Regulations and Guidelines

FDA CFR 21 Part 11: Electronic records: Electronic Signatures

FDA: Food and Drug Administration.

CFR: Code of Federal Regulations.

ERES: Electronic Records and Electronic Signatures.

The title 21 of the Code of Federal Regulations, established by the Food and Drug Administration in 1997 (latest review in April 2018) regulates on electronic records and electronic signatures (ERES). Part 11 defines the criteria under which electronic records and electronic signatures are considered trustworthy, reliable and equivalent to paper records and handwritten signatures.

EU Annex 11: Computerised systems within GMP-regulated activities

EU: European Union

GMP: Good Manufacturing Practice

GLP: Good Laboratory Practice

GCP: Good Clinical Practice

What was to become the Annex 11 was released in 1991 and updated in January 2011. The Annex 11 can be found with the EudraLex (the rules governing Medicinal products in the European Union) volume 4 (good manufacturing practice). The guidelines state that where a computerised system replaces a manual operation, there should be no resultant decrease in product quality, process control or quality assurance. There should be no increase in the overall risk of the process. The Annex 11 is also a requirement for GLP and GCP in Europe, unifying the requirements for the management of electronic records and electronic signatures in regulated companies.

FDA CFR 21 Part 11 & EU Annex 11 Requirements:

Both the FDA CFR 21 Part 11 and the EU Annex 11 share the mutual goal of safe, validated computer systems for drug manufacturing (GMP). Whereas the Part 11 is a regulation, the Annex 11 is only a guideline to comply with GMP principles within the EU. The FDA CFR 21 Part 11 has an international reach whereas the EU Annex 11 is focused on Europe.

Here are some of the industry standards when it comes to complying with the two titles:

  • Access limited to authorised individuals using roles, privileges are assigned to role not individuals.
  • Specific password security
  • Unique user name
  • Audit trail for all changes

Download the RMS-WP-Vxxx-EN to find out how Rotronic comply to the FDA requirements and the EU guidelines. (Gated content)

European Union good distribution practice:

GDP: Good Distribution Practice

The EU GDP are the guidelines on the principles of good distribution practice of active substances for medicinal products for human use.

The Rotronic Monitoring System is a range of hardware devices and a FDA CFR 21 Part 11 and EU Annex 11 compliant software (link to hardware and software) that help end users comply with the above mentioned requirements.

EURopean union good manufacturing practice:

GMP: Good Manufacturing Practice

The EU GMP lays down the principles and guidelines of good manufacturing practice in respect of medicinal products for human use and investigational medicinal products for human use.

The Rotronic Monitoring System is a range of hardware devices and a FDA CFR 21 Part 11 and EU Annex 11 compliant software (link to hardware and software) that help end users comply with the above mentioned requirements.

World health organisation annex 5

WHO: World Health Organisation

The WHO Annex 5 lays down guidelines for the distribution of pharmaceutical products. Depending on the national and regional legislation on pharmaceuticals, the guidelines may apply equally to products for human and for veterinary use.

The Rotronic Monitoring System is a range of hardware devices and a FDA CFR 21 Part 11 and EU Annex 11 compliant software (link to hardware and software) that help end users comply with the above mentioned requirements.

united states pharmacopeia standards

USP: United states Pharmacopeia

The United States Pharmacopeia (USP) establishes written and physical standards for medicines, food ingredients, dietary supplement products and ingredients. These standards are used by regulatory agencies and manufacturers to help to ensure that these products are of the appropriate identity as well as strength, quality, purity and consistency.

The Rotronic Monitoring System is a range of hardware devices and a FDA CFR 21 Part 11 and EU Annex 11 compliant software (link to hardware and software) that help end users comply with the above mentioned requirements.

usp797: Pharmaceutical Compounding - Sterile Preparations

USP: United States Pharmacopeia

The USP797 describes the minimum standards to be followed when preparing compounded sterile human and animal drugs based on current scientific information and best practices for sterile compounding. Sterile compounding is defined as combining, admixing, diluting, pooling, reconstituting, repackaging or otherwise altering a drug or bulk drug substance to create a sterile medication.

The Rotronic Monitoring System is a range of hardware devices and a FDA CFR 21 Part 11 and EU Annex 11 compliant software (link to hardware and software) that help end users comply with the above mentioned requirements.

International Organisation for standardization

ISO: International Organisation for Standardization

The ISO is an independent, non-governmental international organisation with a membership of 164 national standards bodies. Through its members, it brings together experts to share knowledge and develop voluntary, consensus-based, market relevant International Standards that support innovation and provide solutions to global challenges. International Standards give world-class specifications for products, services and systems, to ensure quality, safety and efficiency. They are instrumental in facilitating international trade.

ISO14644-1: Cleanrooms and associated controlled environments - Part 1: Classification of air cleanliness by particle concentration

ISO: International Organisation for Standardization

ISO 14644-1:2015 specifies the classification of air cleanliness in terms of concentration of airborne particles in cleanrooms and clean zones; and separative devices as defined in ISO 14644‑7. Only particle populations having cumulative distributions based on threshold (lower limit) particle sizes ranging from 0,1 µm to 5 µm are considered for classification purposes.

The Rotronic Monitoring System is a range of hardware devices and a FDA CFR 21 Part 11 and EU Annex 11 compliant software (link to hardware and software) that help end users comply with the above mentioned requirements.

IATA:

IATA: International Air Transport Association

TCR: Temperature Control Regulations

WHO: World Health Organisation

CEIV: Center of Excellence for Independent Validators

The International Air Transport Association (IATA) is the trade association for the world’s airlines, representing some 290 airlines or 82% of total air traffic. The Temperature Control Regulations (2016) is a guide targeted at the stakeholders (shipper, freight forwarder, airline…) involved in the transport and handling of pharmaceutical products to safely meet the requirements. The TCR provides the requirements and standards for the transportation and handling of time and temperature sensitive healthcare products, including pharmaceutical product information based upon the WHO guidelines.

Due to the lack of compliance, standardisation, accountability and transparency across the air transport supply chain, the IATA have created a Center of Excellence for Independent Validators (CEIV) in pharmaceutical logistics with the aim of helping the industry to improve the transport and handling of these products to meet the requirements of shippers and manufacturers:

  • European Union Good Distribution Practices (EU GDP)
  • World Health Organisation Annex 5
  • United States Pharmacopeia Standards.

CEIV Pharma ensure that facilities, equipment, operations and staff comply with all applicable standards, regulations and guidelines expected from pharmaceutical manufacturers.

The Rotronic Monitoring System is a range of hardware devices and a FDA CFR 21 Part 11 and EU Annex 11 compliant software (link to hardware and software) that help end users comply with the above mentioned requirements.

HACCP: Hazard Analysis and Critical Control Point

The United States Food and Drug Administration (FDA) states that hazard analysis and critical control points (HACCP) is a management system in which food safety is addressed through the analysis and control of biological, chemical, and physical hazards from raw material production, procurement and handling, to manufacturing, distribution and consumption of the finished product. HACCP is a systematic approach to the identification, evaluation, and control of food safety hazards based on the following seven principles:

  1. Conduct a hazard analysis.
  2. Determine the critical control points (CCPs).
  3. Establish critical limits.
  4. Establish monitoring procedures.
  5. Establish correction actions.
  6. Establish verification procedures.
  7. Establish record-keeping and documentation procedures.

The Rotronic Monitoring System will measure and help monitor all CCPs and the required scientifically based critical limits (temperature, time, relative humidity, water activity...) defined after the hazard analysis. All events are registered within RMS and documents can be stored within the system, based upon the internal systems used, RMS can also offer a solution for Principle 7; Establish record-keeping and documentation procedures.