Application Review Form

IVDRecertification

Application Review Form

Please tick all that apply:

3 Year RENEWAL

Fast Track (expedited)

Directive(s) that apply:

DirectiveNSAI File Number

IVDD (98/79/EC)304./

Instructions:

1. Please complete all relevant sections of the form (excluding the NSAI Review sections). If the data is in supporting documentation, please ensure that there is a clear reference to the exact location of this information.
2. Please submit an unsigned version of this Application in Word as well as a signed copy - either scanned/secured (pdf) copy.
3. All application forms and supporting data to be forwarded in soft copy via one of the following (Hard copies not required)
4. NSAI upload facility: see
5. CD
6. Memory Stick

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

CHECKLIST

Have you remembered to include everything?

Completed application form(Word format, .doc or .docx) & signed applicationform (Word .doc or .docx or .Pdf)

Summary of all substantial changes implemented during the
current product certification cycle

Identification of relevant Harmonized Standards amended during
the product certification cycle, and proof of compliance with theamended standard(s)

Performance/Complaint Analysis

Risk Management Plan / Most recent risk assessment document

*Sterilization Revalidation(s) – Validation protocol and most
recent validation results

Updated Performance Evaluation Study & associated supporting data

DECLARATION(s) BY APPLICANT

In making this application we declare:

• The information in this form is correct
• We have not lodged an application with any other notified body to undertake conformance assessment procedures for the same product(s) / device-related quality system mentioned.
• We undertake to institute and keep up to date a systematic procedure to review experience gained from devices in the post-production phase and to implement appropriate means to apply any necessary corrective actions and notifications, taking account of the nature and risks in relation to this product.
• We agree to inform/notify the Competent Authorities and NSAI of the following

- any event which meets all three basic reporting criteria (A-C) listed in the CRITERIA FOR INCIDENTs TO BE REPORTED BY MANUFACTURERS TO COMPETENT AUTHORITIESin the current MEDDEV 2 12-1 (current revision) which is considered an INCIDENT. Where an event has or could result in INDIRECT HARM (as defined in MEDDEV 2 12-1 (current revision) and that led or might have led to death or serious deterioration in state of health, we should submit a Manufacturer’s INCIDENT Report (in accordance withMEDDEV 2 12-1 (current revision).

-Any action taken to reduce a risk of death or serious deterioration in the state of health associated with the use of a MEDICAL DEVICE that is already placed on the market should be reported through a Field Safety Corrective Action Report (as defined in MEDDEV 2 12-1 (current revision). Such actions, whether associated with direct or indirect harm, should be reported.

- Whilst it may be difficult to determine if a serious deterioration in the state of a patient’s health was or could be the consequence of an erroneous result obtained with an IVD or a diagnostic device, or the consequence of an error by the USER or third party. In cases of doubt a report should be submitted (See MEDDEV 2 12-1 (current revision)).

-In the case of potential errors by USERs or third parties, labelling and instructions for use should be carefully reviewed for any possible inadequacy. This is particularly true for devices used for self-testing where a medical decision may be made by the patient. Inadequacies in the information supplied by the MANUFACTURER that led or could have led to HARM to USERs, patients or third parties should be reported.

In particular, it can be extremely difficult to judge events in which no HARM was caused, but where HARM could result if the event was to occur again elsewhere.

• We agree to pay all applicable fees and understand that non-payment of fees will result in withdrawal of approval.
• We undertake to fulfill the obligations imposed by the quality system approved
• We undertake to keep the approved quality system adequate and effective.
• We agree to inform NSAI of any plan for substantial changes to the quality system or the product-range covered.
• We shall inform NSAI which issued the EC design-examination certificate of any changes to the approved design, wherever the changes could affect conformity with the essential requirements of the Directive or with the conditions prescribed for the use of the device.

• We authorize NSAI to carry out all the necessary inspections and supply it with all relevant information, in particular:

-The documentation on the quality system

-The data stipulated in the part of the quality system relating to design, such as the results of analyses, calculations, tests etc., (where relevant)

-The data stipulated in the part of the quality system relating to manufacture such as inspection reports and test data, calibration data, qualification reports of the personnel concerned, etc.

• On receipt of the CE Mark re-approval from NSAI, it is our intention to commercialize the product. In the event of non-commercialize of the said product we commit to notify NSAI of this decision.
• We authorize and agree to allow NSAI access to all critical subcontractors and crucial suppliers, and all sites where the device or it’s crucial components are produced.
• We agree to allow NSAI access to the Legal Manufacturer’s premises, and /or any of the above listed sites at any time for the purposes of performing unannounced audits.
• As necessary we agree to provide all necessary support in acquiring the necessary travel papers, including VISA, to facilitate NSAI access to the above listed locations.
• We agree to inform NSAI of the periods when the devices identified in this application will not be manufactured.
• We understand that NSAI may end this contract with the Legal Manufacturer if permanent unannounced access to the above listed sites is no longer assured.
• We understand that NSAI may cancel any unannounced audit at any time if the safety and security of NSAI personnel cannot be assured.

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

Section 1 - Manufacturer and Product Details

MANUFACTUER - Please complete the following table

Table 1 – Manufacturers Information

(Legal) Manufacturer’s Name
(Legal) Manufacturer’s Address
Design Site(s):
Manufacturing Site(s):
(i.e. sites of actual manufacture)
Assembly Site(s) if applicable
Sterilization Site(s) if applicable
Scope of Site(s):
(i.e. as shown on the QMS cert)
Name and address of EU Authorized 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
IVD Type / Annex II List B / Self-Test IVDs not covered by Annex II
Conformity Assessment Route
Date of this application (i.e. date of Declaration of Applicant)

NSAI REVIEW

NSAI registration(s):
Product:#

QMS:#

Client QMS Certificatesare valid and scope of registration(s) remains
adequate forproduct family under review

Product family name in line with GMDN

Verify that the conformity assessment selected is appropriate for the type of IVDD

Is the scope of the QMS in line with the Annex Chosen (e.g. design)

Are additional certificates required (e.g. EC type certs)

Has any information above changed during the current product certification
cycle (if so, review & confirm that substantial change notification was
previously received and reviewed by NSAI – see Section 3)

Technical Reviewer: Date:

COMMENTS:

Clinical Reviewer (if applicable): Date:

COMMENTS:

Additional Reviewer (if applicable): Date:

COMMENTS:

QUERIES: No YesNumber(s):

Section 2 - Intended Use of the Device / Labeling and IFU

Please enter a full description of the intended use of the device, and identify contraindications.

Also provide copies of current product labels and Instructions for Use (IFU’s)

Full Description of Intended Use:

Has any of the following been revised or amended during the current product certification cycle? (see Section 3 and provide change details there)

Table 2: Intended Use/Labeling/IFU

Detail / Yes/No Reference the amendment number submitted to NSAI
Intended use
Indications for Use
Patient population
Warnings and precautions
Procedure
Quality Control
Results
Calibration details
Limitation of the procedure
Expected values
Specific performance characteristics
Contraindications

NSAI REVIEW

Intended Use clearly stated Yes No

Do the “intended use” and “contraindication”statements above match information found in product labeling and Instructions for Use? Yes No

Legal Manufacturer and EU Rep.Information included on labeling? Yes No

Does that information match Table 1 above. Yes No

Are correct symbols utilized? Yes No N/A

Technical Reviewer: Date:

COMMENTS:

Clinical Reviewer (if applicable): Date:

COMMENTS:

Additional Reviewer (if applicable): Date:

COMMENTS:

QUERIES: No YesNumber(s):

Section 3 – Review of Changes

Part 1: Substantial changes

Table 3: List of substantial changes

Please provide a complete listing of all substantialchanges made during the current product certification cycle.
Product(s) affected & Amendment # / Description of Change

Part 2: Changes to the Technical Documentation: Has there been any changes to the technical documentationthat apply to the criteria that are listed in Table 4

Yes No

If “Yes” Please list the titles below and provide the data to NSAI;

Table 4: List of Technical changes

Changes to: / Yes / No / N/A / Briefly Describe / Report Number
Buffers
Electrolytes (Na+, Ca++, etc.)
Proteins/Enzymes (e.g., Recombinant, Activity, Affinity, Purity, etc.)
Additives/Stabilizers (e.g., glycerol, 2-mercaptoethanol, etc.)
Reference Standards (medicinal agent, antibody, protein, etc.)
Accessories to IVDs (e.g., pre-processing of biological samples, etc.)
Packaging (vials, etc.)
Software
Instruments/Hardware
Operating Systems
Subcontractors/Suppliers
Others

Technical Reviewer: Date:

COMMENTS:

Clinical Reviewer (if applicable): Date:

COMMENTS:

Additional Reviewer (if applicable): Date:

COMMENTS:

QUERIES: No YesNumber(s):

Section 4 - Product Stability & On-Going Testing

Using Table 5 below, please specify the current shelf-life of the product:

If additional Tables are required, please copy and paste this format underneath Table 5

Table 5 Stability claims

Product name
Model Numbers
Shelf life / Time Period and storage conditions (where applicable, if not please state N/A)
Claimed Shelf life
In use stability
On board stability
Re-constitution
Open vial/bottle
Shipping/Transport Stability
Duration of transport
Expected temperatures
Humidity

Has the product shelf life / expiry date changed during the current product certification cycle? Yes No

• If yes, please explain:

Is the stated shelf life based on accelerated or real time aging Yes No

Please provide an update on any real time aging activities currently underway, or completed during the current product certification cycle: N/A Yes No

Is regular monitoring of the stability of an IVD reagent already on the market completed? Yes No

• If Yes, please explain and provide data:

• If No , please provide a rationale

NSAI REVIEW

All Devices:

Does stated shelf life above match previously approved submission or amendment?

Does the stated shelf life above match the labels/IFU?

Technical Reviewer: Date:

COMMENTS:

Clinical Reviewer (if applicable): Date:

COMMENTS:

Additional Reviewer (if applicable): Date:

COMMENTS:

QUERIES: No YesNumber(s):

Section 5 - Harmonized Standards

Please indicate if any relevantHarmonized Standards have been amended during the current product certification cycle.

Please provide objective evidence of compliance with any revised standards noted below.

In Table 2 below, please list any updatedHarmonized Standards and address how the revised standard has been considered and implemented

In the cases where there have been changes or updates to the technical content/requirement of the standard, please provide evidence of compliance to the new standard.

For see

Harmonized Standard / Year / Compliance
Yes/No / Evidence of Compliance
EN 61010-2-101 / 2002 / Yes / Report # x, pg x, para. X
EN 61326-2-6 / 2006 / Yes / Report # x, pg x, para. X
EN 62304 / 2006 / Yes / Report # x, pg x, para. X
EN 62366 / 2008 / Yes / Report # x, pg x, para. X

Table 2: Compliance with updatedHarmonized Standards

Harmonized Standard / Year / Compliance
Yes/No / Evidence of Compliance

Technical Reviewer: Date:

COMMENTS:

Clinical Reviewer (if applicable): Date:

COMMENTS:

Additional Reviewer (if applicable): Date:

COMMENTS:

QUERIES: No YesNumber(s):

Section 6 – Complaint Summary / Vigilance Reports / Trend Analysis

Please provide a summary analysis of product complaints and Vigilance Reportable Incidents as outlined below

A. COMPLAINTS:

1.Is the device commercialized Yes No

If “No” please explain -

2.Time period of the complaint data being provided –

Last 3yrs –

Lifetime of the device

3.

TOTAL UNIT SALES

TOTAL No. COMPLAINTS

TOTAL No. of REPORTABLE EVENTS (worldwide)

1. Please provide an analysis of complaint data over the stated period of time, in either graphic or table form, summarizing types of complaints, (e.g. performance related, clinical user related, labeling issue, off-label use, product misuse, complaint justified / non-justified) with quantity and % total sales
2. Please provide data on up-to-date QC / Production trends

B. VIGILANCE REPORTS:

Summary of all Vigilance Report(s) submitted to EU Competent Authorities
during the current product certification cycle.

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

C. CORRECTIVE ACTIONS:

In the table below, please provide a summary of corrective actions implemented as a result of vigilance or complaint trends.

Vigilance/complaint number / Corrective action number / Description of corrective action / Corrective action Status

NSAI REVIEW

Suitable rationale if device not commercialized at 3yr renewal

Complaint data & possible trends reviewed

Vigilance reports & possible trends reviewed

Performance issues worldwide considered & reviewed

Review data on up-to-date QC / Production trends

Technical Reviewer: Date:

COMMENTS:

Clinical Reviewer (if applicable): Date:

COMMENTS:

Additional Reviewer (if applicable): Date:

COMMENTS:

QUERIES: No YesNumber(s):

Section 7 – Risk Management / Risk Analysis

Please provide the current Risk Management Plan/ Report and most recently completed Risk Analysis, including a signed and dated conclusion regarding residual/remaining risks. Has EN 14971 Annex H (Guidance on Risk Management of in vitro diagnostic medical devices been considered)

NOTES

- Additional information may be required for devices containing tissue of animal origin, or human blood derivatives

- If applicable please ensure to include relevant risk analysis for IVD Medical Equipment, Software

NSAI REVIEW

Compliance with ISO 14971 – version:

Has Annex H (Guidance on management for in vitro diagnostic medical devices) been considered?

Residual/remaining risks acceptable, based upontype of device, special
circumstances (e.g. drug/device, animal tissue, human blood), and intended
application of the device

Suitable cross-functional team involved in risk assessment

Clinical/Performance risks identified by suitably qualified person (actual clinical risksinvolved in the use, application to the treatment of the clinical condition)

Signed and dated risk-to- benefit conclusion by a qualified individual

regarding residual/remaining risks

Risk analysis comprehensive and adequate

On-going Risk Management Plan suitable

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

NSAI REVIEW

Technical Reviewer:Date:

COMMENTS:

Clinical Reviewer (if applicable):Date:

COMMENTS:

Additional Reviewer (if applicable):Date:

COMMENTS:

QUERIES: No YesNumber(s):

Section 8 – Sterilization

1.Is product provided Sterile? Yes No

If no, please continue to Section 9

Please provide the SterilizationValidation / Revalidation protocol(s) & most recently completed Sterilization Cycle Revalidation Report(s) and populate Table 3 below

Table 3– Sterilization Information Summary

Device sub-family / Cat. Number / Sterilization Method / Sterilization Location / Protocol/ Report No. / Site resp for Release

2. If EtO is utilized for Sterilization, please categorize the device according to the duration of contact below, and provide data in support of the most recently completed residual testing:

A – Limited Exposure

B – Prolonged Exposure

C – Permanent Contact

NSAI REVIEW

Compliance with relevant harmonized standard for sterilization -

If harmonized standard for sterilization is not followed, identify the industry

standard used for cycle determination & validations (e.g. AAMI, TIR)

EtO Residuals compliant with EN ISO 10993-7 – version

Validation / Revalidation schedules defined, documented and maintained

Validation Report reviewed & results support a validated sterilization cycle.

NSAI REVIEW

Technical Reviewer:Date:

COMMENTS:

Additional Reviewer (if applicable):Date:

COMMENTS:

QUERIES: No YesNumber(s):

Section 9 – Clinical Performance Update

For the manufacturer:

1. Provide an updated performance evaluation report that is signed and dated by a relevant clinical expert(s) in compliance with EN 13612 (current revision) and Commission Recommendation (2013/473/EU) point 6
2. Provide a copy of the CV/resume of the relevant clinical expert(s) responsible for the updated performance evaluation

The report should contain adequate updated performance evaluation data in support of the performances claimed and further supported by a reference measurement system (when available), including detailed information on:

• the reference methods,
• the reference materials,
• the known reference values, and
• the accuracy and units of measurement used.

This data should arise from studies in a clinical or other appropriate environment or result from relevant biographical references.

Other key aspects of such an evaluation include:

-Performance history over the past 3 years

-Any changes made to the device;

-Risk Reports including the risk/benefit analysis; and,

-Post market experience and review of the current state of the art (e.g., clinical/scientific literature reviews, review of regulatory databases, etc.).

NSAI REVIEW

TO BE COMPLETED BY NSAI CLINICAL REVIEWER ONLY

NSAI Performance Review

Evaluation is in accordance EN 13612:2002 (Performance evaluation of IVD MDs) for all other devices.

Has adequate performance evaluation data been supplied showing the performances claimed by the Manufacturer & supported by a reference measurement system (when available)?

Review details of the post market clinical follow-up.