World-leading industrial heating solutions provider Watlow™ is now able to offer industry-leading GMP compliance solutions and consulting through its recently acquired Eurotherm® subsidiary.

Demand for Eurotherm’s world-class process control, recording and automation solutions and expertise has become particularly pressing in view of imminent changes to the EudraLex Annex 1 and ISPE GAMP 5 guidelines governing good practice (GxP) manufacturing in life science industries.

Eurotherm has created its suite of Life Sciences Digital Engineered Solutions to ensure processes that are safe, efficient, sustainable and comply with regulations and Quality by Design (QbD) principles.

EudraLex Annex 1 GMP guidelines updated

Annex 1 of the EudraLex, Volume 4, Good Manufacturing Practice (GMP) guidelines for medicinal products for human and veterinary use provides guidance for the manufacture of sterile medicinal products. The revised guidelines come into effect from August 2023 and are designed to keep pace with innovations in regulatory and manufacturing environments, science and technology; they will affect sterile drugs made in the European Union, as well as imported products. Since US manufacturers need to comply with Annex 1 to sell into EU markets, the US FDA and other agencies are adopting matching guidance.

The revised guidelines incorporate quality risk management (QRM) principles into sterile drug manufacturing in line with International Council for Harmonisation (ICH) Q9 and Q10 technical requirements for Pharmaceuticals for Human Use. They also ramp up requirements for manufacturers of medicinal products to use modern production systems, introduce specific requirements for single-use systems (SUS), and harmonise sterile drug manufacturing principles with World Health Organisation (WHO) and Pharmaceutical Inspection Cooperation Scheme (PIC/S) standards.

ISPE GAMP® 5 revisions

The International Society for Pharmaceutical Engineering (ISPE) Good Automated Manufacturing Practice (GAMP®) guidelines were first developed in 2008 to address evolving FDA and other regulatory agency expectations that suppliers and users in the life sciences industries will use systems based on prospective validation following a life cycle model. The GAMP® guidelines are recognised and utilised globally by many regulated companies and their suppliers as the ‘go-to’ guide on computerised systems that are GxP compliant.

The GAMP second edition is intended to keep IT, software engineering and automation good practices up to date with the latest available technologies, services and risk-based approaches with key changes that recognise the need for software development in large or custom systems to allow for iterative, incremental and exploratory methods, promoting an ‘agile model’ as an alternative to traditional linear waterfall methodology.

The revised guidelines highlight the importance of critical thinking, along with Case for Quality principles, to enable efficient risk-based assurance of software throughout the product lifecycle.

In particular, the development appendices update user requirements and functional and design specifications to allow for agile software approaches, while the Electronic Production Records (EPR) appendix now reflects Cloud-based technology and blockchain, redefining expectations for electronic records, electronic signatures and audit trails. Operational appendices now reflect the modern Quality Management System (QMS) IT Infrastructure Library (ITIL) approach to software development, as well as updates on topics such as incident and problem management and operational change and configuration management.

The revised guidelines also address the transition of traditional documents such as installation, operational and performance qualifications (IQs, OQs and PQs) to risk-based records with appropriate tools for modern software development lifecycles, Distributed Ledger Systems (blockchain) that allow use of distributed ledger technology (DLT), and recognise the increasing use of artificial intelligence and machine learning (AI/ML) and how these are applied in GAMP®.

In short, the ISPE GAMP® 5 Second Edition suggests a risk-based approach to compliant GxP computerised systems to support the life sciences industries’ transition from computerised system validation (CSV) to computerised system assurance (CSA).

How Eurotherm helps compliance with the revised requirements

Several new requirements and recommendations are included in the updated version of Annex 1, and they can represent compliance challenges for many sterile drug manufacturers. To support life science companies’ compliance with the revised Annex 1 document, Eurotherm focuses priority on the following topics:

  • Environmental Monitoring Systems: Eurotherm EMS Digital Engineered Solutions can monitor temperature, humidity, pressure, particle counters, and contamination according to the new guidance. Its EMS DES offerings leverage strategic partnerships to deliver pioneering solutions.
  • Indicator of air pressure differences: To meet the Annex 1 requirements that air pressure differences should be continuously monitored and recorded, Eurotherm Store and Forward technology can be embedded in manufacturing systems to reduce the risk of data loss, avoiding gaps in the historic database and support the Data Integrity ALCOA+ principles. Alerts and alarms can be delivered to on-premise or cloud-based repositories and mobile devices.
  • Heat sterilisation: As a leading global supplier of data management technology, Eurotherm offers a solution to help OEMs and end users to meet point 8.50 of Annex 1, by providing off-the-shelf monitoring solutions and redundant control solutions that are cost-effective, easy to qualify and sustain good manufacturing processes.

To aid compliance with ISPE GAMP® 5 second edition, Eurotherm recognises the transformation to modernised risk-based approaches and has adapted its project development, tools, templates, procedures and services to in line with the more agile model laid out in the revised GAMP® 5 document.

This GAMP® 5 engineering approach is already helping life science customers to simplify compliance, using project design, construction and engineering support services that align with the GAMP® 5 good engineering methodology, as well as ISPE GAMP® 5 document templates and products with built-in functions to help meet Category 3 and Category 4 requirements

This is part of a suite of digital engineered solutions and services that Eurotherm has developed to aid GxP compliance in life science applications. These include:

  • High-integrity data management solutions (including cloud-based), with tamper-resistant digital data recording, archiving and reporting technologies, designed to help meet the GxP data lifecycle requirements in line with FDA 21 CFR Part 11, EudraLex Volume 4 Annex 11, and ALCOA+ data integrity principles
  • Industrial automation products and services that aid cybersecurity robustness, helping to protect production processes and data from being compromised by cyber-attacks as part of a defense-in-depth strategy.