The present article provides an overview of the most important aspects related to submissions for in vitro diagnostic medical devices.
Table of Contents
The Health Sciences Authority (HSA), Singapore’s regulatory agency in the sphere of healthcare products, has published a technical reference document dedicated to the content of product registration submissions for in vitro diagnostic (IVD) medical devices in the context of the ASEAN CSDT.
The document provides an overview of the applicable regulatory requirements, as well as additional clarifications and recommendations to be taken into consideration by medical device manufacturers and other parties involved in order to ensure compliance therewith. At the same time, provisions of the guidance are non-binding in their legal nature, and they are not intended to introduce new rules or impose new obligations.
The authority also reserves the right to make changes to the guidance, should such changes be reasonably necessary to reflect corresponding changes to the underlying legislation.
The present document is intended to provide additional guidance on the process and requirements for the preparation of a Product Registration Submission for In Vitro Diagnostic (IVD) medical devices using the ASEAN Common Submission Dossier Template (CSDT). The ASEAN CSDT is aligned with the Global Harmonization Task Force (GHTF) and serves as a unified template for submitting product information to the Health Sciences Authority and other medical device regulatory bodies within the ASEAN countries.
Purpose and Scope
As explained by the authority, the purpose of this document is to:
- Clarify the information that needs to be included in each section of the ASEAN CSDT, and
- Specify the format for this information.
The scope of the guidance covers any and all medical devices intended to be marketed and used in the country. The authority also refers to guidance documents GN-15 and GN-17 for further information.
Terms and Definitions
First of all, the document provides definitions of the most important terms and concepts used in the context of IVD device registration. In particular, the document explains, inter alia, the following terms:
- Calibrator – any substance, material, or article intended by its product owner to be used in the calibration of a measuring instrument or measuring system;
- Control material – any substance, material, or article intended by its product owner to verify the performance of an IVD medical device;
- Instrument – equipment or apparatus intended by the product owner to be used as IVD medical device.
- Near patient testing – any testing performed outside a laboratory environment by a healthcare professional, not necessarily a laboratory professional, generally near to or at the side of the patient; also known as Point-of-Care (POC);
- Performance evaluation – a review of the performance of a medical device based upon data already available, scientific literature, and, where appropriate, laboratory, animal, or clinical investigation.
- Reagent – any chemical, biological, or immunological components, solutions, or preparations intended by the product owner to be used as IVD medical devices.
Specimen receptacle – an IVD medical device, whether vacuum-type or not, specifically intended by the product owner for the primary containment of specimens derived from the human body.
Design Verification and Validation
The guidance also outlines the scope of documents to be included in the submission with respect to design verification and validation-related matters. In particular, the documentation to be provided by the applicant should cover such aspects as:
- Preclinical studies (e.g., physical test data, biocompatibility studies, animal studies and software verification and validation studies);
- Metrological requirements;
- Sterilization validation (if applicable).
The authority also expects the applicants to provide comprehensive information about shelf-life studies and the projected useful life of the product in question.
As further explained by the HSA, the documents to be included in the submission should include sufficient evidence supporting the physical or mechanical properties of the product in question, as well as evidence supporting its electrical safety and electromagnetic compatibility. For instance, should the device be supposed to be compliant with the specifications set forth by the applicable international standard, the manufacturer will be expected to provide a summary of the appropriate test reports and/or relevant certificates demonstrating compliance with the said specifications.
The manufacturer should also provide the details on the exact version of the software used for the device subject to review (the authority mentions that the version number used for internal purposes is not required). The manufacturer should also provide a description of any and all verification, validation, and testing activities carried out with respect to the software, including references to the specific version undergoing such testing.
The scope of the information and documentation to be submitted by the applicant should cover, inter alia, the following aspects:
- Any and all anomalies identified in the course of testing that have not been resolved. For each of them, the manufacturer would have to provide an appropriate justification of why they are acceptable and also inform the public of any plans to have the respective issues resolved.
- Studies related to biocompatibility and toxicology. In this respect, the authority additionally emphasizes that if the tests described in the applicable standard, which is ISO 10993, have not been conducted, the appropriate explanation should be provided as well.
- Details on the biological materials or derivatives, including their description and purpose.
In summary, the present HSA guidance describes in detail the scope of information and documentation to be included in the submissions in order to ensure its completeness. The authority outlines specific documents to be provided with respect to the general description of the device, its compliance with the applicable regulatory requirements and standards, as well as any testing it was subject to.
Preparation of the ASEAN CSDT Dossier
The guidance further outlines the most important considerations for the preparation of the CSDT dossier. It explains that the dossier should be complete, covering sections 3.0 to 4.6.1, and be prepared in English. Non-applicability of any section should be explained clearly by the responsible party, with the appropriate justification provided. Supporting documents such as labeling, certificates, and reports should be attached to the CSDT submission.
These documents should be legible, signed off by the product owner, and must be within their validity period. Furthermore, the document specifies that the level of detail required in the CSDT sections will vary depending on the class of the IVD medical device and its evaluation route.
Executive Summary and Important Safety Information
An executive summary should accompany the CSDT dossier, which includes an overview of the medical device, commercial marketing history, and intended uses, among other elements. The summary should also indicate any novel features, with detailed information about such features provided. For devices subject to any fast-track procedure, a list of regulatory approvals or marketing clearances, along with their status, should be included in the form of a table.
The authority also mentions that relevant copies of certificates or approval letters from reference agencies need to be provided as well. If labeling, packaging, and instructions for use (IFU) are identical to those approved by reference agencies, the respective declaration will be required. At the same time, if there are differences, they should be described in detail with the appropriate justification provided.
Important safety and performance-related information should also be disclosed. This includes a summary of adverse events and field safety corrective actions (FSCAs) related to the device in question. If FSCAs are still ‘open,’ a root cause analysis along with corrective and preventive actions (CAPA) must be provided as well.
Contact Information and Updates
As explained by the HSA, the applicants should also take into consideration the continuous requirement to update the information, especially contact information, in the event of changes. New contact information should be provided through various means, such as during a visit or by mailing the information in an envelope, to protect the subject’s privacy.
In summary, this guidance document constitutes a comprehensive manual for the preparation of a product registration submission for IVD medical devices through the ASEAN CSDT, outlining the content, format, and special considerations for various classes of devices and their evaluation routes. By virtue of the present guidance, the authority highlights the key points related to the submissions in order to improve their overall quality and streamline the processes associated with them.
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