Plasma-derived therapeutics are part of a complex dynamic of global supply chain economics and clinical contributing factors, all of which can affect the ability to obtain the product needed for patient care. Immunoglobulin (Ig), the main driver in current plasma manufacturing, has experienced double digit growth within North American markets, leading to an increased demand the manufacturing community has been challenged to meet.
This challenge of supplying the U.S. market means every gram of plasma a supplier can produce is needed and every change in the industry has market-wide repercussions. So what are the factors contributing to this demand?
A lengthy production cycle
The plasma-derived market is unique in that the therapy used to treat a patient comes from human donors and the plasma used to manufacture products in the U.S. comes only from U.S. donors. This reliance on human plasma donations limits the ability for manufacturers to increase product supply when needed. The testing and handling of human plasma is an important consideration and understandably highly regulated, governing the safe, effective and appropriate use of blood products. This contributes to the time required for production, which can last up to 12 months from the time plasma is donated to the time the product is released to the market. This lengthy production cycle makes forecasting a challenge, particularly if there are changes in the market causing shifts in demand, for example, if a product is removed from the U.S. market by the supplier due to FDA regulations or manufacturing concerns.
Such unanticipated scenarios within the plasma manufacturing space creates supply chain difficulties and increased pressure on existing manufacturers to fill an immediate need for product. A supplier’s manufacturing forecast affects the following year’s supply, and if unforeseen demands occur, adjustments made from collection of plasma to final production may not be seen quickly in the market. As a provider, review your utilization of Ig regularly and communicate with your Ig suppliers and specialty distributor of changes in utilization, particularly if an increase is anticipated. Providers may also consider alternative Ig brands to obtain the total grams when needed.
Greater clinical utilization
The effective use of intravenous immunoglobulin (IVIG) in the treatment of primary immunodeficiency disease (PID) has seen a great effort among the patient and clinical community to increase awareness of the disease. More efficient and better technologies to enhance detection and diagnosis of PID, coupled with improved access to Ig products over time has subsequently increased the number of new patients who may begin treatment in their lifetime.
Additionally, the increased utilization of IVIG for off-label indications has been growing over the past two decades, with some indications eventually being adopted from their off-labeled uses for such conditions as chronic inflammatory demyelinating polyneuropathy (CIDP). However, the expanded utilization of Ig therapies continues to put additional demands on the market from clinicians on behalf of their patients. Clinical considerations a provider may review for the effective use of Ig products include indication for use such as chronic vs acute, and if Ig is considered first line therapy in such indications or if it is used as an adjunctive therapy.
Where are the suppliers?
Costs related to investment in the appropriate infrastructure, the collection of plasma, the necessary FDA regulations and other typical business-related logistics all contribute to creating a high barrier to entry into the plasma-derived business, resulting in relatively few suppliers in the market. The big three suppliers in the market today account for 85% of all North America sales of IVIG, with the remaining five suppliers accounting for the combined 15% remainder. Even as new suppliers begin to enter the Ig space, the aforementioned high barrier to entry into the market means their capabilities are limited to have a large presence in the U.S. market. However, each supplier remains important in the overall balance of supply.
Because each gram of Ig is important in the market, any disruptions in an already small pool of players puts additional pressure on available supply in the pipeline. As production limits the rate of supply, disruptions by any one supplier can cause a ripple effect felt almost immediately in the market. Best practices for procurement during supply interruptions include providers working closely with their Ig supplier and/or specialty distributor to communicate needs on a routine basis and shifting ordering practices to a more frequent basis; e.g. from weekly to daily.
As we are currently experiencing this tight market of Ig products, we have to consider all the dynamics in place that have led to such a high demand in supply. While our patients have benefited from early interventions and clinical diagnosis and treatments, our supply community has been challenged to meet the market with adequate supply. Technological advances in plasma manufacturing are developed over time to help increase efficiency, however, the production cycle continues to be a long and highly regulated process given the precious commodity of human donated plasma to ensure the safe production of this life-saving treatment option.
As an industry, we can strive to understand this dynamic and be better prepared and informed when looking at how we can address the needs of our patients.
