He Annex 15 – Qualification and Validation is one of the classic pillars of European GMP and, precisely for this reason, the EMA has decided to review it in depth within the 2026–2028 plan. This is not a simple “updating”, but rather a change of focus that will have real impact on how validation activities are planned, executed and defended during an inspection.
After analyzing the new EMA GMP inspection plan and the paradigm shift it represents in European regulatory supervision, the next logical step is to delve deeper into one of the texts that will concentrate much of the inspection attention in the coming years: Annex 15. In this second installment we address why the EMA has decided to review it, what conceptual changes it introduces and what message inspectors are sending by moving from an eminently documentary GMPe qualification to an approach clearly based on risk, life cycle and real knowledge of the process.

1. From documentary validation to risk-based validation

The most important change—although not always the most visible—is the explicit reinforcement of the risk-based approach, aligned with:

• I Q9 (R1),
• I Q10,
• The general philosophy of the new EMA inspection plan.

In practice, the new Annex 15 expects companies to:

• justify because They validate something in a certain way,
• They explain the level of validation effort based on the actual risk,
• Avoid legacy “one size fits all” approaches.

It will no longer be enough to show “that it has been validated”; inspectors will want to understand:

• What risks were identified,
• How they influenced the design of the qualification/validation,
• Why the scope is adequate (neither excessive nor insufficient).

2. Clear integration with the Pharmaceutical Quality System (PQS)

Another key change is the formal integration of Annex 15 within the pharmaceutical quality system (Chapter 1):

• Validation is no longer seen as an “isolated technical” activity
• Become part of the product and process life cycle

This implies that future inspections will review whether:

• The validation plans are aligned with the quality strategy,
• Decisions to revalidate or not revalidate are justified,
• Deviations and trends impact the validated status.

In other words: validation becomes a risk management tool, not just a compliance requirement.

3. Greater focus on the life cycle (lifecycle approach)

The new Annex 15 reinforces the concept of complete life cycle, in line with ICH Q12:

Design → qualification → validation → continuous verification

Inspectors will expect to see clear evidence that:

• The validation does not end with the first three batches,
• There are mechanisms of continued process verification (CPV),
• Routine data is actively used to confirm the validated state.

This especially affects complex processes, technology transfers, frequent or incremental changes.
“Static” validation is now considered an obsolete approach.

4. Scope extension: APIs and new technologies

One of the most relevant points is the extension and clarification of the scope of Annex 15, which now:

• Applies more clearly to API manufacturing,
• takes into account advanced and automated technologies.

This includes:

• continuous processes,
• advanced automation,
• Integration with digital systems,
• Interaction with computerized systems (consistent with Annex 11).

On inspection, questions will increase about:

• Interaction between process validation and systems validation,
• Limits of responsibility between production, engineering and quality,
• Technical justification of the models used.

5. Clarification of expectations in qualification (IQ/OQ/PQ)

The new approach to Annex 15 does not eliminate IQ/OQ/PQ, but it does change how they are expected to be applied:

• Less focus on extensive checklists without added value,
• More focus on tests critical for intended use,
• Greater emphasis on qualification based on actual use of the equipment.

During an inspection, this will result in questions such as:

What tests are really critical to product quality?
What risks would be left uncovered if a test is eliminated?
How are the results linked to routine control?

Documentation is still important, but the technical logic behind it is even more so.

6. What inspectors will look for from now on

With the updated Annex 15, GMP inspections will pay special attention to:

• Robustness of Validation Master Plan (VMP),
• Coherence between risk, scope and depth,
• Using actual process data (not just historical reports),
• Change management and its impact on the validated state,
• Integration with deviations, CAPAs and trending,

In summary: less volume, more meaning.

7. Key message of the new Annex 15

The underlying message from the EMA is very clear:
Validation is no longer proving that the process works, but rather proving that you understand it and keep it under control.
Companies that continue to treat validation as a purely documentary exercise will have more difficulties in inspection. Those that use it as a living tool of knowledge and control will be aligned with the new inspector paradigm.

8. Key comparison of the new Annex 15

Aspect	Traditional Annex 15 (previous approach)	New approach Annex 15 (2026–2028)
General philosophy	Qualification as a regulatory requirement to meet	Qualification as a tool for understanding and controlling the process
Regulatory approach	Predominantly prescriptive and documentary	Clearly based on risk and science
Relationship with PQS (Ch. 1)	Implicit relationship, sometimes weak	Explicit integration within the Pharmaceutical Quality System
Scope Justification	Fixed or historical scope (“it has always been done this way”)	Scope defined and defended based on risk
Risk (ICH Q9)	Limited or generic use	Explicit and demonstrable use (live risk assessments)
Validation Master Plan (VMP)	Static and descriptive document	Strategic document, aligned with quality and lifecycle
IR / WHITE / PQ	Checklist approach, many standard tests	Critical focus: evidence relevant to the intended use
Quantity vs. data quality	Lots of documentation, little analysis	Less volume, more interpretation and technical sense
Life cycle	Start-up focused qualification	Qualification throughout the entire life cycle
Continued Process Verification (CPV)	Optional or unstructured	Expected and reviewed in inspection
Routine data	Little used as validation evidence	Actively used to confirm validated status
Change management	Frequent requalification by default	Risk-based impact assessment
Revalidations	Automatic or periodic	Only when the risk justifies it
Deviations and validation	Little connected	Directly connected to the validated state
LAYERS	Treated as isolated events	Evaluated for their impact on validation
Technology transfers	“Independent” qualification per site	Integrated lifecycle approach and process knowledge
Application to APIs	Ambiguous or limited	Clearly also applicable to APIs
New technologies	Treated as an exception	Integrated into the standard validation framework
Automation/digitization	Separate qualification (process vs. system)	Integrated vision with Annex 11
Quality Role	Document review	Active role in risk-based decisions
Inspector expectations	“Is it validated?”	“Why did you validate it like that?”
Type of questions in inspection	Closed and formal	Open, technical and reasoning
Tolerance to legacy approaches	Alta	less and less
Key message	Show that you fulfilled	Show that you understand and control

Quick read for inspection

• Before: “Show me the validation report”
• Now: “Explain to me how you know that this process is still under control today”

9. Key idea for GMP equipment

The new Annex 15 does not eliminate the qualification, but it does eliminate the qualification no critical thinking.

Organizations that continue to accumulate documents without a clear technical narrative will have increasing difficulties in inspection.

Understanding the new approach to Annex 15 is essential, but not sufficient. In the third and final installment of the series we will go one step further and analyze How these changes translate into practical impact for manufacturers, especially for those that have historically been in a more diffuse regulatory zone, such as manufacturers of active substances (APIs). We review what will no longer be acceptable in inspection, what expectations are reinforced, and why preparing in advance will make the difference between a manageable inspection and a critical inspection.