CDER and CBER Issue Guidance on ICH Q8 Manufacturing Submissions

The US Food and Drug Administration's Centers for Drug Evaluation and Research (CDER) and Biological Evaluation and Research (CBER) have released a new Guidance for Industry: Q8 Pharmaceutical Development.

The document suggests which elements drug manufacturers should include in the Pharmaceutical Development section of International Council on Harmonization (ICH) Common Technical Document (CTD) submissions.

"The Pharmaceutical Development section," says the Guidance, "provides an opportunity to present the knowledge gained through the application of scientific approaches and quality risk management," demonstrating the manufacturer's ability to "design a quality product and its manufacturing process to consistently deliver the intended performance of the product."

The twelve-page Guidance suggests elements that should be included in discussions of drug substances, excipients, formulation development, and physicochemical and biological properties.

The Guidance reflects the science- and risk-based approach of the September 2004 Critical Path initiative. While it describes minimum levels of information required in each section of a submission, the Guidance also suggests a solid return for submissions that go beyond the minimum to clearly describe the knowledge gained during development and showing how it evolved: Demonstrating "a higher degree of understanding of material attributes, manufacturing processes, and their controls" can justify "an expanded design space" and bring more regulatory flexibility via

risk-based regulation;

postapproval process improvements, within the design space, without further regulatory review;

fewer postapproval submissions;

real-time quality control, reducing end-product release testing.

The Guidance closes with a half-page glossary, which summarizes the key concepts:

Continuous Process Verification: An alternative approach to process validation in which manufacturing process performance is continuously monitored and evaluated.

Design space: The multidimensional combination and interaction of input variables (e.g., material attributes) and process parameters that have been demonstrated to provide assurance of quality. Working within the design space is not considered as a change. Movement out of the design space is considered to be a change and would normally initiate a regulatory postapproval change process. Design space is proposed by the applicant and is subject to regulatory assessment and approval.

Formal experimental design: A structured, organized method for determining the relationship between factors affecting a process and the output of that process. Also known as "design of experiments."

Lifecycle: All phases in the life of a product from the initial development through marketing until the product's discontinuation.

Process Analytical Technology (PAT): A system for designing, analyzing, and controlling manufacturing through timely measurements (i.e., during processing) of critical quality and performance attributes of raw and in-process materials and processes with the goal of ensuring final product quality.

Process Robustness: Ability of a process to tolerate variability of materials and changes of the process and equipment without a negative impact on quality.

Quality: The suitability of either a drug substance or drug product for its intended use. This term includes such attributes as the identity, strength, and purity.