Refrigerated Medicinal Products: Things to consider

Based on the experience made in GDP inspections, the U.K. Medicines and Healthcare Products Regulatory Agency (MHRA) has published things to consider for the transportation, packing, temperature management, the use of third party couriers and returns of refrigerated medicinal products:

Packing of consignments and temperature management during transportation:

• Refrigerated products should be packed in such a way as to ensure that the required temperatures are maintained throughout the journey
• For small volumes of lower risk products, with short journey times of less than three hours, validated insulated containers can be used
• For extended journeys, gel or ice packs are added to the packaging to maintain appropriate temperatures throughout
• Larger volumes of refrigerated products will generally be shipped in refrigerated transport. This is particularly important if transportation times may be protracted or liable to delay

The decisions made on how to proceed should be based on risk evaluation according to ICH Q9. However the temperature should be controlled and monitored anytime with calibrated devices. All transportation arrangements "should be regarded as an extension of the storage activities and distributors are expected to treat each journey as unique with the length and complexity, as well as any seasonal variations, being considered when choosing the packing method and mode of distribution."

And what about the Mean Kinetic Temperature (MKT)? Here, MHRA clearly describes the agency's thinking:
"The application of Mean Kinetic Temperature (MKT) to temperature monitoring of wholesale products is only appropriate where an acceptable MKT value is provided by the MA holder for a specific product, and the recording of temperature can be confirmed to be consistent and complete from the moment of leaving the manufacturer's premises. In practice the application of MKT fails where a complete chain of temperature recording cannot be allocated to a specific consignment of a product. Attempts to apply MKT have been proposed by wholesalers as an alternative to having adequate temperature control within their warehouses as well as attempting to downgrade the impact of temperature excursions. The use of MKT in the wholesale environment without robust supporting information and methodology is therefore discouraged".

Third party couriers

• All couriers need to be qualified
• Chapter 7 of the EU GDP Guidelines (Outsourced Activities) should be considered

Returns of refrigerated medicinal products

• Because of challenges with refrigerated products, a subsequent resale should not be considered in any event
• Products can only be returned to saleable stock, if:
  - Supporting transport documentation and return forms should be available
  - A trained person should examine the returned product
  - All checks need to be satisfactory and are documented
• If not returned to saleable stock, returns should be stored in a dedicated and marked area awaiting collection by a licensed disposal company.

For other returns, paragraph 6.3 of the EU-GDP Guidelines should be considered.

You will find more in the MHRA Inspectorate Blog "Refrigerated medicinal products, part 2: Transportation, packing, temperature management, the use of third party couriers and returns – some things to consider".