The Pall family of IV filters represents more than 50 years of commitment to the research, design and manufacture of the highest quality filtration devices for healthcare applications. Integrating filtration devices into IV sets provides additional patient safety and gives medical providers confidence in their ability to remove air from the line as well as reduce risks of particulate contamination.
In-line membrane filters are widely used in drug and fluid delivery for the removal of bacteria and large aggregates or particulate material generated during preparation, handling and infusion of drug combinations used in various patient therapies. The performance characteristics of the membrane, in combination with the filter housing design, will determine the safety and efficacy of your drug infusion and delivery system.
Pall offers access to filtration devices for infusion therapy and drug delivery that are non-shedding with low protein binding, high flow rates, absolute pore size ratings, biocompatibility and low extractables. Our membranes have been used for decades by leading medical device and pharmaceutical manufacturers to ensure the safe and effective administration of intravenous drug preparations. As the use and benefits of novel therapeutics expand further, Pall’s expertise and technological capabilities will continue to play a key role in simplifying the preparation and improving the safety of IV drug infusions.
Every time a liquid solution is intravenously supplied to a patient, the potential risk of inadvertent microbial contamination, as well as delivery of unwanted particles and air microemboli must be carefully considered. Particles, such as glass fragments and pieces of plastic, have been found in commercially prepared intravenous (IV) solutions.
When an ampoule is broken to administer medication, glass particles can be drawn into the syringe along with the drug product and administered to a patient. Lipid droplets can form micelles and aggregate in solution, creating large lipid globules that can exceed five microns in size. These aggregates can become trapped in pulmonary capillaries, increasing the risk for infection and potentially hazardous immune reactions. Additionally, drugs such as paclitaxel, ganciclovir and mannitol may precipitate out of solution under certain conditions. The precipitated drugs can lead to vein irritation and phlebitis.
The use of in-line filtration devices helps in preventing particles, aggregates and precipitated drugs from reaching the patient, thus helping reduce the risk of patient complications. Moreover, bacteria retentive membrane devices can provide an effective barrier against microorganisms that may be introduced during preparation, handling and administration of parenteral solutions.
Built on decades of experience in membrane formulation and manufacturing, Pall developed the first polyethersulfone Supor® membrane specifically designed for medical filtration and contamination protection. Our comprehensive portfolio of devices for infusion and drug/fluid delivery incorporates our medical grade Supor membrane. All components and materials of construction in Pall’s IV filtration devices meet the requirements for biosafety, compatibility, toxicity and other internationally recognized standards necessary for medical device development programs. Moreover, the hydrophilic nature of the Supor membrane allows for multiple re-primings as needed during patient treatment.
Chemotherapy has been used in the treatment of cancer since the 1940s. Unfortunately, while effective against malignant cells, chemotherapeutic agents tend to be highly toxic, creating the need for targeted delivery. The general goal of new chemotherapies is to provide more targeted drug delivery, lower the dosage, and hopefully, reduce adverse effects. Potential complications of traditional infusion chemotherapy include infection of the access site, occlusion of the route, drug toxicity, thrombosis, and emboli. Just one of the short-term common side effects associated with chemotherapy is venous fragility. Increased vascular fragility, bleeding and bruising can occur around the IV sites. In addition, there is a risk of developing irritation from anti-neoplastic agents.
The presence of particles in drug preparations is of particular concern when administering chemotherapeutic infusions. Chemotherapeutic agents can crystallize through interaction with some IV solutions or components and either occlude or affect the infusion route. To minimize the complications harmful precipitates can introduce, many drug manufacturers recommend the use of in-line filtration in their dosage and administration instructions. Pall’s portfolio of in-line filtration devices incorporates materials that offer broad drug compatibility as well as resistance to oils and lipids ensuring robust performance even in the presence of harsh substances. In addition to ensuring particulate removal, our hydrophilic membranes also provide excellent bacterial retention performance, reducing the risk of inadvertent contamination associated with the handling and administration of IV solutions.
Pharmacists have a professional and legal responsibility for all aspects of the medication compounding and dispensing process. Each country, region or institution has established pharmacy practice guidelines. In addition, there are professional standards of practice that outline a series of recommendations for practitioners in alternate care sites. The section on Sterile Drug Products for Home Use in the United States Pharmacopeia (USP) chapter <1206> outlines some of the recommendations associated with home use sterile drug preparations but was not established as a compendial requirement. USP <797>, Pharmaceutical Compounding – Sterile Preparations, was published as a revision to <1206> and establishes a series of recommendations and practices (including a chapter on general tests and assays) with regulatory responsibilities for drug compounding sites.
Sterile compounding techniques and other quality control measures are vitally important during drug product preparations. USP Chapter <797> regulates compounding practice, requiring defined and documented quality systems in place. It is primarily concerned with patient safety and was established, among other things, to protect patients from microbiologically contaminated preparations. Pall’s portfolio of devices incorporates a variety of bacterial, viral, fungal and yeast retentive membranes to meet the standards set forth by the USP <797>.
In addition to the regulations established in the USP <797>, pharmacists are also guided by standards established by the American Society of Health System Pharmacists (ASHP). These standards outline the minimum requirements for the operation and management of pharmaceutical services provided by home care pharmacies. The standards affirm the pharmacist’s responsibility for the sterile preparation, quality and integrity of their formulations, thus underscoring the importance of incorporating a bacterial retentive device into the final delivery system. The FDA Modernization Act (FDAMA) of 1997 also includes provisions affecting pharmacy compounding activities. These provisions are intended to ensure bulk pharmaceutical agents are processed through a sterilizing grade membrane to ensure patient safety.
For hospital pharmacy professionals around the world, improving patient outcomes begins with safe and effective preparation of pharmaceutical solutions. Reconstitution of cytotoxic drugs involves specific procedures to protect patients and healthcare workers during handling, dispensing and administration of drugs. Even when following standard preparation techniques, undissolved drug may be present in solutions from incomplete dissolution of lyophilized powder. Pall IV filtration products are designed for pharmaceutical drug administration and provide patient protection from potentially harmful particles.
Selecting the Appropriate In-line Filter
Particulate and Bacterial Retention
When selecting an in-line filter for infusion therapy or drug/fluid delivery, it is important to properly characterize the size and nature of particulate contaminants to be retained or removed. A common risk during long-term IV therapy is contamination of IV solutions with bacteria or fungi. Pall filtration devices with 0.2 µm Supor® membranes allow the passage of aqueous solutions while providing an effective barrier against microbial cells of similar or larger size. In parenteral nutrition applications, where the infused solution contains lipid globules that provide vital nutrients to the patient, the use of an in-line filter with a 1.2 µm Supor membrane is recommended to reduce the risk of yeast contamination while allowing unrestricted passage of suspended lipid micelles.
In applications where the main objective is the removal of such unwanted particulate matter as drug aggregates and precipitates, in-line filtration devices with pore sizes between 0.2 µm and 17 µm are commonly used.
The pore size or rating in a filtration device not only dictates its retention characteristics but also its functional attributes, including flow rate and throughput. For instance, membrane devices with larger pore sizes will exhibit faster flow rates and increased throughput. It is important to note membranes made using different polymers and casting methods, but with the same pore size, can exhibit different flow rates and throughput performance.
Similarly, the degree of porosity of the membrane also has a strong influence on the membrane flow rate and throughput capabilities. Porosity is a measure of how many open spaces or pores are present in a membrane. Flow rate and throughput are directly proportional to the porosity of the membrane. Pall Supor membrane is highly porous and provides high flow rates and excellent filtration efficiency. Combining the correct membrane pore size into a filtration device offering the maximum in patient safety and comfort, while preserving the integrity and flow characteristics of the membrane, is the intention driving Pall’s unique family of devices.
Drug Binding and Compatibility
Critical to the selection of membranes in drug delivery applications is ensuring they have low non-specific binding of the active ingredient. The use of low protein binding membranes is critical in the delivery and admin- istration of today’s biotherapeutic drugs. The low protein binding characteristics of Pall Supor membrane not only provide effective protection against particle and microbial contamination but also protect the integrity and consistency of the therapeutic dose. Supor is specially formulated for critical fluid applications where minimal protein absorption, superior bacterial retention and low pressure drop are required. Pall has undertaken extensive studies to evaluate Supor membrane adsorption characteristics with a variety of commonly infused and/or injected drugs.
Membrane wetting characteristics can be modified by impregnating a surfactant onto the membrane structure, or chemically modifying the base polymer either before manufacturing or after the membrane is produced. Although wetting agents may offer advantages in filtration performance, one must consider the possibility of extractables. Extractables are substances that may leach or otherwise come off the membrane or filtration system and be added to the fluid being infused into a patient. Pall Supor® membrane is inherently hydrophilic (uses no external surfactants) resulting in extremely low levels of extractables and significantly reduces the concern over contamination from a secondary source.
As new drugs continue to be developed, material interactions increase the opportunity for incompatibility. Many different factors can influence the compatibility and stability of drugs including preservatives, buffering systems, temperature and concentration. Chemical reactions, which may include oxidation, reduction, decomposition and complex formation, can also influence the efficacy of drug preparations. Physicochemical interactions including absorption, precipitation, and separation of emulsified systems can also result from material incompatibility. Pall has an extensive library of material compatibility data on our portfolio of hydrophilic membranes for infusion therapy.
Parenteral lipid emulsions are small droplets of oil encapsulated by a phospholipid layer suspended in the aqueous phase. Clinical concerns arise when free oil is liberated due to the emulsion “cracking” or when the droplets clump or enlarge in what is referred to as “creaming”. Lipid emulsions are thermodynamically unstable and demonstrate some degree of instability over time. It may take as long as three days for the instability of an emulsion to become visibly evident. There are two primary types of lipid-based infusion therapies where an in-line filtration device can reduce the occurrence of lipid aggregates reaching the patient.
The first is Total Nutrient Admixtures (TNA), which combines lipid emulsions with amino acids, dextrose and micronutrients in a single bag. TNA treatment has become a standard of practice in homecare, hospitals and long-term care settings. The second type is Total Parenteral Nutrition (TPN). Physical incompatibilities in TPN solutions increase risks to patients. Calcium and phosphate precipitates are possible, along with other chemical incompatibilities when delivering TPN solutions. The presence of a lipid emulsion, as part of the admixture, would visibly obscure the precipitates. In homecare set- tings, filtration provides added safety during infusion of compounded IV admixtures.
TPN and TNA solutions have been shown to promote fungal growth suggesting the use of a 1.2 µm filtration device to remove Candida species may limit the potential for TNA-related sepsis. The presence of oil and lipids in the carrying solution can degrade the filtration membrane rendering it unfit for use in infusion therapy. Supor membrane with 1.2 µm pore size has been extensively used in nutritional therapy because of its proven compatibility with lipid-based solutions.
Added Patient Protection
IV sets, incorporating filtration devices, provide extra value to patients and healthcare institutions and expand business opportunities for healthcare suppliers. The premium performance offered by a filter set can prevent many costly complications associated with healthcare procedures by preventing contamination. When examining the potential added cost and liability of not filtering, budget- conscious health systems recognize filter IV sets as a wise investment. Selection of a medical filtration device with the appropriate specifications is critical to your success.