Quality by Design (QbD) is a systemic approach to develop a pharmaceutical product with ensure that the intended performance of a final drug product is as expected. Where the quality of a product ensure by design not only the final product testing.

As per ICH Q8, pharmaceutical development depends onvarious elements of quality by design. Which are the fundamental basis for the QbD approach to development. Where include –

  • Define the Quality Target Product Profile
  • Identify the Quality Attributes
  • Perform a Risk (Assessment) Analysis
  • Determine the Critical Quality Attributes and Critical Process Parameters
  • Determine the Design Space
  • Identify a Control Strategy


Quality Target Product Profile (QTPP)

Quality Target Product Profile (QTPP) relates to quality, safety and efficacy. Where include summary of the quality characteristics of a drug product that ideally will be achieved to ensure the desired quality, taking into account safety and efficacy of the drug product. For example: the route of administration, dosage form, bioavailability, strength, dissolution, container closure system and stability.

 

Critical Process Parameters (CPP)

Critical process parameters (CPP) in pharmaceutical manufacturing are the key variables that affecting the production process. Where the CPPs are selectedbased upon the effect on critical quality attributes. Therefore, CPPs should be monitored or controlled to ensure the drug product obtains the desired quality. For example: temperature, pH, cooling rate, rotation speed, spray rate, atomization air pressure, air flow etc.

 

Critical Quality Attributes (CQA)

Critical Quality Attributes (CQA) is a physical, chemical, biological, or microbiological property or characteristic that should be within an appropriate limit, range, or distribution to ensure the desired product quality. Where the CQAs are selected based upon the severity of harm. For example: dissolution, assay, impurity etc.

 

Critical Material Attributes (CMA)

Critical material attributes (CMA) relates to input materials and their chemical, physical, biological, or microbiological properties that should be within the limit to ensure the quality. For example: identification, particle size of distribution, related substances etc.

 

Risk (Assessment) Analysis

Risk assessment should review the materials, operations, equipment, storage, distribution and intended use of the product. Where the potential risks of process and equipment should be addressed by the QRM activities and control measures should be taken for each risk.

 

Design Space

Design space is dynamic and begins at drug development and continues to entire lifecycle of the process. The design space includes summary of scientific understanding of product and process, justification and description of multi dimensional space that assure quality.


Examples of CPP and CQA

Sieving & Premixing

  • CPP: Screen size and mixing time
  • CQA: De-agglomeration of granules

Granulation

  • CPP: Spray rate, Air flow, Atomization air pressure
  • CQA: Bulk density, Tapped density, Particle size distribution of granules

Compression

  • CPP: Main compression force (KN), Machine speed (TPH: Tablet per hour), Feeder speed
  • CQA: Dissolution, Assay, Uniformity of dosage unit by weight variation or content uniformity

Coating