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
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
- CPP: Inlet air flow, Time, Temperature, Spray pattern & rate
- CQA: Thickness, Hardness, % of weight gain, Appearance