Overview

G&L Healthcare Advisors was engaged by a biotechnology company developing a 505(b)(2) product designed for enhanced bioavailability.

The formulation included several non-compendial ingredients, raising concerns about the regulatory path for its approval in the US.

The client sought G&L’s expertise to conduct clinical, non-clinical, and Chemistry, Manufacturing, and Controls (CMC) gap analyses to ensure a smooth submission of their US Investigational New Drug (IND) application.

Challenges

G&L identified several regulatory challenges in preparing the product for approval:
Non-compendial ingredients: The formulation contained non-compendial excipients, which required extensive regulatory scrutiny and raised concerns about the need for a non-clinical safety program.
Supplier GMP issues: Potential Good Manufacturing Practice (GMP) compliance issues were identified with the suppliers of these non-compendial ingredients, complicating the regulatory pathway.
Data utilization: The client needed a strategy to maximize the use of ex-US study data to support their US IND submission while ensuring the data met the U.S. Food and Drugs Administration (FDA) standards.

G&L’s Approach and Solution

G&L provided a comprehensive regulatory strategy to address the challenges posed by the non-compendial ingredients and to streamline the IND submission process. Key activities included:
Non-clinical program development: G&L’s gap analysis revealed that a large non-clinical program would be necessary to support the safety of the non-compendial excipients. This helped the client understand the scope of work required and allowed them to explore alternatives.
GMP supplier issues: G&L identified potential GMP issues with the suppliers of non-compendial ingredients and provided guidance on how to address these issues, ensuring compliance with US regulatory expectations.
Maximizing ex-US data: G&L helped the client identify strategies to maximize the use of ex-US study data in their US IND submission. This involved ensuring the quality and relevance of the data for the FDA’s requirements, helping to reduce duplicative efforts and streamline the approval process.
Alternative formulation development: Based on the analysis, the client began investigating alternative formulations using compendial excipients with similar functionalities to the non-compendial ones, which would reduce the scope of the required non-clinical program.
Phased IND protocol: G&L worked with the client to develop a phased IND-opening protocol, incorporating enhanced safety monitoring to support a shorter 6-week IND-opening window.

Impact and Outcomes

The collaborative work between G&L and the client delivered several important outcomes:
Reduced non-clinical workload: By shifting to formulations with compendial excipients, the client was able to reduce the scope of the required non-clinical work, saving time and resources.
Enhanced regulatory strategy: The client implemented a phased IND-opening protocol with increased safety monitoring, which allowed for a more efficient IND-opening process.
Regulatory compliance: G&L’s guidance ensured that the client addressed GMP supplier issues, reducing potential regulatory risks and ensuring compliance with FDA expectations.