What is 21 CFR Part 11 of the US FDA?

In order to guarantee the precision and dependability of electronic records and electronic signatures, as well as their equivalent to handwritten signatures and paper records, the U.S. Food and Drug Administration (FDA) created 21 CFR Part 11 regulations in 1997. 21 CFR Part 11 must be followed by the pharmaceutical, biotech, and other sectors that depend on digital systems for data administration, documentation, and regulatory filings.

21 CFR Part 11's primary requirements are:
1. Electronic Documents:

To guarantee correctness, dependability, and consistency, systems that generate, alter, and preserve electronic data must be validated in accordance with 21 CFR Part 11.

To capture the necessary information, such as the date, time, and any modifications to the record, one must choose safe, computer-generated audit trails.

When the FDA conducts an inspection, these electronic documents should be easily accessible and kept for the necessary amount of time.
To prevent unauthorized access to records and to preserve them from being erased or altered, the systems must be well secured.


2. Electronic Signatures:

Each person must have a distinct electronic signature. When someone uses an electronic signature, an organization needs to have procedures in place to confirm their identification.
To make it simple to track responsibility, the electronic signatures must be connected to the signed document. Essential information such as the name of the signer, the date, and the significance (approval, review, etc.) of the signature must be included in such a document.
An organization is required to attest to the FDA that electronic signatures are just as legally binding as handwritten ones.

3. System Access

System access needs to be tightly controlled to grant only authorized users access. Strong password management and authentication techniques are available. Every activity a person takes within the system must to be traceable.

4. Operational Controls

To ensure that the system's actions or events are occurring in the right order, operational checks must be carried out.
Device checks are necessary to ensure that the computers and sensors used in the electronic record-keeping process are operating properly.

5. Digital Signature Requirements:

Biometrics or Two-Factor Authentication must be implemented to prevent the fraudulent use of electronic signatures.

Why is US FDA 21 CFR Part 11 Critical for Pharmaceutical Leaders?

It ensures that the electronic system used by pharmaceutical companies complies with stringent data integrity, security, and traceability standards.

Here are the reasons why Pharma Leaders are obliged to follow it:

1. Data Integrity and Trust: Since Part 11 sets the foundation to ensure the accuracy and reliability of the electronic records, it also makes them tamper-proof. The regulation helps to gain and maintain the trust of the regulators, partners, and patients. Compliance with this regulation guarantees data integrity, which is essential to delivering high-quality and safe products.

2. Regulatory Compliance: If a company fails to comply with 21 CFR Part 11, it can lead to regulatory actions such as warning letters, fines, or product recalls. By prioritising compliance, pharma leaders can protect their organisations from costly legal matters and damaging the brand’s reputation.

3. Operational Efficiency: Besides ensuring the brand’s reputation, the regulation also helps improve efficiency as it promotes streamlining operations and reducing manual paperwork, making data retrieval easy. In this fashion, it also supports faster decision-making and real-time data access.

4. Global Market Access: Since the FDA is a globally leading regulatory authority, compliance with 21 CFR Part 11 opens up entry gates into the International Markets.

What is GAMP 5?

The GAMP 5 is the updated version of Good Manufacturing Practice, developed by the International Society for Pharmaceutical Engineering (ISPE) in 2008. This framework is a practical guideline for designing, implementing, and managing automated systems. It covers the entire system from concept to decommissioning.

Here are the Key Principles of GAMP 5:

1. Risk-Based Approach:

• GAMP 5 focuses on a risk-based approach to compliance; the organisation must identify and control risks to product quality, patient safety and data integrity. The company must conduct formal risk assessments like FMEA and HACCP to determine the level of testing and validation required depending on the system’s potential impact on patient safety and product quality.

• There must be appropriate controls depending on the identified risks. The highly critical systems require to be thoroughly validated.

2. System Life Cycle Approach (SLC)

• The GAMP 5 supports the management of computerised systems throughout the concept, development, validation, operation, and retirement. The systems also need to be reviewed and improved per the changes in the regulations, evolving business needs and technological advancements.

3. Scalable Validation

• GAMP 5 also supports using a scalable validation approach depending on the system’s complexity, criticality, and risk.

• Organisations can also use Supplier and Vendor Documentation like Factory Acceptance Testing to minimise duplication and streamline validation efforts

4. Category-Based Software Classification

To determine the appropriate validation strategy, GAMP 5 has classified software: Infrastructure Software (Operating systems), Non-configurable software (standard software packages with no customisation), Configurable Software, and Custom Software. The Custom software requires maximum validation efforts.

5. Documentation and Traceability

• GAMP 5 underscores the significance of well-defined documentation, such as User Requirements Specification (URS), Functional Specifications (FS), Design Specifications (DS), and testing documentation (IQ, OQ, PQ).

• It is essential to use a traceability matrix to guarantee all the user requirements are tested and covered in the validation process, proving that all the systems function as intended.

6. Quality by Design

GAMP 5 encourages the design of high-quality systems to comply with the standards right from the early developmental stages and reduce the risk of failure and deviations later.

It also emphasises user involvement to ensure the system meets the business needs and regulatory standards from the start of the process.

7. Data Integrity and Data Governance

The GAMP 5 guidelines are in alignment with other regulatory expectations like the US FDA’s and EU’s guidelines affirm the integrity of electronic records, including the ALCOA+ principles (Attributable, Legible, Contemporaneous, Original, Accurate, Complete, Consistent, Enduring, and Available). It suggests implementing secure, computer-generated audit trails to secure the digital records and track any changes.

Why is GAMP 5 Compliance substantial for Pharma Leaders?

For pharmaceutical leaders, GAMP 5 compliance is essential for the following reasons:

1. Regulatory Alignment: Since GAMP 5 aligns with other global regulations like FDA and EMA, its compliance guarantees that the system is audit-ready and meets the safety, quality, and data integrity requirements.

2. Risk-Based Focus: As GAMP 5 emphasises a risk-based approach, it allows the Pharma Leaders to focus validation efforts on the systems that directly influence product quality and patient safety. It helps to address the risks efficiently and streamline processes, reducing downtime. The leaders do not need to overburden their teams with unnecessary validation tasks.

3. Ensuring Data Integrity: Compliance with GAMP 5 confirms that the computerised systems generate accurate, reliable, and secure data, which is paramount for decision-making and regulatory submissions.

4. Enhancing Operational Efficiency: By implementing GAMP 5, pharmaceutical companies can adopt advanced technologies while ensuring compliance. Automation and innovative systems that comply with GAMP 5 standards reduce manual interventions, accelerate production cycles, and improve overall efficiency, giving companies a competitive edge in a fast-evolving industry.

Following GAMP 5 is crucial for validation systems like Manufacturing Execution Systems (MES), Laboratory Information Management Systems (LIMS), and Quality management systems (QMS) typically used in the pharma industry.

Conclusion

As we conclude this discussion, we would like to emphasise the importance of selecting a system that complies with US FDA 21 CFR Part 11 and GAMP 5 to ensure product quality and patient safety. As the saying goes, ‘A friend in need is a friend indeed,’ and KN Water and Energy Solutions LLP is your reliable partner. We are available 24/7, ready to listen to your challenges and craft tailored solutions. Contact us Now!

FAQs

1) What documentation is needed to prove compliance with 21 CFR Part 11 and GAMP 5?

Documentation like system validation reports, audit trails, user access logs, data integrity records, electronic signature records, and system operating procedures are necessary. Comprehensive documentation demonstrates that your systems are compliant and validated.

2) Can we use cloud-based systems while complying with 21 CFR Part 11 and GAMP 5?

Yes, cloud-based systems can comply with 21 CFR Part 11 and GAMP 5, provided the cloud provider offers the necessary security features, audit trails, and validation support. It’s essential to work closely with the vendor to ensure the system meets regulatory requirements.

3) How do I choose a vendor for a 21 CFR Part 11 and GAMP 5-compliant system?

Look for vendors with a proven track record in compliance, experience in the pharmaceutical industry, and strong support for system validation and training. KN Water & energy Solutions has been a leading company in the pharma market for two decades now. The experience and the expertise we hold are unparalleled. Our systems comply with the world’s most stringent standards, including 21 CFR Part 11 and GAMP 5.

4) What is the difference between validation under GAMP 5 and qualification?

Validation refers to the documented process of ensuring that a system consistently meets its intended purpose (e.g., for manufacturing). In contrast, Qualification refers to specific checks on equipment or processes, ensuring they function correctly. GAMP 5 provides a risk-based framework for both.

5) How can automation help with compliance under 21 CFR Part 11 and GAMP 5?

Automation helps reduce human errors, ensures data integrity through electronic records, and simplifies processes like audit trails, system validation, and user access management. Automated systems are often more reliable and efficient in meeting regulatory requirements.