Elaboration:
The development and manufacture of drug substances (Active Pharmaceutical Ingredients – API) encompass all stages from the initial synthesis or isolation of the active compound to its large-scale commercial production under Good Manufacturing Practice (GMP). This process is guided by the ICH Q11 guideline, which provides a framework for understanding and controlling the manufacturing process.

Key aspects include:

1. Development Phase:

   • Identification of the manufacturing process and its critical parameters.

   • Establishment of Critical Quality Attributes (CQAs) for the drug substance.

   • Development of a control strategy to ensure consistent quality.

   • Consideration of design space and process validation.

2. Manufacturing Process:

   • Selection and control of raw materials, intermediates, reagents, and solvents.

   • Definition of process parameters that affect product quality.

   • Implementation of Process Analytical Technology (PAT) and in-process controls.

   • Scale-up from laboratory to commercial production with risk management principles (ICH Q9).

3. Control Strategy:

   • Integration of quality risk management and scientific understanding.

   • Controls may include material specifications, process monitoring, and end-product testing.

   • Continuous process verification and ongoing lifecycle management.

4. Lifecycle Management:

   • Continuous improvement through change control and post-approval updates.

   • Ongoing assessment of process performance and product quality.

In summary:
ICH Q11 bridges the gap between development and commercial manufacturing, emphasizing a science- and risk-based approach to ensure robust and reproducible production of high-quality drug substances.