• Is the product a medical device?

• How do we determine which classification the device falls under?

• What are the specific regulations for this class of device?

These are just a few of the questions a company needs to address when applying for product approval in various markets.

Methodize can help your company confidently define the classification of your product. Also, because of our experience with devices from all class types, we can develop the most efficient regulatory approval process for your company to follow.

Methodize will carefully review the intended use of the device, indications for use, possible exemptions for your device, the risk level of the device, and other factors before determining the specific classification.

Once you have determined the classification of your device, you may need to start the process of a Premarket Notification (PMN) submission, otherwise known as a 510(k). Most devices that fall into the Class II category require a 510(k) submission to the Center for Devices and Radiological Health (CDRH) within the FDA. The group within the CDRH responsible for recommending your product is called the Office of Device Evaluation (ODE). The ODE consists of a panel of scientific experts that review 510(k) submissions and decide whether a product is substantially equivalent (SE) or not substantially equivalent (NSE).

Methodize can help your company navigate the 510(k) submission process by offering the following services:

• 510k documentation preparation

• Communication with the FDA

• Intermediary with third (3rd) party review and notified body

• FDA audit guidance

• Traditional 510k

• Special 510k (Device Modification)

• Abbreviated 510k Submissions

• Substantial Equivalence (SE) Comparison

• 510(k) Summary Statement

• FDA Labeling

• Indications for Use

• 510k Device Description

• Performance Compliance 21 CFR 807.87 D

• Class III Certification and Summary (for Class III only)

• Final Certification and Disclosure Statement for 510k notifications with Clinical Studies

• 510k Kit Certification

• Sterilization Methods

• Software Documentation

• Third Party Review by Accredited Persons (AP)

• Expedited Review

Section 513(g) of the Federal Food, Drug and Cosmetic Act provides companies that have developed a new or modified device with a method for obtaining the correct classification of their product. The Act states that within 60 days of receiving the 513(g) Request for Classification, the FDA will provide a written statement with the classification and applicable regulatory requirements.

The information obtained from a 513(g) Request for Classification can offer valuable insight as to how to move forward for your company. It helps to discern which regulatory path is necessary (if any). Additionally, if the FDA classifies your product as Class II, you will be able to use the information from the 513(g) in your 510(k) Premarket Notification.

Methodize can help you determine whether a 513(g) Request for Classification is the appropriate next step for your company. Also, we can assist you in the process of filing the request.

Before a clinical trial can begin, a company must submit a formal Investigational Device Exemption (IDE), which permits the company to use the device in a study for the purposes of collecting safety and effectiveness data. In an effort to review the product before a formal IDE is submitted, the FDA introduced the Pre-IDE process. This allows the FDA to obtain a clearer picture of the investigational device and the risks involved before a formal review is conducted.

Early interaction with the agency should help to increase the manufacturer’s understanding of FDA requirements, regulations, and guidance documents, and will allow FDA personnel to familiarize themselves with the new technologies. Increased interaction between FDA and manufacturers should help to speed the regulatory process and minimize delays in the development of useful devices intended for human use.

Methodize can help your company create a well-researched and clearly outlined Pre IDE submission for the FDA.

The FDA Premarket Approval Process is required to ensure the safety and effectiveness of Class III medical devices. Class III devices are those that support or sustain human life, are of substantial importance in preventing impairment of human health, or which present a potential, unreasonable risk of illness or injury.

Due to the invasive nature of Class III products, the Premarket Approval Process is meticulously executed by a scientific review board. Prior to marketing a device, an applicant must receive Premarket Approval from the FDA. FDA regulations provide 180 days to review the PMA and make a determination. However, in reality the review time is normally longer. Before approving or denying a PMA, the appropriate FDA advisory committee may review the PMA at a public meeting and provide FDA with the committee’s recommendation on whether FDA should approve the submission.

Methodize can help you throughout the process of Applying for Premarket Approval. Our services include Pre-Investifational Device Exemption, Investigational Device Exemption, Premarket Approval, Quality System Inspection, and final FDA registration of the device.

Methodize can assist your company if any problems arise after your medical device has entered the market. We will take effective measures to re-establish compliance as quickly as possible.

Methodize will provide surveillance services including, vigilance reporting, responses to FDA 483s and warning letters, development of product recall strategies, complaint handling, failure investigation, problem reporting, device tracking, and any other necessary measures to assure compliance in the U.S. or international markets.

An investigational device exemption (IDE) allows the investigational device to be used in a clinical study in order to collect safety and effectiveness data to support a 510(k) or Premarket Approval Application. Investigational use also includes clinical evaluation of certain modifications or new intended uses of legally marketed devices. All clinical evaluations of investigational devices, unless exempt, must have an approved IDE before the study is initiated. Clinical evaluations of devices include an IDE approved by the Institutional Review Board (IRB) and approval by the FDA if the study involves significant risk, informed consent by all patients, labeling that states “for investigational use only”, monitoring, and required records and reports.

A sponsor of a significant risk device study must submit a complete IDE application to FDA. There are no preprinted forms for an IDE application; however, an IDE application must include certain required information. This involves a long list of items, including report of prior investigations; an investigational plan; description of methods, facilities, controls; examples of the agreement and signatures from involved parties; Pre-IDE information and meetings; waiver requests, etc.

Methodize can help your company submit a thorough and effective IDE application. We know the formatting required by the FDA and how to avoid common problems with IDE applications.

The IND is the means through which a sponsor obtains exemption from the federal law stating that a drug be the subject of an approved marketing application before it is transported or distributed across state lines. When a product is identified as a viable candidate for further development, the sponsor (usually the manufacturer or potential marketer) then focuses on collecting the data and information necessary to establish that the product will not expose humans to unreasonable risks when used in limited, early-stage clinical studies.

FDA’s role in the development of a new drug begins when the drug’s sponsor wants to test its diagnostic or therapeutic potential in humans. At that point, the molecule changes in legal status under the Federal Food, Drug, and Cosmetic Act and becomes a new drug subject to specific requirements of the drug regulatory system.

The IND application must contain information in three broad areas – Animal Pharmacology and Toxicology Studies, Manufacturing Information, and Clinical Protocols and Investigator Information. Once the IND application is submitted, the sponsor must wait 30 days before initiating any clinical trials.

Methodize assists clients with combination medical device products, such as drug/device and biologic/device applications in which the primary mode of action is either the drug or biologic component. We will identify how your product will be regulated by the FDA and develop a plan for your company’s IND documentation.

The CE Mark, which is an abbreviation for the French term “Conformite Europeen”, indicates that a manufacturer is compliant with the legal requirements of the EU “New Approach Directives” and European Regulations. Several types of products require the CE Mark, including medical devices, in-vitro diagnostic devices, toys, and personal protective equipment.

The CE Mark is a symbol of safety, and once obtained, the manufacturer can freely market their product throughout the European Union. Because the CE Mark only applies to European entities, all non-EU manufacturers must appoint a European Authorized Representative. The E.A.R. serves as a contact point between the manufacturer and EU member states competent authorities, and provides their contact information for the manufacturer to place on the products.

Methodize can help your company navigate the complicated CE Marking process (as outlined below), and we also offer European Authorized Representative services.

• Classification of Medical Device – According to the Medical Device Directive 93/42/EEC, a product could be listed under a variety of categories, including Class I, Class IIa, IIb ,Class III, Custom Made, In-vitro Diagnostic, Active Implantable or a combination of these when introduced to the market as a Kit (“Procedure Packs” or “Systems”).

• Identification – During this part of the process it is necessary to identify compliance of the product with European Health and Safety standards. Also, at this point a E.A.R. should be identified along with a Notified Body if the classification of your product requires one.

• Technical Documentation – The technical documentation includes all the evidence necessary to prove compliance with the EU requirements. This involves a variety of subjects, including but not limited to, conformity certificates, quality management systems (e.g. ISO 13485), labeling, packaging, instructions for use, and a Declaration of Conformity.

• Pre-Market Notification – The Pre-Market Notification is the official announcement that a product is about to enter the European market or is being put into service in a specific EU country. In cases of Class I products, the E.A.R. must inform the competent authorities that the product will soon be on the market. However, Class IIa, IIb, and III products do not require such notification.

• CE Mark labeling and Post-Market Surveillance – Once all the above steps are completed, the CE Mark can be applied to the product labeling, packaging, and literature. After entering the market, a company must have a surveillance system in place.

• National Requirements – Beyond the CE Mark, there may be specific national requirements to fulfill. For example, Italy has a separate registration process that medical device companies must adhere to in order to sell in that country.

For all the steps above, Methodize can provide your company with expertise so you can get your product to the European market in the quickest most effective way possible.

ISO 14971:2009 specifies a process for a manufacturer to identify the hazards associated with medical devices, including in vitro diagnostic (IVD) medical devices, to estimate and evaluate the associated risks, to control these risks, and to monitor the effectiveness of the controls. This standard is recognized by the FDA, European Authorities, Heath Canada, and the Australia Therapeutic Goods Administration as the guideline for risk management.

This International Standard does not require that the manufacturer have a quality management system in place. However, risk management can be an integral part of a quality management system.

Methodize can help your company implement ISO 14971 into your quality management system if ISO 13485 is already established. If not, please contact us for how we can assist your company with Quality Management System implementation.

Medical devices sold into the Canadian market must comply with Canadian medical device regulation. Health Canada reviews medical devices to assess their safety, effectiveness and quality before being authorized for sale in Canada.

Before selling in the Canadian market, you need to investigate which, if any, licensure is applicable for your product. If your product is Class I or in vitro diagnostic, you must obtain a Medical Device Establishment License (MDEL). If you sell through a distributor in Canada, then your distributor must have an MDEL.

If your product is classified as Class II, III, and IV medical devices in Canada, then a Canadian Medical Device license (MDL) is required. Canada’s Medical Devices License (MDL) is similar to the US FDA 510(k) process.

Methodize can help you decide which license is appropriate for your product and we will take you through the application process. Methodize can also modify your Quality Management System ISO 13485:2003 to comply with the Canadian requirements.

Each conformity assessment annex of the MDD, IVD and AIMD directives requires that the manufacturer of a medical device must have technical documentation for each product they plan to sell. The term technical file is used to describe the documentation that shows how the device complies with essential requirements. Technical Files are required for Class I, Class IIa and Class IIb devices. For devices that require a design examination (Class III products), the technical construction file (TCF) is called a design dossier.

Technical Files are retained in the premises of the manufacturer or the Authorized Representative for potential review by Competent Authorities and/or Notified Bodies. Design Dossiers must be submitted to the Notified Body for review prior to CE Marking of the product.

The structure of a design dossier or technical file can be broken down into the following sections:

• Introduction

• Essential Requirements Checklist

• Risk Analysis

• Drawings, Designs, Product Specifications

• Chemical, physical and biological tests

• In Vitro Testing – Preclinical Studies

• Biocompatibility Tests

• Bio-stability Tests

• Microbiological Safety, Animal origin tissue

• Coated Medical Devices

• Clinical Data

• Package Qualification and Shelf Life

• Labels – Instructions for Use, Patients Information, Advertising Materials

• Manufacturing

• Sterilization

• Conclusion

• Declaration of Conformity

Methodize has developed design dossiers and technical files for a wide variety of products and companies. We can help you improve your current documentation, provide you with templates to get you started, or work with you from the beginning to develop the documents ensuring compatibility with the regulations.