Tracy Chase, Manager, Proposals & Training, Bellwyck Pharma Services
The increased globalization and complexities of clinical trials have made optimizing the supply chain absolutely critical. Clinical supply chain planning is imperative, as it allows you to develop a strategy and best practices for quickly and efficiently delivering goods to support all the needs of the trial. But, where do you begin?
Having a clinical supply chain plan in place supports systems — both on the site level and the manufacturing level — that will monitor supplies and help align manufacturing, packaging, and logistics aspects of the trial with required activities at the site level. It also allows for forecasting where supplies will be at any given moment, when they’ll arrive at the trial site, and when they will be used at the site.
The clinical supply chain can often be viewed as the last stage of the drug manufacturing process for clinical trials. Because of this, upstream delays tend to have a domino effect of causing further delays on the trial. Preventing these delays can be accomplished through constant communication — phone calls, emails, regular meetings, etc. — between sites and their manufacturing partners. This communication allows sites to be fed the materials they need in a timely manner and materials to be only a correspondence away if they’re needed. Obviously, no one wants to delay the start of the trial, but sometimes upstream delays have eaten away at the available timeline, making it inevitable. In these cases, it’s important for the supply chain to operate as efficiently as possible to not further complicate matters or create additional delays.
Small to midsize sponsor companies often don’t have a clinical supply chain team, so planning committees can vary from company to company. Sometimes, CMC teams are involved in creating clinical supply chain plans. Other times, the clinical operations team is tasked with planning for the supply chain. Regardless of who develops the clinical supply chain plan, they should be well-educated about every aspect of the trial, including its goals and international shipping needs, including importation guidelines and regulations. Additionally, the plan developers should have deep knowledge of their company’s internal capabilities — data generation, data management, how to use that data to determine quantities of materials and products needed, etc. — and keep those capabilities in mind for the context of the trial.
Identifying a few key criteria will help establish and drive the ultimate timeline of the clinical supply chain. First, it’s important to examine the first drug supply deadline – which is typically the first drug dispensing date – for the trial and the trial’s locations. When will your first patients need materials on-site, and where are those sites located? For instance, if supplies are being packaged in North America and the first trial site is in Europe, additional time needs to be built into the plan to account for shipment, importation, and QP release of the materials to ensure that they arrive and are released to the site on time.
Once the milestone dates are known, a good plan of attack is to work backward from there, establishing timelines for when materials will be needed and learning when those items will be available. For example, if translated label texts are being supplied, when will they be available? Have tablets been manufactured and bottled? If not, when will they be available to ship to your secondary packaging facility for labeling?
There is not a standard timeline for the planning and execution of shipping products across the clinical supply chain. However, planning should begin well before the trial begins. The preparation timeline should be determined by the sponsor and its partners by examining the complexity of the trial, the number and types of materials being shipped, global regions included, and many other variables. Ideally, planning will begin many months prior to the study, with extra time allowed for the creation and execution of strategies for unforeseen variables.
In order to prepare an accurate timeline, it is important to gather as much information about the trial as possible. A good first step is to start the supply chain partner relationship as early as possible by asking a few basic questions. In many cases, sponsors are heavily focused on drug development and don’t have much experience on the supply chain side; therefore, it is important that questions are answered early to get a full understanding of the scope of the trial. Some typical questions to ask include:
• What materials are needed?
• How will materials be distributed?
• Where is the study happening?
• How long will the trial last?
• Will multiple shipments be required?
• Will there be multiple incoming lots?
• How soon are materials needed after they’re manufactured?
• What is the shelf life of the materials?
• How many patients have been recruited?
The answers to these broad-stroke questions help pave a more refined path to a clinical supply chain plan.
Regular meetings between the supply chain partner and the sponsor help in the clinical supply chain planning. These meetings establish expectations from the start, ensure all parties understand their roles in the process, all required tasks, the documents that will require approval, how quickly approval must be granted, how material will flow to trial sites, and help create an accurate timeline. Ultimately, regular and scheduled communications will help all parties prepare, organize, and plan for a successful clinical supply chain.
Knowing where materials will be shipped is essential, as certain countries may require import permits. The time it takes to obtain these permits and the documentation needed to complete the application can vary from country to country, so it is important to understand the specific requirements of a given country when building your study timelines. Further to this, some countries’ importation processes can be lengthy, so it is important to understand import time frames and regulations prior to the study commencing.
It is not uncommon for new countries to be added late in the planning process, or even mid-study. Depending on the country, you may face regulatory and importation hurdles to get materials to the site. From the very beginning, it is a best practice to research all the countries your study may include and identify any country-specific requirements that will need to be considered.
Next step is establishing the packaging conditions and label proofs for drug products and materials. Who will be responsible for drug product being released, packaged, and labeled for shipping? What product-specific criteria needs to be considered, for example, cost of material, product stability, availability of supply, and how it will be dispensed? How, exactly will the finished doses be packaged? A kit? A single bottle? Learning these answers will enable you to start planning for any specialty packaging items that may be required.
Determining label requirements is an important piece of the planning process because label text requirements can vary from country to country. Multi-language booklet labels can be used for studies that will occur within multiple countries, as they will help to ensure that labeling will be compliant with all countries and allow your supply to be flexible when exact enrollment in each country is not known. You can consider including text for all potential countries, as there is nothing wrong with including countries in your booklet label that may not end up being used. While you may spend a bit more money up front for a larger booklet label, that cost may be significantly less than the cost of additional labeling campaigns and material delays later, as the lead time on multi-language booklet labels is a minimum of four to six weeks.
In addition, expiry date requirements can vary by country, and there may be times when your product will need to be shipped to a country where the label requires an expiration date. However, some products can have short shelf lives or may not have adequate data to establish shelf-life stability. For example, if a product has an estimated six-month shelf life, but the product will need to be supplied for a year, consideration needs to be given to how you will prepare your supply. Coordinating an on-site expiry extension labeling exercise can be difficult and, in some countries, cannot be permitted at all sites. A tactic commonly used to prevent this occurrence is to label part of the supply with current expiry dates and, once more stability data is available, label the balance of materials with the later date. The sites can use the initial supply of material first, and then get additional material supplied, with later expiration dating, as needed.
Often, sponsors don’t begin thinking about the clinical supply chain until after a final protocol has been released. However, this approach can be problematic as protocols are often amended, despite there being no required changes to packaging. If supply chain is brought into the planning early, the packaging and distribution strategy can be developed alongside the protocol.
Distributing materials to clinical sites across the globe on time can come with some challenges, especially if distributing directly to the trial site, but proper planning up front can help mitigate those challenges. Utilizing local depots in your clinical supply chain planning is an effective way to help ensure that materials will be available to sites in a timely manner when requested, as you remove any uncertainty associated with importation and customs clearances. In addition, depots can help control your overages, as materials can remain at the local depot until they are needed at the site, rather than seeding the site with materials up front that may ultimately never be used.
Shipping containers and methods should also be considered, analyzed, and acquired. Does the final dose need to be temperature-controlled? Is it fragile? Ensuring that your material will arrive to sites free from temperature excursions or damages will prevent time-consuming investigations and potential delays in patient dosing. Supply chain partners can offer both standard and customizable options to ensure materials and drug products reach trial sites on time and safely, while meeting stringent quality standards.
If any of these items are afterthoughts, major amounts of both time and money, or even the trial itself, could be jeopardized. Ultimately, knowing the scope of the trial and all its possible requirements, and properly planning the supply chain around these requirements, will ensure the trial runs smoothly and no one is scrambling to develop last-minute solutions to problems that could have been avoided.
Having material where and when it is needed is the defining goal of a successful clinical supply chain. When a plan runs smoothly, with materials and products properly packaged and labeled, the distribution and importation move fluidly on their own. Very few, if any, intervening steps will be necessary to keep that flow steady and assure all material will reach patients.
It is important to measure on-time delivery rates simply by counting packaged materials that reach trial sites on time versus those that don’t. IVRS systems and ERP databases can be used to actively collect this information, which can be analyzed to identify areas where additional consideration may need to be taken in the future.
Continuous improvement should always be a goal and discussing the status of shipments for a trial in regular intervals throughout the supply chain process in “lessons-learned” meetings is a good way to achieve this. These meetings allow for transparency in the process and an open dialogue about what is happening in the supply chain. Further, if something isn’t executed as was planned, corrective actions can be discussed, as well as possible preventive actions for that issue, and similar ones, in the future.
A trusted partner who understands the clinical supply chain, the intricacies of labeling, and the impacts of importation policies and regulations can put plans in place to circumvent costly trial delays. Your supply chain partner should offer many strategies so trials can be executed on time, patients receive treatment, and all parties reach their goals.
About the Author
Tracy Chase is Manager of Proposals and Training for Bellwyck Pharma Services which supports clinical and commercial packaging and distribution. She has almost 20 years of experience managing small to global size clinical trials in the pharmaceutical industry.
Tracy Chase, Manager, Proposals & Training, Bellwyck Pharma Services