The following edited excerpts are from a panel discussion hosted by the ELPRO Leading Minds Network as part of its Temperature Control Tuesdays™ programming in partnership with Biocom California. The session included Christine Wenner, Senior Clinical Supply Chain Manager, U.S. Clinical Services and Gavin Morgan, Senior Manager, Global Logistics, both of PCI Pharma Services. 

Key Takeaways to Learn About in this Blog Post:

• What impact the global pandemic had on procurement and supplier networks for future project set up.
• How clinical trial stakeholders responded to the challenges of closed borders.
• The effect smart courier selection can have on successful shipments
• What to consider when supplies initially planned for clinical trial use are to be provided for an alternative supply (e.g. named patient supply or compassionate use)
• What needs to be considered when implementing a direct-to-patient model, both as a temporary solution or as a part of a longer term study design.
  
  

At the beginning of the pandemic in particular, the planning and implementation of clinical trials became extremely difficult. From one day to the next stakeholders faced unprecedented challenges. Disruption of supply chains for syringes, vials, book labels, ancillary supplies; the collapse of the global aviation industry and the resulting lack of temperature-controlled shipment capacities; closed borders within Europe; and the restriction on the movement of persons were unforeseen obstacles to overcome. Clinical trial supply used for Early Access Programs (EAPs) or as compassionate use supply by manufacturers faced even more difficult challenges.

PROCUREMENT

Procurement generally involves making buying decisions under conditions of scarcity. If sound data is available, it is good practice to make use of economic analysis methods such as cost-benefit analysis […].
Wikipedia

In conducting clinical trials during the global pandemic, all stakeholders became keenly aware of the truth of this part of the definition of ‘procurement.’ Ancillary supplies, book labels, needles, syringes, and many more–as well as courier capacities to deliver clinical trial supplies to the respective study countries–were procured under the extreme conditions of scarcity. Sound data, on the other hand, were scarcely available, especially at the beginning of the pandemic.

It was literally hitting every aspect of the procurement business.
Christine Wenner, PCI Pharma Services

In April 2020, eighty percent of global flights were affected. For companies relying on passenger flights to deliver their temperature-controlled clinical trial supplies twenty percent of the global air traffic is simply not enough. Vaccine manufacturers organizing a massive vaccine distribution occupied large shippers, always having priority when it came to materials, temperature control units, GPS data loggers, temperature-controlled vehicles or freight capacities on passenger or cargo flights.

We were competing for vehicles, temperature control units, for cargo flight.
Christine Wenner, PCI Pharma Services

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PCI Pharma Services’ Lessons Learned:

• Strongly collaborate with courier partners to avoid situations where priorities changed on short notice, as couriers granted priorities to vaccine transportation orders by the government.
• Clearly communicate to customers delays and priorities to make planning easier for them.
• Plan proactively and early and have a backup upon the backup to cover delays of sometimes several weeks.
• Challenge your Interactive Response Technology (IRT) system to allow changes, within acceptable times and at acceptable cost – with regard to transit times, choice of courier, look ahead periods, and inventory to be held at side.

CLOSED BORDERS 

In March 2020, Italy was one of the first countries to impose a national lockdown, restricting the movement of the population, and officially closing borders. Following that, borders closed very fast within the EU and many other countries. PCI Pharma Services, the sponsors, Contract Manufacturing Organizations (CMO) and Contract Research Organizations (CRO) had to find new ways to get their clinical trial supplies into the respective study countries.

In the pre-Brexit period, clinical trial supplies were shipped into Italy via the UK, via European CMOs, or one of their distribution sites. Fortunately, certain transit routes and ports of entry were pre-approved by the Italian government for COVID-19 medicines. Yet, in order to bring the goods into the sealed country, additional documentation from the Italian Ministry of Health was needed. This is where the in-country CROs came in. Based in the respective country, they were able to enter into close exchange with the respective authorities at short notice.

As the CRO had the relationships with the regulators, they need to get those documents, they need to work with the principal investigator or the Ministry of Health.
Gavin Morgan, PCI Pharma Services

PCI Pharma Services’ Lessons Learned:

• Manage expectations and clearly outline roles and responsibilities, especially when it comes to tasks that go beyond the scope of the ordinary.
• Be creative in finding new ways to enter the country of study – utilize smaller airports, fly into a different port of entry (or even an adjoining country even) then use the road for the “last mile.”
• Keep an eye on transit times and costs – new routes may require extra documents and permissions, transit times may be longer, costs could increase significantly, especially when multiple shipments or large shipments are pending.

It gets the product moving. Absolutely, we can get the product to the site, but it's going to be very costly.
Gavin Morgan, PCI Pharma Services

• Advise the CRO well in advance of what might be expected of them – they are expected to perform their intended task, but it may become necessary for them to work directly with the CMO, the couriers, or the Department of Health.

You may need them to go that extra mile. 

Gavin Morgan, PCI Pharma Services

 

COURIER SELECTION

For the transportation of their supply, the clinical trial industry has always relied on specialist couriers who excel in “white-glove” service (i.e. full management of temperature control and oversight of the shipment). They go the extra mile, contacting the consignee and arranging the delivery – a particularly important service especially during the pandemic, when the delivery of goods has been a real challenge. Even before the pandemic, specialist couriers were relying on passenger flights to place their cargo shipments. However, pre-pandemic, only around five percent of the airlines’ revenue was based on cargo. It was always on passengers and often cargo shipments were deferred in favor of additional passenger baggage. During the pandemic, when almost overnight eighty percent of passenger flights were cancelled, specialist couriers did not have the flights on which to put the cargo.

It really has been the biggest challenge during the last 18 months.

Gavin Morgan, PCI Pharma Services

In this situation, cargo then became a premium. Standard couriers, which had always relied on cargo and maintained their own aircrafts, came into play. These carriers could deliver even when passenger flights were cancelled. However, they usually did not offer the same level of white-glove service or temperature control in transit.

PCI Pharma Services’ Lessons Learned:

• Combine the best of both – They shipped material internationally or within the EU with a standard integrator and let the specialist courier do the ‘final mile’ delivery. Retrieving the product from their local office, they found a way to get that shipment into the hospitals and the pharmacy departments.
• Think outside the box and look for alternatives to get the clinical trial supply to the study participants. If they could not deliver it to the pharmacy directly, they dropped it at a receiving doctor and placed packing information on the inside to ensure that it could get through to its final destination. They also made sure that even if a container was opened, the inner contents were still being left undisturbed.
• Monitor the sites you are delivering to – PCI Pharma Services kept themselves informed of changing receiving days, procedures and processes, and, in order to protect the integrity of the supply, put it into longer-range shippers when delivery was repeatedly delayed at certain sites.
  
  

COMPASSIONATE USE SUPPLIES

During the pandemic, some of PCI Pharma Services’ customers wanted to use clinical trial supplies for either Early Access Programs (EAPs) or Named Patient Programs. In this case, neither the Clinical Trial Application (CTA) nor the Investigational Medicinal Product Dossier (IMPD) apply. Nevertheless, manufacturers had to find out what was needed at a high level in a certain country with regard to quality release. Do they require a qualified person, a GMP certificate, or a pedigree document of the supply chain? What applies if the product has been imported previously for clinical trial use? And what applies if it hasn’t?

Regarding label design, the companies asked themselves: How early do we start thinking about it? Do we consider EAP use not knowing if there is a demand for it in the respective country later on? Alternatively, do we postpone the decision until later and risk having to relabel products?

Do you pay for that upfront, or do you cross that bridge when you get to it?
Gavin Morgan, PCI Pharma Services

The biggest impact PCI Pharma Services saw during the pandemic was that a lot of requirements got waived. Countries were desperate to get some type of supply, and some type of relief or treatment. Whether it was expiring dates, translations into different languages or requirements of Annex 13 – the credo was: Let's move, let's use it!

PCI Pharma Services’ Lessons Learned:

• Gain support within the country from somebody who is able to ask the right questions of authorities and to find out what is required – because each country is slightly different.
• Don’t rely on exceptions to requirements, they are not a trend! As time went by, PCI Pharma Services saw all the rules coming back into play. At all times, close attention had to be given to the conditions imposed by the respective countries on granting exceptions.
  
  

DIRECT-TO-PATIENT / SITE-TO-PATIENT

At the beginning of the pandemic, PCI Pharma Services saw the demand for direct-to-patient or site-to-patient shipments increase by 100 to 150 percent in volume. This happened virtually overnight due to the restriction on the movement of persons. People were not allowed to visit a clinic nor come to an investigator site for dosing.

True direct-to-patient studies require protocol, defined CTAs, and approval by regulators. For ad hoc site-to-patient transfer, however, there was not a full submission. The CRO or the sponsor would get authorization from the respective authorities within the country.

In all cases, authorities expect the companies to do a detailed risk assessment in advance, answering the following questions:

• Is the IMP self-administered?
• Can the product be left with the patient?
• Does a study nurse have to be involved to coordinate all of these things?
• How are 2 °C to 8 °C products handled? Are those suitable for a site-to-patient transfer?
• Does the temperature excursion process need to be adapted? How does one deal with an increased chance of a temperature alarm (false excursion) when delivering the drugs to a patient’s home?
• Is there going to be an on hold, a deviation process, a sort of disposition process?

Answers were required to many organizational questions, such as:

• Who is going to place the book in?
• Who will coordinate the courier and the shipments?
• How is GDPR in Europe ensured and how is the patient confidentiality maintained?
• Who is going to do the site-to-patient transfer? CMO, CRO or the sponsor?
• Is there going to be a need for contactless deliveries at sites due to social distancing?

PCI Pharma Services’ Lessons Learned:

• Outline roles and responsibilities early so as not to loose time when an ad hoc site-to-patient transfer becomes necessary.
• Plan for the eventuality to do a site-to-patient or a direct-to-patient model when considering a new study PCI Pharma Services see more and more sponsors designing their study as a typical standard clinical trial, but putting in their protocol that they are “pre-approved” in case they need to do a Site-to-Patient transfer.
• Keep cost in mind – especially for the specialist courier deliveries.

Hopefully you never need to do them, but if you do, it's something that you need to be prepared for.
Gavin Morgan, PCI Pharma Services

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