Management of supply chains is an increasingly complex process. Regulators demand high quality and reliability, but a lengthy supply chain involving multiple partners across countries makes it harder to ensure that standards are adhered to.
At the same time, drugs need to move quickly and smoothly between sites, with minimal disruption. Biological drugs, which are particularly heat-sensitive and susceptible to contamination, pose tough challenges. So how can pharma companies improve collaboration along the supply chain to minimise process deviations?
Didier Basseras is vice-president global head of clinical supply chain operations at Sanofi, where most of the company’s development programmes consist of large molecules that require a storage temperature of 2–8°C.
“When we consider an end-to-end process, cold chain management is still a supply chain challenge,” Basseras says. “Drugs being stored and transported at correct temperatures to ensure the quality of the drug at the time of delivery is critical.”
The important factors in keeping process deviations to a minimum, Basseras argues, are “maximising the efficiency of cold chain management, reduction of drug transfer and intermediate storage”. He goes on to say that a major part of Sanofi’s strategy is “exploring where temperature excursions are happening at investigator sites, while still having robust control of internal manufacturing operations”.
But the situation becomes more complex at the investigator site level because a number of sites have limited cold chain capacity.
“We must create an optimised solution early in the process, in terms of volume per treatment and minimising kit void space,” Basseras explains. “It’s also important to prioritise printing readable labelling information on packaging to facilitate proper use from caregivers – and avoid time that the product is not being refrigerated.”
Cold capacity and management are key parameters to assess an investigator site against.
“This good manufacturing practice (GMP) purpose, combined with good clinical practice, equates to one seamless process,” Basseras says.
Digital dynamics
When optimising supply chain processes, it’s essential to consider the patients’ home environment.
“Historically, vaccine refrigeration time has been an important consideration, whereas now we must train patients the proper way to handle new bio drugs,” Basseras explains.
Integration of digital tools is helping achieve collaboration across all parties.
“These programmes easily allow information sharing around trials and instructions for drug use,” Basseras explains. “Keeping patients connected digitally by using features such as smart packaging also facilitates better compliance.”
The regulatory environment is becoming increasingly tough, which means that supply chains need to be completely robust. Visibility and traceability along the whole length of the chain are essential if pharma companies are to be fully compliant. Sanofi has addressed that by integrating digital solutions along the chain to record and act on relevant information.
“Capturing the time out of refrigeration (TOR) is an area where digital is offering dynamic solutions, allowing us to better anticipate when the TOR is expected to exceed what stability allows, and when product replacement will be necessary,” says Basseras.
Constantly evolving stability data can create difficulties with the shelf life of drugs.
“To maintain continuity of treatments for all patients requires agility to replace drugs, while also updating the regulatory files to comply with new statements,” Basseras explains.
Good organisation of supply chains across countries and sites is imperative, “for either the recovery of drugs we cannot dispense due to the shelf life not covering the full treatment duration, or to facilitate relabelling in the case of an extension”, he adds.
These processes must be closely managed with quality and regulatory teams in order to be efficient.
One way of increasing the flexibility of the supply chain, Basseras says, is to have “direct shipping to sites from regional platforms. Proper allocation from one central point to sites in different countries can reduce the quantities needed to cover the clinical demand”.
Far from harmonious
This particular allocation model has been successful in Europe’s Schengen zone and the US. But it has not yet been implemented in many of the regions where there are political uncertainties, making material flow management across borders more difficult.
The fact that supply chain regulations across countries are still very far from achieving harmonisation is particularly challenging – differing regulatory environments can be a major hurdle to moving clinical supplies successfully between countries.
Nevertheless, the changes that are occurring in emerging markets such as China are sending a strong signal to the rest of the world.
“China is aligning their clinical regulations with other health bodies worldwide, offering Chinese patients the opportunity to receive the most cutting-edge drugs without delay,” explains Basseras.
Nonetheless, achieving consistency through all elements of a supply chain isn’t easy. While technology plays an important part in improving collaboration between partners, a shared organisational focus is crucial.
“This can be achieved through making supply chain processes more efficient and tailored to the patient’s needs, through practices like the direct-topatient (DtP) model,” says Basseras.
This model, he argues, is a good way of ensuring collaboration throughout a supply chain.
“Since its implementation several years ago, the DtP approach is contributing to better patient service, particularly in the case of patients with disabilities,” explains Basseras. “DtP cuts down on frequent visits to the pharmacy and physician’s office by having the drug delivered directly to the patient.”
Beyond DtP, he adds, there is an “opportunity to combine drug dispensing with collection of patient samples to be dropped at a central lab”.
“This integration of services creates the opportunity for a more efficient supply chain” explains Basseras.
Reverse logistics
Increasingly, pharmaceutical companies make use of outsourcing partners to manage the specialist requirements in the supply chain. Outsourced logistics partners can be a particularly good resource, says Basseras, as they can “offer their expertise for important services like using high-tech shippers for controlled temperature drug delivery, as well as offering digital solutions”.
“Because of the high cost of these temperature-controlled shippers, Sanofi is now using a reverse logistic model, which allows the extension of the use of these shippers around the world through different depots.”
Beyond the logistics role, Sanofi also uses outsourcing partners that can offer GMP services supported with qualified person for late-stage customisation of treatment kits, mainly for secondary pack labelling and relabelling.
“Their role is greatly contributing to the adaptability and flexibility of the global clinical supply chain,” says Basseras.
Like all pharma companies, Sanofi faces the difficulty of predicting demand so that patients receive drugs in a timely manner. Forecasting and managing that demand begins in the clinical trial development stage, says Basseras, “where incorporating technological solutions helps to increase efficiency, from enrolment through data collection and analytics”.
The challenge increases in large clinical trials where a single investigational programme may be taking place in hundreds of sites across more than 50 countries. The use of multiple IT systems adds to the complexity.
“The end-to-end track-and-trace challenge involves many companies, from the manufacturing up to the dispensing of the drug,” Basseras notes.
This requires major collaboration efforts from quality, procurement and supply chain for Master Service agreements (MSAs) as well as Master Quality agreements (MQAs). However, there are strategies to simplify these processes.
“Reducing the number of vendors across the world by building partnerships is helping to decrease the complexity of the chain of custody with opportunities to limit the number of IT solutions, interfaces and tools,” explains Basseras.
Even so, the difficulties of managing inventory when different partners are involved are substantial. Material master data management is a daily challenge in terms of inventory management, both at the hospital level and for all stakeholders along the care chain.
“We have the same number of codes and practices as other large pharma companies that conduct a huge number of trials in the same major hospitals around the world,” says Basseras. “This makes securing the correct operation to dispense the right drug even more critical.”
A new standard for managing clinical trials
There has been growing discussion in the industry in the past year about the possibilities of adopting the GS1 worldwide clinical trial management standard. Sanofi is one of those pioneering its use. Already, Basseras explains, GS1 is being integrated for use “by the entire chain of personnel in pharma labs” and kick-off is anticipated to occur in the first quarter of next year.
Over the last two years, Sanofi Clinical Supply Chain (CSC) has invested in different sites of its R&D business, such as those in Great Valley, Pennsylvania, US, and Montpelier, Vermont, US, to expand its chain capacity and capabilities. This has included incorporating new technologies to connect with patients to achieve better compliance, and using digital capabilities to secure inventory and cold chain, and develop elabelling.
Data analytics are currently being used to better articulate demand management and operations.
“Sanofi CSC is implementing a tool to serve as a backbone across clinical and supply chain dimensions, and to be extended to chemistry, manufacturing and controls (CMC) as an end-to-end solution, helping to achieve the best clinical execution by balancing risk and cost while optimising manufacturing quantities,” Basseras explains.
At the crossroads of clinical, preclinical and regulatory pathways, he believes, CSC is becoming a “control tower within R&D ops to help align demand and execute operations”.
So, in a fast-changing landscape, what does the future hold?
“Gene therapy will be one new challenge to overcome through CSC, alone and through partnerships, because it requires treatment delivery at -80°C,” explains Basseras. “Pharma companies will also have to continue embracing the digital patient journey to accelerate treatment development and delivery in areas of unmet patient need.”
