ModifiedBlue Cross Blue Shield - North CarolinaPolicy N/A

White Blood Cell Growth Factors “Notification” (PDF)

Defines medical necessity criteria, restricted products, FDA indications, dosing/HCPCS mappings, allowed indications, quantity/duration limits, applicable ICD-10 codes, and implementation/change history for white blood cell growth factors for Blue Cross NC (policy effective Jan 1, 2026). Part 1 of 2.

Policy Summary

PayerBlue Cross Blue Shield - North Carolina

PolicyWhite Blood Cell Growth Factors “Notification” (PDF)

Policy CodePolicy N/A

Change TypeCriteria and coding updates (modified trial/failure lists; HCPCS changes)

Effective DateJan 1, 2026

Next Review Date

Key ActionSubmit required medical documentation with prior authorization requests and include completed FDA MedWatch form when claiming trial/failure of preferred biosimilars.

SourceLink

POLICY UPDATE CHANGES

January 2026: Updated trial-and-failure requirements for pegfilgrastim biosimilars; Nyvepria added to restricted products; Fylnetra removed from restricted list (effective 1/1/2026).

April 2025: Added HCPCS Q5148 for Nypozi to dosing table (effective 4/1/2025).

Provider notification issued 10/1/2025 for policy changes effective 1/1/2026.

April 2025: Dosing table updated — Q5148 added for Nypozi; obsolete misc codes removed as of 3/31/2025.

January 2025: Coding update — C9173 used for Nypozi on 1/1/2025; prior misc code C9399 removed.

November 2024: Nypozi added as non-preferred filgrastim product requiring trial/failure of Nivestym and Zarxio; coding entries added.

July 2024: J9361 added for Ryzneuta; maximum units clarified/adjusted.

April 2024: Reclassified pegfilgrastim biosimilars (preferred vs non-preferred); Udenyca Onbody added as non-preferred (effective 4/1/2024).

February 2024: Ryzneuta introduced as non-preferred long-acting product with trial/failure requirement of Udenyca and Ziextenzo.

February 2022: Compendia support now requires NCCN 2A+; chemotherapy risk categories refined and maximum units added.

MultipleRestricted products listed

24 wksDuration of approval

FDA/NCCNAllowed evidence sources

MultipleProduct HCPCS codes tracked

NCCN ≥2ACompendia requirement

ICD-10 rangesApplicable diagnosis codes

Coverage summary

This coverage policy (effective 2026-01-01, last reviewed 2026-01) defines medical necessity criteria, FDA-approved indications, dosing/HCPCS mappings, and product-specific restrictions for white blood cell growth factors (G-CSF and GM-CSF). Covered products include pegfilgrastim products (Neulasta; Neulasta OnPro; biosimilars Fulphila, Fylnetra, Nyvepria, Stimufend, Udenyca/Udenyca Onbody, Ziextenzo), filgrastim products (Neupogen; biosimilars Nivestym, Zarxio, Releuko, Nypozi), tbo-filgrastim (Granix), eflapegrastim (Rolvedon), efbemalenograstim (Ryzneuta), and sargramostim (Leukine) with HCPCS codes tracked per the dosing/coding table (examples: J2506, Q5122, Q5111, Q5120, J1442, Q5148, Q5125, J1447, J1449, J9361, J2820).

The policy scope covers FDA-approved uses and mapped dosing: primary and secondary prophylaxis of febrile neutropenia (FN), treatment of FN, mobilization of hematopoietic progenitor cells, bone marrow transplant (BMT) support (autologous/allogeneic), management of chronic/severe neutropenia, acute hematopoietic radiation exposure (H-ARS), and other hematologic indications when supported by FDA labeling or NCCN compendia (NCCN evidence rating ≥2A required). Quantity/duration limits follow FDA labeling or NCCN 1/2A dosing, with a policy duration of approval of 24 weeks and product-specific maximum units (e.g., Ryzneuta maximum units = 960).

Medical necessity criteria (by product/class and indication)

Product-specific trial and failure requirements (summary of recent changes)

Coverage of specific long-acting pegfilgrastim and short-acting filgrastim biosimilars is conditional on trial and failure of preferred products as specified:

Long-acting pegfilgrastim non-preferred trial/failure requirements

January 2026 requirement (effective 1/1/2026): Trial and failure of preferred pegfilgrastim biosimilar products to include Fylnetra and Fulphila is required prior to coverage of certain non-preferred pegfilgrastim biosimilars (Nyvepria, Stimufend, Udenyca/Udenyca Onbody, Ziextenzo)
Policy notification 10/1/2025 for effective date 1/1/2026
April 2024 requirement (effective 4/1/2024): Trial and failure of preferred pegfilgrastim biosimilar products to include Fulphila and Nyvepria prior to coverage of certain non-preferred pegfilgrastim biosimilars (Fylnetra, Stimufend, Udenyca/Udenyca Onbody, Ziextenzo)
Given 1/8/2024 for effective date 4/1/2024
February 2024 requirement (effective 4/1/2024 per notice): For Ryzneuta (efbemalenograstim alfa-vuxw) as a non-preferred long-acting product, trial and failure of both Udenyca and Ziextenzo required
Effective per notice 4/1/2024

Supporting evidence / compendia requirement (Feb 2022 change)

Supporting compendia and chemotherapy risk definitions: Supporting compendia citations must have NCCN evidence rating of 2A or higher to support use; Chemotherapy risk category definitions are applied corresponding to use of WBC growth factors for primary prophylaxis of febrile neutropeniaNCCN 2A+

Chemotherapy risk categories defined per Carelon Febrile Neutropenia Risk Guidelines

HCPCS and ICD-10 codes referenced

Pegfilgrastim (Neulasta) HCPCSHCPCSCovered

J2506

pegfilgrastim (Neulasta) SC injection

Pegfilgrastim biosimilars HCPCSHCPCSCovered

Q5122	pegfilgrastim-apgf (Nyvepria) SC injection
Q5127	pegfilgrastim-fpgk (Stimufend) SC injection
Q5111	pegfilgrastim-cbqv (Udenyca) SC injection
Q5120	pegfilgrastim-bmez (Ziextenzo) SC injection

Filgrastim HCPCSHCPCSCovered

J1442	filgrastim (Neupogen) IV or SC
Q5148	filgrastim-txid (Nypozi) IV or SC
Q5125	filgrastim-ayow (Releuko) IV or SC
J1447	tbo-filgrastim (Granix) SC injection

Eflapegrastim and efbemalenograstim HCPCSHCPCSCovered

J1449	eflapegrastim-xnst (Rolvedon) SC injection
J9361	efbemalenograstim alfa-vuxw (Ryzneuta) SC injection

Sargramostim HCPCSHCPCSCovered

J2820

sargramostim (Leukine) IV/SC

Other applicable HCPCS (policy note)HCPCS

S0353	Other code referenced as applicable to policy
S0354	Other code referenced as applicable to policy

ICD-10 codes applicableICD-10

C00.0-C49.9	Malignancies range
C4A.0-C4A.9	Malignancies range
C50.011-C79.9	Breast and metastatic malignancy range
C7A.00-C7A.8	Hematologic malignancy range
C7B.00-C7B.8	Hematologic malignancy range
C80.0-C86.6	Malignancy range
C88.2-C96.Z	Malignancy range
D00.00-D09.9	In-situ neoplasms range
Z51.11	Encounter for antineoplastic chemotherapy
Z51.12	Encounter for antineoplastic immunotherapy

HCPCS codes referenced in dosing table (includes product-specific codes added/removed over time)HCPCS

J9361	Ryzneuta (efbemalenograstim alfa-vuxw) SC injection
Q5148	Nypozi (added 4/1/2025)
C9173	HCPCS previously used for Nypozi (historical)
J1449	Rolvedon (added 4/1/2023)
Q5127	Stimufend (added 4/1/2023)
Q5130	Fylnetra (added 4/1/2023)
Q5125	Releuko (added 10/1/2022)
C9096	Releuko (earlier coding, 7/1/2022)
J2506	Neulasta pegfilgrastim code (replaced prior code)
S0353	Other HCPCS code applicable to policy

1–10 of 15

1/2

HCPCS code for Ryzneuta maximum unitsHCPCS

J9361

Maximum Units = 960 (per dosing reference table)

ICD-10 codes applicable to this policyICD-10

C00.0-C49.9	Malignant neoplasms
C4A.0-C4A.9	Malignant neoplasms
C50.011-C79.9	Breast and other malignancies
C7A.00-C7A.8	Hematologic malignancies
C7B.00-C7B.8	Hematologic malignancies
C80.0-C86.6	Malignant neoplasms
C88.2-C96.Z	Malignant neoplasms
D00.00-D09.9	In situ neoplasms
Z51.11	Encounter for antineoplastic chemotherapy
Z51.12	Encounter for antineoplastic immunotherapy

Prior authorization, documentation, and billing actions

Prior Authorization

Authorization required for restricted products

Requests for restricted products require that the request meet the policy's medical necessity criteria and include submission of supporting medical documentation. Some requests (for biosimilar trial/failure or certain product adverse events) specifically require a completed FDA MedWatch form (copy) be provided before an authorization will be considered.

Documentation Required

MedWatch adverse event reporting required for biosimilar trial failure

When a prescriber claims trial/failure of preferred biosimilar products due to an adverse event, the prescriber must complete and submit an FDA MedWatch Adverse Event Reporting Form and provide a copy of the completed form with the authorization request; authorizations will not be considered unless the form is completed and submitted to the FDA.

Background and evidence sources

This policy covers listed pegfilgrastim (long-acting) and filgrastim/tbo-filgrastim/GM-CSF products, mapping each to FDA labeling, typical dosing and HCPCS codes used for billing (examples: pegfilgrastim SC 6 mg once per cycle mapped to J2506 or biosimilar Q-codes; filgrastim IV/SC starting 5 mcg/kg/day mapped to J1442; Nypozi filgrastim-txid mapped to Q5148; Ryzneuta mapped to J9361). The intent is to ensure coverage aligns with FDA indications, product labeling, and to impose product-specific trial/failure requirements for non-preferred or restricted products as specified in the policy.

Evidence sources supporting the policy are FDA package inserts (primary source) and, for non-FDA uses or additional indications, nationally recognized compendia with an NCCN evidence rating of 2A or higher required. The policy includes implementation history and recent material changes (for example, January 2026 changes to preferred/non-preferred pegfilgrastim biosimilar trial requirements) and instructs providers to follow the current dosing/coding table and prior authorization/documentation requirements (including MedWatch submission for biosimilar adverse events).

Revision history (material changes)

2026-01-01revisedLatest

January 2026: Material change — trial and failure requirement for preferred pegfilgrastim biosimilars updated to require trial of Fulphila and Fylnetra prior to coverage of specified non-preferred pegfilgrastim biosimilars (Nyvepria, Stimufend, Udenyca/Udenyca Onbody, Ziextenzo). Nyvepria added to restricted products; Fylnetra removed from restricted products (now unrestricted). Policy notification given 10/1/2025 for effective date 1/1/2026.

2025-04-01coding_change

April 2025: Coding change — HCPCS Q5148 added for Nypozi (filgrastim-txid) to dosing reference table effective 4/1/2025; obsolete codes C9173, J3490, J3590, and J9999 termed 3/31/2025.

Policy Summary

PayerBlue Cross Blue Shield - North Carolina

PolicyWhite Blood Cell Growth Factors “Notification” (PDF)

Policy CodePolicy N/A

Change TypeCriteria and coding updates (modified trial/failure lists; HCPCS changes)

Effective DateJan 1, 2026

Next Review Date

Key ActionSubmit required medical documentation with prior authorization requests and include completed FDA MedWatch form when claiming trial/failure of preferred biosimilars.

SourceLink

On This Page

November 2024 (Nypozi): Nypozi (filgrastim-txid) classified as non-preferred short-acting/filgrastim product requiring trial and failure of both Nivestym and Zarxio

Historical product classification note: Products classified as restricted were historically listed (e.g., Nyvepria, Udenyca/Udenyca Onbody, Ziextenzo at various times); product classifications have changed over time — consult current dosing/coding table for product-specific restrictions

See dosing/coding table for current status

Documentation Required

NCCN support documentation

If relying on NCCN supporting recommendations, medical record documentation demonstrating that ALL NCCN 1 or 2A requirements are met must be provided with the request.

Billing Rule

Quantity and duration limits

Requested quantity and treatment duration must be within the FDA-labeled dosing for the requested indication or NCCN 1/2A supported dosing and must not exceed the policy's maximum units for the duration of approval. Duration of approval is 24 weeks.

Documentation Required

Trial and failure documentation for non-preferred products

Providers must document trial and failure of the specified preferred biosimilar products (as listed in the policy) before coverage of non-preferred pegfilgrastim or filgrastim products will be authorized. Provide clinical documentation showing the required trials and failures per the product-specific trial-and-failure requirements.

J9361
Q5148
J1449
Q5127
Q5130
Q5125
J2506

Prior Authorization

Prior notification / policy implementation dates

Policy notifications were provided in advance of effective dates; providers should obtain prior authorization per plan requirements for products listed as non-preferred or restricted.

Notification 10/1/2025 for effective date 1/1/2026
Example notification 5/2/2023 for effective date 7/1/2023

Billing Rule

Use current HCPCS codes per effective dates

Report the HCPCS code corresponding to the specific product and the applicable effective date per the dosing/coding reference table. Obsolete miscellaneous HCPCS codes were deleted and should not be used after the noted deletion dates.

C9399
J3490
J3590
J9999

January 2025: Coding change — HCPCS C9173 added for Nypozi effective 1/1/2025; C9399 deleted (termed 12/31/2024).

2024-11revised

November 2024: Material change — added Nypozi (filgrastim-txid) as a non-preferred short-acting filgrastim product requiring trial and failure of both Nivestym and Zarxio; associated dosing table updates and HCPCS codes added.

2024-07-01coding_change

July 2024: Coding change — HCPCS J9361 added for Ryzneuta effective 7/1/2024; maximum units for Ryzneuta adjusted.

2024-04-01revised

April 2024: Material change — preferred/non-preferred classifications for pegfilgrastim biosimilars modified (Fulphila and Nyvepria as preferred; Fylnetra, Stimufend, Udenyca/Udenyca Onbody, Ziextenzo non-preferred). Udenyca Onbody added as non-preferred similar to Neulasta OnPro. Policy notification given 1/8/2024 for effective date 4/1/2024.

2024-02added

February 2024: Material change — Ryzneuta (efbemalenograstim alfa-vuxw) added as a non-preferred long-acting product requiring trial and failure of Udenyca and Ziextenzo; coding entries added (policy notice dated 1/8/2024 for effective 4/1/2024).

2022-02-15revised

February 2022: Material change — added requirement that supporting compendia have NCCN evidence rating of 2A or higher and adjusted chemotherapy risk category definitions; policy notification given 12/17/2021 for effective date 2/15/2022.