Sections in This Article
- About Cross Reporting
- Cross Reporting for Non-Company Sponsored Products and Studies
- Cross Reporting in FDA Reporting Rule Set
- Enable Cross Reporting Vault Setting
- Enable Same Agency Cross Reporting
- Cross Reporting Scenarios
- Registration Categories: Investigational vs. Marketing
- Cross Reporting Evaluation of Expectedness Rule Parameter
- Cross Reporting Substance Matching
About Cross Reporting
In extension to the general reporting rules engine, Vault Safety supports evaluating rules for cross reporting scenarios. The following list describes the difference between general and cross reporting:
- In general reporting, the system evaluates either Study or Product Registrations depending on the report type and study type of the case. In other words, the system generates either investigational or marketing reports, not both.
- For cross reporting, the system evaluates additional investigational or marketing registrations, based on where the company products on the Case (or their Substances) are marketed or investigated worldwide. Cross reporting obligations are evaluated after Submissions are generated for general reporting.
Vault Safety supports the following scenarios to automatically generate additional Submissions for cross reporting:
| Scenario | Description |
|---|---|
| Investigational to Marketing | After generating a Submission for a Clinical Trial Case A Case is categorized as a clinical trial case when the Case Report Type is "Study" and the Study Type is "Clinical Trial" or unspecified (blank). per its Study Registrations (general reporting), the system evaluates whether any company Case Products, or their Substances, are marketed elsewhere. This scenario is supported for both same-agency (e.g. FDA IND-to-NDA) and cross-agency reporting. |
| Investigational to Investigational | After generating a Submission for a Clinical Trial Case A Case is categorized as a clinical trial case when the Case Report Type is "Study" and the Study Type is "Clinical Trial" or unspecified (blank). per its Study Registrations (general reporting), the system evaluates whether any company Case Products, or their Substances, are investigated in other studies. |
| Marketing to Marketing | After generating a Submission for a Postmarket Case A Case is defined as postmarket when the Case has either a non-Study Report Type (spontanous case) or a postmarket Study Type (postmarket study case). per its Product Registrations, the system evaluates whether any company Case Products or their Substances, are marketed elsewhere. |
| Marketing to Investigational | After generating a Submission for a Postmarket Case A Case is defined as postmarket when the Case has either a non-Study Report Type (spontanous case) or a postmarket Study Type (postmarket study case). per its Product Registrations, the system evaluates whether the company Case Products, or their Substances, are investigated elsewhere. |
The Reporting Scenario parameter on a Reporting Rule controls whether one or more cross reporting scenarios apply to a rule. Certain rules in the FDA Reporting Rule Set support cross reporting. Cross reporting scenarios can be added to additional rules using the Reporting Scenario parameter. Contact Veeva Services for assistance in adding custom cross reporting rules.
During cross reporting evaluations, the system uses the registration category to match the relevant cross reporting scenarios. Product and Study Registrations can be categorized as Investigational or Marketing.
Generated Submissions must have a unique mapping to a Transmission Profile. In other words, the system does not generate multiple Submissions using the same Transmission Profile.
On a system-generated Submission, the Transmission Message attachment contains a SafetyRuleLog audit log for the reporting rules and scenarios evaluated.
Cross Reporting for Non-Company Sponsored Products and Studies
Vault Safety supports the configurable generation of Cross Reports for Non-Company Sponsored Studies and Products.
Business Admins can specify a Study as a Non-Company Sponsored Study. The system will then consider Investigational→Investigational and Investigational→Marketing (Cross-Agency) cross reporting scenarios for the products within the Study.
Similarly, Business Admins can specify a Product as a Non-Company Product. The system will then consider Marketing→Investigational and Marketing→Marketing (Cross-Agency) cross reporting scenarios for the Product.
Note Vault Safety will not generate cross reports for any Study or Product that is not marked as Non-Company Sponsored and that does not have at least one registration.
Cross Reporting in FDA Reporting Rule Set
Cross reporting is supported for version 3 of the FDA ICSR Reporting Rule Set.
The Active Rule Version on the Safety Rule Set must be set to 3 to activate the cross reporting scenarios. See Manage Reporting Rule Versions for more information.
The following FDA Safety Rules evaluate the Investigational to Marketing (same agency) scenario:
- Downgrade to Non-Serious
- Downgrade to SAE
- SUSAR
- SUSAR (Death)
- SUSAR (Life Threatening)
Enable Cross Reporting Vault Setting
Cross reporting is turned on and off through an application setting.
To turn on cross reporting in your Vault, go to Admin > Settings > ICSR Reporting Settings, and then ensure the Cross-Reporting checkbox is selected.
Enable Same Agency Cross Reporting
The Inv. to Marketing (same agency) field on an Agency determines whether the system can generate two Submissions to the same agency for cross reporting.
This field is enabled for the FDA by default. An admin can enable this field on additional agencies if required.
Cross Reporting Scenarios
Each reporting rule can specify the reporting scenarios it supports using the Reporting Scenario rule parameter.
For same-agency reporting, two Submissions can be generated for the same reporting destination (for example, FDA IND-to-NDA). For cross-agency reporting, the system ensures only one Submission per reporting destination is generated.
Note When generating Submissions for cross reporting, the system ensures only one Submission per registration type (Investigational or Marketing) and Agency is generated. In the event that an Agency has both X→Investigational and X→ Marketing reporting obligations then the system uses the Cross Report Priority field (if enabled) on the Agency to prioritize which Submissions to an agency are generated. See Add an Organization for the options available for this field.
The following cross reporting scenarios are supported:
- 1. Investigational to Marketing (same agency)
This scenario applies to Clinical Trial Cases A Case is categorized as a clinical trial case when the Case Report Type is "Study" and the Study Type is "Clinical Trial" or unspecified (blank). containing Case Products or Substances marketed in the same jurisdiction where they are being investigated.
Note The Inv. to Marketing (same agency) setting must be enabled on the target Agency for this cross reporting scenario to execute.
Investigational to Marketing (Same Agency) Cross Reporting 
The system generates Investigational Submissions for the applicable agencies, based on the Study Registration countries (general reporting scenario).
The system queries each company Case Product with a Drug Role of "Suspect" or "Interacting" to find Marketing Registrations from the following sources:
- The Case Product's Product Registrations.
If the Case Product is part of a Combination Product, the system queries the Combination Product's Registrations instead. The Combination Product Registration designated as the PMOA PMOA stands for Primary Mode of Action and identifies which constituent part provides the primary therapeutic action of the combination product. In Vault Safety, Product Constituents are set as PMOA through the PMOA field on the Product Registration. takes precedence above other registrations. - The Product Registrations of any company Product that shares the same Product Substance (active ingredient) with the Case Product.
- The Case Product's Product Registrations.
The system generates Marketing Submissions for Product Registrations that share the same reporting destination as the Investigational Submissions generated by the general reporting scenario.
To generate these Submissions, a matching Transmission Profile must exist.
Note If Most Conservative Product Criteria is selected, when evaluating cross reportable registrations, only shared products or product substances are considered as eligible products.
- 2. Investigational to Marketing (cross agency)
This scenario applies to Clinical Trial Cases A Case is categorized as a clinical trial case when the Case Report Type is "Study" and the Study Type is "Clinical Trial" or unspecified (blank). containing Case Products or Substances marketed in a different jurisdiction than where they are being investigated.
Investigational to Marketing (Cross Agency) Cross Reporting - The system generates Investigational Submissions for the applicable agencies, based on the Study Registration countries (general reporting scenario).
- The system queries each company Case Product with a Drug Role of "Suspect" or "Interacting" to find Marketing Registrations from the following sources:
- The Case Product's Product Registrations.
If the Case Product is part of a Combination Product, the system queries the Combination Product's Registrations instead. The Combination Product Registration designated as the PMOA PMOA stands for Primary Mode of Action and identifies which constituent part provides the primary therapeutic action of the combination product. In Vault Safety, Product Constituents are set as PMOA through the PMOA field on the Product Registration. takes precedence above other registrations. - The Product Registrations of any company Product that shares the same Product Substance (active ingredient) with the Case Product.
- The Case Product's Product Registrations.
- The system generates Marketing Submissions for Product Registrations with reporting destinations that are different from the Investigational Submissions generated by the general reporting scenario.
To generate these Submissions, a matching Transmission Profile must exist.
Note If Most Conservative Product Criteria is selected, when evaluating cross reportable registrations, only shared products or product substances are considered as eligible products.
- 3. Investigational to Investigational (cross agency)
For Clinical Trial Cases A Case is categorized as a clinical trial case when the Case Report Type is "Study" and the Study Type is "Clinical Trial" or unspecified (blank). , after generating a Submission for the Study Registration (general reporting), the system determines whether any company Case Products, or their Substances, are being investigated or used as comparators in another Study with an Investigational registration in different jurisdictions.
If so, the system generates Submissions for the additional Study with unique reporting destinations.
Note If Most Conservative Product Criteria is selected, when evaluating cross reportable registrations, only shared products or product substances are considered as eligible products.
- 4. Marketing to Marketing (cross agency)
For Postmarket Cases A Case is defined as postmarket when the Case has either a non-Study Report Type (spontanous case) or a postmarket Study Type (postmarket study case). , after generating a Submission for a company Case Product, the system determines whether the Substance (active ingredient) is shared by any company Products with a Marketing Registration in different jurisdictions.
If so, the system generates Submissions for the other company Product with unique reporting destinations.
Note If Most Conservative Product Criteria is selected, when evaluating cross reportable registrations, only shared products or product substances are considered as eligible products.
- 5. Marketing to Investigational (cross agency)
For Postmarket Cases A Case is defined as postmarket when the Case has either a non-Study Report Type (spontanous case) or a postmarket Study Type (postmarket study case). , after generating a Submission for a company Case Product, the system determines whether that Product, or its Substance (active ingredient), is being investigated or used as comparators in another Study with Investigational registrations in different jurisdictions.
If so, the system generates Submissions for the Study with unique reporting destinations.
Note If Most Conservative Product Criteria is selected, when evaluating cross reportable registrations, only shared products or product substances are considered as eligible products.
Registration Categories: Investigational vs. Marketing
A registration can be assigned the Investigational or Marketing category. You can select the Registration Type (registration_type__v) on a Study or Product Registration.
On a Registration Type Controlled Vocabulary, the Registration Category field identifies whether a registration category is Investigational or Marketing.
The following table outlines the system-managed Registration Types and their Registration Category:
| Registration Type | API Name | Registration Category |
|---|---|---|
| Marketing Authorisation Application (MAA) | maa_v |
Marketing |
| Clinical Trial Application (CTA) | cta__v |
Investigational |
| New Drug Application (NDA) | nda__v |
Marketing |
| Abbreviated New Drug Application (ANDA) | anda__v |
Marketing |
| Biologic License Application (BLA) | bla__v |
Marketing |
| Investigation New Drug Application | ind__v |
Investigational |
| Premarket Approval Application (PMA) | pma__v |
Marketing |
| Premarket Notification 510k (510k) | 510k__v |
Marketing |
| Humanitarian Device Exemption (HDE) | hde__v |
Marketing |
If a Registration Type is not specified, the system uses the following logic to classify the Registration Category for Study Cases:
- Investigational: When the Case Study Type is "Clinical Trial" or blank.
- Marketing: When the Case Study Type is any other value, such as Individual Patient Use or Other Study.
Note Study Products with a Study Product Role of 'Investigational' or 'Active Comparator' are considered to be investigational medicinal products.
Cross Reporting Evaluation of Expectedness Rule Parameter
The Cross Reporting without Datasheet Expectedness Substitution ICSR setting determines how the rule engine evaluates the Expected rule parameter for cross reporting scenarios where additional products are found through a Substance lookup.
Note To use this feature, your Admin must enable Cross Reporting without Expectedness Substitution.
If this setting is enabled, the rule engine calculates expectedness in the same way as for General Reporting (that is, without substitution based on cross reportable Datasheets). See the Expected rule parameter help for more information on how General Reporting calculates expectedness.
If this setting is not enabled, the rule engine uses the following logic to calculate expectedness:
- Determines if there are other company Products with the same Substance that have an associated marketing Product Registration.
- If so, the system evaluates expectedness using the Local and Core Datasheets for that company Product.
- If there are no Product Datasheets, the system uses the value from the Expected field on the relevant Case Assessment.
- Determines if there are clinical trial Studies where company Case Products or their Substances have an associated investigational Study Registration.
- If so, the system evaluates expectedness using the Study Product and Study Core Datasheets, if available, otherwise the system uses the Core Datasheet of the substituted product.
- If there are no Study Product, Study, or Product Core Datasheets, the system uses the value from the Expected field on the relevant Case Assessment.
Cross Reporting Substance Matching
Vault Safety supports the following methods of Substance matching when determining the cross reporting obligations for an Agency based on Case Product substances:
| Matching Method | Description |
|---|---|
| Exact Matching | This method is the most restrictive. The cross-reportable Product must include the exact same Substance list as the Case Product. |
| Subset Matching | The cross-reportable Product must include all of the Substances within the Case Product. The cross-reportable Product may include additional Substances in this scenario. Subset matching includes Exact matching scenarios. |
| Partial Matching | This method is the least restrictive. The cross-reportable Product must include at least one of the same Substances as the Case Product. Partial matching includes both Subset and Exact matching scenarios. |
A Business Admin can set the Substance matching method for an Agency using the Cross Reporting Substance Lookup Method field.
The following sections describe each of the available Substance-matching methods.
Exact Matching Method (Most Restrictive)
For an Agency using the Exact Matching method, the system reports to the Agency if the cross-reportable Product contains the exact same Substance list as the Case Product.
The example shown below includes the following criteria:
- All of the Agencies with potentially cross-reportable Products are using the Exact Matching method.
- Product C contains the exact same Substance list as Product A, but Products B and D do not.
As a result, Vault Safety sends a report to the Agency that Product C is registered with for any Cases containing Product A. Reports are not sent to Agencies with only Products B and D registered.
Subset Matching Method
For an Agency using the Subset Matching method, the system reports to the Agency if the cross-reportable Product contains all of the same substances as the Case Product.
The example shown below includes the following criteria:
- All of the Agencies with potentially cross-reportable Products are using the Subset Matching method.
- Products B and C contain all the Substances of Product A, but Product D does not.
As a result, Vault Safety sends a report to the Agencies that Product B and C are registered with for any Cases containing Product A.
Partial Matching Method (Least Restrictive)
For an Agency using the Partial Matching method, the system reports to the Agency if the cross-reportable Product contains at least one of the same Substances as the Case Product.
The example shown below includes the following criteria:
- All of the Agencies with potentially cross-reportable Products are using the Partial Matching method.
- Products B, C, and D each contain at least one of the Substances of Product A.
As a result, Vault Safety sends a report to the Agencies that Product B, C, and D are registered with for any Cases containing Product A.
