How do LIMS, MES and QMS fit together, and do you need separate systems?

1Three systems, one record.

A LIMS, an MES and a QMS each hold part of what regulators treat as one body of records about a product. The names are the industry’s; the regulations set out the records.

The sections in the table are 21 CFR 211.194 on laboratory records,¹ 211.186 on master records,² 211.188 on batch records,³ 211.25 on training,⁴ 211.100 on written procedures and deviations,⁵ 211.192 on investigations⁶ and 211.198 on complaints,⁷ and ICH Q10 section 3.2 on CAPA and change management.⁸

ISA-95, the standard for enterprise-control system integration, places manufacturing execution systems at level 3, manufacturing operations management, and ERP at level 4, business planning and logistics, and deals mainly with the exchange between the two.⁹ It is a reference model for where systems meet, not a rule about how many to buy.

2Where the regulations join them.

The records meet at batch release. Under 21 CFR 211.188 the batch record itself includes “in-process and laboratory control results” and “any investigation made according to § 211.192”.³ Section 211.192 requires the quality control unit to review and approve all production and control records before a batch is released, to investigate any unexplained discrepancy, and to extend that investigation “to other batches of the same drug product and other drug products that may have been associated with the specific failure or discrepancy”.⁶ The quality unit has the authority to review production records “to assure that no errors have occurred or, if errors have occurred, that they have been fully investigated”.¹⁰ FDA adds that an invalidated test result stays in the full batch record given to the quality unit, with the investigation that justified it.¹¹ In the EU, “all records should be available to the Qualified Person”.¹²

They meet again across the product’s life. ICH Q10 expects process and product monitoring to take in feedback from “complaints, product rejections, non-conformances, recalls, deviations, audits and regulatory inspections and findings”, and CAPA to follow from the investigation of each.⁸ It asks the quality manual to identify the quality system’s processes “as well as their sequences, linkages and interdependencies”.⁸ Section 211.180(e) requires a review at least once a year that brings batches, complaints, recalls and investigations together for each drug product.¹³

Training shows how a split can go wrong. An operator’s qualification is a quality record that manufacturing depends on. FDA has said that CGMP records, “whether related to training, discrepancies, or related follow-up actions”, should not be held only in a filing system a firm treats as outside FDA’s inspection, such as a human resources system.¹⁴

3What separate systems must do at the joins.

When records live in different systems, every join is an interface you validate and maintain.

• Annex 11 asks for “appropriate built-in checks for the correct and secure entry and processing of data” wherever systems exchange data electronically, and, for critical systems, a description of “data flows and interfaces with other systems or processes”.¹⁵
• PIC/S expects interfaces to be assessed during validation “to ensure the correct and complete transfer of data”, and says “well designed and qualified automated data transfer is much more reliable than any manual data transfer conducted by humans”.¹⁶
• MHRA expects data transfer to be validated, with an audit trail, and “any changes in the middle layer software” managed through the quality system.¹⁷
• 21 CFR 211.68(b) requires input to and output from a computer system to be checked for accuracy.¹⁸
• Annex 11 puts every change to a system, its configuration included, under a defined procedure, and asks for periodic evaluation that the system stays validated.¹⁵ An upgrade on either side of an interface is such a change.

The draft revision of Annex 11 would go further: where critical data moves between systems, for example from an instrument to a LIMS, it should where possible be based on “validated interfaces rather than on manual transcriptions”.¹⁹ That text is a draft; the version in force is January 2011.²⁰

4Do you need separate systems?

No regulation prescribes how many systems you run. ICH Q10 asks for the quality system’s processes and their linkages to be described, and says it is “not intended to create any new expectations beyond current regulatory requirements”.⁸ Annex 11 applies the same controls to “all forms of computerised systems”.¹⁵ The choice is about where you want the work of joining records to sit.

Whichever you choose, write it down. Annex 11 asks for an up-to-date inventory of systems and their GMP functionality,¹⁵ and ICH Q10’s quality manual describes how the processes link.⁸ For each record type, name the system of record and how the others read it.

5How it runs in Seal.

Seal covers LIMS, ELN, MES and QMS on a shared ontology, with defined record types and relationships across your operations, so a batch links to its samples, results and quality events; see the platform. In manufacturing execution a lab result belongs to the batch step it governs and a deviation opens with the affected material, equipment and procedure in view. In the LIMS a result over its limit opens an investigation linked to its source, method and specification. In the QMS each event opens with its evidence, read from Seal or from the ERP, LIMS, MES and training systems you already run.

You don’t have to replace the systems you have. Start with a defined job and the records it needs, then agree which system owns each record, what can be read or written and how the connection will be verified.