Plasmavigilance: Source plasma joins the call to arms

The United States is the world's leading supplier of plasma for fractionation (PF), producing approximately 70% of the global plasma supply. Source plasma (SP), which is plasma collected by apheresis for the sole purpose of fractionation, comprises more than 80% of PF collected in the United States with over 53 million donations in 2019. Recovered plasma, which is collected via whole blood donation and manufactured as a component, makes up the remaining PF collected domestically. While recovered plasma production has remained stable, SP collections have increased fourto five-fold over the past 15 years.2–4 The growing global demand for plasmaderived medicinal products (PDMPs) continues to fuel the insatiable appetite for PF, which in turn has created an increasing need for SP. Collecting enough SP to meet global demand for PDMPs, especially during the COVID-19 pandemic, remains a challenge. Several factors allow the United States to dominate the global PF supply. First, the practice of donor compensation, although not unique to the United States, is effectively implemented in this country to recruit and retain SP donors. Second, US regulations permit more frequent plasma donations per year (104 times per year) than other countries. As a corollary, the maximum volume of SP a donor could potentially donate is twoto three times greater than most other countries allow. Third, the US plasma industry is composed of a few multi-national for-profit companies that are vertically integrated to efficiently collect SP according to global PDMP demand. Finally, although calls to increase SP collections in lowand middle-income countries have been voiced, a lack of infrastructure and healthcare resources in these countries continues to stymie efforts toward this end. The same factors listed above that allow the United States to dominate the global PF supply also prompt consideration of whether SP collection is safe for donors. Over the years, several efforts have been implemented to ensure donor safety. The Plasma Protein Therapeutics Association (PPTA), an international trade and voluntary standard-setting association representing the SP industry, has been instrumental in setting standards to promote donor safety. Two notable examples are the International Quality Plasma Program (IQPP) Donor Fluid Administration standard requiring plasma centers to provide intravenous fluids during the SP donation for maintenance of euvolemia and the Cross Donation Management standard to prevent donors from violating maximum allowable donation limits. Serum protein depletion has been specifically investigated in plasma donors, and current federal regulations (21CFR630.15 and 21CFR640.65) require donor serum protein monitoring to ensure levels fall within 6–9 g/dl. A recent study investigating whether SP donors were at risk of iron deficiency found no significant difference in ferritin levels between new donors and frequent donors. The IQPP Standard for Recording Donor Adverse Events (IQPP Standard) provides a common language to define and classify donor adverse events (AEs) across the plasma industry. Developing the IQPP Standard paved the way for the initial Plasmavigilance study, which was presented at the 2017 AABB Annual Meeting. This pilot study involved 7.6 million SP donations, revealed an overall AE rate of 20.93 per 10,000 donations, and identified several donor attributes associated with AE risk including gender, age, weight, and donation history. Unfortunately, the IQPP Standard at that time caused misclassification of AEs; the IQPP Standard was updated following the pilot study to address the identified deficiencies. In this issue of Transfusion, Schreiber and colleagues present the next iteration of Plasmavigilance using data collected with the current and updated IQPP Standard. This study is the largest surveillance of SP donors in the United States performed to date: 12,183,183 SP donations from 1.1 million donors at 513 plasma centers across 41 states over a 4-month period. The study provides a robust representation of SP donations in the United States and reveals a very low overall AE rate of 15.85 per 10,000 donations, indicating a safe, well-tolerated procedure. The current study reaffirms previously identified risk factors for AEs among SP donors, including female gender, no prior donation history, low weight (110–124 lb), and age ≤20 years old. Approximately 90% of reported AEs were classified as hypotensive or phlebotomy events. Most of the hypotensive events did not result in loss of consciousness or injury, and most of the phlebotomy events reflected bruising.