New and updated Documents of the ECA Analytical Quality Control Group
The ECA Analytical Quality Control Group (AQCG) continues to develop practical guidance for quality control laboratories. Its current work includes established guidance documents, new publications, survey reports and documents undergoing revision in response to regulatory developments and feedback from the analytical community.
The Analytical Quality Control Group
The AQCG provides a European networking platform for analytical chemists and scientists working in or managing quality control and research and development laboratories. The group promotes discussion of current European and US regulatory expectations, identifies technical challenges and training needs, and supports harmonised approaches through discussion papers and guidance documents. An important part of its work is to facilitate communication between industry, competent authorities and pharmacopoeias.
The group’s areas of interest include laboratory compliance and quality management systems, data integrity and security, data quality management and trend analysis, deviation management and change control, sampling and sample management, qualification and validation of laboratory instruments and systems, and lifecycle approaches to analytical procedures.
Documents Currently Available for Download
The AQCG provides its current guidance documents in the members’ area. Together, these documents address key stages of the analytical quality control lifecycle, from sampling and data generation to laboratory investigations, data governance, instrument qualification, system validation and analytical procedure lifecycle management.
Recommendation
Barcelona, Spain3-5 November 2026
Setting Specifications AND Stability Testing
Sampling and Sample Management (Version 1.0, April 2025)
This guidance addresses the beginning of the analytical process: the sample. Sampling is an error-generating activity, and the reliability of the final analytical result depends not only on the analytical method but also on the quality and representativeness of the sample.
The guidance explains relevant expectations for representative sampling and covers sampling plans, sampling procedures, sample identification, protection, storage, transport, chain of custody and sampling records. It brings together relevant expectations from US cGMP, EU GMP, USP, WHO, FDA and other sources.
The practical message is straightforward. Even a technically excellent analytical method cannot support a meaningful quality decision if the sample is not representative, traceable and protected from contamination, mix-up or deterioration.
Guide for an Integrated Lifecycle Approach to Analytical Instrument Qualification and System Validation (Version 1.0, November 2023)
This guide presents a risk-based lifecycle approach for analytical apparatus, instruments and computerised systems. It links the definition of intended use and risk assessment with specification and selection, qualification and validation, continued performance verification, data integrity, change control, periodic review, data migration, archiving and retirement. The guide also distinguishes bet ween Group A apparatus, Group B analytical instruments and Group C analytical systems. Practical examples include balances, pH meters, UV-visible spectrometers, bioassay software and chromatography data systems.
The lifecycle approach is intended to ensure that qualification and validation activities remain connected to the actual purpose and risk of an instrument or system throughout its operational life.
GMP, GCP and GDP Data Governance and Data Integrity (Version 3.0, December 2022)
Developed jointly by the AQCG and the ECA IT Compliance Group, this guidance takes a broad view of data integrity. It covers the corporate culture and responsibilities needed to protect data, as well as policies, procedures, risk management, training, data ownership, data stewardship, access controls, validation and audit trail review.
The laboratory-related sections address complete and raw data, laboratory records, blank forms, hybrid systems, spreadsheets and chromatographic integration. The guidance makes clear that reliable analytical data depend not only on suitable instruments and validated methods. They also require appropriate governance of the complete data lifecycle, from data generation and review to retention and use.
Out of Specification (OOS) Results (Version 2.1, August 2013)
The OOS procedure addresses laboratory results that fall outside an approved specification or acceptance criterion. It describes a structured investigation beginning with the initial laboratory assessment, followed by a formal review of the analytical records and, where necessary, a full laboratory investigation.
The procedure covers system suitability failures, obvious laboratory errors, reportable values, averaging, retesting, resampling and outlier testing. A central principle is that the original OOS result remains part of the complete data record. Additional testing must be scientifically justified and cannot be used simply to search for a passing result.
An OOS result does not automatically prove that the product or process has failed. It may be caused by a laboratory error, a problem with the sample or analytical system, or an actual product or manufacturing failure. The purpose of the investigation is therefore to establish the facts in a controlled and documented manner.
Out of Expectation (OOE) and Out of Trend (OOT) Results (Version 1.2, July 2023)
This guidance complements the OOS procedure by addressing unexpected values and trends that may arise without a formal specification failure.
An OOE result is an unexpected observation in data for which no particular direction of change is expected. Examples include an unusual result, a shift in the location of results or excessive variability in routine analytical data that should be under statistical control.
An OOT result describes an unexpected pattern in a time-related sequence. This may include a drift in stability data that is inconsistent with the expected behaviour of the product or analytical procedure. OOE and OOT signals can therefore provide an early warning of changes before a formal specification limit is exceeded. The guidance covers control charts, statistical process control, CUSUM and EWMA methods, charts for discrete data, and stability trend approaches based on linear and random-coefficients regression. It also briefly addresses process capability indices.
Analytical Procedure Lifecycle Management (APLM) (Version 1.0, July 2018)
This guidance presents a lifecycle-based approach to the development, validation and ongoing management of analytical procedures. It addresses the relationship between the analytical target profile, method development, risk assessment, robustness, validation and continued procedure performance verification. The document also considers knowledge management, change control and the transfer of analytical procedures across the product lifecycle.
Further documents and supporting publications
In addition to these guidance documents, the AQCG download area contains the results of the 2026 OOS survey, a report on the use of statistical process control in the pharmaceutical industry, and
comparisons of ICH Q2 and ICH Q14.
The download area also includes a recording of the free webinar on the AQCG Guidance on Sampling and Sample Management, as well as a recorded discussion of the recently conducted OOS survey.
Results of the AQCG OOS Survey 2026
To assess current industry practice and provide a sound basis for revising the guidance, the AQCG conducted an industry-wide survey between February and April 2026. The survey received 169 complete responses.
The results can be summarised as follows. The basic principles are largely standardised across the industry. For example, 91% of respondents stated that their procedures clearly define what constitutes an OOS result, while 89% clearly distinguish between OOS, OOT and invalid results. Second-person review is also widely established.
At the same time, the responses identified a clear need for more practical guidance on hypothesis testing and root cause analysis. Participants requested decision trees, practical examples and harmonised approaches, particularly regarding the transition between investigation phases, the confirmation of suspected causes and the handling of inconclusive investigations.
The survey also indicated that the FDA guidance is perceived by some respondents as being strongly focused on small-molecule analytical chemistry. More specific guidance was requested for biologics, non-chromatographic methods and contract laboratories. These findings are being incorporated directly into the revision of the AQCG OOS guidance.
In addition, readers may wish to consult the guidance documents developed by the ECA Pharmaceutical Microbiology Working Group. These documents address the specific requirements and challenges of pharmaceutical microbiology, including the handling of Out of Limit (OOL) results and the exceedance of alert and action levels in environmental monitoring.
The Revision Programme and the Role of Member Feedback
The OOS, OOE/OOT and APLM guidance documents are currently under active revision.
According to the group's current business plan, the OOS update is intended to be completed first. It will take into account the 2022 revision of the FDA's OOS guidance (Investigating Out-of-Specification (OOS) Test Results for Pharmaceutical Production, Level 2 Revision, Guidance for Industry, May 2022).
The revised AQCG document will update the structure and terminology, clarify the treatment of reportable values and averaging, and develop the investigation process through Phase Ia, Phase Ib and Phase II. It will also strengthen the treatment of hypothesis testing, root cause confirmation, retesting, outlier testing and practical investigation examples. The OOS Survey 2026 is being used to inform this update.
The OOE/OOT document is also a work in progress. The new version is expected to expand the treatment of normal analytical data and bring together Shewhart, X-bar, range and standard deviation charts, CUSUM, EWMA, discrete-data charts, process capability, and stability trend limits based on linear and random-coefficients regression.
Recommendation
Barcelona, Spain3/4 November 2026
Setting Specifications and Acceptance Criteria
The APLM Guidance is also being updated. The revision will reflect ICH Q2(R2), ICH Q14 and the ongoing development of USP <1221>. Its objective is to connect the analytical target profile, risk-based development, validation, robustness and ongoing procedure performance verification in a coherent lifecycle approach.
PharmaLab 2026: From Guidance to Discussion
The AQCG will also bring these topics to PharmaLab 2026, which will take place from 23 to 25 November 2026 at the new venue in Darmstadt, close to Frankfurt International Airport. The congress will offer several parallel conferences, poster presentations and three pre-conference workshops.
This year, the ECA Analytical Quality Control Group will organise one of the pre-conference workshops and a dedicated one-day conference track.
Data Quality Management of Aberrant Results - Handling Out of Specification, OOS, and Out of Trend, OOT Results
The pre-conference workshop on 23 November aims to strengthen participants' ability to manage data quality and investigate aberrant results in pharmaceutical laboratories. It will provide a structured approach to handling OOS and OOT results, explain key regulatory and guidance expectations and show how these can be translated into practical laboratory procedures. In addition, participants will apply trend analysis tools and statistical rules to evaluate OOT signals through an interactive Excel-based exercise, which will also address common pitfalls and misinterpretations. The preconference workshop will further cover specific challenges associated with the analysis of small molecules and biopharmaceuticals.
Analytical Procedure Lifecycle Management (APLM)
The dedicated one-day track on 24 November will provide a lifecycle-based and risk-driven framework for developing, validating and maintaining analytical procedures from early development through registration and post-approval change management.
Participants will learn how to apply current USP developments and practical case studies covering analytical target profiles, risk assessment, the method operable design region, validation strategies, precision and replication, platform methods and ongoing procedure performance verification.
The track will address ICH Q2(R2), ICH Q14 and USP <1221>. The aim is to help participants define a fit-for-purpose validation scope, ensure method robustness and independence, and manage changes in an inspection-ready and dossier-ready manner.
Download the Documents
All PharmaLab 2026 participants will have access to the relevant AQCG documents for download. Regardless of whether they attend PharmaLab 2026, interested professionals can also access these documents free of charge in the members' area of the AQCG website. Further information is available at https://analytical.gmp-compliance.org, where interested professionals can also apply for free membership.
About the Author
Dr Markus Funk is Operations Director at CONCEPT HEIDELBERG. He organises and conducts courses and conferences on behalf of the ECA Academy in analytical and GDP topics. He also serves as Administration Manager of the ECA Analytical Quality Control Group.
