Differences Between Calibration and Inspection

Introduction

When auditing pharmaceutical and medical device manufacturing facilities, the author has frequently observed cases where “calibration” and “inspection” are confused. Many companies’ SOPs (Standard Operating Procedures) state that “inspection can be replaced by calibration,” which is based on an incorrect understanding. Calibration and inspection are independent activities with different purposes and roles, and cannot substitute for each other. This article clarifies these differences and explains the importance of proper equipment management.

What is Calibration?

Definition of Calibration

According to JIS Z 8103:2019 (Glossary of terms used in measurement), calibration is defined as follows:

“An operation that, under specified conditions, in a first step, establishes a relation between the quantity values with measurement uncertainties provided by measurement standards and corresponding indications with associated measurement uncertainties and, in a second step, uses this information to establish a relation for obtaining a measurement result from an indication”

This definition was substantially revised in the transition from the 2000 version to the 2019 version to ensure consistency with the International Vocabulary of Metrology (ISO/IEC Guide 99:2007, commonly known as VIM3).

The Essence of Calibration

To understand the essence of calibration, the following key points must be grasped:

1. Calibration is “Understanding the Current State”

Calibration is the process of clarifying the relationship between the values indicated by a measuring instrument and the true values, using reference standards that are traceable to international or national standards. Specifically, it is the work of quantitatively determining the “instrument error” (measurement error), which is the difference obtained by subtracting the true value from the value indicated by the measuring instrument.

2. Calibration Does Not Include Adjustment

Even in the JIS Z 8103:2019 definition, the principle that the act of calibration itself does not include adjusting the instrument to correct errors remains consistent with the previous version (2000). Calibration is purely an activity for understanding the current state of measuring instruments and evaluating their performance.

However, in practical applications, when calibration is outsourced to external calibration agencies, it is common practice to have adjustment work performed simultaneously if the instrument error exceeds acceptable limits. Even in such cases, calibration (measurement) and adjustment (correction) should be conceptually distinguished as separate operations.

3. Ensuring Traceability

One of the most important elements in calibration is measurement traceability. This refers to the property that allows measurement results to be related to national or international standards through an unbroken chain of calibrations, each contributing to the measurement uncertainty. Ensuring traceability guarantees the reliability and international consistency of measurement results.

Regulatory Requirements for Calibration

ISO 9001:2015 Requirements

The international standard for quality management systems, ISO 9001:2015, explicitly states the following requirements in Section 7.1.5.2 “Measurement traceability”:

• Measuring equipment must be calibrated or verified, or both, at specified intervals or before use, against measurement standards traceable to international or national measurement standards
• The calibration status must be identified
• Equipment must be safeguarded from adjustments, damage, or deterioration that would invalidate the calibration status and subsequent measurement results
• When measuring equipment is found to be unfit for its intended purpose, the organization must determine whether the validity of previous measurement results has been adversely affected and must take appropriate action as necessary

Calibration in GMP and QMS Regulations

In pharmaceutical manufacturing, GMP regulations (Good Manufacturing Practice for drugs and quasi-drugs) apply, while in medical device manufacturing, QMS regulations (Quality Management System for medical devices and in vitro diagnostic reagents) apply. These regulations also require appropriate calibration of measuring and testing instruments, as well as retention of calibration records.

Particularly, the 2021 revision of GMP regulations introduced the concept of ICH Q10 (Pharmaceutical Quality System), requiring management of measuring instruments based on quality risk management. This has made it possible to scientifically establish calibration frequency and methods according to the criticality of measuring instruments and their impact on product quality.

What is Inspection?

Inspection is an activity to confirm that measuring instruments are functioning normally and is broadly classified into routine inspection (pre-use inspection) and periodic inspection.

Routine Inspection (Pre-use Inspection)

Purpose of Routine Inspection

Routine inspection is the work of confirming, before using a measuring instrument, that the instrument is operating normally and is in a state capable of appropriate measurement.

Effective Methods for Routine Inspection

Many companies have routine inspection procedures that consist only of formal inspection items such as “confirm that the power switch turns on” or “confirm that the indicator lamp lights up.” However, these are things that can be easily confirmed simply by using the equipment, and are insufficient from a quality assurance perspective.

Truly effective routine inspections should be conducted using one of the following methods:

1. Functional Verification Using Standards

   • Measure standard samples or reference standard materials with known values and confirm that appropriate values (values within acceptable ranges) are obtained
   • This method can demonstrate that the entire measuring instrument system is functioning normally

2. Cross-verification Using Multiple Instruments

   • When standard samples are not available or are difficult to obtain, measure the same specimen using two or more measuring instruments of the same specification and confirm that there is no significant difference in measured values
   • This method is particularly useful in biological measurements or specialized analyses

Recording Routine Inspections

The results of routine inspections must always be recorded. Records should include the date and time of inspection, information about the standard samples used, measurement results, judgment (pass/fail), signature of the person conducting the inspection, etc. These records serve as important evidence to ensure the reliability of measurement results.

Periodic Inspection

Purpose and Content of Periodic Inspection

Periodic inspection is the work of checking the internal mechanisms and wear parts of measuring instruments and performing cleaning, adjustment, parts replacement, etc., as necessary. Generally, because it requires specialized knowledge and special tools or measuring instruments, it is conducted by the equipment manufacturer or specialized contractors.

Main content of periodic inspection:

1. Overhaul (Disassembly Inspection and Repair)

   • Disassemble the equipment and check the wear, deterioration, and contamination status of internal parts
   • Perform cleaning, lubrication, adjustment, and parts replacement as necessary

2. Performance Verification Using Special Measuring Instruments

   • Use special measuring instruments not normally possessed by the company to verify that equipment performance meets specifications
   • Examples: Stray light measurement for spectrophotometers, dead volume measurement for chromatographs, etc.

3. Preventive Maintenance

   • Systematically replace parts expected to deteriorate before failure occurs
   • This prevents interruption of measurements due to sudden failures and the generation of inappropriate measurement data

Frequency of Periodic Inspection

The frequency of periodic inspection should be established considering the following factors:

• Manufacturer’s recommended frequency
• Usage frequency and severity of the usage environment
• Age of the equipment
• Past failure history and calibration history
• Importance of the items being measured (impact on product quality)

ISO 9001:2015 and GMP/QMS regulations require risk-based approach management. Equipment measuring important characteristics or equipment used with high frequency requires periodic inspection at shorter intervals.

Relationship Between Calibration and Inspection

Item	Calibration	Inspection
Primary Purpose	Quantitatively understand the accuracy (instrument error) of measuring instruments	Confirm that measuring instruments are functioning normally
Implementation Timing	Periodically (e.g., once a year) or as needed	Routinely (before use) and periodically
Standards Used	Standards traceable to national standards	Standard samples, reference standards, or equivalent instruments
Result Recording	Calibration certificate (including instrument error and uncertainty)	Inspection record (including pass/fail judgment)
Implementation of Adjustment	Not included in principle (separate operation)	Can be implemented as necessary
Implementer	Accredited calibration organization, manufacturer, or in-house calibration staff	User, maintenance staff, or specialized contractor
Regulatory Requirements	Explicitly required by ISO 9001, GMP/QMS regulations	Indirectly required by GMP/QMS regulations, ISO 9001

Calibration and inspection are in a complementary relationship with each other. Even if the accuracy of a measuring instrument is confirmed through calibration, neglecting daily functional verification (inspection) may result in missing sudden failures or abnormalities. Conversely, even if routine inspections show no abnormalities, without periodic calibration, gradual accuracy degradation cannot be detected.

Therefore, the idea of “replacing inspection with calibration” fails to understand the essence of measuring instrument management and is inappropriate from a quality assurance perspective. Both must be properly planned and implemented as independent important activities.

Aging of Measuring Instruments and Risk-Based Management

Issues Concerning Use of Equipment Beyond Service Life

One of the nonconformities frequently encountered in the author’s audit experience is the case of continued use of measuring instruments that have significantly exceeded their service life (for example, instruments purchased more than 10 years ago).

Audited companies often provide the following defenses:

• “It has never failed and is operating normally”
• “We perform regular calibration, and when calibration drift occurred, we adjusted it appropriately”
• “No problems have occurred in product measurement values”

However, this way of thinking has the following serious problems:

1. Past Performance is Not a Guarantee of the Future

The fact that there has been no failure does not guarantee that there will be no failure from tomorrow onward. Equipment inevitably deteriorates over time, and the longer the period of use, the greater the risk of sudden failure.

2. Frequency and Degree of Calibration Drift

The fact that calibration drift has occurred in the past indicates that the measuring instrument is becoming unstable over time. Even if adjustment is performed during calibration, the possibility that large instrument error will recur during the period until the next calibration is higher than with new equipment.

3. Temporal Decline in Measurement Accuracy

Equipment performance gradually declines even without visible failure. In particular, deterioration of optical components, changes in electronic component characteristics, and wear of mechanical parts cause degradation in measurement reproducibility and linearity. These may not be detectable by normal calibration.

Management by Risk-Based Approach

ISO 9001:2015 and GMP/QMS regulations require measuring instrument management through a risk-based approach. Specifically, calibration frequency and renewal timing should be determined considering the following factors:

1. Importance of Measurement Target

• Equipment used for measuring Critical Quality Attributes (CQA) requires more stringent management
• Equipment used for measuring items with small margins relative to specification values requires high accuracy

2. Age of Equipment

• Progressively shorten calibration frequency according to age
• Example: Once a year for 0-5 years after purchase, twice a year for 5-8 years, three times a year for 8+ years, or consider renewal

3. Past Calibration History

• Analyze trends in calibration drift (magnitude and variation of instrument error) and optimize calibration intervals
• Equipment with repeatedly large calibration drift should be considered for renewal

4. Usage Frequency and Usage Environment

• Equipment used with high frequency or in harsh environments requires calibration and inspection at shorter intervals
• Even for equipment with low usage frequency, attention must be paid to deterioration due to long-term non-use (e.g., solidification of lubricating oil, oxidation of electrical contacts)

Importance of Measuring Instrument Renewal Plans

From a quality assurance perspective, systematic renewal of measuring instruments is essential. Renewal plans should be developed based on the following criteria:

1. Equipment exceeding manufacturer’s recommended service life
2. Equipment for which repair parts are difficult to obtain
3. Equipment with frequent calibration drift
4. Equipment unable to comply with the latest technical standards or regulatory requirements
5. Equipment for which manufacturer support has ended

Rather than the uniform approach of “conducting calibration once a year is sufficient,” it is important to evaluate the condition and risk of individual equipment and perform appropriate management.

Conclusion

Calibration and inspection are independent activities with different purposes, and both must be properly implemented to ensure the reliability of measuring instruments.

Calibration is:

• An activity to quantitatively understand the accuracy (instrument error) of measuring instruments
• Conducted using standards traceable to national standards
• Does not include adjustment work (conceptually a separate operation)
• Explicitly required by ISO 9001 and GMP/QMS regulations

Inspection is:

• An activity to routinely and periodically confirm that measuring instruments are functioning normally
• In routine inspection, functional verification using standard samples is important
• In periodic inspection, overhaul and preventive maintenance are performed
• A necessary activity independent of calibration

In risk-based management:

• Set management intensity according to the importance of measurement targets
• Change calibration frequency according to equipment age
• Optimize management methods by analyzing past calibration history
• Maintain measurement reliability through systematic equipment renewal

In pharmaceutical and medical device companies, proper management of measuring instruments directly affects product quality and safety. By correcting the erroneous understanding that “inspection can be replaced by calibration” and properly implementing both calibration and inspection, true quality assurance can be achieved. Furthermore, properly assessing the risks of aging and formulating long-term management plans including equipment renewal is essential for establishing a sustainable quality assurance system.