DRUG MANUFACTURING & QUALITY CONTROL

Manufacturing is an industrial scale process designed to give safe and consistent drug products to patients worldwide. To ensure safety and efficacy, the entire manufacturing process is strictly regulated and must follow current Good Manufacturing Practices (cGMP).

A crucial first step in the manufacturing process design is to scale up from the smaller scale formulation processes. The increase in scale with increased thermal transient timescales can make scale up a non-trivial operation. To reduce the uncertainties within scale-up, established and proven formulation approaches are typically used where possible.

Each manufacturing process will incorporate individual unit operations which will be different depending on the final dosage form. Commonly employed processing steps may include, spray drying, lyophilization, melt extrusion, milling, granulation, compaction, tableting, coating, and many others. For example, powder blending of the active with excipients is a common operation for solid dosage forms. To ensure uniform mixing and good flow properties, the particle sizes of each component should ideally be equivalent with close to spherical habit or shape. To help achieve these characteristics, milling is common unit operation prior to blending. Post blending, granulation could be used to maintain the uniform blend and stop later segregation. Milling, granulation, and indeed each unit operation are energetic in nature and may induce solid form changes during the manufacturing process or lead to an increased propensity for form changes on storage.

Although drug product equivalence, as currently defined, only requires that the same active molecule be present in equivalent amounts along with the same excipient functionality (lubricant, binder, etc..), individual drug products are complex multicomponent systems. To comprehend the relationship between drug products and therapeutic performance and potential failure modes will often require a more detailed investigation of local chemistry and physical microstructure which are the fingerprints of the individual manufacturing process.

Continuous quality control (QC) is required throughout manufacturing to ensure, at a minimum, blend and content uniformity as well as solid form consistency. To catch induced changes occurring over time and different storage conditions, solid form monitoring is usually required within long-term and accelerated stability studies. Quality control continues to be important after the drug product has been manufactured to investigate failures, patient complaints, and potential contaminants. For drug products that are widely available, counterfeiting is a growing concern that can have a major impact on patient health. Both QC and counterfeit efforts heavily rely on analytical methods, with instrumentation and software is specifically designed to support these activities.