Maximizing the Efficiency of Clinical Trial Supply Chain
Sujay Salvi
Head - Clinical Trial Supplies
Management, SIRO Clinpharm

Partha Chatterjee
Head - Clinical Research
SIRO Clinpharm

Clinical trials are an essential part of the product development process for both pharmaceutical and biotech companies and if run efficiently can provide the company with a competitive advantage. This article discusses various key factors pertaining to an efficient and effective clinical trial supply management.

For a new drug to reach the market it has to undergo a robust clinical trial process which requires considerable amount of investment and can continue in excess of 10 years. The process involves global multicenter trials and recruiting a large number of patients to achieve the trial objectives eg, safety and efficacy. Different types of clinical trial supplies, from investigational products to ancillary supplies are required to conduct clinical trials. The clinical trial supply chain is an integral part of any clinical trial; it constitutes packaging, labeling, storage, distribution to patients located in different geographic locations, and accountability and destruction of clinical trial supplies.

Below are the examples of Clinical Trial Supplies:
  • Clinical Trial Drug Supplies:
  • Investigational Product & Comparators, Background / Rescue Medication
  • Clinical Trial Non Drug Supplies:
  • Equipment & Lab Kits, CRFs, Blinding/Randomization Envelopes
The primary goal of clinical trial supply process is to deliver

The RIGHT SUPPLIES at the RIGHT TIME to the RIGHT INVESTIGATIONAL SITE for the RIGHT PATIENT

Although the basic principles of logistics apply to Clinical trial supply chain, it is different from Pharmaceutical commercial supply chain due to the following aspects:
  • Investigational Products are still under testing hence many aspects of the investigational product are still under 'investigation' or in other words the product needs to be administered to a selective group of patients who has consented for the clinical trial. It is, therefore, extremely critical to have a controlled use of such products right from the lab where it is being produced, till the time it is consumed by the patient, while all the extra supplies are accounted for and destroyed.
  • Investigational Products are exclusively manufactured and packaged depending on the trial design so they are not available off-the-shelf
  • Some investigational products eg Oncology products are very expensive and available in limited quantity, hence any wastage could affect the fate of the clinical trial.
  • Each kit used at the investigational site is accounted for down to the unit level eg tablet, capsule and it needs to be returned to the sponsor for destruction.
  • The trial data is submitted to the regulatory authorities for registration hence clinical trial supply chain is prone to regulatory audits and inspections.
  • The compliance level of the investigational product during the trial has a direct corelation with the final outcome of the trial. If it is not as per the desired level, the entire trial data would be of no use. Hence, one needs to have built-in quality checks in a study design and monitor closely so that the final outcome is achieved.
Therefore, it is imperative to optimize the clinical trial supply chain process with respect to time, quality, safety & integrity, and at the same time, bring in cost efficiencies.

In order to maximize the efficiency of clinical trial supply chain, it's important to know the various challenges associated with the process and the approaches/ techniques to address them.

Geography - Multicenter/ Multinational Trials

One of the biggest challenges is the geographical location of the source and sites.

With the rapid growth in the number and spread of clinical trials, there are many multinational & multi-center trials, where multiple countries across the globe and various hospitals in those countries are involved. The clinical trial supplies need to be delivered at these sites from the source eg, central depot. This could result in longer transit time, for example the central depot could be in USA and the sites in South East Asia.



In most of the countries, the drugs cannot be shipped to sites unless necessary approvals from Regulatory and Ethics committee are in place. Hence the clinical trial supplies cannot be sent in advance.

Global Regulatory Requirements

Regulatory requirements could differ from one country another and inadequate knowledge about it could lead to delays in customs clearance. In many countries, import license is required to import drugs and the invoice should match the import license. The labels on investigational product kits should be as per country regulatory requirements which could be country specific. For example, expiry date on the kits is not mandatory in USA but it is mandatory in India.

These situations could result in longer transit time. In case of delays in clearance, there are chances of improper handling of supplies at the custom warehouse which could ultimately compromise the cold chain and affect the quality of the product. There is also a risk of shipments being misplaced resulting in product wastage.

Product wastage can also be caused due to inaccurate forecasting, eg supplying excess investigational product to sites with low or no recruitment , or supplying products with short expiry date. Such incidences will have an adverse impact on the outcome of the clinical trial.

Poor subject compliance can occur if the investigational product is not available as the subject will not be able to adhere to the protocol specified time regime. This will adversely affect the company's reputation as it is the social and ethical obligation of the sponsor to make the investigational product available to the patients at all times during the trial period; this is also a GCP requirement.

Substandard products resulting from improper handling may jeopardize the clinical trial outcome and there could be chances of data being rejected by the regulatory authorities.

Such issues will also delay the completion of the clinical trial and, in the worst case scenario, could lead to cancellation of the trial all together. The sponsor ultimately could incur heavy losses because of all these issues.
  • Based on years of industry experience, here's a checklist which could help in developing the right clinical trial supply chain strategy. Use of a service provider (local depot)

    The sponsor can appoint local depots in the countries which are participating in the clinical trial. As Clinical Trial Supplies Management is a niche area, many sponsors prefer to outsource it to the experienced partners rather than managing it by themselves. These depots are GxP compliant and provide end-to-end service from receipt till destruction of the investigational product. These depots can be audited and approved by the sponsor's Quality Assurance department. This partnership has many advantages, shorter transit time to sites being the most important advantage. The local depot can receive the drugs from the central depot after DCGI approval is received for the trial & import license is in place. Once the ethics committee approval is in place, the local depot can distribute the supplies to various sites.

    Shorter transit time also ensures lower courier costs. The drugs can be shipped by the central depot/sponsor to the local depot as a bulk supply instead of supplying in bits and pieces, thus there will be fewer shipments imported for a trial resulting in less frequent customs clearance.

    Appointing a local depot will give an added advantage of excellent awareness of local regulatory requirements. The supplies will be always available at the depot and can be dispatched to sites on a short notice. The local depot can provide dedicated resources/project team handling a particular client ensuring a customer-focused approach and prompt action .

    Many clinical trials like Oncology trials require comparators, background or rescue medication. Local depot can also provide support in sourcing the comparators from the local market; this can ease the burden on the sponsor as the sponsor won't have to make arrangements for procuring it centrally and then distributing across the globe. Local sourcing will save time and ensure availability of supplies. By delegating this responsibility to the service provider, the sponsor can increase focus on the investigational product.
  • Selection of the right courier partner

    A courier agency with the right experience and expertise is essential for the Clinical Trial Supply Chain to succeed. Sponsor can directly or through the depot partner appoint a courier agency which is focused on the life sciences and has a proven track record in cold chain management . This will ensure ontime and safe delivery of supplies without any transit issues, eg, excursions, off-loading. Such issues may result in product wastage and add to the overall cost as the product will have to be resupplied to the sites. The courier agency can be audited by Sponsor /Depot partner. The courier agency should have processes in place for conditioning/preconditioning of gel packs, preparation of insulated shippers. They should always use validated shippers and calibrated dataloggers for the shipments.

    The courier agency should track the shipment till delivery and provide the POD and data logger readings to the sponsor/depot partner upon delivery. They should ensure that the supplies are delivered to the right person. In case of any issue, the courier agency must proactively and promptly inform the client.
  • Technology and Innovation

    Technology and innovation play an important role in the optimization of clinical trial supply chain. Multilingual labels or booklet labels are used for multinational clinical trials. Their main advantage is the flexibility of drug supplies. The supplies can be used in more than one country or redistributed between countries. This minimizes the drug wastage and reduces the overall medication cost. This hugely helps in trials where drugs are in short supply or expensive, e.g. Oncology trials. Booklet labels also complement the use of IXRS technology and pooled supplies.

    IXRS (IWR /IVR) - Interactive Web/Voice Response System is used for forecasting, randomization, drug distribution, Inventory Management etc. This system also tracks the expiry date. As this system is linked to randomization, the drug orders are generated as per the patient recruitment and visit schedule. This minimizes product wastage and ensures the availability of supplies at sites. It also underlines the importance of using a local depot in order to manage the JIT (Just in time) delivery to the site.
Case Study

Here's a case study to help demonstrate the how a sponsor can save much of their precious time and co-ordination exercise with an experienced clinical trial supplies vendor.

In a multicentre, randomized, blinded trial number of shipments containing investigational products were sent to the sites. After using these drugs on patients at the sites, these supplies were returned to the depot on an ongoing basis by the sites. The study had a long duration of about three years. After the recruitment target and all the patient visits were over the sponsor asked the depot to provide the drug reconciliation records. As the depot had not done the reconciliation of investigational product at the time of receipt of the returned supplies they faced lot of issues in the accountability. The depot staff spent no. of days in conducting the drug accountability and found that the documentation received from sites was not adequate, mismatch between the quantities mentioned on the returned documents and the physical returned stock received at the depot. Even after spending considerable time in this activity all the kits dispatched to the sites could not be accounted for and finally sponsor had to report them as missing with a great risk of potential audit and inspection finding. This situation could have been easily avoided if the drug accountability was done on a real time basis and all the discrepancies were promptly reported and resolved.

Conclusion:

The number of global multi-center clinical trials is increasing by day. Trial design and dosage regimes are becoming complex, and so are the challenges in clinical trial supply chain. The clinical trial supply chain has evolved over the past few years. The testing phase is over; sponsors nowadays are actively looking to reduce the cost of clinical trial supply chain without compromising the quality and integrity of the trials. The sponsors can achieve this by collaborating with the service providers who are experts in their domain and can provide a customized solution to their clinical trial supply chain requirements.