Guidance for Industry 
Computerized Systems Used in 
Clinical Investigations 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration (FDA) 
Office of the Commissioner (OC) 
May 2007  Contains Nonbinding Recommendations 
 
 
Guidance for Industry 
Computerized Systems Used in 
Clinical Investigations 
 
Additional copies are available from: 
 
Office of Training and Communication 
Division of Drug Information 
Center for Drug Evaluation and Research (CDER) 
 (Tel) 301-827-4573 
 http://www.fda.gov/cder/guidance/index.htm 
or 
 Office of Communication, Training and  
Manufacturers Assistance  
Center for Biologics Evaluation and Research 
 http://www.fda.gov/cber/guidelines.htm 
(Tel) 800-835-4709 or 301-827-1800 
or 
Office of Communication, Education, and Radiation Programs 
Division of Small Manufacturers, International, and Consumer Assistance 
Center for Devices and Radiological Health 
http://www.fda.gov/cdrh/ggpmain.html 
Email: dsmica@fda.hhs.gov 
Fax: 240.276.3151 
(Tel) Manufacturers and International Assistance: 800.638.2041 or 240.276.3150 
or 
Office of Food Additive Safety 
Center for Food, Safety and Applied Nutrition 
(Tel) 301-436-1200 
http://www.cfsan.fda.gov/guidance.html 
or 
Communications Staff, HFV-12 
Center for Veterinary Medicine 
 (Tel) 240-276-9300 
http://www.fda.gov/cvm/guidance/published 
 or  
Good Clinical Practice Programs 
Office of the Commissioner 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Office of the Commissioner (OC) 
May 2007 
  Contains Nonbinding Recommendations 
 
TABLE OF CONTENTS 
 
 
I.  INTRODUCTION.............................................................................................................1 
II.  BACKGROUND...............................................................................................................2 
III.  SCOPE...............................................................................................................................3 
IV.  RECOMMENDATIONS..................................................................................................3 
A.  Study Protocols..............................................................................................................................3 
B.  Standard Operating Procedures...................................................................................................3 
C.  Source Documentation and Retention..........................................................................................4 
D.  Internal Security Safeguards........................................................................................................4 
1. Limited Access.................................................................................................................................4 
2. Audit Trails......................................................................................................................................4 
3.  Date/Time Stamps............................................................................................................................5 
E.  External Security Safeguards.......................................................................................................5 
F.  Other System Features..................................................................................................................6 
1. Direct Entry of Data........................................................................................................................6 
2. Retrieving Data................................................................................................................................6 
3. Dependability System Documentation.............................................................................................6 
4. System Controls...............................................................................................................................6 
5. Change Controls..............................................................................................................................7 
G.  Training of Personnel....................................................................................................................7 
DEFINITIONS..............................................................................................................................8 
REFERENCES..............................................................................................................................9 
APPENDIX A..............................................................................................................................10 
  Contains Nonbinding Recommendations 
 
 
1
Guidance for Industry  
Computerized Systems Used in Clinical Investigations 
 
 
This guidance represents the Food and Drug Administration's (FDA's) current thinking on this topic.  It 
does not create or confer any rights for or on any person and does not operate to bind FDA or the public.  
You can use an alternative approach if the approach satisfies the requirements of the applicable statutes 
and regulations. If you want to discuss an alternative approach, contact the FDA staff responsible for 
implementing this guidance.  If you cannot identify the appropriate FDA staff, call the appropriate 
number listed on the title page of this guidance.  
 
 
 
 
I.  INTRODUCTION  
 
This document provides to sponsors, contract research organizations (CROs), data management 
centers, clinical investigators, and institutional review boards (IRBs), recommendations 
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 
data2 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,3 and 
medical devices, this guidance is intended to assist in ensuring confidence in the reliability, 
quality, and integrity of electronic source data and source documentation (i.e., electronic 
records).   
 
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 efforts4 when applying these 
guidances to source data generated at clinical study sites.  
                                                 
1 This guidance has been prepared by the Office of Critical Path Programs, the Good Clinical Practice Program, and 
the Office of Regulatory Affairs in cooperation with Bioresearch Monitoring Program Managers for each Center 
within the Food and Drug Administration.  
2 Under 21 CFR 312.62(b), reference is made to records that are part of case histories as supporting data; the ICH 
E6 Good Clinical Practice consolidated guidance uses the term source documents.  For the purpose of this 
guidance, these terms describe the same information and have been used interchangeably. 
 
3 Human drugs include biological drugs. 
 
4 In August 2003, FDA issued the guidance for industry entitled Part 11, Electronic Records; Electronic Signatures- 
Scope and Application clarifying that the Agency intends to interpret the scope of part 11 narrowly and to exercise 
enforcement discretion with regard to part 11 requirements for validation, audit trails, record retention, and record 
copying.  In 1996, the International Conference on Harmonisation of Technical Requirements for Registration of 
Pharmaceuticals for Human Use (ICH) issued E6 Good Clinical Practice: Consolidated Guidance. 
 
1  Contains Nonbinding Recommendations 
 
 
FDA's guidance documents, including this guidance, do not establish legally enforceable 
responsibilities.  Instead, guidances describe the Agency's current thinking on a topic and should 
be viewed only as recommendations, unless specific regulatory or statutory requirements are 
cited.  The use of the word should in Agency guidances means that something is suggested or 
recommended, but not required.  
 
 
II.  BACKGROUND  
 
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,5 and accurate) that are expected of paper records 
and must comply with all applicable statutory and regulatory requirements.  FDA's acceptance of 
data from clinical trials for decision-making purposes depends on FDA's ability to verify the 
quality and integrity of the data during FDA on-site inspections and audits.  (21 CFR 312, 
511.1(b), and 812).   
 
In March 1997, FDA issued 21 CFR part 11, which provides criteria for acceptance by 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 FDA and 
industry.  As a result, we 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.   
 
This guidance finalizes the draft guidance for industry entitled Computerized Systems Used in 
Clinical Trials, dated September 2004 and supplements the guidance for industry entitled Part 
11, Electronic Records; Electronic Signatures  Scope and Application (Scope and Application 
Guidance), dated August 2003.  The Scope and Application Guidance clarified that the Agency 
intends to interpret the scope of part 11 narrowly and to exercise enforcement discretion with 
regard to part 11 requirements for validation, audit trails, record retention, and record copying.  
However, other Part 11 provisions remain in effect. 
 
The approach outlined in the Scope and Application Guidance, which applies to electronic 
records generated as part of a clinical trial, should be followed until such time as Part 11 is 
amended. 
 
 
                                                 
5 FDA is allowing original documents to be replaced by copies provided the copies are identical and have been 
verified as such (See, e.g., FDA Compliance Policy Guide # 7150.13).  See Definitions section for a definition of 
original data. 
 
2  Contains Nonbinding Recommendations 
 
III.  SCOPE 
 
The principles outlined in this guidance should be used for computerized systems that contain 
any data that are relied on by an applicant in support of a marketing application, including 
computerized laboratory information management systems that capture analytical results of tests 
conducted during a clinical trial.  For example, the recommendations in this guidance would 
apply to computerized systems that create source documents (electronic records) that satisfy the 
requirements in 21 CFR 312.62(b) and 812.140(b), such as case histories.  This guidance also 
applies to recorded source data transmitted from automated instruments directly to a 
computerized system (e.g., data from a chemistry autoanalyser or a Holter monitor to a 
laboratory information system).   This guidance also applies when source documentation is 
created in hardcopy and later entered into a computerized system, recorded by direct entry into a 
computerized system, or automatically recorded by a computerized system (e.g., an ECG 
reading).  The guidance does not apply to computerized medical devices that generate such data 
and that are otherwise regulated by FDA. 
 
 
IV.  RECOMMENDATIONS 
 
This guidance provides the following recommendations regarding the use of computerized 
systems in clinical investigations. 
 
A.  Study Protocols 
 
Each specific study protocol should identify each step at which a computerized system will be 
used to create, modify, maintain, archive, retrieve, or transmit source data.  This information can 
be included in the protocol at the time the investigational new drug application (IND), 
Investigational Device Exemption (IDE), or Notice of Claimed Investigational Exemption for a 
New Animal Drug containing the protocols is submitted or at any time after the initial 
submission.   
 
The computerized systems should be designed: (1) to satisfy the processes assigned to these 
systems for use in the specific study protocol (e.g., record data in metric units, blind the study), 
and (2) to prevent errors in data creation, modification, maintenance, archiving, retrieval, or 
transmission (e.g., inadvertently unblinding a study). 
 
B.  Standard Operating Procedures 
 
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 
Appendix A.  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. 
 
3  Contains Nonbinding Recommendations 
 
C.  Source Documentation and Retention 
 
When original observations are entered directly into a computerized system, the electronic record 
is the source document.  Under 21 CFR 312.62, 511.1(b)(7)(ii) and 812.140, the clinical 
investigator must retain records required to be maintained under part 312,  511.1(b), and part 
812, for a period of time specified in these regulations.  This requirement applies to the retention 
of the original source document, or a copy of the source document.   
 
When source data are transmitted from one system to another (e.g., from a personal data assistant 
to a sponsors server), or entered directly into a remote computerized system (e.g., data are 
entered into a remote server via a computer terminal that is located at the clinical site), or an 
electrocardiogram at the clinical site is transmitted to the sponsors computerized system, a copy 
of the data should be maintained at another location, typically at the clinical site but possibly at 
some other designated site.  Copies should be made contemporaneously with data entry and 
should be preserved in an appropriate format, such as XML, PDF or paper formats.   
   
D.  Internal Security Safeguards 
 
1.  Limited Access 
 
Access must be limited to authorized individuals (21 CFR 11.10(d).  This requirement can be 
accomplished by the following recommendations.  We recommend that each user of the system 
have an individual account.  The user should log into that account at the beginning of a data 
entry session, input information (including changes) on the electronic record, and log out at the 
completion of data entry session.  The system should be designed to limit the number of log-in 
attempts and to record unauthorized access log-in attempts.   
 
Individuals should work only under their own password or other access key and not share these 
with others.  The system should not allow an individual to log onto the system to provide another 
person access to the system.  We also recommend that passwords or other access keys be 
changed at established intervals commensurate with a documented risk assessment.  
 
When someone leaves a workstation, the person should log off the system.  Alternatively, an 
automatic log off may be appropriate for long idle periods.  For short periods of inactivity, we 
recommend that a type of automatic protection be installed against unauthorized data entry (e.g., 
an automatic screen saver can prevent data entry until a password is entered). 
 
2.  Audit Trails 
 
It is important to keep track of all changes made to information in the electronic records that 
document activities related to the conduct of the trial (audit trails).  The use of audit trails or 
other security measures helps to ensure that only authorized additions, deletions, or alterations of 
information in the electronic record have occurred and allows a means to reconstruct significant 
details about study conduct and source data collection necessary to verify the quality and 
integrity of data.  Computer-generated, time-stamped audit trails or other security measures can 
4  Contains Nonbinding Recommendations 
 
also capture information related to the creation, modification, or deletion of electronic records 
and may be useful to ensure compliance with the appropriate regulation.  
 
The need for audit trails should be determined based on a justified and documented risk 
assessment that takes into consideration circumstances surrounding system use, the likelihood 
that information might be compromised, and any system vulnerabilities.  Should it be decided 
that audit trails or other appropriate security measures are needed to ensure electronic record 
integrity, personnel who create, modify, or delete electronic records should not be able to modify 
the documents or security measures used to track electronic record changes.  Computer-
generated, time-stamped electronic audits trails are the preferred method for tracking changes to 
electronic source documentation. 
 
Audit trails or other security methods used to capture electronic record activities should describe 
when, by whom, and the reason changes were made to the electronic record.  Original 
information should not be obscured though the use of audit trails or other security measures used 
to capture electronic record activities. 
 
3.   Date/Time Stamps 
 
Controls should be established to ensure that the system's date and time are correct.  The ability 
to change the date or time should be limited to authorized personnel, and such personnel should 
be notified if a system date or time discrepancy is detected.  Any changes to date or time should 
always be documented.  We do not expect documentation of time changes that systems make 
automatically to adjust to daylight savings time conventions.  
 
We recommend that dates and times include the year, month, day, hour, and minute and 
encourage synchronization of systems to the date and time provided by international standard-
setting agencies (e.g., U.S. National Institute of Standards and Technology provides information 
about universal time, coordinated (UTC)).  
 
Computerized systems are likely to be used in multi-center clinical trials and may be located in 
different time zones.  For systems that span different time zones, it is better to implement time 
stamps with a clear understanding of the time zone reference used.  We recommend that system 
documentation explain time zone references as well as zone acronyms or other naming 
conventions.  
 
E.  External Security Safeguards 
 
In addition to internal safeguards built into a computerized system, external safeguards should be 
put in place to ensure that access to the computerized system and to the data is restricted to 
authorized personnel.  Staff should be kept thoroughly aware of system security measures and 
the importance of limiting access to authorized personnel. 
 
Procedures and controls should be put in place to prevent the altering, browsing, querying, or 
reporting of data via external software applications that do not enter through the protective 
system software.  
5  Contains Nonbinding Recommendations 
 
 
You should maintain a cumulative record that indicates, for any point in time, the names of 
authorized personnel, their titles, and a description of their access privileges.  That record should 
be kept in the study documentation, accessible for use by appropriate study personnel and for 
inspection by FDA investigators. 
 
We also recommend that controls be implemented to prevent, detect, and mitigate effects of 
computer viruses, worms, or other potentially harmful software code on study data and software. 
 
F.  Other System Features 
 
1.  Direct Entry of Data 
 
We recommend that you incorporate prompts, flags, or other help features into your 
computerized system to encourage consistent use of clinical terminology and to alert the user to 
data that are out of acceptable range.  You should not use programming features that 
automatically enter data into a field when the field is bypassed (default entries).  However, you 
can use programming features that permit repopulation of information specific to the subject.  To 
avoid falsification of data, you should perform a careful analysis in deciding whether and when 
to use software programming instructions that permit data fields to be automatically populated.  
   
2.  Retrieving Data  
 
The computerized system should be designed in such a way that retrieved data regarding each 
individual subject in a study is attributable to that subject.  Reconstruction of the source 
documentation is essential to FDAs review of the clinical study submitted to the Agency.  
Therefore, the information provided to FDA should fully describe and explain how source data 
were obtained and managed, and how electronic records were used to capture data.   
It is not necessary to reprocess data from a study that can be fully reconstructed from available 
documentation.  Therefore, the actual application software, operating systems, and software 
development tools involved in the processing of data or records need not be retained. 
 
3.  Dependability System Documentation 
 
For each study, documentation should identify what software and hardware will be used to 
create, modify, maintain, archive, retrieve, or transmit clinical data.  Although it need not be 
submitted to FDA, this documentation should be retained as part of the study records and be 
available for inspection by FDA (either on-site or remotely accessible).  
 
4.  System Controls 
 
When electronic formats are the only ones used to create and preserve electronic records, 
sufficient backup and recovery procedures should be designed to protect against data loss.  
Records should regularly be backed up in a procedure that would prevent a catastrophic loss and 
ensure the quality and integrity of the data.  Records should be stored at a secure location 
6  Contains Nonbinding Recommendations 
 
specified in the SOP.  Storage should typically be offsite or in a building separate from the 
original records. 
 
We recommend that you maintain backup and recovery logs to facilitate an assessment of the 
nature and scope of data loss resulting from a system failure. 
 
5.  Change Controls 
 
The integrity of the data and the integrity of the protocols should be maintained when making 
changes to the computerized system, such as software upgrades, including security and 
performance patches, equipment, or component replacement, or new instrumentation.  The 
effects of any changes to the system should be evaluated and some should be validated 
depending on risk.  Changes that exceed previously established operational limits or design 
specifications should be validated.  Finally, all changes to the system should be documented. 
 
G.  Training of Personnel 
 
Those who use computerized systems must determine that individuals (e.g., employees, 
contractors) who develop, maintain, or use computerized systems have the education, training 
and experience necessary to perform their assigned tasks (21 CFR 11.10(i)).   
 
Training should be provided to individuals in the specific operations with regard to computerized 
systems that they are to perform.  Training should be conducted by qualified individuals on a 
continuing basis, as needed, to ensure familiarity with the computerized system and with any 
changes to the system during the course of the study.   
 
We recommend that computer education, training, and experience be documented. 
7  Contains Nonbinding Recommendations 
 
 
DEFINITIONS 
 
 
The following is a list of definitions for terms used in, and for the purposes of, this guidance 
document.   
 
Audit Trail:  For the purpose of this guidance, an audit trail is a process that captures details 
such as additions, deletions, or alterations of information in an electronic record without 
obliterating the original record.  An audit trail facilitates the reconstruction of the course of such 
details relating to the electronic record. 
 
Certified Copy:  A certified copy is a copy of original information that has been verified, as 
indicated by a dated signature, as an exact copy having all of the same attributes and information 
as the original. 
  
Computerized System:  A computerized system includes computer hardware, software, and 
associated documents (e.g., user manual) that create, modify, maintain, archive, retrieve, or 
transmit in digital form information related to the conduct of a clinical trial. 
 
Direct Entry:  Direct entry is recording data where an electronic record is the original means of 
capturing the data. Examples are the keying by an individual of original observations into a 
system, or automatic recording by the system of the output of a balance that measures subjects 
body weight. 
 
Electronic Record:  An electronic record is any combination of text, graphics, data, audio, 
pictorial, or other information representation in digital form that is created, modified, maintained, 
archived, retrieved, or distributed by a computer system. 
 
Original data: For the purpose of this guidance, original data are those values that represent the 
first recording of study data.   FDA is allowing original documents and the original data recorded 
on those documents to be replaced by copies provided the copies are identical and have been 
verified as such (see FDA Compliance Policy Guide # 7150.13). 
 
Source Documents:  Original documents and records including, but not limited to, hospital 
records, clinical and office charts, laboratory notes, memoranda, subjects' diaries or evaluation 
checklists, pharmacy dispensing records, recorded data from automated instruments, copies or 
transcriptions certified after verification as being accurate and complete, microfiches, 
photographic negatives, microfilm or magnetic media, x-rays, subject files, and records kept at 
the pharmacy, at the laboratories, and at medico-technical departments involved in a clinical 
trial. 
 
Transmit:  Transmit is to transfer data within or among clinical study sites, contract research 
organizations, data management centers, sponsors, or to FDA. 
8  Contains Nonbinding Recommendations 
 
REFERENCES 
 
FDA, 21 CFR Part 11, "Electronic Records; Electronic Signatures; Final Rule."  Federal 
Register Vol. 62, No. 54, 13429, March 20, 1997. 
FDA, Compliance Program Guidance Manual, "Compliance Program 7348.810  Bioresearch 
Monitoring - Sponsors, Contract Research Organizations and Monitors," February 21, 
2001. 
FDA, Compliance Program Guidance Manual, "Compliance Program 7348.811 - Bioresearch 
Monitoring - Clinical Investigators," September 30, 2000. 
FDA, Good Clinical Practice VICH GL9. 
FDA, Guideline for the Monitoring of Clinical Investigations. 
FDA, Information Sheets for Institutional Review Boards and Clinical Investigators. 
http://www.fda.gov/ic/ohrt/irbs/default.htm 
FDA, E6 Good Clinical Practice: Consolidated Guidance. 
http://www.fda.gov/cder/guidance/959fnl.pdf. 
FDA, Part 11, Electronic Records; Electronic Signatures  Scope and Application, 2003. 
FDA, General Principles of Software Validation; Guidance for Industry and FDA Staff. 
 
9  Contains Nonbinding Recommendations 
 
 
APPENDIX A 
 
 
 
STANDARD OPERATING PROCEDURES 
 
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 
 
 
 
 
 
 
 
10