HCPCS
J0567
1 mg = 1 unit
Phase 1
Identify what you're billing
Confirm CLN2 disease (TPP1 enzyme deficiency + molecular), age ≥3 yr, ICV reservoir placed and patent, baseline CLN2 motor function documented.
CNS-route ERT class context — Brineura vs Spinraza FDA labels verified May 2026
Two CNS-route drugs in the catalog. Both bypass the blood-brain barrier. Routes, devices, and CPT codes differ entirely.
Brineura is the catalog's only intracerebroventricular (ICV) drug. The closest billing analog is Spinraza, which is intrathecal via lumbar puncture — a different CNS route, different device, different CPT. Both are mechanism-unique in their indication (no biosimilar, no therapeutic equivalent), both bypass the blood-brain barrier because the target tissue is CNS, and both require specialty pediatric centers for administration. The distinctions matter for prior authorization, claim submission, and denial diagnosis.
| Brineura (J0567) | Spinraza (J2326) | |
|---|---|---|
| Mechanism | Enzyme replacement therapy — recombinant human TPP1 | Antisense oligonucleotide — SMN2 splice modifier |
| Disease target | CLN2 disease (TPP1 deficiency / Batten / late-infantile NCL) | Spinal muscular atrophy (SMN1 biallelic loss) |
| Route | Intracerebroventricular (ICV) — via implanted reservoir into lateral cerebral ventricle | Intrathecal — lumbar puncture into lumbar subarachnoid space |
| Device | Surgically-implanted Ommaya / Rickham reservoir (one-time CPT 61210 / 61215 prerequisite) | None — standard lumbar puncture each dose |
| FDA indication | CLN2 disease pediatric ≥3 years | SMA pediatric AND adult, all SMA types |
| Dosing | 300 mg ICV q2w (every 14 days), continuous | 4 loading (Days 0/14/28/63) + 12 mg q4mo for life |
| Infusion duration | ~4.5 hr at 2.5 mL/hr + ~1 hr observation | 1–3 minutes intrathecal injection |
| Admin CPT | 96450 (chemo admin into CNS reservoir, including spinal puncture) | 62321 (interlaminar/subarachnoid lumbar injection with imaging) |
| Imaging | Reservoir-patency confirmation per institutional protocol (separate from CPT 96450) | Fluoroscopy / CT bundled into 62321 |
| Sedation/anesthesia | Routinely required for pediatric ~4.5 hr infusion (separate billing) | Often required for pediatric LP (separate billing) |
| Manufacturer | BioMarin Pharmaceutical | Biogen (licensed from Ionis Pharmaceuticals) |
| FDA approval | April 27, 2017 (first CLN2 treatment) | December 23, 2016 (first SMA treatment) |
| Approximate annual WAC | ~$702,000/yr (~26 doses/yr) | ~$375,000/yr (3 maintenance doses/yr after Year 1) |
| Site of care | Restricted certified ICV centers (pediatric neurology / specialty pediatric hospital) | Pediatric hospital, neurology specialty clinic, HOPD, ASC |
Both drugs bypass the BBB because the target tissue is CNS. TPP1 enzyme (Brineura) does
not cross the blood-brain barrier in therapeutic concentrations, so IV administration would not deliver
active enzyme to the brain where CLN2 storage occurs. Nusinersen (Spinraza) likewise cannot cross the
BBB to reach spinal motor neurons. Direct CNS delivery is the only viable route for both. The ICV /
intrathecal distinction reflects target distribution (Brineura needs broad cortical / cerebellar
coverage achievable via ventricular CSF flow; Spinraza targets spinal motor neurons reachable via lumbar
intrathecal).
Brineura is not a Spinraza substitute — and vice versa. The diseases are unrelated
(CLN2 lysosomal enzyme deficiency vs SMA SMN1 motor-neuron loss), the products are mechanism-distinct,
and the routes are not interchangeable. Brineura cannot be delivered intrathecally by LP (insufficient
cortical/cerebellar coverage and not FDA-labeled), and Spinraza cannot be delivered ICV (the LP route
is FDA-labeled and the lumbar drug distribution targets motor neurons). Do not co-bill.
Dosing schedule & unit math FDA label verified May 2026
From the FDA-approved Brineura prescribing information (BLA 761052). Single fixed dose — not BSA- or weight-based.
Standard dosing
| Element | Value | Notes |
|---|---|---|
| Dose | 300 mg ICV | Single fixed dose; not weight- or BSA-based |
| Frequency | Every 14 days (q2w) | ~26 infusions per year |
| Infusion rate | 2.5 mL/hr fixed | Via ICV access through implanted reservoir |
| Infusion duration | ~4.5 hours | Approximately 4.5 hr drug + ~1 hr post-infusion observation |
| Pretreatment | 30–60 min before infusion | Antihistamine, antipyretic, ± corticosteroid (per FDA label) to mitigate hypersensitivity |
| Patient age | ≥3 years | FDA-labeled minimum age for initiation |
| Continuous therapy | No defined endpoint | Continued unless tolerability fails or disease progression renders therapy futile |
Worked example — per-infusion unit math
# Calculate units
Dose: 300 mg × (1 unit / 1 mg) = 300 units
Kit: 2 × 150 mg vials (single-dose) + 1 intraventricular electrolytes diluent vial
No partial-vial waste with standard 300 mg dose — both 150 mg vials are used in full
# Drug claim line
J0567 · 300 units · modifier JZ (single-dose vials, no waste)
# Procedure claim line
96450 · 1 unit · chemo admin into CNS reservoir (includes spinal puncture / reservoir access)
(anesthesia or moderate sedation co-billed separately under appropriate anesthesia CPT)
# Annual totals (~26 q2w doses/yr)
J0567 annual units: 26 × 300 = 7,800 units
Approximate WAC: 26 × ~$27,000 ≈ ~$702,000/year
Dose: 300 mg × (1 unit / 1 mg) = 300 units
Kit: 2 × 150 mg vials (single-dose) + 1 intraventricular electrolytes diluent vial
No partial-vial waste with standard 300 mg dose — both 150 mg vials are used in full
# Drug claim line
J0567 · 300 units · modifier JZ (single-dose vials, no waste)
# Procedure claim line
96450 · 1 unit · chemo admin into CNS reservoir (includes spinal puncture / reservoir access)
(anesthesia or moderate sedation co-billed separately under appropriate anesthesia CPT)
# Annual totals (~26 q2w doses/yr)
J0567 annual units: 26 × 300 = 7,800 units
Approximate WAC: 26 × ~$27,000 ≈ ~$702,000/year
Worked example — lifetime cost framing
# Continuous therapy from initiation onward
Annual WAC: ~$702,000
Treatment duration: continuous — no FDA endpoint
Cumulative cost runs into the millions over a multi-year course
# Plus one-time reservoir placement
CPT 61210 / 61215 + facility / anesthesia — billed once before initiation
Plus ongoing periodic reservoir-patency verification per institutional protocol
Brineura is among the most expensive chronic specialty drug therapies in US clinical use.
Annual WAC: ~$702,000
Treatment duration: continuous — no FDA endpoint
Cumulative cost runs into the millions over a multi-year course
# Plus one-time reservoir placement
CPT 61210 / 61215 + facility / anesthesia — billed once before initiation
Plus ongoing periodic reservoir-patency verification per institutional protocol
Brineura is among the most expensive chronic specialty drug therapies in US clinical use.
Single fixed dose — no weight or BSA calculation
Brineura is dosed at 300 mg per infusion regardless of patient weight, BSA, or age within the ≥3-year-old indication. The kit ships with 2 × 150 mg vials of cerliponase alfa + 1 intraventricular electrolytes diluent vial per dose. Both 150 mg vials are used in full to deliver the 300 mg dose, so JZ (no waste) is the appropriate modifier on every claim per CMS's July 2023 single-dose container policy — JW does not apply.
Pre-infusion preparation: reconstitute / mix per FDA label, administer pretreatment
medications (antihistamine, antipyretic, ± corticosteroid) 30–60 min before infusion —
required by boxed warning to mitigate life-threatening hypersensitivity / anaphylaxis.
Confirm reservoir patency per institutional protocol, and monitor vital signs throughout the ~4.5 hr
infusion plus the ~1 hr post-infusion observation period. Document pretreatment timing, infusion
start/stop, vital sign trends, and any infusion-related events in the medical record — these
are commonly requested on post-payment audit. Resuscitation equipment must be immediately
available; ECG monitoring is recommended every 6 months for patients without cardiac history
(and more frequently for those with documented cardiac abnormalities).
Required documentation at initiation: TPP1 enzyme activity assay; CLN2 molecular
genetic test report; baseline CLN2 Clinical Rating Scale motor function score; confirmation of
implanted ICV reservoir with patency verification; pediatric neurology specialist as prescriber;
age ≥3 years.
NDC reference FDA NDC Directory verified May 2026
| NDC (10-digit) | NDC (11-digit) | Package | Use |
|---|---|---|---|
68135-770-01 |
68135-0770-01 |
Brineura cerliponase alfa kit — 2 × 150 mg / 5 mL drug vials + 1 intraventricular electrolytes diluent vial | Standard dispensing unit — one kit = one 300 mg ICV dose |
Use 11-digit NDC, not 10-digit. Payers expect the padded 11-digit NDC with N4 qualifier
in CMS-1500 Box 24A shaded area and UB-04 Box 43. BioMarin labeler code 68135 (San Rafael, CA). Verify
current carton NDC against the FDA NDC Directory at billing time — BioMarin occasionally reissues
carton NDCs.
Single-source product, no biosimilar. Brineura is the only cerliponase alfa product
approved in the U.S. There is no generic, biosimilar, or therapeutic equivalent as of May 2026. The
molecule is a recombinant human enzyme (biologic), but no biosimilar pathway has been initiated.
Phase 2
Code the claim
ICV via implanted reservoir — CPT 96450 is the predominant admin code. Reservoir placement is billed separately as a one-time prerequisite.
Administration codes CPT verified May 2026
Brineura is delivered through a surgically-implanted CNS reservoir. CPT 96450 is the predominant administration code; reservoir placement uses CPT 61210 / 61215 as a one-time prerequisite.
| Code | Description | When to use |
|---|---|---|
96450 |
Chemotherapy administration, into CNS (e.g., intrathecal), requiring and including spinal puncture | Primary admin code for each Brineura infusion. Despite the descriptor language referencing chemotherapy, 96450 is the predominant payer-accepted code for therapeutic substance administration into an implanted CNS reservoir, including non-chemotherapy ERT like Brineura. Code is reported once per encounter regardless of infusion duration. |
96365 + 96366 |
Therapeutic IV infusion, initial up to 1 hour (96365) + each additional hour (96366) | Alternate per payer. Some payers prefer 96365 + 96366 for the ~4.5 hr infusion with a reservoir-access modifier or NTE annotation describing the ICV route. Verify per payer before submitting; 96450 is the predominant 2026 code. |
61210 |
Burr hole(s); for implanting ventricular catheter, reservoir, EEG electrode(s), pressure recording device, or other cerebral monitoring device | One-time prerequisite for new ICV reservoir placement (new burr hole + catheter + reservoir). Billed once before Brineura initiation, typically in inpatient or hospital outpatient surgical setting. |
61215 |
Insertion of subcutaneous reservoir, pump, or continuous infusion system for connection to ventricular catheter | One-time prerequisite alternative for reservoir-only placement when a ventricular catheter is already in place. Billed once before Brineura initiation. |
| Anesthesia / sedation codes | e.g., 00635 spine puncture anesthesia, 00640 spinal cord positioning anesthesia, 99151–99153 moderate sedation, or general anesthesia codes (per pediatric anesthesia) |
Co-billed for the routine pediatric sedation or general anesthesia required for the ~4.5 hr ICV infusion. Separate claim line; separate documentation (time, depth, monitoring). |
62321 |
Interlaminar/subarachnoid lumbar injection with imaging guidance | NOT for Brineura. This is the Spinraza (intrathecal LP) code, not the ICV reservoir code. Submitting 62321 for Brineura will trigger denial. |
96413 |
Chemotherapy IV infusion, initial up to 1 hour | NOT for Brineura. This is IV chemotherapy administration; Brineura is not IV and is not chemotherapy. |
The #1 Brineura admin coding error is using CPT 96365 (therapeutic IV infusion)
without ICV / reservoir-access annotation, or using CPT 62321 (intrathecal LP). Brineura is neither
IV nor intrathecal — it is intracerebroventricular via implanted reservoir. CPT 96450 is the
predominant code; if your billing system defaults to 96365 for "infusion," override at the encounter
level with 96450, and annotate the reservoir access in the NTE segment.
Reservoir placement is one-time and prerequisite. CPT 61210 / 61215 is billed once
before the first Brineura dose, almost always in the inpatient or hospital outpatient surgical
setting under general anesthesia by a pediatric neurosurgeon. The reservoir-placement claim is
completely separate from any J0567 dose claim. Patency verification (per institutional protocol)
precedes each Brineura infusion but is generally not separately billable from 96450.
Pediatric sedation / anesthesia is the norm. Most CLN2 patients are young children
with neurodegenerative disease who cannot remain still for the ~4.5 hr ICV infusion. Anesthesia or
deep sedation by an anesthesiologist (or moderate sedation by the proceduralist where feasible) is
the standard pathway. Bill the appropriate anesthesia or sedation CPT separately under its own
time-based documentation rules. Coordinate scheduling so anesthesia, reservoir-patency check, and
infusion are co-located on the same encounter.
Modifiers CMS verified May 2026
JZ — required on every Brineura claim (no waste)
Effective July 1, 2023, CMS requires modifier JZ on claims for single-dose container drugs when no drug is discarded. Brineura is supplied as a kit of 2 × 150 mg single-dose vials sized to deliver exactly the 300 mg standard dose — both vials are used in full, no partial-vial waste occurs at the standard dose. JZ is the default modifier on every Brineura claim line.
JW — not typical for Brineura
JW (drug discarded) is not typical for Brineura because the kit pack-size matches the standard 300 mg dose with no waste at single-dose-vial level. If a non-standard partial dose is administered (rare, per FDA label and clinical practice) and partial-vial discard occurs, follow your MAC's JW reporting rule on a separate claim line with documented mg discarded. The default is JZ.
Modifier 25 — situational
Use modifier 25 on the E/M code when a significant, separately identifiable E/M service (e.g., a neurology disease-progression assessment or sedation pre-op assessment) is performed on the same day as a 96450 infusion encounter. Document the E/M elements distinct from the infusion service.
340B modifiers (JG, TB)
For 340B-acquired Brineura at eligible academic medical centers and children's hospitals, follow your MAC's 340B modifier policy (JG primary, TB informational where applicable). Pediatric Medicaid + 340B is a common payer / acquisition combination for the CLN2 patient population.
Reservoir-access modifiers — per payer
Some payers that accept 96365 + 96366 (instead of 96450) for Brineura administration require a reservoir-access annotation in the NTE segment or a payer-specific modifier; there is no universal HCPCS modifier for ICV reservoir access. Verify per payer before submitting, and annotate the route ("Intracerebroventricular via implanted Ommaya reservoir") explicitly in the claim narrative.
ICD-10-CM diagnosis codes FY2026 verified May 2026
E75.4 is the primary code. Brineura is approved specifically for the CLN2 subtype; molecular and enzyme assay confirmation in the PA documents the specific diagnosis.
| ICD-10 | Description | Use |
|---|---|---|
E75.4 | Neuronal ceroid lipofuscinosis (Batten / Spielmeyer-Vogt / Kufs disease) | Primary code — required. ICD-10 does not subtype CLN2 separately; the molecular and TPP1 enzyme assay in the PA documents the specific CLN2 / TPP1 deficiency diagnosis. |
G31.81 | Alpers disease | Secondary code where clinically relevant for overlapping neurodegenerative phenotype; some payers accept E75.4 alone as sufficient. |
R56.9 | Unspecified convulsions | Supplementary code for documented seizures (a common CLN2 manifestation); not primary for Brineura. |
G40.x | Epilepsy and recurrent seizures (specify type) | Supplementary for documented epilepsy subtype; not primary for Brineura. |
R26.x | Abnormalities of gait and mobility | Supplementary for documented motor decline (CLN2 Clinical Rating Scale endpoint); not primary. |
F84.x | Pervasive developmental disorders | NOT appropriate as primary for Brineura. |
G31.9 | Degenerative disease of nervous system, unspecified | NOT appropriate — CLN2 has a specific code (E75.4). |
Submitting Brineura with any primary code other than E75.4 is a near-automatic denial.
ICD-10 E75.4 covers the full neuronal ceroid lipofuscinosis group (CLN1 through CLN14) at the code
level — the system does not subtype CLN2 separately. The TPP1 enzyme activity assay and the
CLN2/TPP1 molecular genetic test report in the PA submission are the determinative documents that
confirm the CLN2 / TPP1 deficiency subtype for which Brineura is FDA-approved. Brineura is NOT
approved for other NCL subtypes (CLN1, CLN3, CLN5, CLN6, CLN7, CLN8) and will deny if those subtypes
are documented.
Site of care & reservoir placement Verified May 2026
Brineura is administered at restricted certified pediatric centers with ICV-administration capability — typically pediatric neurology specialty clinics, children's hospitals, or academic medical centers with pediatric neurosurgery, anesthesia, and neurology support. The reservoir-placement neurosurgical procedure (CPT 61210 / 61215) is performed once before therapy initiation, almost always in an inpatient or hospital outpatient surgical setting under general anesthesia by a pediatric neurosurgeon. The ongoing q2w infusions are typically in HOPD or pediatric specialty clinic settings with anesthesia / sedation support.
| Setting | POS | Claim form | Electronic |
|---|---|---|---|
| Children's hospital inpatient (reservoir placement; some initial cycles) | 21 | UB-04 / CMS-1450 | 837I |
| Children's hospital HOPD (q2w infusions) | 22 | UB-04 / CMS-1450 | 837I |
| Pediatric neurology specialty clinic | 11 or 19 | CMS-1500 / UB-04 (per facility billing) | 837P / 837I |
| Academic medical center pediatric clinic | 22 or 19 | UB-04 / CMS-1500 | 837I / 837P |
| Pediatric ASC (rare; certified for ICV access) | 24 | UB-04 / CMS-1500 | 837I / 837P |
Reservoir-implant prerequisite workflow: (1) confirm TPP1 enzyme deficiency + CLN2
molecular diagnosis; (2) PA approval for Brineura; (3) schedule reservoir-placement neurosurgical
procedure (CPT 61210 burr hole + reservoir, or CPT 61215 reservoir-only if catheter exists); (4)
post-implant imaging confirming placement and patency; (5) ~2–4 week wound healing window per
surgeon protocol; (6) first Brineura infusion. Document each step in the medical record —
payers commonly request reservoir placement op note + post-implant imaging with the first J0567
claim.
Restricted ICV-administration sites. Brineura is generally administered only at
certified pediatric centers with the staff and infrastructure for ICV reservoir access, sterile
technique, pediatric sedation/anesthesia, and ~5+ hour observation. Many payer policies explicitly
require administration at a specialty pediatric center; an attempt to administer at a community
clinic or general infusion center will typically be denied on site-of-care grounds. Verify the
center's certification status with BioMarin RareConnections during PA.
Reservoir-patency verification before each infusion: per institutional protocol,
confirm reservoir patency and absence of infection before each q2w infusion (e.g., aspiration check,
CSF appearance, neurosurgery clearance for first few cycles). This is generally bundled into the
96450 infusion encounter and not separately billable, but document the check in the medical record
— payers may request evidence on audit.
Claim form field mapping Verified May 2026
CMS-1500 / 837P for professional billing; UB-04 / 837I for facility (HOPD / inpatient) billing.
Per-infusion drug + admin claim — CMS-1500 / 837P (or UB-04 / 837I)
| Information | CMS-1500 box | Notes |
|---|---|---|
| NPI | 17b | Rendering provider (pediatric neurologist, infusion proceduralist, or facility NPI) |
| NDC qualifier + 11-digit NDC + UoM + qty | 24A shaded area | Format: N468135077001UN2 (2 vials per 300 mg dose). Use the kit NDC. |
| HCPCS J0567 + admin CPT 96450 | 24D | Each on its own line. Add description "Brineura (cerliponase alfa) 300 mg ICV via implanted Ommaya reservoir" in NTE. |
| Drug units (mg) | 24G | 300 (each unit = 1 mg per J0567 descriptor) |
| JZ modifier | 24D | Append to J0567 line (single-dose vials, no discard) |
| Anesthesia / sedation CPT | 24D (separate line) | 00635 / 00640 anesthesia codes, or 99151–99153 moderate sedation if proceduralist-administered, on a separate claim line with time documentation |
| ICD-10 | 21 | E75.4 (neuronal ceroid lipofuscinosis) as primary; G31.81 / seizure codes as secondary where applicable |
| PA number | 23 | Required by all major payers; obtain via BioMarin RareConnections or direct payer submission |
| Billed charge | 24F | Provider acquisition + appropriate margin; reimbursement is ASP+6% (Medicare) or per payer contract |
| Route documentation | NTE / Box 19 | Critical for Brineura — "Intracerebroventricular (ICV) via implanted Ommaya reservoir; infusion ~4.5 hr at 2.5 mL/hr per FDA label" |
One-time reservoir-placement claim (separate encounter)
The reservoir-placement neurosurgical procedure is billed on a separate encounter, typically by the pediatric neurosurgeon (professional) and the facility (UB-04). Use CPT 61210 (new burr hole + reservoir) or 61215 (reservoir-only, catheter in place) with appropriate anesthesia codes. Document the post-implant imaging confirming placement and patency. Submit op note + post-implant imaging with the first J0567 dose claim to forestall the common "reservoir not documented" denial.
Route documentation in NTE is non-negotiable. Brineura's ICV route is unusual enough
that many payer adjudication systems will flag a J0567 claim without an explicit route note. Always
include "Intracerebroventricular (ICV) via implanted Ommaya reservoir" in the NTE segment / Box 19,
plus the dose, infusion duration, and reservoir-placement date.
Form references: NUCC (CMS-1500) · NUBC (UB-04).
Phase 3
Get paid
Universal PA. TPP1 enzyme assay + CLN2 molecular confirmation + age ≥3 + reservoir placed + baseline motor function gate every PA and reauth.
Payer policy snapshot Reviewed May 2026
Universal prior auth. TPP1 enzyme assay + CLN2 molecular confirmation + Ommaya reservoir placement are universal gates.
| Payer | PA? | Key requirements | Benefit channel | Re-auth |
|---|---|---|---|---|
| UnitedHealthcare Cerliponase alfa medical policy |
Yes | TPP1 enzyme deficiency + CLN2 molecular confirmation; age ≥3 yr; ICV reservoir placed and patent; baseline CLN2 Clinical Rating Scale motor function; pediatric neurology prescriber; restricted certified site | Medical benefit (Part B) | 12 mo w/ updated CLN2 motor function + reservoir patency + tolerability assessment |
| Aetna CLN2 disease therapy clinical policy bulletin |
Yes | Both enzyme assay + molecular confirmation; age criteria met; reservoir placement op note; specialist prescriber | Medical benefit | 12 mo w/ updated motor function + tolerability |
| Anthem / Carelon Lysosomal storage / ERT policy |
Yes | TPP1 assay + CLN2 genetic testing both required; reservoir verified; pediatric neurology prescriber | Medical benefit (medical injectable management) | 12 mo w/ functional assessment |
| Cigna / Express Scripts Brineura coverage policy |
Yes | Same: TPP1 deficiency + CLN2 molecular + reservoir + specialist prescriber + restricted site | Medical benefit via Accredo specialty | 12 mo |
| BCBS (representative) Rare disease ERT biologics |
Yes | TPP1 enzyme assay + CLN2 molecular both required; reservoir placement; some plans require genetic counselor consult | Medical benefit | 12 mo |
| Pediatric Medicaid (state) State-specific; PA via PBA / state PDL |
Yes | State-specific but mirrors commercial: TPP1 deficiency + CLN2 molecular + age ≥3 yr + reservoir + baseline motor function + specialist prescriber. EPSDT obligates coverage of medically necessary services for children. | State Medicaid medical benefit (Part B-equivalent) | 12 mo per state policy |
Pediatric Medicaid is a primary Brineura payer. EPSDT (Early and Periodic Screening,
Diagnostic, and Treatment) obligates state Medicaid programs to cover medically necessary services
for children, including disease-modifying therapy for CLN2 disease. All major state Medicaid programs
cover Brineura with PA as of Q2 2026; PA timelines run 30–60 days. Coordinate via BioMarin
RareConnections from intake to address common documentation gaps (most frequently: stale TPP1 enzyme
report, missing reservoir post-implant imaging, missing baseline CLN2 Clinical Rating Scale score).
Annual reauthorization centers on motor function trajectory. Payers want documentation
that the patient continues to derive meaningful clinical benefit — specifically, that motor
function decline has slowed compared to natural-history controls. Use the CLN2 Clinical Rating Scale
(motor + language subscales) at baseline and at each annual reauth. Document tolerability (infusion-related
reactions, reservoir complications). Some payers will discontinue coverage if rapid progression
continues despite therapy — document the clinical decision-making with the prescriber.
What to document for approval
- TPP1 enzyme activity assay (dried blood spot or leukocyte) showing deficient activity from a CLIA-certified lab
- CLN2 / TPP1 molecular genetic test report confirming biallelic pathogenic variants
- Reservoir placement op note + post-implant imaging confirming placement and patency
- Baseline CLN2 Clinical Rating Scale (motor + language subscales) score
- ICD-10 E75.4 (neuronal ceroid lipofuscinosis) as primary
- Patient age ≥3 years at initiation
- Specialist prescriber (pediatric neurologist)
- Restricted certified ICV-administration site
- For reauth: updated CLN2 motor function score, tolerability assessment, reservoir patency status
Medicare reimbursement Q2 2026
Medicare Part B covers Brineura as a physician-administered ICV drug. Pediatric Medicaid is the dominant primary payer; Medicare is rare given pediatric indication.
Q2 2026 payment snapshot — Brineura
Effective April 1 – June 30, 2026 · ASP+6% per CMS Part B Drug Pricing File
HCPCS
J0567
1 mg = 1 unit
Standard dose
300 mg ICV
~26 doses/yr (q2w)
Annual WAC
~$702K/yr
~$27K per 300 mg infusion
ASP+6% binding: the per-mg ASP figure shown elsewhere on this page is bound to the
CMS Part B Drug Pricing File and refreshes each quarter. Sequestration (~2%) reduces actual paid
amount to roughly ASP+4.3%. Where Brineura ASP is not yet published for the current quarter (it is a
low-volume orphan drug and CMS may delay or omit publication), MAC pricing may default to WAC or
invoice pricing. Verify the current-quarter ASP file before relying on a specific per-mg figure.
Why Medicare is rarely the primary payer for Brineura
Brineura is approved for pediatric patients ≥3 years with CLN2 disease — a rapidly progressive neurodegenerative disorder that typically presents in early childhood. The patient population is almost exclusively pediatric, and CLN2 disease typically does not allow patients to age into Medicare eligibility (life expectancy historically ≤ mid-teens, though Brineura extends it). The dominant primary payer is pediatric Medicaid (often combined with commercial pediatric insurance via parents' plans). Medicare may apply only in the rare disabled-pediatric SSI / SSDI scenario.
Code history
- April 27, 2017 — FDA approval of Brineura (BLA 761052); first FDA-approved CLN2 treatment
- 2018 — permanent HCPCS J0567 assigned ("Injection, cerliponase alfa, 1 mg")
- 2018–2026 — quarterly ASP publication in CMS Part B Drug Pricing File where utilization is sufficient; otherwise MAC manual pricing
- Q2 2026 — J0567 remains the only HCPCS for cerliponase alfa; no biosimilar pathway initiated
Patient assistance — BioMarin RareConnections BioMarin verified May 2026
- BioMarin RareConnections: 1-866-906-6100 — central support hub for benefits investigation, PA, copay assistance, and patient/caregiver education for all BioMarin rare-disease products including Brineura
- Brineura Copay Program (commercial patients only): as low as $0 copay; annual benefit caps apply — verify current limits with RareConnections. Excludes Medicare, Medicaid, TRICARE, VA, CHIP, and other federal program patients.
- BioMarin Patient Assistance Program (BioMarin PAP): free drug for uninsured / underinsured patients meeting income limits (typically ≤500% FPL)
- Bridge Program: starter supply available for new starts pending coverage determination (eligibility criteria apply)
- Beyond Batten Disease Foundation: beyondbatten.org — CLN2/Batten-specific advocacy, family support, research funding
- Foundation backup: Patient Advocate Foundation Copay Relief Program (rare disease fund); HealthWell Foundation rare disease fund; NORD patient assistance — verify quarterly for open Batten / lysosomal storage disease fund status
- Batten Disease Support and Research Association (BDSRA): bdsra.org — family support, research, and policy advocacy across all Batten subtypes
- Web: brineura.com · biomarin-rareconnections.com
Need to model what a specific patient will actually pay after copay assistance, deductible, coinsurance,
and OOP max? Run a CareCost Estimate — Brineura ICV infusion,
reservoir placement, and pediatric Medicaid scenarios pre-loaded.
Copay card excludes federal program patients. Medicaid (the dominant Brineura payer
for pediatrics), TRICARE, VA, CHIP, IHS, and other government-insured patients are not eligible for
the Brineura copay card. For these patients, the path is pediatric Medicaid coverage (with the
program's normal cost-share) + BioMarin PAP for uninsured / underinsured + foundation backup (PAF,
HealthWell, NORD, BDSRA, Beyond Batten) for additional copay relief.
Phase 4
Fix problems
TPP1 / CLN2 confirmation, reservoir-placement documentation, age boundary, and wrong-CPT (96365 instead of 96450) drive denials.
Common denials & how to fix them
| Denial reason | Common cause | Fix |
|---|---|---|
| #1 — TPP1 / CLN2 genetic confirmation missing | PA submitted with clinical / phenotypic description only, without TPP1 enzyme assay or CLN2 molecular genetic test report | Submit both the TPP1 enzyme activity assay (dried blood spot / leukocyte) showing deficient activity AND the CLN2/TPP1 molecular genetic test report confirming biallelic pathogenic variants — both from CLIA-certified labs. Phenotype-only or "presumed CLN2 disease" notes do not satisfy this requirement. |
| #2 — No Ommaya reservoir documented | J0567 dose claim submitted without evidence of implanted reservoir (op note, post-implant imaging) in the record | Reservoir placement (CPT 61210 / 61215) is a prerequisite. Submit the neurosurgical op note and post-implant imaging with the first J0567 claim, and reference the reservoir-placement date in NTE for subsequent claims. If no reservoir is in place, do not proceed with Brineura administration. |
| #3 — Wrong CPT (96365 / 96413 / 62321 instead of 96450) | Billing software default to IV infusion (96365 / 96413) or intrathecal LP (62321) for "infusion" | Override to CPT 96450 (chemo admin into CNS reservoir, including spinal puncture). Annotate route as "Intracerebroventricular via implanted Ommaya reservoir" in NTE. Some payers accept 96365 + 96366 + reservoir-access annotation — verify per payer. |
| #4 — Pediatric <3 yr attempted | PA submitted for child younger than 3 years with confirmed CLN2 disease | FDA label requires age ≥3 years. Wait until the 3-year threshold. Document the CLN2 diagnosis, baseline motor function, and family counseling in the interim; submit PA at the qualifying age. |
| #5 — Baseline CLN2 motor function not documented | PA submitted without baseline CLN2 Clinical Rating Scale (motor + language subscales) or equivalent functional assessment | Document baseline motor function using the CLN2 Clinical Rating Scale at PA submission, and at each annual reauth. This is the standard endpoint for assessing Brineura clinical benefit and is required by most payer reauth policies. |
| #6 — Adult patient (off-label by mechanism) | Brineura requested for adolescent or adult with CLN2 disease beyond pediatric indication | The FDA label is pediatric ≥3 yr. CLN2 patients who have aged into adolescence/adulthood with the disease (rare given natural history) may not meet PA criteria at some payers. Discuss with prescriber and payer; off-label coverage decisions are case-by-case. |
| Wrong ICD-10 (not E75.4) | Primary code submitted as G31.9 (unspecified degenerative) or other non-specific neurodegenerative code | Resubmit with E75.4 (neuronal ceroid lipofuscinosis) as primary. Secondary codes (G31.81, seizure / motor codes) are acceptable as supplementary but not primary. |
| Non-specialist prescriber | Brineura prescribed by general pediatrician or neurologist without CLN2 expertise | Most payers require pediatric neurology specialist (often a CLN2-experienced neurologist at a children's hospital or academic medical center). Refer to a CLN2 specialty center for initiation; specialty office can co-manage with general pediatrician thereafter. |
| Site-of-care denial (community clinic / general infusion) | Brineura administration attempted at non-certified general infusion center | Brineura requires a restricted certified pediatric center with ICV access, sterile technique, sedation, and observation capability. Reroute to the appropriate specialty pediatric site; verify center certification with BioMarin RareConnections. |
| Stale TPP1 / CLN2 documentation at reauth | Original assay / genetic test report is old; payer asks for "current" documentation | The original CLN2 genetic test result does not expire (a confirmed CLN2 patient remains a CLN2 patient). Reference the original report by lab, date, accession number; provide a copy. If a payer specifically requires fresh testing, repeat the molecular test (the diagnosis will not change). |
| Reservoir complication (infection, malfunction) | Reservoir-related adverse event during therapy; payer requests evidence of patency before resuming doses | Document the complication, the neurosurgery management (drain, replacement, antibiotics), and the post-resolution patency confirmation. Pause J0567 dosing during reservoir-out time; resume only with documented patency. |
| NDC format / qty mismatch | 10-digit NDC submitted when payer requires 11-digit; or qty does not match the 2-vial kit configuration | Use 11-digit padded NDC. Report qty as 2 vials per 300 mg dose (kit configuration); confirm kit NDC against current FDA NDC Directory. |
| J0567 priced at $0 (low-volume / no published ASP) | Brineura is orphan with low utilization; CMS may delay or omit ASP publication for some quarters | If ASP is missing for the current quarter, MAC may default to WAC or invoice pricing. Submit itemized invoice, 11-digit NDC, dose in mg, and PA approval letter. Most MACs manually price after documentation. |
Frequently asked questions
ICV vs intrathecal — what's the billing difference?
Brineura is intracerebroventricular (ICV) — via a surgically-implanted reservoir (Ommaya / Rickham) with a catheter into a lateral cerebral ventricle. Spinraza is intrathecal — via lumbar puncture into the lumbar subarachnoid space. The routes are anatomically and procedurally distinct. ICV is used when broad cortical / cerebellar coverage via CSF flow is needed (Brineura targets stored material throughout the brain in CLN2); intrathecal is sufficient when the target is spinal motor neurons (Spinraza). Brineura billing: CPT 96450 (chemo admin into CNS reservoir, including spinal puncture). Spinraza billing: CPT 62321 (interlaminar/subarachnoid lumbar injection with imaging guidance).
Ommaya reservoir placement billing?
Reservoir placement is a one-time neurosurgical prerequisite billed separately from Brineura doses. CPT 61210 covers placement when a new burr hole is required (burr hole + ventricular catheter + reservoir); CPT 61215 covers reservoir-only placement when a catheter is already in place. The neurosurgical procedure is typically performed in the inpatient or hospital outpatient setting (POS 21 or 22) under general anesthesia by a pediatric neurosurgeon, with separate facility (UB-04) and professional (CMS-1500) billing. Document placement op note + post-implant imaging confirming position and patency; payers commonly request these with the first J0567 dose claim.
TPP1 enzyme assay requirements?
Universal payer PA gate. Submit a TPP1 (tripeptidyl peptidase 1) enzyme activity assay performed on dried blood spot or leukocytes from a CLIA-certified laboratory, showing deficient activity consistent with CLN2 disease. The report must include methodology (typically fluorometric enzyme assay), the measured TPP1 activity (with reference range), and an interpretive statement. Some labs report TPP1 activity as a percentage of normal mean — CLN2 patients typically show profoundly deficient activity (often <5% of normal). The enzyme assay is generally paired with molecular CLN2/TPP1 genetic testing for diagnostic confirmation.
CLN2 genetic testing requirements?
Universal. Submit a molecular genetic test report from a CLIA-certified laboratory confirming biallelic pathogenic variants in the CLN2 / TPP1 gene. Sanger sequencing or NGS panel testing of TPP1 is the standard methodology. The report must identify the specific variants (with HGVS nomenclature where applicable), classify them per ACMG criteria (pathogenic / likely pathogenic), and confirm biallelic (compound heterozygous or homozygous) inheritance. The combination of deficient TPP1 enzyme activity + biallelic TPP1 pathogenic variants is the definitive CLN2 diagnosis.
CPT 96450 vs 96365 — which is correct?
CPT 96450 (chemotherapy administration, into CNS, requiring and including spinal puncture) is the predominant payer-accepted code for Brineura ICV infusion via implanted reservoir. Despite the chemotherapy descriptor, 96450 is the standard CPT for therapeutic substance administration into an implanted CNS reservoir, including non-chemotherapy ERT like Brineura. Some payers accept CPT 96365 (therapeutic IV infusion, initial up to 1 hour) + 96366 (each additional hour) with a reservoir-access annotation or modifier — verify per payer. The choice is payer-specific; 96450 is the predominant 2026 code.
Anesthesia or sedation co-billing for pediatric ICV?
Most CLN2 patients are young children with neurodegenerative disease who require sedation or general anesthesia for the ~4.5 hr ICV infusion. Anesthesia or sedation is billed separately under appropriate anesthesia CPT — e.g., 00635 (spine puncture anesthesia), 00640 (positioning anesthesia), or moderate-sedation 99151–99153 when performed by the proceduralist. The anesthesia or sedation claim is separate from 96450 and from the J0567 drug claim and has its own time-based documentation requirements. Coordinate scheduling so anesthesia, reservoir-patency verification, and infusion are co-located on the same encounter day.
Pediatric Medicaid as primary payer?
Pediatric Medicaid is a primary payer for many Brineura patients. EPSDT (Early and Periodic Screening, Diagnostic, and Treatment) obligates state Medicaid programs to cover medically necessary services for children, including disease-modifying therapy for CLN2 disease. All major state Medicaid programs cover Brineura with PA as of Q2 2026; PA timelines run 30–60 days. State PA criteria mirror commercial. CLN2 patients commonly qualify for disability-based Medicaid (SSI), which combines with parent commercial coverage in coordination-of-benefits arrangements that vary by state.
Brineura vs Spinraza — both CNS-route ERTs?
Both deliver therapeutic agents directly to the CNS to bypass the blood-brain barrier, but the routes, diseases, mechanisms, and billing all differ. Brineura is intracerebroventricular via implanted reservoir for CLN2 disease (enzyme replacement); Spinraza is intrathecal via lumbar puncture for SMA (antisense oligonucleotide). Brineura uses CPT 96450; Spinraza uses CPT 62321. Brineura is q2w continuous; Spinraza is 4 loading doses + q4mo maintenance. Brineura requires a one-time surgical reservoir-placement prerequisite (CPT 61210/61215); Spinraza uses standard lumbar puncture each dose. There is no clinical overlap between the two products' indications.
BioMarin RareConnections enrollment — how does it work?
BioMarin RareConnections (1-866-906-6100) is the central hub for Brineura support, the same hub used for other BioMarin rare-disease products (Voxzogo, Vimizim, Naglazyme, Aldurazyme, Palynziq, Roctavian, Kuvan). Enroll the patient at the time of prescription. RareConnections handles benefits investigation, PA submission and follow-up, copay assistance enrollment, specialty pharmacy / specialty distributor coordination, site-of-care identification (certified pediatric ICV centers), and reauth coordination. Enrolling at intake (not just for PA fights) materially shortens time-to-first-dose — typical RareConnections-coordinated start (including reservoir-placement scheduling) is 6–12 weeks vs longer for unsupported submissions.
What is the annual WAC cost of Brineura?
Approximately $702,000 per year WAC for the 300 mg q2w schedule (~26 doses/yr at ~$27,000 per 300 mg dose). This is among the highest catalog chronic specialty drug costs — comparable to other ultra-rare disease ERTs. Lifetime cost extends from age 3 onward, with no FDA endpoint — cumulative drug cost can reach the multi-million-dollar range. Net price after BioMarin RareConnections support, commercial copay assistance, and pediatric Medicaid rebates is materially lower and varies by plan. The one-time reservoir-placement procedure and ongoing anesthesia / sedation costs are additional.
Reference
Sources & methodology
Every claim on this page is sourced. Methodology and review history below.
Source documents
- FDA — BRINEURA (cerliponase alfa) Prescribing Information
- DailyMed — BRINEURA label search
- Brineura.com — patient / caregiver site
- BioMarin RareConnections
- CMS — Medicare Part B Drug ASP Pricing File
- CMS — HCPCS quarterly update file
- CMS — JW Modifier and JZ Modifier policy
- FDA Press Announcement — Brineura approval (Apr 2017)
- Beyond Batten Disease Foundation
- Batten Disease Support and Research Association (BDSRA)
- NORD — CLN2 disease / late-infantile NCL
- FDA National Drug Code Directory
- BioMarin Pharmaceutical — manufacturer
- AMA — CPT code reference (96450, 61210, 61215)
- DailyMed — BRINEURA current label (setid 485ab3c5-0359-4878-872f-2fe1e7df4047)
- Schulz A et al. — Study of intraventricular cerliponase alfa for CLN2 disease (CLN2 Study 190)
About this page
We maintain this page as a living reference. Medicare ASP pricing references are bound to our underlying CareCost data layer and refresh automatically when CMS publishes new quarterly files. Coding and policy content is reviewed at least quarterly and updated whenever a source document changes.
Found an error? Email hello@carecostestimate.com.
Refresh cadence
| Element | Cadence | How it's refreshed |
|---|---|---|
| HCPCS / ASP (J0567) | Quarterly | Bound to CMS Part B Drug Pricing File; ASP publication may be delayed for low-volume orphan drugs |
| Payer policies (UHC, Aetna, Cigna, Anthem, BCBS, state Medicaid) | Semi-annual | Manual review against published payer policy documents |
| HCPCS / CPT / modifier rules | Quarterly | 96450 admin, 61210/61215 reservoir, JZ/JW modifier conventions |
| NDC, dosing, FDA label | Event-driven | Tied to FDA label revision date |
| CNS-route ERT class comparison (vs Spinraza intrathecal) | Semi-annual | Updated as competing CNS-direct therapies enter the market |
Reviewer
SME-audited 2026-05-22 — corrections applied. Verified against current
DailyMed Brineura label (setid 485ab3c5-0359-4878-872f-2fe1e7df4047, revision August 5, 2024). Boxed
warning for HYPERSENSITIVITY REACTIONS INCLUDING ANAPHYLAXIS confirmed and corrected (page previously
stated "None"). Section 5 W&P verified: 5.1 hypersensitivity/anaphylaxis; 5.2 meningitis & ICV
access-device infections; 5.3 device-related complications (material degradation after ~4 yr);
5.4 cardiovascular adverse reactions; 5.5 infusion-associated reactions. ECG q6 mo monitoring added.
FDA BLA 761052, April 27, 2017 approval verified. Age ≥3 yr indication verified. CPT 96450 vs
96365 payer-specific guidance verified.
Change log
- — Verified FDA label (DailyMed setid 485ab3c5-0359-4878-872f-2fe1e7df4047, rev. Aug 5, 2024) and corrected boxed warning from "None" to "HYPERSENSITIVITY REACTIONS INCLUDING ANAPHYLAXIS." Added device-degradation (~4 yr) and ECG q6mo monitoring detail per current W&P. Confirmed BLA 761052, age ≥3 yr, CPT 96450 primary admin, CPT 61210/61215 reservoir prerequisite, BioMarin RareConnections (1-866-906-6100) active. Pivotal trial citation (Schulz et al., NEJM 2018, CLN2 Study 190) added to sources.
- — Initial publication. FDA approval April 27, 2017 (BLA 761052) — first FDA-approved CLN2 disease treatment. ICV via implanted Ommaya reservoir; CPT 96450 primary admin code; CPT 61210/61215 one-time reservoir-placement prerequisite. CNS-route ERT class context vs Spinraza intrathecal documented. Payer policies: UHC, Aetna, Cigna/Express Scripts, Anthem/Carelon, BCBS, pediatric Medicaid (EPSDT). TPP1 enzyme deficiency + CLN2 molecular confirmation are universal PA gates; reservoir placement + baseline CLN2 motor function are universal initiation requirements.
Methodology
Every claim on this page is sourced inline. Coding guidance reflects current CMS HCPCS conventions and the CPT codebook. Payer policies are read directly from each payer's published medical policy documents. We do not paraphrase from billing-software vendor blogs. The TPP1 enzyme deficiency + CLN2 molecular confirmation + reservoir placement combination is the determinative coverage and clinical-readiness lever for this drug and is made explicit in multiple sections rather than buried in a footnote. The CPT 96450 vs 96365 choice is acknowledged as payer-specific rather than presented as universal.