How to write a superb Cold Chain Validation Plan

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Introduction to cold chain validation procedures.

Understanding how to write a superb Cold Chain Validation Plan could make you a very sought after person since the release of a recent Cold Chain Validation has quite suddenly focussed a lot of attention on the fact that the cold chain may not be as cold as is required i.e. controlled substances (while in transit) are being damaged by being stored in temperatures out-with the regulatory mandated requirements. 
The facts release indicated that nearly a quarter (23%) of all drugs distributed in the USA, could be or are of unknown efficacy. The distribution of these temperature sensitive products in vehicle containers that lacked validated methods of maintaining the correct internal temperature or even the ability to produce a validated history of what the actual conditions were; has rendered these products 'adultered', i.e. of unknown efficacy or safety. Vehicle body internal temperatures; with seasonal variations, can range from a high of 50 to a low of -40 (degrees centigrade). In contrast the mandated internal temperature for distribution containers for standard drugs and medical products is 2 to 8 (degrees centigrade), with much lower temperatures specified for some drugs.

This shocking news has certainly guaranteed that Cold Chain Validation compliance will be top of everyone's audit list, specifically when drug interactions with the end user are considered as critical. The implications of products being damaged and out of specification may induce many companies to replace doubtful goods or even trigger the regulators into initiating product recalls. This problem is expected to create a veritable stampede as distributors scramble to ensure that all the vehicles and containers they used in this essential everyday service, are rendered Cold Chain compliant, as soon as is possible.

Those who are not familiar with the requirement can find it all here - Cold Chain Legislation. There are now clearly defined requirements for the verification of all elements and aspects of the product temperature while in transit. It is essential to realize that temperature mapping of temperature controlled containers, trailers and or other containment devices used in transporting temperature sensitive controlled substances may only be one aspect of your overall validation requirements.

cGMP procedures mandates that pharmaceutical produce in transit or storage must not be subjected to temperatures that can induce unwanted changes to their efficacy, quality or purity.
21 CFR part 211.142 refers.

Why understanding how to write superb cold chain validation is suddenly very maketable.

There is now legislation in nearly all countries to ensure that all regulatory controlled drugs are protected from exposure to out of specification climatic conditions by rigid adherence to cold chain compliance practices and procedures. It is now commonly accepted that there are many instances where the efficacy of drugs has been directly impaired because their stored climatic conditions were not strictly monitored and temperatures were allowed to exceed specified safe maximums and at times minimums. So care must be taken to ensure that the procurement process for all such climatic equipment is comprehensive enough to specify which parameters are critical and require constant monitoring and management. An analysis of these requirements User Requirements Specification (URS) should be developed to ensure that the storage conditions are correctly specified and safely engineered.

Lack of continuous monitoring has allowed drugs to be permanently damaged due to poor handling procedures i.e. cabinets doors left open, cabinets switched off inadvertently or even cabinets accessed to frequently. These errant conditions would have been observed had continuous monitoring systems been in use. However with properly engineered alarm systems they can be immediately identified and prevented from causing product damage. This is where the emphasis is now being applied - Cold Chain Validation verification will ensure that all temperature controlled transportation and or holding areas, such as; rooms, fridges, freezers, trailers, delivery vans and haulage lorries, are cGMP compliant.

In a recent project where the product went through a six stage production process. From start to finish the product had to be maintained sub minus 20ºC. At times there were several days between processes, also some processes were much faster than others, inevitably product queues developed as product waited between process stages. During this processing and in between stages, the product was held in 3cumt mobile freezers (122 of them) running at minus 25ºC.

On a regulatory visit the regulators decided to investigate this process. They were very persistent and thorough. All the freezer cabinets and all temperature controlled transport containers and trailers were run through the full range of functional tests. They all failed their defrost cycle and subsequently required extensive reworking. The failures were in large down to the cabinet control systems. However there were fundamental design requirements that the company did not have in their URS.

The under listed requirements were agreed with the regulators as FDA minimums for holding controlled product in an engineered climatically (hot or cold) controlled environment./div>

The Urgency for Compliant Cold Chain Transportation.

According to a recent study conducted by the U.K. based Medicines and Healthcare Products Regulatory Agency (MHRA), a staggering 43% of critical and major product deficiencies are related to ineffective temperature control and monitoring during storage and transportation.

Similarly the World Health Organization (WHO) recently maintained that 25% of all vaccine products arrive at their final destination in a degraded state. Given the high cost of conducting global clinical trials and the even higher cost of failure, regulatory agencies and pharmaceutical companies alike now demand that every party involved in the pharmaceutical supply chain - transportation and logistics providers included − conform to GxP guidelines and immediately activate procedures to attain Cold Chain Validation compliance.

1. WHO’s “Good distribution practices for pharmaceutical products” and “Guide to good storage practices for pharmaceuticals”

1. FDA’s “cGMP / 21 CFR 211”

1. U.S. Pharmacopeia (USP) <1079> “Good Storage and Shipping Practices”

1. Canada’s “Guidelines for Temperature Control of Drug Products during Storage and Transportation”

1. Ireland’s “Guide to control and monitoring of storage and transportation temperature conditions for medicinal products and active substances”

1. EU’s “Guidelines on Good Distribution Practice of Medicinal Products for Human Use” (94/C 63/03)

It is anticipated that these finding will move all things to do with - product quality in transit - to the top of visiting regulators inspection lists. The obvious priority being the thermal validation of transit containers - be they demountable or integral to a motor vehicle.

Validation of these containers and or vehicles is not difficult and can be tackled (using our fully detailed documents) by most technicians and or laboratory assistants.

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