Differences in Change Application Requirements for Medical Device Regulations Between Japan and the United States

Introduction

Medical devices are products that directly affect human life, and therefore stringent regulations are imposed throughout their lifecycle—from development and marketing to post-market surveillance. When modifying a product, appropriate applications must be submitted according to the nature of the changes. This article examines the differences between Japan’s and the United States’ medical device change application systems. The objective is to organize the fundamental knowledge necessary for medical device manufacturers engaged in international business expansion.

Japan’s Medical Device Change Application System

1. Legal Framework

In Japan, change management for medical devices is conducted in accordance with the “Act on Securing Quality, Efficacy and Safety of Pharmaceuticals, Medical Devices, Regenerative and Cellular Therapy Products, Gene Therapy Products, and Cosmetics” (commonly referred to as the Pharmaceuticals and Medical Devices Act, or PMD Act). Changes to approved medical devices are classified into the following three categories based on their content:

• Partial Change Approval Application (PAPR)
• Minor Change Notification (MCN)
• Post-Approval Change Management Protocol (PACMP)

2. Partial Change Approval Application (PAPR)

When changes significantly affect the quality, efficacy, or safety of a product, a Partial Change Approval Application is required. Specifically, the following types of changes fall under this category:

• Changes to intended use or indications for use
• Significant changes to shape, structure, or operating principles
• Changes to raw materials (particularly materials of biological origin)
• Design changes affecting performance or safety
• Changes to sterilization methods
• Changes to software with significant impact on device functionality

The review period for new medical device approvals at the Pharmaceuticals and Medical Devices Agency (PMDA) has been improving, with target periods of 10 months for standard devices and 6 months for priority devices under the SAKIGAKE designation system (introduced in 2014 for innovative medical devices). However, change applications may still require substantial review periods depending on the complexity of the changes. During this period, the changes cannot be implemented in principle, which can significantly impact product development cycles.

3. Minor Change Notification (MCN)

For minor changes that do not affect quality, efficacy, or safety, a Minor Change Notification suffices. The notification must be submitted within 30 days after implementing the change, and prior approval from PMDA is not required. The following types of changes fall under this category:

• Changes to the name or address of manufacturing facilities (when not affecting manufacturing processes)
• Minor changes to manufacturing methods (not affecting critical processes)
• Minor changes to specifications and test methods
• Changes to labeling (excluding warnings and contraindications)
• Changes that do not require Quality Management System (QMS) conformity assessment

It should be noted that the boundary between what constitutes a “minor change” versus a change requiring approval can sometimes be ambiguous. Manufacturers are encouraged to consult with PMDA or utilize the pre-consultation system when uncertain about the appropriate classification.

4. Post-Approval Change Management Protocol (PACMP)

This is a new system introduced through the 2020 amendment to the PMD Act, which became effective in August 2021. Under this system, manufacturers submit a change plan and evaluation methodology to PMDA for advance confirmation. Once the plan is approved, changes implemented in accordance with the protocol only require notification of results, rather than a full approval application. Even changes that would normally require a Partial Change Approval Application can be handled through notification alone if they are executed according to an approved change protocol.

The PACMP system is conceptually similar to the United States’ FDA guidance on manufacturing changes, but adoption in Japan has been gradual as manufacturers become familiar with the requirements and benefits. As of 2025, PMDA has been actively encouraging the use of PACMP to streamline change management while maintaining safety standards.

United States Medical Device Change Application System

1. Legal Framework

In the United States, the Food and Drug Administration (FDA) regulates medical devices under the “Federal Food, Drug, and Cosmetic Act” (FD&C Act). Change management primarily involves the following application types:

• PMA Supplement (Premarket Approval Supplement)
• Special 510(k)
• 30-Day Notice
• Annual Report
• Changes Being Effected (CBE)
• Letter to File (internal documentation)

2. PMA Supplement (Premarket Approval Supplement)

This application is required for significant changes to medical devices that have received PMA approval (Class III devices). Depending on the nature of the change, these are classified as follows:

Panel Track Supplement: Changes of highest significance, such as adding new indications for use. These require review by an FDA advisory panel and typically take 180 days or longer for review.

180-Day Supplement: Significant design changes, major manufacturing process changes, or other modifications that could affect safety or effectiveness. FDA aims to review these within 180 days.

Real-Time Supplement: Relatively minor changes that still require review, such as certain labeling changes or manufacturing site additions. FDA aims to review these within 90 days, with many being processed more quickly.

30-Day Notice: Manufacturing process changes, particularly those related to quality system modifications, where the change may be implemented 30 days after FDA receives the notice unless FDA objects.

3. Changes Related to 510(k)

Changes to medical devices that received 510(k) clearance (primarily Class II devices) are handled as follows:

New Traditional 510(k): Required when changes significantly affect safety or effectiveness, or when the modified device is no longer substantially equivalent to the predicate device. The review target is 90 days under the FDA’s MDUFA (Medical Device User Fee Amendments) performance goals, though actual review times can vary.

Special 510(k): Used for design changes made under design controls when there is no change to the intended use. This streamlined pathway allows for a 30-day review target. The Special 510(k) program was established to encourage manufacturers to make improvements while maintaining regulatory oversight.

Letter to File: Minor changes that do not affect safety or effectiveness and do not require FDA notification. These are documented internally as part of the manufacturer’s quality system.

4. Changes Being Effected (CBE)

For certain supplements to PMA or 510(k) devices, manufacturers may implement changes immediately upon submitting the notification to FDA. This is typically limited to changes that do not significantly affect safety or effectiveness but still warrant FDA awareness. The CBE pathway provides flexibility while maintaining regulatory oversight.

5. Letter to File (Internal Documentation)

This corresponds to Japan’s Minor Change Notification, but under certain conditions, no notification to FDA is required—changes are simply documented internally. The following types of changes may fall under this category when they do not affect product safety or effectiveness, though in some cases summary performance data submission may be necessary:

• Editorial changes to labeling that do not affect safety or effectiveness information
• Component supplier changes (when equivalence can be demonstrated)
• Minor changes to manufacturing processes
• Improvements to quality control testing methods

FDA guidance documents, such as “Deciding When to Submit a 510(k) for a Change to an Existing Device” (issued in 1997 and updated in 2017), provide detailed criteria for determining when a new submission is required. Manufacturers are expected to maintain robust documentation systems to justify their decisions regarding change classifications.

Key Differences Between Japanese and United States Change Application Systems

1. Implementation of Changes Before Approval

In Japan, when a Partial Change Approval Application is required, changes cannot be implemented in principle until approval is obtained. In the United States, while PMA Supplements also generally require approval before implementation, the 30-Day Notice system allows changes to be implemented if FDA does not object within 30 days. Additionally, the Changes Being Effected (CBE) pathway permits immediate implementation for certain qualifying changes, providing greater flexibility for manufacturers.

2. Degree of Discretionary Judgment

In the United States, systems such as Letter to File exist where companies can implement changes and merely document them based on their own judgment, without submitting to FDA. In Japan, even minor changes fundamentally require notification, and the scope of corporate discretion tends to be narrower compared to the United States. However, the introduction of PACMP in 2021 has begun to provide Japanese manufacturers with more flexibility for pre-planned changes.

3. Review Periods and Transparency

Application Type	Japan	United States
Major changes (new approval/PMA Supplement)	6-10 months (PMDA targets)	180 days (PMA 180-Day Supplement target)
Moderate changes	Similar to new approval process	90 days (Real-Time Supplement, Special 510(k))
Minor changes with notification	30 days after implementation (no review)	30 days (30-Day Notice) or immediate (CBE)
Minor changes (documentation only)	Limited application (MCN required)	Widely applicable (Letter to File)

While Japan’s Partial Change Approval Applications may require periods similar to new applications, explicit review period targets for change applications have not been as clearly defined as in the United States. In the United States, the framework establishes more granular review periods—30 days, 90 days, 180 days, etc.—depending on the type of change. For example, for 510(k) submissions, an official 90-day target is presented under the MDUFA performance goals negotiated between FDA and industry, providing greater transparency regarding review timelines.

It should be noted that these are targets, and actual review times may vary. The FDA’s performance in meeting these goals is publicly reported, which contributes to accountability and continuous improvement efforts.

4. Advance Confirmation of Change Plans

Japan’s PACMP and the United States’ various expedited review mechanisms share similar concepts of pre-planning changes. However, Japan’s PACMP is a relatively new system, implemented in August 2021, and adoption has been gradual as manufacturers and regulators develop experience with its use. In the United States, efficiency in change management has been pursued over a longer period, with established pathways and extensive guidance documents. FDA has issued numerous guidance documents (such as “Manufacturing Changes and Additions for Premarket Approval Applications” updated in 2019) that provide detailed criteria for change classification.

The PACMP system represents Japan’s efforts to align more closely with international best practices while maintaining the rigor required for patient safety. As more manufacturers gain experience with PACMP and as PMDA publishes additional guidance, the system is expected to become more widely utilized.

Considerations for Corporate International Strategy

1. Impact on Development Planning

Because change application requirements and review periods differ between Japan and the United States, companies conducting global development must create development schedules aligned with the most stringent regulations. In particular, when implementing changes that require a Partial Change Approval Application in Japan, longer review periods should be anticipated compared to the United States. Companies should factor in these timelines during the initial product development phase to avoid delays in global launches.

For products intended for both markets, it is advisable to engage in early dialogue with both PMDA and FDA through pre-submission meetings or consultation programs. These interactions can clarify regulatory expectations and potentially identify opportunities for streamlined pathways.

2. Establishing Change Management Systems

Companies engaged in international expansion must build change management systems capable of responding to the regulations of each country. Particular attention should be paid to the fact that different countries may require different documentation and procedures for the same change. Effective change management systems should include:

• Clear procedures for classifying changes according to each regulatory framework
• Documentation requirements aligned with each jurisdiction’s expectations
• Tracking systems to monitor the status of change applications across multiple countries
• Training programs to ensure staff understand the nuances of different regulatory systems

Many companies have adopted electronic quality management systems (eQMS) that can manage change control processes across multiple jurisdictions, helping to ensure consistency and compliance.

3. Utilizing New Systems

Regulatory authorities are also working to improve the efficiency of change management, through systems such as Japan’s PACMP and various expedited review systems in the United States. By proactively utilizing these new systems, development cycle time may be shortened in some cases.

In Japan, manufacturers are encouraged to engage with PMDA’s consultation services to determine whether PACMP is appropriate for their anticipated changes. In the United States, FDA’s pre-submission program allows manufacturers to discuss planned changes and obtain feedback on the appropriate regulatory pathway before making formal submissions.

Additionally, both countries have been exploring opportunities for parallel review and information sharing. While formal work-sharing agreements remain limited, ongoing dialogue through bilateral regulatory cooperation initiatives (such as the Global Medical Device Harmonization activities) may create additional efficiencies in the future.

4. Responding to International Harmonization

In recent years, harmonization efforts between Japan and the United States have progressed, but Japan still maintains some unique regulatory requirements. Meanwhile, the United States tends to place greater emphasis on international standards such as those from the International Medical Device Regulators Forum (IMDRF), which succeeded the Global Harmonization Task Force (GHTF) after GHTF concluded its activities in 2012.

IMDRF, established in 2011, includes regulatory authorities from the United States, European Union, Japan, Canada, Australia, Brazil, China, Russia, Singapore, and South Korea. The forum develops harmonized guidance documents on topics including regulatory pathways, quality management systems, clinical evaluation, and adverse event terminology. While IMDRF guidance documents are non-binding, many member countries have adopted them or used them as the basis for national regulations.

Companies must understand these trends and establish systems capable of responding quickly to regulatory changes in each country. Key areas to monitor include:

• Updates to ISO 13485 (Quality Management Systems for Medical Devices) and related QMS requirements
• Evolving requirements for clinical evidence and post-market surveillance
• Cybersecurity requirements for connected medical devices (both FDA and PMDA have issued guidance on this topic)
• Software as a Medical Device (SaMD) regulations, which continue to evolve rapidly
• Artificial intelligence and machine learning-based medical devices, for which both regulatory authorities are developing specific frameworks

Japan has been particularly active in recent years in updating its regulatory framework to align with international trends while maintaining appropriate safeguards. The PMD Act amendments of 2020 included provisions for addressing emerging technologies and improving the efficiency of regulatory processes.

Conclusion

While the medical device change application systems in Japan and the United States serve the same fundamental purpose, they operate through different approaches. Companies must understand these differences and conduct change management that is both efficient and compliant. Although continued regulatory harmonization across countries is anticipated, for the foreseeable future, strategic planning that addresses differences in each country’s systems remains necessary.

For companies aiming to expand medical devices globally, change management is a critical business function that cannot be avoided. It is our hope that this article will serve as a useful resource for practitioners involved in medical device change applications.

As the medical device industry continues to evolve, with increasing complexity in devices (particularly those incorporating software and artificial intelligence), regulatory frameworks will necessarily continue to adapt. Manufacturers should remain engaged with regulatory authorities through industry associations, consultation programs, and public comment opportunities to help shape future regulations while ensuring patient safety remains the paramount concern.

By maintaining robust quality systems, investing in regulatory expertise, and actively monitoring regulatory developments in key markets, medical device companies can navigate the complexities of international change management while bringing innovative products to patients in a timely manner.