Hardly!  But Part 11 (21 CFR Part 11), which applies to records in electronic form and the use of electronic signatures required by predicate rule (i.e., those records required to be signed by GMP regulations), has been scrutinized and discussed among regulators and the industry over the years, and the industry is still waiting on the final revised ruling. Since its effective date in 1997, followed by the issuance of several associated draft guidance documents, this regulation for Electronic Records and Electronic Signatures has caused a stir in the industry.  The FDA is now re-examining Part 11 as it applies to all FDA regulated products.

In 2003, the FDA published its Guidance for Industry on Part 11, a combined effort by CDER, CBER, CDRH, CFSAN, CVM and ORA, in response to the industry’s concerns that the 1997 regulation was too restrictive and might inhibit manufacturers from using electronic records and electronic signatures, and might result in excessive cost to comply.  The Guidance announced the withdrawal of the previously issued draft guidance documents, described FDA’s enforcement discretion as it applies to Part 11, but provided assurance that the regulation remains in full effect for predicate rule record requirements, and for electronic records which includes:

“Records that are required to be maintained under predicate rule requirements and that are maintained in electronic format in place of paper format.

Records that are required to be maintained under predicate rules, that are maintained in electronic format in addition to paper format, and that are relied on to perform regulated activities.”

If you’re breathing a sigh of relief thinking that Part 11 is no longer a concern, consider this typical pitfall.  Just when you were ready to say “our official copy is the paper copy”, re-consider the key statement above “records…that are maintained in electronic format…and that are relied on to perform regulated activities”. 

 It’s common to surmise that less attention can be given to Part 11 requirements by thinking the paper copy is the one used to make decisions.  But is it really?  When you ask one of your staff to look up the disposition status of a batch, do they start to shuffle through a pile of paper, or do they turn to their computer keyboard and pull it up electronically?  More likely the latter, and this is why the FDA states in the Guidance that “the Agency may consider you to be using the electronic record instead of the paper record”. That is, the Agency may take your business practices into account in determining whether Part 11 applies.

What’s the difference?  Suppose that a firm has two validated, Part 11 compliant computers that are not interfaced.  One maintains laboratory test results and one maintains batch manufacturing information.  The firm’s Production and Quality Unit Management need a system that combines information from both of the computers, so an Access database is created by IT that will provide a data storage and reporting system with the combined data.  This Access database is not likely Part 11 compliant or validated.  The firm claims to use the paper record from the individual computer systems to make GMP decisions and not the Access database.

However, the firm’s Managers have access to this database.  The defense is that the database is used for “tracking purposes only” and the paper record from the validated computers is used to make any GMP decisions.

What’s the risk?  The possibility exists that the Access database can be used to make a GMP decision.  Here’s an example.  Suppose that a laboratory “out of specification” result occurs on a given lot number of raw material, and the investigation requires QA to ensure that all potentially affected batches using this material are reviewed.  QA queries the Access database on the computer (pulling up the electronic record on the computer screen).  However, there is a code error in the database, which resulted in mis-populating the material lot number by one batch, i.e., the identity of the material used and product batch numbers are not matched correctly.  The decision of which batches might be affected is based on the incorrect information on the Access database. 

Now, a GMP decision has been made based on incorrect information and an electronic record has been created in the Access database which doesn’t match the validated computer electronic records; the code error affected the accuracy and reliability of the electronic record in the Access database that was used to make the GMP decision, based on an invalid (non-Part 11 compliant) electronic record.  

There are at least four non-compliance issues in this example:  (1) the Access database isn’t validated as required by Part 11, (2) the electronic record in the Access database is neither accurate, nor reliable, (3) an invalid electronic record has been used to make a GMP decision, and (4) electronic records have been created in two systems with disparities. 

Part 11 compliance is critical to the reliability of electronic records and should be considered whenever a computer is used to store and retrieve GMP information that could in any way be used to make a GMP decision.  Part 11 continues to be part of FDA inspections and is key to data integrity compliance, especially in the Laboratory.  It’s much easier to comply with the regulation than it is to rectify a potential mistake.

Please contact Carol Brandt (c.brandt@LachmanConsultants.com) for any questions relative to Part 11 issues and/or Roy Sturgeon (r.sturgeon@lachamnconsultants.com) for your compliance-related questions or concerns.