September 6, 2024
PPTA considers that the current mpox outbreak is not a concern for the safety margins of plasma-derived medicinal products manufactured by PPTA member companies. This assessment is also shared by other concerned parties (AABB, WHO).
On August 14, 2024, WHO has declared outbreak of mpox, a viral disease caused by monkeypox virus (MPXV), a public health emergency of international concern (PHEIC) (WHO). This is the second time mpox has been declared PHEIC, with the first PHEIC being observed between July 2022 and May 2023 following a multi-country outbreak in countries where the virus had not been seen before (WHO, CDC, ECDC). People who use plasma-derived medicinal products are understandably concerned about whether their therapies remain safe, with respect to MPXV. To address this issue, PPTA has summarized currently available facts.
MPXV does not spread easily between people. The virus is transmitted between humans (human-human transmission) through close contact with infectious material from the skin lesions of an infected person. It also spreads through large respiratory droplets during prolonged face-to-face contact and through touching lesion material or contaminated surfaces or objects that may carry infection, such as bedding, linen, and personal hygiene/eating utensils (fomites). There is evidence that transmission can also occur during sexual intercourse (CDC). The clinical presentation of disease varies from mild to more severe, depending on the clade of MPXV.
The safety margins of plasma-derived medicinal products are not affected by MPXV based on the following facts:
- There is no reported evidence for the transmission of MPXV by blood and blood components, including plasma and plasma-derived medicinal products. While MPXV DNA has been detected in blood and semen (Noe et al, 2022, WHO Q&A), infectivity was not demonstrated in blood or plasma. The risk of transfusion-transmission of MPXV at this stage therefore remains only theoretical (AABB). For plasma-derived medicinal products, any risk is mitigated due to the effectiveness of established manufacturing processes (see below).
- The MPXV belongs to the Poxviridae virus family, like smallpox, vaccinia and cowpox viruses. Due to their large size (approximately 140-260 nm in diameter, 220-450 nm in length) and their lipid envelope, this group of viruses is susceptible to virus inactivation and removal steps typically used in manufacturing processes of plasma derivatives. These include caprylate- or solvent-detergent (S/D) treatments (Kindermann et al., 2022), low pH incubation, pasteurization, dry-heat treatments and nanofiltration (AABB Bulletin, 2006). Poxviruses have even been shown to be removed by sterile filtration as used during the manufacture of plasma derivatives (Berting et al., 2005).
- Symptoms generally associated with mpox include raised temperature/fever, fatigue, headache, enlarged lymph nodes and skin lesions. Therefore, donor screening procedures make it highly unlikely that any person showing disease symptoms typical of mpox would be accepted for donation.
Given the currently available scientific evidence, PPTA considers that MPXV infectivity does not occur in plasma or is low. Due to the characteristics of the virus and multiple, complementary steps with significant and robust virus inactivation and virus removal capacity utilized during manufacturing of plasma-derived medicinal products, PPTA considers that the current mpox outbreak is not a concern for the safety margins of plasma-derived medicinal products manufactured by PPTA member companies.
References:
WHO. WHO Director-General declares mpox outbreak a public health emergency of international concern
AABB. Monkeypox Virus
WHO. Multi-country monkeypox outbreak in non-endemic countries.
https://www.who.int/emergencies/disease-outbreak-news/item/2022-DON385
CDC. Monkeypox. https://www.cdc.gov/poxvirus/monkeypox/index.html
ECDC. Risk assessment: Monkeypox multi-country outbreak.
https://www.ecdc.europa.eu/en/publications-data/monkeypox-multi-country-outbreak-first-update
CDC. Mpox. How it spreads
https://www.cdc.gov/poxvirus/mpox/if-sick/transmission.html
Noe S, Zange S, Seilmaier M, et al. Clinical and virological features of first human monkeypox cases in Germany. Infection. 2023;51(1):265-270. doi:10.1007/s15010-022-01874-z
WHO Q&A. Monkeypox.
https://www.who.int/news-room/questions-and-answers/item/mpox
Kindermann J, Karbiener M, Kreil TR. Orthopox viruses and the safety margins of solvent-detergent treated plasma-derived medicinal products. Transfusion. 2022. 62(12):2454-2457
Berting A, Goerner W, Spruth M, Kistner O, Kreil TR. Effective poxvirus removal by sterile filtration during manufacture of plasma derivatives. J. Med. Virol. 2005. 75:603-7