The annual meeting of APSARD is an opportunity to bring experts together to share knowledge and build collaborative relationships for improving research and clinical practice. In the symposium, “Are Differences in Long-Acting Stimulant Formulations Clinically Meaningful?,” Dr. Andrew Babiskin, Dr. Thomas Spencer, Dr. Roberto Gomeni, and Dr. Ann Childress will discuss the newest findings regarding the bioequivalency and clinical implications of brand and generic formulations of extended release methylphenidate drugs, and FDA product-specific guidance on bioequivalent drug development.

Clinician Takeaways:

Clinicians will gain an improved understanding of the clinical implications of differing pharmacokinetic (PK) profiles in extended release methylphenidate (MPH ER) formulations used for ADHD.

Researcher Takeaways:

Researchers will gain familiarity with FDA requirements for Bioequivalence in extended release methylphenidate (MPH ER) formulations.

The Talks:

Dr. Andrew Babiskin, will review the FDA product-specific guidances (PSGs) on how to develop generic drug products that are therapeutically equivalent to specific reference listed drugs. Although rate of absorption (Cmax) and extent of absorption (AUC) are sufficient to establish bioequivalence (BE) for many extended release drugs, MPH ER requires additional partial exposure/AUC (pAUC) measures. This presentation will 1) discuss general principle of BE assessment, 2) present the current BE recommendations in the published PSGs for MPH ER drug products, and 3) delineate the rationales for pAUC recommendations for these products.

Thomas Spencer, MD, will present results of an FDA sponsored study to address BE in pharmacodynamic (PD) effects between MPH ER formulations intended to be similar in PK (OROS MPH (Concerta), and Mallinckrodt generic) compared to a MPH ER formulation with a different PK profile (Quillivant XR). Findings showed similar PD effects for the two compounds with similar PK profiles and intended duration (Concerta and Mallinckrodt generic), but less robust PD effects for the compound with differing PK (Quillivant) and statistically different effects from Concerta in later hours.

Roberto Gomeni, PhD, will present a model based approach maximizing the clinical benefit of MPH formulations. The clinical benefit of a treatment is defined as the ratio between clinical improvement and risk of tolerability and safety. A drug-disease model is described that accounts for pharmacokinetics, the placebo response, the exposure-response relationship, and the tolerability and safety issues. The optimization of the clinical benefit was achieved based on a convolution-based model. The results of the analysis identified an optimized dose and in-vitro/in-vivo release suitable to provide a sustained clinical response and an improved control of the safety and tolerability issues with respect to conventional formulations.

Ann Childress, MD, will discuss pharmacodynamics differences of MPH ER products and impact on patients from a clinician’s perspective. MPH ER formulations contain an immediate-release (IR) MPH component. The percentage of IR to ER MPH varies from approximately 20% to 50% in marketed MPH ER products. Comparative data from MPH studies were compiled along with a list of available generics from the FDA website. Incidental reports from patients were collected. Not all MPH products behave the same, and formulation may have a significant impact on patient outcomes. It is important to know which generics the patients are receiving and to careful assess onset, duration and magnitude of drug effects to determine which generic is best for an individual.