PIC/S Annex 15 Consultation (Qualification & Validation)

What Manufacturers Should Do Before the Scope of Annex 15 Expands to APIs

The Pharmaceutical Inspection Co-operation Scheme (PIC/S) has opened a public consultation on proposed revisions to Annex 15 (Qualification and Validation) of the PIC/S Good Manufacturing Practice (GMP) Guide. Highlighted by the Therapeutic Goods Administration (TGA) in March 2026, the Annex 15 consultation proposes two changes with far‑reaching implications for industry:

• extending the scope of Annex 15 to active substance manufacturers, and
• aligning validation expectations more explicitly with ICH Q9 (R1) on Quality Risk Management.

With the concept paper consultation closing in early April 2026, manufacturers should view this not simply as a future regulatory update, but as an immediate signal to assess validation maturity, governance and lifecycle control, particularly where active pharmaceutical ingredients (APIs) are concerned.

Why the Annex 15 consultation matters: validation strategy as inspection currency

Annex 15 has long been the global reference point for qualification and validation activities across facilities, utilities, equipment, processes and computerised systems. For finished dosage form (FDF) manufacturers, it already functions as a baseline expectation during GMP inspections. What has changed over the last decade is how inspectors use Annex 15.

• Rather than checking for the presence of protocols and reports alone, inspectors increasingly assess whether validation activities demonstrate genuine process understanding, robust control strategies and effective lifecycle oversight.
• In this sense, validation strategy has become one of the clearest ways regulators assess whether quality is built into operations, rather than inspected in after the fact.

For active substance manufacturers, Annex 15 has historically been described as optional supplementary guidance, sitting alongside the requirements of EU GMP Part II and ICH Q7 Good manufacturing practice for active pharmaceutical ingredients. The current consultation proposes to remove that ambiguity. Once Annex 15 formally applies to API sites, inspectors will expect to see the same level of structured lifecycle thinking that is already expected of finished product manufacturers.

What’s being proposed: expanded scope and alignment with ICH Q9 (R1)

The PIC/S–EMA concept paper sets out a targeted revision with two core objectives.

• First, it proposes extending the scope of Annex 15 to be mandatory for manufacturers of chemical and biological active substances, with compliance assessed during EU and PIC/S inspections.
• Second, it proposes updating Annex 15 to better reflect the intent of ICH Q9 (R1), the guideline on Quality Risk Management.

The timing is not accidental. The concept paper explicitly links the revision to lessons learned from the nitrosamine contamination incidents in sartans, where investigations identified recurring weaknesses at API manufacturers. These included insufficient process and product knowledge, inadequate investigation practices and weaknesses in contamination control. In regulatory terms, these are validation‑related failures: not simply documentation gaps, but failures to understand and control processes across their lifecycle.

The alignment with ICH Q9 (R1) is equally significant. The inclusion of Q9 was intended to address the over‑formalisation of risk management, where risk assessments became an end in themselves rather than a tool for better decision‑making. Applied to Annex 15, this signals a shift away from checklist‑driven qualification towards risk‑based justification of what is qualified, how rigorously, and why.

What this means for your validation lifecycle

For both API and finished dosage form manufacturers, the proposed changes elevate expectations across the entire validation lifecycle.

• Validation Master Plans (VMPs) will need to clearly articulate scope, rationale and governance, particularly where API manufacturing operations have historically relied on less formalised structures. Inspectors are likely to look for evidence that the VMP is a living document—reviewed, updated and used to guide decisions—rather than a static compliance artefact.
• User Requirements Specifications (URS) take on renewed importance in this context. For equipment, utilities and computerised systems used in API manufacture, traceability from URS through design qualification (DQ), installation qualification (IQ), operational qualification (OQ) and performance qualification (PQ) becomes critical. Gaps in traceability often signal deeper issues in process understanding and risk assessment leading to inadequate testing.
• Process Performance Qualification (PPQ) should clearly link to development knowledge, scale‑up rationale and identified critical quality attributes (CQAs) and critical process parameters (CPPs). Continued Process Verification (CPV) is no longer a ‘nice to have’; it is a core element of demonstrating ongoing control, particularly where API processes are complex, multi‑step or outsourced.

Practical readiness checklist for API and FDF sites

While the consultation remains open, manufacturers can take practical steps to assess readiness:

• Confirm that validation governance documents explicitly cover API operations, including pilot and commercial scales.
• Review quality risk management activities to ensure they support decisions, not just documentation.
• Ensure traceability from URS through to the qualified state for critical systems and equipment.
• Evaluate CPV programmes to confirm they generate meaningful trend data and include defined escalation pathways.
• Confirm the integration between development knowledge, technology transfer and commercial validation.

These activities are not about anticipating the final Annex 15 wording, but about strengthening fundamentals that will remain relevant, regardless of future changes.

How to structure effective consultation feedback

While feedback on the concept paper closed in early April 2026, feedback on the draft Annex 15 guideline will close in June 2026. Regulators have been clear that they value practical, experience‑based feedback during consultations. Submissions that simply restate agreement or disagreement add limited value. Instead, organisations should focus on:

• Areas where additional clarity would support consistent implementation across industry.
• Potential unintended consequences, particularly for smaller or less mature API manufacturers.
• Transitional considerations, such as realistic timelines for updating legacy validation frameworks.
• Alignment with existing guidance, including ICH Q7 Good manufacturing practice for active pharmaceutical ingredients, and national GMP expectations.

It is important to distinguish between issues of regulatory clarity and internal capability gaps. Regulators won’t adjust guidance to accommodate poor practice, but they may clarify expectations where ambiguity could lead to inconsistent interpretation.

Common gaps inspectors are likely to probe

There are several areas likely to attract increased scrutiny as Annex 15 scope expands:

• Traceability is a recurring theme. Inspectors may examine whether organisations coherently link development studies, risk assessments and validation outcomes, or whether these documents exist as disconnected documents.
• Data integrity remains a foundational concern. Validation data, particularly electronic data generated during qualification and CPV, must be attributable, legible, contemporaneous, original and accurate. Weaknesses here undermine confidence in the entire validation lifecycle.
• Supplier and contractor qualification is another focus area. Where organisation outsources critical activities, including utilities, laboratories or API steps, they must clearly define and justify validation responsibilities and oversight for inspectors.

A practical Annex 15 action plan

For organisations seeking a pro-active approach in preparation for the anticipated adoption (by PIC/S) at the end of 2026, a staged roadmap can help prioritise effort:

• First 30 days: conduct a high‑level gap assessment against Annex 15 principles, focusing on API scope, governance and risk management maturity.
• Next 90 days: remediate high‑risk gaps, particularly those affecting traceability, CPV and data integrity. Update validation governance documents where needed.
• By 150 days: embed lifecycle oversight through defined metrics, review cycles and management visibility. Organisations must integrate validation into broader pharmaceutical quality system governance.

Looking ahead for Annex 15

The proposed revision of PIC/S Annex 15 represents more than an administrative update. It reflects a broader regulatory expectation that validation should demonstrate real process knowledge, effective risk management and sustained control across the product lifecycle.

For API manufacturers in particular, the message is clear: Annex 15 thinking is no longer optional. Organisations that act now will better position themselves not only for future inspections, but for more robust, resilient manufacturing operations.

PharmOut Services & Training

PharmOut can support manufacturers in translating the proposed PIC/S Annex 15 changes into practical, inspection‑ready outcomes.

Our Validation services include Annex 15 gap assessments, API and finished dosage form validation strategy reviews, validation master plan remediation, and development of risk‑based qualification and continued process verification frameworks aligned with ICH Q9 (R1).

PharmOut also delivers targeted training on lifecycle validation, risk‑based decision‑making and inspection readiness. Explore elearning and public courses via onlinegmptraining.com, or contact us via the website or via email to tailor workshops to your needs.

Note! Online and in-person Annex 15 training will be available through PharmOut once the annex content has been finalised for publication. Watch this space!

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