1/35
1 3 2 / 5 3 6 4 21 CFR Part 11 7 5 8 6 Closed System / Access Control 9 61 : ID/Password 9 62 9 63 9 64 (System Security Architecture) 9 65 ID/Password 10 66 Access Log 11 67 (HR) 11 68 12 7 Electronic Record 13 8 Audit Trail 14 81 Audit Trail? 14 82 Audit Trail 14 83 Trigger 15 831 Trigger 15 832 Audit Trail Table 15 833 Trigger Script 17 9 Electronic Signature 19 91 Electronic Signature? 19 92 20 921 20 922 Table (rtsignset) 21 923 Table (rtsignsetdt) 21 924 Table (rtsign) 22 925 22 93 ID/Password 24 94 24 95 24 96 26 10 27 Part 11 28 2/35
1, GMP, KGMP, GMP (Electronic Record ER 1 ) (Electronic Signature ES) FDA 21 CFR Part 11 ( Part11 ) Part11, FDA, Part11 Part11 Part11, GMP / /, GMP Part11, (ERP ) GMP Part11 ERP,,, Validation Validation GMP 1 ER Entity Relationship ER Electronic Record ER(Entity Relationship) 3/35
Validation Validation [ISPE GAMP Forum, GAMP4 ] [GAMP4] [, Automated System Validation ] (?) Part11 Part11 Part11 Part11 Par11, 4/35
2 / Part11 Part11?? Access Electronic Record Audit Trail Electronic Signature Part11 Part11 Part11 4 Data Data PC,, Data DBMS (DBMS ) DBMS Part11 5/35
3, ( ) DBMS RDB GMP Validation Part11 ( ) 6/35
4 21 CFR Part 11 Part11 [, 21 CFR Part 11 ] Part 11 1997 8 20 (FDA) Part11,,, FDA,,,,, Part 11 41 23, 19 Part 11,, Part 11 Part11 [ Part11 ] ( 5 ) (Closed System) 7/35
5 o (Access Control) o ID/Password o Audit Trail 8/35
6 Closed System / Access Control 61 : ID/Password (Closed System) Access [ 113 (4)] ID/Password ID/Password ID/Password Password 2 (Biometrics) [ 11200 (b)] (,, ) 62 ( ) 63, FDA,,, 3-tier 64 (System Security Architecture) 9/35
ID/Password 3 Main System Unit Program / 3 Part11 3 [ / ] 4 [ ], 3 [ / ][ ] Main System Unit Program ( ) Login Logout 65 ID/Password ID/Password ID/Password [ 11300] 10/35
ID/Password : 6, ID Password 1 Password Password, Password ( ), DBMS DBMS 66 Access Log Access Log Login, Logout Access Log DB connection error Login (login ) DBMS shutdown, DB (logout / ) PC shutdown (logout ) Access Log Login Logout, Part11 Audit Trail Access Log Audit Trail 8 67 (HR) ID/Password Validation Validation Closed System ID/Password, Validation ( ERP ) 11/35
68 [User]Table [Unit Program ]Table / / Table, [Unit Program]Table / /, [Unit Program ]Table ( ) Unit Program,, Unit Program Access Log, 64 3 [ / ], [Unit Program ]Table [Write],[Read] column 3 9 12/35
7 Electronic Record Electronic Record Part11 113 Definitions (6) Electronic record means 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 -- (6) (Electronic record),,,,,,,,, Record Data, Data :, Record : Data Record ( ), DBMS DBMS DBMS DBMS DBMS DBMS DBMS, DBMS Backup (Backup DBMS Backup ) Restore (Restore DBMS Restore ) DBMS (Super User, ) DBMS (,,, ) 13/35
8 Audit Trail 81 Audit Trail? Audit Trail /, Audit Trail Part 11 Audit Trail Part11 Audit Trail [ 1110 (e)] / / (time-stamp) Audit Trail Audit Trail,,, 82 Audit Trail Audit Trail / / Script Audit Trail Table / / DBMS Trigger Audit Trail Table Audit Trail / / SQL Audit Trail SQL Script Audit Trail SQL, Audit Trail Code, Transaction SQL 2 SQL Validation Audit Trail Audit Trail DBMS Trigger / Audit Trail Table Audit Trail Script Record Audit Trail 5 DBMS Trigger (MS Access Trigger, MS Access ) Trigger Audit Trail Script 14/35
, Trigger DBMS Trigger, Part11 Audit Trail (Action) Audit Trail 83 Trigger Trigger 831 Trigger Part11 Audit Trail Audit Trail FDA, FDA Audit Trail (Risk Assessment ) Audit Trail 832 Audit Trail Table Table Audit Trail Table Audit Trail Table Table Table column Audit Trail Table Table, Table Audit Trail Table Table Relation 15/35
) [ Table : rtuser] [Audit Trail Table : rtuser_at] - MS SQL 2000 16/35
833 Trigger Script Trigger Script DBMS SQL Table / 3 ) [ Table : rtuser] [Audit Trail Table : rtuser_at] - MS SQL 2000 - [log_id] column MS SQL (Oracle Sequence ) 17/35
18/35
9 Electronic Signature 91 Electronic Signature? (ES) Part11 ES Part11, Part11 (Digital Signature)[ 113 (5)], Open System, Part11 19/35
92 921 ( [ 1170] ) ( (Table) ) (, Table relation ) DBMS DBMS RDBMS RDB entity relation DB Modeling Normalization Table Primary Key (64 ) 3 Table 3 Table Table Column / ( Table Column ) Table : [rtsignset] ( )Table : [rtsignsetdt] Table : [rtsign] 20/35
922 Table (rtsignset) [rtsignset]table, Table, Column, [rtsignset]table, DB [rtsignset]table / 923 Table (rtsignsetdt) [rtsignsetdt]table Table, Table Part11 [ 11100 (a)] [ (kind)]column [ (kind)]column column 21/35
Table relation 924 Table (rtsign) [rtsign]table Table [ (sign_no)]column (max ) [ (sign_set_no)][ (sign_id)]column [rtsignsetdt]table [ (deputy_yn)]column [rtsignsetdt][kind] [rtsignsetdt]table [rtsign]table [ (content)]column [rtsignset][sign_set_name] [rtsignsetdt]table relation [rtsignsetdt]table relation, [rtsignsetdt]table, relation [rtsign]table [rtsign]table [rtsignsetdt]table [rtsignsetdt]table [rtsign]table 925 921, Table 22/35
) ) 23/35
93 ID/Password ID/Password [ 11200 (a) (1) ] ID/Password 2 Login Password, Part11 2,, ID/Password [ 11200 (a) (1) (i)][ 11200 (a) (1) (ii)]id/password (continuous period) (subsequent signings) (password) (continuous period)? Login?? ( ), ID/Password 2 ID/Password Popup ID/Password (lock) 94 Part11, [ 11100 (a)], [ 11100 (b)], [ 11200 (a) (2)], ( ID/Password Part11 ) 923 [rtsignsetdt]table [ (kind)]column [ ]/[ ] 95 Part11 24/35
[ 1150 (a) (1)] & (Time-Stamp) [ 1150 (a) (2)] [ 1150 (a) (3)] FDA [/s/] ( ) ID (Time- Stamp) / FDA Warning Letter Thomas W Abrams Barbara Chong [rtsign]table ID, ID [user]table join [rtsign]table 25/35
26/35 96
10 FDA 21 CFR Part 11 Electronic Records; Electronic Signatures: Final Rule ISPE GAMP Forum, GAMP4, The Good Automated Manufacturing Practice(GAMP) Guide for Validation of Automated System, ISPE, 200112, Automated System Validation, wwwvalidationcokr, 200212, 21 CFR Part 11, wwwvalidationcokr, 2003 3, GAMP, wwwvalidationcokr, 2003 2 27/35
Part 11 Section Sub Content 111 Scope 111 Scope (a) The regulations in this part set forth the criteria under which the agency 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 Part 11,,,, 111 Scope (b) This part applies to records in electronic form that are created, modified, maintained, archived, retrieved, or transmitted, under any records requirements set forth in agency regulations This part also applies to electronic records submitted to the agency under requirements of the Federal Food, Drug, and Cosmetic Act and the Public Health Service Act, even if such records are not specifically identified in agency regulations However, this part does not apply to paper records that are, or have been, transmitted by electronic means Part 11,,,,, Federal Food, Drug, and Cosmetic Act / Public Health Service Act # # 111 Scope (c) Where electronic signatures and their associated electronic records meet the requirements of this part, the agency will consider the electronic signatures to be equivalent to full handwritten signatures, initials, and other general signings as required by agency regulations, unless specifically excepted by regulation(s) effective on or after August 20, 1997 Part 11, ( 1997 820 ) 111 Scope (d) Electronic records that meet the requirements of this part may be used in lieu of paper records, in accordance with Sec 112, unless paper records are specifically required, Sec 112, Part 11 111 Scope (e) Computer systems (including hardware and software), controls, and attendant documentation maintained under this part shall be readily available for, and subject to, FDA inspection Part 11,, FDA 112 Implementation 112 Implementation (a) For records required to be maintained but not submitted to the agency, persons may use electronic records in lieu of paper records or electronic signatures in lieu of traditional signatures, in whole or in part, provided that the requirements of this part are met 28/35
Section Sub Content Part 11 112 Implementation (b) For records submitted to the agency, persons may use electronic records in lieu of paper records or electronic signatures in lieu of traditional signatures, in whole or in part, provided that: 112 Implementation (b) (1) The requirements of this part are met; and Part 11 112 Implementation (b) (2) The document or parts of a document to be submitted have been identified in public docket No 92S-0251 as being the type of submission the agency accepts in electronic form This docket will identify specifically what types of documents or parts of documents are acceptable for submission in electronic form without paper records and the agency receiving unit(s) (eg, specific center, office, division, branch) to which such submissions may be made Documents to agency receiving unit(s) not specified in the public docket will not be considered as official if they are submitted in electronic form; paper forms of such documents will be considered as official and must accompany any electronic records Persons are expected to consult with the intended agency receiving unit for details on how (eg, method of transmission, media, file formats, and technical protocols) and whether to proceed with the electronic submission docket( ) No 92S-0251 Docket Docket # 113 Definitions 113 Definitions (a) The definitions and interpretations of terms contained in section 201 of the act apply to those terms when used in this part Section 201 113 Definitions (b) The following definitions of terms also apply to this part: 113 Definitions (1) Act means the Federal Food, Drug, and Cosmetic Act (secs 201-903 (21 USC 321-393)) (Act)Federal Food, Drug, and Cosmetic 113 Definitions (2) Agency means the Food and Drug Administration (Agency)FDA 113 Definitions (3) Biometrics means a method of verifying an individual's identity based on measurement of the individual's physical feature(s) or repeatable action(s) where those features and/or actions are both unique to that individual and measurable (Biometrics) 113 Definitions (4) Closed system means an environment in which system access is controlled by persons who are responsible for the content of electronic records that are on the system (Closed system) 29/35
Section Sub Content # (, ), 113 Definitions (5) Digital signature means an electronic signature based upon cryptographic methods of originator authentication, computed by using a set of rules and a set of parameters such that the identity of the signer and the integrity of the data can be verified (Digital signature), originator # 113 Definitions (6) Electronic record means 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 (Electronic record),,,,,,,,, 113 Definitions (7) Electronic signature means a computer data compilation of any symbol or series of symbols executed, adopted, or authorized by an individual to be the legally binding equivalent of the individual's handwritten signature (Electronic signature),, 113 Definitions (8) Handwritten signature means the scripted name or legal mark of an individual handwritten by that individual and executed or adopted with the present intention to authenticate a writing in a permanent form The act of signing with a writing or marking instrument such as a pen or stylus is preserved The scripted name or legal mark, while conventionally applied to paper, may also be applied to other devices that capture the name or mark (Handwritten signature) #, 113 Definitions (9) Open system means an environment in which system access is not controlled by persons who are responsible for the content of electronic records that are on the system 1110 Controls for closed systems (Open system) Persons who use closed systems to create, modify, maintain, or transmit electronic records shall employ procedures and controls designed to ensure the authenticity, integrity, and, when appropriate, the confidentiality of electronic records, and to ensure that the signer cannot readily repudiate the signed record as not genuine Such procedures and controls shall include the following:,,, 30/35
Section Sub Content 1110 Controls for closed systems (a) # # # Validation of systems to ensure accuracy, reliability, consistent intended performance, and the ability to discern invalid or altered records 1110 Controls for closed systems 1110 Controls for closed systems 1110 Controls for closed systems 1110 Controls for closed systems 1110 Controls for closed systems 1110 Controls for closed systems (b) (c) (d) (e) (f) (g),,, # #, The ability to generate accurate and complete copies of records in both human readable and electronic form suitable for inspection, review, and copying by the agency Persons should contact the agency if there are any questions regarding the ability of the agency to perform such review and copying of the electronic records,, #,, Protection of records to enable their accurate and ready retrieval throughout the records retention period Limiting system access to authorized individuals Use of secure, computer-generated, time-stamped audit trails to independently record the date and time of operator entries and actions that create, modify, or delete electronic records Record changes shall not obscure previously recorded information Such audit trail documentation shall be retained for a period at least as long as that required for the subject electronic records and shall be available for agency review and copying,, (time-stamp ), audit trail audit trail # audit trail Use of operational system checks to enforce permitted sequencing of steps and events, as appropriate Use of authority checks to ensure that only authorized individuals can use the system, electronically sign a record, access the operation or computer system input or output device, alter a record, or perform the operation at hand,,,, 31/35
Section Sub Content 1110 Controls for closed systems (h) #,, Use of device (eg, terminal) checks to determine, as appropriate, the validity of the source of data input or operational instruction 1110 Controls for closed systems 1110 Controls for closed systems 1110 Controls for closed systems 1110 Controls for closed systems 1110 Controls for closed systems 1130 Controls for open systems 1150 Signature manifestations (i) (j) (k) (k) (1) (k) (2) Determination that persons who develop, maintain, or use electronic record/electronic signature systems have the education, training, and experience to perform their assigned tasks /,,,, The establishment of, and adherence to, written policies that hold individuals accountable and responsible for actions initiated under their electronic signatures, in order to deter record and signature falsification # Use of appropriate controls over systems documentation including: : Adequate controls over the distribution of, access to, and use of documentation for system operation and maintenance,, Revision and change control procedures to maintain an audit trail that documents time-sequenced development and modification of systems documentation audit trail # audit trail # Persons who use open systems to create, modify, maintain, or transmit electronic records shall employ procedures and controls designed to ensure the authenticity, integrity, and, as appropriate, the confidentiality of electronic records from the point of their creation to the point of their receipt Such procedures and controls shall include those identified in Sec 1110, as appropriate, and additional measures such as document encryption and use of appropriate digital signature standards to ensure, as necessary under the circumstances, record authenticity, integrity, and confidentiality,,,,, Section 1110(Closed system ),,, (open system ) 32/35
Section Sub Content 1150 Signature manifestations (a) Signed electronic records shall contain information associated with the signing that clearly indicates all of the following: 1150 Signature manifestations 1150 Signature manifestations 1150 Signature manifestations 1150 Signature manifestations 1170 Signature/record linking 11100 General requirements 11100 General requirements 11100 General requirements 11100 General requirements 11100 General requirements (a) (1) (a) (2) (a) (3) (b) (a) (b) (c) (c) (1) : The printed name of the signer; # # ID The date and time when the signature was executed; and The meaning (such as review, approval, responsibility, or authorship) associated with the signature (,, ) The items identified in paragraphs (a)(1), (a)(2), and (a)(3) of this section shall be subject to the same controls as for electronic records and shall be included as part of any human readable form of the electronic record (such as electronic display or printout) (b) (a)(1), (a)(2), (a)(3) ( ) # Electronic signatures and handwritten signatures executed to electronic records shall be linked to their respective electronic records to ensure that the signatures cannot be excised, copied, or otherwise transferred to falsify an electronic record by ordinary means Each electronic signature shall be unique to one individual and shall not be reused by, or reassigned to, anyone else #, Before an organization establishes, assigns, certifies, or otherwise sanctions an individual's electronic signature, or any element of such electronic signature, the organization shall verify the identity of the individual,,, Persons using electronic signatures shall, prior to or at the time of such use, certify to the agency that the electronic signatures in their system, used on or after August 20, 1997, are intended to be the legally binding equivalent of traditional handwritten signatures,, (1997 820 ) The certification shall be submitted in paper form and signed with a traditional handwritten signature, to the Office of Regional Operations (HFC-100), 5600 Fishers Lane, Rockville, MD 20857 33/35
Section Sub Content 11100 General requirements (c) (2) the Office of Regional Operations (HFC-100), 5600 Fishers Lane, Rockville, MD 20857 Persons using electronic signatures shall, upon agency request, provide additional certification or testimony that a specific electronic signature is the legally binding equivalent of the signer's handwritten signature 11200 Electronic signature components and controls 11200 Electronic signature components and controls 11200 Electronic signature components and controls 11200 Electronic signature components and controls 11200 Electronic signature components and controls 11200 Electronic signature components and controls 11200 Electronic signature components and controls 11200 Electronic signature components and controls 11300 Controls for identification codes/passwords (a) (a) (1) (a) (1) (i) (a) (1) (ii) (a) (2) (a) (3) (b),, Electronic signatures that are not based upon biometrics shall: : Employ at least two distinct identification components such as an identification code and password ID 2 #, # When an individual executes a series of signings during a single, continuous period of controlled system access, the first signing shall be executed using all electronic signature components; subsequent signings shall be executed using at least one electronic signature component that is only executable by, and designed to be used only by, the individual, : When an individual executes one or more signings not performed during a single, continuous period of controlled system access, each signing shall be executed using all of the electronic signature components, Be used only by their genuine owners; and Be administered and executed to ensure that attempted use of an individual's electronic signature by anyone other than its genuine owner requires collaboration of two or more individuals Electronic signatures based upon biometrics shall be designed to ensure that they cannot be used by anyone other than their genuine owners Persons who use electronic signatures based upon use of identification codes in combination with passwords shall employ controls to ensure their security and integrity Such controls shall include: 34/35
Section Sub Content 11300 Controls for identification codes/passwords 11300 Controls for identification codes/passwords 11300 Controls for identification codes/passwords 11300 Controls for identification codes/passwords 11300 Controls for identification codes/passwords (a) (b) (c) (d) (e) ID Maintaining the uniqueness of each combined identification code and password, such that no two individuals have the same combination of identification code and password ID Ensuring that identification code and password issuances are periodically checked, recalled, or revised (eg, to cover such events as password aging) ID,, (, ) Following loss management procedures to electronically deauthorize lost, stolen, missing, or otherwise potentially compromised tokens, cards, and other devices that bear or generate identification code or password information, and to issue temporary or permanent replacements using suitable, rigorous controls,,,, ( ) Use of transaction safeguards to prevent unauthorized use of passwords and/or identification codes, and to detect and report in an immediate and urgent manner any attempts at their unauthorized use to the system security unit, and, as appropriate, to organizational management ID ( ) # password 3 id # login 5 Initial and periodic testing of devices, such as tokens or cards, that bear or generate identification code or password information to ensure that they function properly and have not been altered in an unauthorized manner ID 35/35