# Manage Combination Products Vault supports end-to-end case processing for postmarketing combination products, including those with device constituents. This includes submission rules that adhere to the FDA's postmarketing safety reporting (PMSR) requirements for combination products. These products contain multiple constituents and any combination of drug, device, and biologic components. You can set up and manage combination products using the _Combination Product_ type of _Product_. A _Combination Product_ can contain multiple _Product Constituents_ and _Combination Product Registrations_. _Product Registrations_ are a key part of setting up _Combination Products_, as Vault relies on these registrations to generate the appropriate _Submission_ records for each constituent part. A _Product Constituent_, also known as "constituent part," is a single drug, device, or biologic component within a combination product. When processing _Cases_ concerning a specific _Combination Product_, Vault generates _Case Assessments_ for each _Product Constituent_. Once the _Case_ is _Approved_, Vault generates the required _Transmissions_, determined by the _Product Registrations_ and your Vault's reporting rules. ## Prerequisites To use this feature, you must enable Combination Products. ## Add a Combination Product To add a _Combination Product_: 1. Navigate to **Business Admin > Objects > Products**. 2. Select **Create**. 3. In the _Create Product_ window, select **Combination Product**. 4. Select **Continue**. 5. On the _Create Combination Product_ page, complete the following fields: * **Organization**: Select the _Organization_ to which the product belongs. When adding a _Case Product_, the _Case_ must be associated with this organization to allow users to select this product. * **Product Name**: Enter the primary name of the product. Vault references the product using the value that you enter in this field. When a _Case Product_ references this _Product_ record, Vault uses this field to generate the _Case Product_ name. * **Combination Type**: Select one of the following options: * **Single Entity**: Multiple components combined and produced into a single entity. * **Co-Packaged**: Multiple separate products packaged together into a single product. * **Cross-Labelled**: Multiple products packaged separately but are intended for use together. * **Abbreviation**: Enter the abbreviated name for the product. This field is for reference only * **Generic Name**: Enter the generic name for the product. For _Device_\-type products, Vault uses this for FDA E2B(R2), FDA VAERS E2B(R3), and FDA MedWatch 3500A report generation. * **Manufacturer**: Select the organization that manufactures the product, if it is different from the value selected in the _Organization_ field. For _Device_\-type products, Vault uses this for FDA E2B(R2), FDA VAERS E2B(R3), and FDA MedWatch 3500A report generation. * **Core Datasheet**: Select the core _Datasheet_ for the product family, which Vault uses to detect expectedness for an adverse event and the suspect or interacting _Case Products_. 6. Select **Save**. ### Combination Product Type {#combo-type} If you have configured the _Combination Product Type_ field on the _Product_ object, Vault populates a value based on whether the product is comprised of drugs, devices, or both. To determine the setting, Vault considers: * The [_Product Type_][2] field across all active _Product Constituents_. * The [_Registered As_][3] field across all active _Product Registrations_ for the _Product Constituents_. Vault does not consider inactive records when populating a value. As _Product Constituents_ and their _Product Registrations_ are added, edited, deleted, or inactivated, Vault reevaluates the _Combination Product Type_. ## Combination Product Constituents Product constituents are the individual components that make up a combination product. When you add a _Combination Product_ to your Vault, you must also add the applicable _Product Constituents_.
### Add a Product Constituent {#add-constituent} To add a _Product Constituent_: 1. Navigate to the _Combination Product_ to which you want to add the _Product Constituent_. 2. Expand **Product Constituents**. 3. Select **Create**. 4. On the _Create Product Constituent_ page, complete the following fields: * **Combination Product**: The parent _Combination Product_ for which this product is a constituent part. Vault populates this field when you create the _Product Constituent_ from the _Combination Product_ record. * **Constituent Product**: Select the _Product_, or select **Create Product** to add a new _Product_. * **Name**: Enter the name of the constituent product, as it should appear when being referenced throughout Vault. * **Product Type**: Vault populates this field, based on the type specified on the associated _Product_ record. To update this value, edit the associated _Product_ record. 5. Select **Save**. ## Combination Product Registrations When you promote an _Inbox Item_ with a _Combination Product_ to a _Case_, Vault uses the _Product Registration_ data to populate certain fields, calculate expectedness, and generate _Submissions_. When setting up _Combination Products_, we recommend that you add the following _Product Registrations_: 1. Create _Product Registrations_ for the entire _Combination Product_. For _Combination Products_ with device constituents, you can use the _Registered As_ field to specify whether device constituents should be exported in E2B files generated for that jurisdiction. 2. Create additional _Product Registrations_ for each _Product Constituent_. You can designate which constituent is the Primary Mode of Action (PMOA) on the _Product Registration_, which is used to designate the primary _Case Product_ in _Combination Product Cases_.
### Add a Combination Product Registration {#add-a-combination-product-registration} To add a _Combination Product Registration_: 1. Navigate to the _Product_ to which you want to add the _Product Registration_. 2. Expand the **Registrations** section. 3. Select **Create**. 4. On the _Create Product Registration_ page, complete the [applicable fields][1]. 5. Select **Save**. #### Product Registration Fields {#product-registration-fields}
Field Description
Organization
(organization__v)

Vault populates this field with a reference link to the Organization on the parent Product parent.

If the Registration Holder/Applicant field is blank, Vault maps this field to the Registration Holder field on a Case Product.
Product
(product__v)		 Vault populates this field with a reference link to the parent Product record.
Product Constituent
(product_constituent__v)		 The Product Constituent for which this registration applies. Vault populates this field when you create the Product Registration from the Product Constituent.
Product Type
(product_type__v)		 Vault populates this field with the product type of the parent Product.
Combination Type
(combination_type__v)

For combination products, select the combination type.

Vault maps this field to the Case Product and uses the information in FDA VAERS E2B(R3) report generation.
Registration Name
(name__v)		 Enter a name for the Product Registration. Vault references the registration using the name that you enter in this field.
Registration Number
(registration_number__v)

Enter the product authorization or application number for the country where the product is marketed.

For U.S. registrations, ensure that the value adheres to the FDA E2B(R2) format requirements for data element B.4.k.4.1 (Authorisation / Application Number).

Vault maps this field to the Case Product and uses the information in E2B, FDA MedWatch 3500A, and PADER report generation.
Registration Applicant/Holder
(registration_holderapplicant__v)		 Vault maps this field to the Registration Holder field on Case Products. If this field is blank, Vault maps the value in the Organization field.
MAH
(reporting_organization__v)

Depending on your Admin's configuration, this field may be named Reporting Organization.

If you have a Marketing Authorization Holder (MAH) that manages your ICSR reporting obligations for this registration, select the organization. Selecting an organization creates an MAH Distribution List, and thereby a reporting obligation, for this registration.
Transmission Profile
(transmission_profile__v)		 Select the Transmission Profile Vault should use when generating Submissions for this registration. We recommend setting this field when you have a Transmission Profile corresponding to this reporting destination and report type.
PMOA
(pmoa__v)

Specify if the product is designated as the Primary Mode of Action (PMOA).

The product designated as the PMOA is set as the primary Case Product on Cases concerning the Combination Product. The reporting rules engine uses the PMOA registration to match the Transmission Profile when generating Submissions for Cases involving the Combination Product.
Registration Date
(registration_date__v)

Enter the date the product was registered.

This field is for reference only.
Registration Type
(registration_type__v)

Select the registration type.

Vault uses this field in FDA MedWatch 3500A and PADER report generation.

This field is needed to correctly match Transmission Profile Scope records for any organization with multiple Transmission Profiles for the same destination Agency.
Country
(country__v)

Select the country where the product is registered and authorized.

Vault maps this field to the Registration Country field on a Case Product and uses the information in E2B report generation.
Route of Administration
(route_of_administration__v)

Select the route of administration TermID code.

Vault maps this field to the first Case Product Dosage record for the Combination Product.
Compounding Type
(compounding_type__v)

For compounded products, select the compounding type.

Vault maps this value to Case Products and references it in report generation for E2B and FDA MedWatch 3500A formats.
Agency
(agency__v)

Based on the Country selected on the Product Registration, Vault populates this field with the Agency assigned jurisdiction over that country.

Any configured reporting rules generate submissions to this agency when a Case Product references this Product Registration.
Local Datasheet
(datasheet__v)

Select the local Datasheet for this Product Registration. A local Datasheet is specific to a country or region, listing expected adverse events that apply to that product registration.

Vault uses Datasheets to detect expectedness for an adverse event and the suspect or interacting Case Products.
Registered As
(transmission_product_type__v)		 Select the product type for this registration from the picklist.

Vault maps this field when generating Transmissions for this registration, then uses that value to determine whether to export Device type of Combination Product Constituents on E2B transmissions.

For more information, see Exclude Device Constituents from E2B Exports.

When generating an FDA 3500A form for a non-Combination type of Company Product, this field determines which section of the form is populated, as follows:

  • If the Registered As field is set to Device or OTC Device, Vault populates the Suspect Medical Device sections.
  • If the Registered As field is not set to Device or OTC Device, Vault populates the Suspect Product(s) section.
  • If the Company Product has multiple FDA registrations (a device and a non-device, for example), Vault populates the Suspect Product(s) section.
  • If the Company Product has no FDA registration, Vault populates the Suspect Product(s) section.

For information on how the product type for a registration is used when evaluating reporting rules, see the Product Registration Type rule parameter.

This field does not appear on layouts by default, but you can add it to Transmission layouts. Depending on your configuration, this field may be labeled Transmission Product Type.
Default Registration
(default_registration__v)

Designates the registration as the most current or commonly used registration for the selected country.

If the registration is the most commonly used for the selected country, select the checkbox. During data entry, in the Case Product Registration field, this registration is prioritized in the picklist, though all active Product Registrations remain available for use.
### Make a Combination Product Registration Inactive You can set a _Product Registration_ record to a _Deleted_ state type so that the reporting rules engine no longer considers it when determining a _Case_'s reportability. With this setup, if the _Product Registration_ was used in any existing _Cases_, it is available for follow-up scenarios. #### Prerequisite To use this feature, you must enable Inactivate Product & Study Registrations. #### Make a Product Registration Inactive To make a _Product Registration_ inactive: 1. In the _Product Registration_ record, select the **State** button and select **Deprecated** from the picklist. Depending on your configuration, the inactive state may have a different label. 2. In the _Change Object Status_ dialog, select **Yes**. Similarly, if you need to reactivate the record, complete the steps detailed above but select **Active** from the picklist. ## Combination Product E2B Export Vault supports generating compliant FDA E2B(R2) and EMA E2B(R3) files for combination products, including device-related elements. For FDA E2B(R2) files, there is a separate section appended to the file for combination product elements. For EMA E2B(R3) files, combination product elements are nested under other sections. ## Exclude Device Constituents from E2B Exports E2B files generated for a _Combination Product Case_ include both _Device_ and _Drug_ types of _Product Constituents_. Because certain jurisdictions do not accept combination product submissions, you can configure a _Transmission_ to exclude _Device_ types of _Product Constituents_ from E2B files generated for _Combination Product_ reports. ### Prerequisites Ensure the following fields appear on layouts and the appropriate user groups have edit permissions: * **Product Registration**: _Registered As_ field (depending on your Admin's configuration, this field may be labelled _Transmission Product Type_) * **Study Registration**: _Transmission Product Type_ field * **Transmission Profile**: _Exclude Device Constituents by Default_ field ### Exclude Devices for Submissions To exclude device constituents, populate the **Registered As** field on Product Registrations and the **Transmission Product Type** field on Study Registrations to any _Transmission Product Type_ value other than _Combination Product_. If left blank, Vault continues to transmit device constituents by default. When evaluating reporting rules and generating submissions, Vault looks at the _Transmission Product Type_ on the _Product Registration_ or _Study Registration_ being used to generate each _Submission_. When evaluating whether to exclude the device constituents for a given jurisdiction, if there are multiple registrations, Vault applies the following logic:
Transmission Product Type Setting E2B Generation
Combination Product or blank on any Registration All Product Constituents are transmitted, including devices.
Any value other than Combination Product or blank on all Registrations Device-related data elements are omitted. Only non-device Product Constituents are transmitted.
If you're submitting a report to a destination where a product is not registered, you can use the _Exclude Device Constituents by Default_ field on a _Transmission Profile_ to specify how Vault should treat products in unregistered jurisdictions. ### Exclude Devices for Distributions The _Transmission Product Type_ on registrations are not used for _Distributions_. To omit device constituents, select the **Exclude Device Constituents by Default** checkbox on the _Transmission Profile_ corresponding to the _Distribution_. ## Frequently Asked Questions About Combination Products ### How does Vault calculate Expectedness for Combination Product Cases? For each _Case Assessment_ created for a _Product Constituent_ of a _Combination Product_, Vault calculates the expectedness using the _Datasheets_ related to the associated _Product_. ### Can I set up Watchlists for a Combination Product? Yes. You can create _Watchlists_ for _Combination Products_. When you add a _Combination Product_ to a watchlist, that watchlist applies to any _Case_ with _Product Constituents_ that belong to that _Combination Product_. However, if you create a watchlist for an individual _Product_ that happens to be a _Product Constituent_, the watchlist only tracks _Cases_ involving the standalone _Product_. ### How are Submissions generated for Cases concerning combination products? Vault uses _Combination Product Registrations_ to evaluate reporting obligations and the target health agency for _Submissions_. Vault assigns the appropriate _Transmission Profile_ and due dates for _Submissions_, based on the primary product type, report type, and product registration country. For example, for a _Case_ concerning a _Combination Product_ combining the drug Cholecap with the biologic Labrinone, both registered in the United States, Vault generates the following _Submissions_: * For the drug Cholecap, Vault generates a _Submission_ using the FDA E2B(R2) format and the CDER _Transmission Profile_. * For the biologic Labrinone, Vault generates a _Submission_ using the FDA E2B(R2) format and the CBER _Transmission Profile_. If configured by your Admin, Vault can also create _Transmissions_ for device constituents of combination products. ### How are Case reporting due dates calculated for combination products? {#case-reporting} For _Combination Products_ with a drug or biologic constituent and a device constituent, submissions adhere to the following due dates, based on the receipt date: * For a _Case_ classified as a public health risk, Vault generates a submission due in five (5) days. * For a non-serious _Case_ classified as a malfunction but not a public health risk, Vault generates a submission due in 30 days. * Otherwise, Vault generates a submission due in 15 days. Standard Reporting Rule Sets provides more information on the reporting timelines that Vault uses. ### Does Vault support FDA 3500A reporting elements for combination products? Yes. Vault generates compliant FDA 3500A forms for combination-type product submissions, including the required reporting elements for _Combination Products_. ### Does Vault support Device Only for combination products? No. A _Combination Product_ is a _Product_ containing multiple constituents and any combination of drug, device, and biologic components. Vault does not support configuring combination products as device only. [1]: #product-registration-fields [2]: #add-constituent [3]: #registered-as