GRF-25-08 Rev. 16.1Page 1 of 51

Medical Devices – Substantial Change Review Form

Applicant Information and Instructions

Significant/ Substantial Change Notification Covering Product Family-

MDD 252. NSAI Use Only – Amendment Number-/

AIMD 253. NSAI Use Only – Amendment Number-/

TSE Human Blood Medicinal Substances

P/O number:

This is a:

Regular/ Standard Review Fast Track (expedited)

Modular submission (prior agreement only)

If OBLs apply to this product, please state the relevant product families below:

/; /; /

DECLARATION(s) BY APPLICANT

In signing this form, the manufacturer is verifying that the requirements of the Directive will be applied in full when the change has been implemented.

Signed on behalf of the Manufacturer: / Date:
Name (please print):
Position / Title:
Contact person (if different to Manufacturer):
e-mail: / Phone:

INSTRUCTIONS

  1. Please complete all relevant sections of the form (excluding the NSAI Review sections).
  1. Please enter as much information onto the form as possible - avoid entering “see Technical File/Design Dossier”. If the data is in supporting documentation, please ensure that there is a clear reference to the exact location of this information.
  1. Please submit an unsigned version of this Application in Word as well as a signed copy - either scanned/secured (pdf) copy.
  1. All application forms and supporting data to be forwarded in soft copy via one of the following (Hard copies not required)
  2. NSAI upload facility : see
  3. CD or Memory stick to the appropriate address

Europe / N. America
NSAI
1 Swift Square,
Northwood,
Santry, Dublin 9
Ireland
Phone : (01) 807 3929
Fax : (01) 807 3996
/ NSAI Inc.
402 Amherst Street
Nashua
NH 03063
USA
Phone : (603) 882 4412
Fax : (603) 882 1985

  1. Supporting documents should be in SEARCHABLE format
  1. Applications and supporting documentation must be in English
  1. Please send a representative sample of the device(s). This is particularly important for new/novel devices. Any video of procedures/simulated use would also be helpful, if available.

APPLICANTS’ SUBMISSION CHECKLIST

Completed application form (Word format, .doc or .docx)

Application (min. Signed Declaration page(s)) scanned

Sample of device(s)

QMS certificates for any sites in Table 1 NOT registered with NSAI

Type Examination Certificate if required

Declaration of Conformity

Labelling & IFU

Essential Requirements Checklist

Performance/Complaint Analysis

Risk Management documentation

Sterilisation Validation(s) – if sterile/intended to be sterilised

Stability data – if necessary

Biocompatibility data – if necessary

Electrical Safety Testing data – if necessary

Software/firmware lifecycle documents – if necessary

Bench Testing data – if necessary

Clinical investigation(s) report(s) and supporting documents per MEDDEV 2.7.1.

NSAI Equivalence table RF-25-28 if using equivalent route

NSAI Post Market Surveillance (PMS) and Post Market Clinical Follow Up (PMCF) RF-25-27

Note – NSAI do not accept “For Information Only Data” (FIO); all attributes tested shall have clinically relevant specifications

For Transfers

Copy of existing Notified Body Certificate(s)

(If not already supplied)

Transition Plan

Contact details for existing Notified Body

(NSAI will not contact the existing Notified Body prior to agreement with the Manufacturer)

For Own Brand Labeller (OBL)

Copy of the OEM (maker’s) CE Certificate and last assessment reports from their Notified Body

Copy of the OEM’s Declaration of Conformity

Traceability between OEM cert & devices covered in this application

Copy of the contract between OBL & OEM outlining responsibilities

Index for Technical documentation/Design dossier (version/date), listing supporting documents

Copy of the OEM’s Instructions for Use/Labelling

For Tissue of Animal Origin falling under Commission Regulation 722/2012

Please complete Section 16.1

For Human Blood Derivatives

Please complete Section 16.2

For Medicinal Substances.

Please complete Section 16.3

Table of Contents:

Applicant Information and Instructions

DECLARATION(s) BY APPLICANT

INSTRUCTIONS

APPLICANTS’ SUBMISSION CHECKLIST

Section 1 – Manufacturer and Product Details

Section 2 – Nature of Change

Section 3 – Intended Use of the Device

Section 4 – Correct Classification and Appropriate Annex

Section 5 – Existing Legislation

Section 6 – Labelling and IFU

Section 7 – Solutions to Essential Requirements and Harmonised Standards

Section 8 – Performance/ Complaint Analysis

Section 9 – Risk Management

Section 10 – Sterilisation

10.1 – Sterilisation Validation

10.2 – Maintenance of Sterility over shelf life

Section 11 –Biocompatibility

Section 12 –Medical Electrical Equipment and Systems

Section 13 – Device Testing

13.1 – Device Design Testing

13.2 - Device Stability

Section 14 - Clinical Testing (Animal Model)

14.1 In Vivo Clinical Performance

14.2 In Vivo Device Performance

Section 15 – Clinical Performance (Human)

15.1 Clinical Evaluation

Section 16.0-Appendices

16.1 – Regulation 722/2012 : TSE

16.2 – Human Blood Derivative(s)

16.3 – Devices incorporating Medicinal Substances

Section 17 – Design Dossier

Section 18 – Critical Process Changes

Section 19 - NSAI Queries

19.1 Queries, Responses and Dispositions.

19.2 Query Status Table 14:

Section 20 - Conclusion of Assessment

Approval

Section 1 – Manufacturer and Product Details

Table 1 – Manufacturers Information & Summary Product data

(Legal) Manufacturer’s Name
(Legal) Manufacturer’s Address
Design Site(s):
Manufacturing Site(s):
(i.e. sites of actual manufacture)
Assembly Site(s) if applic.:
Sterilisation Site(s) if applic.:
Scope of Site(s):
(i.e. as shown on the QMS cert)
Name and address of EU Authorised Representative
(if applicable)
Product/Product Family Name:
(In compliance with NB/MED/2.5.1/REC4 & NBOG’S Best Practice Guide 2006-2)
GMDN Reference Number: / See
Declaration of Conformity included - Location within submission :
MDD ONLY :
Class / III IIb IIa Is Im / Rule(s)
Rationale
Conformity Assessment / Annex II / V (+VII) / V + III / VI
Full QA / Prodn QA / + Type Testing / Product QA
AIMD ONLY :
Conformity Assessment / Annex 2 / Annex 3 + 5
Full QA / Production QA + Type Testing
ALL DEVICES :
Clinical Strategy-
- Clinical data from: / Clinical Investigation
Literature (Equivalence)
Combination
Date of this application (i.e. date of Declaration of Applicant)

NSAI REVIEW

NSAI registration(s) if new site(s) -

If Annex II is “Design” included in scope Yes No

Scope of registration(s) adequate to cover the product family

Client QMS Certificates are valid and scope of registration(s) remains adequate for product family under review

Product family name in line with GMDN & remains valid

DoC reviewed - lists model numbers

Type Testing Certificate required – No Yes

if YES – Supplied, Valid

NSAI REVIEW

Technical Reviewer Date:

COMMENTS:

Clinical Reviewer (if applicable) Date:

COMMENTS:

Additional Reviewer (if applicable) Date:

COMMENTS:

QUERIES No YesNumber(s)

Section 2 – Nature of Change

  1. Device Description:
  1. Please provide a clear, detailed description of the change(s):
  1. Did the change(s) arise from a vigilance or performance issue

Yes No

If “Yes” – please advise -

If”No” what was the rationale/motivation for each change(s) made:

  1. Does the change involve an addition to the members of the product family Yes No

If “Yes” – please complete Table 2 below:

Table 2 – New Model/Catalogue Numbers

Sub-Family / NEW Model/Catalogue Number(s) / Description / Class
  1. Please advise what models are affected by the change

Table 3 – Affected Model/Catalogue Number

Sub-Family / AFFECTED Model/Catalogue Number(s) / Description / Class
  1. Impact of change

Table 4-Impact of Change

Impact / Yes / No
  1. Is there a change to the solutions (documented evidence ) to the ERs?

  1. Is there a change to the Harmonised Standards?

  1. Does the change introduce new hazards which have not been previously addressed?

  1. Does the change adversely affect the risk profile associated with the existing hazards?

  1. Does the change alter the details on intended use and /or compliance with the essential requirements given in the design/type approval dossier?

  1. Does the change mean that the device will have different end users or be used in a different manner?

  1. Does the change mean that the clinical data /performance evaluation data for the original device is not sufficient to confirm conformity of the changed device with the required characteristics and performance?

NSAI REVIEW

Change adequately described

Modifications/changes considered vs. approved product family

Validity of reason(s) for change

NSAI REVIEW

Technical Reviewer Date:

COMMENTS:

Clinical Reviewer (if applicable) Date:

COMMENTS:

Additional Reviewer (if applicable) Date:

COMMENTS:

QUERIES No YesNumber(s)

Section 3 – Intended Use of the Device

  1. Please state the current Intended Use –
  1. For class III and Class IIb implantables ONLY,

Please outline the “Indications for use” (i.e. specific patient population intended for this device/family).

  1. Is there a change in Intended Use Yes No
  1. Is there a change in Indications for Use Yes No

NSAI REVIEW

Agreed that this section is not required Yes No

Reviewer Date:

Comments:

  1. Please enter a full description of the revised intended use and/ or indications for use of the device-
  1. Does this change impact the classification/rule Yes No

If “No” please justify -

NSAI REVIEW

Revised Intended Use clearly stated

Revised Intended Use in line with labelling

Impact of Revised Intended Use assessed – including classification/rule

NSAI REVIEW

Technical Reviewer Date:

COMMENTS:

Clinical Reviewer (if applicable) Date:

COMMENTS:

Additional Reviewer (if applicable) Date:

COMMENTS:

QUERIES No Yes Number(s)

Section 4 – Correct Classification and Appropriate Annex

  1. Please state the current MDD Classification- Rule:
  2. Is there a change in Classification Yes No

NSAI REVIEW

Agreed that this section is not required Yes No

Reviewer: Date:

Comments:

  1. MDD Only – Please enter the revised Classification of the device based on the change, along with the Rule & Rationale for the choice

Class

Rule

Rationale

NSAI REVIEW

All Rules reviewed

Intended Use described supports Classification

Agree with Classification - Yes No

NSAI REVIEW

Technical Reviewer Date:

COMMENTS:

Additional Reviewer (if applicable) Date:

COMMENTS:

QUERIES No YesNumber(s)

Section 5 – Existing Legislation

1. Is the product OBL (Own Brand Labelled) Yes No

*You are not the actual Maker of the device – and the identical product carries CE marking by the Maker.

NSAI REVIEW

Agreed that this section is not required Yes No

Reviewer: Date:

Comments:

Please complete all questions in this section:

  1. Has there been a change to the Maker’s CE cert Yes No

If “Yes” – please provide the Notified Body’s review of the change

Report/ Document Ref.

  1. If the Maker uses NSAI as their Notified Body, please provide the file reference for the review of the change(s) –

MDD : 252. /

AIMD: 253. /

NSAI REVIEW

Revised OEM cert

Report provide

Review adequate

NSAI REVIEW

Technical Reviewer:Date:

COMMENTS:

Additional Reviewer (if applicable): Date:

COMMENTS:

QUERIES No YesNumber(s)

Section 6 – Labelling and IFU

  1. Is there a change to the Labelling/IFU Yes No

If “No” please justify -

NSAI REVIEW

Agreed that this section is not required Yes No

Reviewer: Date:

Comments:

Please supply a sample of the revised draft labelling & IFU in English.

  1. Location of the sample Label(s) & IFU in the supporting documentation
  1. Please clarify the exact nature of change(s) to the labelling/IFU based on the proposed change(s) under review –
  1. Are the requirements of EN 15223-1 & EN 1041 being met

Yes No

Version of Standard –

If “No” Please justify -

  1. Is the device Medical Electrical Equipment Yes No

If “Yes”

a) Are the requirements of EN 60601-1 being met:

Yes No N/A

Version of Standard:

If “No” please justify -

b) Are the requirements of EN 60601-1-6 being met:

Yes No N/A

Version of Standard:

If “No” please justify -

6. Do any vertical labelling standards apply Yes No

(i.e. device-specific standards that require labelling)

If “Yes”, please list (including current version) -

If compliance with these vertical labelling standards is not claimed, please justify -

NSAI REVIEW

Labels reviewed – details

All relevant parts of ER 13, particularly 13.3 (MDD) or ER 14 (AIMD) met

IFU reviewed – details

All relevant parts of ER 13, particularly 13.6 (MDD) or ER 15 (AIMD) met

Ensure traceability between the Risk Management File and the CER and labelling

Symbols & Markings on ME Equipment/System are per Table D.1, D.2, D.3 of EN 60601-1

Markings & IFU in line with EN 60601-1-2 (EMC)

For OBL – OEM IFU claims in line with OBL IFU

Vertical labelling standards -

NOTE – If an issue is identified with the sample labelling, ensure that the corrective action(s) are applied to all labelling operations.

NSAI REVIEW

Technical Reviewer Date:

COMMENTS:

Clinical Reviewer (if applicable) Date:

COMMENTS:

Additional Reviewer (if applicable) Date:

COMMENTS:

QUERIES No YesNumber(s)

Section 7 – Solutions to Essential Requirements and Harmonised Standards

Please indicate how relevant Essential Requirements (Annex I) of the Directive are met for the proposed changes.

  1. Location of the revised solutions to Essential Requirements in the supporting documentation

FOR CLASS I STERILE devices: In particular ER 8

FOR CLASS I MEASURING devices: In particular ER 10

  1. For devices other than Class I Sterile &/or Measuring please ensure there is specific reference to the design elements associated with this application and demonstrate how the design outputs meet the design inputs through design verification and validation
  1. Please list the relevant revised/updated Harmonised Standards in Table 5 below

Table 5 – Applicable Harmonised Standards List

Standard / Year / Full Compliance
Yes/No

FOR MDD CLASS I STERILE devices: In particular Harmonised Standards relating to sterility

FOR MDD CLASS I MEASURING device: In particular Harmonised Standards relating to the measuring function.

NSAI REVIEW

Class I Sterile

ER 8 adequately addressed -

Harmonised Standards for Sterilisation -

Class I Measuring

ER 10 adequately addressed -

Harmonised Standard(s) for Measuring -

Other classes of MDD devices & AIMDs

ERC Document Rev.

ERs identified as N/A

Agree with non-applicability

Has each subpart in the ERs been adequately addressed, if applicable

Solutions to ERs complete

Ref to the supporting documentation adequate

Harmonised standards used

Adequately demonstrates that design outputs meet design inputs through design verification & validation activities

NSAI REVIEW

Technical Reviewer Date:

COMMENTS:

Clinical Reviewer (if applicable) Date:

COMMENTS:

Additional Reviewer (if applicable) Date:

COMMENTS:

QUERIES No YesNumber(s)

Section 8 – Performance/ Complaint Analysis

  1. Is the change due to Vigilance or Performance Issue Yes No

NSAI REVIEW

Agreed that this section is not required Yes No

Reviewer Date:

Comments:

  1. If “Yes” please give details -
  1. HasNSAI received the Vigilance Report(s) Yes No

If “Yes” please provide the relevant Unique Identifier number(s) –

`If “No” please:

(a)Justify:

(b)If applicable, please submit a copy of the Competent Authority report(s) along with the completed NSAI Vigilance Form located at [ -“Vigilance Reporting”] to

  1. Has this product been the subject of product recalls or Incident Reports in other Regulatory geographies outside EU? If yes, please summarize and provide details with supporting documentation.
  1. For those failure modes associated with the identified Root Causes, please clarify if the Occurrence Rates outlined in the Risk Management File required an update based on the observed real world rates.

NSAI REVIEW

Vigilance reports reviewed

Trending data supplied reviewed

Negative review/refusal assessed

NSAI REVIEW

Technical Reviewer Date:

COMMENTS:

Clinical Reviewer: Date:

COMMENTS:

Additional Reviewer Date:

COMMENTS:

QUERIES No YesNumber(s)

Section 9 – Risk Management

  1. Did the proposed change affect or change any existing risks

Yes No

If “No” please justify -

  1. Did the proposed change introduce any new risks Yes No

If “No” please justify -

  1. Was the Risk review documented Yes No

(e.g. during change control process, update to FMEA, Memo to file etc.)

If “No” please justify -

  1. If no update to Risk Management File, please provide rationale:

NSAI REVIEW

Agreed that this section is not required Yes No

Reviewer Date:

Comments:

MANUFACTURERS – Where reviewed and updated, please provide

Risk Mgmt File - Risk Analysis, Risk Management Report, including a signed and dated conclusion regarding residual/remaining risks, which clearly identifies or highlights risk(s) in relation to the proposed change(s).

NOTE: Additional information may be required for devices containing tissue of animal origin, human blood derivatives or medicinal substances: see APPENDICES.

FOR CLASS I STERILE devices: In particular risks related to sterility

FOR CLASS I MEASURING devices: In particular risks related to measuring function.

  1. Risk management per EN ISO 14971 latest version Yes No

Version of Standard:

If “No” please justify -

  1. Which of the multifunctional team provided the clinical input – i.e. risks associated with the clinical use of the device

Please justify the appropriateness of their expertise -

  1. Please provide a traceability matrix linking the contraindications, warnings and precautions from Risk Management File to the Instructions For Use and Clinical Evaluation Report.
  1. If applicable, have relevant risk documentation for Medical Electrical Equipment, systems &/or Software been included Yes No

If “No” please justify -

NSAI REVIEW

Signed & dated conclusion regarding residual/remaining risks

Residual/remaining risks acceptable, based on intended application of the device

Compliance with ISO 14971 – version:

Suitable cross-functional team

Contra-indications/Warning/Precautions in IFU originate in Risk file

Risk analysis adequate

Solutions adopted by Manufacturer conform to safety principles, taking account of the generally accepted state of the art

Adequately covers the proposed changes

NSAI REVIEW

Technical Reviewer Date:

COMMENTS:

Clinical Reviewer (if applicable) Date:

Clinical risks (actual risks involved in the use, application of the treatment or deployment of the device) identified by suitably qualified person

COMMENTS:

Additional Reviewer (if applicable) Date:

COMMENTS:

QUERIES No YesNumber(s)

Section 10 – Sterilisation

10.1 – Sterilisation Validation

  1. Is the product provided sterile or intended to be sterilised prior to use Yes No
  1. Does the proposed change affect sterilisation Yes No

If “No” please justify -

NSAI REVIEW

Agreed that this section is not required Yes No

Reviewer: Date:

Comments:

MANUFACTURERS - Please provide the necessary sterilisation validation protocol(s) & report(s) and populate Table 6 below for the proposed changes