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Monoclonal Antibodies for Coronavirus Treatment

The gold standard of managing any viral disease is vaccination. However, to help patients right now, the focus is on therapies such as monoclonal antibodies.

Coronavirus: hold for vaccination, prepare for therapy

 

The gold standard of managing any viral disease is vaccination. However, the development, testing and production of vaccines takes time: In the absolute best-case scenario, a vaccine against the current Coronavirus will be available at the end of the year. To help patients right now, the spotlight is on potential therapies such as monoclonal antibodies.

 

A number of existing medicines are currently being tested for their suitability against Covid-19 the disease caused by SARS-COV-2. Apart from medication used to treat lung diseases, these are mainly:

 

  • Antiviral medicines, originally developed for the treatment of HIV, hepatitis or the two-other known coronavirus diseases, Severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). These drugs block the reproduction of the viruses or prevent them from entering lung cells. 
  • Immunomodulators which have been developed, for example, against rheumatoid arthritis or inflammatory bowel diseases. They are designed to limit an overreacting defense reaction in the body in such a way that it does not cause any more damage than the viruses themselves1. In Covid-19 patients, this overreaction of the immune system has been observed to target the lungs2, causing more damage than the virus itself.

 

   

FILL IN THE FORM AND DOWNLOAD THE TECHNICAL REPORT „Binding of Monoclonal Antibodies to Pall Supor™ AEF Intravenous Filters“

FILL IN THE FORM AND DOWNLOAD THE TECHNICAL REPORT „Binding of Monoclonal Antibodies to Pall Supor™ AEF Intravenous Filters“

When safety counts rely on proven quality

Posidyne® ELD Filter
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Posidyne® ELD Filter

Air-eliminating filter designed for 96-hour particle, bacteria, and endotoxin retention

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ELD96

Supor® AEF Intravenous Filter
Medical

Supor® AEF Intravenous Filter

The Supor AEF Intravenous Filter Set is an air-eliminating filter indicated for use with any IV administration set for the removal of inadvertent particulate debris and microbial contamination.

Part Number:

AEF1

TNA Intravenous Filters for Parenteral Nutrition
Medical

TNA Intravenous Filters for Parenteral Nutrition

Air-eliminating filter set for lipid-containing nutritional IV administration.

Part Number:

TNA1

 

Antibodies to up the ante

 

Monoclonal antibodies (names ending in ‘-mab’) belong to the group of immunomodulators. At present, more than 100 monoclonal antibody drugs are approved in the US and the EU. Many monoclonal antibodies (i.e. clones of a single parent cell) are currently under investigation for the treatment of Covid-19:

 

Lenzilumab targets a cytokine (a mediator between cells) found to be up-regulated in the serum of COVID-19 patients; clazakizumab is an anti-interleukin (IL)-6 antibody presently used in psoriasis arthritis; canakinumab is an IL-1 antibody applied in auto-immune diseases; leronlimab blocks a cellular receptor involved in HIV infection and tumor metastases; eculizumab inhibits the so-called “complement protein C5” of the immune system and is used to treat rare diseases; and tocilizumab is an antibody against the IL-6 receptor crucial in arthritis (it is being investigated together with an anti-malaria drug called hydroxychloroquine). Other antibodies studied for Covid-19 or currently included in recruitment phases are bevacizumab (slows the growth of blood vessels and used in cancer therapy), nivolumab (targets a ‘cell death’ receptor found on cancer cells), as well as sarilumab and siltuximab (two IL-6 inhibitors).

 

No results are currently available for these studies. More antibody drug studies are planned but are not yet recruiting

 

Antibodies and particles: an issue

 

Clinical studies support the hypothesis that non-proteinaceous particles from infusion solutions and infusion equipment trigger inflammatory responses, respiratory distress, potential interruption of the microcirculation, hematological, renal and systemic complications3-5.

 

In contrast to these non-proteinaceous particles, immunogenic reactions are observed for aggregates formed by proteins. In addition, proteinaceous particles possess the potential to reduce the efficacy or safety of the protein drug product, says a German review6.

 

Protein drugs have the potential for aggregation in the form of subvisible particles (<100 µm). Once resuspended, the protein drugs are diluted, which reduces protein stability and increases the likelihood of protein aggregation7. Aggregation may also occur in an IV infusion system, from exposure of the protein drug to interfaces in the infusion system for example bags, tubes and filter units. Some authors see the problem of particle contamination as mainly related to the preparing and administrating of injectable drugs, rather than through the contamination of marketed products, however particle contamination may occur throughout administration8.

 

Therapeutic protein products such as monoclonal antibody drugs are commonly administered parenterally by intravenous (IV) routes of administration.

 

A way to overcome the negative aspects associated with proteinaceous and non-proteinaceous particles is the usage of intravenous in-line filters, which are incorporated in the infusion set close to the patient.

 

Antibodies and in-line filters: no issue

 

“Unique analysis of more than 300 marketed protein drug products revealed that already around 16% of all these products are filtered during preparation or administration”7.

 

Some manufacturers have already incorporated filtration instructions for monoclonal antibodies: For instance, for siltuximab a 0.2 µm filter is recommended, for cetuximab a 0.22 µm filter and for infliximab a ≤ 1.2 µm filter is recommended. For other protein drugs, the pore size of the filter has a wide range from 0.2 µm to 5 µm or even larger6.

 

One concern is that monoclonal antibodies could potentially bind to and be eliminated by the filters. The evidence produced by Pall Medical’s years of testing protein-based antibody drugs should however help to allay those concerns. For instance, one technical report evaluated the compatibility of Pall Supor AEF Intravenous filters (AEF1E and AEF1NTE, containing a 0.2 μm low protein binding Supor membrane) with monoclonal antibody drugs hours9. The results showed that binding of antibodies to the membrane and therefore potential loss of the active substance was < 0.1% and hence “negligible”.

 

Summary

 

A number of monoclonal antibodies are currently under investigation for the treatment of Covid-19. As these are protein products, there is a risk of protein aggregation in form of particles, which have been associated with adverse outcomes for patients. In-line filters can be an effective solution for removing particles, with manufacturers recommending their use for some products and studies with Pall AEF1 filters have shown negligible binding of antibodies to the filter membrane.

 

References:

 

  1. VFA (2020) Therapeutic medicines against the coronavirus infection Covid-19 – Germany, April 7, 2020. [online] VFA. Available at: https://www.vfa.de/de/englische-inhalte/therapeutic-medicines-coronavirus-covid-19 [Accessed 05 May. 2020].
  2. Morris, A. (2020). Why does coronavirus make some sick and not others? The science behind immune reactions.  USA, April 23, 2020. [online] azcentral. Available at: https://eu.azcentral.com/story/news/local/arizona-health/2020/04/14/severe-covid-19-infections-hijack-immune-system-science-behind-reactions/2962883001/ [Accessed 05 May. 2020].
  3. Boehne, M et al. (2013). In-line filtration minimizes organ dysfunction: New aspects from a prospective, randomized, controlled trial. BMC Pediatrics, 13 (21), 1-8
  4. Jack, T et al. (2012). In-line filtration reduces severe complications and length of stay on pediatric intensive care unit: a prospective, randomized, controlled trial. Intensive Care Med, 38, 1008-1016
  5. Schmitt, E. et al. (2019). In-line filtration of intravenous infusion may reduce organ dysfunction of adult critical patients. Critical Care, 23 (373), 1-11
  6. Werner, BP. et al. (2015). Particle contamination of parenteralia and in-line filtration ofproteinaceous drugs. Intern J Pharm, 496, 250-267
  7. Pardeshi, N. et al.  (2017). Microparticles and Nanoparticles Delivered in Intravenous Saline and in an Intravenous Solution of a Therapeutic Antibody Product. J Pharm Sci, 106, 511-520
  8. Perez, M. et al. (2016). Particulate Matter in Injectable Drugs: Evaluation of Risks to Patients. Pharmaceutical Technology in Hospital Pharmacy, 1 (2), 1-13
  9. Saunders, D. (2014). Binding of Monoclonal Antibodies to Pall SuporTM AEF intravenous Filters. Technical Report, Pall Medical 09.3377