Pharmacy and Clinical Supplies

Designing, implementing and monitoring pharmacy operations and clinical supplies for the STREAM clinical trial was essential but complex. At its core, a well-functioning supply chain for clinical supplies was key for maintaining their quality, preventing stock outs and subsequently avoiding treatment interruptions. When planning for a trial, the elements that need to be in place to achieve this should not be underestimated. An overarching consideration is the need for sufficient numbers of staff with appropriate qualifications and experience and ensuring detailed monitoring and standardization procedures are in place to meet the needs of a clinical trial.

Learn more about pharmacy and clinical supply chains

Successful implementation of the STREAM clinical trial required sufficient quantities of clinical supplies to be available at the trial sites for participants recruited into the trial. Treatment interruptions due to medicine shortages or stock outs would be detrimental for participants and for trial outcomes. A team of pharmacists made sure all investigational medicinal products (IMPs) (i.e., medicines administered to participants in the trial) were available for timely dispensing to participants. IMP flow from manufacturers to participants had to be carefully planned and executed throughout the trial. Despite many challenges in managing IMPs, none of the recruited participants had to interrupt their treatment due to IMP shortages or stock outs.

In addition to supply of IMPs, other supplies including laboratory supplies, medical consumables and test kits were made available to trial sites under the supervision of the Sponsor pharmacists. For Stage 2, clinical supplies were secured via multiple providers, including Vital Strategies (the trial Sponsor), the trial sites, and IQVIA, the trial’s contract research organization (CRO). Sponsor pharmacists ensured all clinical supplies met minimum quality requirements to ensure consistency across all trial sites.

Vital Strategies was specifically responsible for the supply of: IMPs for three of the four regimens evaluated in Stage 2, medical consumables, pharmacy auxiliaries (e.g., counting trays, pill cutters, label printers, labels, and plastic bags), laboratory reagents and consumables that could not be sourced locally, small laboratory equipment (e.g., centrifuges and microscopes), tests (e.g., visual acuity tests, microbiology test kits), export packaging for samples, and any other supplies that could not be sourced locally. Portable hearing tests were also procured which provided sites tablet based audiometry for the detection of hearing loss among participants. These supplies were managed through a complex supply chain which consisted of: 

  • Sourcing

  • Procurement

  • Shipping from suppliers to an intermediary warehouse

  • Receipt in the intermediary warehouse

  • Relabeling (one IMP needed an additional label)

  • Inventory management at the intermediary warehouse

  • Consolidation and preparation for onward shipping to the trial sites

  • Shipping to the trial sites

Learn more about the role of pharmacists

Pharmacists played a key role in the STREAM clinical trial. Vital Strategies pharmacists ensured:

  • A functioning clinical supply chain was in place;

  • Only IMPs manufactured per Good Manufacturing Practices (GMP) and Good Clinical Practice (GCP) were used in the trial;

  • All IMPs were purchased, transported, and stored according to regulations and guidelines and in compliance with standard operating procedures (SOPs);

  • IMP storage conditions set by the manufacturers were respected and documented throughout the supply chain;

  • All quantities of purchased IMPs were accounted for and any unused IMPs were properly disposed;

  • All site pharmacies were regularly monitored and their compliance with GCP guidelines, the trial protocol, and the trial’s Pharmacy Plan was evaluated;

  • All records related to IMPs were maintained.

Vital Strategies pharmacists worked closely with site pharmacists who were responsible for ensuring:

  • All IMPs received at the sites were securely stored in accordance with manufacturers’ storage conditions;

  • IMPs were only used as indicated in the protocol and any deviations were documented;

  • Only eligible participants received prescribed IMPs;

  • Prescribed IMPs were repacked and labeled as per the trial’s Pharmacy Plan;

  • Participants were properly counseled about the use of prescribed IMPs and need to return any unused IMPs;

  • Proper stock keeping and reconciliation for each IMP batch received;

  • All study files and prescriptions related to STREAM were properly filed and securely stored.

The scope and scale of the STREAM trial offered an excellent opportunity to identify successes and areas for improvement for future trials. Read a case study here. And to learn about those lessons learned, click on the boxes below.

Illustration of a female professional talking to a male clinician.

Pharmacy operations and clinical supply chain management in Kampala, Uganda: A commitment to capacity building

In 2017, the Makerere University Lung Institute (MLI) situated in the Mulago National Referral Hospital became a STREAM trial site for STREAM Stage 2. MLI is globally recognized as an essential TB treatment facility, but had limited experience with complex, multi-country phase III TB trials. This would bring complexities that had not been encountered at the site before and highlights the commitment from the MLI staff and the Sponsor to strengthen pharmacy operations and clinical supply chain management.

STREAM required a wide variety of supplies and Investigational Medicinal Products (IMPs) to be available at trial sites during the trial. Therefore, the first priority was to ensure that MLI had the proper pharmacy infrastructure and capacity to receive, store, dispense and maintain IMP accountability. This meant preventing stockouts or oversupply that could put a strain on IMP availability or cause IMP wastage due to expiry, or inappropriate storage respectively. With support of the STREAM Sponsor, Vital Strategies, MLI was able to modify one of its office spaces into a pharmacy and obtain necessary approvals for its function.

Temperature excursions can impact the stability, safety, and quality of IMPs, which could reduce their effectiveness; thus, IMPs must be stored in a temperature-controlled environment to preserve the pharmacological effects. When creating a sustainable pharmacy within MLI, a fully insulated and temperature-controlled storage unit was needed to achieve the required storage conditions for IMPs. Before the STREAM trial, storing IMPs for participants enrolled in clinical trials treated at the MDR-TB ward was not possible. Physicians and pharmacists had to walk from one end of the hospital to the other to drop off prescriptions and bring IMPs back for administration. Therefore, STREAM provided temperature-controlled storage units in the TB ward, to make IMPs available closer to the participants and the time between participant prescription and the administration of their IMPs was reduced, and as well as the waiting time for participants and providers.

Vital Strategies, MRC CTU at UCL, and MLI study team at the site initiation visit in Kampala, Uganda.
Vital Strategies, MRC CTU at UCL, and MLI study team at the site initiation visit in Kampala, Uganda.

Another area of capacity building was establishing a pharmacy team able to manage the complexity of the trial. STREAM trial participants received different combinations of up to 13 medicines during the 9-month minimum treatment period and MLI received 36 different batches of IMPs throughout the trial. The site hired a dedicated pharmacist to manage IMPs for STREAM which helped ensure adequate supplies and medications were available for trial participants.

To implement STREAM, the MLI pharmacy team had to address levels of complexity they had not experienced before and take on responsibilities specific to the trial which were new to them. The pharmacists’ activities involved managing import permits for incoming IMP shipments, stock management, repacking and dispensing prescribed IMPs for participants during their hospital stay and home treatment. The Sponsor pharmacists and the MLI team worked together to build systems that did not exist before as required. For example, to prevent any stockouts of IMPs which could interrupt treatment for participants, pharmacists at MLI created a robust database for trial drug management. Unfortunately, due to challenges with stable internet availability this system could not be used and a paper-based system had to be followed. The STREAM Sponsor pharmacists and MLI team also worked together to create a well-designed strategy to continuously monitor for risks that could cause such disruptions.

STREAM was the first trial I’ve ever participated in as a pharmacist. My standards and practice have enormously improved with the help of the STREAM trial management team. I really appreciate their efforts in lifting the standards for clinical trial pharmacists at all STREAM sites.

Ivan Segawa, STREAM Pharmacist in Kampala, Uganda

At the heart of the team’s success when faced with significant challenges was their resilience and agility. This was seen when building relationships with the National Drug Authority (NDA), which oversees the import of medicines, including IMPs, for clinical trials, to ensure succinct supply chains. The country of Uganda prides itself on its well established drug regulatory system overseen by the NDA and the pharmacy team quickly discovered that the importation of clinical supplies was lengthy and challenging resulting in long lead times for import permits and initial shipment licenses taking an average 69 days and 227 days, respectively. STREAM pharmacists fostered strong relationships with NDA representatives subsequently to better understand the process and regulatory agency requirements to mitigate potential bottlenecks and to ensure the site had the most up-to-date information regarding changes to the regulatory process. In doing so, turnaround times for permits and shipments decreased to 53 days in 2018 and further down to 36 in 2019.

The pharmacy team at MLI took on the STREAM clinical trial with expertise in pharmacy operations, but not necessarily experience with pharmacy needs for phase III TB trials. Through collaboration and an open commitment to strengthening capacity, the team built excellent and sustainable pharmacy operations and supply chain management systems. It is testament to this commitment that meant MLI avoided major stockouts and ensured all trial participants could continue their treatment without any interruptions.