Quality by Design is not about documentation. It is about understanding how materials and processes influence product quality and patient safety.
The pharmaceutical control strategy develops step by step, as outlined below:
I. Identification of Critical Material Attributes (CMAs)
CMAs are physical or functional properties of raw materials that can impact product quality, such as particle size, polymorphic form, moisture, viscosity, density, and excipient variability. These are identified using prior knowledge, literature, and early development studies.
II. Risk Assessment of Material Attributes
Structured tools such as Ishikawa diagrams and FMEA are used to assess the impact of material variability on dissolution, content uniformity, stability, and bioavailability. High-impact attributes are classified as critical.
III. Translation into Process Understanding
CMAs are evaluated during manufacturing steps such as blending, granulation, compression, and coating to understand how variability influences process performance and links to Critical Process Parameters.
IV. Establishment of In-Process Controls
In-process controls such as granule moisture, blend uniformity, tablet weight, hardness, and coating weight gain are implemented to detect process drift early and prevent batch failure.
V. Setting of Scientifically Justified Specifications
Specifications are based on clinical relevance and demonstrated process capability. They should define true quality limits and not compensate for weak process control.
VI. Application of PAT Tools
PAT tools such as NIR, Raman spectroscopy, moisture sensors, and torque monitoring provide real-time insight into process behavior and shift quality assurance from end testing to process understanding.
VII. Enabling Real-Time Release Testing
When validated PAT models and strong process capability are established, product release can be based on real-time process data rather than extensive end-product testing.
VIII. Integrated Control Strategy
A robust control strategy integrates CMAs, CPPs, IPCs, specifications, PAT tools, and risk management into a single scientifically justified system.
IX. Regulatory Perspective
Regulators expect clear linkage between materials, processes, and controls to ensure consistent product quality throughout the lifecycle.
Read also: Difference Between QbD and DoE
Resource Person: Moinuddin Syed. Ph.D, PMP®