Drug Registration in Malaysia: A Comprehensive Guide to Regulatory Compliance 4 Apr 2025, 2:11 pm

Malaysia has developed a robust and evolving regulatory system to govern the safety, efficacy, and quality of medicinal products. At the core of this system is the 1984 regulation – Control of Drugs and Cosmetics Regulations (CDCR). These regulations set the legal foundation for drug registration in the country and empower the Drug Control Authority (DCA) to oversee the full lifecycle of pharmaceutical products — from registration and licensing to post-market surveillance and enforcement.

Serving as the operational arm of the DCA, the National Pharmaceutical Regulatory Agency (NPRA) functions as the secretariat and handles all administrative and scientific activities associated with product registration. Together, these entities ensure that Malaysian consumers have access to safe, effective, and high-quality medicinal products.

Regulatory Framework and Core Requirements

Under Regulation 7(1) of the CDCR 1984, it is explicitly stated that, unless otherwise provided, no person shall manufacture, sell, supply, import, possess, or administer any medicinal product unless:

• The product is registered with the DCA, and
• The individual or entity holds the appropriate license issued under the regulations.

This clause makes product registration and licensing mandatory and underscores the Malaysian government’s commitment to upholding pharmaceutical standards and protecting public health.

What Qualifies as a “Product”?

An essential first step in the registration process is determining whether an item falls within the definition of a “product” as per Regulation 2 of the CDCR 1984. The definition includes:

• Any drug intended for administration to humans or animals for a medicinal purpose, or
• Any drug to be used as an ingredient in a preparation for such a purpose.

The term “drug” is broadly defined under the 1952 Sale of Drugs Act and encompasses substances used for diagnosing, treating, preventing, or curing diseases, as well as for purposes like contraception, inducing anesthesia, modifying physiological functions, controlling body weight, or promoting general well-being.

Product Classification

Once a product is determined to fall under the regulatory definition, it must be correctly classified. This step is critical, as different categories require different documentation, fees, and evaluation pathways. Categories of products include:

• New Drug Products
• Biologics
• Generic Products
• Health Supplements
• Natural Products
• Veterinary Products

If a product falls into a grey area, such as medical device-drug-cosmetic interphase (MDDCI), the applicant may submit a Classification Form to the NPRA for official guidance. These interphase categories are particularly relevant for combination products or those with therapeutic claims that may overlap regulatory boundaries.

Eligibility and Role of the Product Registration Holder (PRH)

Only companies incorporated in Malaysia and registered with the Companies Commission of Malaysia (SSM) are eligible to act as the Product Registration Holder (PRH). The PRH must have a permanent address in Malaysia and be involved in the healthcare or pharmaceutical sector.

If the applicant is not the owner of the product, they must provide written authorization from the product owner designating them as the PRH. This entity then becomes solely responsible for all regulatory matters, including submission accuracy, product quality, and communication with the NPRA.

Key Responsibilities of the PRH

The PRH has a legal obligation to maintain the accuracy and integrity of all information submitted to NPRA. The PRH must:

• Ensure that all submissions are complete, truthful, and timely
• Respond to requests for supplementary information, documents, or samples within the stipulated deadlines
• Notify the Authority of any changes in product composition, manufacturing site, packaging, labeling, or ownership
• Monitor and report any adverse events or product issues
• Maintain compliance with current Good Manufacturing Practice (cGMP)

Regulation 8(5) requires notification within 14 days of any change to submitted information. Failure to comply may lead to the application being rejected or the registration being withdrawn. Under Regulation 8(9), knowingly submitting false or misleading information constitutes an offence.

Importantly, in the event of disputes with product owners or third parties, NPRA will only correspond with the PRH and will not intervene in private contractual matters. It is the PRH’s duty to resolve these disputes independently.

Online Submission via the QUEST System

Malaysia’s registration process is fully digitized through the QUEST system, an online portal managed by NPRA. All submissions must be completed through this system.

To use QUEST, applicants must:

• Register for a QUEST membership
• Purchase a USB Token containing a User Digital Certificate from MSC Trustgate.com Sdn. Bhd.
• Install the token on their computer system for secure login and data submission

This system streamlines application tracking, fee payment, and communication with the Authority. However, the PRH is responsible for safeguarding their token. Any fraudulent use may result in severe penalties and revocation of access.

Application Fees

The CDCR allows NPRA to charge applicants for the cost of product evaluation and related investigations. Fee details are outlined in Appendix 9 of the NPRA guidelines. Key points include:

• Fees must be paid via the QUEST system using FPX, credit card, or through official bank instruments
• Each application requires a separate payment
• Once submitted and accepted, fees are non-refundable
• Applications submitted without payment or with incorrect fees will not be processed

Applicants are advised to carefully review the fee schedule and confirm payment details to avoid delays or rejections.

Preparing the Submission

Thorough preparation is vital for a successful application. Applicants should take the following steps:

1. Determine the product category and confirm the classification
2. Identify the appropriate evaluation pathway (standard, abridged, verification-based)
3. Prepare all required documentation and data
4. Schedule a Pre-Submission Meeting (PSM) with NPRA for guidance, if needed

Pre-submission meetings are particularly useful for complex products, biologics, or those involving new chemical entities. Guidance documents on how to conduct these meetings are available on the NPRA website.

Data Exclusivity in Malaysia

Malaysia provides data exclusivity for new drug products that contain a New Chemical Entity (NCE) or that are registered for a new indication. This protection covers undisclosed, unpublished data submitted for scientific evaluation. To qualify, the data must have been generated through considerable effort and not be in the public domain.

There are two main types of protection:

• Data exclusivity for new drugs with a New Chemical Entity
• Data exclusivity for a second indication of an already registered drug

Details of drugs granted data exclusivity can be found in the public registers on the NPRA website.

Post-Registration Obligations

Product registration is not the end of the regulatory journey. Once approved, the PRH must continue to meet a range of obligations:

• Notify NPRA of any changes in product details, manufacturing processes, or contact information
• Submit periodic safety reports and adverse event data
• Maintain updated records and documentation on product efficacy and safety
• Obtain prior approval before making any changes to the product formulation, packaging, or label
• Inform NPRA if the product is withdrawn from the market or discontinued

In cases where the PRH ceases operations, NPRA must be notified immediately. It is the responsibility of the existing PRH to manage any ownership transfers or re-registration efforts.

Conclusion

Malaysia’s drug registration process is designed to protect public health while supporting industry innovation. Governed by the 1984 Control of Drugs and Cosmetics Regulations and administered through the NPRA, the system ensures that all medicinal products meet rigorous standards before they are made available to the public.

From product classification and PRH responsibilities to the QUEST submission process and data exclusivity protections, every step is carefully regulated. Companies looking to enter the Malaysian pharmaceutical market must be prepared to navigate a thorough and structured process. With diligence, transparency, and proper planning, the process can be completed efficiently, contributing to both business success and public safety.

Written by: Ames Gross – President and Founder, Pacific Bridge Medical (PBM)

Navigating Medical Device Registration in Malaysia: A Comprehensive Guide 2 Apr 2025, 7:55 pm

Malaysia’s healthcare sector continues to grow rapidly, supported by a robust regulatory environment aimed at ensuring the safety, quality, and performance of medical devices. Central to this framework is the Medical Device Act 2012 (Act 737. Under this Act, all medical devices must be registered with the Medical Device Authority (MDA) before they can be imported, exported, or marketed in Malaysia. This article outlines the full registration process, responsibilities, and regulatory requirements, based on the guidelines issued by the MDA.

Regulatory Background and Key Stakeholders

Act 737 establishes the legal framework for regulating medical devices in Malaysia. The Medical Device Authority, under the Ministry of Health, is tasked with overseeing the implementation and enforcement of the Act.

The Act defines a medical device as any instrument, apparatus, implement, machine, appliance, software, material, or other similar or related article intended for use in healthcare. These may be used for diagnosis, prevention, monitoring, treatment, or alleviation of disease or handicap — but do not include drugs.

Two parties are recognized as responsible for registering a medical device in Malaysia: the local manufacturer and, in the case of foreign-made devices, the authorized representative (local agent) of the overseas manufacturer.

Overview of the Registration Process

The Malaysia medical device registration process is carried out online via the Medical Device Centralized Online Application System (MeDC@St). Before submitting an application, the applicant must complete several preliminary steps, including classification, grouping, and conformity assessment.

1. Determining Whether a Product is a Medical Device

The first step is to determine whether the product in question qualifies as a medical device under Section 2 of the Medical Device Act 2012.

2. Classifying the Medical Device

Medical devices in Malaysia are categorized into four classes—Class A (lowest risk), Class B, Class C, and Class D (highest risk)—based on intended use and risk to patients.

Medical devices in Malaysia are grouped into distinct categories based on their functionality and nature:

Non-active devices:

• General devices for anesthesia, infusion, and orthopedic use
• Non-active implants (e.g., cardiovascular, orthopedic, soft tissue)
• Devices for wound care and dental procedures

Active devices:

• Equipment requiring electrical or mechanical power, such as ventilators and monitors
• Devices used in imaging, therapy, or patient monitoring
• Software considered as standalone medical devices

Active implantable medical devices:

• Devices like pacemakers, drug delivery implants, and other permanently installed tools that use an internal energy source

Each device must be assigned to a specific category code (e.g., MD 0102 for infusion devices or MD 1302 for vital signs monitors), which must be included in the application.

3. Grouping the Medical Device

If a device has multiple models or components, it may be grouped under specific rules. Proper grouping ensures that a single registration covers all relevant components and models.

4. Conformity Assessment and Compilation of Technical Documentation

The next step involves conducting a conformity assessment. This process ensures that the device meets the Essential Principles of Safety and Performance as outlined in the Third Schedule of the Medical Device Regulation 2012.

Applicants must:

• Compile evidence of conformity into the Common Submission Dossier Template (CSDT),
• Prepare a Declaration of Conformity using the approved template,
• Appoint a registered Conformity Assessment Body (CAB) to verify the documentation and issue a certificate of conformity.

The CSDT format and contents are specified in the MDA’s guidance documents and must be strictly followed.

5. Appointing a CAB

Conformity assessments must be carried out by a registered CAB. The CAB evaluates the technical documentation, verifies compliance with essential safety and performance principles, and issues the relevant certificate and assessment report.

6. Submitting the Registration Application via MeDC@St

Once all documentation is complete and verified by a Malaysian CAB, the applicant can submit the registration via MeDC@St. This web-based system serves as the official platform for all device registration activities.

Applicants must first create a MeDC@St account. Once logged in, they can initiate a new application form, which is divided into eight main parts:

• General information
• Manufacturer information
• Grouping details
• CSDT documentation
• Supporting documents for CSDT
• Post-market vigilance history
• Declaration of Conformity
• Attestation for registration

Each section requires specific data and document uploads. Key information includes device classification, intended use, product description, conformity documentation, and any prior market clearances (e.g., from the US FDA or CE Mark).

Key Details Required in the Application

For general information, the applicant must disclose whether the device contains any drug or poison, and confirm its type (general or in-vitro diagnostic). Classification details must be supported by justification in line with regulatory guidelines.

Information about the manufacturer must include address, contact information, and website details. For devices grouped under one application, a list of all constituent models or components must be uploaded.

For sterile or measuring Class A devices, validation reports are required.

Applicants must upload the complete CSDT dossier, including design, risk analysis, clinical evidence (if applicable), manufacturing process, and labeling. Supporting documents and specific elements of the CSDT must be cross-referenced during the submission.

Post-market history must include details of recalls, adverse events, bans in other countries, or rejections by other regulatory authorities.

The Declaration of Conformity should be signed and printed on the manufacturer’s letterhead. The attestation letter must be printed on the establishment’s letterhead, signed, and stamped by the authorized contact person listed in the establishment license.

What Happens After Submission

Upon submission, the MDA reviews the application. If the application is found lacking in information, it may be returned.

Returned applications are flagged in the applicant’s MeDC@St dashboard and accompanied by email notification. The applicant has 90 days to correct and resubmit the application. Failure to do so within the deadline will result in automatic withdrawal of the application, although the applicant may submit a new one at any time.

Reasons for Refusal

The MDA may refuse registration under the following conditions:

• The device does not fulfill the registration requirements
• The product does not meet the legal definition of a medical device
• Incorrect classification of the device

In such cases, the authority will notify the applicant, and a fresh submission may be required if the applicant still seeks registration.

Post-Market Obligations

Even after registration, manufacturers and authorized representatives must monitor the safety and performance of their devices. This includes:

• Reporting adverse events and field safety corrective actions
• Submitting updates or renewals when significant changes are made to the device
• Ensuring proper labeling and usage instructions remain current

Recent Regulatory Update

To support a smoother registration process, the MDA recognizes prior approvals from major regulatory markets, particularly the European Union and the United States. Medical devices that have received CE Marking or hold an EC Declaration of Conformity under EU legislation are considered eligible for Malaysia’s conformity assessment process. These documents can serve as key evidence of compliance during the registration of devices in Malaysia.

In light of the ongoing transition to the European Union’s new Medical Device Regulation (MDR) and In Vitro Diagnostic Regulation (IVDR), the MDA has issued an important update regarding the acceptance of expired EC certificates. This revision affects both initial registrations and re-registrations for all classes of medical devices and in vitro diagnostic (IVD) devices.

According to the new guidance, expired EC certificates issued under the former directives — Directive 90/385/EEC (Active Implantable Medical Devices), 93/42/EEC (Medical Devices), and 98/79/EC (IVDs) — may still be accepted under specific conditions. These include:

• The device must remain compliant with the relevant EU directive under which it was originally certified.
• There must be no significant changes made to the device’s design.
• The device must not pose any unacceptable risk to users or patients.

In addition to meeting these conditions, manufacturers are required to provide supporting documentation. This may include a confirmation letter from the notified body or a self-declaration letter from the manufacturer affirming continued compliance with the relevant directive and device specifications.

For devices that have already been registered in Malaysia using an EC certificate under the former EU directives, the update does not affect their current approval status. However, when re-registration is due, applicants must either present a valid certificate under the new EU MDR or IVDR, or demonstrate that the three specified conditions continue to be met.

Conclusion

Malaysia’s medical device registration process under Act 737 is detailed and well-structured, aiming to balance patient safety with industry innovation. Manufacturers and representatives seeking to enter the Malaysian market must understand and comply with every stage of the process — from product classification and grouping to documentation and conformity assessment.

With the assistance of registered CABs and a clear application pathway through MeDC@St, stakeholders can effectively navigate the system. However, strict adherence to submission requirements and deadlines is essential to avoid delays, returns, or outright rejection of applications.

Understanding the scope of the regulations and maintaining open communication with the Medical Device Authority will help ensure a smoother registration process and long-term compliance in one of Southeast Asia’s most promising healthcare markets.

Written by: Ames Gross – President and Founder, Pacific Bridge Medical (PBM)

Understanding Japan’s Drug Master File System: A Comprehensive Guide 28 Mar 2025, 5:51 pm

The Drug Master File (DMF) system in Japan serves as a critical regulatory mechanism enabling pharmaceutical manufacturers, both domestic and foreign, to confidentially register the quality and manufacturing data of drug substances, intermediates, and related materials with Japan’s review authority. Managed by the Pharmaceuticals and Medical Devices Agency (PMDA), this system is designed to facilitate the approval of pharmaceutical products by allowing finished drug manufacturers to reference the DMF during the drug approval process. This article provides a comprehensive overview of the DMF system, its scope, procedures, requirements, and implications for international stakeholders.

Purpose and Overview of the DMF System

The Japanese DMF system is primarily intended to protect the proprietary information of manufacturers while allowing regulatory authorities to verify the quality and consistency of components used in finished pharmaceutical products. By submitting an DMF, drug component manufacturers can ensure that their confidential manufacturing and quality control information remains protected, even as it is used during drug product evaluation.

DMF registration is voluntary, yet it is often essential for manufacturers whose materials are used in multiple pharmaceutical products. Registered information typically includes manufacturing methods, specifications, test procedures, and stability data.

Eligibility and Registration Requirements

Foreign manufacturers are also required to appoint an in-country caretaker—a person or entity residing in Japan—to handle administrative matters and correspondence and act as a liaison with the PMDA. Importantly, all documents submitted must be in Japanese, necessitating close coordination with the in-country caretaker.

The DMF system covers a broad range of substances and materials used in pharmaceuticals. These include:

1. Drug substances, intermediates, and materials for pharmaceutical products, especially those with special dosage forms. However, substances used in over-the-counter (OTC) drugs—except those with new active ingredients—are typically excluded.
2. New excipients and novel pre-mix excipients that differ from existing formulations.
3. Containers and packaging materials, particularly those used in drug delivery or storage.

DMF Application and Submission Process

Application Format and Documentation

The DMF application must be submitted using designated forms outlined in Japan’s pharmaceutical regulations, accompanied by:

• Two copies of the registration form (original and duplicate).
• A Flexible Disk (FD) or CD-R containing the application data.
• Supporting documentation including specifications, test methods, stability data, and manufacturing process descriptions.

Notably, the application form must be physically signed by the representative of the foreign manufacturer. The in-country caretaker may not sign or seal the form on behalf of the foreign applicant.

Content of DMF Registration

DMF registration includes the following key items:

• Drug substance name and site of manufacture.
• Manufacturing method and controls.
• Specifications and test methods.
• Stability data, storage conditions, and shelf life.
• Safety data, particularly for new excipients.
• License or accreditation details.
• Information about the in-country caretaker.

The DMF essentially forms a subset of the documentation required for drug product approval and is subject to review during that process.

Confidentiality and Public Disclosure

Upon registration, a Master File Certificate is issued to the applicant. This certificate contains no confidential information. However, the PMDA publishes non-confidential details on its website, including the DMF number, registration date, registrant name and address, and a general description of the registered item.

Applicants for drug product approval who intend to reference a DMF must also include certain publicly available DMF details in their applications, along with a copy of the DMF certificate and an agreement with the DMF holder.

Updates and Changes to the DMF

Changes to registered items are categorized as either major changes, requiring an application for amendment, or minor changes, which can be notified post hoc. Minor changes must be reported within 30 days of implementation, and the DMF holder must provide documentation demonstrating adequate validation and control.

Examples of minor changes include modifications that do not impact product quality, efficacy, or safety. Major changes – such as alterations in manufacturing methods that affect product characteristics – require prior approval and submission of updated documentation.

Before making any change, the DMF holder must notify any affected drug product manufacturers. If the change significantly impacts a product’s characteristics, a new DMF registration may be required rather than a simple amendment.

Special Procedures for DMF Consultations

The PMDA offers simple consultations for DMF-related matters. These sessions allow applicants to confirm whether a proposed change qualifies as a minor update, requires a partial change approval, or mandates a new DMF registration. Consultations are classified based on the product type – new drug or generic drug.

DMF holders are advised to seek guidance in complex cases, particularly those involving safety concerns or potential changes in drug substance properties.

Responsibilities of the In-Country Caretaker

Given the requirement that all documentation be in Japanese and the PMDA’s communication protocol, the in-country caretaker plays a pivotal role in the DMF process. This representative:

• Acts as the primary contact for PMDA inquiries.
• Manages the submission of applications and notifications.
• Coordinates with the foreign manufacturer to ensure data integrity and regulatory compliance.

Changes to the in-country caretaker must be submitted as a minor change notification.

Transferring DMF Ownership

The transfer of an DMF to a third party must follow formal procedures, including:

• Submission of a contract between the transferor and transferee.
• Confirmation that no manufacturing site or process changes have occurred.
• Reissuance of relevant documentation under the new owner’s name.

Implications for Drug Approval Applications

If a pharmaceutical product references an DMF, the drug approval application must:

• Indicate the DMF registration number and issue date.
• Specify the version of the registered data being quoted.
• Include a copy of the DMF certificate and relevant contractual documentation.

In cases where the DMF registration is still in progress, the drug application may proceed with a provisional notation. However, the approval process will only commence once the DMF number is issued and updated in the application.

During the product approval review, the PMDA may contact the DMF holder (via the in-country caretaker for foreign applicants) for additional information. If any updates to the DMF are required, they must be submitted before the product can be approved.

Conclusion

Japan’s DMF system offers a robust framework for protecting proprietary manufacturing information while ensuring the quality and safety of pharmaceutical products. It enables both domestic and international manufacturers to contribute to the Japanese drug market while maintaining confidentiality and regulatory compliance.

Foreign manufacturers seeking to enter the Japanese pharmaceutical market must carefully navigate the DMF system, ensuring they meet all procedural, linguistic, and regulatory requirements. The role of the in-country caretaker is particularly critical in bridging regulatory and communication gaps.

Ultimately, the DMF system reinforces Japan’s commitment to transparency, safety, and efficacy in pharmaceutical regulation, while recognizing the global nature of modern drug manufacturing.

Written by: Ames Gross – President and Founder, Pacific Bridge Medical (PBM)

Understanding Singapore’s Drug Master File (DMF) Guideline: A Strategic Tool for Therapeutic Product Registration 28 Mar 2025, 5:47 pm

Navigating regulatory landscapes can be daunting, especially when dealing with proprietary drug substance information. For pharmaceutical companies planning to register therapeutic products in Singapore, understanding the requirements of a Drug Master File (DMF) is essential. In August 2024, Singapore’s Health Sciences Authority (HSA) updated its DMF guideline as part of the broader “Guidance on Therapeutic Product Registration.” This blog post unpacks the purpose, structure, and lifecycle of the DMF submission process in Singapore and offers practical insights for applicants and DMF holders alike.

What is a Drug Master File (DMF)?

A DMF is a confidential, detailed document that provides information on the manufacturing, processing, and packaging of a drug substance. The DMF is typically used to support a product registration application without revealing proprietary details to the applicant of the final drug product.

The purpose of a DMF is to allow the drug substance manufacturer (also known as the DMF Holder) to protect trade secrets while still providing sufficient technical data for regulatory evaluation. In essence, it enables collaboration between different parties in the supply chain without compromising intellectual property.

The Structure of a DMF: Open vs Closed Parts

One of the most essential features of Singapore’s Drug Master File (DMF) system is its two-part structure, which allows for a careful balance between regulatory transparency and the protection of proprietary information. This design reflects a global best practice, enabling regulators to access all necessary technical information for product evaluation while simultaneously ensuring that sensitive manufacturing details are not shared beyond what is strictly necessary.

1. Open Part of the DMF (Applicant’s Part)

The open part, sometimes referred to as the “applicant’s part,” contains information that is shared both with the product registration applicant and the Health Sciences Authority (HSA). This section includes details necessary to demonstrate the general acceptability and consistency of the drug substance, but it excludes confidential elements such as proprietary manufacturing processes.

According to the ICH Common Technical Document (CTD) structure adopted by HSA, the open part generally includes the following sections of Module 3.2.S (or Part II.S in the ASEAN CTD):

• S.1 – General Information: This section covers the drug substance name, manufacturer, chemical structure, molecular formula, and other identifiers like the CAS number.
• S.2.1 – Manufacturer(s): Identifies the name, address, and responsibilities of all manufacturers involved in the production and quality control of the substance.
• S.3 to S.7 – Additional Quality Information: These include characterisation (S.3), control of drug substance (S.4), reference standards (S.5), container closure system (S.6), and stability data (S.7).

2. Closed Part of the DMF (Restricted or Confidential Part)

The closed part of the DMF is where the proprietary “know-how” lives. This section contains confidential, sensitive information related to the drug substance’s manufacturing process that the DMF Holder does not wish to share with the applicant or any other third party except the regulatory agency.

This portion corresponds to sections S.2.2 to S.2.6 of Module 3.2.S, which cover the following:

• S.2.2 – Description of Manufacturing Process and Process Controls: This section provides detailed step-by-step information on how the drug substance is synthesized or derived, including all in-process controls and critical steps.
• S.2.3 – Control of Materials: Details of raw materials, solvents, reagents, and intermediates used during synthesis. It may include information about the specifications and suppliers of starting materials, which can be highly proprietary.
• S.2.4 – Controls of Critical Steps and Intermediates: Identifies which steps in the manufacturing process are considered critical to quality and what tests or controls are applied at those stages.
• S.2.5 – Process Validation and/or Evaluation: Describes the evidence supporting that the process, as designed, consistently produces material of acceptable quality.
• S.2.6 – Manufacturing Process Development: A narrative of the history and rationale behind how the current manufacturing process was established. It may include discussion of alternative methods, scalability considerations, or lessons learned during development.

Submission Requirements: Who Submits What?

The DMF submission process involves two main stakeholders—the applicant and the DMF Holder—each with different responsibilities.

From the Applicant:

• Submit the open part of the DMF in PDF format as part of the application dossier.
• Include a Letter of Access, which authorizes the HSA to refer to the DMF.
• Provide a copy of the acknowledgment email from the HSA confirming receipt of the Letter of Access.

From the DMF Holder:

• Complete the Online DMF Submission Form (accessible via a government portal).
• Submit a cover letter referencing the Response ID from the form.
• Provide the complete DMF (both open and closed parts) in softcopy.
• Submit a copy of the Letter of Access.

All files must be provided electronically, either on CD/DVD or through cloud-based file sharing (EasiShare). The use of hard copies is discouraged and will not trigger assignment of a DMF number.

The Role of the Letter of Access

The Letter of Access is a pivotal document that links the therapeutic product application to the DMF. It serves multiple purposes:

• Authorizes HSA to reference the DMF during evaluation.
• Identifies the specific product (name, dosage form, and strength) it supports.
• Declares the local applicant responsible for registration.
• Confirms the obligation to notify HSA and the applicant of any DMF changes that may affect product safety or quality.

A sample format of the Letter of Access is available in the HSA’s Appendix 11B to ensure consistency and completeness.

Confidentiality Assurance for DMF Holders

To safeguard proprietary information, the closed part of the DMF is treated as confidential and accessed solely by HSA for evaluation purposes. It will not be disclosed to the applicant or any third party unless explicitly authorized by the DMF Holder in writing.

This approach balances regulatory transparency with business confidentiality, promoting trust between stakeholders in the drug supply chain.

Assignment of DMF Numbers

Once the required documents are submitted in the correct format, the HSA assigns a unique DMF number and issues an acknowledgment email. It’s important to note that:

• The DMF number does not imply approval or rejection. It merely indicates receipt.
• All future communications with HSA should reference the assigned DMF number.

DMF Lifecycle and Evaluation

The DMF undergoes two key phases during product registration:

1. Screening Phase

• The DMF is checked for completeness alongside the drug application (NDA, GDA, or MIV-1).
• Any deficiencies in the open or closed parts are communicated:
  • Closed part queries go directly to the DMF Holder.
  • Open part queries are sent to both the DMF Holder and the applicant.

2. Evaluation Phase

• The DMF is evaluated in conjunction with the drug application.
• Evaluation queries follow the same distribution pattern as screening queries.
• The DMF Holder is responsible for addressing all issues and submitting complete responses to HSA.

If an existing DMF is referenced, a new Letter of Access specific to the current application must be submitted.

DMF Updates and Maintenance

Both DMF Holders and applicants are responsible for ensuring that the DMF remains current. If any changes are made to the DMF:

• A Table of Summary of Changes must be provided, detailing the section modified, the current and proposed version, and the rationale for the revision.
• The Online DMF Submission Form must be resubmitted with updated documents.
• Any changes impacting drug substance or product specifications may trigger the need for a post-approval variation to be submitted by the product registrant.

For example, adding a new manufacturer to section S.2.1 would require:

• Notifying HSA through an updated submission.
• Updating the Letter of Access and application dossier as needed.
• Ensuring compliance with the broader post-approval process outlined in Chapter F of the HSA guidance.

Cancelling a DMF

If a DMF is no longer required to support a therapeutic product, the DMF Holder can request cancellation. Once processed, the DMF is considered closed. Any future application referencing this cancelled DMF would be treated as a new DMF, and all relevant documentation would need to be resubmitted.

Practical Takeaways

• Plan Early: Initiate DMF coordination well in advance of the product registration timeline.
• Ensure Completeness: Submissions lacking required documents or formatting will delay the assignment of a DMF number.
• Maintain Confidentiality: Use the correct channels (e.g., EasiShare) for submission of proprietary information.
• Coordinate Closely: Communication between the applicant and DMF Holder is vital for timely response to queries and updates.
• Stay Compliant: Regularly review the DMF to ensure it reflects current manufacturing practices and notify HSA of any changes promptly.

Conclusion

The DMF guideline issued by Singapore’s Health Sciences Authority provides a clear, structured framework for protecting proprietary drug substance information while facilitating regulatory review. For pharmaceutical companies and contract manufacturers looking to enter or maintain a presence in the Singapore market, adhering to these guidelines is not just a compliance requirement—it’s a strategic necessity.

By understanding the lifecycle of the DMF, the roles of each stakeholder, and the expectations around submission and maintenance, companies can ensure a smoother regulatory journey and contribute to a more transparent and trustworthy drug approval process in Singapore.

For the latest forms and submission tools, visit HSA’s website and access the Online DMF Submission Form.

Written by: Ames Gross – President and Founder, Pacific Bridge Medical (PBM)

Taiwan’s Regulatory Framework for Regenerative Medicine 24 Mar 2025, 9:08 pm

Introduction

Regenerative medicine is an innovative and rapidly evolving field that leverages genes, cells, and their derivatives to reconstruct or repair human body structures and functions, ultimately aiming to treat or prevent diseases. This field has the potential to revolutionize healthcare by offering new therapeutic options for conditions that are currently difficult or impossible to treat with conventional medicine.

In Taiwan, regenerative medicine is categorized into regenerative medical technology and regenerative medical preparations, each of which is regulated by distinct frameworks to ensure safety, efficacy, and compliance with international standards. The regulatory oversight is managed by the Taiwan Food and Drug Administration (TFDA), along with the Center for Drug Evaluation (CDE) and other relevant authorities. The regulations continue to evolve to keep pace with scientific advancements and ensure that Taiwan remains competitive in the global biomedical industry.

Regulatory Classification

Regenerative Medical Technology

Regenerative medical technology in Taiwan is governed by the Medical Act and the Regulations on the Implementation or Use of Specific Medical Technology Inspections and Medical Instruments. These regulations outline the scope of regenerative medicine and define the criteria for its approval and oversight.

The key definitions within this regulatory framework include the following:

1. Human Cell Tissues refer to human cells, tissues, body fluids, or derivatives that are obtained through non-genetic engineering methods.
2. Specific Medical Technology encompasses medical procedures such as cell therapy, cosmetic surgery, and other restricted medical technologies that require regulatory approval.
3. Cell Therapy Technology involves the use of human cell tissues, without the combination of drugs, to reconstruct body structures, restore function, or treat diseases. However, certain medical procedures are excluded from this classification, including blood transfusion, blood preparation, bone marrow and peripheral blood hematopoietic stem cell transplantation, artificial reproduction, and other exclusions as designated by the central competent authority.

Regenerative Medical Preparations

Regenerative medical preparations are classified as biological drugs and are regulated under the Pharmaceutical Affairs Act and the draft Regenerative Medical Preparations Regulations. These preparations contain genes, cells, and their derivatives and are specifically developed for human therapeutic purposes.

There are four main categories of regenerative medical preparations:

1. Gene Therapy Preparations refer to medications that introduce recombinant genes into the human body to treat, prevent, or diagnose diseases.
2. Cell Therapy Preparations consist of products made by processing cells or their derivatives, which are then used for therapeutic, preventive, or diagnostic purposes.
3. Tissue Engineering Preparations include processed and modified tissues or cells designed to repair, regenerate, or replace damaged human tissues and organs.
4. Composite Preparations are a combination of medical devices and regenerative medical products, formulated to enhance overall therapeutic outcomes.

Registration Process

Regenerative Medical Technology

Medical institutions intending to perform cell therapy must submit applications through the Cell Therapy Technology Case Submission Window of the Center for Drug Evaluation (CDE). The application process involves multiple steps, ensuring a thorough review before approval.

Step-by-Step Application Process

The registration process for regenerative medical technology begins with preliminary registration, where medical institutions must submit their proposed implementation plan to the CDE. Once registered, they receive a tracking number, which is used throughout the approval process.

Following registration, institutions must proceed with the application submission phase, during which they submit a full application along with the necessary supporting documents to both the TFDA and CDE. The submission package should include the physician’s qualification proof, evidence of an accredited cell preparation site, and a detailed implementation plan outlining the scope and methodology of the proposed therapy.

The approval process depends on whether human trials are required. For therapies that do not necessitate human clinical trials, the approval is relatively streamlined. However, for therapies that require additional scrutiny, institutions may need to provide clinical trial data and additional documentation before obtaining approval.

Fast-Track Therapies

Certain well-established cell therapies benefit from an expedited approval process, as they have been deemed low-risk based on previous successful applications and regulatory precedent. These therapies include:

• Autologous CD34+ selection peripheral blood stem cell therapy
• Autologous immune cell therapy (e.g., CIK, NK, DC, TIL, gamma-delta T)
• Autologous adipose stem cell therapy
• Autologous fibroblast therapy
• Autologous bone marrow mesenchymal stem cell therapy
• Autologous chondrocyte therapy

For cell therapies not included in the fast-track list, institutions must submit Phase II human clinical trial data, as well as supporting domestic and international literature that demonstrates the safety and efficacy of the proposed therapy.

Practitioner Requirements

To ensure patient safety and maintain high-quality standards, physicians who perform cell therapy techniques must meet the following requirements:

• They must be specialists in a relevant field with experience in regenerative medicine.
• They must complete TFDA-accredited training courses that provide an in-depth understanding of cell therapy techniques and safety protocols.
• They should have actively participated in clinical trials related to the specific cell therapy being implemented.

Additionally, cell preparation sites must adhere to Good Tissue Practice (GTP) standards and receive official accreditation before commencing operations. This accreditation ensures that the preparation and handling of cells meet stringent regulatory and quality control measures.

Once approved, medical institutions must comply with post-approval obligations, which include reporting treatment outcomes and monitoring for adverse reactions. If significant adverse events occur, the institution may be required to modify or halt the therapy in accordance with TFDA guidelines.

Regenerative Medical Preparations

Regenerative medical preparations follow biologics and biosimilars regulatory pathways, ensuring that all products meet stringent quality and safety requirements before reaching the market. The process involves site registration and product registration, which are essential steps for manufacturers seeking approval to distribute their regenerative products.

Site Registration

Manufacturers of regenerative medical preparations must undergo site registration, which includes inspections and reviews to verify compliance with Good Manufacturing Practice (GMP) standards. The requirements for site registration differ based on the country of origin of the manufacturer:

• Non-PIC/S Member Countries: Manufacturers located in countries that are not members of the Pharmaceutical Inspection Co-operation Scheme (PIC/S) must undergo foreign on-site GMP inspections by TFDA. These inspections evaluate the production facilities and ensure compliance with international safety and quality standards.
• PIC/S Member Countries: Manufacturers from countries that are part of PIC/S may submit a Plant Master File (PMF) review instead of undergoing an on-site inspection. The PMF review provides detailed documentation of the manufacturing process, site controls, and compliance with GMP requirements.

Product Registration

Once the manufacturing site has been approved, the next step is product registration, which requires manufacturers to submit an application in the Common Technical Document (CTD) format. The CTD is an internationally recognized standard for regulatory submissions and ensures consistency in the evaluation process.

To facilitate the submission process, TFDA mandates that all applications be submitted electronically through the ExPress eCTD platform. This digital platform allows for streamlined review and tracking of applications, reducing administrative burdens and improving efficiency.

The product registration process includes a comprehensive review of:

• Preclinical data demonstrating the safety and efficacy of the preparation.
• Clinical trial results, where applicable, to support product claims.
• Manufacturing quality control measures ensuring product consistency and compliance with regulatory standards.

Registration Timelines

1. Regenerative Medical Technology

The overall timeline for regenerative medical technology approval is approximately 6 to 9 months, including:

1. CDE Registration – 7 days
2. Administrative Screening – 14 days
3. Technical Review – 30 days
4. Final Approval – 30 days
5. GTP Certification – 60 days

2. Regenerative Medical Preparations

Approval for biologic and biosimilar products follows a longer timeline:

• PMF Review – 200 days (excluding deficiency response periods)
• Technical Document Review – 90 days
• Biologics Product Registration – 360 days
• Biosimilar Product Registration – 300 days

Compliance and Oversight

The Taiwan Food and Drug Administration (TFDA) maintains strict oversight of regenerative medical technology and preparations by conducting routine and unscheduled inspections of medical institutions and cell preparation sites. These inspections ensure compliance with Good Tissue Practice (GTP) and Good Manufacturing Practice (GMP) regulations and help maintain the safety and efficacy of regenerative medicine procedures and products.

The TFDA’s compliance framework is designed to prevent misconduct, ensure adherence to approved protocols, and mitigate risks associated with regenerative medical treatments. Medical institutions and manufacturers must follow strict operational and reporting requirements, and any violations may lead to regulatory actions, including suspension or revocation of approvals. Institutions may face penalties if they:

• Deviate from their approved treatment plan – Medical institutions must strictly follow the approved protocols for regenerative medicine. Any modifications to the plan require prior approval from the TFDA.
• Fail to report adverse events – If a patient experiences an adverse reaction or an unexpected outcome related to regenerative therapy, the institution must promptly report the event to the TFDA. Failure to do so can result in sanctions and suspension of the therapy.
• Do not submit mandatory annual reports – Institutions conducting regenerative medical procedures must provide annual reports detailing treatment outcomes, patient responses, and any adverse effects. These reports allow regulators to monitor safety and effectiveness over time.
• Violate GTP or GMP regulations – All cell preparation sites must adhere to GTP standards, ensuring the highest quality in cell handling, processing, and storage. Similarly, manufacturers of regenerative medical preparations must comply with GMP regulations to maintain product safety and consistency.

In addition to routine inspections, the TFDA has the authority to conduct surprise audits, review documentation, and impose corrective actions if non-compliance is detected. If an institution fails to address compliance issues within a specified timeframe, the TFDA may suspend or revoke the institution’s ability to provide regenerative medical treatments.

By maintaining a rigorous compliance and oversight framework, the TFDA helps safeguard public health and uphold the credibility of Taiwan’s regenerative medicine sector. These regulations ensure that only safe, effective, and high-quality regenerative therapies reach patients, fostering continued innovation while prioritizing patient safety.

Conclusion

Taiwan’s regulatory framework for regenerative medicine ensures strict oversight and adherence to global safety and efficacy standards. As the field continues to advance, Taiwan remains committed to fostering innovation while prioritizing patient safety and regulatory compliance.

Written by: Ames Gross – President and Founder, Pacific Bridge Medical (PBM)

Singapore Medical Device Registration: An Overview 24 Mar 2025, 8:17 pm

Overview of Singapore’s Medical Device Registration Process

The Health Sciences Authority (HSA) of Singapore is responsible for overseeing the registration of medical devices to ensure their safety, efficacy, and quality before they can be marketed and used within the country. The registration process for medical devices follows specific evaluation routes, which are determined based on multiple factors. These factors include the risk classification of the device, whether the device has received prior approvals from overseas reference regulatory agencies, and the duration for which the device has been marketed safely in other jurisdictions. The chosen evaluation route determines the required documentation, associated fees, and turnaround time (TAT) for the registration process.

Evaluation Routes

To streamline the regulatory process, HSA has established different evaluation routes for medical devices. The evaluation route that applies to a particular device depends on its classification and approval history.

Class A Registration

Medical devices that fall under Class A are exempt from product registration requirements. However, companies intending to market Class A devices in Singapore must complete the Class A Exemption List in the MEDICS system as part of their dealer’s license application.

Class B, C, and D Registration

For medical devices classified as Class B, C, or D, the registration requirements vary based on whether the device has been approved by overseas reference regulatory agencies. Several evaluation routes are available, each with its own conditions and requirements.

Full Evaluation

If a medical device has not received approval from any of Singapore’s recognized overseas reference regulatory agencies, it must undergo a full evaluation. This process involves a comprehensive review of the device’s safety, effectiveness, and compliance with regulatory standards.

Abridged Evaluation

Medical devices that have already been approved by at least one overseas reference regulatory agency may qualify for an abridged evaluation. This route allows for a reduced regulatory burden and faster processing time compared to the full evaluation process.

Expedited Class C Registration (ECR-1)

To qualify for the expedited Class C registration under the ECR-1 route, the medical device must meet the following criteria:

• The device must have received approval from at least one overseas reference regulatory agency.
• The device must have been marketed for at least three years in the jurisdiction where it received approval.
• There must be no reported safety issues related to the device anywhere in the world.
• The device must not have been previously rejected or withdrawn by either HSA or any overseas reference regulatory agency.

Expedited Class D Registration (EDR)

The expedited Class D registration process follows a similar approach, with additional requirements:

• The device must have received approval from at least two overseas reference regulatory agencies.
• The device must not have been rejected or withdrawn by HSA or any other regulatory authority.

Immediate Registration (IBR)

For certain Class B devices, immediate registration is available under two different conditions:

• Condition 1 requires that the device has been approved by at least one overseas regulatory agency, has been marketed safely for at least three years, and has not been subject to any safety issues, rejections, or withdrawals.
• Condition 2 requires that the device has been approved by at least two overseas reference regulatory agencies and has not been subject to any safety issues, rejections, or withdrawals.

Immediate Registration for Medical Mobile Applications

Standalone medical mobile applications classified as Class B or Class C may qualify for immediate registration if they have been approved by at least one overseas regulatory agency and have no reported global safety issues or prior rejections.

Devices Not Eligible for Expedited Registration

Certain types of medical devices are excluded from expedited registration and must undergo either the full or abridged evaluation routes. These include:

• Hip, knee, and shoulder joint replacement non-bioactive implants, which fall under Class C.
• Active implantable medical devices, such as pacemakers and neurostimulators, which fall under Class D.
• Implantable devices that come into direct contact with the central circulatory system or central nervous system.
• Hip, knee, and shoulder joint replacement bioactive implants.
• Devices that contain a registrable drug component in a secondary role.
• In vitro diagnostic (IVD) assays used for HIV testing (screening and diagnosis) and blood or tissue donor compatibility testing.

Overseas Reference Regulatory Agencies

Singapore recognizes approvals from several overseas reference regulatory agencies. Medical devices that have been approved by these agencies may qualify for abridged, expedited, or immediate registration, provided that the approval is for the same intended use as in the Singapore market. The recognized agencies include:

• The Therapeutic Goods Administration (TGA) in Australia. The recognized approval in Australia is the Device Registration License.
• Notified Bodies (NB) in the European Union. EC certificates are required.
• Health Canada (HC). Like Australia, the recognized approval in Canada is the Device Registration License.
• The Ministry of Health, Labour, and Welfare (MHLW) in Japan. Recognized approvals include the two types of Pre-market certification – Ninsho from a Japanese registered certification body or a Shonin from the MHLW
• The United States Food and Drug Administration (US FDA). Recognized approvals include 510 clearance, De Novo approval, and Premarket approval (PMA)

It is important to note that Class B, C, and D medical devices classified as Class I or Class II exempt by these overseas regulatory agencies do not qualify for Singapore’s expedited registration routes based on those approvals.

Priority Review Scheme

The Priority Review Scheme is designed to facilitate faster registration and market entry for Class B, C, and D medical devices that must undergo full evaluation. This scheme offers a reduction of 35 percent in turnaround time compared to the standard full evaluation route. However, Class D devices that contain a registrable drug component in a secondary role are excluded from the Priority Review Scheme.

There are two routes under the Priority Review Scheme. The first route applies to medical devices that fall within five key healthcare areas and address an unmet clinical need. The second route applies to other medical devices that do not meet these specific criteria but still qualify for expedited processing under the scheme.

Route 1

A medical device qualifies for Route 1 if it falls within one of the following five healthcare areas:

• Cancer
• Diabetes
• Ophthalmic diseases
• Cardiovascular diseases
• Infectious diseases

Additionally, the device must either be intended for the diagnosis or treatment of a condition that currently has no existing treatment options or represent a breakthrough technology that provides a significant improvement over existing solutions.

Route 2

Devices that do not meet the criteria for Route 1 may still qualify for priority review under Route 2, which allows for an accelerated review process under specific conditions.

Recent Regulatory Updates

New Guideline for Next-Generation Medical Devices

The Health Sciences Authority (HSA) has introduced a new guideline to streamline the approval process for next-generation medical devices. This guideline allows manufacturers to leverage existing data from previously registered devices, reducing redundant testing. It applies to Class B, C, and D devices that share the same product type and validation criteria with their predecessors but are submitted under the FULL route.

Cybersecurity Labelling Scheme for Medical Devices

Singapore has launched a Cybersecurity Labelling Scheme for Medical Devices to enhance data protection in healthcare. The scheme evaluates devices based on four levels of security certification. The voluntary program targets connected medical devices such as neurology equipment, pacemakers, and insulin pumps. The initiative is a response to growing cyber threats in the healthcare industry, emphasizing the importance of securing medical devices against potential breaches.

Revised Change Management Program for SaMD

HSA has updated its Change Management Program (CMP) for Software as a Medical Device (SaMD) to improve regulatory pathways for post-market changes. The updated framework now includes machine learning (ML)-enabled SaMD and introduces a risk-based approach to evaluating changes. This revision allows for more efficient regulatory oversight while maintaining patient safety, with manufacturers encouraged to engage with HSA before submitting updates.

Conclusion

The medical device registration process in Singapore is designed to ensure that all medical devices entering the market meet rigorous safety and efficacy standards. The evaluation route selected for a device impacts the regulatory requirements, processing time, and approval likelihood. By leveraging overseas regulatory approvals and utilizing expedited pathways or the Priority Review Scheme where applicable, companies can optimize their registration strategy for faster market access. Understanding the nuances of Singapore’s regulatory framework is crucial for medical device manufacturers aiming to introduce new products efficiently and in compliance with local regulations.

Written by: Ames Gross – President and Founder, Pacific Bridge Medical (PBM)

Regulation of Software as a Medical Device in Taiwan 5 Mar 2025, 8:41 pm

Introduction

Software as a Medical Device (SaMD) is an evolving sector within the medical device industry, providing essential tools for healthcare applications such as diagnostics, treatment planning, patient monitoring, and telemedicine. Taiwan’s regulatory framework for SaMD is overseen by the Taiwan Food and Drug Administration (TFDA) under the Ministry of Health and Welfare (MOHW). The TFDA is responsible for ensuring that all medical software products that fall within its jurisdiction meet stringent safety, quality, and effectiveness standards before they are allowed to enter the market. This article provides a comprehensive overview of Taiwan’s regulatory landscape for SaMD, covering its definition, classification, registration process, and regulatory requirements.

Definition of Medical Device Software

According to Taiwan’s “Guidelines for Classification of Medical Software,” medical device software refers to applications that collect, store, analyze, display, and convert health-related data for use in medical institutions, personal home care, and remote healthcare services. The software must be designed with a medical purpose in mind and should contribute to the diagnosis, treatment, or management of a patient’s health condition.

It is important to note that not all medical software is classified as a medical device. Determining whether software falls under this category requires an assessment based on several key factors. These factors include the software’s function, intended purpose, method of use, and potential risks to patient safety. Specifically, regulatory authorities assess whether the software:

1. Complies with Article 3 of the Medical Device Act – This involves determining if the software meets the definition of a medical device under Taiwanese law.
2. Is Listed in the Regulations Governing the Classification of Medical Devices – If the software appears in the regulatory classification list, it will be subject to specific requirements.
3. Has Diagnostic or Therapeutic Functions – Software that plays a role in diagnosing or treating diseases is more likely to be regulated.
4. Is Critical to Disease Treatment – The extent to which the software contributes to treating a disease is a significant consideration.
5. Aids in Disease Diagnosis – Software that provides clinical decision support or assists medical professionals in diagnosing conditions may be subject to regulation.
6. Poses a Risk to Human Health – If the software has the potential to cause harm to patients or interfere with medical decision-making, it will likely be classified as a medical device.

Regulatory Classification of Medical Device Software

SaMD products in Taiwan are classified into different categories based on their function, intended use, and potential risk level. The classification system ensures that software is appropriately regulated according to its complexity and impact on patient health. The four primary categories of medical device software include:

1. Accessories for Medical Equipment – This category includes software that is integrated into a medical device to control its operation or enhance its functionality. Examples include software used to control diagnostic imaging machines, infusion pumps, or patient monitoring systems.
2. Stand-alone Software – This type of software is independent of a specific medical device and is often used to process and analyze medical data. It may include applications that assist healthcare professionals in interpreting diagnostic test results.
3. Mobile Applications (Apps) – These are software applications that can be installed on mobile devices such as smartphones, tablets, or wearable gadgets. If the app is designed for medical purposes, such as monitoring blood glucose levels for diabetic patients, it will be subject to medical device regulations.
4. Recording Media – This includes software that is stored on physical media such as CDs, SD cards, or USB drives. Software that is downloaded from the internet and meets the definition of a medical device is also subject to regulation.

Examples of SaMD Classification

To further clarify the classification of SaMD, the TFDA has provided examples of how different types of software are categorized based on their function and level of risk:

• Class I Medical Device: Software that primarily transmits, stores, or displays medical images without making any modifications to the data. An example is a basic X-ray image viewer that does not alter or analyze the image.
• Class II Medical Device: This includes software with more advanced capabilities, such as medical image processing tools, computer-assisted detection (CADe) systems, and surgical treatment planning software. These programs assist healthcare professionals in analyzing medical data but do not replace human decision-making.
• Class III Medical Device: This category includes software that claims to replace professional medical judgment by making autonomous disease diagnoses or treatment recommendations. Artificial intelligence (AI)-based diagnostic tools that function independently without human oversight fall under this category.

Regulatory Process for SaMD Registration

The TFDA has established a structured regulatory process that companies must follow before marketing their SaMD products in Taiwan. This process includes two key steps:

1. Quality System Documentation (QSD) Registration

Manufacturers of Class II and III medical devices, as well as some Class I devices, must establish a Quality Management System (QMS) that complies with TFDA regulations. The QSD registration process ensures that medical device manufacturers follow rigorous quality control measures throughout their production process. To obtain QSD approval, manufacturers must submit the following documentation:

• Basic manufacturer information and a signed authorization letter
• A valid ISO 13485 certification
• A detailed quality manual and quality system procedures (waived for manufacturers from the U.S., EU, and Japan with equivalent certifications)
• A list of manufacturing and testing equipment
• Production process diagrams outlining the steps involved in device manufacturing

2. Product Registration

In addition to obtaining QSD approval, manufacturers must complete a separate product registration process. This step involves submitting:

• A registration application and authorization letter
• Product labeling, packaging insert, and carton labeling drafts
• A Free Sales Certificate (FSC) from the country of origin, issued within the last two years
• Preclinical and quality control test reports
• Documentation detailing the product’s structure, specifications, and intended use
• Clinical evidence, if requested by the TFDA
• Radiation safety information for relevant devices
• Essential Principles (EP) of safety and performance for Class III devices

Priority Review for SaMD

The TFDA provides a priority review pathway for Software as a Medical Device (SaMD) products that address urgent and critical medical needs. This expedited review process is designed to ensure that innovative and essential medical software can reach the market faster while maintaining rigorous safety and efficacy standards.

To qualify for priority review, the SaMD product must meet specific criteria outlined by the TFDA. Firstly, priority review is available for software that is specifically developed to treat life-threatening diseases for which no alternative treatments currently exist. These products must demonstrate that they offer a unique and essential solution in the medical field.

Secondly, software intended for the diagnosis or management of rare diseases, as defined by the Rare Disease and Orphan Drug Act, may also be eligible for priority review. Given the limited availability of treatment options for rare diseases, the TFDA aims to facilitate the availability of SaMD that can aid in early detection, monitoring, and management of these conditions.

Finally, priority review is granted to SaMD products that have received government research funding and are undergoing or planning to conduct clinical trials within Taiwan. This provision is aimed at encouraging local innovation and ensuring that domestically developed medical software can quickly transition from research and development to clinical use.

By offering a priority review process, the TFDA seeks to balance the need for timely access to advanced medical technologies with stringent regulatory oversight. This approach supports the development of high-quality medical software that meets international safety and performance standards while addressing critical healthcare needs in Taiwan.

Post-market Change Applications

In March 2022, the Taiwan Food and Drug Administration (TFDA) issued guidelines for post-market change applications related to Software as a Medical Device (SaMD). These guidelines help manufacturers assess whether modifications require regulatory approval to maintain compliance with safety and performance standards.

Changes that do not require approval include minor bug fixes, security patches, interface design updates, and upgrades to peripheral hardware such as keyboards or monitors, as long as these do not impact the software’s intended use or functionality.

However, approval is required for significant modifications that could affect performance, compatibility, or clinical outcomes. Examples include altering the core algorithm, changing the intended use, adding new diagnostic or analytical functions, upgrading to a non-backward-compatible operating system, or restructuring key software components such as databases and middleware.

By clarifying these requirements, the TFDA ensures that SaMD products continue to meet safety and efficacy standards while allowing for necessary technological advancements.

Conclusion

Taiwan’s regulatory framework for SaMD ensures that all software-based medical devices meet stringent safety, effectiveness, and quality requirements. Companies seeking market entry must carefully navigate the TFDA’s classification and approval process, establish a robust quality management system, and provide comprehensive documentation. The priority review pathway offers an expedited process for innovative medical software, while clear classification guidelines help distinguish between regulated and non-regulated products. As the field of SaMD continues to advance, Taiwan’s regulatory policies will likely evolve to accommodate new technologies, including artificial intelligence, telemedicine, and digital health applications. The integration of emerging technologies into medical software highlights the importance of continuous regulatory updates to maintain safety and efficacy standards while fostering innovation in the healthcare sector.

Written by: Ames Gross – President and Founder, Pacific Bridge Medical (PBM)

Taiwan: Registration of Medical Device and Drug Combination Products 5 Mar 2025, 8:28 pm

Definition of Combination Products in Taiwan

Combination products are classified based on the “Key Points for Combination Product Determination.” These products fall into two main categories. The first category includes a single product that integrates pharmaceuticals and medical devices, where the components are combined physically, chemically, or through other means, and are manufactured by a single entity. The second category consists of a set or package containing two or more pharmaceutical and medical device items that are intended to be used together. These products are designed to work synergistically to achieve a combined therapeutic effect, ensuring better treatment outcomes for patients. Given the complexity of combination products, regulatory frameworks must clearly define their classification and approval processes.

Regulatory Classification

The regulatory classification of combination products is determined by their Primary Mode of Action (PMOA). This refers to the principal mechanism through which the product achieves its intended therapeutic effect. If the primary effect is achieved through the pharmaceutical component, then the product is classified and regulated as a drug. Conversely, if the main effect is achieved through the medical device component, the product is categorized and regulated as a medical device. In cases where the PMOA is unclear, the Taiwan Food and Drug Administration (TFDA) may seek advice from an external committee to make a final determination on the classification.

To ensure that applicants have a clear understanding of how their product will be regulated, the TFDA encourages them to first submit an application for combination product determination. Once the PMOA is identified, the TFDA will determine the product attributes and designate the relevant division that will serve as the main regulatory body. If the product’s primary mode of action is attributed to a drug, the TFDA Drug Division will be the primary reviewer, while the Medical Device and Cosmetic Division will provide additional support. If the product’s primary mode of action is attributed to a medical device, the Medical Device and Cosmetic Division will be the main reviewer, with the Drug Division offering supplementary support. The regulatory clarity provided by this classification process helps streamline the approval pathway, reducing unnecessary delays in market entry.

Registration Process

When the PMOA is a Pharmaceutical

For combination products where the primary mode of action is pharmaceutical, the Marketing Authorization Application (MAA) process begins with site registration. The manufacturing site must first obtain a Plant Master File (PMF) registration. If the manufacturer is located in a non-PIC/S (Pharmaceutical Inspection Co-operation Scheme) member country, Taiwan will require a foreign on-site factory inspection. However, for manufacturers located in a PIC/S member country, it is possible to coordinate the review process using the PMF documentation.

To qualify for a simplified PMF review, applicants must submit documentation that includes a list of GMP inspections conducted within the past five years. This list should provide details such as the date of inspection, the topics covered, and the scope of the inspection. Additionally, an inspection report from the most recent GMP evaluation conducted by the local competent health authority must be provided. This report should also include a GMP certificate or any other equivalent GMP approval documents.

Once the site registration process is completed, the next step is product registration. The application must be submitted in the Common Technical Document (CTD) format. However, for generic pharmaceutical products, the contents of Module 5, which pertains to clinical data, are not required. New drug applications must be submitted electronically via the TFDA ExPress platform using the Electronic Common Technical Document (eCTD) format. This format is based on ICH eCTD Specification V3.2.2. While Modules 2 to 5 of the application can be submitted with supporting documents in English, Module 1, which contains administrative documents, must be submitted in Chinese. The key documents required for registration include manufacturing site registration documents, a quality system documentation report, risk evaluation and mitigation strategy (REMS) documentation if applicable, clinical study status reports, and bridging study evaluations when necessary.

When the PMOA is a Medical Device

For combination products where the primary mode of action is attributed to a medical device, the first step in the registration process is Quality System Documentation (QSD) registration. This requirement applies to some Class I medical devices and all Class II and Class III medical devices. Manufacturers must establish a quality management system that ensures compliance with regulations governing facility operations, equipment maintenance, personnel management, production processes, quality control, storage and logistics, and handling of customer complaints. Before a medical device can be marketed, the physical manufacturing site must apply for QSD document review and obtain a QSD approval letter issued by the TFDA.

Manufacturers that do not hold an ISO 13485 certificate or any equivalent conformity verification document must undergo an on-site audit by the TFDA or its designated organization before the final QSD approval is granted. However, manufacturers located in the United States, the European Union, and Japan may qualify for an abbreviated QSD application process. To qualify for this pathway, manufacturers must submit recognized audit reports such as the MDSAP (Medical Device Single Audit Program) report, an audit report issued by the U.S. FDA, or a PMDA audit report from Japan.

After QSD registration, the applicant can proceed with product registration. While it is possible to submit the Marketing Authorization Application (MAA) before obtaining QSD approval, the final product license will only be issued once the QSD approval letter has been submitted to the TFDA. Products that do not have locally approved predicate devices (essentially equivalent devices) are classified as new devices and will undergo a more stringent review process. In addition to standard documentation requirements, Class II and Class III devices may require additional preclinical testing and safety documentation. For example, devices that generate ionizing radiation must provide documentation supporting radiation safety. Additionally, clinical evidence may be required on a case-by-case basis at the discretion of TFDA reviewers.

Registration Timelines

The timeline for registering a combination product varies depending on whether the PMOA is a pharmaceutical or a medical device.

For pharmaceutical products, the Plant Master File (PMF) review typically takes 200 calendar days, excluding any clock stop periods during deficiency responses. The on-site GMP inspection also takes approximately 200 calendar days. For new drug applications, the total approval time ranges from 200 to 360 days, depending on whether clinical data is required.

For medical devices, the QSD on-site inspection process takes approximately 240 days, while the QSD document review takes about 120 days. The total registration timeline for new medical devices varies depending on their classification. For Class II medical devices, the process takes 140 days, whereas for Class III medical devices, it takes 200 days. If the device is considered new with no locally approved predicate, the timeline extends to 220 days due to additional review requirements.

Regulatory Fees

The cost of registering a combination product depends on its classification. The below fees are all Taiwanese government fees. The administrative fee for PMOA determination is NT$10,000. For pharmaceutical combination products, the Plant Master File (PMF) review fee is NT$120,000, while the GMP on-site inspection fee ranges from NT$600,000 to NT$700,000. The registration fee for new chemical entities (NCEs) is NT$1,500,000, while the cost of generic drug registration varies from NT$80,000 to NT$140,000.

For medical device combination products, the QSD registration fee is NT$60,000. The registration fee for Class I medical devices is NT$15,000, for Class II medical devices it is NT$58,000, and for Class III medical devices it is NT$100,000. The cost for priority review is NT$180,000, and for new medical devices with no local predicate, the fee is NT$130,000.

Conclusion

The regulatory framework for drug-device combination products in Taiwan is determined primarily by the Primary Mode of Action (PMOA). Pharmaceutical-led products must comply with GMP regulations and eCTD submissions, while medical device-led products must complete QSD registration and additional device-specific reviews. Manufacturers should carefully assess their product’s classification and ensure compliance with all TFDA requirements to facilitate the approval process and achieve timely market entry.

Written by: Ames Gross – President and Founder, Pacific Bridge Medical (PBM)

Singapore Drug Registration: A Comprehensive Guide 5 Mar 2025, 4:32 pm

Singapore has a well-structured and rigorous regulatory framework for drug registration, which is overseen by the Health Sciences Authority (HSA) under the Health Products Act (HPA). The HSA is responsible for evaluating, approving, and regulating therapeutic products before they can be supplied in the country. Companies that intend to engage in the manufacturing, importing, or wholesaling of pharmaceutical products must obtain the relevant licenses to legally operate within Singapore. The entire registration process is designed to ensure that only high-quality, effective, and safe pharmaceutical products reach the market, thereby protecting public health.

Key Regulatory Framework for Drug Registration in Singapore

The Health Products Act (HPA) mandates that all therapeutic products must be registered before they can be legally supplied within Singapore. In addition to the mandatory product registration, companies involved in the pharmaceutical supply chain may also need to obtain one or more of the following licenses, depending on their specific business activities:

• Manufacturer’s Licence (ML): Required for companies that manufacture therapeutic products within Singapore.
• Importer’s Licence (IL): Required for companies that import therapeutic products into Singapore from other countries.
• Wholesaler’s Licence (WL): Required for companies that engage in the wholesale distribution of therapeutic products in Singapore.

The regulatory requirements established by the HSA aim to ensure the quality, safety, and efficacy of all pharmaceutical products available in the Singaporean market.

Categories of Product Registration Applications

Companies seeking to register a therapeutic product in Singapore must determine the appropriate product registration application category based on the nature of their product. The HSA classifies registration applications into the following categories:

1. New Drug Application (NDA)

New Drug Applications (NDAs) apply to pharmaceutical products that contain new active ingredients, new combinations of active ingredients, or new formulations. NDAs are further classified into three subcategories:

• NDA-1: This category applies to the first strength of a product that contains a new chemical or biological entity that has never been registered before.
• NDA-2: This category applies to products that contain a new combination of registered chemical or biological entities, products that involve a new dosage form or new route of administration, or products that are intended for a new indication or patient population.
• NDA-3: This category applies to subsequent strengths of a product that has already been registered or submitted under NDA-1 or NDA-2.

2. Generic Drug Application (GDA)

Generic Drug Applications (GDAs) apply to products that are bioequivalent to an already registered reference product. These applications are divided into two subcategories:

• GDA-1: This category applies to the first strength of a generic chemical product that is identical in composition to a currently registered product.
• GDA-2: This category applies to subsequent strengths of a registered generic product, provided that the product name and dosage form remain identical to the registered GDA-1 product.

Documents Required for Drug Registration in Singapore

The documentation required for a drug registration application depends on the type of product being registered and whether it has already been approved by other regulatory agencies. The HSA requires applicants to submit one of the following types of evaluation dossiers:

• Full Evaluation Dossier: Required for new drugs that have not been evaluated or approved by any other regulatory agency.
• Abridged Evaluation Dossier: Required for drugs that have already been approved by at least one major regulatory agency.
• Verification Evaluation Dossier: Required for drugs that have been approved by a stringent regulatory authority and have no significant differences from the approved product.

Step-by-Step Registration Process

Step 1: Pre-Submission Preparations

Before submitting an application, companies must ensure that they have compiled all necessary documents required for the registration process. At this stage, applicants are strongly encouraged to seek clarifications from the HSA through a pre-submission inquiry or by requesting a pre-submission consultation.

Step 2: Application Submission

Once the pre-submission preparations are complete, applicants must:

1. Complete the application form using the HSA’s online Pharmaceutical Regulatory and Information System (PRISM). Before accessing PRISM, companies must have an active Company Registration for e-Services account.
2. Submit the complete evaluation dossier to the HSA within two working days after submitting the PRISM application, if it has not already been submitted electronically.

Step 3: Application Screening

After submission, the HSA conducts an initial screening to identify any deficiencies in the application. If additional information is required, the applicant must provide the necessary documents within 20 working days. Failure to respond within this timeframe will result in the application being rejected, and a new application must be submitted.

Step 4: Application Evaluation and Decision

Once the application dossier passes the screening stage, it proceeds to the evaluation stage, where the HSA conducts a thorough review to determine if the product meets the necessary regulatory standards. A regulatory decision is then made based on the outcome of this evaluation.

Processing Timelines for Drug Registration in Singapore

The target processing timelines for drug registration in Singapore are as follows:

• Full evaluation dossiers: Processed within 270 working days.
• Abridged evaluation dossiers: Processed within 120-240 working days.
• Verification evaluation dossiers: Processed within 60-120 working days.

It is important to note that these timelines do not account for any delays caused by the need for additional information from the applicant. Depending on the number of input requests made by the HSA and the response time of the applicant, the actual evaluation period may extend beyond the stated timelines.

In exceptional cases, priority review may be granted for life-saving drugs that address critical unmet medical needs.

Registration Exclusivity and Patent Linkage System

Under the Health Products (Therapeutic Products) Regulations 2016, the efficacy and safety data used to register a product are granted 5 years of registration exclusivity. During this exclusivity period, a competitor cannot register a similar product using the same data unless explicit consent is obtained from the original registrant.

In addition, Singapore has implemented a patent linkage system as part of its obligations under the US-Singapore Free Trade Agreement. Applicants must declare whether a patent exists for the therapeutic product being registered. If the product is patented, the application will fall under one of the following categories:

• Category A1: The applicant owns the patent or has obtained consent from the patent owner.
• Category A2: The applicant seeks registration upon the expiry of the patent (applications cannot be made more than 18 months before patent expiry).
• Category B: The applicant believes the patent is invalid or that the drug does not infringe on the patent.

For Category B applications, the HSA requires notification to be sent to the patent holder, providing them an opportunity to take legal action if necessary.

Recent Regulatory Updates

Expedited Minor Variation Applications

The HSA has introduced a new framework to expedite the review of minor variations for certain pharmaceutical products. To qualify for an expedited review, a drug must meet specific eligibility criteria:

• There must be no alternative medicine available in Singapore.
• The drug must be required for national procurement.
• There must be an urgent need for the product.

To assist applicants, the HSA will launch an online form to guide them in determining eligibility for this expedited review program. If an applicant submits the required documentation for an expedited review, the HSA will evaluate the request and determine within five working days whether the application qualifies.

Updates to Appendix 7 for Drug Registration

The HSA has implemented revisions to Appendix 7 of the drug registration guidelines. The following changes have been introduced:

• The requirement to include the date of manufacture on the outer packaging or inner label has been removed.
• The warning statement regarding alternative uses of biosimilar products is no longer mandatory on package labels.
• There is now greater flexibility regarding the inclusion of the product owner’s name, drug manufacturer’s name, or registrant’s name and address on the outer drug carton or package insert.

Faster Evaluation Timelines for New Drug Applications

Singapore’s Therapeutic Products Branch, Health Products Regulation Group has improved its evaluation process for New Drug Applications (NDAs), Generic Drug Applications (GDAs), and Major Variation Applications (MAV-1). Companies can expect to receive their first-round evaluation feedback earlier than before. Additionally, a new web tool has been introduced to provide clearer timelines for drug approval.

Implementation of the eCTD Portal

In late September 2024, the HSA announced the launch of an eCTD (electronic Common Technical Document) portal program, which will begin in early 2025. The eCTD portal version 1.0 is an improvement over the previous version 0.9 and will initially be in a voluntary test phase from March to September 2025. This phase will allow companies to submit new drug applications, generic drug applications, and Drug Master File (DMF) applications electronically. While the eCTD format is widely used by Western pharmaceutical companies, it remains uncertain whether its use will become mandatory in Singapore in the future.

Project Orbis Information Now Available

The HSA website now includes dedicated information about Project Orbis, a US FDA initiative that involves multiple international regulatory agencies, including Singapore, working together on the accelerated approval of cancer treatments. This provides transparency and guidance for pharmaceutical companies looking to participate in Project Orbis.

Written by: Ames Gross – President and Founder, Pacific Bridge Medical (PBM)

Understanding Medical Device Registration in Japan 3 Mar 2025, 3:53 pm

Japan has a well-defined regulatory framework for medical devices, ensuring their safety, efficacy, and quality before they reach the market. The process is governed by two key regulatory authorities: the Ministry of Health, Labour and Welfare (MHLW) and the Pharmaceuticals and Medical Devices Agency (PMDA).

Regulatory Authorities

The Ministry of Health, Labour and Welfare (MHLW) is responsible for administrative actions related to medical devices. These actions include issuing guidance, approving medical devices under the Act on Securing Quality, Efficacy, and Safety of Products Including Pharmaceuticals and Medical Devices (PMD Act), and determining whether a product qualifies as a medical device.

The Pharmaceuticals and Medical Devices Agency (PMDA) is tasked with conducting product reviews, assessing safety measures, and carrying out post-market surveillance to ensure continued compliance with regulatory requirements.

Medical Device Classification

Medical devices in Japan are categorized into four classes based on their risk level:

• Class I (Extremely low risk) – Examples of devices in this category include surgical instruments and dental mirrors.
• Class II (Low risk) – This class includes devices such as MRI scanners and infusion pumps.
• Class III (Medium risk) – Examples of medium-risk devices include artificial joints and pacemakers.
• Class IV (High risk) – High-risk devices include heart valves and implantable defibrillators.

The specific registration requirements vary depending on the classification of the device. Additionally, device classification is determined based on three main criteria:

1. Device class
2. Japan Association has JMDN code list (JAAME)
3. Substantial equivalence with predicate devices

Medical device classifications in Japan can differ from those in other regulatory regions. For example, Class II products in the U.S. may be classified as Class III in Japan.

Registration Process

In order to market medical devices in Japan, foreign manufacturers must register their products through a Japanese Marketing Authorization Holder (MAH) or a Designated Marketing Authorization Holder (DMAH). The specific registration process depends on the classification of the device:

Class I Devices:

Manufacturers of Class I medical devices must submit a notification to the PMDA before marketing their products in Japan.

Class II Devices:

For Class II devices where certification standards exist, manufacturers must obtain certification from a Registered Certification Body. If no certification standards exist, the manufacturer may need to obtain approval from the PMDA.

Class III Devices:

For Class III devices that have established certification standards, certification by a Registered Certification Body is possible. If certification standards are not available, the manufacturer must seek approval from the PMDA.

Class IV Devices:

All Class IV devices, which carry the highest risk, require approval from the PMDA.

Class III and IV Device Registration Sub-Categories

For higher-risk devices (Class III and IV), registration falls into three sub-categories:

• Me-too or generic devices: These have an existing JMDN code and are based on a previously registered technical file.
• Improved devices: These have an existing JMDN code, but require a new technical file due to modifications.
• New devices: These have no appropriate JMDN code, no predicate device, and usually require local clinical trials before approval.

For In Vitro Diagnostics (IVDs), devices are classified into Classes I-III.

If the classification of a device is unclear, manufacturers may visit and discuss the matter with the regulatory affairs division of local prefectures to seek clarification.

PMDA Consultation Process

Before proceeding to a formal PMDA Consultation session, manufacturers can take advantage of one or two free PMDA consultations. Each free session lasts for 30 minutes and is primarily aimed at advising which formal PMDA consultation should be pursued. During this session, the PMDA may or may not answer specific questions.

For the free consultation, manufacturers are generally required to submit a short PowerPoint presentation (maximum 15 slides) introducing their company and product. If bringing Japanese Key Opinion Leaders (KOLs) to the meeting, it is important to ensure they are truly recognized KOLs rather than mid-level Japanese doctors. Additionally, conducting a rehearsal beforehand is highly recommended to clarify speaking roles and emphasize key slides.

Types of Formal PMDA Consultations

• Zenpan Sodan (General Introductory Consultation): This session is intended to provide general guidance on regulatory pathways. A short PowerPoint introducing the company and product should be submitted before the meeting. The goal is to understand the PMDA’s recommendations and determine the next appropriate consultation.
• Kaihatsumae Sodan (Pre-Development Consultation): This is a formal PMDA consultation session, and it involves a deeper review, covering required testing, supporting data, and other pre-development aspects.
• Rinsho Yohi Sodan (Clinical Trial Consultation): This is a formal PMDA consultation session and focuses on whether additional clinical trials are necessary. It evaluates existing non-clinical data, foreign clinical data, trial protocols, and, if a new trial is required, defines criteria such as patient numbers and study design.
• Please note there are also other types of PMDA consultations too.

Each type of PMDA meeting has different government fees and presentation requirements. Additionally, manufacturers should budget sufficient time for these consultations, as scheduling the first free consultation typically takes 2-3 weeks, while subsequent formal PMDA meetings may take up to 4 months to arrange.

For devices that require certification, a Registered Certification Body (RCB) evaluates compliance with applicable safety and efficacy standards. This process ensures that the device meets Japan’s regulatory requirements before being marketed.

For devices that require approval from the PMDA, the PMDA will conduct a comprehensive product review to assess their safety and efficacy.

This structured regulatory framework ensures that only safe and effective medical devices enter the Japanese market. By enforcing stringent safety measures, Japan maintains high healthcare standards and protects patient safety.

Registration Requirements

For a successful medical device registration in Japan, manufacturers must prepare a registration dossier that includes the following components:

• Dossier application and STED (Summary of Technical Documentation). Information such as product name, manufacturing
• QMS application, which involves either a paper or on-site audit, is required every five years.
  • This application must include details such as a manufacturing flow chart, floor plan, ISO 13485 certificate, and quality manual.
  • It is similar to ISO 13485:2003, but it is not identical. The QMS review is conducted simultaneously with the product application review and can be performed either on paper or on-site.
  • However, even with MDSAP certification, some medical products such as radiopharmaceuticals for IVDs still require an on-site audit
  • Manufacturers holding MDSAP certification must still submit a QMS application and pay an additional $2,000 per registered factory on top of the standard government fees.
• Foreign Manufacturer Registration (FMR) application
  • Previously known as Foreign Manufacturer Accreditation (FMA) before 2014
  • FMA (License process) required more facilities to be audited
  • FMR (Accreditation process) reduces the number of facilities needing accreditation (now limited to the design facility, main assembly plant, sterilization site, and domestic distribution center)
  • The FMR process is a paper exercise and is not overly complex
• Reliability Investigation Application Form (required for high-risk devices only)

Recent Regulatory Updates

Japan Advances Regulatory and Reimbursement Frameworks for SaMD Products

After a slow start, Japan is now taking decisive action to modernize its regulatory and reimbursement systems for Software as a Medical Device (SaMD) to keep pace with global healthcare innovation. The Pharmaceuticals and Medical Devices Agency (PMDA) has introduced several initiatives aimed at accelerating the review process and integrating SaMD products more effectively into the Japanese healthcare system.

Streamlining SaMD Approvals through Enhanced Review Protocols

A key regulatory development occurred on March 13, 2023, when the PMDA decided that SaMD products would undergo a priority review process with a target completion time of six months. This decision follows the success of the Trial Implementation of Priority Review for Program Medical Devices, which began in September 2022. To qualify for this priority review, SaMDs must either be introduced in Japan for the first time or launched simultaneously in global markets. Additionally, they must offer innovative approaches in treatment or diagnosis that provide significant benefits over existing technologies.

In a further regulatory enhancement, the PMDA considered a new two-stage approval mechanism during its May 29, 2023 meeting. This approach allows for an initial approval based on demonstrated efficacy, followed by a comprehensive assessment using post-market safety and efficacy data. The updated guidance outlines distinct registration criteria for diagnostic, therapeutic, and preventive SaMD products, ensuring a clear pathway for regulatory approval while maintaining patient safety.

Refining Reimbursement Strategies to Support SaMD Integration

Reimbursement policies for SaMD products were a focal point during the Chuikyo meeting (Chuikyo is the reimbursement body in Japan)  on July 26, 2023, which discussed fiscal year 2024 reimbursement strategies. The discussion centered on tailoring reimbursement models to reflect the clinical value of SaMD products. Various models, including adjustments to existing medical fees, the application of medical fee premiums, and cost-based evaluations, are under consideration. Additionally, authorities are exploring performance-based reimbursement models, where payment structures are adjusted based on real-world clinical benefits observed post-deployment.

Aligning with International Standards and Practices

To enhance Japan’s competitiveness in the global digital health space, Chuikyo has analyzed reimbursement rates applied in international markets. This alignment ensures that Japan’s pricing structure remains competitive and reflects the innovative nature and clinical benefits of SaMD products. Furthermore, the PMDA launched the “Dash for SaMD2” program to improve regulatory efficiency, expand its SaMD review team, and establish a subscription-based consultation service for SaMD developers.

In its five-year plan (2024-2028) announced on January 22, 2024, the PMDA also committed to finalizing all SaMD registration reviews within six months, ensuring a faster and more predictable regulatory process.

Future Outlook

Japan’s proactive approach in regulating and reimbursing SaMD products underscores its commitment to fostering rapid technological innovation in healthcare. By optimizing both approval processes and reimbursement models, Japan is not only expediting the adoption of advanced medical technologies but also positioning itself as a leader in the global digital health sector.

Written by: Ames Gross – President and Founder, Pacific Bridge Medical (PBM)