Regulatory Gap Analysis to Assess Internal Cold Chain Compliance

Perform periodic Regulatory Gap Analysis to assess and maintain your Cold Chain Compliance (Storage, Handling and Distribution).

Cold chain concept refers to all resources that are required to maintain temperature sensitive pharmaceutical products within temperature limits (e.g. 2-8ºC, 15-25ºC) as specified by manufacturers or producers. In the Pharmaceutical field, Good Storage and Distribution Practices now provide cold chain regulatory and compliance requirements for the storage and distribution of temperature-sensitive products, including Good Distribution Practices for Pharmaceutical Products, World Health Organization (QAS304.068), Guidelines on Good Distribution Practice of Medicinal Products for Human Use, European Medicines Agency (EMEA 94.C 63/03), Guidelines for Temperature Control of Drug Products during Storage and Transportation, IDGPSA, Health Canada (Guide-0069), Guidance for temperature-controlled medicinal products: Maintaining the quality of temperature sensitive medicinal products through the transportation process, Parenteral Drug Association (PDA, Technical report Nº39 revised 2007) and Good Storage and Shipping Practices - General Chapters, United-States Pharmacopoeia USP <1079>.

Cold chain compliance can be reached only when all the stakeholders involved in the pharmaceutical supply chain (manufacturer, wholesalers, transporters, pharmacy...) have addressed individually and as partners their quality issues in terms of handling, storage, distribution and transportation of temperature-sensitive pharmaceutical products.

A Gap Analysis to assess Cold Chain Compliance
The pharmaceutical cold chain concept implies all necessary means to maintain therapeutic products in the specified manufacturer's temperature limits during all the distribution process (manufacture, storage, transportation, final use).

A non-observance of the cold chain or a deficiency in its monitoring mechanisms usually affects the products' therapeutic properties and consequently generates deficiency quality risks (absence of therapeutic effects, intoxication or other non indexed reactions). The respect of the cold chain initially implies to know well constraints which surround it and traps to be avoided.

The general principles for good cold chain compliance can be summarized as follows:

1. The good quality of pharmaceuticals must be maintained throughout distribution networks. Thus, these products will reach the hospital, and therefore the consumer, without any deterioration of their therapeutic properties
2. The Quality Control service must make sure that conditions of storage are observed at any moment, including transport.
3. Standardized Operation Procedures (SOP) should describe all operations likely to affect the quality of pharmaceuticals or the distribution, including the reception of deliveries, storage and recording of storage conditions.
4. Instruments and equipments used should be adequate to ensure a good conservation and distribution of pharmaceuticals.

Gap Analysis on all Handling, Storage and Distribution areas and processes
Cold chain gap analysis shall apply onto all sectors that have a potential impact on the cold chain and product integrity such as, to name only a few:

• Staff members (training, etc.)
• Documentation and SOPs
• Reception area
• Storage Area
• Monitoring of storage area
• Transportation (processes, quality agreement, etc.)
• Temperature monitoring during transportation
• Management of returned products
• Return of non defective Products
• Emergency plan / drugs Recall

Stakeholders of the pharmaceutical supply chain must be aware of some of their responsibilities in regard to cold chain and product integrity. Companies shall be equipped with a Quality Assurance (QA) department having the responsibility to define each staff member functions and responsibilities in the cold chain, to regularly train the staff in regard to the Good Distribution Practices (trainings should be documented) as well as before the application of a new or modified procedures.

Adequate procedures shall be present for the transportation of pharmaceuticals, and particularly in respect with the cold chain aspects. Procedures shall take care of various points, including the corrective actions in the case of unfavourable events during transportation, the necessary documentation for loadings and the traceability accompaniment (exp: goods itinerary, temperature controls, staff in charge of the transportation, etc.), the control of changes, and the handling of pharmaceuticals during the cold chain transportation process, particularly when pharmaceutical products are waiting for loading (Truck/Plane) on docks where the temperature is not controlled. Periodic inspections with defined intervals should be carried out to make sure that procedures are applied, with these inspections being documented.

Stakeholders must be sure that pharmaceuticals to be distributed, consigned from everywhere, are manufactured, stored and transported to its premises in conformity with the GMPs and cold chain requirements. Communications should be done to customers and service suppliers for all the information concerning the pharmaceutical cold chain transport and storage specifications. Also, stakeholders should carry out audits in its service suppliers in order to make sure that the distributed products are manufactured, packed, stored and transported in accordance with the applicable requirements.

Importance of Stability and Temperature Excursions Studies
Stability and temperature excursion study results can be of extreme importance for a future good management of the pharmaceutical supply chain. Stability and temperature excursion reports shall stand as the basis to define the conditions and condition limits (temperature...) that will be considered for the compliance of warehousing, handling and transportation processes.

A Special Attention to Pharmaceutical Transportation and Distribution
Carriers, logistic service providers and transporters should be targeted for a special attention to know if an uninterrupted temperature control system is set up in the vehicles used for the transportation process, if the carrier has a loading traceability system or if Quality Assurance procedures are available and applied.

The stakeholders shall make sure that the means of transportation are adequate for the transportation cold chain process, and provided with equipments such as a cooling and heating system adapted to seasons, calibrated temperature recording equipment, and regulated alarms (Min/Max.) being set according to the specified temperatures for the transportation of Pharmaceuticals.

When not using a temperature-controlled mode of transportation, packing systems shall be available and qualified for the transportation of cold chain pharmaceuticals. Such systems should be adequately designed and qualified to protect products and maintain the temperature range during the shipping and transportation under the various seasonal weather conditions.

Regulatory gap analysis is an essential starting point in assessing and controlling cold chain compliance, and should be periodically performed in order to maintain your cold chain compliance level.