This brief document should introduce important facts regarding Electronic System Validation according to 21 CRF Part 11 to interested colleagues. The Code 21 of Federal Regulations (CFR) Part 11 is a FDA guideline which is effective since August 20, 1997 http://www.fda.gov/ora/compliance_ref/part11/frs/background/11cfr-fr.htm. In addition, an Enforcement Policy was published in July 1999 http://www.fda.gov/ora/compliance_ref/part11/FRs/updates/cpg-esig-enf-noa.htm. For submissions to the FDA it regulates requirements of electronic systems, electronic records, electronic data acquisition and electronic signatures under GLP, GCP, and GMP conditions. The aim is to make electronic documents of the same value as handwritten papers. All computerized systems including networks, stand alone units, desktop applications, process control systems including older systems already in use in the companies before August 20, 1997 fall under this law. They all have to be checked also for their compliance and brought in a status compliant with CRF 11.

There is a list of six dockets which were published by the FDA:

1. Glossary of terms (Sept. 2001)
   http://www.fda.gov/ohrms/dockets/dockets/00d1543/00d1543.htm
   
   
2. Procedures and controls of validation (Sept. 2001)
   http://www.fda.gov/ohrms/dockets/dockets/00d1538/00d1538.htm
   http://www.fda.gov/cdrh/comp/guidance/938.pdf
   
   
3. Electronic copies of electronic records (Nov. 2002)
   http://www.fda.gov/ohrms/dockets/dockets/00d1540/00d1540.htm
   http://www.fda.gov/ohrms/dockets/98fr/00d-1540-gdl0001.pdf
   
   
4. Timestamps (March 2002)
   http://www.fda.gov/ohrms/dockets/dockets/00d1542/00d1542.htm
   
   
5. Audit trails
   http://www.fda.gov/ohrms/dockets/dockets/00d1541/00d1541.htm
   
   
6. Archiving (Sept. 2002)
   http://www.fda.gov/ohrms/dockets/98fr/00d-1539-gdl0001.pdf
   http://www.fda.gov/ohrms/dockets/dockets/00d1539/1.htm

FDA Guidance Documents concerning electronic submissions:
http://www.fda.gov/cder/guidance/index.htm#electronic_submissions

• Guidance for Industry: Part 11, Electronic Records; Electronic Signatures - Scope and Application (Finalized August 2003)
  http://www.fda.gov/cder/guidance/5667fnl.pdf

EPA projects concerning electronic reporting systems:
http://www.epa.gov/cdx

• Cross-Media Electronic Reporting Regulation (CROMERR):
  http://www.epa.gov/exchangenetwork/cromerr/index.html

In national guidelines, as in the German "Chemikaliengesetz" (Version 2 July 2008), remarks can be found about the generation of computer-based data (annex 1, chapter 8.3): "The date and the person generating the data have to be identified. A complete audit trail is required which shows all changes to data and the original data. For all data changes, the person who performs the change and the date of the change have to be recorded. All changes have to be commented." (http://bundesrecht.juris.de/chemg/anhang_1_73.html).
The complete law (in German) can be found under http://bundesrecht.juris.de/chemg/index.html.

Please feel free to contact the Committee for Scientific Standards if you have interesting information or paper to add