What is 21 CFR Part 11

Title 21 in the federal regulations are regulations which regulates the Food and Drugs in United States of America. Part 11 within this Code of Federal Regulations is related to US Food and Drug Administration (FDA) guidelines about electronic records and electronic signatures.
The regulations in this part set forth the criteria under which the US FDA considers electronic records, electronic signatures, and handwritten signatures executed to electronic records to be trustworthy, reliable, and generally equivalent to paper records and handwritten signatures executed on paper. 21 cfr Part 11 became effective in August 1997

21 CFR Part 11, states the requirements for procedures for creating, modifying, maintaining, archiving, retrieving, and transmitting electronic records and electronic signatures by virtue of which they can be considered or rendered to be trustworthy, reliable and equivalent to paper records.

CFR 21 Part 11 requires that a drug manufacturer ,medical device manufacturer and biologics developers and all other industries regulated by FDA to implement controls for their electronic system, like audits, documentation for software , system validations, audit trails, electronic signatures, and for systems which are handling the electronic data which is required to be maintained by the FDA predicate rules or the systems which process data used for demonstration of compliance of a requirement or a rule.

CFR21 part 11 also applies to the electronic submissions made to FDA like ANDA, NDA.
Many drug manufacturers and felt that the 21CFR11 is bit difficult to implement in the way it is desired in the regulations and US FDA has listed the points why they gave relaxations at some points of implementation in CFR 21 part 11 are as follows.

1.Unnecessarily restrict the use of electronic technology in a manner that is inconsistent with FDA’s stated intent in issuing the rule.
2.Significantly increase the costs of compliance to an extent that was not contemplated at the time the rule was drafted.
3.Discourage innovation and technological advances without providing a significant public health benefit.
In an effort towards proper implementation US FDA released a guidance document in August of 2003 the

US FDA published the ‘Part 11, Electronic Records; Electronic Signatures — Scope and Application’ guidance which describes how US FDA intends to exercise enforcement discretion and sets forth the following considerations related to Part 11:

US FDA has made an announcement on 8-july-2010 with respect to implementation of cfr 21 part 11 as follows

The US (FDA) will be conducting a series of inspections in an effort to evaluate industry’s compliance and understanding of Part 11 in light of the enforcement discretion described in the August 2003 ‘Part 11, Electronic Records; Electronic Signatures — Scope and Application’ guidance (Guidance). The Agency intends to take appropriate action to enforce Part 11 requirements for issues raised during the inspections that do not fall under the enforcement discretion discussed in the Guidance.

1. CFR 21 Part 11 remains in effect since the issuance of the guidance and the exercise of enforcement discretion applies as identified in the guidance.
2.The guidance sets out certain conditions related to the validation, audit trail, record retention, record copying, and legacy systemswhere the US FDA says they do not intend to take enforcement action to enforce compliance. also FDA mentions that ‘Conversely, violations of CFR 21 part 11 requirements that do not fall within the guidance’s discretion can lead to enforcement action to enforce compliance depending on the importance of the violation’.
3.Records must also be maintained or submitted in accordance with regulatory requirements outside of Part 11, and we will enforce all predicate rule requirements, including predicate rule record and recordkeeping requirements.

Only part so far routinely enforced is access control, where as 21CFR11 the “predicate rules” which required the records to be kept in the first place are still in effect. If electronic records are illegible, inaccessible, or corrupted the manufacturers are still subject to those requirements.

Paper documents are still considered if a pharma company keeps “hard copies” of all mandatory records, for regulatory purpose the paper documents are also considered as authoritative documents.
A drug manufacturer is required to make a claim very carefully about the “hard copies” of mandatory records are authoritative document. Hence to the “hard copy should be an accurate and complete copy of its electronic source and can be used for regulatory purposes.

US FDA is expected to begin conducting the CFR 21 Part 11 focused inspections soon.

Also see CFR 21 part 11 and its application on computarised systems used in clinical trials US FDA guidelines, below

CFR 21 part 11 and its application on computarised systems used in clinical trials

CFR 21 part 11 and its application on computerised systems used in clinical trials , clinical studies , clinical investigations.

There is an increasing use of computerized systems in clinical trials to generate and maintain
source data and source documentation on each clinical trial subject. Such electronic source data and source documentation must meet the same fundamental elements of data quality (e.g.,attributable, legible, contemporaneous, original and accurate) that are expected of paper records and must comply with all applicable statutory and regulatory requirements. FDA’s acceptance of data fromclinical trials for decision-making purposes depends on US FDA’s ability to verify the quality and integrity of the data during US FDA’S on-site inspections and audits. (21 CFR 312, 511.1(b), and 812).

21 CFR part 11 was issued in march 1997 which provides criteria for acceptance by US FDA,under certain circumstances, of electronic records, electronic signatures, and handwritten signatures executed to electronic records as equivalent to paper records and handwritten signatures executed on paper.

After the effective date of 21 CFR part 11, significant concerns regarding the interpretation and implementation of part 11 were raised by both US FDA and Industry. As a result, US FDA had decided to reexamine 21 CFR part 11 with the possibility of proposing additional rulemaking, and exercising enforcement discretion regarding enforcement of certain part 11 requirements in the interim.

In May 2007 US FDA issued a guidance to address above issue , ie. Computerized Systems Used in Clinical Investigations , the recommendations made by US FDA are not legally enforceable but is the current thinking of US FDA and one should learn through this about how to implement 21 cfr part 11 in computerized systems used in clinical trials , clinical studies , clinical investigations .

It has given recommendations to sponsors of clinical trial , clinical study , contract research organizations (CROs), data management centers, clinical investigators, and institutional review boards (IRBs), regarding the use of computerized systems in clinical investigations. The computerized system applies to records in electronic form that are used to create, modify, maintain, archive, retrieve, or transmit clinical data required to be maintained, or submitted to the FDA. Because the source data are necessary for the reconstruction and evaluation of the study to determine the safety of food and color additives and safety and effectiveness of new human and animal drugs and medical devices,

Standard Operating Procedures with respect to CFR 21 PART 11. 

There should be specific procedures and controls in place when using computerized systems to create, modify, maintain, or transmit electronic records, including when collecting source data at clinical trial sites. A list of recommended standard operating procedures(SOPs) is provided in such SOPs should be maintained either on-site or be remotely accessible through electronic files as part of the specific study records, and the SOPs should be made available for use by personnel and for inspection by FDA.

Standard operating procedures (SOPs) and documentation pertinent to the use of a computerized
system should be made available for use by appropriate study personnel at the clinical site or
remotely and for inspection by FDA. The SOPs should include, but are not limited to, the
following processes.


*System setup/installation (including the description and specific use of software,
hardware, and physical environment and the relationship)
*System operating manual
*Validation and functionality testing
*Data collection and handling (including data archiving, audit trails, and risk assessment)
*System maintenance (including system decommissioning)
*System security measures
*Change control
*Data backup, recovery, and contingency plans
*Alternative recording methods (in the case of system unavailability)
*Computer user training
*Roles and responsibilities of sponsors, clinical sites and other parties with respect to the
use of computerized systems in the clinical trials

Also see 
Continue reading this article here 21 cfr part 11 FDA guidelines regarding the use of computerized systems in clinical investigations. as shown below

US FDA revised and issued rule for reporting safety information /adverse events / adverse reactions during clinical trials.

US FDA revised and issued rule for reporting safety information /adverse events / adverse reactions during clinical trials.

The United States Food and Drug Administration on 28-09-2010 has revised and issued its final rule for reporting an adverse reaction or adverse event in any clinical trial , where in earlier rule it was not mandatory to report certain adverse reaction or adverse event .

This rule has made it mandatory for a sponsor or investigator of a clinical trial to report with in 15 days of becoming aware about adverse reaction or adverse event.

The reports should include following findings.
1.Findings from clinical or epidemiological studies that suggest a significant risk to study participants
2.Serious suspected adverse reactions that occur at a rate higher than expected
3.Serious adverse events from bioavailability studies which determine what percentage and at what rate drug is absorbed by the bloodstream and bioequivalence studies which determine whether a generic drug has the same bioavailability as the brand name drug

This rule also specifies with example about when one should immediately report an ADR or ADE to US FDA and when one should wait till next event to be observed so that it will clarify all questions and drought amongst sponsors or investigators of a clinical trial of a of investigational drugs and biologics.

US FDA has also made it mandatory to report all adverse reactions and adverse event to be reported while performing, bioeqivalencestudy for ANDA and .Bioavailability and pharmacokinetic studies and any epidemiological study which suggest that the adverse reaction or adverse event may cause serious harm to public health.

It is one of the remarkable steps towards ensuring public health, in some of latest happening.
This final rule will make easier for US FDA to review of critical safety information and help them to monitor the safety of investigational drugs and biologics

These changes will be able to protect health of people participated in a clinical trials, also in new rule some definitions and reporting standards are also revised so as to make them more consistent with those by ICH (International organizations, the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use ) and the World Health Organization’s Council for International Organizations of Medical Sciences. The new rule is made to ensure harmonized reporting of globally conducted clinical trials.

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Title 21 CFR Part 11 of the Code of Federal Regulations deals with the United States Food and Drug Administration (FDA) guidelines on electronic records and electronic signatures (ERES). Part 11, as it is commonly called, defines the criteria under which electronic records and electronic signatures are considered to be trustworthy, reliable and equivalent to paper records (Title 21 CFR Part 11 Section 11.1 (a)).

Practically speaking, Part 11 requires drug makersmedical device manufacturers, biotech companies, biologics developers, CROs, and other FDA-regulated industries, with some specific exceptions, to implement controls, including audits, system validations, audit trails, electronic signatures, and documentation for software and systems involved in processing electronic data that are (a) required to be maintained by the FDA predicate rules or (b) used to demonstrate compliance to a predicate rule. A predicate rule is any requirement set forth in the Federal Food, Drug and Cosmetic Act, the Public Health Service Act, or any FDA regulation other than Part 11. [1]

The rule also applies to submissions made to the FDA in electronic format (e.g., a New Drug Application) but not to paper submissions by electronic methods (i.e., faxes). It specifically does not require the 21CFR11 requirement for record retention for tracebacks by food manufacturers. Most food manufacturers are not otherwise explicitly required to keep detailed records, but electronic documentation kept for HACCP and similar requirements must meet these requirements.

As of 2007, broad sections of the regulation have been challenged as excessive, and the FDA has stated in guidance that it will exercise enforcement discretion on many parts of the rule. This has led to confusion on exactly what is required, and the rule is being revised. (An update was posted on April 1, 2010 on the FDA Website). In practice, the requirements on access controls are the only part routinely enforced. The “predicate rules” which required the records to be kept in the first place are still in effect. If electronic records are illegible, inaccessible, or corrupted the manufacturers are still subject to those requirements.

If a regulated firm keeps “hard copies” of all required records, the paper documents can be considered to be the authoritative document for regulatory purposes and the computer system need not meet these requirements.[citation needed] Firms should be careful to make a claim that “hard copies” of required records are authoritative document. In order for the “hard copy” produced from its electronic source be considered as the authoritative document, the “hard copy” must (a) be a complete and accurate copy of its electronic source and (b) be used exclusively for regulated activities. The current technical architecture of computer systems increasingly makes the burden of proof for the complete and accurate copy requirement extremely high.[citation needed]


  • Subpart A – General Provisions
    • Scope
    • Implementation
    • Definitions
  • Subpart B – Electronic Records
    • Controls for closed systems
    • Controls for open systems
    • Signature manifestations
    • Signature/record linking
  • Subpart C – Electronic Signatures
    • General requirements
    • Electronic signatures and controls
    • Controls for identification codes/passwords


Various keynote speeches by FDA insiders early in the 21st century (in addition to high-profile audit findings focusing on computer system compliance) resulted in many companies scrambling to mount a defense against rule enforcement that they were procedurally and technologically unprepared for. Many vendors of software and instrumentation released Part 11 “compliant” updates, which proved to be either incomplete or insufficient to fully comply with the rule. Complaints about the wasting of critical resources, non-value added aspects, in addition to confusion within the drug, medical device, biotech/biologic and other industries about the true scope and enforcement aspects of Part 11 resulted in the FDA release of:

This document was intended to clarify how Part 11 should be implemented and would be enforced. But, as with all FDA guidances, it was not intended to convey the full force of law—rather, it expressed the FDA’s “current thinking” on Part 11 compliance. Many within the industry, while pleased with the more limited scope defined in the guidance, complained that, in some areas, the 2003 guidance contradicted requirements in the 1997 Final Rule.

In May 2007, the FDA issued the final version of their guidance on computerized systems in clinical investigations. This guidance supersedes the guidance of the same name dated April 1999; and supplements the guidance for industry on Part 11, Electronic Records; Electronic Signatures — Scope and Application and the Agency’s international harmonization efforts when applying these guidances to source data generated at clinical study sites.

FDA had previously announced that a new Part 11 would be released late 2006. The Agency has since pushed that release date back. The FDA has not announced a revised time of release. John Murray, member of the Part 11 Working Group (the team at FDA developing the new Part 11), has publicly stated that the timetable for release is “flexible.”

See also

External links



DR ANTHONY MELVIN CRASTO, Born in Mumbai in 1964 and graduated from Mumbai University, Completed his Ph.D from ICT, 1991,Matunga, Mumbai, India, in Organic Chemistry, The thesis topic was Synthesis of Novel Pyrethroid Analogues, Currently he is working with GLENMARK PHARMACEUTICALS LTD, Research Centre as Principal Scientist, Process Research (bulk actives) at Mahape, Navi Mumbai, India. Total Industry exp 30 plus yrs, Prior to joining Glenmark, he has worked with major multinationals like Hoechst Marion Roussel, now Sanofi, Searle India Ltd, now RPG lifesciences, etc. He has worked with notable scientists like Dr K Nagarajan, Dr Ralph Stapel, Prof S Seshadri, Dr T.V. Radhakrishnan and Dr B. K. Kulkarni, etc, He did custom synthesis for major multinationals in his career like BASF, Novartis, Sanofi, etc., He has worked in Discovery, Natural products, Bulk drugs, Generics, Intermediates, Fine chemicals, Neutraceuticals, GMP, Scaleups, etc, he is now helping millions, has 9 million plus hits on Google on all Organic chemistry websites. His friends call him Open superstar worlddrugtracker. His New Drug Approvals, Green Chemistry International, All about drugs, Eurekamoments, Organic spectroscopy international, etc in organic chemistry are some most read blogs He has hands on experience in initiation and developing novel routes for drug molecules and implementation them on commercial scale over a 30 year tenure till date Dec 2017, Around 35 plus products in his career. He has good knowledge of IPM, GMP, Regulatory aspects, he has several International patents published worldwide . He has good proficiency in Technology transfer, Spectroscopy, Stereochemistry, Synthesis, Polymorphism etc., He suffered a paralytic stroke/ Acute Transverse mylitis in Dec 2007 and is 90 %Paralysed, He is bound to a wheelchair, this seems to have injected feul in him to help chemists all around the world, he is more active than before and is pushing boundaries, He has 9 million plus hits on Google, 2.5 lakh plus connections on all networking sites, 50 Lakh plus views on dozen plus blogs, He makes himself available to all, contact him on +91 9323115463, email amcrasto@gmail.com, Twitter, @amcrasto , He lives and will die for his family, 90% paralysis cannot kill his soul., Notably he has 19 lakh plus views on New Drug Approvals Blog in 216 countries......http://newdrugapprovals.wordpress.com/ , He appreciates the help he gets from one and all, Friends, Family, Glenmark, Readers, Wellwishers, Doctors, Drug authorities, His Contacts, Physiotherapist, etc

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