Quality by Design (QbD) Requirements in the EU and UK

Quality by Design has become a central expectation in pharmaceutical development, even though it is not legally mandatory in either the EU or the UK. Both EMA and MHRA align fully with ICH Q8(R2), Q9(R1), Q10, Q11, and Q12, and expect a clear demonstration of product and process understanding for every new or complex formulation.

Below is a summary of what regulators in both regions expect during development and dossier submission.

1. QbD is Optional but Strongly Encouraged

Neither EMA nor MHRA mandates QbD. However, products developed using QbD principles consistently face fewer regulatory questions, fewer post-approval changes, and stronger lifecycle management flexibility. For complex or modified-release generics, QbD is often indispensable.

2. Core ICH Guidelines Followed in EU and UK

Both agencies rely on the same ICH framework:

• ICH Q8(R2): Pharmaceutical Development, QTPP, CQAs, CMAs, CPPs, DOE
• ICH Q9(R1): Quality Risk Management
• ICH Q10: Pharmaceutical Quality System
• ICH Q11: Drug Substance Development
• ICH Q12: Lifecycle Management, Established Conditions (ECs)

3. Key Development Elements Expected by EMA & MHRA

a. QTPP and CQA Identification

• A structured QTPP followed by a scientific mapping of CQAs is essential. Regulators expect justification for each identified attribute.

b. Risk Assessments (ICH Q9)

• Initial (QTPP → CQA) and secondary (CQA → CMA/CPP) assessments should be data-driven, not hypothetical. Tools such as FMEA, Fishbone, and HACCP are commonly evaluated.

c. Design of Experiments (DOE)

• DOE remains the most robust tool for understanding interactions and developing a design space. For modified-release, OSDs, suspensions, and complex liquids, DOE-based justification is almost always expected.

d. Design Space (Optional)

• Both EMA and MHRA accept design space proposals, and once approved, changes within the space do not require variations under ICH Q12.

e. Control Strategy

• Regulators expect a risk-based control strategy covering CMA, and CPP, in-process tests, and finished-product specifications.

f. Lifecycle Management

• ICH Q12 is fully implemented in the EU and UK. Established Conditions, PACMPs, and risk-based post-approval proposals significantly reduce regulatory burden.

4. Practical Differences Between EU and UK

While both regions align with the same ICH guidelines, the pathways differ:

• EU: Centralised and national submissions under Variation Regulation 1234/2008.
• UK: Standalone national review with MHRA-specific variation guidance post-Brexit.

Conclusion

QbD may be technically optional, but it has become a de-facto requirement for robust development, regulatory predictability, and lifecycle flexibility in the EU and UK. A structured QTPP, scientific CQA mapping, risk assessments, DOE-driven understanding, and a strong control strategy collectively form the foundation of successful submissions in these markets.

Read also: Quality by Design (QbD) and Design Space in Pharmaceutical Development

Resource Person: Moinuddin Syed. Ph.D, PMP®