Supply chain management readiness, Part 3: process
by Marc Puich | June 4, 2019
(Note: this post is the third part of a four-part series on supply chain planning for personalized therapies such as cell therapies, gene therapies, or neoantigen cancer vaccines. Here are links to Part 1 and Part 2. You can also find Vineti's Supply Chain Readiness Checklist here.)
How exactly will your personalized therapeutic product move out of the research lab and into the "real world"?
At Vineti, we support our partners in thinking through these types of questions every day. Intentionally prioritizing your supply chain strategy early will save your team significant time and cost later. In our last post, I covered the "Who," What," and "When" of setting up the ecosystem required for your cell therapy, gene therapy, or neoantigen product. Now let's dig into what steps to establish in order for the process to flow as smoothly as possible across those ecosystem participants. Success depends on defining and communicated broadly all facets of the therapy's "real world" process requirements.
1. Is your dosing fully established?
While this may seem obvious in a more traditional drug, dosing a personalized medicine is more dynamic since the products themselves are living and dynamic. Depending on the mode of action (e.g. an active antigenic response through gene editing) of the product and other sequenced investigational products (e.g. recombinant antibodies or small molecule product), there may be several small clinical trials early in development to establish an efficacious dose while attempting to tier outside effects (e.g. cytokine storm syndrome). The sequencing and dosing of other therapies, like chemotherapy, may require adjustments between trial and trial arms. And you may find that your therapy requires the same dose, but administered over sequential time periods such as monthly or bi-weekly.
2. Is your collection protocol established?
Starting patient material acquisition will be dependent on one or many different types of medical centers and healthcare staff -- surgeons and/or apheresis staff being the most common -- who must adhere to specific requirements defined with your treatment's SOP. Although the industry is working toward greater standardization to ease the workload on these Healthcare Provider teams, for the time being, each therapy requires a significant amount of (often unique) detail on how and what to collect from donors and patients -- and how to care for the collected material from the moment of collection to shipment. It is critical to work through and document each and every dependency required of these partners to ensure consistency and quality. This protocol creation often takes significantly longer than expected, so be prepared for your team to refine it multiple times over six months or more. Where possible, your suppliers may be able to provide best practices gleaned from seeing these processes implemented across a number of companies.
3. Are your products going to be frozen?
Whether to freeze a manufactured cell or gene therapy is a major strategic decision with benefits and trade-off. While the primary upside of freezing is to significantly reduce the risks associated with the short shelf-life of the bioactive products, there are still challenges related to exact temperature-controlled storage, defrosting procedures, and management of storage devices (LN2 dewars) within medical center pharmacies. Products that are never frozen are under greater time pressure, but may also forego an additional two-to-four "legs" within the supply chain process to and from a facility for freezing and defrosting. Additionally, in considering how these therapies will scale, the reliability, consistency, and risks of the cryopreservation process in collection locations need to be understood. In either case, the management team must agree upon the preferred set of upsides and plan in detail how to address the challenges associated with each choice.
4. Has everyone agreed to the specific data that must be tracked within the Chain of Identity (COI) and Chain of Custody (COC)?
The COC and COI for each product are required by the FDA and EMA in order to guarantee process compliance and ensure patient safety. In order to do this, these records must be set up to capture a multitude of different data types relating to Patient Identification, Donation Information, Product Identification, and Transport Tracking Information. At each step in the process, the data captured must be detailed and format-consistent. Here are some high-level examples of the key identifiers that need to be associated to assure a complete view of the Chain of Identity:
As the therapy moves from a research lab to a human trial, it is critical that all of this required data be identified upfront. You'll also need to define your processes for how to collect and manage the data within a single record and develop the ability for regulatory oversight to have access to this information at any point in time.
(Note: we will be publishing more blog posts related to COC and COI in the coming weeks, so check back in if this topic is of particular interest.)
5. Is your labeling plan established?
When it comes to your supply chain, the product label is of utmost importance to guarantee that the product is flowing through the process correctly. Although a seemingly routine detail, how your product will get labeled and what it will be labeled with is one of the most challenging process specifics to nail down in practice.
The first question of how your therapy will be labeled means sorting out where the label printers will reside (in your facility and shipped to the collection site in the kit, or on-premise at the collection site) and who will do the printing (your supply chain team or the HCP staff). In either case, maintaining these GMP-compliant labels requires set-up and ongoing maintenance. For the question of what goes onto the label, the goal is to include the regulatory-required information and just enough of other information without overloading the label and providing a distraction. This information must be easily read and utilized in order to prevent product mix-ups at any point in the supply chain and meet various regulatory needs (which can vary country by country). Because of this significant potential patient safety risk, existing labeling standards can provide a starting point -- including ISBT 128 and Single European Code -- although they are not explicitly designed to cover the highly dynamic, distributed personalized therapeutic process. Lastly, if your product is going to be shipped amongst regions/countries, the label will also need to address language differences amongst product process destinations.
For an overview of this Supply Chain Readiness series, you can download a copy of Vineti's Supply Chain Readiness Checklist.
Marc Puich has extensive experience in pharmaceutical manufacturing systems and cell therapy workflows and is Vice President of Business Development at Vineti. If you'd like to see how Vineti's Personalized Therapy Management (PTM) platform can help you solve your advanced therapy supply chain and workflow challenges, please contact us to schedule a demo.