An Assessment of the ‘Elevens’: EU’s Annex 11 and FDA 21 CFR Part 11

Back to the Future

The EU published Annex 11 in 1992 as one of several guidance documents that supplements the 27-member states’ GMP rules. It applies to all human and veterinary (though not extra-terrestrial) products made or sold in the EU. Annex 11 was created to ensure that when a computer is used in place of a manual operation in the manufacture of pharmaceuticals, there is no further risk to limb or paw when it comes to product quality, efficacy or patent safety. While Annex 11 is not a legal requirement, it is a strongly recommended guideline, as a popular pair of fictional pirates may have once voiced.

  • Quality system
  • Corrective and preventative action (CAPA)
  • Material supply
  • Process controls
  • Laboratory testing
  • Clinical trials
  • Records and documentation
  • Product release
  • Storage
  • Distribution

Annex 11 and Medical Devices

Although the EU guideline wasn’t drafted with medical devices in mind, medtech manufacturers can benefit from aligning their activities with Annex 11, said Browning, a former FDA investigator who helped draft Part 11. “Annex 11 represents the clearest thinking yet from the EU on the use of electronic recordkeeping and electronic signatures in a regulated environment,” he said. “Complying now with Annex 11 will help medical device manufacturers go a long way toward meeting future European medical device expectations,” especially from a notified body auditor’s viewpoint.(4)

2011: A ‘Key Changes to Annex 11’ Odyssey

In addition to including computerized systems, electronic forms and signatures, the updated Annex 11 also weighs in on a few other key points:

  • Electronic Signature and Archiving: Electronic signatures should be permanently linked to corresponding records and include time and date they were applied. Data can be archived but checked for accessibility, readability and integrity.
  • Risk Management: As part of an organization’s risk management system, decisions about validation and data integrity controls should be based off a documented risk assessment of the company’s computer system. Risk assessments should be conducted to evaluate when a supplier audit is needed and to build audit trails.
  • Security: For enhanced security, access to physical and logical controls should be restricted to authorized individuals. Management systems should be created to record the identity of persons entering, changing, confirming or deleting data by time and date.

Non-Supernatural Challenges to EU Compliance

Seeking approval for a new drug or device in most regions of the world is costly and challenging. It’s even more so the case in Europe, where manufacturers must often meet the requirements of multiple regulatory agencies in addition to the European Medicines Agency (EMA). Human and veterinary drugs that fall under the scope of centralized procedures require use of the EMA’s marketing authorization applications (MAAs). Yet thousands of pharmaceuticals not under the umbrella of those procedures must submit applications to the national regulatory agencies of any number of individual countries or mutual-recognition agreements.


It’s no fiction that Annex 11 and Part 11, collectively, entail greater GMP preparation and vigilance of electronic data on the part of life sciences companies. But at the same time, they also provide clear direction of the regulatory expectations. In a more technologically sophisticated global environment, life sciences companies that invest in digital data solutions find they help take the fear our of what can be an unsettling experience. Better yet, companies taking advantage of technological solutions find greater efficiencies, faster speed to market and increased ROI from the resulting quality data and compliant products.

  1. “Annex 11 and 21 CFR Part 11: Comparisons for International Compliance” white paper by Orlando Lopez. 2012.
  2. “The Rules of Governing Medicinal Products in the European Union: Volume 4, Good Manufacturing Practice Medicinal Products for Human and Veterinary Use.” European Commission. June 30, 2011.
  3. “What the Revised European Union’s Annex 11 Means to Life Sciences Companies” white paper by Martin Browning. MasterControl.



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