storage, transportation and distribution- dedicated SOP’s and training should be implemented and documented, in addition to securities pro-active actions required for narcotic material handling, storage and distribution. Training program, requirements, frequency and documentation should be based on Good Manufacturing Practice standards and principles.
- Equipment, facility and packaging Validation
Warehouse, storage equipment, containers, packaging, vehicles and other system which may have an impact on product quality or GMP should be qualified including Design Qualification, Installation Qualification, Operational Qualification and Performance Qualification.
- Computerized system and software validation
Warehouse computerized system and software for inventory management, monitoring, alarms, track & trace and others should be validated according to 21CFRpart 11, GAMP and Annex 11 standards. For more information refer to article: Computerized System Validation
Qualification and Validation for the facility, equipment, utilities,software and computerized systems should be completed before using it for product/material storage and distribution.
The validation activities scope may vary from one facility to another. Below examples for recommended qualification and validation stages:
- URS (User Requirements Specifications)
- Validation Plan
- Risk Assessment
- DR (Design Review)
- DQ (Design Qualification)
- IQ (Installation Qualification)
- OQ (Operational Qualification) including Passive shipping systems
- PQ (Performance Qualification) including Active shipping
- Ambient temperature profile
- Computerized System and software Validation
- Monitoring and alarm software Validation
- Facility Qualification
- Warehouse management system Validation
Material and product handling procedures should be clearly defined and cover all relevant aspects. SOPs should define all areas including (but not limited to) delivery, receipt, storage, transportation, shipment and distribution. Conditions and procedures for receiving and shipping areas, where the product is not stored for long time period but may subject the product to non-controlled environment, should be clearly defined. Product’s status determination and quarantine procedures should be defined and implemented.