Key Terminologies in Quality by Design (QbD) (P1)

Quality by Design (QbD) is a systematic approach to product development that begins with predefined objectives, emphasizing product and process understanding as well as process control, based on sound scientific knowledge and quality risk management. In QbD, identifying and comprehending fundamental terminologies is crucial. Below is an explanation of the four initial terms in QbD: QTPP, CQA, CMA, and CPP.

1. Quality Target Product Profile (QTPP)

• Definition: QTPP (Quality Target Product Profile) is a prospective summary of the desired quality attributes that a product must achieve to ensure its intended quality, based on its safety and efficacy.

QTPP outlines the overall quality objectives of the product, including:

• • • Dosage form (e.g., tablets, capsules, injectable solutions)
    • Route of administration (e.g., oral, intravenous)
    • Dosage strength
    • Purity
    • Stability
    • Drug release characteristics (e.g., immediate release, extended release)
    • …
• Role: QTPP serves as a guideline for product design and development, forming the foundation for research activities, formulation selection, manufacturing process establishment, and control strategy development.
• Example: The QTPP of a generic Sunitinib hard capsule may include objectives such as bioavailability and stability.

2. Critical Quality Attribute (CQA)

• Definition: CQA (Critical Quality Attribute) refers to physical, chemical, biological, or microbiological properties that must be maintained within specified limits to ensure the desired product quality. After identifying QTPP, attributes that directly impact product safety and efficacy are evaluated and designated as CQA (often determined using FMEA methodology).
• Role: Identifying CQA helps focus resources on researching and controlling the most critical factors to ensure the product meets quality expectations.
• Example: For Sunitinib hard capsules, CQA may include dissolution, uniformity of dosage units, hardness, and impurities.

3. Critical Material Attribute (CMA)

• Definition: CMA (Critical Material Attribute) refers to the physical, chemical, biological, or microbiological properties of raw materials (e.g., active pharmaceutical ingredients (APIs), excipients, packaging) and intermediate products that directly impact the CQA of the final product.
• Role: Controlling CMA ensures the consistency of raw materials at every stage, thereby minimizing risks that could affect product quality.
• Example: CMA may include API particle size, moisture content, crystalline form, or granule properties such as particle size and moisture content after wet granulation

4. Critical Process Parameter (CPP)

• Definition: CPP (Critical Process Parameter) refers to process parameters at each stage of manufacturing, where variability could impact the CQA of the product. Thus, these parameters must be identified and tightly controlled to ensure the desired quality outcome.
• Role: Identifying and controlling CPP ensures process stability, minimizing risks that could compromise product quality.
• Example: CPP in the tablet compression stage may include compression speed and pre-compression force.

Relationship Between QTPP, CQA, CMA, and CPP:

QTPP, CQA, CMA and CPP are interrelated components within the QbD framework:

1. QTPP defines all the objectives of the product.
2. CQA represents the critical quality attributes that must be met to achieve QTPP.
3. CMA consists of raw material characteristics (API and intermediates) that influence CQA.
4. CPP includes process parameters that must be controlled to ensure CQA compliance.

Understanding and managing QTPP, CQA, CMA, and CPP is essential for ensuring product quality throughout its lifecycle.

References:

1. Application of quality by design in the current drug development
2. PQLI Guide: Part 1 – Product Realization using QbD: Concepts & Principles
3. IPQLI Guide: Part 2 – Product Realization using QbD: Illustrative Example
4. Quality by Design for ANDAs: An Example for Immediate-Release Dosage Forms