Manage Combination Products

Learn how to configure combination products for case processing and submissions.

About Combination Products

Vault supports end-to-end case processing for postmarketing combination products, including those with device constituents. This capability includes submission rules that adhere to the FDA’s postmarketing safety reporting (PMSR) requirements for combination products. Combination products contain multiple constituents and any combination of drug, device, and biologic components. You can create combination products by applying the Combination Product object type to a Product.

You can set up and manage Combination Products with 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 Transmissions for each constituent part. A product constituent is a single drug, device, or biologic component within a combination product. In Vault, these are managed using the Product Constituent object.

When processing Inbox Items and Cases concerning a Combination Product, Vault downloads and 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:

Navigate to Business Admin > Objects > Products.
On the Products page, select Create.
In the Create Product window, select Combination Product, and then select Continue.
On the Create Combination Product page, complete the following fields:
- Organization: Select the organization to which the product belongs. For a Case Product to appear for selection on a Case, the organization must match.
- Product Name: Enter the primary name of the product. Vault references the product using the name that you enter in this field. When a Case Product references this Product, Vault uses this field to generate the Case Product Name.
- Combination Type: Select from the following options to describe the combination type:
  - Single Entity: Multiple components that are combined and produced into a single entity.
  - Co-Packaged: Multiple separate products that are packaged together into a single product.
  - Cross-Labelled: Multiple products that are 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, this field is used in report generation for FDA E2B(R2), FDA VAERS E2B(R3), and FDA MedWatch 3500A report formats.
- Manufacturer: Select the organization that manufactures the product, if it is different from that selected in the Organization field. For Device-type Products, this field is used in report generation for FDA E2B(R2), FDA VAERS E2B(R3), and FDA MedWatch 3500A report formats.
- Core Datasheet: Select the core Datasheet for the product family. Vault uses Datasheets to detect expectedness for an adverse event and the suspect or interacting Case Products.
Select Save.

Combination Product Constituents

Product constituents are the individual components that make up a combination product. When you add a Combination Product to your Vault, add the Product Constituents.

Note: Product Constituents reference Product records. Before you can add a Product Constituent, you must set up the Products.

Add a Product Constituent

To add a Product Constituent:

Navigate to the Combination Product to which you want to add the Product Constituent.
Expand Product Constituents and then select Create.
On the Create Product Constituent page, complete the following fields:
- Combination Product: The parent Combination Product for which this product is a constituent part. When you create the Product Constituent from the Combination Product record, Vault populates this field.
- Constituent Product: (Required) Select the Product, or select Create Product to add a new Product.
- Name: Enter the name of the product constituent as it should appear when being referenced throughout Vault.
- Product Type: Vault populates this field, based on the product type specified on the associated Product record. To edit this value, edit the Product record.
Select Save.

Combination Product Registrations

When an Inbox Item with a Combination Product is promoted to a Case, Vault uses the information entered in Product Registrations to populate certain fields, calculate expectedness, and generate transmissions.

When setting up Combination Products, we recommend that you add the following Product Registrations:

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.
Create additional Product Registrations for each Product Constituent. You can designate which constituent is the Primary Mode of Action (PMOA) using the PMOA field on the Product Registration, which designates the primary Case Product in Cases with Combination Products.

Note: Ensure each Combination Product is set up with a Product Registration designating the Product Constituent that is the PMOA. The PMOA registration is used to generate transmissions involving the Combination Product using the appropriate ICSR report type.

Add a Combination Product Registration

To add a Combination Product Registration:

Navigate to the Product to which you want to add the Product Registration.
Expand Registrations and then select Create.
On the Create Product Registration page, complete the applicable fields.
Select Save.

Product Registration Fields

Field	Description
Organization (`organization__v`)	Vault populates a link to the organization on the parent Product record. 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 a 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 record.
Product Type (`product_type__v`)	Vault populates this field with the product type of the parent Product record.
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`)	(Required) 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. Note: Removing the last remaining MAH/Reporting Organization from an MAH Distribution List also deletes the MAH Distribution list. Warning: Use caution when setting this field. Reporting obligations are for Distributions only and override agency submission rules. Do not select an agency such as the FDA or EMA.
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`)	Select Yes or No, depending on whether 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 field to the Case Product and uses the information in E2B report generation.
Agency (`agency__v`)	Based on the country selected on the Product Registration, Vault populates this field with the Agency assigned jurisdiction over that country. If 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 following options: Drug Biologic Device Vaccine Combination Product Nutritional Cosmetic OTC Drug OTC Device Vault maps this field when generating Transmissions for this registration, then uses that value to determine whether to export device-type 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 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 named 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 Safety Rule 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:

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.
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

By default, E2B files generated for a combination product case include both device-type and drug-type product constituents.

Because certain jurisdictions do not accept combination product submissions, you can configure a Transmission to exclude device-type 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:

The Registered As field on Product Registration layouts and the Transmission Product Type field on Study Registration layouts.
- Depending on your Admin’s configuration, this field may be named Transmission Product Type on Product Registration records.
The Exclude Device Constituents by Default field on Transmission Profile layouts.

Exclude Devices for Submissions

To exclude device constituents, set 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 field on the Transmission Profile corresponding to the Distribution.

Frequently Asked Questions About Combination Products

How does Vault automatically 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 will track only Cases involving the standalone Product.

Configure Adverse Event Watchlists provides more information about how to set up watchlists.

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. Based on the primary product type, report type, and product registration country, Vault assigns the appropriate Transmission Profile and due dates for submissions.

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.

How are Case reporting due dates calculated for combination products?

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.

Reporting Rule Sets provides more information on the reporting timelines that Vault uses.

Do we 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.

FDA MedWatch 3500A Generation Data Mapping provides more information about the 3500A formats that Vault supports.

Do we 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.