CurrentCapital BluecrossPolicy MP 2.383

Orphan Drugs and Humanitarian Use Device (HUD)

Covers medical necessity criteria and coverage considerations for FDA-designated orphan drugs and Humanitarian Use Devices when no other Capital BlueCross medical policy applies; affects providers submitting requests for these products under applicable Capital BlueCross benefit programs.

Policy Summary

PayerCapital Bluecross

PolicyOrphan Drugs and Humanitarian Use Device (HUD)

Policy CodePolicy MP 2.383

Change TypeRoutine review — no material changes

Effective DateAug 1, 2025

Next Review Date

Key ActionSubmit prior authorization demonstrating FDA orphan designation and marketing approval for orphan drugs or HDE and IRB oversight for HUDs.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

FDA orphanOrphan designation required

FDA approvalMarketing approval required

IRB oversightHUD coverage condition

≤8,000/yrHUD threshold

When no other policy

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Coverage Criteria

inv-01: Orphan Drug — Covered when ALL of the following are met:

Orphan Drug — Covered when ALL of the following are met:

Orphan drug coverage criteria: Drug has FDA Orphan Drug designation; Drug is listed on the FDA website as a designated orphan product with marketing approval; Drug has FDA marketing approval; Prescribed for a member who is a medically appropriate candidate; Use is consistent with peer-reviewed published medical literature or other appropriately recognized resources (e.g., NCCN, AHFS, Micromedex, ICER); Use is consistent with FDA-approved indications.

All conditions required

inv-02: Humanitarian Use Device (HUD) — Covered when ALL of the following are met:

Humanitarian Use Device (HUD) — Covered when ALL of the following are met:

HUD coverage criteria: FDA has designated the device as a Humanitarian Use Device (HUD); Device has FDA-approved Humanitarian Device Exemption (HDE); Device is used at facilities that have Institutional Review Board (IRB) oversight and approval; Use is consistent with FDA-approved indications; Device is prescribed for a member who is a medically appropriate candidate.

All conditions required

All other uses of a drug designated as an orphan product or a device designated as a Humanitarian Use Device (HUD) that do not meet the specific coverage criteria listed above are considered investigational.

Uses that are not consistent with FDA‑approved indications or that are not supported by peer‑reviewed published medical literature or other appropriately recognized resources (for example, NCCN, AHFS, Micromedex, ICER) are considered investigational and not medically necessary under this policy.

Initial Therapy Criteria

inv-15: Orphan drug initial coverage requirements

Orphan drug initial coverage requirements

Orphan drug initial: Drug has FDA Orphan Drug designation; Drug is listed on the FDA website as a designated orphan product with marketing approval; Drug has FDA marketing approval; Prescribed for a member who is a medically appropriate candidate; Use is consistent with peer-reviewed published medical literature or other appropriately recognized resources (e.g., NCCN, AHFS, Micromedex, ICER); Use is consistent with FDA-approved indications.

See coverage criteria above

Coding and Definitions

Coding guidance (not a code list)mixed

No codes listed

HUD population threshold

HUD population thresholdNot more than 8,000 individuals in the United States per year

Regulatory basisDefined by FDA under the Humanitarian Device Exemption (HDE) provisions (Section 520(m) of the FD&C Act)

Implication for coverageDevices meeting the HUD threshold may qualify for HDE marketing pathway and are assessed on probable benefit vs. risk rather than full effectiveness demonstration

Provider Actions and Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required when coverage is requested for an orphan drug or a Humanitarian Use Device (HUD). Requests must document the drug or device's FDA designation/approval and demonstrate that the proposed use is consistent with FDA-approved indications and supporting clinical evidence.

Applies to requests for orphan drugs and HUDs
Include FDA designation/approval documentation

Denial Risk

Triggers for Denial

Requests may be denied if the orphan drug or HUD lacks FDA designation or marketing approval, if use is inconsistent with FDA‑approved indications, or if supporting clinical evidence and authoritative references (e.g., peer‑reviewed literature, NCCN, AHFS, Micromedex, ICER) are not provided.

No FDA orphan designation or HDE/marketing approval

Definitions

Orphan Drug / Rare Disease

DefinitionA drug or biologic for prevention, diagnosis, or treatment of diseases or conditions affecting fewer than 200,000 persons in the United States or where there is no reasonable expectation that the cost of developing and making the drug available will be recovered from U.S. sales

Designating authorityDesignation is granted by the FDA Office of Orphan Products Development (OOPD)

Regulatory statusOrphan drugs may be FDA approved for marketing or may remain experimental; a list of designated orphan products with marketing approval is maintained by the FDA

Humanitarian Use Device (HUD) / Humanitarian Device Exemption (HDE)

DefinitionA Humanitarian Use Device (HUD) is a medical device intended to benefit patients with a disease or condition that affects not more than 8,000 individuals in the United States per year

FDA pathway (HDE)

Site of Care

Note

Use HUDs only at IRB‑oversight facilities

HUDs must be used only at facilities that have Institutional Review Board (IRB) oversight and approval; include confirmation of the facility’s IRB oversight in the request.

Background

Orphan drugs are intended to prevent, diagnose, or treat diseases or conditions that affect a relatively small population. By FDA definition, an orphan drug targets a disease or condition that affects fewer than 200,000 persons in the United States or a condition where recovery of development costs is unlikely. These products may receive orphan designation from the FDA Office of Orphan Products Development to encourage development for rare diseases; coverage under this policy requires the drug to also have FDA marketing approval and meet the other criteria specified in the policy.

Policy Summary

PayerCapital Bluecross

PolicyOrphan Drugs and Humanitarian Use Device (HUD)

Policy CodePolicy MP 2.383

Change TypeRoutine review — no material changes

Effective DateAug 1, 2025

Next Review Date

Key ActionSubmit prior authorization demonstrating FDA orphan designation and marketing approval for orphan drugs or HDE and IRB oversight for HUDs.

SourceLink

On This Page

Use inconsistent with FDA‑approved indications

Insufficient supporting clinical evidence or authoritative references

Documentation Required

Required Documentation

For HUDs, include documentation of Institutional Review Board (IRB) oversight/approval and evidence that use is consistent with FDA‑approved indications. For orphan drugs include FDA Orphan Drug designation and FDA marketing approval documentation. In all cases submit supporting clinical evidence and/or citations to recognized resources (e.g., peer‑reviewed literature, NCCN, AHFS, Micromedex, ICER).

HUD: IRB oversight/approval documentation and HDE details
Orphan drug: FDA Orphan Drug designation listing and FDA marketing approval
Supporting references: peer‑reviewed literature or recognized drug/device resources

Step Therapy

Step Therapy Cross‑Reference

Refer to the related step therapy policy for cancer treatment sequences. This policy does not enumerate step therapy sequences itself; see MP 2.373 Step Therapy Treatment in Cancer for applicable step requirements.

Cross-reference: MP 2.373 for cancer treatment step therapy requirements

Humanitarian Device Exemption (HDE) is the marketing application for a HUD (Section 520(m) of the FD&C Act) and is exempt from the usual effectiveness requirements; approval is based on probable benefit outweighing risk

Use restrictionsHDE approval is subject to certain conditions and use restrictions and considers probable risks and benefits compared with available alternatives

Institutional Review Board (IRB)

DefinitionAn Institutional Review Board (IRB) is an appropriately constituted group formally designated to review and monitor biomedical research involving human subjects

AuthorityThe IRB has the authority to approve, require modifications to secure approval, or disapprove research

Role for HUD useIRB oversight and approval is required for use of HUDs at facilities and serves to protect the rights, safety, and welfare of human research subjects