1What an MES does.
A manufacturing execution system manages manufacturing operations, between the business systems that plan production and the control systems that run equipment. A widely used way to place it is ISA-95, also known as IEC 62264, an international set of standards for integrating logistics systems with manufacturing control systems. Its model has five levels.¹
| Level | What it covers |
|---|---|
| 0 | The physical production processes: machinery and other assets on the floor. |
| 1 | Sensing and manipulating the process: sensors, smart devices and valves. |
| 2 | Monitoring and supervisory control: programmable logic controllers (PLCs) and distributed control systems (DCSs). |
| 3 | Manufacturing operations management: MES and other systems, such as SCADA, that manage manufacturing operations. |
| 4 | Business planning and logistics, including enterprise resource planning (ERP). |
ISA says the standard deals “primarily” with the interface between levels 3 and 4, and Part 2 of the series specifies the information exchanged between level 3 manufacturing systems and level 4 business systems.¹
FDA’s guidance on computer software assurance, written for medical device manufacturers, gives a plain description of the range. An MES “may be used to manage workflow, track progress, record data, and establish alerts or thresholds based on validated parameters”; another may be used “to automatically control and adjust established critical production parameters (e.g., temperature, pressure, process time)”.² The guidance treats a failure of the first kind as something that may disrupt operations without affecting the process parameters, and changes to the second kind as possibly affecting the device’s safety or effectiveness.²
No GMP regulation requires an MES. For drugs, 21 CFR 211.68 says automatic, mechanical or electronic equipment, “including computers, or related systems that will perform a function satisfactorily, may be used” in manufacture, provided it is routinely calibrated, inspected or checked under a written programme.³
2What an eBR is.
An electronic batch record is the batch record GMP already requires, kept electronically. In the US, 21 CFR 211.188 requires a batch production and control record for each batch with “complete information relating to the production and control of each batch”: an accurate reproduction of the master record, and documentation of each significant step, including dates, major equipment, component lots, weights and measures, in-process and laboratory results, actual yield and percentage of theoretical yield, labelling records, sampling, the people who performed and checked each step, and any investigation.⁴ The master record it reproduces is defined in 211.186.⁵ In the EU, Chapter 4 of the GMP guide sets out the contents of the batch processing record in paragraph 4.20, and says documentation may be “paper-based, electronic or photographic media”.⁶
Keeping the record electronically brings in the rules for electronic records. Part 11 applies to records in electronic form kept under any of FDA’s records requirements, and electronic records that meet it may be used in place of paper.⁷ FDA’s data integrity guidance confirms that electronic signatures with appropriate controls can replace the handwritten signature 211.186 asks for on a master production and control record.⁸ In the EU, Annex 11 applies, and where a system records batch certification it should allow only Qualified Persons to certify release, using an electronic signature.⁹
3How an MES and an eBR differ.
The two overlap because an MES that directs execution against a master record produces the batch record as it runs. They are still different kinds of thing.
| MES | eBR | |
|---|---|---|
| What it is | A system that manages production operations, at ISA-95 level 3¹ | A record: the batch production record, in electronic form⁴ |
| Required by GMP | No; computers “may be used”³ | The batch record is required; the electronic form is a choice⁴⁷ |
| Scope | Workflow, progress tracking, data, alerts and thresholds, and the interface with business systems such as ERP²¹ | The complete history of one batch⁴⁶ |
| What is validated | The platform and each workflow it runs⁸ | The system that creates and keeps the record¹⁰⁹ |
| Control in use | Changes to the system and its configuration follow a defined procedure⁹ | Reviewed and approved by the quality control unit before the batch is released;¹¹ in the EU, the batch is certified by a Qualified Person¹² |
4What validation means for each.
Validating an MES platform is not the same as validating the batch records it runs. FDA’s data integrity guidance uses this as its example: qualifying the MES platform “ensures that it meets its relevant requirements and specifications; however, it does not demonstrate that a given MPCR generated by the MES contains the correct calculations.” Each CGMP workflow, such as creating an electronic master production and control record, is an intended use to be checked through validation, with the extent “commensurate with the risk posed by the automated system”.⁸
Section 211.68 sets the operating controls. Changes to master production and control records may be made only by authorised personnel, input to and output from the system are checked for accuracy at a degree and frequency based on its complexity and reliability, and backup data are kept exact, complete and secure.³ Automation can also take the place of one of two people. Where components are weighed or added, or yields calculated, by automated equipment under 211.68, one person checks what the equipment did, instead of one person doing the step and a second verifying it, and the batch record identifies the person checking the step the equipment performed.³¹³¹⁴⁴
Annex 11 adds expectations for an MES in the EU: built-in checks on data exchanged electronically with other systems, an audit trail of GMP-relevant changes and deletions considered on the basis of risk, with the reason for each change documented, and, for records supporting batch release, printouts that show whether any data changed since original entry.⁹
5How it runs in Seal.
Seal is one platform for manufacturing execution, laboratory, quality, training and inventory. Manufacturing execution defines the operations, instructions, checks and review gates, and the electronic batch record retains what happened, so a result or deviation links to the step it concerns. Each step keeps what GMP asks the batch record to show: the date, the equipment, the component lot, the weights and measures, and who performed and checked the work. See MES in Seal and electronic batch records.
A process change is released as a new version with its specifications, tests and approval, and executed batch records keep the version they ran. Where an existing MES or ERP stays in place, Seal connects the records the job needs and you agree which system owns them. The MES comparison sets out the other products in the category.
References
- 1ISA-95 Series of Standards: Enterprise-Control System Integration, International Society of Automation. https:/
/ www. isa. org/ standards- and- publications/ isa- standards/ isa- 95- standard (read 6 November 2026) - 2Computer Software Assurance for Production and Quality Management System Software, Guidance for Industry and FDA Staff, FDA, February 2026. https:/
/ www. fda. gov/ regulatory- information/ search- fda- guidance- documents/ computer- software- assurance- production- and- quality- management- system- software (read 6 November 2026) - 321 CFR 211.68, Automatic, mechanical, and electronic equipment, eCFR. https:/
/ www. ecfr. gov/ current/ title- 21/ chapter- I/ subchapter- C/ part- 211/ subpart- D/ section- 211. 68 (read 6 November 2026) - 421 CFR 211.188, Batch production and control records, eCFR. https:/
/ www. ecfr. gov/ current/ title- 21/ chapter- I/ subchapter- C/ part- 211/ subpart- J/ section- 211. 188 (read 6 November 2026) - 521 CFR 211.186, Master production and control records, eCFR. https:/
/ www. ecfr. gov/ current/ title- 21/ chapter- I/ subchapter- C/ part- 211/ subpart- J/ section- 211. 186 (read 6 November 2026) - 6EudraLex Volume 4, Chapter 4: Documentation, European Commission, January 2011. https:/
/ health. ec. europa. eu/ system/ files/ 2016- 11/ chapter4_ 01- 2011_ en_ 0. pdf (read 6 November 2026) - 721 CFR 11.1, Scope, eCFR. https:/
/ www. ecfr. gov/ current/ title- 21/ chapter- I/ subchapter- A/ part- 11/ subpart- A/ section- 11. 1 (read 6 November 2026) - 8Data Integrity and Compliance With Drug CGMP: Questions and Answers, Guidance for Industry, FDA, December 2018. https:/
/ www. fda. gov/ media/ 119267/ download (read 6 November 2026) - 9EudraLex Volume 4, Annex 11: Computerised Systems, revision 1, European Commission, January 2011. https:/
/ health. ec. europa. eu/ system/ files/ 2016- 11/ annex11_ 01- 2011_ en_ 0. pdf (read 6 November 2026) - 1021 CFR 11.10, Controls for closed systems, eCFR. https:/
/ www. ecfr. gov/ current/ title- 21/ chapter- I/ subchapter- A/ part- 11/ subpart- B/ section- 11. 10 (read 6 November 2026) - 1121 CFR 211.192, Production record review, eCFR. https:/
/ www. ecfr. gov/ current/ title- 21/ chapter- I/ subchapter- C/ part- 211/ subpart- J/ section- 211. 192 (read 6 November 2026) - 12EudraLex Volume 4, Chapter 1: Pharmaceutical Quality System, European Commission, in operation since 31 January 2013. https:/
/ health. ec. europa. eu/ document/ download/ e458c423- f564- 4171- b344- 030a461c567f_ en?filename=vol4- chap1_ 2013- 01_ en. pdf (read 6 November 2026) - 1321 CFR 211.101, Charge-in of components, eCFR. https:/
/ www. ecfr. gov/ current/ title- 21/ chapter- I/ subchapter- C/ part- 211/ subpart- F/ section- 211. 101 (read 6 November 2026) - 1421 CFR 211.103, Calculation of yield, eCFR. https:/
/ www. ecfr. gov/ current/ title- 21/ chapter- I/ subchapter- C/ part- 211/ subpart- F/ section- 211. 103 (read 6 November 2026)
AQuestions and answers
Does FDA require an MES or electronic batch records?
No. 21 CFR 211.188 requires a batch production and control record for each batch, and 211.68 allows computers and automated equipment to be used. Paper batch records remain acceptable. If you keep the record electronically, Part 11 applies to it and the system must be validated for its intended use.
Where does an MES sit relative to ERP and process control systems?
In the ISA-95 model, ERP is at level 4, business planning and logistics. The MES is at level 3, manufacturing operations management. PLCs and distributed control systems are at level 2, with sensors and the physical process below them. The standard deals mainly with the information exchanged between level 3 and level 4.
Do you validate an MES once, or each master batch record in it?
Both. FDA’s data integrity guidance says qualifying the MES platform shows it meets its requirements, but not that a given electronic master record contains the correct calculations. Each workflow, such as an electronic master production and control record, is an intended use to validate, much as a paper master record is checked before it is used.
Can automated equipment replace one of the two people on a weighing step?
For some operations, yes. Under 21 CFR 211.101 and 211.103, when components are weighed or added, or yields are calculated, by automated equipment that meets 211.68, one person checks what the equipment did, instead of one person doing the step and a second verifying it. The batch record then identifies the person who checked the step the equipment performed.
Who approves an electronic batch record before the batch is released?
In the US, the quality control unit reviews and approves production and control records before a batch is released or distributed. In the EU, a Qualified Person certifies each batch, and where a computerised system records that certification, only Qualified Persons should be able to certify, using an electronic signature.