SUPAC Guidance on Qualitative Changes The USFDA SUPAC (Scale-Up and Post-Approval Changes) guidance categorizes formulation changes based on their impact on product performance. A qualitative change refers to the replacement or removal of an excipient, classified as a Level 3 change, which is considered major and requires regulatory approval. Key Regulatory Requirements for Level 3…
A BE study may or may not be required, depending on several factors. Here’s a structured approach to determine whether regulatory agencies like the FDA or EMA would require a BE study for this type of qualitative formulation change: Regulatory Perspective on Excipients in Bioequivalence Regulatory agencies consider excipients when evaluating bioequivalence, especially when they…
Paragraph IV (Para IV) Filing is a certification under the Hatch-Waxman Act that allows a generic drug applicant to challenge a brand-name drug’s patent by claiming either non-infringement or patent invalidity. If successful, the first applicant receives 180 days of market exclusivity, creating a significant commercial advantage. However, the brand-name company can sue within 45…
While traditional Average Bioequivalence (ABE) works well for most drugs, some cases require advanced approaches. Certain drugs exhibit high intra-subject variability (>30% coefficient of variation, CV), making it difficult to demonstrate BE using traditional methods. SABE is a statistical approach that adjusts BE acceptance limits based on the drug’s inherent variability, preventing unnecessary study failures…
Bioequivalence (BE) studies traditionally rely on pharmacokinetic (PK) parameters, but for locally acting drugs—such as inhalation products, nasal sprays, and topical formulations—systemic drug levels may not reflect therapeutic effect. Thus, alternative BE approaches are essential. Key Methods Pharmacodynamic (PD) Studies – Instead of plasma drug concentration, PD studies measure surrogate markers or direct clinical effects,…
Bioequivalence (BE) studies are typically conducted in a single-dose design, but in some cases, steady-state BE studies are required to ensure therapeutic equivalence. When Are Steady-State BE Studies Needed? Drugs with Non-Linear Pharmacokinetics Drugs with a Long Half-Life Modified-Release (MR) Formulations Enzyme Inducers or Autoinduction Drugs Narrow Therapeutic Index (NTI) Drugs Regulatory Perspective Study Design…
