Transcript Concetti generali di un processo di validazione
Requirements for Computer Systems in the clinical practice
Danilo Neri, PhD Pomezia, 13 Settembre 2005
Requirements for Computer Systems in the clinical practice
Fundamental Requirements for clinical data Security Integrity Traceability Data shall be (regardless the format !) attributable legible contemporaneous (timeliness) original Accurate
Different implications for different environments CLOSED Security Integrity Traceability Records are fully under Responsibility of the Firm OPEN Security Integrity Traceability Responsibility of Records is shared with Third Parts
Requirements for Computer Systems in the clinical practice
Evolution of Computer System in GCP: the old Scenario
Case History Paper CRF Clinical DB (eCRF) w/o eSignature
1. Data are registered in the paper Case History 2. Data are reported in the CRF Paper Form 3. Data are migrated in the Clinical DB (option: Electronic Signature)
Compliance Requriments for Computer Systems Source Data Verification
Case History Paper CRF Clinical DB (eCRF) w/o eSignature
ICH E6 for Computer Systems 21 CFR Part 11 Requirements (Closed System) Protection of Privacy (21 CFR Part 21, EU 95/46/EC) Regulations
ICH E6 Requirements for Computer Systems (1.2) 5.5.3.a Ensure and document that the electronic data processing system(s) conforms to the Sponsor’s established requirements for completeness, accuracy, reliability, and consistent intended performance (i.e. validation).
International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use - ICH Harmonised Tripartite Guideline – Guideline For Good Clinical Practice
ICH E6 Requirements for Computer Systems (2.2) Par. 5.8: Integrity of Data and Computer Software The credibility of the numerical results of the analysis depends on the quality and VALIDITY of the method and software used both for data management (data entry, storage, verification,correction and retrieval) and also for processing the data statistically. The computer software used for data management and statistical analysis should be reliable and documentation of appropriate software testing procedures should be available.
International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use – ICH Harmonised Tripartite Guideline – Guideline Guideline for statistical principle on Clinical trial
Code of Federal Regulations 21 CFR Part 11; Eletronic Records; Electronic Signature August, 1997 Electronic Signature Criteria set forth for 21 CFR Part 11 Electronic Records Criteria set forth for Electronic Record Electronic Signature EQUIVALENCE Paper Record Handwritten Signature RECORD LIFE CYCLE
•creation •modifying •maintenance •archiving •retrieving •transmission
21 CFR Part 11 Requirements for Electronic Records Control for Closed Systems [ref. §11.10] -
The use of closed systems to manage electronic records implies:
(a) (b) (c) (d) (e) (f) (g) (h) (i) (l) Validation of computer system Accurate and complete copies of records Protection of the data Limiting access Audit trails Operational system checks Authority checks Control on validity of input actions Adequate education and training Control on documentation distribution and change control procedure application
What is Computer System Validation? CSV is the documented evidence, to a high degree of assurance, that a computer system performs its intended functions accurately and reliably.
Documented evidence High degree of assurance intended functions accurately and reliably
ISO equivalent Requirements (The Quality is) The totality of characteristics of an entity that bear on its ability to satisfy stated and implied need. [ISO 8402: 1994]
Note: In ISO/IEC 14598 the relevant entity is a software product An entity is a product, process, person, activity, machine, service, system, department, company, institution, or organization.
GAMP Validation Lifecycle User Requirements Specification Functional Specification Design Specification Risk
related to
Risk Performance Qualification Operational Qualification
related to
System Build Installation Qualification
Validation Deliverables User Requirements Specifications Decommissioning Plan/Report De commissioning Audit Report SOPs Installation Operational Performance Qualification Protocol & Reports Functional Specifications Design Specifications Test Plan System Acceptance Testing Unit Testing
Part 11 vs ICH E6 Requirements (1/2)
Requirement Validation of Computer system Accurate and Complete Copies of Record Data Protection Part 11 11.10.(a) 11.10.(b) 11.10.(c) Limiting Access Audit Trail 11.10.(d) 11.10.(e) ICH E6 5.5.3.a
4.9.7
2.10; 4.9.1; 5.5.3.f
§ 2.11; 5.5.3.d
4.9.3; 5.5.3.c
Part 11 vs ICH E6 Requirements (2/2)
Requirement Operational System check Authority Check Device Check Training System Documentation Part 11 11.10.(f) 11.10.(g) 11.10.(h) 11.10.(i) 11.10.(k) ICH E6 2.6
4.9.1
2.11; 4.1.5; 4.9.3
5.5.3.e
- 2.8
5.5.3.b
Requirements for Computer Systems in the clinical practice
Evolution of Computer System in GCP: the current Scenario
Case History Network Clinical DB (eCRF) + eSignature
1. Data are registered in the Case History 2. Data are directly recorded in the Clinical DB through remote access and electronically signed
Compliance Requriments for Computer Systems Source Data Verification
Case History Network Clinical DB (eCRF) + eSignature
ICH E6 for Computer Systems 21 CFR Part 11 Requirements (Open System + eSig Reqs) Protection of Privacy (21 CFR Part 21, EU 95/46/EC) Regulations
21 CFR Part 11: Requirements for Open Systems Control for Open Systems [ref. §11.30] -
The use of open systems to manage electronic records implies:
Controls for Closed System (see previous slide); several requirements (I.e. Device Checks) might be enforced Document encryption Digital signatures standards
21 CFR Part 11: Requirements for Electronic Signatures [ref. §11.50; 11.70; 11.100] -
The use of Electronic Signature (ES) for signing Electronic Records (ER) implies:
Using ES when required by the predicate rule(s) ES manifestation ES / ER linking Procedure for managing attribution and use of ES
Fundamental requirement: Signature-Record Linking
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.
Ref. §11.70. Preamble 15,53,107,108,109,110,11,112,113
Signed Record IMMUTABLE BY ORDINARY MEANS Signature
Requirements for Computer Systems in the clinical practice
Electronic Case History
Evolution of Computer System in GCP: the near next Scenario
Network Paper CRF Clinical DB (eCRF) + eSignature Printed Case History
1. Data are registered directly in the electronic Case History (ECH) 2. Case History are printed based upon ECH 3. Data are reported in paper CRF and then migrated to the clinical DB or directly entered in the Clinical DB
Current use of Computer System for Electronic History Case
Requirements for Computer Systems Regulations Ministry of Health Rules Quality ISO requirements Regulations ICH E6 for Computer Systems 21 CFR Part 11 Requirements (Open System + eSig Reqs) Privacy related local laws (DL675/196, DL196/2003) Protection of Privacy (21 CFR Part 21, EU 95/46/EC)
Electronic Case History + eSignature Printed Case History
?
Network Paper CRF Clinical DB (eCRF) + eSignature
Source Data Verification
Requirements for Privacy Protection Legal “trigger” Directive 95/46/EC, 24 October 1995 Member States shall protect the fundamental rights and freedoms of natural persons, and in particular their right to privacy with respect to the processing of personal data
Directive 95/46/EC: Processing of Personal Data Any operation or set of operations which is performed upon personal data, whether or not by automatic means, such as:
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collection
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recording
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organization
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storage
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adaptation or alteration,
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retrieval
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Consultation
• • •
use
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disclosure by transmission dissemination or otherwise making available
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alignment or combination blocking, erasure or destruction
Directive 95/46/EC, 24 October 1995 Chapter I, Art. 2
Directive 95/46/EC: Application Field Processing of personal data wholly or partly by automatic means Processing of personal data which form part of a filing system or are intended to form part of a filing system
Directive 95/46/EC, 24 October 1995 Chapter I, Art. 3
Directive 95/46/EC: Data Quality Controller has to ensure that data are:
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Processed fairly and lawfully
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Collected for specified, explicit and legitimate purposes
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Adequate, relevant and not excessive in relation to the purposes
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Accurate and, where necessary, kept up to date
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Kept in a form which permits identification of data subjects for no longer than is necessary
Directive 95/46/EC, 24 October 1995 Chapter II, Art. 6
Directive 95/46/EC: Data Subject’s Rights
• Information • Access to Data • Right to object
Directive 95/46/EC: Data Subject’s Information Data subject has to know:
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Identity of the Controller (or Representative)
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Purpose of the Data Processing
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Recipient of the Data
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Own rights
Directive 95/46/EC, 24 October 1995 Chapter II, Art. 10
Directive 95/46/EC: Data Subject’s Access to Data Data Subject has to obtain from the Controller:
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Information about subject’s personal data effective use, data undergoing process, logic involved in any automatic processing of data, own rights
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Erasure or blocking of data not compliant to 95/46/EC
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Notification about data disclosure to third parties
Directive 95/46/EC, 24 October 1995 Chapter II, Art. 12
Directive 95/46/EC: Confidentiality of Processing “Any person acting under the authority of the controller or of the processor, including the
“
processor himself, who has access to personal data must not process them except on instructions from the controller, unless he is required to do so by law.”
Directive 95/46/EC, 24 October 1995 Chapter II, Art. 16
Directive 95/46/EC: Security of Processing
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Safely processing
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Protection against accidental or malicious
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loss
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alteration
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unauthorized disclosure or access
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Security measures implementation
Directive 95/46/EC, 24 October 1995 Chapter II, Art. 17
Local Laws application
Italian laws DL675/196, DL196/2003 include the statements of EU directive
The Technical attachment B dedicated to Electronic data management.
The law and the Technical attachment B address nearly the same requirements set forth by pharmaceutical regulations, such as 21 CFR Part 11
Requirements set forth by the Technical Attachment for data management (1.2) (2) Le credenziali di autenticazione consistono in un codice per l'identificazione dell'incaricato associato a una parola chiave riservata conosciuta solamente dal medesimo oppure in un dispositivo di autenticazione in possesso e uso esclusivo dell'incaricato, eventualmente associato a un codice identificativo o a una parola chiave, oppure in una caratteristica biometrica dell'incaricato, eventualmente associata a un codice identificativo o a una parola chiave. Security Management (5) La parola chiave, quando è prevista dal sistema di autenticazione, è composta da almeno otto caratteri oppure, nel caso in cui lo strumento elettronico non lo permetta, da un numero di caratteri pari al massimo consentito; essa non contiene riferimenti agevolmente riconducibili all'incaricato ed è modificata da quest'ultimo al primo utilizzo e, successivamente, almeno ogni sei mesi. In caso di trattamento di dati sensibili e di dati giudiziari la parola chiave è modificata almeno ogni tre mesi. Password Management
Requirements set forth by the Technical Attachment for data management (2.2) (13) I profili di autorizzazione, per ciascun incaricato o per classi omogenee di incaricati, sono individuati e configurati anteriormente all'inizio del trattamento, in modo da limitare l'accesso ai soli dati necessari per effettuare le operazioni di trattamento. ; User Profiles (19.3) (Il documento programmatico sulla Sicurezza (DPS) deve contenere) l'analisi dei rischi che incombono sui dati; Risk Analysis (19.4) (Il documento programmatico sulla Sicurezza (DPS) deve contenere) le misure da adottare per garantire l'integrità e la disponibilità dei dati, nonchè la protezione delle aree e dei locali, rilevanti ai fini della loro custodia e accessibilità Backup (19.5) (Il documento programmatico sulla Sicurezza (DPS) deve contenere) la descrizione dei criteri e delle modalità per il ripristino della disponibilità dei dati in seguito a distruzione o danneggiamento Restore
ISO Requirements
Implementation of ISO Quality System in hospital management has been recommended by the Ministry of Health
The Electronic Case History may be a powerful and fundamental key point of the Quality System provided that following requirements are met:
Traceability
Clarity
Accuracy
Trustworthiness
Completeness
Implied requirements almost equal to the ones set forth by pharmaceutical regulations
Electronic Data for Source Data Verification Ministry of Health Rules Quality ISO requirements Privacy related local laws (DL675/196, DL196/2003) Only if these requirements are met, Electronic Case History can be used for Source Data Verification
Electronic Case History + eSignature Printed Case History Network Paper CRF Clinical DB (eCRF) + eSignature
Source Data Verification
Conclusions
Requirements for data managed by Computer System are increasing due to the increment of Computer System in the product life cycle
Electronic Case History might be used provided that they verify the provisions set for Regulated Records
The checklist for Computer System Compliance may be used in order to justify the use of Electronic Case History within the Source Data Verification