Usage Examples
- We ran the tablet under QbD, so the granulation space sits in P.3.3 instead of a fixed set point.
- That is a set of proven acceptable ranges, not a design space, and the assessor will say so.
- The QbD story is only worth as much as the control strategy it produced.
What is Quality by Design (QbD)?
Quality by Design is a systematic pharmaceutical development approach that fixes quality targets before experimentation, then builds product and process understanding until quality is designed into the manufacturing process rather than tested into the finished batch.
Quality by Design exists because quality cannot be tested into a product after the fact. ICH Q8(R2) says exactly that: quality should be built in by design. Traditional development fixed set points empirically and defended them with end-product testing, which left manufacturers unable to explain why a batch failed and unable to move a parameter without a regulatory filing.
Quality by Design covers the development work that produces a control strategy: the quality target product profile, the critical quality attributes, the risk assessment linking material attributes and process parameters to those attributes, and an optional design space. Quality by Design is not the quality system that runs commercial manufacture, and it is not a regulatory status a company can hold or claim.
Quality by Design is applied through the CTD, not through a separate deliverable. The development narrative lands in 3.2.P.2, the design space is described with the manufacturing process and process controls in P.3.3, and the overall control strategy is summarised where the drug product specification is justified in P.5.6. Assessors read the linkage, not the volume of data.
Not to be confused with
- Design space
- a design space is one optional output of a Quality by Design programme, not a synonym for it. ICH Q8(R2) lists the design space as an example of what an enhanced approach can produce; a QbD submission with a fully justified control strategy and no design space is still QbD.
- Quality risk management (ICH Q9)
- QRM is the risk methodology QbD runs on, and it applies across development, manufacturing, distribution, inspection and submission review. QbD is a development approach that consumes QRM; QRM is not confined to development.
- Pharmaceutical quality system (ICH Q10)
- Q10 is the quality management model governing the commercial phase and change management. QbD generates the product and process understanding; the PQS is where changes to that process are subsequently managed.
- Process validation
- validation demonstrates that a defined process performs reproducibly. QbD decides what the process should be and which parameters are critical in the first place; continuous process verification, in which process performance is continuously monitored and evaluated, is the QbD-aligned alternative to conventional validation.
There is no QbD checklist to certify against. These are the obligations a QbD-based dossier actually has to carry.
What you must do
- 1Define the quality target product profile as the basis of design, covering route of administration, dosage form, bioavailability, strength and stabilityICH Q8(R2) Part II Section 1
- 2Identify the drug product's critical quality attributes, determine which material attributes and process parameters affect them, and define a control strategy from that understandingICH Q8(R2) Part II Section 1
- 3Scale the effort, formality and documentation of quality risk management to the level of risk, and link every risk evaluation to protection of the patientICH Q9(R1) Section 3
- 4Support any proposed design space with multivariate data; a combination of proven acceptable ranges does not constitute oneICH Q8(R2) Part II Section 2.4.5
- 5Treat movement out of the approved design space as a change that normally initiates a regulatory post approval change processICH Q8(R2) Part II Glossary
- 6Identify which elements of the dossier are Established Conditions, because any change to an EC necessitates a submission to the regulatory authorityICH Q12 Section 3.2.1
Common mistakes
Presenting a set of univariate proven acceptable ranges as a design space
ICH Q8(R2) Section 2.4.5 states outright that a combination of proven acceptable ranges does not constitute a design space. The claim gets struck in assessment, and the operational flexibility the whole programme was built to buy never materialises.
Developing a design space at pilot scale and assuming it transfers
ICH Q8(R2) requires the applicant to justify the relevance of a design space developed at small or pilot scale to the proposed production scale process and to discuss the scale-up risks. Where the space is meant to span scales it must be expressed in scale-independent parameters, such as shear rate rather than agitation rate. Skip that and the approved space becomes a deficiency.
Treating QbD as a data-volume exercise
ICH Q8(R2) is explicit that it is the knowledge gained and submitted, not the volume of data collected, that forms the basis for science-based submissions and their regulatory evaluation. Unlinked DoE appendices add review cycles and buy no regulatory flexibility.
When This Matters
- We ran the tablet under QbD, so the granulation space sits in P.3.3 instead of a fixed set point.
- That is a set of proven acceptable ranges, not a design space, and the assessor will say so.
- The QbD story is only worth as much as the control strategy it produced.
Frequently Asked Questions
No. The ICH Q8(R2) annex states it does not introduce new regulatory requirements, and an applicant may choose an empirical approach, a more systematic quality by design approach, or a combination of both. What is mandatory is the pharmaceutical development content of CTD section 3.2.P.2 itself, whichever approach produced it.
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