Electronic Records or Paper Records: Which is the “Official” Record?

Introduction: A Common Yet Problematic Claim

During my consulting engagements, I frequently encounter the following assertion from pharmaceutical companies:

“In our company, the responsible person thoroughly reviews all records and signs (or affixes a seal) to them. Therefore, the paper record is the official (original) record.”

This claim is fundamentally based on the assumption of good faith—that all responsible persons always act with integrity and in accordance with regulations. However, regulatory authorities, particularly those in Europe and North America, conduct their inspections based on an opposing principle: the presumption of potential misconduct.

The Reality of Corporate Fraud: Lessons from History

Why do regulators adopt this cautious stance? History provides clear evidence that when companies face financial pressures or other crises, management may indeed direct employees to commit fraud. Consider these well-documented cases:

In Japan alone, several high-profile incidents have occurred:

• A long-established restaurant in Osaka was found to be reusing food ingredients
• A company in Nagoya falsified the origin of eel products
• A Tokyo-based confectionery manufacturer used expired milk in its products

All of these companies ultimately went bankrupt, and investigations revealed that in each case, the fraudulent activities were orchestrated by senior management, not rank-and-file employees.

This pattern is consistent globally. Generally, individual employees have no incentive to commit fraud independently—there is simply no personal benefit that would justify the risk. However, when executives under pressure issue directives, employees may feel compelled to comply.

This reality underlies the regulatory approach to data integrity and electronic records management. Regulatory authorities must design their requirements to prevent not just accidental errors, but deliberate manipulation—even when that manipulation might be ordered from the top of an organization.

The “Typewriter Excuse” Debate

The Company’s Argument

In the past, pharmaceutical companies in the United States attempted to make the following argument to the FDA:

“The true record is the paper record. We are merely using computers as tools to create these records—essentially as sophisticated typewriters.”

Their reasoning was straightforward: if the computer is functioning only as a typewriter—a device for producing paper documents—then 21 CFR Part 11 (FDA’s regulation on electronic records and electronic signatures) should not apply to their systems.

This argument became known as the “Typewriter Excuse.”

FDA’s Response

The FDA rejected this argument decisively. The agency stated that Part 11 would not apply only in cases where “computers are truly being used like typewriters, such as when no electronic record is created.”

The FDA’s reasoning highlighted a critical technical distinction between typewriters and computers:

Typewriters: Characterized by “One-Time Printing”—once a character is typed onto paper, that specific document exists as a unique, unreproducible artifact. You cannot print the same document again.

Computers: Store electronic records indefinitely, allowing unlimited reproduction. The same document can be printed repeatedly, at any time, with any modifications made to the underlying electronic record.

This fundamental difference creates significant opportunities for fraud. Using computer systems, an individual could:

1. Modify the electronic record
2. Print a new version of the document
3. Backdate their signature on the newly printed document
4. Destroy evidence of the original record

The printed output would appear legitimate, but would actually represent a falsified record.

The Critical Statement on Metadata

Paul Motise, who led the Part 11 program at the FDA during its development, made a statement that remains highly relevant today:

“Printouts cannot be inherently trusted because they do not contain the metadata information necessary to reconstruct the data or reproduce it from the original raw data.”

This statement identifies the core issue: paper printouts lack audit trails. There is no way to determine from the paper alone whether the electronic record has been modified, when it was modified, by whom, or what the original data showed. The paper provides no mechanism for detecting tampering.

Understanding Hybrid Systems

Definition and Structure

It is essential to understand that hybrid systems represent a specific architecture where:

• Records are maintained electronically in a computer system
• Only the signatures (whether handwritten, stamped, or typed) are applied to paper printouts

The critical point is this: In a hybrid system, the actual record remains electronic. The paper serves merely as a signed approval artifact, not as the complete official record.

Regulatory Inspection Approach

When regulatory inspectors audit a company using a hybrid system, they employ a specific methodology:

1. They review the electronic records in the computer system
2. They verify the signatures on the paper printouts
3. They compare the two to detect any discrepancies or evidence of tampering

The primary objective of this inspection approach is fraud detection. By maintaining both electronic records and paper signatures, the company creates multiple data points that can be cross-verified.

The Prohibition on Deleting Electronic Records

This leads to an absolutely critical requirement that many companies misunderstand:

Even though signatures have been applied to paper printouts, the underlying electronic records must NEVER be deleted.

Deleting the electronic records after obtaining signatures on paper:

• Eliminates the audit trail
• Removes the ability to verify data integrity
• Prevents detection of potential fraud
• Violates fundamental principles of 21 CFR Part 11 and equivalent regulations

The electronic record, with its complete metadata and audit trail, is essential for demonstrating compliance and maintaining data integrity throughout the required retention period.

Modern Data Integrity Context

The Evolution to Data Integrity Principles

Since the original implementation of 21 CFR Part 11 in 1997 and the Japanese ER/ES Guidance in 2005, the regulatory landscape has evolved significantly. The contemporary focus has shifted to comprehensive data integrity principles, often summarized by the acronym ALCOA+:

• Attributable: Data must be traceable to the individual who generated it
• Legible: Data must be readable and permanent throughout its lifecycle
• Contemporaneous: Data must be recorded at the time the activity is performed
• Original: The first capture of data or a certified true copy
• Accurate: Data must be free from errors and reflect true observations

The “+” represents additional modern requirements:

• Complete: All data must be retained; nothing should be deleted or omitted
• Consistent: Data must be recorded in a standardized manner
• Enduring: Data must remain accessible throughout the required retention period
• Available: Data must be readily retrievable for review and inspection

Current Regulatory Framework (2024-2026)

FDA Updates: In October 2024, the FDA published final guidance titled “Electronic Systems, Electronic Records, and Electronic Signatures in Clinical Investigations: Questions and Answers (Revision 1).” This guidance emphasizes:

• Risk-based approaches to electronic system validation
• The critical importance of metadata preservation
• Enhanced requirements for audit trail review
• Explicit expectations for hybrid systems, noting that electronic records must be maintained regardless of paper signatures

Japanese ER/ES Guidance: Japan’s ER/ES Guidance has been updated with a comprehensive revision published in March 2024. The Japan CRO Association released detailed explanations emphasizing:

• The three fundamental requirements: authenticity (真正性), readability (見読性), and preservation (保存性)
• Alignment with FDA Part 11 principles
• Specific guidance for decentralized clinical trials (DCT)
• Clarification on electronic consent processes

Comparison: Paper-Based vs. Electronic Records Systems

The following table illustrates the critical differences between traditional paper-based systems and properly implemented electronic records systems:

Aspect	Paper-Based System	Electronic Records System	Hybrid System Risk
Audit Trail	No automatic audit trail; difficult to detect modifications	Complete, time-stamped audit trail showing all changes, by whom, and when	Electronic audit trail may be deleted if records are improperly managed
Metadata	Limited metadata (date of signature only)	Comprehensive metadata: creation time, modification history, user IDs, system information	Lost if electronic records are deleted after paper signature
Reproducibility	Cannot reproduce identical copy; each printout is unique	Can reproduce exact record with all associated data	Risk of producing modified versions if electronic record is altered
Storage Requirements	Large physical space, environmental controls needed	Minimal physical space, server-based storage	Requires both electronic and paper storage
Retrieval Speed	Slow; requires manual search	Fast; searchable by multiple parameters	Can be slow if electronic records not properly maintained
Fraud Detection	Difficult; requires forensic analysis of physical documents	Relatively easy with proper audit trail review	Impossible if electronic records are deleted
Regulatory Compliance	Acceptable but less preferred by regulators	Preferred if properly implemented	High risk if not properly managed
Long-term Preservation	Paper degrades; ink fades; documents can be physically destroyed	Can be preserved indefinitely with proper backup and migration strategies	Risk of losing electronic component

Conclusion: Best Practices for Record Management

Based on current regulatory expectations and data integrity principles, organizations should adopt the following practices:

For Electronic Records Systems:

1. Implement robust audit trail functionality that cannot be disabled
2. Ensure all metadata is captured and preserved automatically
3. Validate systems thoroughly before use in GxP environments
4. Conduct regular audit trail reviews as part of quality oversight
5. Maintain electronic records for the entire required retention period

For Hybrid Systems: If your organization uses a hybrid system where electronic records are signed on paper:

1. Never delete electronic records after obtaining paper signatures
2. Maintain both the electronic record (with full audit trail and metadata) and the signed paper copy
3. Clearly document in your procedures which record (electronic or paper) is defined as the “official” record for each process
4. Train staff on the importance of maintaining both forms of the record
5. During internal audits, verify that electronic records are being preserved appropriately
6. Prepare to provide both forms to regulatory inspectors

Understanding Regulatory Expectations: Remember that regulatory inspectors will:

• Expect to see complete electronic records with audit trails
• Compare electronic records against signed paper documents
• Look for discrepancies that might indicate tampering
• Verify that your procedures accurately describe your actual practices
• Assess whether staff understand the importance of maintaining electronic records

The fundamental principle remains clear: electronic records, with their comprehensive audit trails and metadata, provide the transparency and traceability essential for ensuring data integrity in pharmaceutical operations. Any approach that undermines these capabilities—such as deleting electronic records after obtaining paper signatures—fundamentally compromises regulatory compliance and patient safety.

In an era of increasing regulatory scrutiny on data integrity, organizations must recognize that electronic records are not merely convenient alternatives to paper—they are, when properly managed, superior tools for ensuring the trustworthiness and reliability of pharmaceutical data.