In pharmaceutical manufacturing, compliance with 21 CFR Part 11 is critical for ensuring the integrity of electronic records and signatures within Manufacturing Execution Systems (MES). This paper proposes a comprehensive framework for implementing electronic signatures and data integrity controls in MES, aligning with 21 CFR Parts 11, 210, 211, ICH Q7, and EudraLex Volume 4 Annex 11. The methodology includes system design, user access controls, audit trails, and data lifecycle management, validated through risk-based assessments. Key findings demonstrate that tailored electronic signature configurations (none, single, or double) based on process criticality reduce compliance risks while enhancing operational efficiency. Automated data capture and true-copy transmission further ensure data integrity. Challenges such as manual data entry and generic account usage are addressed through procedural and technical controls. This study underscores the importance of data integrity by design, offering practical guidance for pharmaceutical manufacturers to achieve regulatory compliance and safeguard patient safety.

21 CFR Part 11, Manufacturing Execution System, Electronic Signatures, Data Integrity, Pharmaceutical Manufacturing, Audit Trail, Regulatory Compliance, GMP, Data Lifecycle Management, Risk Assessment

U.S. Food and Drug Administration, “21 CFR Part 11: Electronic Records; Electronic Signatures,” Code of Federal Regulations, Title 21, 1997.

International Society for Pharmaceutical Engineering (ISPE), “GAMP 5: A Risk-Based Approach to Compliant GxP Computerized Systems,” 2008.

European Commission, “EudraLex Volume 4, Annex 11: Computerized Systems,” Good Manufacturing Practice (GMP) Guidelines, 2011.

ICH, “Q7: Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients,” 2000.

Rockwell Automation, “FactoryTalk PharmaSuite MES,” https://www.rockwellautomation.com/en-us/products/software/factorytalk/operationsuite/mes/life-sciences.html

Siemens, “Opcenter MES: Manufacturing Execution System for Life Sciences,” https://plm.sw.siemens.com/en-US/opcenter/

SimplerQMS, “21 CFR Part 11 Compliance: Requirements and Checklist,” https://simplerqms.com/21-cfr-part-11-requirements/

Siemens, “SIMATIC PCS 7 Process Control System,” https://www.siemens.com/global/en/products/automation/process-control/simatic-pcs-7.html

U.S. Food and Drug Administration, “21 CFR Part 211: Current Good Manufacturing Practice for Finished Pharmaceuticals,” Code of Federal Regulations, Title 21, 2023.

Dell Technologies, “PowerEdge Servers for Industrial Automation,”

Advantech, “Industrial PCs for Harsh Environments,” https://www.advantech.com/en/industrial-automation

Microsoft, “SQL Server for Enterprise Data Management,” https://www.microsoft.com/en-us/sql-server

ValGenesis, “ValGenesis VLMS for Life Sciences Validation,” https://www.valgenesis.com/solutions/validation-lifecycle-management-system.

SAP, “SAP Crystal Reports for Business Reporting,” https://www.sap.com/products/technology-platform/crystal-reports.html.

MasterControl, “Audit Trail Best Practices for Compliance,” https://www.mastercontrol.com/glossary-page/21-cfr-part-11/

M. Wollschlaeger, T. Sauter, and J. Jasperneite, “The future of industrial communication,” IEEE Industrial Electronics Magazine, vol. 11, no. 1, pp. 17–27, Mar. 2017.

Veeva Systems, “Data Archiving Strategies for Life Sciences” https://www.veeva.com/resources/

Pharmaceutical Technology, “Pharmaceutical Compliance Management Software,” https://www.pharmaceutical-technology.com/buyers-guide/pharmaceutical-compliance-management-software/

European Union, “General Data Protection Regulation (GDPR),” Regulation (EU) 2016/679, 2016.

International Society for Pharmaceutical Engineering (ISPE), “GAMP Good Practice Guide: A Risk-Based Approach to Compliant Electronic Records and Signatures,” 2010.

A. Kusiak, “Smart manufacturing,” International Journal of Production Research, vol. 56, no. 1–2, pp. 508–517, 2018.

R. Y. Zhong, X. Xu, E. Klotz, and S. T. Newman, “Intelligent manufacturing in the context of Industry 4.0: A review,” Engineering, vol. 3, no. 5, pp. 616–630, 2017.

Honeywell, “Experion PKS: Process Knowledge System,” https://www.honeywellprocess.com/en-US/solutions/control-systems/experion-pks.