How do you move from paper batch records to electronic batch records?

1What the batch record must still contain.

Going electronic doesn’t change what a batch record has to hold. Under 21 CFR 211.188 it includes an accurate reproduction of the master record, checked, dated and signed, and documentation that each significant step was accomplished: dates, major equipment, each batch of component used, weights and measures, in-process and laboratory results, yields, labelling, sampling, investigations and the identity of the people who performed and checked each step.¹ EU GMP Chapter 4 asks for much the same in the batch processing record, including dates and times, quantities actually weighed, in-process results, yields and signed authorisation for any deviation.² For record retention and review, FDA states that paper and electronic record-keeping systems “are subject to the same requirements”.³

What changes is how and when each entry can be checked. Part 11 requires “operational system checks to enforce permitted sequencing of steps and events, as appropriate”,⁴ and Annex 11 expects built-in checks where systems exchange data.⁵ On paper, those checks fall to people: the checker at each step and the reviewer after the batch.

2Map each paper element to an electronic control.

Three of these change the most. FDA confirms that although 211.186(a) specifies a “full signature, handwritten”, an electronic signature with appropriate controls fulfils it.³ Under 211.68(c), automated equipment can satisfy the requirement for one person to perform a step and another to check it, if “one person checks that the equipment properly performed the operation”.⁶ And Annex 11 expects records supporting batch release to produce printouts “indicating if any of the data has been changed since the original entry”, and a system used for certification to allow only Qualified Persons to certify, by electronic signature.⁵

3Validate the workflow, not only the software.

FDA is explicit that each CGMP workflow is an intended use to validate. Its example is an MES: qualifying the platform “does not demonstrate that a given MPCR generated by the MES contains the correct calculations”, an MPCR being a master production and control record; validating the workflow does, much as a paper master record is reviewed before it is used in production.³ The extent of validation should be “commensurate with the risk posed by the automated system”.³

Annex 11 sets the standard for replacing a manual operation: “no resultant decrease in product quality, process control or quality assurance”. It asks for test scenarios that cover “system (process) parameter limits, data limits and error handling”.⁵ For a batch record that means testing the failure paths, not only the normal run: an out-of-limit value, a wrong material, a correction, a deviation, an interrupted step. Under 211.68(b), input to and output from the system must be checked for accuracy, to a degree based on its complexity and reliability.⁶

A validated electronic record also changes review. Chapter 4 allows that where a validated process is continuously monitored and controlled, automatically generated reports “may be limited to compliance summaries and exception/ out-of-specification (OOS) data reports”.² It is one of the provisions behind review by exception. FDA expects audit trails to be reviewed with the record they belong to, and where 211.22 requires data review before release, the audit trail is reviewed then too.³

4Decide which record is official, and plan for outages.

For each required record, FDA recommends that you “determine in advance whether you plan to rely on the electronic record or paper record”, and document that decision, for example in an SOP.⁷ If you print a record from the system but still rely on the electronic record to perform regulated work, FDA may consider you to be using the electronic record.⁷ Mixed records are allowed if the predicate rules are met and content and meaning are preserved,⁷ but PIC/S discourages hybrid systems and says they “should be replaced whenever possible”.⁸

Plan for the system being unavailable. Annex 11 asks for provisions to keep critical processes running “in the event of a system breakdown (e.g. a manual or alternative system)”, with the time to bring them in based on risk, documented and tested.⁵ Design data capture so nothing waits to be saved: FDA notes that an EBR system can save automatically after each entry, like recording each entry indelibly on a paper batch record.³

5Migrate what is active; keep what is closed.

Move master data and current master records with checks that data “are not altered in value and/or meaning during this migration process”.⁵ Decide for each open batch whether it finishes on paper or moves, so it has one official record: Chapter 4 expects it to be clearly defined which record relates to each manufacturing activity and where that record is.² PIC/S expects migration under documented protocols, with verification that it is complete.⁸ Closed paper batch records don’t need re-keying. They stay the record, as originals or as “true copies”, for at least one year after the batch’s expiry date in the US,⁹ and in the EU for one year after expiry or at least five years after Qualified Person certification, whichever is longer.² If you use electronic signatures for FDA records, certify them to FDA before or at the time of first use.¹⁰

Start with one representative product. Classify each line of its paper record as an instruction, a verification, an entry, a calculation, a signature or an exception path, and build the workflow from that, rather than copying every line into a field. Write the user requirements from that classification, as Annex 11 asks they be based on documented risk assessment and GMP impact.⁵ Then scale the patterns that worked to the next product.

6How it runs in Seal.

In Seal the approved master record becomes an executable workflow that checks materials, equipment, training, limits and signatures as the work happens, and batches in progress keep the version they started with. Seal’s guidance for the move is to classify each line of the legacy record before migration rather than copy it into a field, to migrate active master data, open batches, current inventory and equipment state with controlled reconciliation, and to define tested contingency for outages; see electronic batch records.

Closed paper packets can often stay in a validated archive rather than being re-keyed. If you want their history as data, Neil reads scanned batch records into values, each linked to its place on the scan, and sends anything unclear to a person; the scan stays the original (paper records). Paper and spreadsheets compares the two ways of working.