Recommendation for Clarifying FDA Policy in Evaluating "Sameness" of Higher Order Structure for Generic Peptide Therapeutics.

Recognizing the approach of a dramatic expansion of peptide therapeutics reaching the marketplace in recent years, led by GLP-1 receptor agonists such as semaglutide and liraglutide, the Center for Drug Evaluation and Research (CDER) branch of the US Food and Drug Administration (FDA) issued a final guidance in 2021 that was intended to assist generic drug producers in meeting Abbreviated New Drug Application (ANDA) obligations to establish "sameness" of their active peptide drug relative to that produced by innovator companies. Research and a published report by FDA scientists on best practices followed, which promulgated the use of nuclear magnetic resonance (NMR) and principal component analysis (PCA) and established a quantitative standard by which "sameness" of higher order structure for the applicant's peptide drug could be judged. A key requirement is that drug product samples be analyzed directly and non-invasively, a condition which in practice restricts sample modification to the addition of a small amount of deuterium oxide to allow signal lock and spectral data alignment (as required for NMR analysis).

Analysis of capacitive coupling within microelectrode array.

Capacitive coupling within high-density microelectrode arrays can degrade neural recording signal or disperse neural stimulation current. Material deterioration in a chronically implanted neural stimulation/recording system can cause such an undesired effect. We present a simple method with an iterative algorithm to quantify the cross-coupling capacitance, in-situ.

A LabVIEW based experiment system for the efficient collection and analysis of cyclic voltametry and electrode charge capacity measurements.

Cyclic voltametry and recording of stimulation electrode voltage excursions are two critical methods of measurement for understanding the performance of implantable electrodes. Because implanted electrodes cannot easily be replaced, it is necessary to have an a-priori understanding of an electrode's implanted performance and capabilities. In-vitro exhaustive tests are often needed to quantify an electrodes performance.

A multifunctional neural electrode stimulation ASIC using NeuroTalk interface.

The NeuroTalk interface, described in a companion paper allows for a standardized method of communication with implanted modules that contain custom application specific integrated circuits (ASIC). Here, we describe an example of one such ASIC that has been designed for use in a visual prosthesis. The ASIC is small enough to be incorporated within a 16-channel multielectrode stimulation array implanted in the cortex.

Neuro Talk. An interface for multifunctional neural engineering ASICs.

With the availability of modern application specific integrated circuit (ASIC) design tools, simulation packages, and low-cost commercial silicon foundry processes, it is becoming increasingly easy for any laboratory, or small company, to develop a custom ASIC. For stimulation, as well as recording, chips that perform specialized functions can be designed, fabricated, and tested within a time period of 2-3 months. In many cases, the desired functionality can only be obtained by using VLSI design methods.