Common Mistakes in Validation Documentation in Pharmaceuticals

Validation documentation is the fundamental layer to follow regulatory guidelines within the pharmaceutical space; it provides documented proof that the systems, processes and equipment are being used and performing as intended. Validation documentation can relate to equipment qualifications, process validations or computerized systems validations. Validation documentation must be completed adequately to comply with the Good Manufacturing Practices.

Yet the majority of regulatory observations received by pharmaceutical companies are not necessarily due to the fact that validation requirements were not met, it could be due to incomplete or inconsistent validation documentation being available. Even minor documentation errors may create significant problems during an inspection/audit from agencies such as the U.S. Food & Drug Administration.

The purpose of this article is to discuss the most commonly made errors related to validation documentation and to provide recommendations for avoiding these mistakes.

Why Validation Documentation is Critical

The purpose of validation documentation is many-fold in that it:

• Validates that you have performed validation of products as they are required by regulatory regulations.
• Provides a traceable history of all validation activities performed.
• Validates quality and safety of your product.
• Provides a means to ensure that processes are performed in a consistent manner.

The regulators depend on documentation and will state that if documentation is missing, the actions are considered as not being done.

Common Mistakes in Validation Documentation

1. Incomplete Documentation

One of the biggest problems is there is no complete information.
Examples include:

• Test results are missing
• Protocols are incomplete
• Acceptance criteria are not present
• Scope of the Item is never defined

When documentation is incomplete, verification of whether proper validation has been done cannot be accomplished.

How to Avoid: Do not approve protocols or reports until every section of the document is totally and completely filled out. Use a checklist of required items to verify these items.

2. Poorly Defined User Requirements

User Requirements Specification (URS) are the basis for validation. Most companies do not produce valid User Requirement Specification documents.
Common Problems Associated:

• Most User Requirements Specification Statements are not detailed enough
• Some URS statements do not contain any critical requirements
• Some URS statements contain no reference to essential paths of traceability

Negative Impact: If User Requirements Specifications are not clear in their definitions, they do not cover all testing needed for validation.
Suggestion: Develop clear and easily understood User Requirements Specifications that are testable.

3. Lack of Traceability

Traceability ensures that you test and validate all requirements.
Common Errors:

• There is no traceability matrix to track all URS requirements
• There are no links between the URS, FS and testing requirements
• Not all of the URS requirements have been verified

What to Do: Have a traceability matrix that links all of the URS to testing requirements.

4. Repetitive Documentation with Copy-Paste

The most common problem is not modifying existing templates for reuse.
Problems include:

• You are putting in irrelevant information from the template
• You are putting in the wrong equipment into the documentation
• You are using incorrect information in the documentation

Potential Risk: Regulatory agencies will identify that the documentation was copied and you lose your credibility.
Best Practice: For any document, you will need to modify the document in your own manner to represent only the current process.

5. Inadequate Risk Assessment

ICH Q9 Quality Risk Management suggests that a risk-based method should be used for validation; Failure to do a thorough risk assessment can lead to testing that is not backed by an adequate risk assessment; not properly documenting risk assessments (e.g., through supporting documents) and there being no clear link between the completed risk assessment and the validation.

Improvements can be made through the use of structured risk assessment and documented records of the complete risk assessment.

6. Missing or Weak Acceptance Criteria

Acceptance criteria are how you define success.
Common issues where acceptance criteria are not used:

• Not defined
• Too broad/subjective
• Not in accordance with the regulations.

Impact: Testing has no meaning if there are no defined criteria.
Solution: Improvements can be made by defining the acceptance criteria and making them measurable and obtainable.

7. Improper Handling of Deviations

It is acceptable to have deviations during validation, however deviations that are not handled correctly are a significant risk.
Common mistakes in managing deviations include:

• Not documenting deviations
• Not performing a root cause analysis (into the cause of the deviation)
• Not taking corrective action.

Best Practice: Document all deviations and investigate thoroughly to correct the deviation and prevent re-occurrence through CAPA.

8. Inconsistent Data Recording

Data integrity is a major area of concern and is quite easily compromised due to:

• Overwriting data
• No timestamps on the records
• No audit trails available to determine the validity of the record

The creation and maintenance of documentation are essential to support the integrity of the record; Therefore, record keeping must be designed around the ALCOA+ data integrity principles:

• Attributable
• Legible
• Contemporaneous
• Original
• Accurate

9. Lack of Version Control

The management of documentation must be controlled.
Some mistakes that happen with versioning:

• Utilizing the wrong or dated version
• Not maintaining a chain of revisions
• Having multiple uncontrolled copies

Solution: The overall solution is to create a good document management system.

10. Poor Review and Approval Process

Documents get approved without being properly reviewed.
Problems that result from approval without proper review:

• A cursory review
• No signature
• Invalid approval order

Impact: The result is that substantial, material deficiencies are left undetected.
Solution: The overall solution is to establish a multi-level review and an appropriate approval workflow.

11. Incomplete Training Records

All staff members involved in validation need to receive training.
Some errors made in training documents:

• No training records
• Untrained staff performing validations
• No record of competency

Solution: The overall solution is to maintain training records and ensure competency.

12. Failure to Update Documents After Changes

Change control is essential. Errors made when updating documents after change:

• Failing to update a document after the system changes
• Using prior validation documentation
• Ignoring re-validation requirements

Best Practice: Link documentation for validation with change control systems.

13. Overcomplicated Documentation

There are; some organizations create documents that are needlessly complicated.
Problems with over complicated documentation:

• Hard to read
• Increase likelihood of error
• Takes longer to do

Solution: The overall solution is to write documents simply, clearly and practically.

14. Lack of Alignment with Regulations

Validation documentation must align with regulation:

• 21 CFR Part 11
• GAMP 5

Failure to comply with these regulations results in regulatory observations.

Impact of Poor Validation Documentation

Poor validation documentation can have serious repercussions on the quality system such as:
- Regulatory Warnings or Observations
- Recalls of Products
- Increased Approval Time for Products
- Damage to Corporate Reputation
It can lead to plant shutdown (in the most extreme cases)

Practices for Validation Documentation

1. Use a Structured Approach

Establish criteria, standards and template(s) for documentation.

2. Ensure the Integrity/Accuracy of Data

Strictly adhere to ALCOA+ principles.

3. Maintain Traceability

Link all requirements, tests and results through documentation.

4. Implement an Effective Review Process

Qualified personnel must verify that all documentation meets the established criteria for verification.

5. Use a Risk Based Validation Approach

Evaluate the risk associated with each system/process.

6. Train Employees on Validation Requirements

Provide training to employees assigned to a validation project.

7. Keep Validation Documentation Audit Ready

Validation documentation must be clear, complete and easily accessible.

Role of Quality Assurance (QA)

Responsibilities of QA include the following:

• Review of validation documents
• Regulatory Compliance Assurance
• Approval of validation protocols and reporting
• Deviation Monitoring and Corrective and Preventive Action (CAPA) Monitoring

The quality assurance organization must verify that all validation documentation meets the requirements set forth by regulators.

Digital Transformation and Documentation Challenges

As digital solutions are utilized more, there is an extensive list of challenges regarding digital documentation.
Some of these challenges:

• Mismanagement of Electronic Records
• No audit trail associated with electronic records
• Potential risks associated with Data Security

As it relates to electronic records, Companies must comply with the provisions of 21 CFR Part 11.

Validation documentation is essential to all pharmaceutical quality systems and it is not simply a regulatory requirement or obligation. Organizations do not fail due to a lack of validating documentation process; rather, they often lack adequate validating documentation that meets the expectations of applying regulatory requirements.

Avoiding common validating documentation mistakes, such as failure to provide sufficient documentation, poor traceability, inadequate risk assessment and weak review processes, will aid pharmaceutical companies in achieving compliance with regulatory agencies and maintaining quality pharmaceutical products.

Having a well-documented validating documentation process provides evidence of control, evidence of consistency and evidence of commitment to patient safety and therefore is one of the primary pillars of successful pharmaceutical production.

Frequently Asked Questions (FAQs) on Common Mistakes in Validation Documentation

Q1. What is meant by validation documentation?

Answer: It is the evidence of systems and processes working as intended as documented.

Q2. Why should you have validation documentation?

Answer: To ensure compliance with regulations, traceability of requirements and product quality.

Q3. What is commonly done wrong in validation documentation?

Answer: Not having completed or well-defined documents.

Q4. How is traceability defined in validation?

Answer: By linking requirements to tests and the results.

Q5. What is the meaning of ALCOA+ ?

Answer: These are principles of data integrity that help ensure the data is reliable.

Q6. What regulation governs electronic records?

Answer: 21 CFR Part 11.

Q7 What is GAMP 5?

Answer: The 5th version of GAMP gives you a framework to do your validation.

Q8. How can errors be avoided?

Answer: By planning, reviewing, training and using a risk-based methodology.

Get ready to use editable Validation Protocols in MS-Word FormatView List

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