Compliance in the Cloud: ISO 27001 Information Security Management Systems

Hello good people of the world! Today’s post is continuing the series on compliance in the cloud. In the last post, we looked at the FDA’s 21CFR11, which is the legal statute medical device, pharmaceutical, and biologic manufacturers must adhere to when using computer systems for electronic records and/or signatures as part of their manufacturing process for products sold in the United States.

But 21CFR11 is old (1997!) and vague, really only covering at a high-level the requirements for impacted computer systems. Industry has filled in the details, and the ISO standards are a good example of that.

ISO 27001 covers Information Security Management Systems and costs about US$130. Firms may reference ISO certification as evidence of 21CRF11 compliance, such as Microsoft’s statement here.

Below is a summary of the procedural and/or engineering controls required by the standard. You’ll see a lot of overlap with the CFRs, other industry guidance like GAMP5, and other regulations like MHRA’s data integrity expectations.

Management of Policies

1. Policies shall be defined, approved by management, and distributed to employees.
2. Policies shall be reviewed at a planned interval and must be revised when processes change.
3. Responsibilities shall be defined.
4. Duties shall be segregated to avoid conflicts of interest.
5. Communication with relevant authorities shall be maintained.
6. Communication with relevant special interest groups and forums shall be maintained.
7. Information security shall be addressed in all projects.

Human Resource Security

1. Background checks shall be employed.
2. Responsibilities related to information security shall be documented and understood.
3. Training relevant to job functions shall be mandated and documented.
4. A formal disciplinary process shall exist for employees who have committed an information security breach.
5. Responsibilities shall be managed appropriately upon employee termination.

Asset Management

1. An inventory of assets shall be maintained.
2. Each asset shall have an assigned owner.
3. Acceptable use of each asset shall be documented.
4. Distribution and return of assets shall be managed.

Information Classification

1. Information shall be classified in terms of legal requirements, regulatory requirements, confidentiality, etc.
2. Procedures shall exist for the labeling of information by classification.
3. Management of assets shall take into consideration the classification of information associated with the asset.

Media Management

1. Removable media shall be managed per procedure.
2. A procedure shall exist for the proper disposal of media.
3. Procedures shall exist for the physical transfer of media, including protecting against unauthorized transfer, and damage/corruption of media during transfer.

Access Control

1. A procedure shall exist for access control.
2. User access shall be limited to the networks, systems, and information required to perform their job duties.
3. A procedure shall exist for the registration and de-registration of users.
4. A procedure shall exist for the access provisioning of users to all applicable systems.
5. The allocation of privileged access rights shall be restricted and controlled.
6. Authentication information shall be controlled through a formalized process.
7. Asset owners shall review user access at planned intervals.
8. User access shall be removed at appropriate times, such as employee termination.

Cryptography

1. Procedures shall exist for the use of cryptographic controls to protect information.

Physical Security

1. Security perimeters shall be defined to protect areas containing sensitive information.
2. Secure areas shall employee physical entry controls.
3. Physical protection against external and environmental threats shall be established.
4. Procedures shall exist for working in secure areas.

Equipment

1. Equipment shall be protected from problems with supporting utilities.
2. Cabling shall be protected from interception, interference, and damage.
3. Equipment shall be maintained on planned intervals.

Operations Security

1. Operating procedures shall exist.
2. Change management procedures shall exist.
3. Resource use and process capacity shall be measured and understood.

Backup

1. Backup and restore procedures shall be documented and tested on planned intervals.

Logging

1. Event logs shall be employed, retained, and reviewed on planned intervals.
2. Logs shall be protected from tampering, unauthorized access, and loss.
3. Administration activities shall be logged and reviewed on planned intervals.
4. Clocks used by systems shall be synchronized to a single reference time source.

Development Processes

1. Software development procedures shall be documented.
2. Changes to systems in the development lifecycle shall be controlled.
3. Development environments shall be secured.
4. Security functionality shall be tested during development.
5. Acceptance testing shall be established for all new versions of software.
6. Test data shall be controlled.

Suppliers

1. Risks associated with supplier access shall be documented and mitigated.
2. Risks and mitigations shall be communicated and agreed upon with suppliers.
3. Suppliers shall be audited on planned intervals.
4. Changes to supplier relationships shall be controlled.

Incidents

1. Procedures shall exist for the management of incidents.
2. End users shall be required to report incidents.
3. Corrective and preventive actions shall be applied to the management of incidents.

Business Continuity

1. Procedures shall exist for the continuity of business processes during adverse events.
2. Business continuity procedures shall address information security concerns.

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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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Oral Solid Dose – Isolation and Containment

Hello good people of the world! Today we’re going to talk about isolation and containment considerations in oral solid dose manufacturing. The purpose of isolation and containment is to control the level of pharmaceutical ingredient exposure to personnel and the environment. It is typically not possible to eliminate all exposures, so we try to reduce it to a tolerable level, which must be defined.

The CFRs and other regulations require manufacturers to limit exposure to customers of any undesirable substance. Limits have been established by industry group and regulatory bodies, and quantify things such as Allowable Daily Exposure (ADE).

Things to look at when considering isolation and containment include:

• Material flow
• Personnel flow
• Operator interventions
• Sampling
• Waste flow
• Maintenance procedures
• Utility interactions

Isolation and containment risks must be evaluated and mitigated to get a solid handle on the implications. A multi-disciplinary approach must be used. Migations may include:

• Physical barriers
• Air control
• Cleaning procedures
• Disposables
• Training

What considerations come in to play in your isolation/containment strageties? Comment below!

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