Selecting an IV-Inline Filter for the New Monoclonal Antibody Therapeutics for SARS-CoV-2 Patients

November 24, 2021

Share this page

In recent months, the U.S. Food and Drug Administration has issued emergency use authorizations (EUA) for three monoclonal antibody (mAb) therapies for the treatment of mild-to-moderate COVID-19 in non-hospitalized patients with laboratory-confirmed SARS-CoV-2 infection who are at high risk for progressing to severe disease and/or hospitalization.1 These potent mAbs are directed against the spike protein of SARS-CoV-2, blocking the virus’ attachment and entry into human cells and thereby reducing the viral load.

 

The three anti-SARS-CoV-2 mAb products are:

1.     bamlanivimab plus etesevimab

2.     casirivimab plus imdevimab

3.     sotrovimab

According to the Health Care Providers Fact Sheets2,3,4, all three mAb therapeutics must be administered via the intravenous (IV) route (except in the case of casirivimab plus imdevimab, where subcutaneous injection is an acceptable alternate route of administration when intravenous infusion is not feasible and would lead to delay in treatment).5

In addition, the use of an IV in-line filter is either required or strongly recommended for all three COVID-19 mAb therapeutics.

Unfortunately, the selection of an appropriate IV in-line filter for infusing mAb used for the treatment of COVID-19 is not a trivial undertaking and identifying a suitable product can be challenging.

 

Statements regarding the routes of administration and the use of IV in-line filters according to the Health Care Providers Fact Sheets

 

Product

Statements

regarding the routes of administration

Statements

regarding the use of IV in-line filters

 

bamlanivimab

plus etesevimab2

 

Administer bamlanivimab and etesevimab together as a single intravenous (IV) infusion via pump or gravity.

 

 

Use of an in-line or add-on 0.2/0.22 micron polyethersulfone (PES) filter is strongly recommended.

 

casirivimab

plus imdevimab3

 

REGEN-COV may be administered by intravenous infusion or subcutaneous injection.

 

Administer the entire infusion solution in the bag via pump or gravity through an intravenous line containing a sterile, in-line or add-on 0.2-micron polyethersulfone

(PES) filter.

 

 

sotrovimab4

 

Sotrovimab must be administered after dilution by intravenous (IV) infusion.

 

 

Use of a 0.2 micron polyethersulfone (PES) filter is strongly recommended.

 

To select the right IV in-line filter, six crucial questions must be asked and answered:

  • Is a specific membrane recommended by the drug manufacturer for the IV in-line filter?
  • Is a specific pore size recommended by the drug manufacturer for the IV in-line filter?
  • Is the selected IV in-line filter suitable for the recommended infusion regime?
  • Does the selected filter membrane of the IV in-line filter bind mAbs?
  • To which extent does the IV in-line filter retain particles (i.e., protect the patients from possible harmful effects of particles)?
  • Is the selected IV in-line filter intended to use for medical applications?

 

Fact-checking: Our Supor™ AEF1 IV in-line filters

 

 

Does our AEF1 Supor™ IV in-line filter meet the drug manufacturer requirements to use a polyethersulfone (PES) membrane?

 

Yes. Injectable drugs may require filtration for the purpose of preparation and/or administration.6 In the case of protein-based drugs, such as mAbs, manufacturers usually recommend a low-protein binding membrane. In the case of the mAb therapeutics for SARS-CoV-2 patients, the manufacturers gave more information regarding the selection of an appropriate IV in-line filter membrane. The Health Care Providers Fact Sheets recommend the use of a PES membrane for all three mAb therapeutics. 

 

 

 

 

 

Statements regarding the use of an appropriate filter membrane according to the Health Care Providers Fact Sheets

 

Product

Statements regarding the use of an appropriate filter membrane

 

bamlanivimab

plus etesevimab2

 

Use of an in-line or add-on 0.2/0.22 micron polyethersulfone (PES) filter is strongly recommended.

 

 

casirivimab

plus imdevimab3

 

Administer the entire infusion solution in the bag via pump or gravity through an intravenous line containing a sterile, in-line or add-on 0.2-micron polyethersulfone (PES) filter.

 

 

sotrovimab4

 

 

Use of a 0.2 micron polyethersulfone (PES) filter is strongly recommended.

 

Fact-checking: Our AEF1 Supor™ IV in-line filters contain a PES membrane and therefore meet the drug manufacturer requirements.

 

Does our AEF1 Supor™ IV in-line filter meet the drug manufacturer requirements to use a membrane with a 0.2/0.22 pore size membrane?

 

Yes. IV in-line filters are classified by their pore size, such as 0.2, 1.2, 5 microns (µm). The size designation gives the ability of the IV in-line filter to retain particles and organisms. The pore size required may be defined by the instructions for use of a drug or solution. The Health Care Providers Fact Sheets recommend the use of an IV in-line filter with a 0.2 or 0.2/0.22 micron pore size.

 

Statements regarding the use of an appropriate pore size according to the Health Care Providers Fact Sheets

 

Product

Statements regarding the use of an appropriate pore size

 

bamlanivimab

plus etesevimab2

 

 

Use of an in-line or add-on 0.2/0.22 micron polyethersulfone (PES) filter is strongly recommended.

 

casirivimab

plus imdevimab3

 

Administer the entire infusion solution in the bag via pump or gravity through an intravenous line containing a sterile, in-line or add-on 0.2-micron polyethersulfone (PES) filter.

 

 

sotrovimab4

 

 

Use of a 0.2 micron polyethersulfone (PES) filter is strongly recommended.

 

Fact-checking: Our AEF1 Supor™ IV in-line filters are 0.2 micron IV-line filters and therefore meet the drug manufacturer requirements.

 

Is our AEF1 Supor™ IV in-line filter suitable for the recommended infusion regime for SARS-CoV-2 patients?

 

Yes. One of the complications of therapy with mAb is the occurrence of infusion-related reactions and knowledge about the maximum tolerated infusion rate and the different ways of reducing infusion reactions while finding the perfect infusion rate will help to make administration of mAbs more patient-friendly.7 An IV in-line filter is an important infusion component and potential negative effects of flow rate variability must be considered.8,9 Following infusion / administration regimes are recommended for the mAb therapeutics according to the Health Care Providers Fact Sheets.

 

Statements regarding the appropriate administration and infusion rate & time according to the Health Care Providers Fact Sheets

 

Product

Statements regarding administration

Statements regarding the infusion rate & time

 

bamlanivimab plus etesevimab2

 

Administer bamlanivimab and etesevimab together as a single intravenous (IV) infusion via pump or gravity.

 

The maximum infusion rate varies from 260 mL/hr to 310 mL/hr and the minimum infusion time varies from 21 to 70 minutes depending as well on the patient weight as on the size of the prefilled 0.9% sodium chloride infusion bag used.

 

 

casirivimab

plus imdevimab3

 

Administer the entire infusion solution in the bag via pump or gravity through an intravenous line containing a sterile, in-line or add-on 0.2-micron polyethersulfone (PES) filter.

 

The maximum infusion rate varies from 165 mL/hr to 310 mL/hr and the minimum infusion time varies from 20 to 49 minutes depending as well on the dose of casirivimab and imdevimab as on the size of the prefilled 0.9% sodium chloride or 5% dextrose infusion bag used.

 

 

sotrovimab4

 

Do not administer as an IV push or bolus.

 

Administer the entire infusion solution in the bag over 30 minutes.

 

 

Fact-checking: Our AEF1 Supor™ IV in-line filters are compatible with all standard clinical infusion administration sets, including use with infusion pumps and gravity infusions and meet the requirements for the recommended infusion regime for the mAb therapeutics for SARS-CoV-2.

 

Does our AEF1 Supor™ IV in-line filter bind mAbs?

 

Binding or adsorption of mAbs to an IV in-line filter membrane may lead potentially to drug loss. To minimize this risk, we evaluated the compatibility of our AEF1 Supor™ IV in-line filters containing a 0.2 µm low protein binding Supor membrane with immunoglobulins (IgG).10 Two typical monoclonal antibody drug administration scenarios were simulated by infusion of radiolabelled IgG in saline. The results of this study demonstrated that “with a full clinical evaluation, Pall Supor™ AEF1 in-line filters can potentially be used during infusion of monoclonal antibody-based drugs.”

 

Further, B.P Werner investigated the protein recovery rate of 19 biopharmaceutical products, including mAbs with a variety of filters, including our AEF1 Supor™ IV in-line filter.11 Overall, protein recovery after filtration was very high in most of all cases and protein adsorption was also not noted for filters with a diameter of 25 mm or 28 mm. Werner concluded that protein adsorption on the filter membrane will be negligible for high dosed antibodies. Table 1 illustrates the protein adsorption effectiveness of our AEF1 Supor™ IV-inline filter with MabThera that was the first therapeutic mAb to target cells that have the CD20 marker on their surface.

 

Table 1: Protein Adsorption as Determined by high-performance size exclusion chromatography11

 

Product

Before Filtration

Pall AEF1 IV in-line filter

 

MabThera® 100 mg (1.5 mg/mL)

 

100 ± 1.25

 

98.59 ± 0.78

 

 

MabThera® 100 mg (1.5 mg/mL) – stir stress

 

 

100 ± 1.61

 

98.36 ± 1.58

 

MabThera® 100 mg (4 mg/mL)

 

100 ± 0.64

 

99.94 ± 0.56

 

 

Fact-checking: Our Supor AEF1 Supor™ IV in-line filters can potentially be used for the infusion of mAb drugs without drug loss, including mAb therapeutics for SARS-CoV-2.

 

Does our AEF1 Supor™ IV in-line filter retain particles?

 

Yes. Protein formulations, such as mAb formulations, include the risk and potential for proteinaceous particles, especially when product design such as formulation, manufacturing process unit operations or packaging/device are not fully optimized. Such proteinaceous particles have been hypothesized to provide some risk for unwanted immunogenicity, and hence industry typically aims in reducing these proteinaceous particles.11 Hence, IV in-line filters should have the capability to diminish particles effectively of all sizes, from small 1 µm particles to large 25 µm particles. In this regard B.P. Werner analyzed the filtration effectiveness of a variety of filters, including our AEF1 IV in-line filter. All filters in his study were able to diminish the number of particles.

 

Fact-checking: Our AEF1 Supor™ IV in-line filters retain particles.

 

Is our AEF1 IV in-line filter intended to use for medical applications?

 

Yes. Not all filters on the market are intended to use for medical applications, beside their potential effectiveness in retaining particles, low protein binding performance and meeting the requirements of the drug manufacturer regarding type of the membrane and pore size.  B.P. Werner also analyzed our Acrodisc® and PharmAssure® filters. Both are syringe filters, PharmAssure® is registered for medical applications but mainly for use in pharmacy to prepare drugs, whereas Acrodisc® is only for laboratory applications.11

 

Fact-checking: Our AEF1 Supor™ IV in-line filters are intended to use for medical applications.

 

Summary: An increasing number of monoclonal antibodies is already available or in the process of being approved for the treatment of COVID-19 patients. These drugs have been issued with clear recommendations regarding filtration. Treating clinicians and pharmacists should be aware of the differences with filtration devices and check with our Scientific and Laboratory Services (SLS) and/or our Clinical Specialist team for more information.

 

Our AEF1 Supor™ IV in-line filters tick all 6 boxes and is our recommendation for filtering the new monoclonal antibody treatments for SARS-CoV-2 patients.

 

 

The products advertised within this blog are CE marked under the Medical Devices Directive (93/42/EEC) and FDA 510k registered. Please check with the local Pall office for availability.

 

References

Share this page

Dr. Volker Luibl, MBA

Dr. Luibl is Pall Medical’s accomplished Demand Generation Marketing Manager with extensive expertise in medical device and clinical science.
Dr. Luibl is Pall Medical’s accomplished Demand Generation Marketing Manager with extensive expertise in medical device and clinical science.
Read more
  • Medical Industries
  • Author
  • Sort By
Results