EPPM 21.3

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ombination products are defined as therapeutic and diagnostic products comprising two or more regulated components – i.e. drug/device, biologic/ device, drug/biologic, or drug/device/ biologic – that are physically, chemically, or otherwise combined or mixed and produced as a single entity (21 CFR 3.2(e)). This broad definition includes products ranging from pre-filled syringes to drugcoated implants. For medical device companies, combination products provide an attractive route to improving performance or extending lifecycles. Broadly speaking, drugs and implants are used together for two reasons: the device as a drug delivery vehicle or the drug is included to enhance the performance of the device. For medical device developers, the most relevant examples involve the addition of a drug to an existing medical device (antimicrobial catheters, steroidcoated pacemaker leads, and antibiotic bone cements, for example). Polymer selection is a critical component of medical device development, and the same guidelines apply when choosing a polymer for a combination product. Combination product developers should ensure that their chosen polymer(s), as with any key component, will be available in the grade necessary for an implant and that the manufacturer can provide the needed documentation and support.

PATHWAY TPU EXCIPIENTS TPU use in combination products is increasing. Non-biodegradable TPU excipients, including Lubrizol Life Sciences’ Pathway offering, are versatile and customisable to a broad range of chemical and physical properties (Fig. 1).


The ability to modify TPU chemistry makes these excipients compatible with a wide range of APIs (hydrophobic and hydrophilic) and allows them to provide different drug-release kinetics (short and long-term) depending on the application. TPUs come in a range of durometers and are amenable to many processing methods, including hot-melt extrusion (HME), solvent casting, and injection moulding. Lubrizol’s TPUs have a long history of in vivo safety, stability, and biocompatibility. As a result, they have been used for decades in biomedical applications such as pacemakers and defibrillators. Additionally, Pathway TPUs have established Drug Master Files (DMFs) and are manufactured under IPEC-PQG GMP guidelines. PRODUCTS AND PRODUCTION PROCESSES The drugs incorporated with devices may be either impregnated or surface-coated. Many polymers – including polyolefins, polyurethanes, and ethylene-co-vinyl

Nick DiFranco

acetate polymers – have been combined with drugs through HME. Silicone rubber can also be combined with drugs through reactive injection moulding. In cases where temperature sensitivity is an issue, drug loading may be accomplished with the use of solvents. Drug-eluting devices can take several forms (Fig. 2). In the case of matrix-type products, the drug is uniformly dispersed throughout the polymer. Drug release from matrix-type products typically follows first-order kinetics, often with an initial burst of drug and a release rate that decreases over time. In cases where a device is hollow or surface protection is critical, a drug-containing coating made from biodurable or biodegradable materials can be applied. These may demonstrate a wide range of release rates depending on composition, thickness, and environment. Reservoir-type combination products are less common for modifying medical devices. The drug-filled stent, for

Fig. 1 Pathway TPU excipients: A versatile drug delivery option

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