Keeping the Show on the Road

Lipid nanoparticles (LNPs) are a great way to encapsulate and protect fragile molecules, such as nucleic acids, from degradation and deliver them to specific tissues and cells (1). A large number of RNA- and DNA-based therapies have made use of LNPs – perhaps most notably, gene therapies. As a contract manufacturer, it’s incredibly rewarding to work with a number of clients to help deliver their potentially life-changing advanced medicines. But there are also challenges when working with LNPs, especially when it comes to supply chain management.

Many of the raw materials that go into these therapies and the final drug products themselves are transported via cold chain – at temperatures as low as -80 °C. Even during the manufacturing process, there are restrictions on how long a product can be outside the confines of the cold storage unit. Temperature monitors are needed in each cold storage unit and each is fitted with alarms to indicate if a unit is opened or if there is an excursion. Back-up cold storage capacity is also available in the unlikely event that something goes wrong with the main units. And, as a CDMO, we must rely on our logistics providers to use validated shipping lanes, trucks, and temperature monitors to transport the drug product to its final destination. Clearly, finding a reliable logistics provider is important.

One thing that often catches developers and sponsors off guard is underestimating the lead times associated with LNP-encapsulated products. Many of these therapies have specialized raw materials that are only manufactured by a limited number of companies, with set slots in their production schedules. When we begin working with a client, they may request a supplier we haven’t worked with before – and that means we need to dispatch our quality team to audit and approve the supplier. These factors can extend lead times considerably compared with a product that uses more commonly used or off-the-shelf components and approved suppliers. In our experience, the sooner a company starts working with us, the better we can avoid potential delays from the beginning.

Dealing with COVID-19

The COVID-19 pandemic has caused numerous issues in supply chains. Some of our clients, for example, have struggled to secure flights for their products, forcing them to validate new shipping lanes. With cold chain products, such changes are more challenging, because companies must ensure there are no temperature or safety issues. Specialized temperature-controlled containers for cold chain transport have also been in short supply. And there have been delays in customs – a problem that also applies to raw materials. For us, flexibility has been key, as well as continuous communication with clients and their shipping partners. This has enabled us to avoid delays in most cases and minimize delays where they have occurred.

However, the pandemic has certainly revealed the importance of building redundancy into the supply chain where possible, and fully understanding the supply chain of all items you require for manufacturing. And that doesn’t just apply to critical, expensive items, but also everyday consumables. For example, the industry is seeing shortages of basic items, such as face masks, beard covers, and other attire required for aseptic processing – items that companies have historically paid little attention to as they were always so easily sourced. At Exelead, we are fortunate to have set our safety stocks at a level that has enabled us to continue “business as normal” during the pandemic with no delays to our customers. We’re also looking at adding backup sources for certain items, but we are confident that we have enough of everything we need to get us through the year.

Another crucial aspect for us right now is keeping clients up to date. Communication was important before COVID-19, but now – given the high uncertainty in the world – customers need to know that they can count on their partners more than ever before. As well as general updates on a customer’s product and project, we also send updates regarding the status of where we are in the plant, what we’re working on, and the safety of employees. If anyone tests positive for the virus, we will also notify customers (though, thankfully, we have not had to do this yet). But a conversation shouldn’t be one-way, so we’ve also ensured that the communication path is open for clients to ask questions or raise concerns.

The safety of our own employees is paramount – and we’ve put a lot of thought into how we can keep as many employees away from the manufacturing site as possible through homeworking, but without disrupting the manufacture of products. Right now, only those employees essential to the manufacture and testing of the products are on site. We are careful to monitor and follow all CDC guidelines to protect employees and the manufacturing environment.

The long-term impact

Supply chain robustness has been an important topic since well before COVID-19, with some companies and contract manufacturers taking the topic more seriously than others. Broadly speaking, the industry has coped well with the epidemic; companies have moved quickly to mitigate risks and gaps in the supply chains. But some businesses will have found serious chinks in their armor after taking ease of sourcing for granted. I don’t think this will be the case going forward. The fragile nature of the supply chain has been exposed – and the industry can learn from this. Setting appropriate safety stocks for certain items – without going overboard or hoarding – will soon become the norm…

If you are a developer with needs in the LNP space, we encourage you to come to us as early as possible. LNPs are complex products with complex supply chains, so even before you have a manufacturing date it is good practice to engage with partners so that the project can run smoothly. As soon as you know the key materials you are going to need, we can give you an estimate on when we will be ready. Coming to us early also gives us the time to really look at our supply chain, contact suppliers, and qualify them, if required. An LNP product will likely require cold chain and may rely on difficult-to-source raw materials. The sooner we start the conversation, the easier it will be to meet your projected timelines and keep things on track – despite COVID-19.

It is imperative that the pharma industry keep the supply chain moving for the medicines it produces. We regularly encapsulate late-stage cancer drugs, treatments for neurological diseases, and other groundbreaking therapies. One mishap during transit could not only be extremely expensive, but also potentially devastating for a patient in a clinical trial. In short, all of our employees appreciate the importance of the products they are working with; we treat every medicine we work with as if it is extremely precious – because it is. After all, it may be a patient’s last option.