Tag Archives: 21CFR11

Computer System Lifecycle: Considerations

Hello good people of the world! Today’s post is an overview of the lifecycle of a computer system in regulated industries (pharmaceutical, biologics, and medical device manufacturing). It is based on my almost 20 years experience in the field, and will provide you at a high level the things you should be thinking about with respect to computer systems.

1. Requirements Elicitation
Before anything else, we must understand the requirements around the need for a computer system. This could be the hardest step, and is definitely the most important. Spending extra time and expertise here can prevent a lot of problems downstream. Know who your stakeholders are, and elicit their requirements better than they do. You will often (always ?) find end-users may not know what their requirements are, or may not be able to communicate them effectively. Understand the business process you are trying to automate, and ensure you are talking to all stakeholders: end-users, administrators, managers, etc.

2. Supplier Selection
Once you know what your requirements are, you’re going to find someone to help you met your requirements. At this stage it is important to vet your suppliers to make sure they have the required experience and expertise to deliver a solution to meet your requirements. Supplier selection in regulated industries includes a Supplier Audit.

3. Planning
Now is the time to document your plan. Traditionally this plan is called a Validation Plan, or Validation Project Plan, or Project Validation Plan, but I like calling it a Quality Assurance Plan. Validation is one (big) part of ensuring the quality of the delivery of your new computer system, but your planning needs to encompass all quality considerations. Your plan should include:
– change management procedure to be followed in implementing the system
– updates to your system inventory
– business continuity impact assessment
– risk management considerations (project risk, compliance risk, etc.)
– data privacy considerations
– HR data access considerations
– GxP regulatory determination (e.g., System-Level Impact Assessment (SLIA))
– plan for leveraging supplier documentation
– test strategy for backup, archive/retrieval, restore
– system release strategy
– data migration strategy (if applicable)

4. Specifications
Once your plan is in plan (and agreed upon by all stakeholders), now is the time to specify how the system will meet requirements. Depending on the time of system, risk, GxP impact, etc., deliverables of this stage may be a Functional Specification (FS), Functional Risk Assessment (FRA), Design Specification (DS), Configuration Specification (CS), Requirements Trace Matrix (RTM).

5. Verification
Now that your system is specified, it’s time to test it. Again, depending on the project scope, this stage could include an overall Test Plan, draft SOPs (admin, operating, end-user, etc.), protocol generation, RTM update, business continuity and disaster recovery plans, functional testing, training curricula development, and user-acceptance testing (UAT).

6. Release
Everything has gone well and it’s time to put the system into production use. Be sure to consider: SOP approval/effectiveness, updating the RTM again, any testing in production (such as IQ), system release notification, creating an index of system documentation, closing the Quality Assurance Plan with a report (what actually happened versus what was planned), and closing the change control.

7. Operation
Once the system is in use and everyone is happy, the work is not done! Maintain activities should include: change management, incident/problem management, periodic review of the validated state, periodic testing of backups and disaster recovery, and maintaining the system documentation index.

8. Retirement
Hopefully after many years of service, the time will come to retire your computer system. Be sure to consider data archiving and retrieval in this (final) stage of the computer system lifecycle.

Did I miss anything? Comment below.

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Compliance in the Cloud: 21 CFR Part 11 Requirements

Hello good people of the world! Today’s post is the next in the series on compliant software in the cloud. Today we’re taking a deep dive into the FDA’s 21st Code of Federal Regulations, Part 11 (21CFR11). If you’re not familiar, 21CFR11 is an ancient (written in the late 1990s) regulatory statute on the use of electronic records and electronic signatures in regulated industries such as medical device, pharmaceutical, and biologic manufacturing. Despite it’s age, 21CFR11 is the governing statute for the use of computer systems in regulated spaces, so it’s critical that we understand it well.

In this post, I’ll give a abridged version of each applicable section of the statute, and then detail the engineering and procedural requirements that are typically used to meet the statute in the design, development, and implementation of a cloud-based computerized system. Let’s go!

Subpart B §11.10, Controls for Closed Systems

  • 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. Controls used require the following:
    • Validation
    • Legibility
    • Record Protection
    • Limited System Access
    • Secure Audit Trails
    • Operational System Checks
    • Authority checks
    • Device Checks for data validity
    • Training
    • Policies in place for operational adherence
    • Control of Distribution
    • Change Control Procedures

Engineering requirements:

  • System shall employ HTTPS and other modern web application security technology per according to ISO/IEC 27001 and ISO/IEC 27018 standards
  • System shall employ user-level security, ensuring each user is required to maintain a unique username and password to access the system
  • System shall employ role-based permissions and limit access to only functionality required by the job role
  • System shall employ audit trail to ensure compliant activities are documented with username, time/date stamp, and reason for signature
  • System shall employ electronic signatures with username, time/date stamp, and reason for signature for GxP-related activities

Procedural requirements:

  • System shall be validated
  • Audit trails shall be reviewed
  • Appropriate training shall be assigned and managed
  • Use and administration procedures shall exist
  • Change control procedures shall exist

Subpart B §11.50, Signature Manifestation

Requirements for signature manifestation:

  • Signed electronic records shall contain information associated with the signing that clearly indicates all of the following:
  • The printed name of the signer; The date and time when the signature was executed; and
  • The meaning (such as review, approval, responsibility, or authorship) associated with the signature.

These are 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).

Engineering requirements:

  • System shall employ electronic signatures with username, time/date stamp, and reason for signature for GxP-related activities

Procedural requirements:

  • System shall be validated
  • Audit trails shall be reviewed
  • Appropriate training shall be assigned and managed
  • Use and administration procedures shall exist
  • Change control procedures shall exist

Subpart B §11.70, 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.

Engineering requirements:

  • System shall employ electronic signatures with username, time/date stamp, and reason for signature for GxP-related activities
  • Electronic signatures shall be linked to specific records and cannot be transferred by any means.

Subpart C §11.100, General Requirements

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.

  • 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.
  • 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.

Engineering requirements:

  • System shall employ user-level security, ensuring each user is required to maintain a unique username and password to access the system
  • System shall employ role-based permissions and limit access to only functionality required by the job role
  • System shall employ electronic signatures with username, time/date stamp, and reason for signature for GxP-related activities
  • Electronic signatures shall be linked to specific records and cannot be transferred by any means.

Procedural requirements:

  • Procedure shall exist for systems users to sign testimony that their electronic signature is equivalent to their handwritten signature and for this testimony to be communicated to the agency

Subpart C §11.300, Controls for Identification codes/passwords

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:

  • Maintaining the uniqueness of each combined identification code and password, such that no two individuals have the same combination of identification code and password.
  • Ensuring that identification code and password issuances are periodically checked, recalled, or revised (e.g., to cover such events as password aging).
  • 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.
  • 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.

Engineering requirements:

  • System shall employ user-level security, ensuring each user is required to maintain a unique username and password to access the system
  • System shall employ role-based permissions and limit access to only functionality required by the job role
  • System shall require each user have a unique username and password
  • System shall expire passwords after a set amount of time
  • System shall lockout users after a set amount of failed login attempts
  • System shall have documented password strength requirements
  • System shall obfuscate passwords when entered and displayed on User Interfaces
  • System shall store passwords in an encrypted manner, and never display, store, or transmit passwords in plain text

Procedural requirements:

  • Procedures shall exist for the administration of users into the system
  • Procedures shall exist for the routine use of computer systems

What Engineering or Procedural requirements do you think are critical for cloud-based computer systems? Comment below!

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Can SharePoint Online be Compliant?

Microsoft_SharePoint_2010_Foundation

SharePoint is an off-the-shelf configurable software solution that has been offered by Microsoft since 2001. It is popular in many industries (including Biotech, Pharmaceutical, and Medical Device) for document management, local Intranet, and many other applications. However, if SharePoint is being used for any GxP purpose, you better believe it is subject to 21CFR11 and/or Annex 11. Continue reading Can SharePoint Online be Compliant?

Evaluating 3rd Party Software Solutions

Software Solutions

Hello good people of the world! This post is about evaluating 3rd party software solutions for GMP use and is based on this excellent questionnaire from the Canada-based company Montrium: 17 Must-Ask Questions for Demonstrations of Regulated EDMS’

The following are some topics to focus on:

Continue reading Evaluating 3rd Party Software Solutions

Considerations in SaaS Validation

SaaS Qualification

Hello good people of the world! Today’s post is about qualifying Software as a Service (SaaS), also known as “cloud-based” or “hosted” software. Simply, SaaS is any computer system in which any server is not hosted by the system owner. Here are some key considerations in qualifying SaaS computer systems:

Continue reading Considerations in SaaS Validation

SharePoint 2013 in a GMP Environment

SharePoint

Hello good people of the world! Today’s post is about implementing and using Microsoft SharePoint 2013 in a regulated (GMP) environment.

Microsoft has published a comprehensive guide to SharePoint 21CFR11 compliance, which can be downloaded for free here.

Basic software requirements are:

Continue reading SharePoint 2013 in a GMP Environment