Final answer:
The correct option is D.
For long-term safety demonstration of a permanent implant in a PMA submission, Carcinogenicity testing is essential. Toxicokinetics helps to assess systemic exposure and its relationship to toxicity, and is crucial for determining safe human dosing levels.
Step-by-step explanation:
When a company is submitting a Premarket Approval (PMA) for a permanent implant, it is critical to ensure long-term safety of the device. Among the tests listed, D. Carcinogenicity is absolutely necessary to demonstrate long-term safety. This is because while other tests, such as intracutaneous irritation, genotoxicity, and acute toxicity may contribute to understanding the short-term safety profile, carcinogenicity studies assess the potential for the implant to cause cancer over a longer period, which is crucial for permanent implants.
These evaluations are a part of comprehensive non-clinical testing programs required by regulatory agencies like the FDA. They incorporate toxicokinetic data to describe systemic exposure in animals, assess the relevance of toxicity findings for human safety, and help predict risk and safety in human clinical use.
Additionally, toxicokinetics is an integral part of non-clinical toxicity studies to understand the systemic exposure achieved in animals and its relationship to dose and toxicity. It involves measuring concentrations of the compound and/or metabolites over time to determine plasma AUC and Cmax values. This information is essential for selecting the no observed adverse effect level (NOAEL) to define the human equivalent dose and the maximum recommended starting dose in first-in-human clinical trials.
Other biosafety considerations also come into play, including in vitro and in vivo pharmacokinetic studies to optimize absorption and ensure metabolic stability, and to assess potential drug interactions, which contribute to the overall safety and efficacy profile of the implantable device.
The complete question is given below:
A company is submitting a PMA for a permanent implant. The company has performed biocompatibility testing based on ISO requirements and believes the package is complete. Which of the following testing does the company absolutely need to demonstrate long-term safety of its device: A. Intracutaneous irritation B. Genotoxicity C. Acute toxicity D. Carcinogenicity