“Complete” seems like a simple unambiguous word.  So why do so many firms struggle with complying with the following two predicate rules of cGMP compliance?

  • 21 CFR 211.188 Batch production and control records (here)

“Batch production and control records shall be prepared for each batch of drug product produced and shall include complete information relating to the production and control of each batch.”

  • 21 CFR 211.194(a) Laboratory records (here)

“Laboratory records shall include complete data derived from all tests necessary to assure compliance with established specifications and standards, including examinations and assays…”

Similarly, this requirement is stated in the MHRA “GXP” Data Integrity Guidance and Definitions, March 2018.(here)

“The organisation needs to take responsibility for the systems used and the data they generate. The organisational culture should ensure data is complete, consistent and accurate in all its forms, i.e. paper and electronic.”

Over the years technology has progressed, and production and laboratory records have shifted from solely paper to a combination of paper and electronic.  During this shift, the procedures for ensuring the completeness of records have struggled to keep pace.  In the traditional paper-based systems the main concern was to ensure all of the activities, information and data were accurately captured contemporaneously in hardcopy.  The records review activities focused on the pertinent hardcopy documents: logbooks (e.g., material and equipment use logs), batch records and laboratory notebooks.  A thorough review process for these hardcopy documents could assure that all the pertinent information/data was recorded, and no other batch related information/data existed elsewhere (other logbooks, batch records, worksheets or notebooks) that was not included in the batch records.

With the advent of computerized laboratory and manufacturing systems the complexity of record reviews brought a need for new review procedures and additional reviewer skills.  Reviewers currently not only need to be familiar with the manufacturing process and laboratory testing procedures, they also need to be fluent in the computerized systems that house the electronic records.  Reviewers are now tasked with reviewing the electronic data and the associated audit trails.  As part of the review process, the reviewer needs to be able to verify that the complete electronic data has been reported to ensure compliance.  Establishing effective procedural and system configurational controls as part of the equipment qualification process it critical.  If adequate controls are in place limiting the workspace for electronic records, the data reviewers can focus their review to the confined workspace.  Furthermore, if meaningful record naming conventions are in place, the data reviewer can quickly, and accuracy, verify whether the complete batch related data has been reported.  The effectiveness of controls should however, be further verified by a periodic system-wide review to ensure all data in the computerized systems are accountable and no “orphan data” exists.

My experience indicates firms continue to struggle with ensuring the complete batch data has been reported and all data within GMP computerized systems is accountable.  The following are some examples of extra (not accountable) data that is found in GMP computerized systems:  R&D data, equipment output data not currently documented in batch production records, data for multiple reprocessing activities, data for failed runs, data from unauthorized operations, data from secondary chromatographic channels, hypothesis testing data, equipment maintenance data, etc.

The only way to ensure the complete electronic data is reported is to supplement the record review process with an audit of GMP computerized systems for extra data on a justified schedule.  For example, for chromatographic data the system administrator or a QA resource should periodically ensure all electronic data on the system has been reviewed and locked from change.  Any unaccountable data found should be the subject of a formal investigation.  Similar audits should be performed for all computerized systems within the laboratory and manufacturing.  Whether hardcopy or electronic records, complete means complete!

For further information and assistance on the topic of Complete Electronic Data, please contact either Ron George, Ph.D. at: r.george@staging.lachmanconsultants.flywheelsites.com, or Thu Truong, J.D. at: t.truong@staging.lachmanconsultants.flywheelsites.com.