Concept of Quality by design (QbD) in bio manufacturing
Quality by design (QbD) is the standard approach used for demonstrating and achieving consistent, high quality product. Rather than relying on just the post production testing, QbD practice rather encourages to improve quality at every stage of the process, from project inception to commercialization of the product. QbD facilitates amplification of the quality into the product. US FDAhas acknowledged the fact that testing does not always result in higher product quality. Encouraging to have one of the main goal in manufacturing as product by quality using QbD approach, ICH has introduced it in the documentations ICH Q8 (R2), Q9, Q10 & Q11 with ICH Q8/Q9/Q10 Questions & Answers along with additional ICH Q1 WG (emphasizing on the product specifications). In order to implement the QbD proposed in the documents, initially few objective were laid which are as follows:
1) To achieve clinical performance based product quality
2) To improve process design in order to reduce product variability
3) To boost product development progress & manufacturing efficiency
4) More effective root cause analysis (RCA) & post-approval change management
For proper implementation of these objectives, it is crucial to get a grip of the elements of the QbD. In the pharmaceutical industry's QbD approach to product development, a candidate identifies patient-centered traits deemed crucial to quality, transforms them into drug product critical quality attributes (CQAs), and alongside determines an association between formulation/manufacturing variables and CQAs to safely provide a drug product with such CQAs to the patient. The elements of QbD are outlined below:
1) A quality target product profile (QTPP) that lists the pharma product's CQAs
2) Understanding and designing products, including identifying critical material attributes (CMAs)
3) Understanding and designing processes, particularly identifying critical process parameters (CPPs), fully grasping scale-up principles, and connecting critical material attributes (CMAs), CPPs,and CQAs
4) A control plan with requirements for the drug substance(s), excipient(s), and drug product as well as controls for each stage of production
5) Process capabilities and continuous improvement
QTPP is the foundation of quality by design (QbD), ensuring that drug products are consistently manufactured to the desired quality, safety, and efficacy. It defines the critical quality attributes (CQAs) of the drug product, which are the physical, chemical, biological, or microbiological properties or characteristics that should be within an appropriate limit, range, or distribution to ensure the desired product quality. The QTPP also identifies the critical process parameters (CPPs) that control these attributes. By understanding the relationship between CQAs, CPPs, container closing systems, pharmacokinetics and patients outcomes, companies can identify and mitigate potential problems early on, which can save time and money also that this can help to improve the efficiency and effectiveness of product development and manufacturing. These are therefore considered essential elements of QTPP.[1]
For example, the QTPP for a new ibuprofen tablet formulation might identify dissolution, purity, and stability as CQAs identifier. Also the manufacturing process for the ibuprofen tablet formulation might be designed to control the particle size and distribution of the ibuprofen powder, which are CPPs that affect the dissolution of the tablet and using in-process testing to ensure that the dissolution rate of the tablets meets the QTPP specification.
ICH Q8 (R2) provides us the guidance to the product design which tells us if the pr...
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