Regulatory Affairs Domain RAD Overview Regulatory Affairs Domain

Overview RAD Purpose & Benefits Common RAD Definitions System Components Connection between System Components Differences from Old System

RAD Purpose & Benefits Purpose A collaborative environment to develop global regulatory plans and submission documents that result from those plans A controlled electronic environment to create and edit regulatory submissions One Medtronic global regulatory tracking system that allows regulatory staff to easily find information about global submissions & approvals Intended to replace existing local databases and tracking spreadsheets Provides a platform to add complete tracking of approved drug products at a later phase Efficient publishing of both paper and electronic submission The RAD system gives us global view of all submissions, correspondence and approvals.

RAD Purpose & Benefits Purpose RAD replaced previous solution that utilized Desktop Client & EZ Subs Previous system was not robust enough to support evolving global requirements Previous system made heavy use of Virtual Documents and foldering to model and maintain Submission Geography-Product relationships

1. RAD Purpose & Benefits 21 CFR 11 compliant electronic archive for regulatory files A more efficient way to make submission documents available to the geographies Creation of electronic submissions (eCTD) and more efficient creation of paper Reports allow efficient tracking of regulatory metrics Global visibility and reporting for submission, correspondence & approval data across Medtronic

Common RAD Definitions Introduction RAD introduces new terms that will be used for regulatory tracking across Medtronic All new terms have a common global definition Some of the terms will be mapped to country specific regulatory procedures and terms as appropriate. As we review the terms think about how they equate to local terms you currently use. New terminology is required to give us a common regulatory language across Medtronic. But of course local terms – particularly with they are used by regulators – will still be there. We recommend that your local procedures map regulatory terminology in your country to RAD system terminology.

2. Common RAD Definitions Products Family Devices: A marketing brand name or other similar grouping that can be used to define a collection of customer facing numbers. Each Business Unit will have its own documented definition of a device family. Drugs: The international non-propriety name assigned by WHO or the generic name assigned by USAN Product Device: customer facing number (CFN) providing the product features of form, fit, or function of an end item thereby distinguishing each product variation within a product Drug: Each new combination of Generic Name, Concentration and Pharmaceutical Form (Dosage Form) is a drug product. Components Each product may be composed of multiple components. For example a kit may have 3 different device products. A combination product may have a drug and device component. *The definition of a drug product is still under discussion.

2. Common RAD Definitions Products Each family has multiple products assigned to it within the database. Each product may have multiple components FAMILY Product 1 Product 2 Component 3 Component 1 Component 2 Component 4

Combination Product Notes 2. Common RAD Definitions Products Combination Product Notes A combination product regulated as a drug in some countries and a device in others should have 2 families – one drug family and one device family Combination products regulated consistently around the world should be created as a single combination product family using the definition that best aligns to how they are regulated.

Common RAD Definitions Submission Terms - Application A top level grouping that keeps related submissions together. For example in the US, a PMA groups the original PMA and all related supplements. The definition will vary for each country Applications are created under a family and contain multiple products Applications are in one or more countries Each country needs guidance on how these levels within the system will be used EXAMPLES US – An original PMA is an application. Europe – a Design Examination Certificate (CE Cert) is an application,

Common RAD Definitions Submission Terms - Event A request to approve something, a notice to a regulatory agency of an intended change, or a change to a submission file maintained within Medtronic. Events are created under an Application Events can be related to one or more products within the application Each country needs guidance on how these levels within the system will be used EXAMPLES: US – the original PMA is the first event under the application. Each PMA Supplement is an addition event under the PMA application Europe – The first design dossier sent to get a CE Cert is the first event under the application. A change notification is an additional event under the certificate application Japan -

Common RAD Definitions Submission Terms – Sequence & Assembly The package of information sent to a regulatory agency at any one time. The “fedex box” for paper submissions, the sequence according to the eCTD definition for drugs. Assembly The collection of documents that makes up a sequence. For paper submissions this is a collection of binders, for electronic submissions it may be a CD. Each sequence is related to one event Each assembly is related to one sequence EXAMPLES US – When the original PMA is sent, it is the first sequence under the PMA event. The first response to questions is a 2nd sequence under the event for the original PMA Europe – When the original Design Dossier is sent to the notified body, it is the first sequence under the Design Dossier Event. The first response to questions is a 2nd sequence under the same event

2. Common RAD Definitions Submission Terms Family 1 to many 1 to many Product Country 1 to many Applications can relate to one or more products within the family Events can related to one or more products within the application Application 1 to many Event 1 to many Sequence 1 to 1 Assembly

2. Common RAD Definitions Other Terms for Regulatory Tracking Project A grouping of events that support a common regulatory goal. For example, a manufacturing site change that requires multiple submissions to gain approval for all impacted products. Note: Medtronic only uses projects to group events within a single country Reference A record of correspondence, telephone log, or other information related to a submission. Registration The record of an approval Task An activity to be done that is associated with a submission, correspondence or product. Tasks can have due dates and be assigned to a specific person. References, Tasks can be associated with Project, Families, Products, Applications, Events or Sequences. Registrations can only be associated with Applications and Events

RAD is composed of 3 basic parts: 3. System Components RAD is composed of 3 basic parts: Documentum Webtop version 6.5 InSight Publisher (IP) InSight Registration Planning & Tracking (RPT) RAD refers to all components of the system used together

4. Connection between System Components SAP (R3) Product Numbers Data for document properties and folder structure Webtop 6.5 Document creation Routing and approval of documents Regulatory archive for documents InSight Manager (IP & RPT) Data about submissions Data about correspondence Data about approvals Reporting Submission Publishing This slide shows at a high level how the various components of the system are related. Documents linked to database records Approvals GTS

System Connections InSight entities & Webtop folders Family Country Application Event Sequence Data is created in InSight first You can then create folders in Webtop based on the InSight data The system will automatically keep the folder name matching the InSight entity name

System Connections InSight entities & Webtop folders Creation of new entities (e.g. families, products, applications, events and sequences) happens in InSight As a 2nd step, corresponding folders are created in within Webtop A configurable model was developed to map Webtop menu items (context) to template folder structure creation Webtop user interface (UI) components were developed to connect to InSight real time for some properties to give a consistent view (e.g. products)

System Connections EMC Documentum (Business Object Framework) RAD utilizes the Business Objects Framework Type and Service based business objects (TBO and SBO) architecture was used for folders and documents TBO features include: Lifecycle assignment during the creation and import of documents (Note: special archive folder has a lifecycle) Cascading of meta-data between the Regulatory tracking database and folder/document properties SBO Features include: Prune minor versions on approval Assign major version number on approval Dynamic folder creation based on Webtop menu context

Utilize workflow for review and approval System Connections EMC Documentum Workflow Utilize workflow for review and approval Approval process includes the option for electronic signature or just audit trail creation The system provides the ability to manage collections of documents within a folder structure and route for review and approval Document and Folder lifecycle management is controlled within the workflow process

System Connections Families A family is created in InSight (on the left). You can then create the family folder in Webtop based on the InSight field. The family name and the family folder name will always stay the same. Business Unit values and Product Number values on the family in InSight will show up on the family folder properties in Wetop.

System Connections Applications An application is created in InSight (left screen). You can create an application folder in Webtop to match it. The name of the application and the name of the application folder will always be the same between InSight and Webtop. The application number in InSight will appear on the application folder properties in Webtop.

System Connections Applications Product numbers on the application in InSight show up on the Product Info tab of the application folder in Webtop

System Connections Events Events are created in InSight (left screen). You can then create a corresponding event folder in Webtop. The event name in InSight and the event folder name in Webtop will always match. The event number in InSight will always appear on the Event info tab of the Event folder in Webtop. If the event is part of a project in InSight, the project name will appear on the Event info tab in Webtop and the Project info tab will be populated with more information about the project.

System Connections Events Product numbers on the event in InSight will show up on the Product Info tab on the event folder in Webtop.

5. Differences from Old System RAD is a new system – not an upgrade to the existing system The old “Global Dossier” system is a highly customized system with a rigid structure – which makes it unreliable. RAD relies on commercially available software configured for Medtronic

5. Differences from Old System 01, 02, and 03 folders are gone There will still be an area in Webtop for “local files” Country folders are only created if there is a submission ( planned, under construction, or complete) Product folders are created at a family level only To “plan” a submission, the geography needs to create the structure in InSight (Application, event sequence) to support it. Submissions could be “planned” the same day they are sent – though we would not encourage this as best practice.