Manufacturing Execution Systems & Electronic Production Records Management: A Building Block for Pharma 4.0™ & Your Organisation’s Digitalization Journey

This blog is a companion to ISPE GAMP^® 5: A Risk-Based Approach to Compliant GxP Computerized Systems (Second Edition) and the ISPE GAMP® Good Practice Guide: Manufacturing Execution Systems - A Strategic and Program Management Approach.

Pharma 4.0™

Pharma 4.0™ is the life sciences implementation of Industry 4.0, also referred to as “the 4th industrial revolution.” Each iteration of industry advancement reduces some amount of unskilled labor while creating other more technical human activities with the expectation of more efficient, accurate and humanly safe operations and products. Briefly, these are

The life sciences regulatory and guidance environment is evolving as industry moves into the Pharma 4.0™ paradigm. Revisions to ISPE GAMP^® 5 and related good practice guidance publications are aimed at providing support and flexibility in the design and implementation of computerized systems at all stages of life sciences product invention, development, and production.

It is also important to note that “Pharma 4.0™” applies to all life sciences products including pharmaceuticals, medical devices, and hybrid products, as well as equipment and systems facilitating development and production of activities.

The GAMP^® 5 key concepts provide the framework for adhering to regulated activities:

• Product and Process Understanding
• Life Cycle Approach within a QMS
• Scalable Life Cycle Activities
• Science-Based Quality Risk Management
• Leveraging Supplier Involvement

Manufacturing Execution Systems inherently utilize and create electronic records throughout manufacturing and thus are a key component of enhancing accuracy, timeliness, and overall availability of data. GAMP^® 5 Second Edition contains updates to Appendix S2 Electronic Production Records in this regard.

Your Company and MES

Manufacturing execution involves functionality across the enterprise, from raw material specification, quality evaluation and status, inventory, and usage (traceability) through intermediates and products involving Enterprise Resource Systems (ERP), specification systems, Laboratory Information Management Systems (LIMS), Manufacturing Control, Automation and more. Manufacturing execution can be looked at as the sum or Domain of functions needed for managing all related operations.

Strategic Assessment

To determine industry needs of a life sciences manufacturer it is often seen that computer systems are selected, then companies retrofit operations to them (not strictly the case, but typical of current standard company practices). What is needed is a strategic assessment to evaluate the enterprise related to the product(s) to establish the baseline needs and goals. This needn’t be a herculean effort but should be thorough enough to ensure each affected facility and department has input and has gained an understanding of the path forward at a high level.

Adapted from: GAMP^® Good Practice Guide: Manufacturing Execution Systems – A Strategic and Program Management Approach (2010).

How Systems Fit into A Design Paradigm

ISA standards are utilized in defining the overall structure, as well as specific designs of systems. Here the focus is on ISA95: Enterprise-Control System Integration, and ANSI/ISA88: Batch Control (which is not limited to “batch” but also applies to continuous manufacturing).

The ISA95 hierarchical model (depicted by the following ISPE figure based on ANSI/ISA 95.03-2005 “Enterprise-Control System Integration Part 3: Activity Models of Manufacturing”) is often misinterpreted to define specific systems for each level. This model is a functional hierarchy.

Traditionally it has often been assumed by industry that a system resides in one of the levels which is incorrect given the broad functionality in many current computer systems related to manufacturing. For example, what about a Distributed Control System (DCS) that also manages the lifecycle of recipes? While the bulk of the system lies in level 1 and 2, recipe management including asset management is at level 3.

In designing an enterprise structure, outcomes can be improved by defining the functionality needed to execute operations, then choosing appropriate systems and integration strategies with functionality defined by that structure. These are NOT strict level boundaries at the system level!

Of course, this can be more complicated when updating facilities with existing systems that need to remain in place while augmenting functionality by upgrades or staging replacement strategies. Regardless, clearly defining the necessary current and future functionality fitting the ISA models leads to creation of an evolutionary path to be followed as equipment and systems are implemented or augmented going forward in time.