1. INTRODUCTION
1. INTRODUCTION
1.1. Purpose
1.1. Purpose Medical devices undergo changes as part of their product life cycle. This guidance document is intended to aid registrants in determining whether a Change Notification has to be submitted for a medical device that is registered on the Singapore Medical Device Register (SMDR). Under the Health Products (Medical Devices) Regulations 2010, registrants are required to notify changes concerning registered medical devices to the Authority.
1.2. Background
1.2. Background Medical devices are classified into four risk classes (A to D) based on the classification rules set out in GN-13: Guidance on the Risk Classification of General Medical Devices and GN-14: Guidance on the Risk Classification of In-Vitro Diagnostic Medical Devices. Class A represents the lowest risk medical devices and Class D represents the highest risk medical devices. These guidelines to Change Notification are based on the principles of safety, quality and efficacy of medical devices supplied in Singapore. Changes to a medical device can affect its safety, quality or efficacy and must be approved prior to the modified device being supplied in Singapore, unless otherwise indicated.
1.3. Scope
1.3. Scope This guidance document applies to all medical devices registered on the SMDR. It sets out points for consideration by the registrant when a registered medical device is in the process of modification. Owing to the various possible scenarios for changes made to a device, it is not the intention of this guidance document to describe every permutation and type of change that can occur. The registrant and/or the product owner may contact the Medical Devices Branch at hsa_md_info@hsa.gov.sg, for any clarifications regarding the classification of specific changes to a registered medical device. MEDICAL DEVICE GUIDANCE DECEMBER 2017 HEALTH SCIENCES AUTHORITY – HEALTH PRODUCTS REGULATION GROUP Page 6 of 53 This guidance document is also applicable to situations when a registered device undergoes any changes or proposed changes, including labelling changes, as a result of a reportable Adverse Event (AE) or an on-going Field Safety Corrective Action (FSCA).
1.4. Definitions
1.4. Definitions Definitions that do not indicate they are set out in the Act or Regulations are intended as guidance in this document. These definitions are not taken verbatim from the above legislation and should not be used in any legal context. These definitions are meant to provide guidance in layman terms. ACCESSORY: An article that is intended specifically by its product owner to be used together with a particular medical device to enable or assist that device to be used in accordance with its intended purpose. An accessory typically is intended to be used for one or more of the purposes as described in the definition of medical device and therefore should be considered a medical device. CONTROL MECHANISM: for the purpose of this guidance document, a means for verifying or checking that the specifications or outputs of the medical device meet a standard or predetermined result. LABEL (as set out in the Act): in relation to a health product or an active ingredient, means any written, printed or graphic representation that appears on or is attached to the health product or active ingredient or any part of its packaging, and includes any informational sheet or leaflet that accompanies the health product or active ingredient when it is being supplied. MEDICAL DEVICE GUIDANCE DECEMBER 2017 HEALTH SCIENCES AUTHORITY – HEALTH PRODUCTS REGULATION GROUP Page 7 of 53 INTENDED PURPOSE/INTENDED USE (as set out in the Regulations): in relation to a medical device or its process or service, means the objective intended use or purpose, as reflected in the specifications, instructions and information provided by the product owner of the medical device. MEDICAL DEVICE: means a medical device as described in the First Schedule of the Act. OPERATING PRINCIPLE: For the purpose of this guidance document, the means by which a medical device produces or brings about a desired or appropriate effect. PRODUCT OWNER (as set out in the Regulations): in relation to a health product, means a person who — (a) supplies the health product under his own name, or under any trade mark, design, trade name or other name or mark owned or controlled by him; and (b) is responsible for designing, manufacturing, assembling, processing, labelling, packaging, refurbishing or modifying the health product, or for assigning to it a purpose, whether those tasks are performed by him or on his behalf. QUALITY MANAGEMENT SYSTEM: for the purpose of this guidance document, means certification to ISO 13485 or its equivalent. REGISTRANT (as set out in the Act): in relation to a registered health product, means the person who applied for and obtained the registration of the health product under the Act. R4 ► INDIRECT CONTACT: In relation to the nature of body contact of medical device, includes devices that contact the blood path at one point and serve as a conduit for entry into the vascular system. E.g. blood transfusion tubes, blood bags, etc. MEDICAL DEVICE GUIDANCE DECEMBER 2017 HEALTH SCIENCES AUTHORITY – HEALTH PRODUCTS REGULATION GROUP Page 8 of 53
2. HOW TO USE THIS GUIDANCE
2. HOW TO USE THIS GUIDANCE When several simultaneous changes are being implemented on a registered device, this guidance document should be used to assess each change separately. If a Change Notification is required, the registrant shall describe how the modified device differs from the previously registered device (or device type) using Annex 2. Registrants are reminded that the determination of documents and the category of Change Notification (e.g. notification, technical) should be made through reference to all change types for the registered device included in the application. Changes to accessories of registered medical devices will also come within the purview of this document. Some changes that will NOT qualify for Change Notification and require the submission of a NEW Pre-market Product Registration include: Change to the intended purpose of a registered medical device; Change to the risk classification of a registered medical device; Addition of model that do not fulfil the grouping criteria, including permissible variants, as listed in the GN-12 guidance documents on Grouping of Medical Devices for Product Registration; Change to the medicinal substance in a device that incorporates a medicinal product in an ancillary role; R4 ► Addition of medical devices with device proprietary names different from the registered devices, into a device listing. Unless the devices with different proprietary names qualify to be listed together under one SMDR listing based on GN-12 guidance documents on Grouping of Medical Devices for Product Registration. The registrant and/or the product owner should contact the Medical Devices Branch, if there are any queries on whether a change in the registered device may require a new product registration. MEDICAL DEVICE GUIDANCE DECEMBER 2017 HEALTH SCIENCES AUTHORITY – HEALTH PRODUCTS REGULATION GROUP Page 9 of 53 CATEGORIES OF CHANGES Changes to registered medical devices that require the submission of a Change Notification are classified into four categories namely: 1) Technical Changes for Class C and D medical devices affect the safety, quality or efficacy of these medical devices. These require HSA’s approval prior to implementation of the change(s) in Singapore. 2) Review Changes (closed list of changes) for Class A and B medical devices affect the safety, quality or efficacy of these medical devices. These require HSA’s approval prior to implementation of the change(s) in Singapore and are as follows: (i) Change(s) to indications for use of the registered medical device (except reduction of indications for use not arising due to device safety, quality or efficacy concerns); (ii) R4 ► Addition of new model(s) (except addition of new models falling under 6Aii/6Aiii/6Aiv of the Flowchart 6A) to a registered medical device listing; (iii) Removal and/or revision of warnings, precautions and contraindications; (iv) Modification of approved method of use, including change from “Professional use only” to “Home use”. 3) Administrative Changes include changes to the administrative documents and information submitted at the point of registration of the medical device. These require HSA’s approval prior to implementation of the change(s) in Singapore. 4) Notification Changes may be implemented immediately upon receipt of the acknowledgement email from HSA after submission via MEDICS, unless the change is in the context of, or is a consequence of a reportable Adverse Events (AEs) or Field Safety Corrective Actions (FSCAs). MEDICAL DEVICE GUIDANCE DECEMBER 2017 HEALTH SCIENCES AUTHORITY – HEALTH PRODUCTS REGULATION GROUP Page 10 of 53 R4.1 ► The implementation of such changes can only proceed after the FSCA/local AE cases have been reported to MDB. NOTE: ‘Notification’ changes which are incorrectly classified will be rejected upon review and further supply of the affected device will be prohibited. Subsequent supply will be subject to approval of the change in the correct Change Notification category. R4 ►Table 1 - Categories of Change Notification for Class A, B, C and D listings Risk Classification Technical Changes Review Changes Administrative Changes Notifications Class A √* √ √ Class B √* √ √ Class C √ √ √ Class D √ √ √ *Closed list of changes
2.1. Addition and Changes to Non-sterile Class A Medical Devices in a
2.1. Addition and Changes to Non-sterile Class A Medical Devices in a Closed System Non-sterile Class A medical devices that are specifically intended for use with a registrable medical device in a closed SYSTEM should be included in the product registration of that SYSTEM. Upon successful registration of the medical device SYSTEM, these non-sterile Class A devices would be listed on the SMDR. For such non-sterile Class A devices that are listed together with other registrable medical devices as a closed SYSTEM on the SMDR, a Change Notification submission would be required only when there are changes to the listing information of these devices on the SMDR. There will be no processing fees for these Change Notifications. R4.2 ► -- MEDICAL DEVICE GUIDANCE DECEMBER 2017 HEALTH SCIENCES AUTHORITY – HEALTH PRODUCTS REGULATION GROUP Page 11 of 53
2.2. Changes to Medical Devices due to an AE and/or FSCA
2.2. Changes to Medical Devices due to an AE and/or FSCA Changes to medical devices may arise from the occurrence of AEs or FSCAs. The proposed changes to the medical devices in these situations are intended to have an impact on the safety, quality and/or efficacy of the medical device. These changes to the medical devices require a Change Notification and may only be implemented after HSA’s review and approval. R4 ► Documents and information to be submitted in support of proposed changes may include the following information: Product owner’s Field Safety Notice (FSN) or Dear ‘Healthcare Professional’ Letter (DHCPL) and/or other risk communication documents; Product owner’s Health Hazard Evaluation (HHE); Product owner’s Root Cause Analysis (RCA); Product owner’s Corrective and Preventive Action (CAPA) to reduce likelihood of recurrence of device issue; Product owner’s CAPA effectiveness/ validation. If there is no change to the aforementioned documents submitted under FSCA reporting, applicant is not required to re-submit them in the Change Notification application. The FSCA reference number should be indicated within the Annex 2 to GN-21: Summary Table of Change Notification for reference. In situations where some of the above documents have yet to be submitted to HSA, or where further information is required, HSA may request for them. The determination of the category of change for Change Notification applications submitted in the context of, or as a consequence of or arising from open reportable AEs or on-going FSCAs shall be based on the type of change as per the flowcharts in the Section 4 of this document. MEDICAL DEVICE GUIDANCE DECEMBER 2017 HEALTH SCIENCES AUTHORITY – HEALTH PRODUCTS REGULATION GROUP Page 12 of 53 Changes submitted in the context of, or as a consequence of or arising from open reportable AEs or on-going FSCAs would require prior approval from HSA before implementation. This clause applies to all registered medical devices (Class A to D) regardless of the category of change selected. Exception to this clause shall require the registrant to possess a written advice from HSA that states otherwise.
3. CHANGE TYPE ASSESSMENT FLOWCHARTS
3. CHANGE TYPE ASSESSMENT FLOWCHARTS The twelve flowcharts detailed in this section present guiding principles for identification of the category of Change Notification applicable for each proposed type of change to the registered medical devices. The “Main Flowchart” shall be used to determine the applicable flow chart for a specific change. Examples of changes are included in the flowcharts for ease of reference. Please note that the examples are not meant as an exhaustive list. Full description of each final change type in the flowcharts can be found in Annex 4 to GN-21: Change Types Submission Reference List. This change type should be indicated in MEDICS and Annex 2 to GN-21: Summary Table during submission of CN application. MEDICAL DEVICE GUIDANCE DECEMBER 2017 HEALTH SCIENCES AUTHORITY – HEALTH PRODUCTS REGULATION GROUP Page 13 of 53 Main Flowchart This flowchart describes the general types of changes that can be made to a medical device, and leads to more detailed categorisation in flowcharts 1.1 to 6. Applicants are advised to proceed through the entire flow, and identify all relevant changes impacting the medical device and SMDR listing prior to submission. Yes No R4.2 ► Go to Flowchart 2.4 Yes Yes No Is there a change in manufacturing facility, process or quality management system (QMS)? Go to Flowchart 1.1 Go to Flowchart 1.2 Go to Flowchart 2.1 Go to Flowchart 2.2 Go to Flowchart 2.3 Go to Flowchart 3 Go to Flowchart 4 Go to Flowchart 5 Is there a change to listing information of a registered medical device? Go to Flowchart 6 Collate all relevant changes. Assess if changes qualify to be grouped in a single application (ref. GN-21, Section 5) before submitting application(s). Yes Yes Yes Yes Yes Yes Yes No No No No No No No R4.2 ► Is there a change to the software for an in-vitro diagnostic device (IVD)? R4.2 ► Is there a change to the software for a general medical device (GMD)? Is there a change to design or specifications for an in vitro diagnostic device (IVD)? Is there a change in sterilisation facility, process or quality management system (QMS)? Is there a change to design or specifications for a general medical device (GMD)? Is there a change to labelling? Is there a change to materials for an in vitro diagnostic device (IVD)? Is there a change to materials for a general medical device (GMD)? MEDICAL DEVICE GUIDANCE DECEMBER 2017 HEALTH SCIENCES AUTHORITY – HEALTH PRODUCTS REGULATION GROUP Page 14 of 53 Flowchart 1.1: Change to Manufacturing Facility and its Process and/or Quality Management System Is there a change to the manufacturing process that affects the medicinal substances with no change in registered medical device specifications? Example – Change in manufacturing process of drug paclitaxel, with no change in final registered paclitaxel-eluting stent specifications Is there a change in the manufacturing process to Additive Manufacturing (3D- printing), or to refurbish a registered device? Example – Change from milling to selective laser sintering for dental implant. Is there a change to the manufacturing site and/or processes that result in a change in specifications of a registered medical device? Example – Change in bonding process resulting in change in catheter tip diameter specification Is there a change in sterilisation method and related processes? Is there an addition, deletion, or shift of manufacturing facilities with no change to specifications of a registered medical device? Example – Transfer of manufacturing activities from Location A to Location B with no change to manufacturing process Is there an update of QMS certificate for manufacturing facilities that involves only: • Update of QMS validity date; • Change in scope of QMS certification which does not affect the registered medical device; • Change in certification body? No Change Notification Required Kindly contact the Medical Devices Branch for further advice Change Type 1B Class C&D: Technical Class A&B: Notification Change Type 1C Class C&D: Technical Class A&B: Notification Refer to Flowchart 1.2 Change in Sterilisation Facility, and its Process and/or QMS Change Type 1A All risk classes: Notification Change Type 1E All risk classes: Notification Yes No Yes Yes Yes Yes Yes No No No No No MEDICAL DEVICE GUIDANCE DECEMBER 2017 HEALTH SCIENCES AUTHORITY – HEALTH PRODUCTS REGULATION GROUP Page 15 of 53 Flowchart 1.2: Change to Sterilisation Facility and its Process and/or Quality Management System Is there a change in sterilisation method and related processes for a registered medical device? Example – Change in moist heat sterilisation parameters, or change in sterilisation method from ethylene oxide to gamma radiation, or change from batch release to parametric release Is there a change in sterile primary packaging? Example – Removal of tray from sterile packaging, or change from foil laminate to Tyvek pouch Is there an addition, deletion, or shift of sterilisation facilities with no change to sterilisation process? Example – Transfer of sterilisation activities from Location A to Location B with no change to sterilisation process Is there an update of QMS certificate for sterilisation facilities that involves only: • Update of QMS validity date; • Change in scope of QMS certification which does not affect the registered medical device; • Change in certification body? No Change Notification Required Change Type 1D Class C&D: Technical Class A&B: Notification Change Type 2Ai Class C&D: Technical Class A&B: Notification Change Type 1A All risk classes: Notification Change Type 1E All risk classes: Notification Yes Yes Yes Yes No No No No MEDICAL DEVICE GUIDANCE DECEMBER 2017 HEALTH SCIENCES AUTHORITY – HEALTH PRODUCTS REGULATION GROUP Page 16 of 53 Flowchart 2.1: Changes in Design or Specifications of an In-vitro Diagnostic (IVD) Medical Device R4.2 ► Is there a change to the specification of a registered IVD kit/system/ analyser which requires additional pre-clinical OR clinical validation? Example – Change in stability/shelf-life of IVD reagents No No Change Type 2Aiii All risk classes: Notification Example – Changes that improve device design, ergonomics, and/or aesthetic modification of the device. Yes R4.2 ► Is there a change to the control mechanisms, operating principles and/or design characteristics of a registered IVD kit/system/ analyser? Examples – Change from a quantitative assay (measurement of an analyte) to a qualitative assay (detection of an analyte) Change from immunofluorescence to ELISA Yes Is there a change to software of a registered IVD system? No Yes Change Type 2Ai Class C&D: Technical Class A&B: Notification Change Type 2B Class C&D: Technical Class A&B: Notification R4.2 ► Refer to Flowchart 2.4 Changes to Software of Medical Devices (IVD) MEDICAL DEVICE GUIDANCE DECEMBER 2017 HEALTH SCIENCES AUTHORITY – HEALTH PRODUCTS REGULATION GROUP Page 17 of 53 Flowchart 2.2: Change to Design and/or Specifications of General Medical Devices Is there a change to the control mechanisms/ operating principles of a registered medical device? Example - Addition of a footswitch to an X-ray system that previously do not operate via a footswitch mechanism. Change Type 2Ai Class C&D: Technical Class A&B: Notification Yes No No Is there a change to the design characteristics/ specification of the registered medical device, which would require additional pre-clinical studies (e.g. shelf life/stability studies, mechanical testing) or / and clinical data to support the safety and effectiveness of the changed device? Example – Change in the shelf life for surgical sealant from 12 months to 24 months Is there a change to the software of medical device? Change Type 2Aiii All Risk Classes: Notification Example- Change to the grip of a steerable ablation catheter to provide improved ergonomic comfort for the healthcare professional without changing the functionality R4.2 ► Refer to Flowchart 2.3: Change to Software of Medical Devices (GMD) Yes Yes No Change Type 5Ai Class C&D: Technical Class A&B: Review Change Type 2B Class C&D: Technical Class A&B: Notification Is there a change to the design characteristics/ specification of the registered medical device, which expands the approved indication of use? Example – Change in flow rate of a ventilator to allow for use in paediatric population, in addition to adult patients Addition of a transducer in an ultrasound system which expands the indication of use for trans-cardiac purposes Yes No MEDICAL DEVICE GUIDANCE DECEMBER 2017 HEALTH SCIENCES AUTHORITY – HEALTH PRODUCTS REGULATION GROUP Page 18 of 53 R4.2 ► Flowchart 2.3: Change to Software of General Medical Devices (GMD) * Software refers to Standalone software and/or Software embedded in medical device system. Is there a change to software that modifies an algorithm that affect the diagnostic or therapeutic function? Example - An algorithm change to X-ray system with enhanced sensitivity software for image enhancement which improves the detection rate of lesions. Is there a change to software with addition of new features or software applications that affect any diagnostic or therapeutic functions of a medical device? Example - A software change that allows the blood oxygen monitor to also report blood CO2 concentrations. Is there a change to software that includes addition or removal of alarm function, such that a response to this change impacts the treatment of patient? Example - Addition to software of an early warning alarm in electrocardiogram to signal a potential cardiac event such as atrial fibrillation. Is there a change to software that impacts the performance characteristics of the registered medical device such that the treatment or diagnosis of the patient is altered? Example - upgrade of software version changes the performance characteristics like specificity or sensitivity of the diagnostic medical device. Is there a change to software that includes change in the operating system compared to existing software version number registered with the medical device? Example - A change in the operating system from Linux to Windows. Is there a change to software which impacts the control of the device that may alter diagnostic or therapeutic function? Example - Software changes in Insulin pump that enables the insulin dosage to be controlled based on readings from compatible (continuous) blood glucose monitors. Change Type 2Ai Class C&D: Technical Class A&B: Notification Change Type 2Aii All risk classes: Notification Examples - • Software changes solely to correct an inadvertent software error which does not add new functions, does not pose any safety risk and is intended to bring the system to specification. • Software changes to incorporate interfacing to other nonmedical peripherals such as printers etc. and which has no diagnostic or therapeutic function. • Software changes carried out to only modify the appearance of the user interface with no risk to diagnostic or therapeutic function of the device. Yes No No No No No Yes Yes Yes Yes Yes No MEDICAL DEVICE GUIDANCE DECEMBER 2017 HEALTH SCIENCES AUTHORITY – HEALTH PRODUCTS REGULATION GROUP Page 19 of 53 R4.2► Flowchart 2.4: Change to Software of In-vitro Diagnostic Devices (IVD) Does the software change affect the performance characteristics of: IVD analyser and/or Compatible IVD test kits Yes No Change Type 2Aii All risk classes: Notification Submit Change Notification for: IVD analyser listing(s) Submit Change Notification for: IVD analyser listing(s) and any affected IVD test kits listing(s) Change Type 2Ai Class C&D: Technical Class A&B: Notification CN is to be submitted for all affected listings where the performance characteristics are affected MEDICAL DEVICE GUIDANCE DECEMBER 2017 HEALTH SCIENCES AUTHORITY – HEALTH PRODUCTS REGULATION GROUP Page 20 of 53 Flowchart 3: Change to Materials of General Medical Devices Yes Is the change in material for an in vitro (IVD) diagnostic (IVD) device? Is there a change in radiation source (e.g. radioisotopes) or type of medicinal substances in the medical devices that incorporate medicinal substances in an ancillary role? Example- Change in medicinal substance from Tacrolimus to Everolimus in a drug eluting stent Yes Yes No No Refer to Flowchart 4 Change to materials of in vitro diagnostic devices (IVD) Submit new Premarket Application Yes Is there a change in type, source, processing and/or supplier of biological materials (including cells, tissues and/or derivatives of animal, human, microbial or recombinant origin) without a change in the intended purpose of the biological material? Example- Change in source of hyaluronic acid from Streptococcus zooepidemicus to Streptococcus equi Is there a change in material or material formulation (of non-biological origin) including changes to device coating or surface modification techniques that is intended to make direct/indirect contact with body tissues and fluids or is absorbed by the body with no change to the performance specification? Example- Replacement of catheter surface coating from PEBA to PEEK Is there a change to materials that are used for shielding in medical devices emitting ionising radiation? Example- Change in shielding material of X-ray system from lead to tungsten Is there a change to concentration or drug specification of medicinal substances in medical devices that incorporate medicinal substances in an ancillary role? Is there a change in material which results in design and/or specifications change of a registered general medical device? No Change Notification Required Refer to Flowchart 2.2 Change to design and/or specifications of general medical devices Yes No No No No No Change Type 3A Class C&D: Technical Class A&B: Notification Has the material been reviewed in a previous device application, from the same product owner, and does the new material in this device have the same nature of body contact and contact duration as in the previously reviewed device? Change Type 3C Class C&D: Technical Class A&B: Not applicable Change Type 3D Class C&D: Technical Class A&B: Not applicable Yes Change Type 3Bi Class C&D: Technical Class A&B: Notification Change Type 3Bii All Risk Classes: Notification No Yes Yes MEDICAL DEVICE GUIDANCE DECEMBER 2017 HEALTH SCIENCES AUTHORITY – HEALTH PRODUCTS REGULATION GROUP Page 21 of 53 Flowchart 4: Change to Materials of In Vitro Diagnostic Medical Devices Is the change in material for a general medical device? Is there a change in radiation source? Example – Change of radioisotopes in radioimmunoassays Is there a change in material (including chemical and biological substances) which results in a change to the performance specifications of the registered in vitro diagnostic (IVD) medical device? Example – Change in preservatives resulting in revalidation of shelf life/stability Is there change in material which results in design specifications change of the registered in vitro diagnostic (IVD) medical device? Example – Change in material from a polyclonal antibody coated microplate to a monoclonal antibody coated microplate in an immunoassay. No Change Notification Required Refer to Flowchart 3 Change to materials of general medical devices Submit new Premarket Application Change Type 4A Class C&D: Technical Class A&B: Notification Refer to Flowchart 2.1 Change to design and/or specifications of IVD medical devices Yes Yes Yes Yes No No No No MEDICAL DEVICE GUIDANCE DECEMBER 2017 HEALTH SCIENCES AUTHORITY – HEALTH PRODUCTS REGULATION GROUP Page 22 of 53 Flowchart 5: Changes to Labelling All changes to labelling of the medical devices that involve addition, removal and/or revision of the approved indications for use Change Type 5F All Risk Classes: Notification Yes All changes to labelling of the medical devices that involve addition, removal and/or revision of warnings, precautions and/or contraindications Is there a change to the approved method of use which requires preclinical or clinical data to support the changes in demonstrating continual safety and effectiveness of the device? Example- Metallic implant (initially labelled as MR safe) is re-labelled as MR conditional. OR Involves a change from ‘professional use only’ to ‘home use’? Does the change involve only rephrasing of existing information in instructions for use? Example – Change from Avoid exposure to temperature and humidity extremes to keep away from sunlight Does the change involve labelling changes that ONLY: • Involve changes in layout, colour, font sizes and design, without change in prominence of precautions, warning and contraindications? • Involve addition and/or removal of languages not required by the Authority? • Involve the addition of reference agencies’ approvals? • Involve the addition or changes of barcodes without impact to device listing information? • Involve the addition of a Unique Device Identification (UDI) and standardisation of date format to conform to UDI requirements without impact to device listing information? Does the change involve a reduction of indications for use? Does the change involve an addition of contraindications, warnings and/or precautions? Change Type 5C Class C&D: Technical Class A&B: Review Change Type 5D All Risk Classes: Notification Change Type 5E All Risk Classes: Notification Yes No Yes Yes Yes Yes No No No Yes Change Type 5Aii All Risk Classes: Notification Change Type 5Ai Class C&D: Technical Class A&B: Review No Change Type 5Bii All Risk Classes: Notification Change Type 5Bi Class C&D: Technical Class A&B: Review No Yes Other labelling changes No MEDICAL DEVICE GUIDANCE DECEMBER 2017 HEALTH SCIENCES AUTHORITY – HEALTH PRODUCTS REGULATION GROUP Page 23 of 53 Flowchart 6: Changes to Registered Medical Devices Listing Information * This refers to the primary change under this category. For consequential changes to the device listing information, please refer to other flowcharts. Is there an addition of new medical devices to a device listing? Please refer to Flowchart 6A: Addition of new medical devices to a device listing Is there a deletion of models from the device listing? Change Type 6B All Risk Classes: Notification Yes Yes No No Is there ONLY a change to the Product Name; AND/OR Product Identifier of the registered medical device? Change Type 6C All Risk Classes: Administrative Yes No Is there a change in the product owner including changes in product owner Name and Address? Change Type 6D All Risk Classes: Administrative For all other changes limited to listing information, please contact the Medical Devices Branch, Health Sciences Authority for advice. Yes No MEDICAL DEVICE GUIDANCE DECEMBER 2017 HEALTH SCIENCES AUTHORITY – HEALTH PRODUCTS REGULATION GROUP Page 24 of 53 Flowchart 6A: Addition of New Medical Devices to a Device Listing Is there an addition of new device of the same design, which only involves: • New models within the existing range of sizes already registered? • An increase or reduction in the number of identical devices in a pack of a registered device without breach of individual primary packaging? • An increase or reduction of volume that does not affect specifications of device? (e.g. shelf life, stability, performance and sterility) • Addition of models due repackaging of existing models within the same SMDR listing in different combinations without breach of individual primary packaging? Change Type 6Aii All Risk Classes: Notification Yes Yes Is there an addition of new device or software identifier with no change to the performance characteristics or specifications of the device? Examples – • changes that improve device ergonomics, aesthetic modification of the device • Software changes solely to correct an inadvertent software error which does not add new functions, does not pose any safety risk and is intended to bring the system to specification. • Software changes to incorporate interfacing to other nonmedical peripherals such as printers etc. and which has no diagnostic or therapeutic function. • Software changes carried out to only modify the appearance of the user interface with no risk to diagnostic or therapeutic function of the device. Change Type 6Aiii All Risk Classes: Notification No No R4.2 ► Is there an addition of Class A medical device accessories that complement the registered medical device as a system. Example- Addition of tubing connector (Class A) to a ventilator system Yes Change Type 6Aiv All Risk Classes: Notification Change Type 6Ai Class C & D: Technical Class A & B: Review Example- Addition of two new stent lengths, which are not within range of sizes already registered, to the FAMILY of stent. No MEDICAL DEVICE GUIDANCE DECEMBER 2017 HEALTH SCIENCES AUTHORITY – HEALTH PRODUCTS REGULATION GROUP Page 25 of 53 APPLICATION PROCESS FOR CHANGE NOTIFICATION Upon identifying all applicable categories of changes based on the flowcharts in Section 4, the changes may be grouped as per guidelines below, and submitted as a single Change Notification application for the medical device listing(s). NOTE 1. For changes within one dossier and involving listings of a single risk class: Multiple changes (Notification, Administrative, Review and Technical changes) will be considered in one CHANGE NOTIFICATION application if they are submitted together. Fees and assessment done will follow the highest change category in that application. 2. For changes in two or more dossiers involving listings of a single risk class: a) Applicants can submit one CHANGE NOTIFICATION application on MEDICS for (i) identical administrative and notification changes to multiple SMDR listings or (ii) where the same new product is added to multiple SMDR listings, if the changes are submitted together. Non-identical changes in any one listing may result in the entire CHANGE NOTIFICATION application being rejected. b) Applicants can submit one CHANGE NOTIFICATION application for technical changes to the same medical device that is part of multiple device listings (as part of a FAMILY, SYSTEM, GROUP, TEST KIT). Product identifiers listed in each of the SMDR device listings selected must be the same. Example: A change in design (Technical change) to a Calibrator (Product identifier: AB1234) that is listed as part of the following SYSTEMS that have been listed separately on SMDR: SMDR device listing number Name of device listing Models listed on SMDR DE12345 APEX Troponin Test system APEX Troponin test strip (AT987) APEX wash buffer (AT654) APEX calibrator (AB1234) DE98765 APEX CK-MB Test System APEX CK-MB test strip (AC786) APEX wash buffer (AC423) APEX calibrator (AB1234) Change to the APEX calibrator (AB1234) in SMDR listings, DE12345 and DE98765, can be submitted in one CHANGE NOTIFICATION application. c) Non-identical administrative changes and technical changes that do not fall under the categories above: Applicant to submit separate CHANGE NOTIFICATION application for each change on MEDICS. 3. Identical changes involving SMDR listings of different risk classes may be submitted in one CHANGE NOTIFICATION application only for the following categories of change. Change in product owner (6D) Change in manufacture and/or sterilisation site (1A) Change only involves an update of QMS certificate validity date (1E) Addition of identical Class A accessories (6Aiv) MEDICAL DEVICE GUIDANCE DECEMBER 2017 HEALTH SCIENCES AUTHORITY – HEALTH PRODUCTS REGULATION GROUP Page 26 of 53 4. Identical changes arising from open Field Safety Corrective Actions (FSCAs) or reportable Adverse Events (AEs) involving SMDR listings of different risk classes, please seek advice from MDB on applicable requirements prior to the submission of the application on MEDICS. Please note that it is not possible to submit a new Change Notification application if there is a pending Change Notification application for the same product. The registrant has the option of either: a. Withdrawing the pending Change Notification application and submitting a new change notification application, or b. Submitting a new Change Notification application once the pending Change Notification application is completed. Single applications submitted with changes belonging to multiple categories (Notifications, Administrative, Technical and Review changes) shall be classified based on the most stringent category of change in that application, and evaluated accordingly. The fees and Turn-Around-Time (TAT) will follow the most stringent category applicable.
3.1. Requirements for Change Notification
3.1. Requirements for Change Notification Applicant is required to submit the following: a. All supporting documents listed in Annex 1 as applicable for the change types. b. Duly completed Annex 2 to GN-21: Summary Table of Change Notification c. Duly signed Annex 3 to GN-21: Medical Device Safety and Performance Declaration Registrants are reminded that the determination of documents required for Change Notification should be made with reference to all submitted changes, and not solely on one category of change. MEDICAL DEVICE GUIDANCE DECEMBER 2017 HEALTH SCIENCES AUTHORITY – HEALTH PRODUCTS REGULATION GROUP Page 27 of 53 The application process for the assessment of Change Notification application for registered Class A to D medical devices is summarized below: Upon the successful submission of the Change Notification application on MEDICS, no further amendment of the application will be allowed unless otherwise advised by HSA. As application fees and TATs for Change Notification applications are based on a per-application basis, HSA recommends the judicious grouping of different categories of changes that affect each device listing, before submission of each Change Notification. Refer to Section 6 and Section 7 of this guidance document for the TATs and the fees applicable for each Change Notification category. An application for changes categorised as ‘Technical Change’ or ‘Review Change’ will be evaluated. An evaluation decision is made based on the outcome of the Authority’s evaluation of the submitted information. The decision can be one of the following: The Change Notification is approvable – where Authority assessed that the changes made to the registered medical device meet prevailing requirements of safety, quality and efficacy for its intended purpose and may be registered for local supply; or Registrant identifies change that requires CHANGE NOTIFICATION Screening of application Evaluation of application Regulatory Decision Registrant submits Change Notification application Evaluation Decision Verification of documentation Technical/Review change Administrative change/Notification MEDICAL DEVICE GUIDANCE DECEMBER 2017 HEALTH SCIENCES AUTHORITY – HEALTH PRODUCTS REGULATION GROUP Page 28 of 53 The Change Notification is non-approvable – where the response provided by the applicant fails to address the deficiencies highlighted during the input request, or failure to adhere to specified time as stated in input request or provide information requested for within reasonable timeframe, or where changes made to the registered medical device does not meet prevailing requirements of safety, quality or efficacy for its intended purpose.
3.2. Implementation and Supply
3.2. Implementation and Supply Changes to the registered devices may be implemented upon approval of the respective Change Notification applications by the Authority. R4 ► Upon approval of the Change Notification application, companies may concurrently supply both the original registered medical device and the changed medical device (subject of the Change Notification) only if both versions of the medical device conform to the Essential Requirements for Safety and Performance for medical devices as stipulated in the First Schedule of the Health Products (Medical Devices) Regulations. Companies shall ensure that appropriate mechanisms are in place to differentiate and identify the changed device from the original version based on device or manufacturing attributes (e.g. through batch/ lot/ serial number and manufacturing date), and maintain relevant inventory records on file to ensure traceability of both versions as part of their quality management system (QMS) requirements. All relevant records on file shall be made available to the Authority upon request. MEDICAL DEVICE GUIDANCE DECEMBER 2017 HEALTH SCIENCES AUTHORITY – HEALTH PRODUCTS REGULATION GROUP Page 29 of 53 This concurrent supply of the unchanged original device may not be applicable for changes to medical devices implemented as a consequence of reportable AEs or FSCAs. Such changes typically impact the safety, quality and/or efficacy of the medical device and any further supply of the affected and/or corrected stocks shall be solely based on the written advice from HSA to the registrant in the context of the respective AE or FSCA cases. For the concurrent supply of old-label and new-label stock in the context of change(s) in product owner (6E) Change Notifications, companies will additionally be required to inform HSA of the proposed timeline for phasing out of old inventory stock with old product owner contact information from the market at the point of submission of the CN. Company should ensure there is appropriate communication to the affected consignees on any change in the product owner contact information in the interim, for the proposed period of concurrent supply. Concurrent supply for this scenario may be allowed by the Authority for stipulated timeline upon review of the information provided. In the context of change in manufacture and/or sterilisation site (1A) change notifications that is to replace existing sites for the registered device with new sites, companies who require concurrent supply of the devices from the old and new sites will additionally be required to inform HSA of the proposed timeline for phasing out of the manufacturing activity in the old site which should be supported by valid QMS certificate for the old site. Concurrent supply for this scenario may be allowed by the Authority for stipulated timeline upon review of the information provided. MEDICAL DEVICE GUIDANCE DECEMBER 2017 HEALTH SCIENCES AUTHORITY – HEALTH PRODUCTS REGULATION GROUP Page 30 of 53
4. CHANGE NOTIFICATION TURN-AROUND-TIME (TAT)
4. CHANGE NOTIFICATION TURN-AROUND-TIME (TAT) Applicants should ensure that the dossiers are complete before submission. Incomplete submissions and untimely responses to queries will result in unnecessary delays to the review process and inevitably prolong the overall processing timeline. Table 3 - Change Notification TAT for Class A (sterile) listings Risk Classification TAT for Change Notification (in working days) Class A (sterile) 20 Table 4 - Change Notification TAT for Class B, C and D listings Risk Classification TAT for Change Notification (in working days) Review Changes Administrative Changes Technical Changes Class B 45 30 Not applicable Class C Not applicable 30 75 Class D* Not applicable 30 90 *For TATs with regards to changes to the medicinal product in Class D medical devices that incorporate a registrable medicinal product in an ancillary role, please contact HSA. The target TAT for Change Notification applications commences from the date of submission of the application and does not include ‘stop-clock time’ due to input requests for clarifications and additional information. The TATs published in Tables 3 and 4 above shall be applied based on the highest category of change selected for that application (e.g. if a Technical Change MEDICAL DEVICE GUIDANCE DECEMBER 2017 HEALTH SCIENCES AUTHORITY – HEALTH PRODUCTS REGULATION GROUP Page 31 of 53 and an Administrative Change for a Class C medical device listing are submitted in one application, the TATs for a Technical Change for a Class C medical device shall apply). TATs shall apply to each application on a per- application basis.
5. CHANGE NOTIFICATION FEES
5. CHANGE NOTIFICATION FEES The fees applicable for the Change Notification applications are summarized in Table 5 below. Fees chargeable for applications that includes multiple changes will depend upon the highest category of change selected (e.g. if a Technical Change and an Administrative Change for a Class C medical device listing are submitted in one application, the fees for a Technical Change for a Class C medical device shall apply). All fees are non-refundable once the application has been submitted via MEDICS. Withdrawal or rejection of the application will result in forfeiture of the fees charged. Table 5 - Change Notification Fees Risk Class Notification Change Administrative Change Review Change Technical Change Class A (Sterile) Not applicable $25 $25 Not applicable Class B $500 $500 Class C $500 Not applicable $1700 Class D (including devices incorporating medicinal products in an ancillary role) $500 $2800 MEDICAL DEVICE GUIDANCE DECEMBER 2017 HEALTH SCIENCES AUTHORITY – HEALTH PRODUCTS REGULATION GROUP Page 32 of 53
Annex 1 — Change Notification Submission Requirements
ANNEX 1 to GN-21: Change Notification Submission Requirements This is provided to assist the registrant in determining the required documents for types of changes proposed. NOTE: All the required documents must be submitted for the relevant sections of the CSDT to support the proposed changes to the device. The documentary requirements are meant to cover the broadest aspect for each category of change. If any required documents as defined in the respective category in this checklist are not available or applicable for the change proposed, please provide a clarification or justification as appropriate. Please also refer to GN-15 for the relevant templates/documents which may be required for the registered devices. Mandatory documents to be submitted for all Change Notification application: Completed Annex 2 to GN-21: Summary Table of Change Notification; Completed Annex 3 to GN-21: Medical Device Safety and Performance Declaration. Additional documentary requirements for Class B, C and D devices are listed below. Additional documentary requirements for Class A devices are separately listed in the last section of Annex 1. Documentary Requirements: 1. Change in Manufacturing Facility, Process and Quality Management System (QMS) 1A* 1B 1C 1D 1E B-D: Notification B: Notification C and above: Technical B: Notification C and above: Technical B: Notification C and above: Technical B-D: Notification All changes to manufacturing and/or sterilisation facilities with no changes to the specifications of a registered medical device and/or sterilisation process All changes in manufacturing process to Additive Manufacturing, or to refurbish a registered device All changes to manufacturing site and/or processes that result in a change in specifications of a registered medical device All changes to sterilization method and related processes of a registered medical device All changes to Quality Management System (QMS) certificates for manufacturing and sterilization facilities Quality Management System certificate(s) If applicable If applicable MEDICAL DEVICE GUIDANCE DECEMBER 2017 HEALTH SCIENCES AUTHORITY – HEALTH PRODUCTS REGULATION GROUP Page 33 of 53 - Continued - 1. Change in Manufacturing Facility, Process and Quality Management System (QMS) 1A* 1B 1C 1D 1E B-D: Notification B: Notification C and above: Technical B: Notification C and above: Technical B: Notification C and above: Technical B-D: Notification Device labelling with changes are highlighted/identified If applicable If applicable If applicable Declaration letter from product owner on company letterhead confirming no change to existing device specifications and/or sterilization process Sterilization validation report (including sterlisation protocol, sterilisation standards applied. Sterility Assurance Level, Sterilsation revalidation report) If applicable Post sterilisation functional test report Summary of new manufacturing process Device validation studies Risk Analysis (If applicable) * For changes in manufacturing/ sterilization site of medical devices containing medicinal products in an ancillary role, please contact the Medical Devices Branch, Health Sciences Authority for further advice. MEDICAL DEVICE GUIDANCE DECEMBER 2017 HEALTH SCIENCES AUTHORITY – HEALTH PRODUCTS REGULATION GROUP Page 34 of 53 Documentary Requirements: 2. Changes in Design or Specifications of a registered medical device (GMD and IVD) 2Ai 2Aii 2Aiii 2B B: Notification C and above: Technical B-D: Notification B-D: Notification B: Notification C and above: Technical Changes to the control mechanisms, operating principles, sterile primary packaging and/or design characteristics of a registered medical device. Unless the change only involves a change to the software version number such as: • Software changes solely to correct an inadvertent software error which does not add new functions, does not pose any safety risk and is intended to bring the system to specification; • Software changes which augment interfacing to other nonmedical peripherals such as printers or VDUs and which has no diagnostic or therapeutic function; • Software changes which only modifies the appearance of the user interface with no risk to diagnostic or therapeutic function of the device. Unless the change only involves a design change that does not affect performance characteristics and/or specifications of the medical device (e.g. changes that improve device ergonomics, aesthetic modification of the device) All changes in specifications of a registered medical devices (including shelf life, stability, expiry date) Pre-clinical studies * Refer to Documentation Guidelines for Software Changes table below Risk Analysis Clinical studies (If applicable) Device labelling with changes MEDICAL DEVICE GUIDANCE DECEMBER 2017 HEALTH SCIENCES AUTHORITY – HEALTH PRODUCTS REGULATION GROUP Page 35 of 53 Documentation Guidelines for Software Changes FSCA related software change Non- FSCA related software change Technical/ Review/ Notification change Evidence to demonstrate that the software issue has been resolved. Example- Test cases verification Remaining software anomalies (bugs or defects) including those that affect the functionality of the device should be assessed. Company has to provide justification/explanation why the software with the remaining anomalies is still deemed acceptable for release. Technical/ Review change Evidence that the Software changes have been validated. Software version number validated is the same software version to be supplied after the changes. Example- Validation report for changes Remaining software anomalies (bugs or defects) including those that affect the functionality of the device should be assessed. Company has to provide justification/explanation why the software with the remaining anomalies is still deemed acceptable for release. Notification change Detailed summary of software changes (can be included in the Annex 2, Summary Table of change). To include information on the incremental changes or revisions to the software from the registered software version. Note- for In vitro diagnostic (IVD) devices, performance validation of the IVD analyzer & assay conducted using software is acceptable in lieu of the software validation report. MEDICAL DEVICE GUIDANCE DECEMBER 2017 HEALTH SCIENCES AUTHORITY – HEALTH PRODUCTS REGULATION GROUP Page 36 of 53 Documentary Requirements: 3. Changes in Materials in a General Medical Device 3A 3Bi 3Bii 3C 3D B - Notification C and above - Technical B - Notification C and above - Technical B-D: Notification B - NA C and above - Technical B - NA C and above - Technical All changes in type, source, processing and/or supplier of biological materials (including cells, tissues and/or derivatives of animal, human, microbial or recombinant origin) without a change in the intended purpose of the biological material. All changes in material or material formulation (of non-biological origin) including changes to device coating or surface modification techniques that is intended to make direct/indirect contact with body tissues and fluids or is absorbed by the body, with no change in device performance specifications. Unless the material has been reviewed in a previous device application and the new material has the same nature of body contact and contact duration. All changes to materials that are used for shielding in medical devices emitting ionising radiation. All changes to concentration or drug specification of medicinal substances in medical devices that incorporate medicinal substances in an ancillary role. Preclinical Studies (e.g. biocompatibility) (e.g. biocompatibility, mechanical) (e.g. biocompatibility, mechanical testing, sterilization validation) (e.g. radiation safety validation report summary) Contact the Medical Devices Branch for further advice. Clinical Studies (If applicable) Biological Safety Data (e.g. viral validation report) Information of Sources/Donors List of material(s) making direct/ indirect contact with human body MEDICAL DEVICE GUIDANCE DECEMBER 2017 HEALTH SCIENCES AUTHORITY – HEALTH PRODUCTS REGULATION GROUP Page 37 of 53 - Continued - 3. Changes in Materials in a General Medical Device 3A 3Bi 3Bii 3C 3D B - Notification C and above - Technical B - Notification C and above - Technical B-D: Notification B - NA C and above - Technical B - NA C and above - Technical Information on radiation source Contact the Medical Devices Branch for further advice. Information on materials for shielding of radiation Justification for choice of identified referenced device (provide device registration & model number), with consideration to the device intended use, indications of use, nature of body contact and contact duration. MEDICAL DEVICE GUIDANCE DECEMBER 2017 HEALTH SCIENCES AUTHORITY – HEALTH PRODUCTS REGULATION GROUP Page 38 of 53 Documentary Requirements: 4. Change to Materials of In Vitro Diagnostic Medical Devices 4 A Class B: Notification Class C & D: Technical All changes in material (including chemical and biological substances) which results in a change to the performance specifications of the registered in vitro diagnostic (IVD) medical device Pre-clinical performance evaluation data Example – Shelf life studies, specificity and sensitivity studies Clinical performance evaluation data Information on source of material Example – Certificate of Analysis (COA), Certificate of Compliance (COC) All changes to the radiation source require a new premarket submission. Example – Radioisotopes in radioimmunoassays MEDICAL DEVICE GUIDANCE DECEMBER 2017 HEALTH SCIENCES AUTHORITY – HEALTH PRODUCTS REGULATION GROUP Page 39 of 53 Documentary Requirements: 5. Changes to Labelling 5Ai 5Aii 5Bi 5Bii 5C 5D 5E 5F B: Review C & above: Technical B-D: Notification B: Review C & above: Technical B-D: Notification B: Review C & above: Technical B-D: Notification B-D: Notification B-D: Notification All changes to the labelling of medical devices that involve addition and/or revision of the approved indications for use Unless the change only involves a reduction of indications for use All changes to labelling of the medical devices that involve removal and/or revision of warnings, precautions and/or contraindications Unless the change involve an addition of contraindicat ions, warnings and/or precautions Labelling changes that modify the approved method of use OR Involves a change from ‘professional use only’ to ‘home use’ Change involves only rephrasing of existing information in instructions for use Labelling changes that involve: Changes in layout, colour, font sizes and design, without change in prominence of precautions, warning and contraindications Addition and/ or removal of languages not required by the Authority Addition of reference agencies’ approvals (e.g. CE marking) Addition or change in barcodes without impact to device listing information Addition of a Unique Device Identification (UDI) and standardisation of date format to conform to UDI requirements without impact to device listing information Other labelling Changes Regulatory approval documents from reference agencies for the change MEDICAL DEVICE GUIDANCE DECEMBER 2017 HEALTH SCIENCES AUTHORITY – HEALTH PRODUCTS REGULATION GROUP Page 40 of 53 - Continued - 5. Changes to Labelling 5Ai 5Aii 5Bi 5Bii 5C 5D 5E 5F B: Review C & above: Technical B-D: Notification B : Review C and above: Technical B-D: Notification B : Review C and above : Technical B-D: Notification B-D: Notification B-D: Notification Device information Device labelling with changes highlighted Declaration of conformity document Pre-clinical studies Clinical studies Risk Analysis Software validation report (For software only) Other relevant documents supporting proposed changes submitted (If applicable) MEDICAL DEVICE GUIDANCE DECEMBER 2017 HEALTH SCIENCES AUTHORITY – HEALTH PRODUCTS REGULATION GROUP Page 41 of 53 Documentary Requirements: 6. Changes to registered medical devices listing information 6Ai 6Aii/ 6Aiii 6Aiv 6B 6C 6D B: Review C & above: Technical B-D: Notification B-D: Notification B-D: Notification B-D: Administrative B-D: Administrative B-D: Administrative Addition of new medical devices to a device listing 6Aii Unless the change involves the addition of the same design, that only involves: New models within the existing range of sizes already registered; An increase or reduction in the number of identical devices in a pack of a registered device without breach of individual primary packaging; An increase or reduction of volume that does not affect specifications of device (e.g. shelf life, stability, performance and sterility); Addition of models due repackaging of existing models within the same SMDR listing in different combinations without breach of individual primary packaging. 6Aiii Unless change involves the addition of a new device or software identifier with no change to the performance characteristics or specifications of the device Unless the change involves the addition of Class A medical device accessories that complement the registered medical device as a closed system All deletions of models from device listing All changes to Product Name and/or identifier All changes in the product owner A change in product owner address Annex 2 - List of Configurations with the new models highlighted MEDICAL DEVICE GUIDANCE DECEMBER 2017 HEALTH SCIENCES AUTHORITY – HEALTH PRODUCTS REGULATION GROUP Page 42 of 53 - Continued - 6. Changes to registered medical devices listing information 6Ai 6Aii/ 6Aiii 6Aiv 6B 6C 6D B: Review C & above: Technical B-D: Notification B-D: Notification B-D: Notification B-D: Administrative B-D: Administrative B-D: Administrative Device description, including justification, for deletion/ addition of device models to be grouped within the registered listing Device labelling With changes highlighted/ identified beside each amended section With changes highlighted / identified beside each amended section With changes highlighted/ identified beside each amended section With changes highlighted/ identified beside each amended section With changes highlighted/ identified beside each amended section Declaration of conformity document Letter of Authorisation (GN-15) For sterile Class A Pre-clinical studies If applicable If applicable Clinical studies (If applicable) Risk analysis (If applicable) Software report (If applicable) * Refer to Documentation Guidelines for Software Changes table above MEDICAL DEVICE GUIDANCE DECEMBER 2017 HEALTH SCIENCES AUTHORITY – HEALTH PRODUCTS REGULATION GROUP Page 43 of 53 - Continued - 6. Changes to registered medical devices listing information 6Ai 6Aii/ 6Aiii 6Aiv 6B 6C 6D B: Review C & above: Technical B-D: Notification B-D: Notification B-D: Notification B-D: Administrative B-D: Administrative B-D: Administrative Manufacturing information Declaration Letter On Registrant’s letterhead to state (1) The added models are class A non-sterile (2) The added device name and identifier of the class A non-sterile device (3) The name of product owner (4) Name and address for the manufacturing site(s) of the class A non- sterile device From product owner on company letterhead to state that there is no change to device in all aspects, including intended use, technical specifications. From product owner on company letterhead, to state that they will undertake responsibility to provide post market support and assistance related to the medical devices <state device name> already supplied under the former product owner’s name (if applicable) Quality management system certificate Regulatory approval documents from reference agencies. MEDICAL DEVICE GUIDANCE DECEMBER 2017 HEALTH SCIENCES AUTHORITY – HEALTH PRODUCTS REGULATION GROUP Page 44 of 53 Documentation guidelines for Class A device changes Where relevant, the following documents are to be submitted in support of proposed changes. Document Requirements Class A (sterile) IVD Class A (sterile) Class A (non-sterile) Letter of Authorisation R4.1► Change to Product Name and/or Identifier: Declaration from product owner, on company letterhead, to state that there is no change to device in all aspects, including intended use, technical specifications R4.1► Change to product owner: Declaration from product owner on company letterhead, to state that they will undertake responsibility to provide post market support and assistance related to the medical devices <state device name> already supplied under the former product owner’s name (if applicable) On Registrant’s letterhead to state (1) The models are class A non-sterile (2) The device name and identifier of the class A non-sterile device (3) The name of product owner (4) Name and address for the manufacturing site(s) of the class A non-sterile device R4.2►Evidence that proposed additional models qualify to be grouped within the registered listing. e.g. IFU, patient information leaflet and promotional material (including brochures and catalogues) MEDICAL DEVICE GUIDANCE DECEMBER 2017 HEALTH SCIENCES AUTHORITY – HEALTH PRODUCTS REGULATION GROUP Page 45 of 53 Document Requirements - Continued - Class A (sterile) IVD Class A (sterile) Class A (non-sterile) A list of all materials of animal, human, microbial and/or recombinant origin used and manufacturing process if applicable Sources of all materials of animal, human, microbial and/or recombinant origin used and manufacturing process if applicable Information on sterilisation method(s) and validation standard(s) used Software validation report If applicable Proof of Quality Management System (QMS) – E.g. ISO 13485 certificate, conformity to US FDA Quality System Regulations, Japan MHLW Ordinance 169 or attestation stating adequate QMS MEDICAL DEVICE GUIDANCE DECEMBER 2017 HEALTH SCIENCES AUTHORITY – HEALTH PRODUCTS REGULATION GROUP Page 46 of 53
Annex 2 — Summary Table of Change Notification
ANNEX 2 to GN-21: Summary Table of Change Notification Guidelines on completing the Summary Table of Change Notification This summary table is to be completed and submitted for all Change Notification applications (Technical Changes, Review Changes, Administrative Changes, and Notifications). List the proposed changes, according to the “Category of change” categories in GN-21, to the registered medical device(s) in the summary table below. All applicable types of changes are to be included; any change not specified in this table will not be included for the change notification application. Information to be included in the table is explained below: (i) Type of changes: Please state clearly the type of change, category of change and SMDR device listing number. - With reference to the ‘type of changes’ categories in GN-21, highlight the type of change proposed. - Specify the SMDR device listing number for the registered medical device(s) included in this change (if the proposed change is identical and applicable to identical devices across multiple device listings on the SMDR; list the applicable device listings). Confirm these device(s) subjected to the change. NOTE All applicable types of changes are to be included. If the types of change proposed affects/results in another type of change, all types of changes shall be included. For example, change in material of device and change (update) of labelling often occur together. (ii) Present: Please state clearly the current scope and aspects of the device to be changed. (iii) Proposed: Please state clearly the proposed scope and aspects of change. (iv) Reason for change: Please state clearly the rationale for the proposed scope and aspects of change. (v) Status of proposed change in reference agencies: Please state the reference agency status (approved/authorised for marketing) for these proposed changes. (vi) Indicate in the check box if the medical device(s) in this Change Notification application is a subject of an on-going field safety corrective action. MEDICAL DEVICE GUIDANCE DECEMBER 2017 HEALTH SCIENCES AUTHORITY – HEALTH PRODUCTS REGULATION GROUP Page 47 of 53 Please select the correct box. The change(s) in this Change Notification application is/are related to field safety corrective action and/or reportable adverse events. Yes No Type of Changes Present Proposed Reason for change # Status of proposed change in reference agencies* Justification for not submitting documents as specified in Annex 1 to GN-21: Change Notification Checklist Type of change: e.g. Change in material: Delivery tube material changed from polyvinyl chloride (PVC) to silicone Category: Notification SMDR Device listing no(s): (same tubing is in all the SMDR Device listing below) (i) DE 001111, (ii) DE 002222, (iii) DE 003333, (iv) DE 004444. Delivery tube material: polyvinyl chloride (PVC) Delivery tube material silicone Improve patient safety by changing to DEHP- free tubing material Australia TGA – pending EU Notified Body – approved/authoris ed for marketing Health Canada – not supplied US FDA – not supplied Japan MHLW – not supplied MEDICAL DEVICE GUIDANCE DECEMBER 2017 HEALTH SCIENCES AUTHORITY – HEALTH PRODUCTS REGULATION GROUP Page 48 of 53 Type of Changes Present Proposed Reason for change # Status of proposed change in reference agencies* Justification for not submitting documents as specified in Annex 1 to GN-21: Change Notification Checklist Type of change: e.g. Change in Manufacturing Facility Category: SMDR Device listing no(s): DE 005555 Name and address of current manufacturing facility A Name and address of new manufacturing facility B Reason for product owner’s decision to move manufacturing activities from facility A to facility B Australia TGA – pending EU Notified Body – approved/authoris ed for marketing Health Canada – not supplied US FDA – not supplied Japan MHLW – not supplied * Applicable for changes to add new models, and revision to indications of use only # Indicate the HSA FSCA Reference no. (e.g. HSA 600:41/01-000/15/01) for changes related to reportable FSCA/ local AE, if applicable. MEDICAL DEVICE GUIDANCE _______ DECEMBER 2017 ___________________________________________________________________________________________ HEALTH SCIENCES AUTHORITY – HEALTH PRODUCTS REGULATION GROUP Page 49 of 51
Annex 3 — Medical Device Safety and Performance Declaration
ANNEX 3 TO GN-21: Medical Device Safety and Performance Declaration Template Safety and Performance Declaration Template [To be printed on Company Letterhead of Registrant] Medical Devices Branch Pre-Marketing Division Health Products Regulation Group Health Sciences Authority [Date] Dear Sir/Madam, [Name of Company], the Registrant of the medical device(s) stated below, hereby declare that the medical device(s) in this Change Notification application, The change(s) to the medical device in this Change Notification application is/are not due to field safety corrective action(s) and/or local reportable adverse events Medical device(s) in this Change Notification application conform(s) to the Essential Requirements for Safety and Performance as laid out in the Health Products (Medical Devices) Regulations The added model(s) is/are not a subject of an open reportable adverse event and/or an on-going field safety corrective action, and does not contain corrections that are the subject of an ongoing field safety corrective action and/or local adverse event. (If applicable) This declaration shall apply to the following medical device(s): [List containing product names of medical devices] I, the Registrant, am aware that a false declaration is an offence under the Health Products Act (Cap. 122D) and may result in the cancellation of registration of the above medical devices under Section 37(1) of the Act. Yours Sincerely, [Signature] [Full Name and Title of Senior Company Official] [Company stamp] MEDICAL DEVICE GUIDANCE _______ DECEMBER 2017 HEALTH SCIENCES AUTHORITY – HEALTH PRODUCTS REGULATION GROUP Page 50 of 53
Annex 4 — Change Types Submission Reference List
ANNEX 4 to GN-21: Change Types Submission Reference List This annex lists the change types available for submission of Change Notification applications. Refer to flowcharts under section 4 of this Guidance, for guiding principles in identifying the type and category of Change Notification applicable for each proposed type of change to the registered medical device. 1. Change in Manufacturing Facility, Process and Quality Management System 1A Addition, deletion, or shift of manufacturing and/or sterilisation facilities with no change to specifications of a registered medical device and/or sterilisation process 1B Changes in the manufacturing process to Additive Manufacturing (3D-printing), or to refurbish a registered device 1C Changes to manufacturing site and/or processes that result in a change in specifications of a registered medical device 1D Changes to sterilisation method and related processes 1E Changes to Quality Management System (QMS) certificates for manufacturing and sterilisation facilities - an update of QMS certificate validity date - a change of QMS certificate scope for one of the multiple existing manufacturing facilities (that is not due to safety, quality and/or efficacy of the device) - change only involves a change in certification body with no change in scope of the certification 2. Changes in Design or Specifications of a registered medical device 2Ai All changes to the control mechanisms, operating principles, sterile primary packaging and/or design characteristics of a registered medical device 2Aii - Unless the change only involves minor software changes, such as: Software changes solely to correct an inadvertent software error which does not add new functions, does not pose any safety risk and is intended to bring the system to specification Software changes which augment interfacing to other non-medical peripherals such as printers or VDUs and which has no diagnostic or therapeutic function Software changes which only modifies the appearance of the user interface with no risk to diagnostic or therapeutic function of the device 2Aiii - Unless the change only involves a design change that does not affect performance characteristics and/or specifications of the medical device (e.g. changes that improve device ergonomics, aesthetic modification of the device, etc.) 2B All changes in specifications of a registered medical device 2C Changes to the IVD analyser that does not impact the performance specifications of the test kits MEDICAL DEVICE GUIDANCE _______ DECEMBER 2017 HEALTH SCIENCES AUTHORITY – HEALTH PRODUCTS REGULATION GROUP Page 51 of 53 3. Changes to materials in a General Medical Device 3A All changes in type, source, processing and/or supplier of biological materials (including cells, tissues and/or derivatives of animal, human, microbial or recombinant origin) without a change in the intended purpose of the biological material 3Bi All changes to materials or material formulation (of non-biological origin), including changes to device coating or surface modification techniques, that involve materials that make direct/indirect contact with body tissues and fluids, or are absorbed by the body, with no change in device performance specifications 3Bii - Unless the material has been reviewed in a previous device application and the new material has the same nature of body contact and contact duration 3C All changes to materials that are used for shielding in medical devices emitting ionising radiation 3D All changes to concentration or drug specifications of medicinal substances in medical devices that incorporate medicinal substances in an ancillary role 4. Changes to materials in an In-Vitro Diagnostic (IVD) Medical Device 4A All changes in material (including chemical and biological substances) which results in a change to the performance specifications of the registered in vitro diagnostic (IVD) medical device 5. Changes to labelling of medical device 5Ai All changes to the labelling of medical devices that involve addition and/or revision of the approved indications for use 5Aii Changes only involves a reduction of indications for use 5Bi All changes to the labelling of medical devices that involves removal and/or revision of warnings, precautions and/or contraindications 5Bii Changes only involves addition of contraindications, warnings and/or precautions 5C Labelling changes that modify the approved method of use OR involves a change from 'professional use only' to 'home use' 5D Labelling changes that involves rephrasing of existing information in instructions for use 5E Labelling changes that involve: Changes in layout, colour, font sizes and design without change in prominence of precautions, warnings and contraindications Addition and/or removal of languages not required by the Authority Addition of reference agencies’ approvals (e.g. CE marking) Addition or change in barcodes without impact to device listing information Addition of a Unique Device Identification (UDI) and standardisation of date format to conform to UDI requirements without impact to device listing information 5F Other labelling changes MEDICAL DEVICE GUIDANCE _______ DECEMBER 2017 HEALTH SCIENCES AUTHORITY – HEALTH PRODUCTS REGULATION GROUP Page 52 of 53 6. Changes to registered medical devices listing information 6Ai Addition of new medical devices to a device listing 6Aii - Unless change only involves the addition of new devices of the same design, that only involves: New models within the existing range of sizes already registered An increase or reduction in the number of identical devices in a pack of a registered device without breach of individual primary packaging An increase or reduction of volume that does not affect specifications of device (e.g. shelf life, stability, performance and sterility). Addition of models due to repackaging of existing models within the same SMDR listing in different combinations without breach of individual primary packaging 6Aiii - Unless change involves an addition of new device or software identifier with no change to the performance characteristics or specifications of the device 6Aiv - Unless changes only involves the addition of Class A medical device accessories that complement the registered medical device as a closed system 6B All deletion of models from device listing 6C All changes to product name AND/OR product identifier 6D All changes to product owner, including changes to product owner name and address Contact Officers: Medical Devices Branch Pre-marketing Cluster Health Products Regulation Group Health Sciences Authority 11 Biopolis Way, #11-03 Helios Singapore 138667 www.hsa.gov.sg Email: hsa_md_info@hsa.gov.sg