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Avoiding Obstacles
March 2009This article was published in the European Pharmaceutical Contractor publication
Pharmarama provide seven steps to ensure the correct procurement and delivery of cold chain clinical trial supplies.
Clinical trial supplies management can be a notoriously difficult logistical task. The opportunity for deviation is further enhanced by having to manage the movement of cold chain material (typically classified as 2°-8°C). This article will look at the most common obstacles encountered when procuring and moving cold chain products, with a focus on comparator products.
More and more clinical trials are utilizing comparator drugs and, especially in oncology, most of the existing products are cold chain. There is much to consider when moving cold chain products: gone are the days of throwing in a few gel packs and hoping for the best. The standard expected now is much higher, and correctly so. Regulatory and logistical requirements often shape the delivery protocol. Medicines requiring controlled temperature storage conditions must be distributed in a manner that always ensures that their quality will not be adversely affected.
The World Health Organization’s policy on Good Distribution Practice (GDP) broadly mirrors the attitudes published by bodies such as the Food and Drug Administration (FDA), European Medicines Evaluation Agency (EMEA) and the Medicines and Healthcare products Regulatory Agency in the UK (MHRA). In essence, the regulations are harmonious. Any deviations in storage conditions could adversely affect product quality and often require disposal of product at significant cost. One large CRO conducting an oncology trial had to dispose of nearly £2 million of product simply because the product was not transported under sufficiently controlled temperature.
The method used was not validated and was chosen rather than to a more expensive and robust solution. These unforeseen costs can spiral your tight budget out of control and potentially delay the trial itself. This is one of many problems and there are numerous other challenges commonly encountered when shipping cold chain products. Here are seven top tips that you can use to minimize disruption to your clinical trial.
CHOOSE YOUR VENDOR CAREFULLY
Many vendors exist in the marketplace from which to procure your comparator drug. The vendor should be a company that specializes in clinical trial supplies – always ensure that the vendor you select has experience and knowledge in moving this type of product. A good company will be able to advise you on the best option for your project. A good vendor will always have technical agreements in place with its freight forwarders and will often involve them in any discussions with you.
You should also ensure that you have a technical agreement in place with the vendor and build a good working relationship with them. They should come up with options that you would not have contemplated, drawn from their measurable experience. Consider the vendor as another member of your project team and give them accountability to manage the entire supply process for you.
MINIMISE THE NUMBER OF STEPS FROM THE MANUFACTURER TO YOU
Logic dictates that the number of steps in the supply chain increases the overall risk of deviation. It is always wise to procure product from a vendor who has direct relationships with the manufacturer concerned to ensure that the number of times the product is handled is at a minimum. This also reduces the risk of counterfeit products arriving at your or your vendor’s warehouse.
It is worth noting that some manufacturers refuse to supply product for use in clinical trials, so do ensure that you forge a good relationship with your selected vendor. This relationship should make it far easier to obtain stability data, which could save rejection of the product, should a deviation occur.
AUDIT, AUDIT, AUDIT!
Your vendor should always be audited as part of your organization’s quality assurance program. At present, there is no legal obligation for them to formally audit their logistical partners. However, in the UK, the MHRA are introducing plans to ensure that companies audit all freight partners (whatever size) and declare details of this on their licenses. Currently, the prestigious comparator vendors exceed this requirement and do site audit their partners.
During the audit, it is always prudent to inspect their working technical agreement with the shipper. Many large global freight forwarders offer cold chain shipment services. It is wise to remember that should you wish to actively control your order, a global freight forwarder may not be able to offer you a completely dedicated service. Also, if any deviations occur due to poor handling then they will not be forthcoming with taking responsibility. Always try to work with one contact: the vendor.
USE A SUITABLE VALIDATED METHOD
There are many solutions to shipping variable quantities of product. From one pack to 100,000 packs, the best solution is one that has been extensively validated and demonstrated. The days of shipping product with gel packs should be a thing of the past. There are many sophisticated units that work on passive cooling for example. Such units have been found to keep the cold chain cycle unbroken for up to 12 days, despite only being officially validated for four days. Of course, these represent a considerable cost due to their weight, but peace of mind is guaranteed.
Other systems to note are ones that work by insulation. These systems are usually validated for up to 96 hours at normal outside temperatures. The preferred, and most costly, is of course the use of a refrigerated vehicle. It is always wise to insist that the shipment is dedicated, that it is not shared with any other customers. This ensures that there is no cross contamination. A good quality vendor for comparator product will always recommend the use of a properly validated solution and coordinate it for you. Be wary of taking the cheaper option which invariably carries greater risk; it pays to invest to prevent risk.
USE OF SPECIFIC TEMPERATURE MONITORING EQUIPMENT WITH SHIPMENT
It goes without saying that suitable temperature monitoring devices should accompany all shipments. Some of the products mentioned previously have inbuilt devices; a dedicated van will have its own too. There is much debate amongst quality professionals over whether to include a backup device packed with the product. Some argue that a secondary temperature monitoring device could provide confusion, especially if the readings are different to the primary device, as it can then be unclear as to which readings are to be used to confirm shipment compliance.
On the other hand, if a secondary device is not included and the primary source fails, there is no backup to ensure compliance and the product may have to be destroyed. When deciding what level of temperature monitoring to deploy, seek advice from your quality assurance colleagues in tripartite with the vendor.
ENSURE THE VENDOR HAS ADEQUATE COLD CHAIN STORAGE FACILITIES
Many vendors have varying standards of cold chain storage facilities. Some have simple domestic fridges (needless to say, don’t use them!), others have expensive, validated and constantly monitored walk-in facilities. Always ensure that the vendor can accommodate the volume of product you will purchase and that they have sufficient temperature monitoring in place. A quality assurance audit will inspect this during the course of the assessment.
PREPARE FOR CUSTOMS AND EXCISE
For shipments in and out of the EU, customs (and the FDA in US imports) play a pivotal role and hold a very powerful position. Should anything not be in order, they will have no hesitation in holding shipments until the query has been resolved. During this time, they will store the product in an uncontrolled manner and thus the suitability of the packaging solution is tested.
Some instances have occurred where the goods have been taken out of the container and placed into a normal fridge amongst foods. Other horror stories include the customs officials opening the container and switching off the refrigeration controls! Always ensure that you have the appropriate documents required for swift clearance and, where needed, provide this for the vendor so that they can accompany the shipment. Your vendor will work closely with the freight forwarder and utilize their experience. Many a shipment has been stuck in customs for more than the validated time period, resulting in an out of specification product.
Always ensure that working days and public holidays are considered: it is very difficult to clear a delivery over the weekend when the product can potentially go out of specification. Above all else, plan for the unexpected. Plan each stage in minute detail and make sure that you and your vendor work closely together to ensure the product moves smoothly from factory to the required location. The potential for disruption to the trial will undoubtedly be minimized.
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