When are IV filters required?

_{The information below summarizes published literature and drug labeling and is not a Pall product performance or clinical outcome claim. Filter selection and use must follow the device Instructions for Use.}

Why do parenteral formulations (IV drugs) require in-line filtration prior to administration?

Although parenteral formulations (IV drugs) are sterile preparations intended for direct administration into the systemic circulation they can be supplied as solutions, suspensions, emulsions, or powders for injection or infusion. There are many reasons why the manufacturer may include a requirement for filtration in their instructions for use. It is essential the requirements are followed to provide the necessary protection to the patient.

Worldwide regulations for parenteral products require them to be essentially free from particulates or free from readily detectable foreign matter. Parenteral drugs can be provided in many formats including concentrated and ready-to-use solutions and freeze-dried formulations, which need reconstituting and diluting prior to use. These may then be provided in various packaging types including plastic, glass with rubber stoppers, or glass ampules. All these variants give the opportunity for particles to form/be introduced. Infusion of particulates has been shown to be involved in clinical complications such as phlebitis, granuloma, arterial embolism, modulation of immune response and inflammatory reaction, microcirculation deterioration, and even death (2) because of organ failure (3).

What does the recent article published by Hospital Pharmacy indicate?

The recently updated chart of IV drugs to be used with a syringe or in-line filter published in Hospital Pharmacy (1) includes an extensive list of drug formulations of different categories including monoclonal antibody (mAb) formulations, antimicrobial drugs, cancer drugs and more. Figures 1–3 graphically summarize the distribution of number of drugs requiring filtration by pore size, requirement, and drug category as listed in the article. The detailed list of drugs is available in the paper (1).

Monoclonal antibody formulations constitute over ¼ of the list and may require filtration during preparation and/or administration with a 0.2/0.22 µm filter; the common requirements for these are low protein binding and/or polyethersulfone (PES) membrane. The list of drugs requiring filtration increases all the time; the paper by Ipema only includes drugs approved by the FDA to 2019. In addition to these, many of the recently approved mAb formulations for COVID-19 treatment for example bamlanivimab and etesevimab, casirivimab and imdevimab (administered together) and sotrovimab also recommend the use of 0.2/0.22 µm polyethersulfone (PES) membrane in-line filter during administration. (4–6)

Ultimately, the selection of an appropriate in-line IV filter for administration or syringe filter for preparation is not a trivial undertaking. Even if the drug manufacturer includes information, such as pore size, membrane type, and intended use (preparation and/or administration) of the appropriate filter there are many options.

What are the points to consider while selecting an in-line or syringe filter for IV drug administration?

When selecting an appropriate syringe filter for preparation or in-line filter for IV drug administration, there are many considerations such as:

• Performance claims of the filter – Are they indicated for this use?
• Target population (adult or pediatric) – Different size filters will have different hold up volumes and allow different flow rates if used under gravity.
• Length of use – Will the formulation be administered for 24 hours or longer, and if so, are the filters indicated for this use?
• Manufacturer’s instructions – Even the same drug type from different manufacturers may have different requirements for filtration.
• Does the filter manufacturer have any data on drug binding to the filter?

Our Scientific Lab Services (SLS) and our Clinical Specialists are here to help you and offer advice on filter selection. We have previously carried out testing on different formulation with our filters and can perform similar testing as required.

Fig 1. Distribution of number of IV drugs requiring filtration by different pore size.

Fig 2. Distribution of number of IV drugs requiring filtration for (A) preparation, (B) in-line administration.

Fig 3. Distribution of number of IV drugs requiring filtration by drug category. Category “Other” includes drugs like immunosuppressant, vasodilator, diuretic, neurology treatment, antithrombotic, etc.

Regen-Cov is a trademark of Regeneron Pharmaceuticals, Inc. Any other third-party trademarks are the property of their respective owners.

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FAQs

1. Why do IV drugs require filtration?

   Manufacturers may recommend filtration in their instructions due to the possible presence of particulates from the manufacturing process or the drug itself (1)

2. How many FDA-approved drugs require IV filtration?

   93 drugs approved between 2011 and 2019 require filtration during preparation or administration. 1

3. Which drug categories most often require filtration?

   Monoclonal antibodies, antimicrobial drugs, and cancer therapies are among the most common. 1

4. What pore size is typically recommended for monoclonal antibodies?

   Most require 0.2/0.22 µm low-protein-binding filters, often made of polyethersulfone (PES). 1,4-6

5. What factors should be considered when selecting an IV filter?

   Filter performance, patient population, infusion duration, manufacturer instructions, and drug-binding data.

References

1. Ipema JH, Zacher JM, Galka E, Nazari J, Varabyeva A, Yu M, et al. Drugs to Be Used With a Filter for Preparation and/or Administration-2019. Hosp Pharm. 2021;56(2):81-87. doi:10.1177/0018578719867660.
2. Jack T, Boehne M, Brent BE, Hoy L, Kӧditz H, Wessel A, et al. In-line filtration reduces severe complications and length of stay on pediatric intensive care unit: a prospective, randomized, controlled trial. Intensive Care Med. 2012;38(6):1008-1016. doi:10.1007/s00134-012-2539-7.
3. Schmitt E, Meybohm P, Herrmann E, Ammersbach K, Endres R, Lindau S, et al. In-line filtration of intravenous infusion may reduce organ dysfunction of adult critical patients. Crit Care. 2019;23(1):373. Published 2019 Nov 22. doi:10.1186/s13054-019-2618-z.
4. Eli Lilly and Company. Fact Sheet for Health Care Providers Emergency Use Authorization (EUA) of Bamlanivimab and Etesevimab. A2.0—ETE-NL0007-EUA HCP-20211222. https://www.fda.gov/media/145802/download. Published [2021]. Accessed [2021 Sep 16].
5. Regeneron Pharmaceuticals, Inc. Fact Sheet for Health Care Providers Emergency Use Authorization (EUA) Of Regen-Cov™ (casirivimab and imdevimab). REC.22.01.0022. https://www.regeneron.com/downloads/treatment-covid19-eua-fact-sheet-for-hcp.pdf. Published [2021]. Revised [2022 Jan]. Accessed [2021 Sep].
6. GlaxoSmithKline LLC. Fact Sheet for Healthcare Providers Emergency Use Authorization (EUA) of Sotrovimab. STR: XFS-P. https://www.fda.gov/media/149534/download. Published [2022]. Revised [2022 Mar]. Accessed [2021].

Authors bio

Dr. Smruti Ragunath, PhD - Senior Application Specialist

Dr. Ragunath is a Medical’s Senior Application Specialist at Pall Medical, part of Cytiva with knowledge in membrane application and drug formulations.

Dr. Sam Spiers, PhD - Senior Technical Specialist

Dr. Spiers is a Senior Technical Specialist at Pall Medical, part of Cytiva with knowledge in membrane application and drug formulations.