Biologies combination biologic/device products

Preclinical Safety Evaluation of Biopharmaceuticals Combination Products (Biologic/Device)... 

If the device component of the biologic/device combination product has already been cleared or approved as a stand-alone product, some aspects of device functionality will be known. However, the effect of the biologic will need to be investigated. In the case where the device and biologic are physically associated with each other, the process used to join the two components can affect device performance in a variety of ways. Easily determined parameters such as dimensions and clearances must be confirmed. More subtle issues arise when physical performance and durability are assessed. Additional manufacturing procedures associated with the antibody coating could, at least in theory, alter the properties of the entire device. In some cases, test methods that have been successfully employed for stand-alone devices may need to be modified to accurately assess all relevant parameters that must be considered for the combination product. 

In order to present clearly and specifically the unique preclinical testing challenges associated with the early-stage development of biologic/device combination products, an antibody-coated stent will be used as a model. For this particular case study the antibody chosen for manufacturing has either not yet been approved for use in humans or, if it has, not for the newly targeted indications. In addition, the combination product utilizes a previously approved stent and delivery system. 

Finally, a major challenge for both developers and regulators of biologic-device combination products is the potential need to reconsider the way that certain key parameters typically associated with preclinical assessment, such as dose in the case of the biologic and durability in the case of the device, are defined, measured, and analyzed. 

In terms of antibody-coated stents, the following is a list of potential antibody-containing species that could, in theory, be eluted directly from the surface of the implanted biologic/device combination product, in vivo (Figure 34.2) ... 

Based on the inherent complexity of biologic/device combination products, together with the assumption that the potential in vivo adverse effects of the... 

General Biologic/Device Considerations The following is a list of potential unique considerations for assessing the safety of biologic-device combination products ... 

Assessment of biologic/device combination product functionality needs to include all of the testing typically performed on bare metal stents (BMS). In the case of our antibody-coated stent model the BMS have been previously approved by CDRH, allowing some of the BMS data to be cross-referenced and not repeated when the effect of the antibody coating on the functionality of the device is considered negligible. These judgments must be made on a case-by-case basis and should be confirmed with the Office for Device Evaluation. 

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