Enhancing Regulatory Science for Advancing Pharmaceutical Quality and Manufacturing (U01) Clinical Trials Optional

Background

FDA regulates pharmaceutical drug products to ensure a continuous supply of high quality drugs in the United States. In regulating the pharmaceutical manufacturing sector, new technologies can improve drug quality, address shortages of medicines, and lower drug costs. To help achieve this, FDA encourages development and adoption of emerging manufacturing technology to modernize pharmaceutical manufacturing. Advanced manufacturing holds great promise for improving the American market for drugs and biologicals and, results in a more robust manufacturing process with fewer interruptions in production, fewer product failures (before or after distribution), and greater assurance that the drug products manufactured in any given period of time will provide the expected clinical performance. In other words, encouraging the development and adoption of emerging manufacturing technologies may lead to improved manufacturing, and therefore improved product quality and availability throughout a product's lifecycle.

The complexity of drug products has been increasing over the years, in part due to, the increasing number of poorly soluble drugs, targeted drug delivery to traditionally un-druggable sites, and increasing focus on personalized and precision medicine. In the realm of drug products, complexity may arise from the active ingredient, the formulation, the dosage form, etc. In order to prepare for the increase in complex products, the Office of Pharmaceutical Quality is considering best practices and paths forward in the risk-based quality assessment of complex drug products.

While the development of emerging technology is critical to modernizing pharmaceutical manufacturing and improving quality, FDA also recognizes that the implementation of emerging technology could present challenges to both industry and FDA. By the very nature of an approach being new or innovative in pharmaceutical industry, a limited knowledge and experiential base about the technology may exist. This program aims to address knowledge and experience gaps identified for emerging manufacturing technology and support the development and adoption of such technology in the pharmaceutical sector.

Project Objectives

The goal of this program is to support the advancement of regulatory science that can (1) facilitate the implementation and the assessment of emerging manufacturing technology in the pharmaceutical sector; (2) expand the knowledge base related to complex products and formulation development, analysis, and manufacturing control to advance risk-based quality assessment of new and generic drug products

Identified emerging technologies should be sufficiently developed and likely ready for industrial implementation for the purpose of product quality enhancement. The results and knowledge developed in this program can be utilized by industry, academia, and industry to support the implementation of the identified emerging technologies and to ensure that FDA regulatory policies reflect state-of-the-art manufacturing science. Specifically, the expected project outcomes should enable (1) developing tools and approaches for risk-based quality assessment, (2) establishing science-based quality standards and policies, and/or (3) providing training tools for both the industry and/or the regulatory bodies for the identified emerging technology.

Potential research projects could include those that focus on characterizing complex drug substances (including botanical drug substances) and complex drug product dosage forms. Projects could include related control strategies to ensure the product quality, especially those which can help solve potential regulatory questions related to drug quality. Specific topics could relate to the following:

1. Appropriate analytical methods for complex drug substances or products

2. In-process controls during manufacturing processes to ensure product quality

3. Raw material quality control

NOTE: Proposals should clearly describe the potential impacts of the proposed technology on readiness for broad implementation in pharmaceutical industry, control strategy, and/or regulatory evaluation for complex drug substances and complex drug product dosage forms.