---
title: "EU GMP Annex 15 and Annex 11: A Guide for Chromatography Projects"
description: Understand the difference between EU GMP Annex 11 and Annex 15, with chromatography examples covering qualification, audit trails and data integrity
---

[Chromatography Equipment Insights | Peak Biotech](https://peakbiotech.com/insights)

# [EU GMP Annex 15 and Annex 11: A Guide for Chromatography Projects](https://peakbiotech.com/insights/eu-gmp-annex-15-and-annex-11-a-guide-for-chromatography-projects)

 Written by [Malene Linderoth](https://peakbiotech.com/insights/author/malene-linderoth) | Oct 26, 2026, 7:45:24 AM

A chromatography system can measure pressure accurately and still respond incorrectly to a pressure alarm. An automated collection valve can switch as commanded while directing the wrong part of the elution profile into the product fraction.

Assessing these functions involves calibration, equipment qualification and computerised system validation. EU GMP Annex 15 and Annex 11 address connected aspects of this work.

 

## Which GMP Framework Applies?

For active substance manufacture, including peptide APIs and biological active substances, EU GMP Part II provides the basic framework. It includes provisions for qualification and computerised systems. Annex 15 may be used as supplementary optional guidance without adding requirements to Part II.

Annex 15 addresses qualification and validation for medicinal product manufacture. Additional guidance, including Annex 2 for biological active substances and medicinal products, may also be relevant to the manufacturing activity.

 

## What is the Difference Between Annex 15 and Annex 11?

Annex 15 addresses qualification and validation of facilities, equipment, utilities and processes. Annex 11 addresses computerised systems used in GMP activities.

| Guidance | Main Focus | Chromatography Example |
| --- | --- | --- |
| Annex 15 | Suitability of equipment and processes for their intended use | Demonstrating operation within the specified flow range |
| Annex 11 | Reliable computerised functions and data integrity | Verifying automated fraction collection and electronic records |

Annex 15 explicitly links the documents by referring computerised systems used in medicinal product manufacture to Annex 11.

 

## What does Annex 15 Cover?

Annex 15 connects user requirements with documented evidence of suitability. A justified, documented risk assessment determines the qualification and validation scope.

The user requirements specification, or URS, establishes the requirements assessed during qualification.

| **Qualification Activity** | **What it Establishes** |
| --- | --- |
| Design qualification, DQ | The design meets GMP expectations and the URS |
| Installation qualification, IQ | Installation matches approved drawings and specifications |
| Operational qualification, OQ | Equipment operates as designed, with testing of upper and lower operating limits and/or worst case conditions |
| Performance qualification, PQ | Equipment performs effectively and reproducibly according to the approved process method and product specification |

PQ testing may use production materials, qualified substitutes or simulated product demonstrated to behave equivalently under normal operating conditions, with worst case batch sizes.

 

## What does Annex 11 Cover?

Annex 11 addresses computerised systems comprising hardware and software. Applications should be validated and IT infrastructure qualified.

Computerised system validation, often abbreviated to CSV, establishes documented evidence that the system fulfils its intended use. The extent of validation and data integrity controls is based on a justified, documented risk assessment.

Relevant topics include requirements traceability, testing, access control, data storage, backup, controlled changes and periodic evaluation.

Applied to chromatography, these principles support reliable records of process measurements, operating parameters and collection events for subsequent review.

 

## How do Calibration, Qualification and Validation Differ?

In the context of Part II, calibration checks an instrument against a reference or traceable standard to demonstrate that its results remain within specified limits across an appropriate measurement range.

Equipment qualification demonstrates suitability for intended use. Process validation addresses consistent delivery of the required product quality. These activities are connected, and Annex 15 includes instrument calibration within IQ.

For example, calibrating a pressure transmitter addresses its measurement. Testing the associated control function establishes whether the pump responds correctly at the defined threshold. Checking the event record addresses another part of the function.

 

## How do Audit Trails Differ from Event Logs?

In engineering practice, alarm and event logs record operational occurrences, while audit trails record changes and deletions of data relevant to GMP. Recording an alarm and retaining the history of a changed operating parameter serve different purposes.

Annex 11 calls for assessment of system generated audit trails based on risk. It also addresses recording operator identity and the date and time of data entry, changes, confirmation and deletion.

For active substance manufacture, Part II section 5.43 expects records of data changes that retain the previous entry and identify who made each change and when. It also describes controls to prevent data from going unrecorded.

 

## How do the Annexes Work Together in Chromatography?

Consider automated fraction collection based on a detector signal.

The detector is upstream of the collection valve. The liquid takes time to travel between those points, so collection logic needs to account for the volume between them and the operating flow. Valve response also affects when liquid is directed into the selected collection route.

Verification can follow the complete function, including the detector signal, the programmed collection condition, the transport delay, the valve response and the recorded collection event.

Fault handling belongs in the same assessment. If valve position feedback is available, what should happen when the commanded position is not confirmed?

This is an engineering example of how equipment behaviour, software execution and records interact. Annex 11 identifies parameter boundaries and error handling as considerations for testing.

 

## Is Annex 11 being Revised?

The European Commission opened consultation on a revised Annex 11 on 7 July 2025. Consultation closed on 7 October 2025.

As of 23 October 2026, the Commission’s EudraLex page still lists the January 2011 version. The 2025 consultation draft has not replaced that version on the official list.

 

## From Guidance to Equipment Specification

Qualification planning begins while equipment requirements and design are being developed.

For a chromatography project, the practical next step is to define the required flow paths, instrument functions and automated behaviour, together with how their correct operation will be demonstrated.

 

## Sources

[European Commission: EU GMP Part II, Basic Requirements for Active Substances](https://health.ec.europa.eu/document/download/bd537ccf-9271-4230-bca1-2d8cb655fd83_en?filename=2014-08_gmp_part1.pdf)

Particularly sections 5.3, 5.4, 12.3 and the glossary.

[European Commission: Annex 15, Qualification and Validation](https://health.ec.europa.eu/document/download/7c6c5b3c-4902-46ea-b7ab-7608682fb68d_en?filename=2015-10_annex15.pdf)

Particularly Principle, General, sections 3.1 to 3.14 and the glossary.

[European Commission: Annex 11, Computerised Systems](https://health.ec.europa.eu/document/download/8d305550-dd22-4dad-8463-2ddb4a1345f1_en?filename=annex11_01-2011_en.pdf)

Particularly Principle and sections 1, 4, 7, 9, 10, 11 and 12.

[European Commission: Annex 2, Manufacture of Biological Active Substances and Medicinal Products for Human Use](https://health.ec.europa.eu/document/download/380fdf24-8a1e-4f65-809b-e08d990d5f9e_en?filename=2018_annex2_en.pdf)

[European Commission: Consultation on revised Annex 11, Chapter 4 and new Annex 22](https://health.ec.europa.eu/consultations/stakeholders-consultation-eudralex-volume-4-good-manufacturing-practice-guidelines-chapter-4-annex_en)

Last reviewed: 23 October 2026. Version status checked against the European Commission’s [EudraLex Volume 4 page](https://health.ec.europa.eu/medicinal-products/eudralex/eudralex-volume-4_en).

[View full post](https://peakbiotech.com/insights/eu-gmp-annex-15-and-annex-11-a-guide-for-chromatography-projects)

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