Risk-based use of immunoglobulins due to reduced blood plasma donations

The supply of immunoglobulins¹⁾ in Austria is limited due to reduced plasma donations.

Currently, there is a critical situation regarding plasma donations as a starting material for the production of these medicinal products. There is too little plasma available worldwide. Therefore, the Austrian Federal Office for Safety in Health Care (BASG), in coordination with the "Verband der pharmazeutischen Industrie Österreichs" (PHARMIG), informs about the supply situation with immunoglobulins.

• At the beginning of the COVID-19 pandemic, there was a temporary drop in plasma donations of more than 50% in the USA²⁾ in Q2/2020 (compared to the same period in 2019) and also a significant drop³⁾ in Austria.
• Through extensive measures, the negative effect of the pandemic can only be partially cushioned by the manufacturers.
• The further course of the pandemic and the effects on plasma collection cannot yet be

There is also a discrepancy between the limited supply of raw materials (plasma) and the simultaneously increasing global demand for immunoglobulins⁴⁾. The marketing authorisation holders are aware of these difficulties and are making the greatest possible efforts to ensure the supply in Austria also in the future. However, joint efforts of all parties involved are needed to ensure the supply of immunoglobulins in Austria in the long term.

Plasma, the most important raw material for the production of immunoglobulins, is obtained from plasma donations and from blood donations

• The increasing demand for plasma for the production of immunoglobulins and other medicinal products from plasma is mainly covered by direct plasma donations.
• With plasma obtained from blood donations, the demand for plasma could not be met, neither in Austria nor worldwide.

Critical situation: too little plasma available worldwide (decline in donations, exacerbated again by the COVID-19 pandemic)

• A decrease in plasma donations can be observed in the EU and the USA²⁾.

• While patients in other regions (e.g. USA) can be completely supplied with plasma-derived medicines from their own country, the supply of plasma-derived medicines to patients in Europe depends on plasma donations from the USA for about 40%⁵⁾.

• In addition, due to the COVID-19 pandemic in Austria, there was a significant decrease in donations of around 26% in 2020 compared to 2019. So far, there has not been a full recovery in donations³⁾.

• 4 EU countries (Austria, Hungary, Czech Republic and Germany) raise more than 55% of the plasma (direct plasma donation & whole blood donation) that is processed into medicines in the European Union⁵⁾⁶⁾.

• For the past 6 years, a decline in plasma donations has also been recorded in Austria³⁾.

Discrepancy between limited raw material supply and simultaneously increasing demand for immunoglobulins

• All plasma available to the industry is used for the production of immunoglobulin preparations.
• Due to the tense donation situation worldwide and the associated shortage of raw materials, the immunoglobulin products most affected by this and approved in Austria are already showing restrictions in their ability to be marketed and are consequently already listed in the shortages catalogue of the BASG.
• An increase in the global demand for immunoglobulins is expected in the coming years, which will further increase the dependence on US plasma⁵⁾.
• The increasing global demand for immunoglobulins combined with a shortage of raw materials is leading to an aggravation of the supply situation.
• The discrepancy between supply and demand is leading to increased international competition for the drug immunoglobulin.

Marketing authorisation holders make the greatest possible efforts to ensure the supply in Austria also in the future

• The marketing authorisation holders are aware of their legal responsibility to supply.
• Demand is planned with the greatest possible care.
  • However, due to the reasons mentioned above, it is currently not possible to plan supply for more than the short to medium term.
• In Austria, the supply of immunoglobulins can currently still be guaranteed.
  • However, a further increase in demand (e.g. due to new indications such as secondary immunodeficiencies) cannot be met in the short term for the reasons mentioned above.
  • Due to a lead time⁷⁾ of 6-12 months of the entire manufacturing cycle, from plasma donation to the final product, the decrease in plasma donations in Q2/2020 has already been noticeable in the supply since Q1/2021.
  • Depending on the further course of the pandemic, the supply situation is therefore not expected to return to normal until 2022.

• Joint efforts of all stakeholders are needed to ensure a sustainable supply of immunoglobulins.

Austria's situation

In Austria, the following medicinal products are affected by the restrictions in supply:

Marketing authorisation holder: Baxalta Innovations GmbH

Marketing authorisation holder: Baxter AG

Marketing authorisation holder: Biotest Pharma GmbH

Marketing authorisation holder: CSL Behring GmbH

Marketing authorisation holder: Kedrion S.p.A.

Marketing authorisation holder: Octapharma Pharmazeutika Produktionsges.m.b.H

Marketing authorisation holder: LFB - Laboratoire Francais du Fractionnement et des Biotechnologies SA

BASG recommendations

Since the needs of patients cannot be adequately met domestically, the BASG, after review and for reasons of public health protection, has issued a parallel export ban to another countries of the European Economic Area for the above-mentioned medicinal products and published them in the catalogue according to the regulation on ensuring the provision of medicinal products.

Recommendations for healthcare professionals

Due to the precarious COVID-19-related situation of reduced blood plasma donations and thus reduced production capacities of drugs with immunoglobulins, a proactive risk prioritisation in the application is requested. Physicians should therefore pay attention to a risk-based application depending on the supply of immunoglobulins, so that the treatment of patients with primary immunodeficiency or in the approved indications can be guaranteed.

_{1) Immunoglobulins (IG) are antibody concentrates from human plasma. They are the active ingredient in many medicinal products for the treatment of, for example, primary and secondary immunodeficiencies, autoimmune diseases and chronic inflammatory diseases of the nervous system.
2) Source: “Pandemic-Related IVIG Shortage Has Not Happened—Yet”, Pharmacy Practice News, 22. Jänner 2021
3) Source: IG Plasma.
4) Source: Hartmann, J., Klein, H.G. Supply and demand for plasma-derived medicinal products - A critical reassessment amid the COVID-19 pandemic. Transfusion, 2020;60:2748–2752.
5) Source: Marketing Research Bureau: Reports 2017, https://marketingresearchbureau.com.
6) Only in 4 European countries (Austria, Hungary, the Czech Republic and Germany) is direct plasma donation and monetary compensation for donors permitted.⁵⁾.
7) Lead Time: Time period from plasma donation to released medicinal product (up to 60 days quarantine storage, plasma pooling, several fractionation steps, purification, virus inactivation steps, filling, freeze-drying, testing, batch release, logistics).}

Further inquiry note

medicineshortage@basg.gv.at