Abbreviated 510(k)

Group Paper

(RGA 6100)

Prepared by:

Tosha Dave, Dhara Desai

Cheryl Lowe, Sonia Martorano

& Suyog Khare

1/31/2015

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INTRODUCTION:

Premier Device Consultants (‘Premier’) has been contracted by the Laser Therapeutics Company

(‘Company’), main office located at 800 Commonwealth Avenue, Boston, Massachusetts, to

develop a regulatory strategy for their medical device that is in its final stages of development.

On January 15, 2015, representatives from Premier met with a team of individuals from the

Company which included representatives from their Research & Development, Quality

Assurance, and Marketing Departments to discuss the device and begin formulating a plan for

bringing the device to commercial market. As part of the organization’s business plan, the

Company intends to market the device in the United States by the end of the second quarter of

2015 and is considering future expansion into other global markets.

Device Description:

The Company is developing a laser device which uses solid state laser for surgical procedures of

the eye. The device, which will be referred as NEULASER, delivers a double frequency visible

beam and a diode laser within acceptable ranges (532nm, 635nm). NEULASER uses a standard

laser probe, similar to other medical devices currently on the market and will be delivered for

surgical procedures with the usual accessory implements required for such surgical procedures.

The laser probe will be the only portion supplied sterilized using the appropriate sterilization

method. The intended use for NEULASER will be broad for use in various types of surgical

procedures of the eye to treat vascular disorders and the related abnormalities of the retina.

Considering there are currently other similar devices on the market, the Company would like to

employ the least burdensome approach for obtaining regulatory approval for NEULASER. In

addition, the Company is considering expanding the intended use for the product and is

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exploring whether to develop additional bench data using additional predicate devices or submit

the bench data currently accrued to expedite regulatory approval. Premier has been contracted to

advise the Company in these endeavors.

Device Classification:

The first step in bringing NEULASER to market is to identify the regulatory requirements based

on the classification of the device. With the information obtained from the Company,

particularly, the indication for use of the device and its technological characteristics, the Premier

consultant assigned to the project accessed the Food and Drug Administration’s Classification

Database and searched for the product code to identify the applicable regulation and determine

the type of application required for FDA clearance. Given that the device would be used for

surgical procedures of the eye, the medical specialty for NEULASER was determined to be

‘Ophthalmic’ and the consultant searched through the database using the Ophthalmic Review

Panel filter (21 CFR 886). In addition, the consultant searched through the available databases to

identify the regulatory path used by the manufacturers of other similar devices (Product

Classification, 2015). The consultant determined that NEULASER fell under product code,

HQF, and as an Ophthalmic laser was a Class II device subject to 21 CFR Part 886 Section 4390

for immediate submission (Product classification, 2015).

Selecting the Premarket Submission:

Considering the Company’s desire to market NEULASER in the second quarter of 2015, and its

desire to expand the intended use for the device, the Premier consultant made the following

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recommendations on the appropriate regulatory path for a successful device launch in the

commercial market:

Recommendation #1:

The Company was advised that since there were several predicate devices approved for

commercial distribution in the United State with the same intended use and technological

characteristics as NEULASER, demonstrating substantial equivalence to one or more of those

devices and submitting an abbreviated 510(k) application would be the least burdensome

approach for regulatory approval.

Recommendation #2:

Premier, based on their regulatory experience, has come across similar laser devices being used

for other indications such as plastic surgery and dermatologic procedures. The Company may

choose to explore in those areas for the expanded use of the device.

Recommendation # 3:

For the desired “Extended Use” of NEULASER, the company was advised to acquire additional

set of nonclinical data, while the Abbreviated 510(k) is being reviewed. Company should also

prepare for an Investigational Device Exemption (IDE) for the expanded intended use. Once the

Abbreviated 510 (k) is cleared and the product is in the commercial market; the Company can

submit the IDE to FDA and begin the clinical trial after 30 days, unless the FDA notifies that the

investigation may not begin (IDE approval process, 2014). The revenue obtained, from the

commercial sale of NEULASER, can be utilized in the clinical trial. A Traditional 510(k)

submission is advised to support the Substantial Equivalent rationale.

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DETAILED REGULATORY STRATEGY:

Establishment Registration:

Premier initiates a full-proof regulatory strategy by making sure that the company’s

establishment and all other facilities associated with the device development process and

distribution are registered under 21 CFR 807.20 and all the information for registration is current

(Overview of Device Regulation, 2014). The establishment registration fees of $3,313 must have

been paid for each of them before December 31, 2014 (Device Registration and Listing, 2014).

The Establishment Registration Number is 3005245883.

Development of Quality Management System (QMS):

Premier made sure that the Company has a Quality Management System in place under the

provisions of the Quality System Regulation (QSR). The Company’s Quality Management

Manual and standard operating procedures (SOPs) were reviewed and found to be deficient.

Premier recommended a revision to the structure of QMS as shown in Figure 1. Additionally,

SOPs were revised and employees were trained accordingly. The Company’s senior management

team was charged with ensuring that all the Company’s SOPs are being followed. Premier

further recommended that the position of Manager of Quality Assurance be elevated to a senior

position within the Company (Sall, 2014).

Premier met with the lead engineer, manager of Quality Assurance and the lead scientist for

device development to review the documentation related to the device development process to

ensure compliance with the design control provisions of QSR (21 CFR 820.30) and also make

themselves familiar with the International Organization for Standardization (ISO) requirements

and recommendations (ISO 13485 , ISO 14971). Although the procedures followed were

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documented, Premier determined that they were not in total compliance with both FDA and ISO

guidance and revisions were suggested.

Given that the NEULASER probe will be provided sterilized and Company does not have

required facility and personnel for that service; they identified a vendor to provide sterilization

service. Premier will provide guidance to the Quality Assurance Manager in performing the

vendor audit to ensure the compliance with the applicable regulations. The QA manager was also

advised to confirm that the Sterilizer has registered with FDA for the services provided.

Figure 1: Quality Management system (Sall, 2014)

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Premier also reviewed the Corrective Action Preventive Action (CAPA) strategies of the

company and suggested ideal structure of the CAPA (Shown in Figure 2) system that should be

implemented revising the current strategies.

Figure 2: Ideal CAPA structure for the Company (Sall, 2014)

NEULASER- Detailed Description:

The NEULASER probe is easy to use. The device works on visible laser using double diode

ranging from 532nm to 635nm visible laser beam. The device delivers a green 532 nm double

frequency beam, and a visible 635 nm Diode laser aiming beam that can be directed to selected

site within the eye by an Ophthalmologist (FDA, 2007). The operator can easily handle and

modulate laser intensity. The laser delivery system works on the basis YAG (neodymium-doped

yttrium aluminum garnet; Nd: Y3Al5O12) laser principle (FDA , 2009): is a crystal that is used

as a lasing medium for solid-state lasers. The dopant, triply ionized neodymium, Nd(III),

typically replaces a small fraction (1%) of the yttrium ions in the host crystal structure of the

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yttrium aluminum garnet (YAG), since the two ions are of similar size. It is the neodymium ion

which provides the laser activity in the crystal, in the same fashion as red chromium ion in ruby

lasers (Nd: YAG Laser, 2014). As the NEULASER comes under laser products the 21 CFR

1040.10 and 21 CFR 1040.11 apply. As the laser probes will be supplied sterilized, they can only

be used once.

The image of NEULASER is shown above (Laser Probe for Ophthalmology, n.d.).

Classification of NEULASER:

Device name: NEULASER

Device type: Disposable device for therapeutic purpose

Device Classification: Class II

Intended Use: treatment of retinal and corneal wall, and retinal photocoagulation

Medical Specialty: Ophthalmology

Applicable CFR: 21 CFR 886.4390

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Submission type: Abbreviated 510(k)

Preparation for submission of Abbreviated 510(k)

Premier directed the Company for preparation of all the documents required for a successful

submission of Abbreviated Premarket notification 510(k). All the documents are listed below are

in order for the submission of Abbreviated 510(k).

Medical Device User Fee Cover Sheet:

This sheet is the Form FDA 3601. Premier advised the Company to pay the fees under MDUFA

III for the review of the Abbreviated 510(k) submission. A unique Identification Number is

provided when the Fee is paid. The printed copy of the MDUFA cover sheet includes that unique

ID number. (Content of 510 (k), 2014)

Cover sheet –Form FDA 3514:

This form consists of five- pages. Premier recommended the Company to fill out only the part

that are applicable for the NEULASER, as completion of this form is not mandatory. This form

provides the Office of Device Evaluation (ODE) with all the general information related to the

NEULASER for a submission in a standardize format (Sall, 2014).

The Cover Letter:

The Company was notified that this page must include Name, Address, Contact number and Fax

number of the Laser Therapeutics Company itself and not Premier. This section also requires a

brief device information. It was required to put the submission type as Abbreviated 510 (k) on

this letter (Sall, 2014).

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Table of Contents:

The company was suggested to create a “User Friendly” documents through numbering all the

pages of 510(k) consecutively and if possible, to create selectively chosen index tabs for each

section (Sall, 2014).

The Standard Data Form FDA 3654:

The company was suggested to put the level of compliance, adopted throughout the device

development process, with the FDA- recognized standards (Sall, 2014).

The conformity standards (consensus standard):

NEULASER qualifies for Abbreviated 510(k) submission as it meets the following criteria:

1. General controls:

All the applicable general controls provisions [especially Adulteration and misbranding

(F, D & C Act section 501,502 subsequently)] were maintained.

2. A guidance document exists:

Guidance on the Content and Organization of a Premarket Notification for a Medical

Laser (Product classification, 2015)

3. The FDA has recognized relevant consensus standards including

IEC 60601-2-22 Third Edition 2007-05 Medical electrical equipment – Part 2-22:

Particular requirements for basic safety and essential performance of surgical,

cosmetic, therapeutic and diagnostic laser equipment.

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IEC 60825-1 Edition 2.0 2007-03 Safety of laser products – Part1: Equipment

classification, and requirements [Including: Technical Corrigendum 1 (2008),

Interpretation Sheet 1 (2007), Interpretation Sheet 2 (2007)]

ISO 10936-2 Second edition 2010-01-15 Optics and photonics – Operation

microscopes – Part 2: Light hazard from operation microscopes used in ocular

surgery

ISO 15004-1 First edition 2006-06-01 Ophthalmic instruments – Fundamental

requirements and test methods – Part 1: General requirements applicable to all

ophthalmic instruments (Product Classification, 2015)

Statement for indication of use:

Company was advised to include the 510(k) application number, Device name and indicated use

for word to word as “treatment of retinal and corneal wall, and retinal photocoagulation” as

shown initially in the device classification.

Statement of Substantial Equivalence [21 CFR 807.93 (Content of 510 (k), 2014)]:

The NEULASER device has the identical intended use and similar technological characteristics

as the device currently in the commercial market, Alcon Ophthalas 532 Eyelite. There are minor

differences between NEULASER and Alcon Ophthalas 532 Eyelite designs; however, the basic

operating principles remain the same. Therefore, the Alcon Ophthalas 532 Eyelite was selected

as the predicate device. It will be used for treatment of retinal and corneal wall, and retinal

photocoagulation same as the predicate device. The laser probe will also be useful in treatment of

other vascular and intravitreal abnormalities. The NEULASER system will be using a slit lamp

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technology utilizing laser for modification of internal and external retinal and/or vascular tissues

through coagulation or cutting the tissue. The laser delivery system uses same principle as its

predicate device. The NEULASER provides better laser intensity and suitability for better and

easier utilization by the ophthalmologist.

As the NEULASER fulfills the requirement of similar intended use and technological

characteristics to the selected predicate device, Alcon Ophthalas 532 Eyelite, under 21 CFR

807.92 (a)(3); the Substantial Equivalence is prominently addressed (CFR- Code of Federal

Regulation Title 21, 2014).

Other reference devices can be use as reference devices. The Next Generation Laser has the same

intended use for retinal photocoagulation and laser trabeculolasty (FDA, 2007); IRIS Medical

OcuLight SL/SLx (FDA, 2002) delivers similar power, delivery system and intended use; and

Meditec Link (FDA, 1998) has the similar intended use and technological characteristics.

Truthful and Accuracy Statement, 21 CFR 807.87(k)

Premier advised the Company to assign this responsibility to the Head of Regulatory

Department. The statement is then framed as:

“I certify that, in my capacity as Director of Regulatory Affairs of Laser Therapeutics Company,

a medical device manufacturer, I believe to the best of my knowledge, that all data and

information submitted in the premarket notification are truthful and accurate and that no

material fact has been omitted.”

This section also requires the signature of the responsible person, the position of that person in

the Company, assigned 510(k) number (CFR- Code of Federal Regulation Title 21, 2014).

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Proposed Labeling (21 CFR 801):

The proposed label should also include following warning stickers:

(CFR- Code Of Federal Regulations Title 21, 2014)

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NEULASERLaser type: Solid state visible light laser

Laser Classification: Class IIIb

Wavelength: 532 nm, 635 nm

Power output: 5 mW

Indication: treatment of retinal and corneal

wall, and retinal photocoagulation

Warning: Avoid direct exposure to beam

Risks: Blindness, Irreversible eye damage,

Decreased vision, Decreased Contrast

sensitivity, Dry eye syndrome

Manufactured and distributed by:

Laser Therapeutics Company,

800 Commonwealth Ave.

Boston, MA 02115

Manufactured on: 01/31/2015

(Laser Safety, 2015)

The proposed package insert/ user guide / Operator’s manual is also required to be included with

labeling documentation.

After collection of the all the required documents for the Abbreviated 510(k), the company was

mandated to send Two Copies to the address:

Food and Drug Administration

Center for Devices and Radiological Health

Document Mail Center - WO66-G609

10903 New Hampshire Avenue

Silver Spring, Maryland 20993-0002

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Post submission Considerations for 510(k):

Premier counseled the Company that the company responsibilities does not end here; the

company has to develop a post- marketing surveillance strategy for any records or adverse event

reporting. The Company must report to FDA as soon as the Company or any company personnel

becomes aware of any case of serious injury or death under the provisions of 21 CFR 803

(Mandatory Reporting Requirements: Manufacturers, Importers and Device User Facilities,

2015). The Company is required to inform FDA through submission of a 3500A form within 30

from the first case of death that came into manufacturer’s knowledge. If any adverse event takes

place, requiring immediate remedial action, then the Company is required to report FDA within 5

working days by submission the 3500A form (Sall, 2014).

SUMMARY:

In summary, Premier Device Consultants, contracted by the Laser Therapeutics Company

(manufacturer) to develop a regulatory strategy for its NEULASER device, performed an

evaluation of the Company’s regulatory preparedness. Premier made an assessment regarding

compliance with the federal regulatory requirements necessary for obtaining market approval for

the NEULASER and other products currently under development. Premier was able to identify

areas in the Company’s Quality Management System, SOPs, and documentation practices that

were in need of improvement in order for the Company to be in full regulatory compliance in

anticipation of the Premarket Notification 510(k). Given the Company’s senior management

team’s commitment to ensuring organizational improvement and the Company’s stated goal of

obtaining clearance to market their NEULASER device by the end of the second quarter of 2015,

Premier considers the Company to be in a strong position for ensuring regulatory compliance

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over the next several months. To reach that goal, Premier has made the following

recommendations for organizational improvement:

1. Restructure of the quality management system

2. Development of new SOPs and revision of current procedures to reflect current practices

3. Training employees on all required SOPs and good documentation practices

4. Train requisite staff on applicable CFRs and relevant ISO guidance documents

5. Train staff on adherence to good manufacturing practices and good laboratory practices

In addition to providing a regulatory strategy and organizational recommendations, Premier has

offered its continued assistance to the Company in developing audit plans for vendors involved

in the development, validation, sterilization, distribution of the device, and post market

considerations. Moreover, Premier Consultants has offered its services in preparing and

submitting the premarket application for the NEULASER device and providing further

consultation relative to developing regulatory strategies for the Expanded intended use of the

NEULASER.

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BIBLIOGRAPHY

(n.d.).

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