Understanding Legibility: A Fundamental Requirement for Electronic Records

Basic Concept of Legibility

The term “legibility” (見読性, kendokusei in Japanese) is rarely used in everyday life, but it represents an extremely important concept in the management of electronic records for pharmaceutical product approval applications. Legibility refers to the requirements for outputting electromagnetic records (electronic records) in a human-readable format and maintaining them in a state where their content can be understood.

Unlike paper records, electromagnetic records cannot be read directly by the human eye. Data is stored internally in computers as digital signals of zeros and ones, and must be converted into a format that humans can understand through some method. For this reason, compared to storage on paper media, when storing in electromagnetic record format, it is essential to have in place measures that allow output in a human-readable form.

Three Output Formats Required by the Japanese ER/ES Guidelines

The Japanese ER/ES Guidelines (“Regarding the Use of Electromagnetic Records and Electronic Signatures in Applications for Approval or Permission of Pharmaceuticals, etc.,” implemented in April 2005) require output in the following three formats to ensure legibility.

1. Display on Display Devices

It must be possible to view the content of electromagnetic records on a computer screen. The content displayed must accurately match the stored content.

2. Printing on Paper

It must be possible to output the content of electromagnetic records to paper media. There must be no loss of output due to issues such as printer resolution.

3. Copying to Electromagnetic Recording Media

It must be possible to copy the content of electromagnetic records to electromagnetic recording media such as CD-Rs. This requirement is often misunderstood, as will be discussed later.

The Concept of “Legible” at the FDA

The U.S. Food and Drug Administration (FDA) uses the term “Legible” as the equivalent of legibility in Japanese regulations. FDA’s 21 CFR Part 11 (implemented in 1997) defines requirements for electronic records and electronic signatures, with the concept of legibility occupying an important position.

The requirement sought by the FDA is not simply “readability” but rather that “data can be identified so that appropriate actions can be taken upon viewing it.” In other words, data must be output in a format where its meaning can be understood.

Specifically, it is insufficient for data to be displayed merely as numbers or codes such as “1” or “2.” It must be output in a form where the meaning is clear, such as “Male” or “Female,” or “Inpatient” or “Outpatient,” or “Normal” or “Abnormal.” Not only code values but also their meanings (decoded values) must be stored simultaneously and be capable of being output.

Common Misconception: What “Copying to Electromagnetic Recording Media” Means

Among the legibility requirements, a particularly common misconception concerns “copying to electromagnetic recording media.”

Incorrect Understanding

Many people understand this requirement as “database dumps” or “creating backup files.” However, this is clearly incorrect.

Correct Understanding

What regulatory authorities require is outputting to electromagnetic recording media such as CD-Rs in a format similar to printing on paper. Specifically, the following formats are applicable:

• Output in PDF format
• Output in Microsoft Excel format
• Output in Microsoft Word format
• Output in statistical analysis software (such as SAS) dataset format (depending on the case)

What is important is that these formats must be readable with standard software. When regulatory authority inspectors take electromagnetic records away, they must be in a state where they can “identify the data so that appropriate actions can be taken.”

Difference from Backup

Copying to electromagnetic recording media and system backup have completely different purposes and methods. While backup aims at data recovery in case of system failure, copying to electromagnetic recording media is intended for inspection and review by regulatory authorities.

Relationship with Data Integrity: ALCOA+ Principles

Legibility is positioned as part of the broader concept of data integrity. Internationally, the “ALCOA+ Principles” are widely recognized as principles for ensuring data integrity.

Principle	Term	Description
Attributable	Attributability	Data can be identified as to who created or modified it
Legible	Legibility	Data is readable and understandable
Contemporaneous	Contemporaneity	Data is recorded simultaneously with the activity
Original	Originality	The original record or its true copy
Accurate	Accuracy	Data accurately reflects the facts
Complete	Completeness	All necessary data is present (+)
Consistent	Consistency	Data is consistent and chronological (+)
Enduring	Endurance	Data is maintained throughout the retention period (+)
Available	Availability	Data can be accessed when needed (+)

Among these, Legible (legibility) is positioned as a fundamental element of the ALCOA+ principles and corresponds completely to the “legibility” requirements in the Japanese ER/ES Guidelines.

Latest Regulatory Trends

Trends in Japan

In March 2024, the Japan Association of Clinical Research Organizations (JCROA) published the “Revised Edition ‘Commentary on ER/ES Guidelines'” and “Commentary on ER/ES Guidelines for General Users.” These documents provide more detailed and accessible explanations of the three principles of authenticity, legibility, and preservation, designed to be understandable even for those who are not IT specialists.

The revised edition provides detailed references to the migration of electromagnetic records and data format conversion, presenting specific procedures for responding to technological obsolescence.

Trends at the FDA

In October 2024, the FDA issued final guidance on the use of electronic systems, electronic records, and electronic signatures in clinical investigations. This guidance provides a contemporary interpretation of how Part 11 requirements should be applied in the context of increasing use of digital health technologies (DHT) and real-world data (RWD).

The guidance emphasizes that even when using cloud-based systems or mobile applications, the basic requirements for ensuring data legibility, accuracy, and completeness remain unchanged.

Progress in International Harmonization

The Japanese ER/ES Guidelines are recognized as having essentially equivalent content to FDA 21 CFR Part 11, with no significant differences in practical application. The Ministry of Health, Labour and Welfare has clarified this intent in public comments.

Furthermore, ICH E6(R2) “Guideline for Good Clinical Practice” (implemented in 2018) also provides detailed provisions on quality and integrity requirements for electronic records, with global harmonization progressing.

Practical Considerations

Key Points for Ensuring Legibility

1. Storage of Decoded Values: For coded data, ensure that their meanings (decoded values) are also stored simultaneously and can be output
2. Use of Standard Formats: Use formats readable with widely available software such as PDF and Microsoft Office formats
3. Retention of Metadata: Ensure that metadata such as data creator, creation date and time, and change history can also be output
4. Response to Long-term Storage: Considering technological obsolescence, establish procedures for data migration and format conversion as necessary to maintain legibility throughout the retention period

Preparation for Inspections

To prepare for regulatory authority inspections, it is important to confirm the following points:

• Can you demonstrate the ability to output electromagnetic records in three formats (display on screen, printing on paper, copying to electromagnetic recording media)?
• Is the output data complete and accurate, and in a format where its meaning can be understood?
• Are procedures for ensuring legibility documented and properly implemented?
• Is there a mechanism in place to maintain legibility throughout the data retention period?

Summary

Legibility is a basic and important requirement when using electromagnetic records. Not only must “data be readable,” but it must also be maintained in a state where “its meaning can be understood and appropriate actions can be taken.”

In particular, regarding copying to electromagnetic recording media, it is important to correctly understand that this means output in standard formats such as PDF, not database dumps.

While referencing the latest guidance and commentaries published in 2024, it is essential to build systems and procedures that appropriately meet legibility requirements, including from a data integrity perspective, for pharmaceutical product approval applications.

References

• Ministry of Health, Labour and Welfare “Regarding the Use of Electromagnetic Records and Electronic Signatures in Applications for Approval or Permission of Pharmaceuticals, etc.” (April 1, 2005)
• Japan Association of Clinical Research Organizations “Revised Edition ‘Commentary on ER/ES Guidelines'” (March 2024)
• FDA “21 CFR Part 11 – Electronic Records; Electronic Signatures” (1997)
• FDA “Electronic Systems, Electronic Records, and Electronic Signatures in Clinical Investigations: Questions and Answers” (October 2024)
• ICH E6(R2) “Guideline for Good Clinical Practice” (2018)