CurrentCignaPolicy 0068

Tissue-engineered skin substitutes and related grafts (coverage criteria)

This Cigna Coverage Policy governs medical necessity and coverage criteria for tissue-engineered skin substitutes, unprocessed grafts, and related products for burns, diabetic foot ulcers, venous stasis ulcers, dural repair and selected surgical uses billed to Cigna-administered plans.

Policy Summary

PayerCigna

PolicyTissue-engineered skin substitutes and related grafts (coverage criteria)

Policy CodePolicy 0068

Change TypeNo material clinical or coverage changes

Effective DateN/A

Next Review DateN/A

Key ActionObtain prior authorization with documentation of prior standard wound therapy failure, wound chronicity, and evidence of adequate perfusion (palpable pedal pulse or ABI ≥ 0.70).

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

~100+listed products

≥0.70ABI threshold

<12%HbA1c threshold

4–5application limits

12 wkstime window

Coverage Criteria and Product-Specific Indications

inv-01: General covered graft types

Each of the following skin grafts is considered medically necessary for wound coverage:

Covered grafts: autologous skin graft (CPT 15040-15261); unprocessed allogeneic human, cadaver skin graft (CPT 15271-15278; HCPCS Q4100); unprocessed xenogeneic pig skin graft (CPT 15271-15278; HCPCS Q4100)

inv-02: Breast reconstruction products

Products listed are considered medically necessary when used in association with a covered, medically necessary breast reconstruction procedure.

Breast reconstruction indication: Products such as AlloDerm, AlloMax, Cortiva, DermACELL, FlexHD, GalaFLEX when used in association with a covered, medically necessary breast reconstruction procedure

Application and product HCPCS/CPT codes specified per product

inv-03: Burn wounds

Policy Summary

PayerCigna

PolicyTissue-engineered skin substitutes and related grafts (coverage criteria)

Policy CodePolicy 0068

Change TypeNo material clinical or coverage changes

Effective DateN/A

Next Review DateN/A

Key ActionObtain prior authorization with documentation of prior standard wound therapy failure, wound chronicity, and evidence of adequate perfusion (palpable pedal pulse or ABI ≥ 0.70).

SourceLink

On This Page

Biobrane: Temporary covering of a partial-thickness freshly debrided or excised burn wound

CPT 15271-15278; HCPCS Q4100/C9399

Biobrane-L: Temporary covering of a partial-thickness freshly debrided or excised burn wound AND adjunct to meshed autograft

CPT 15271-15278; C5271-C5278

Integra Meshed: Postexcisional treatment of a full-thickness or deep partial-thickness burn AND sufficient autograft is not available or is contraindicated

HCPCS Q4105/Q4104/Q4108

Epicel: Use according to FDA HDE for individuals with deep dermal or full-thickness burns comprising ≥ 30% total body surface area>= 30% TBSA

CPT 15150-15157

inv-04: Diabetic foot ulcers (product-specific criteria)

Products listed are considered medically necessary when ALL of the following are met (product-specific exceptions noted):

Common DFU criteria: Standard therapy has failed for the product-specified duration (commonly >4 or >6 weeks); patient has type 1 or type 2 diabetes; HbA1c < 12%; treated foot has adequate blood supply as evidenced by palpable pedal pulse or ABI ≥ 0.70HbA1c < 12%; ABI >= 0.70

Duration and allowed number of applications vary by product

Apligraf: Full-thickness DFU >3 weeks duration after standard therapy failure; initial treatment limited per label (typically 1 initial application; up to total of 4 within 12 weeks if indicated); beyond 12 weeks additional applications considered not medically necessary>3 weeks; application limits per labeling

HCPCS Q4101

Products with ~4-5 application initial limits: Examples (Actigraft, DermACELL AWM, EpiFix, Kerecis variants, Grafix, Oasis) used for partial or full-thickness DFU >4 weeks after standard therapy failure; initial treatment limited to product-specific number of applications (commonly 4-5); additional applications permitted up to product-specific maxima within 12 weeks when evidence of wound healing is present; additional applications beyond 12 weeks are considered not medically necessary>4 weeks; initial 4-5 applications; ABI >=0.70

HCPCS vary by product

AlloPatch / Dermagraft / Integra (6-week criteria): Full-thickness DFU >6 weeks duration after standard therapy failure; HbA1c <12%; ABI ≥0.70; initial and additional application limits specified per product>6 weeks; application limits vary

Examples: AlloPatch Q4128; Dermagraft Q4106; Integra Q4105

Kerecis Omega3 Marigen Shield: Partial or full-thickness DFU >4 weeks duration after standard therapy failure; HbA1c <12%; ABI ≥0.70; initial limited to 5 applications; additional up to 12 in 12 weeks if evidence of healing; beyond 12 weeks not medically necessaryinitial 5; up to 12 in 12 weeks

HCPCS A2019

Treatment time limits: Additional applications beyond 12 weeks are generally considered not medically necessary regardless of wound status for many products12 weeks

Repeated across multiple product sections

inv-05: Venous stasis ulcers

Products are considered medically necessary when BOTH required clinical criteria are met.

Common VSU criteria: Partial- or full-thickness venous stasis ulcer >4 weeks duration for which standard therapy has failed AND treated lower extremity has adequate blood supply evidenced by palpable pedal pulse or ABI ≥ 0.70>4 weeks; ABI >= 0.70

Initial application limits vary (commonly 4-5); additional applications allowed up to product-specific maxima in 12 weeks when evidence of healing; beyond 12 weeks not medically necessary

Apligraf for VSU: Apligraf considered medically necessary when both common VSU criteria are met; initial treatment limited to four applications; additional up to four in 12 weeks if evidence of healinginitial 4 applications

HCPCS Q4101

Grafix for VSU: Grafix considered medically necessary when both common VSU criteria are met; initial treatment limited to five applications; additional up to six in 12 weeks if evidence of healinginitial 5; up to 6 in 12 weeks

HCPCS Q4132/Q4133

inv-06: EpiFix — Venous Stasis Ulcers

Covered when BOTH of the following are met

EpiFix venous ulcer criteria: 1) partial- or full-thickness venous stasis ulcer >4 weeks duration for which standard wound therapy has failed; 2) treated lower extremity has adequate blood supply evidenced by a palpable pedal pulse or ABI ≥ 0.70.

Conditions of coverage: Initial treatment limited to four applications. Additional applications up to a maximum of four in 12 weeks are considered medically necessary when evidence of wound healing is present (e.g., epithelialization and reduction in ulcer size). Applications beyond 12 weeks are considered not medically necessary.

inv-07: Grafix — Venous Stasis Ulcers

Covered when BOTH of the following are met

Grafix venous ulcer criteria: 1) partial- or full-thickness venous stasis ulcer >4 weeks duration for which standard wound therapy has failed; 2) treated lower extremity has adequate blood supply evidenced by a palpable pedal pulse or ABI ≥ 0.70.

Conditions of coverage: Initial treatment limited to five applications. Additional applications up to a maximum of six in 12 weeks are considered medically necessary when evidence of wound healing is present (e.g., epithelialization and reduction in ulcer size).

inv-08: Oasis Ultra Tri-Layer Matrix — Venous Stasis Ulcers

Covered when BOTH of the following are met

Oasis venous ulcer criteria: 1) partial- or full-thickness lower extremity venous stasis ulcer of four weeks duration for which standard wound therapy has failed; 2) treated lower extremity has adequate blood supply evidenced by a palpable pedal pulse or ABI ≥ 0.70.

inv-10: Paraesophageal/hiatal hernia repair and other surgical uses

Products such as Phasix ST Mesh and GORE BIO-A Tissue Reinforcement are considered medically necessary when used with a covered hiatal hernia or related procedure

Hernia repair association: Considered medically necessary when used in association with a covered, medically necessary hiatal hernia repair when ANY of the listed surgical criteria are met

Parotidectomy use: AlloDerm considered medically necessary when used with a covered, medically necessary parotidectomy

inv-11: Covered Products and Application Mapping

Products are covered for the listed clinical indications when billed with the associated application CPT/HCPCS and product HCPCS codes as mapped below.

Product listing: Multiple named biologic products are mapped to specific clinical reasons (wound care, burn care, tendon repair, soft tissue reinforcement, pericardial repair, nerve repair, etc.) and to CPT/HCPCS application codes (commonly 15271-15278 and C5271-C5278) and product HCPCS (e.g., Q4100, C9399, product-specific Q-/C- codes)

See product rows in chunks 36-55 for exact mappings.

Applications: Common application codes include CPT 15271-15278 and temporary C5271-C5278 for skin substitute/wound covering procedures; some products use no specific application code and rely on product HCPCS or other CPT codes (e.g., 46707, 64910, 15777, 17999)

Specific mappings listed per product.

inv-12: Covered product-indication mappings

Products and their listed 'Reason(s) for Request' and 'Application CPT/HCPCS Codes' are presented as covered indications when the clinical use matches the stated reason and appropriate coding is used.

product_entry: Each product listed (e.g., Pro3 Amniotic Fluid, ProgenaMatrix, Strattice, RECELL, etc.) has associated 'Reason(s) for Request' and 'Application CPT/HCPCS Codes'—coverage relies on matching product to indication and code.

See individual product lines in chunks 54-67 for exact product-code pairs.

inv-13: Wound care: indications for skin substitute use

Covered when ALL of the following are met

Wound readiness and prior therapy: Wound is chronic (not healed within 30 days–3 months) AND wound is free of infection, coagulum, sinus tracts, tunnels, cellulitis, eschar and necrotic tissue AND no exposure of joints/tendons/ligaments/bone30 days–3 months

Standard wound therapy appropriate to wound type must have been attempted (off-loading for DFU, compression for venous ulcers)

Perfusion and circulation: Adequate blood supply evidenced by palpable pedal pulse or ABI ≥ 0.70ABI ≥ 0.70

Alternative measures such as transcutaneous oxygen pressure ≥30 mmHg were used in trials

Patient medical optimization: Underlying medical conditions (eg, diabetes, hypertension) are adequately managed and HbA1C ≤12% for DFU patientsHbA1C ≤12%

Per trial eligibility and clinical recommendations

inv-14: Supported indications

Supported indications (evidence supports use)

Breast reconstruction: Use of acellular dermal matrices (e.g., AlloDerm) during tissue expander and implant reconstruction to provide coverage or recreate inframammary fold in appropriate candidates

Evidence supports AlloDerm for postmastectomy breast reconstruction

Prevention of Frey's syndrome after parotidectomy: Interposition barriers including AlloDerm reduce incidence of subjective and objective Frey's syndrome versus no barrier

Meta-analyses and RCTs report significant reductions

Dural grafting and selected surgical uses: Dural grafts described as standard of care in many neurosurgical/skull-based procedures where primary closure is difficult

Textbooks cited for dural graft use

Autologous whole blood clot (ActiGraft PRO) for hard-to-heal DFU: AWBC plus standard of care showed higher 12-week healing rates vs SOC alone in multicenter RCT

Trial inclusion criteria and outcomes cited

inv-15: Unproven/insufficient indications

Not supported / insufficient evidence

Other proposed indications for AlloDerm: Insufficient evidence to support AlloDerm for abdominal wall reconstruction in contaminated fields, many hernia repairs, cleft palate repair, lower eyelid surgery, oral surgery and other listed uses

Case series and retrospective reviews predominate; outcomes variable and randomized comparative data lacking

inv-16: AlloPatch Pliable for nonhealing diabetic foot ulcers

Covered when ALL of the following trial-like criteria are met (evidence from randomized trial):

AlloPatch DFU criteria: age ≥18; type 1 or 2 diabetes; DFU ≥1 cm² and ≥4 weeks duration failing prior treatment; no signs of infection; adequate circulation (dorsum TcPO2 ≥30 mmHg or ABI ≥0.7 and ≤1.2); wounds failing to reduce >20% during screening; application weekly up to 12 weeks; healed defined as 100% reepithelialization without drainage/dressingas listed

RCT showed higher healing at 12 weeks but small sample and short follow-up

inv-17: AmnioBand for venous leg ulcers and diabetic foot ulcers

Covered when ALL of the following trial-like criteria are met (evidence from randomized trials):

AmnioBand VLU/DFU criteria: age ≥18; adequate circulation (ABI >0.75 or SPP >30 mmHg or TcPO2 >30 mmHg); VLU area >1 cm² and ≤20 cm² for VLU trial; ulcer duration >1 month; clean granulating base after compression therapy screening; exclusion of infection and other causes; weekly or biweekly application with SOC up to 12 weeks; healing defined as macroscopic wound closure at 12 weeksas listed

VLU trial: 75% healed at 12 weeks vs 30% SOC; DFU trial: improved healing and faster time to closure

inv-18: Apligraf for venous stasis ulcers and full-thickness DFUs

Covered when ALL of the following are met (per FDA-labeled/trial criteria):

Apligraf criteria: Noninfected partial- or full-thickness venous stasis ulcers ≥1 month nonresponsive to medical management OR full-thickness neuropathic DFUs nonresponsive to standard therapy; HbA1c <12% for diabetics; ulcer free of sinus tracts, tunnels, cellulitis, eschar, necrotic tissue and osteomyelitis; adequate arterial supply (palpable pedal pulse or ABI ≥0.70); used with standard wound care; one initial application with up to 4 total in 12 weeks if indicatedas listed

Safety/efficacy beyond 5 applications not reported

inv-19: DermACELL for diabetic foot ulcers

Covered when ALL of the following trial-like criteria are met (evidence from multicenter RCT):

DermACELL DFU criteria: Single full-thickness target DFU Wagner grade 1 or 2; wound area ≥1 cm² and ≤25 cm²; wound depth ≤9 mm; adequate circulation (TcPO2 ≥30 mmHg or ABI 0.8–1.2 or biphasic Doppler); healed defined as complete reepithelialization with no drainage confirmed on two consecutive visitsas listed

DermACELL had statistically higher healing at 16 weeks vs conventional care

inv-20: DermACELL — Diabetic Foot Ulcer (evidence-supported scenario)

Covered when trial-like clinical criteria are met based on available RCT evidence

DermACELL for DFU - required conditions: Single, full-thickness target DFU (Wagner grade 1 or 2) with wound area ≥1 cm² and ≤25 cm², wound depth ≤9 mm, adequate circulation (e.g., TcPO2 ≥30 mmHg or ABI 0.8–1.2 or biphasic Doppler), and has received standard wound care; documented monitoring and follow-up for healing up to 16 weeks.see node text

Based on Walters et al. RCT showing higher proportion healed at 16 weeks vs conventional care.

inv-21: Dermagraft — FDA-indicated DFUs

Covered when all FDA-labeled conditions are met

Dermagraft indication criteria: Full-thickness lower extremity DFU (forefoot, toes or heel) >6 weeks duration refractory to standard wound care; patient diabetic with A1C <12%; ulcer free of sinus tracts/tunnels/infection/osteomyelitis/cellulitis/eschar/necrotic tissue; adequate blood flow (palpable pedal pulse or ABI ≥0.70); used with standard wound care; label limits initial application and allows additional applications up to product labelingsee node text

Label limits initial and repeat applications; up to 8 applications over 12 weeks if healing evident.

inv-22: DermACELL, FlexHD, GalaFLEX — Breast reconstruction and soft tissue support

Coverage stance varies by indication and evidence strength

Accepted use in breast reconstruction: DermACELL and FlexHD have evolved into accepted skin substitutes for postmastectomy/breast reconstruction based on case series and comparative retrospective data showing comparable outcomes to AlloDerm.evidence largely case series/retrospective

Providers should document indication and expected benefit.

GalaFLEX uses: GalaFLEX (P4HB) is FDA 510(k) indicated for soft tissue support in plastic and reconstructive surgery; evidence for use in breast reconstruction is primarily retrospective but used in some settings.retrospective evidence

Insufficient evidence for high-risk ventral/incisional hernia repair per review.

inv-23: Dural substitutes (DuraGen, Dura-Guard, DuraMatrix, Durepair)

Covered when used as dura mater repair in neurosurgical procedures where dural closure is difficult

Dural grafts indication: Use as a dural substitute for repair of dura mater defects to prevent CSF leakage when primary dural closure is difficult or not possible; device-specific FDA 510(k) status supports these indicationsdevice labeling

Medical textbooks and RCTs support use in neurosurgical contexts.

inv-25: GORE BIO-A — Soft tissue reinforcement (labelled uses)

Covered for FDA 510(k) approved soft tissue reinforcement indications

GORE BIO-A approved uses: Use for reinforcement of soft tissue including hernia repair, muscle flap reinforcement, perforated tissue repair and general tissue reconstruction per FDA 510(k) approval; appropriate when primary closure is not possible (e.g., disrupted crural fibers, large defect, tenuous closure)device labeling and surgical judgment

Routine mesh use in PEHR is not recommended; other indications lack established safety/efficacy.

inv-26: Product‑specific coverage evidence summary

Coverage and evidentiary summary by product and indication:

GORE BIO‑A — hiatal/paraesophageal hernia repair: May be appropriate when primary crural closure is not possible (e.g., disrupted crural fibers, large defect, tenuous or tensioned crural closure); routine mesh use in PEHR is not recommended

Observational evidence and surgical textbook guidance cited

Grafix — diabetic foot ulcers and VLUs: Randomized trials and assessments report Grafix improves healing and time to healing for partial and full-thickness DFUs and as adjunctive therapy for VLUs; insufficient evidence for complex DFUs with exposed tendon/bone

Trial and case series evidence summarized

Integra IDRT / Omnigraft — DFUs and burns: PMA approval and randomized trial evidence support use for certain nonhealing DFUs (>6 weeks, no exposed capsule/tendon/bone) and for thermal injuries when sufficient autograft unavailablePMA labeling and trial evidence

Use per labeled criteria

Kerecis Omega3 (FSG) — DFUs: Randomized controlled trials show higher healing rates and greater percent area reduction versus standard care or collagen alginate at 12–24 weeks for DFUs

RCTs cited (Dardari, Lantis, Lullove)

inv-27: Oasis Wound Matrix — conditions for use

Covered when ALL of the following are met:

Oasis candidacy: Patient has a partial- or full-thickness DFU >4 weeks duration or a venous stasis ulcer ≥1 month that has failed standard wound care; participating in ongoing medical management; A1C <12%; ulcer free of sinus tracts/tunnels/cellulitis/eschar/necrotic tissue; viable tissue at wound edges; adequate arterial blood supply (palpable pedal pulse or ABI ≥0.70)A1C < 12%; ABI >= 0.70

From product-specific guidance in policy.

inv-28: Kerecis Omega3 (fish skin graft) — trial context

Evidence summary (not explicit coverage criteria):

Trial population and procedures: Adults ≥18 with DFU ≥4 weeks, ulcer through dermis but not into tendon/muscle/bone, index ulcer size 1–25 cm²; initial 2-week SOC screening; randomized to SOC plus fish skin graft up to 12 weeks vs SOC with collagen alginate dressing; primary outcome percent closed at 12 weeks12-week endpoint

Single RCT showed higher closure with fish skin (67% vs 32%).

inv-31: Insufficient evidence — generalized conclusion

Summary of coverage-relevant evidence statements from this section

Insufficient evidence for many products: For numerous listed products (e.g., AxoGuard, Axolotl, BellaDerm, BioFix family, many Biodesign grafts) the published peer-reviewed evidence is insufficient (primarily case series, retrospective reviews, small RCTs or animal studies) to support safety and efficacy for the proposed indications

Supports restrictive coverage stance or requirement for additional evidence.

inv-32: Anal Fistula Plug — unfavorable evidence

Evidence specific to Anal Fistula Plug (Surgisis / Biodesign)

Anal Fistula Plug evidence: Randomized trials and reviews reported no consistent benefit versus standard surgical approaches, high failure/recurrence and complication rates (failure up to 59%, recurrence up to 75%), and variable outcomes depending on fistula type and patient factors; appropriate candidate selection is not well-established

Trials cited: Jayne 2021, van Koperen 2011, Ortiz 2009.

inv-34: Product-specific coverage considerations

Coverage stance by product — generally require adequate peer-reviewed evidence or explicit FDA indication:

Product-specific consideration: Each product is assessed individually; coverage is contingent on adequate peer-reviewed evidence or explicit FDA indication for the requested clinical useevidence of safety and efficacy

Many products summarized lack sufficient evidence and may require prior authorization justification.

inv-35: Coverage — evidence-based requirement

Products are assessed individually; coverage is contingent on adequate evidence of safety and efficacy for the requested indication.

General evidence requirement: Coverage considered when peer-reviewed evidence demonstrates safety and efficacy for the specific clinical indication and product, and when FDA clearance/approval supports that useevidence of safety and efficacy

Most products in this section are described as having insufficient evidence

Products with limited evidence: Examples (Fortiva, Gentrix/MatriStem, GORE BIO-A fistula plug, GraftJacket Xpress, Integra Reinforcement Matrix, Membrane Wrap/Graft, Matrix HD, MemoDerm, Miamnion) are noted as lacking sufficient peer-reviewed evidence and may require strong justification for coverageinsufficient evidence

Requests for these items require supporting justification or may be denied

Exception for FDA-cleared wound devices with supportive trials: Integra Flowable Wound Matrix has a randomized, placebo-controlled trial showing improved closure rates in a small DFU population; such evidence may support coverage in similar clinical scenarios with matching inclusion criteriatrial evidence with similar patient population

Single small RCT cited; further studies recommended

For multiple listed advanced skin substitute products, the policy specifies a treatment time window: additional applications beyond 12 weeks are considered not medically necessary regardless of wound status. This 12‑week limit is stated repeatedly in product-specific sections (for example, EpiFix, Oasis, Kerecis, Apligraf, Dermagraft, AmnioBand and others) and applies to initial and repeat application rules where noted.

When additional applications within the 12‑week window are allowed, they are typically conditional on documented evidence of wound healing (for example, epithelialization and reduction in ulcer size) and must not exceed the product‑specific maximum number of applications described in the policy.

The policy states that each product listed in the coverage tables is considered not medically necessary for any indication not specifically listed in the policy. Requests for use outside the product/indication mappings provided in the policy should be treated as not medically necessary unless explicit supportive evidence and coding are provided consistent with policy criteria.

Providers submitting requests for off‑label or unlisted indications should include clinical justification and supporting peer‑reviewed evidence and should confirm appropriate HCPCS/CPT coding per the policy; absent that, the request may be denied as not medically necessary.

The policy enumerates a large number of named products that are described as experimental, investigational, or unproven for any indication. Examples include (but are not limited to) many commercial amniotic/placental allografts, small‑intestinal submucosa products, various dermal matrices, synthetic scaffolds and other proprietary branded grafts and flowable preparations as listed in the policy product tables.

Because these products are listed as investigational or unproven, the policy indicates they lack sufficient peer‑reviewed evidence to support safety and effectiveness for the proposed uses; coverage for these products would therefore be unsupported absent compelling, indication‑specific evidence.

Within the cited policy sections for product lists and application mappings there are no additional, explicit blanket exclusions beyond those already stated (for example, the 12‑week limit for additional applications and the rule that unlisted indications are considered not medically necessary). Specific product entries may describe limited coding options (e.g., “No specific code”) or note insufficient evidence for particular uses, which functionally restrict coverage but are not presented as separate categorical exclusions in the referenced chunks.

Billing Codes, HCPCS and CPT Mapping

Covered graft codes (examples)mixedCovered

15040-15261	Autologous skin graft (CPT codes)
15271-15278	Unprocessed allogeneic human, cadaver skin graft / unprocessed xenogeneic pig skin graft (CPT codes)
Q4100	HCPCS code associated with certain unprocessed graft products

Breast reconstruction product codesmixedCovered

15777	Procedure application code for breast reconstruction products (CPT/HCPCS listed)
Q4116	AlloDerm product HCPCS code
Q4100	AlloMax product HCPCS code (also listed C1781)
C1781	AlloMax product HCPCS code (alternate)
Q4122	DermACELL product HCPCS code
Q4128	FlexHD product HCPCS code
C9399	Miscellaneous HCPCS code referenced for some products

Burn and wound product codesmixedCovered

15271-15278	Application CPT/HCPCS codes listed repeatedly for burn and wound products
C5271-C5278	Alternate application codes referenced
Q4100	Biobrane and other product HCPCS code
C9399	Alternate product HCPCS code
Q4105	Integra HCPCS code
Q4104	Integra Bilayer Matrix HCPCS code
Q4108	Integra Matrix Wound Dressing HCPCS code
A2012	Suprathel HCPCS code
Q4182	Transcyte HCPCS code
A2019	Kerecis Omega3 Marigen Shield HCPCS code

Diabetic foot ulcer product codesmixedCovered

15275-15278	Application CPT/HCPCS codes for many diabetic foot ulcer products
Q4101	Apligraf HCPCS code
Q4106	Dermagraft HCPCS code
Q4186	EpiFix HCPCS code
Q4132	Grafix HCPCS code
Q4151	AmnioBand HCPCS code
Q4168	AmnioBand alternate HCPCS code
Q4122	DermACELL HCPCS code
Q4133	Grafix alternate HCPCS code
Q4158	Kerecis Omega3 Wound HCPCS code

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Covered CPT/HCPCS Codes for EpiFixmixedCovered

15271-15278	Application CPT/HCPCS code range referenced for product application
Q4186	EpiFix Amniotic Membrane product HCPCS code

Covered CPT/HCPCS Codes for GrafixmixedCovered

15271-15278	Application CPT/HCPCS code range referenced for Grafix application
Q4132	Grafix product HCPCS code
Q4133	Grafix product HCPCS code (alternate)

Covered CPT/HCPCS Codes for Oasis Wound MatrixmixedCovered

15271-15278	Application CPT/HCPCS code range referenced for Oasis Ultra Tri-Layer Matrix
C5271-C5278	Application CPT/HCPCS alternate codes for Oasis
Q4102	Oasis product HCPCS code
Q4124	Oasis product HCPCS code

Dural repair product HCPCS codesHCPCSCovered

Q4100	Generic HCPCS product code used for multiple dural and biologic graft products
C1763	Dural graft product HCPCS code
C9399	Miscellaneous product code referenced with several dural products
C1781	Product HCPCS code referenced for SYNTHECEL Dura Repair

Product and application codes for listed biologic/amniotic products (extensive list)mixed

15271-15278	Application CPT/HCPCS code range used repeatedly for wound care products
C5271-C5278	Application CPT/HCPCS alternate codes
Q41xx / C17xx / Q42xx / A2020 / J3590 / Q4xxx	Multiple product HCPCS codes listed for numerous specific products (see policy text)

Common Application and Product Codesmixed

15271-15278	Application CPT range for skin substitutes/wound coverings as mapped in this policy
C5271-C5278	Application temporary codes used alongside CPT 15271-15278
Q4100	Product HCPCS frequently used for listed biologic products
C9399	Product HCPCS alternative code used for some products

Detailed Product HCPCS/CodesHCPCS

C1763	Product HCPCS cited for certain grafts
C1781	Product HCPCS cited for certain grafts/meshes
Q4271	Complete FT product HCPCS
Q4270	Complete SL product HCPCS
Q4236	carePATCH product HCPCS
A6010	CellerateRX product HCPCS
Q4156	Clarix 100 / Neox 100 product HCPCS
Q4264	Cocoon membrane product HCPCS
Q4193	Coll-e-Derm product HCPCS
Q4229	Cogenex Amniotic Membrane product HCPCS

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Procedure CPT CodesCPT

64910	NeuraGen peripheral nerve repair CPT
64999	Unlisted procedure code used for some nerve protector applications
46707	GORE BIO-A Fistula Plug application CPT for anorectal fistulas
15777	OrthADAPT / Permacol listed application CPT for soft tissue reinforcement
17999	Unlisted code referenced in product mapping

Product and application codesmixed

Q4100	Product HCPCS code referenced for many biologic graft products
C9399	Product HCPCS code referenced for many biologic graft products
15271-15278	CPT range cited for application of various wound care membranes and grafts
C5271- C5278	CPT/HCPCS-like references associated with skin substitute applications in document
15777	CPT code cited for certain soft tissue reinforcement applications
17999	Unlisted procedure code cited for some applications
J3590	HCPCS used for some injectable biologic products
C1763	Product HCPCS/CPT cross-reference for certain implants/scaffolds
C1781	Product HCPCS referenced for several scaffolds/patches
C9356	Product HCPCS for TenoGlide tendon protector

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Procedure CPT codes (device-related)CPT

15011-15018

CPT range associated with RECELL Autologous Cell Harvesting Device applications

Device 510(k) clearances mentionedmixed

BK190349	RD2 system 510(k) approval (Nov 8, 2019)
BK200464	RD2 System additional 510(k) clearance (Mar 3, 2020)
BK210570	RD2 Ver.02 System 510(k) clearance (June 22, 2021)

Device and product identifiers discussed (no billing codes listed in this excerpt)mixed

No codes listed

510(k) clearances citedmixed

K182681	AC5 Topical Gel 510(k) clearance (Dec 14, 2018)
K190129	AC5 subsequent 510(k) (Mar 11, 2020)

PMA/approvalsmixed

PMA	TransCyte FDA PMA approval for full- or partial-thickness burns

General FDA 510(k) referencesmixed

510(k)

Oasis and Phasix ST referenced as FDA 510(k) cleared products

No billing codes listed in this sectionmixed

No codes listed

Products with FDA 510(k) clearance mentioned (no billing codes listed)mixed

No codes listed

Regulatory / product references (no billing codes listed in this section)mixed

No codes listed

No CPT/HCPCS codes listed in this sectionmixed

No codes listed

Ankle-Brachial Index (ABI) — clinical threshold

ThresholdAn ankle-brachial index (ABI) of ≥ 0.70 is required to demonstrate adequate blood supply for lower-extremity wound coverage.

Clinical contextABI used to assess perfusion for diabetic foot ulcers (DFUs) and venous stasis ulcers (VSUs) prior to skin substitute use.

Documentation noteRecord ABI measurement and method (e.g., Doppler-derived ABI) within 60 days of application when submitting prior authorization.

Hemoglobin A1c (HbA1c) — clinical threshold

ThresholdHemoglobin A1c (HbA1c) requirement: less than 12% for diabetic patients considered for skin substitute therapy.

Clinical contextGlycemic control recommendation applies to DFU candidates (optimize diabetes management to maximize healing).

Documentation noteInclude most recent HbA1c result in prior authorization submission (value and date).

Ankle-brachial index (ABI) — clinical threshold repeated

ThresholdAn ankle-brachial index (ABI) of ≥ 0.70 is required to demonstrate adequate blood supply for lower-extremity wound coverage.

ApplicationABI requirement cited for both diabetic foot ulcers and venous stasis ulcers when evaluating candidacy for skin substitutes.

Alternative measuresTranscutaneous oxygen or other perfusion tests may be acceptable per trial/device criteria; document method and result.

Ulcer duration before consideration — > 4 weeks

ThresholdUlcer duration: greater than 4 weeks (chronic wound defined as not healed within 30 days to 3 months; many product criteria specify >4 weeks) before advanced skin substitute consideration.

Standard therapyApply after failure of appropriate standard wound therapy (off-loading for DFU, compression for VLU) during the chronicity period.

Documentation noteDocument dates and types of prior standard wound care attempted during the screening period (e.g., 2-week SOC lead-in in trials).

Time window for additional applications — Within 12 weeks

Time windowAdditional applications beyond the initial treatment are allowed only within a 12-week window; applications beyond 12 weeks are considered not medically necessary.

Application limitsInitial and total allowed applications are product-specific (commonly 4–5 initial applications; additional applications permitted within 12 weeks when evidence of healing is present).

Denial riskRequests for applications after 12 weeks risk denial as not medically necessary per policy language.

Hemoglobin A1C — 12%

ThresholdHemoglobin A1c (HbA1c) should be ≤ 12% (policy expresses HbA1c <12% or HbA1c ≤12% in trial-derived criteria).

ApplicationRequirement applies to diabetic patients considered for DFU-specific products (document most recent HbA1c).

RationaleOptimized glycemic control expected to maximize wound healing potential per trial inclusion and device labeling.

Ankle-Brachial Index (ABI) — 0.70

ThresholdAnkle-Brachial Index (ABI) requirement: ABI ≥ 0.70 to demonstrate adequate perfusion for lower-extremity wound therapy candidacy.

Clinical useABI ≥ 0.70 is cited across DFU and VSU product sections (used with palpable pedal pulse as alternative evidence).

DocumentationInclude ABI value and date (within recent 60 days per trials) when requesting prior authorization.

DFU size for trial — > 1 cm2 and < 28 cm2

Size rangeDiabetic foot ulcer (DFU) trial eligibility example: index ulcer area > 1 cm² and < 28 cm².

Trial screeningMany trials used a standard-of-care screening period prior to randomization and applied size thresholds at enrollment.

Documentation noteRecord measured ulcer area (cm²) at time of request to match trial-derived criteria when applicable.

Transcutaneous oxygen pressure — 30 mmHg

ThresholdTranscutaneous oxygen pressure (TcPO2) threshold used in trials: ≥ 30 mmHg to indicate adequate limb perfusion.

Alternative metricsTrials and device criteria accept TcPO2, skin perfusion pressure, or ABI within specified ranges as evidence of adequate circulation.

DocumentationProvide TcPO2 value and testing date when available for prior authorization and trial-matching submissions.

Ankle-brachial index (ABI) — >= 0.70 (trial requirement)

ThresholdAnkle-brachial index (ABI) ≥ 0.70 required for trial/device eligibility or demonstration of adequate perfusion in DFU candidates.

Label/Trial consistencyABI ≥ 0.70 appears consistently in product labeling and trial inclusion criteria for DFU-related products.

Documentation noteRecord ABI method (e.g., Doppler) and date; acceptable alternative perfusion measures should be documented if ABI not available.

Transcutaneous oxygen measurement — >= 30 mmHg

ThresholdTranscutaneous oxygen measurement (TcPO2) ≥ 30 mmHg used in trial eligibility and device criteria to demonstrate adequate perfusion.

ContextTcPO2 cited for AlloPatch, DermACELL and other trial-derived inclusion criteria as an objective perfusion measure.

DocumentationInclude TcPO2 value and test date when available; acceptable alternatives include ABI or toe pressures per product guidance.

HBA1c for diabetes trials — < 12%

ThresholdHbA1c for diabetes trials: < 12% (trial eligibility and product labeling commonly require HbA1c below 12%).

Trial contextKerecis and other DFU trials excluded patients with HbA1c >12% to optimize healing potential in study populations.

Documentation noteProvide most recent HbA1c and date when requesting coverage to match trial-derived criteria.

DermACELL wound size/depth inclusion (trial) — wound area 1 cm2 and 25 cm2; wound depth 9 mm; Wagner grade 1 or 2

Wound areaTrial inclusion example (DermACELL): wound area ≥ 1 cm² and ≤ 25 cm².

Wound depthMaximum wound depth in trial: ≤ 9 mm.

Severity gradingWagner grade 1 or 2 required in the DermACELL trial eligibility.

Dermagraft perfusion threshold (label) — ABI 0.70 or palpable pedal pulse

Perfusion thresholdDermagraft labeling: adequate perfusion evidenced by ABI ≥ 0.70 or presence of a palpable pedal pulse.

A1C requirementDermagraft labeling requires A1C < 12% for diabetic patients as part of selection criteria.

Application limitsDermagraft indicated for one initial application; if healing observed, up to eight total applications over 12 weeks may be considered per label and policy.

Dermagraft A1C threshold — A1C < 12%

A1C thresholdDermagraft A1C threshold: A1C < 12% required for diabetic patients in labeling and policy criteria.

Clinical implicationEnsure patients are under routine medical diabetes management with documented A1C prior to application.

Documentation noteInclude A1C value and date in authorization materials to match labeled criteria.

Index ulcer size — 1 cm6 and 25 cm6 (Kerecis trial eligibility)

Index ulcer sizeKerecis trial eligibility example: index ulcer area ≥ 1 cm² and ≤ 25 cm².

Trial contextKerecis RCTs used an initial SOC screening period and size limits when randomizing DFU patients to fish skin graft vs SOC.

Documentation noteProvide measured index ulcer area to align with trial-derived inclusion criteria when relevant to coverage requests.

Ankle-Brachial Index (ABI) — ABI 0.70 required for Oasis candidacy

ABI requirementOasis candidacy: ankle-brachial index (ABI) ≥ 0.70 or palpable pedal pulse required to demonstrate adequate arterial blood supply.

A1C requirementDiabetic patients considered for Oasis should have A1C < 12% and be participating in ongoing medical management.

Wound conditionUlcer must be free of sinus tracts, tunnels, cellulitis, eschar and necrotic tissue; viable tissue around wound edges required.

Prior Authorization, Documentation, and Practice Requirements

Billing Rule

Coverage requires submission per policy criteria — use correct codes

Coverage determinations must follow the relevant criteria outlined in this Coverage Policy. Reimbursement is provided only if the requested service meets the policy conditions, is submitted with covered diagnosis and procedure codes, and aligns with the applicable benefit plan and laws/regulations.

Submit requests with the most appropriate CPT/HCPCS/ICD codes effective on the date of service.
Claims lacking covered codes will be denied as not covered.

Prior Authorization

Prior authorization required — include product name, indication, and coding

Prior authorization is required for covered advanced biologic products and for many graft/matrix applications listed in this policy. Include the product name, intended clinical indication, wound characteristics, and matching HCPCS/CPT codes when requesting authorization.

State the product name and corresponding HCPCS/CPT codes being billed.
Provide the intended anatomic site and clinical reason for the request.
If applicable, reference the FDA-labeled indication for the product.
Confirm product regulatory status (e.g., 510(k), PMA, HCT/P) in the submission.

Prior Authorization

Prior authorization: document wound chronicity, prior standard therapy, and perfusion

Provide documentation that conventional/standard wound therapy was attempted and failed per the policy-specified lead-in periods before advanced biologic use. Document wound chronicity, prior treatments, and objective perfusion measures.

Document duration of ulcer (commonly >4 weeks or as specified for product).
Describe prior standard wound therapy (e.g., off‑loading, debridement, compression for VLU) and the run‑in period results.
Provide perfusion evidence: palpable pedal pulse and/or ABI (commonly ≥0.70) or equivalent objective tests (TcPO2, toe‑brachial index).

Step Therapy

Application sequencing and product-specific application limits

Application limits and sequencing: many products have maximum initial and cumulative application counts and time windows. Requests for additional applications beyond policy limits or beyond 12 weeks are generally not medically necessary.

Apligraf: one initial application; if coverage <100% and wound not progressing, up to four total applications within 12 weeks may be used.
Dermagraft: one initial application; if healing observed, up to eight total applications within 12 weeks may be allowed per labeling.
Grafix/Oasis/other products: observe stated limits (e.g., initial treatments limited to 4–5 applications with additional applications allowed only within a 12‑week window when healing is evident).
Additional applications beyond 12 weeks are considered not medically necessary.

Prior Authorization

Prior authorization should reference FDA indication and labeled-use documentation

Some products have specific labeled FDA PMA/510(k) indications (e.g., Integra IDRT/Omnigraft, Apligraf, Dermagraft). Prior authorization should reference the exact FDA‑labeled indication and provide documentation that the ulcer meets those labeled criteria when applicable.

Include device regulatory status (PMA, 510(k)) and cite the labeled indication in the request.
For Integra IDRT/Omnigraft: document diabetic foot ulcer duration (>6 weeks) and absence of exposed capsule, tendon or bone when claiming labeled PMA indication.

Note

Confirm regulatory status (PMA/510(k)/HCT/P) before authorization

Confirm regulatory status and market availability before authorizing. Some products are processed/marketed as HCT/Ps (21 CFR Part 1271) or have had market suspensions or manufacturer actions that affect availability.

When applicable, indicate whether the product is regulated as an HCT/P and provide manufacturer/processing accreditation (e.g., AATB).
Check for recent market or regulatory actions (e.g., product suspension) that may affect coverage/availability.

Prior Authorization

Prior authorization — provide regulatory and supporting evidence for products with limited data

Evidence expectations: for products lacking robust published peer‑reviewed evidence, prior authorization may require submission of supporting clinical studies and clear clinical justification. Many devices/products are described as having insufficient evidence to support safety and effectiveness for certain indications.

Submit relevant peer‑reviewed studies, FDA clearance/approval documentation, and rationale for use when evidence is limited.
Be aware that products with insufficient evidence may be denied or considered not supported for the requested indication.
Fortiva and many other named products lack sufficient evidence and are at higher risk for denial.

Billing Rule

Coding and billing documentation — match codes to product and indication

Coding, billing, and indication matching are critical. Claims may be denied for coding mismatches, unsupported indications, or when services are billed without the covered codes required by this policy.

Use the most appropriate CPT/HCPCS codes as of the effective date of service.
Requests that lack a matching HCPCS/CPT code for the product or for the intended application may be denied.
Applications for venous stasis ulcers or DFUs require documentation of failure of standard wound therapy and adequate perfusion (ABI ≥0.70 or palpable pedal pulse) or risk denial.

Denial Risk

Contraindicated wound conditions — do not apply advanced biologics to infected/necrotic wounds or exposed critical structures

Contraindications and wound conditions that preclude use of skin substitutes or grafts should be documented. Products are contraindicated for infected wounds, necrotic tissue, exposed joints/tendons/ligament/bone, tunnels/sinuses, or inadequate blood supply.

Confirm the treated wound is free of infection, necrosis, sinus tracts/tunnels, and exposed critical structures before authorization.
If contraindicating features are present, document alternative plans or justify why the product is still indicated.

Documentation Required

Required and suggested clinical and regulatory documentation for authorization requests

Required and suggested documentation elements to include with authorization requests to support medical necessity and reduce denial risk.

Patient comorbidities and relevant management (e.g., diabetes control, HbA1c <12% when specified).
Wound characteristics: size, depth, Wagner grade, contamination status, presence/absence of exposed tendon/bone, and prior debridement adequacy.
Objective perfusion measures: ABI, TcPO2, toe brachial index, or documented palpable pulses within timeframe specified by product trials.
Prior treatments attempted and duration (e.g., off‑loading, compression, debridement) and run‑in screening results from standard‑of‑care periods used in trials.
Device/product specifics: brand, product version, HCPCS/CPT codes, FDA status, and manufacturer processing or accreditation (e.g., AATB).
For products with limited evidence, include pertinent clinical studies and regulatory status documentation.

Step Therapy

Step therapy: standard wound care expected before advanced biologics

Step‑therapy expectations: although no formal step‑therapy program is specified, standard wound care is expected first. Many randomized trials included a run‑in period of standard care before authorization of advanced products.

Document participation in and failure of standard wound care (off‑loading, compression, debridement, infection management) prior to advanced product use.
For DermACELL and other products, provide prior standard therapy documentation consistent with trial inclusion criteria.

Prior Authorization

Product‑specific selection and labeling requirements

Special patient selection and product-specific criteria to note when requesting authorization.

Oasis: patient should be in ongoing medical management with HbA1c <12% for diabetic foot ulcers.
Apligraf: initial application indicated; up to four total applications in 12 weeks if adherent/progression criteria met.
Dermagraft: product labeling limits initial and repeat applications; document wound eligibility (no infection/osteomyelitis) and adequate perfusion.
Integra IDRT: prior‑authorization should document that the ulcer meets labeled PMA criteria (e.g., >6 weeks duration, no exposed bone/tendon/capsule).

Denial Risk

Denial risk — insufficient evidence, off‑label use, and specific products of concern

Denial risks for products or indications lacking adequate evidence or used off‑label. Certain devices (e.g., Anal Fistula Plug, Fortiva) and many listed products have insufficient evidence and pose elevated denial risk.

Anal Fistula Plug: randomized trials and reviews show high failure/recurrence and severe complications — high risk of denial.
Fortiva porcine dermis and multiple other products are noted as having insufficient evidence to support use for soft tissue reinforcement — include literature or expect denial.
Requests for off‑label uses or unsupported indications without strong evidence are likely to be denied.

Note

Consider established comparators and document rationale when selecting advanced products

Consideration of established comparators and surgical alternatives when appropriate. Where evidence shows no benefit over standard surgical options, established comparators should be tried or documented.

For anal fistula and other surgical conditions, document prior surgical options or rationale for selecting the biologic/device versus established surgical comparators.
Medical directors may exercise clinical judgment; provide clear comparative rationale and supporting evidence when requesting coverage for newer techniques.

Background, Definitions and Evidence Context

This policy addresses indications for a broad range of tissue‑engineered skin substitutes and unprocessed grafts used to cover and manage wounds and to support reconstructive procedures. Covered clinical contexts include acute and chronic wound coverage (such as burns, diabetic foot ulcers, and venous stasis ulcers) as well as selected surgical and reconstructive uses (for example, breast reconstruction and dural repair) where product‑ and indication‑specific criteria are met.

Coverage is product‑specific and contingent on meeting stated clinical criteria (for example, failure of standard therapy, documented wound chronicity, and adequate perfusion) and on adherence to application limits, coding requirements, and prior authorization processes described in the policy.

Tissue engineered skin substitutes — definition and scope

DefinitionTissue-engineered skin substitutes are bioengineered skin products (human skin equivalents) that may be acellular (matrix/scaffold) or cellular (contain living cells) used as temporary or permanent wound coverings.

ComponentsAcellular products provide a scaffold (e.g., collagen, hyaluronic acid); cellular products contain living fibroblasts/keratinocytes (allogeneic or autologous).

IndicationsUsed for burns, chronic wounds (DFU, VLU), breast reconstruction, duraplasty and other surgical applications when criteria are met.

Adequate blood supply — Presence of a palpable pedal pulse or an ankle-brachial index (ABI) of 0.70.

DefinitionAdequate blood supply: presence of a palpable pedal pulse or an ankle-brachial index (ABI) of ≥ 0.70 is required to consider skin substitute application for lower-extremity wounds.

Alternative measuresTrials and devices also accept transcutaneous oxygen pressure (TcPO2 ≥ 30 mmHg) or toe pressures when documented.

DocumentationRecord method and result of perfusion testing (ABI, TcPO2, toe pressures) within the timeframe specified by product/trial criteria.

Evidence of wound healing — Clinical signs such as epithelialization and reduction in ulcer size used to justify additional applications.

DefinitionEvidence of wound healing: clinical signs such as epithelialization and reduction in ulcer size used to justify additional applications within the allowed 12-week window.

Policy useAdditional graft applications are permitted when documentation shows graft adherence or wound progression (e.g., epithelialization), per product-specific limits.

DocumentationInclude serial wound measurements and clinical notes demonstrating epithelialization or percent area reduction when requesting repeat applications.

Application mapping — The CPT/HCPCS procedure codes associated with clinical use

Application codesCommon application CPT/HCPCS codes mapped to product use include CPT 15271-15278 and temporary C5271-C5278; use the listed application code when submitting claims.

Product-to-code mappingPolicy maps specific product HCPCS (e.g., Q41xx, C17xx, Q42xx) to clinical indications; include both application and product codes on requests when provided.

Unlisted scenariosSome products list 'No specific code' and may require use of unlisted procedure codes (e.g., 17999) or miscellaneous HCPCS—confirm coding before submission.

Product HCPCS codes — The HCPCS codes used to bill the graft or membrane product

HCPCS examplesProduct HCPCS codes used in the policy include Q4100, C9399 and many product-specific Q-/C- codes (see detailed product rows for exact codes).

Billing guidanceWhen billing, provide the specific product HCPCS and matching application CPT/HCPCS codes as listed to align with coverage mappings.

Prior authorizationPrior authorization requests should include the product HCPCS and product name to match the policy's product-code mapping entries.

biologic skin substitute — definition

DefinitionBiologic skin substitute: skin harvested from a donor source (autograft, allograft, or xenograft) used for temporary or permanent wound coverage; may be resorbed or incorporated.

ExamplesIncludes autograft, cadaveric human dermis, porcine or fish-derived grafts used to provide coverage and a scaffold for healing.

RegulationDonated biologic skin products may be regulated as HCT/Ps or devices depending on processing and intended use.

tissue-engineered skin substitute (HSE) — definition

DefinitionTissue-engineered skin substitute (HSE): bioengineered skin products that are acellular (matrix/scaffold) or cellular (contain living fibroblasts/keratinocytes), used as temporary or permanent coverings to promote wound healing.

Product typesAcellular HSEs provide scaffolds for host cell infiltration; cellular HSEs supply living cells to the wound environment.

Clinical useUsed for burns, DFUs, VLUs and other chronic wounds when selection criteria are met.

Acellular skin substitute — definition

DefinitionAcellular skin substitute: cadaveric human dermis or other matrix with cellular material removed; serves as a scaffold for host cell infiltration and tissue remodeling.

ExamplesProducts such as DermACELL (acellular human dermis), Oasis (porcine-derived acellular collagen matrix), and Integra (acellular bovine collagen matrix) fall into this category.

Regulatory noteMany acellular products are regulated via FDA 510(k) or as HCT/Ps depending on processing and claims.

Cellular skin substitute — definition

DefinitionCellular skin substitute: matrix containing living cells (e.g., fibroblasts, keratinocytes) that may be allogeneic or autologous; designed to actively promote healing.

ExamplesApligraf and Dermagraft are cellular products regulated via FDA PMA with labeled indications for selected ulcers.

Clinical implicationCellular products often have specific labeled application limits and patient selection criteria (e.g., A1C, perfusion).

Banked human tissue — definition

DefinitionBanked human tissue: donated skin or placental tissue minimally processed and not structurally changed; regulated under HCT/P rules rather than as a medical device.

ExamplesGrafix (cryopreserved placental membrane), AmnioBand and EpiFix are examples of products regulated as or derived from banked human tissue.

Regulatory noteSuch products are subject to FDA 21 CFR Part 1271 and AATB standards where applicable.

Apligraf — product definition

ProductApligraf: a bilayered living skin equivalent FDA PMA-approved for certain venous stasis ulcers and full-thickness DFUs nonresponsive to standard care; selection criteria include A1C <12% and ABI ≥ 0.70.

Application limitsOne initial application is indicated; up to four total applications in 12 weeks may be used if wound not progressing and coverage partial.

Clinical requirementsUlcer must be free of sinus tracts, tunnels, cellulitis, eschar, necrotic tissue or osteomyelitis; used with compression (VLU) or standard diabetic ulcer care.

AmnioBand/Guardian — product definition

ProductAmnioBand/Guardian: human amnion and chorion allograft membrane used as a wound scaffold in hydrated or dehydrated forms for chronic wounds including DFUs and VLUs.

Trial sizingAmnioBand trial inclusion used perfusion thresholds (ABI>0.75 or TcPO2>30 mmHg) and size limits for VLU/DFU trials (e.g., VLU area criteria), with weekly or biweekly application schedules up to 12 weeks.

RegulationProcessed per FDA HCT/P regulations and AATB standards as applicable.

DermACELL — product definition

ProductDermACELL: acellular human dermis processed with MatrACELL to remove >97% donor DNA; proposed for DFUs, VSUs, burns, and breast reconstruction with evidence supporting DFU use in RCTs.

Trial criteriaDermACELL RCT included single full-thickness DFU Wagner grade 1 or 2, wound area ≥1 and ≤25 cm², depth ≤9 mm, and objective perfusion criteria (TcPO2 ≥30 mmHg or ABI 0.8-1.2).

LimitationsEvidence for complex DFUs that probe to tendon/bone is limited and primarily case series; document trial-like criteria when seeking coverage.

EpiFix — product definition

ProductEpiFix: an amnion/chorion membrane allograft processed by Purion containing growth factors, cytokines and ECM proteins; proposed for acute and chronic wounds with RCT evidence supporting DFU and VLU use.

FormatsAvailable as membranes/sheets and micronized powder (evidence for micronized powder and other indications is lacking).

Application limitsPolicy limits initial and additional applications per product-specific coverage rules (commonly 4 initial applications for EpiFix in VSU).

Dermagraft — product definition

ProductDermagraft: a cryopreserved dermal substitute approved by FDA PMA for lower-extremity full-thickness DFUs refractory to standard care and meeting labeled criteria (A1C <12%, adequate perfusion).

Label limitsInitial application limited; if healing observed, up to eight applications over 12 weeks may be considered per labeling and policy.

Clinical requirementsUlcer must be free of sinus tracts, tunnels, infection, osteomyelitis, cellulitis, eschar or necrotic tissue; adequate blood flow required (ABI ≥ 0.70 or palpable pedal pulse).

DuraGen / Dura-Guard / DuraMatrix / Durepair — product definition

ProductsDuraGen / Dura-Guard / DuraMatrix / Durepair: collagen-based resorbable dural substitutes (bovine-derived or bovine pericardium) FDA 510(k) approved for repair of dura mater defects to prevent CSF leakage.

Clinical useUsed when primary dural closure is difficult or not possible; supported by textbooks and comparative trials showing no significant differences in complications for certain approaches.

Coding noteApplication and product HCPCS codes vary by product; include device-specific coding in authorization requests.

GORE BIO-A — product definition

ProductGORE BIO-A: synthetic bioabsorbable copolymer scaffold (PGA:TMC) FDA 510(k) approved for soft tissue reinforcement including hernia repair and related reconstructions.

SizesAvailable in multiple sizes (examples: 7x10 cm, 8x8 cm, 9x15 cm, 10x30 cm, 20x20 cm, 20x30 cm).

Clinical guidanceAppropriate for reinforcement when primary closure is not possible (e.g., disrupted crural fibers, large defect); routine mesh use in PEHR not recommended.

GORE BIOA — product definition (additional)

ProductGORE BIO‑A: synthetic bioabsorbable copolymer fiber (PGA:TMC) used for soft tissue reinforcement; FDA 510(k) Class II device for hernia and related repairs.

Clinical evidenceObservational studies report variable recurrence and infection rates; evidence for other indications remains limited.

Regulatory noteDevice cleared via 510(k); providers should document surgical scenario justifying mesh use when primary closure is tenuous.

Grafix — product definition

ProductGrafix: cryopreserved human placental membrane products (GrafixCore/Prime/PL) containing extracellular matrix and viable cells, proposed for acute and chronic wounds including DFUs and VLUs.

RegulationGrafix is regulated as banked human tissue and the manufacturer is AATB-accredited; multiple formulations are available (Grafix PRIME, CORE, PL).

Clinical evidenceRCTs and case series report improved healing for DFUs and VLUs; evidence for complex DFUs with exposed tendon/bone is limited and primarily case series.

Integra IDRT / Omnigraft — product definition

ProductIntegra IDRT / Omnigraft: bovine collagen-based dermal regeneration template with FDA PMA approval for specific thermal injuries and certain diabetic foot ulcer indications (>6 weeks duration, no exposed capsule/tendon/bone) when used with standard care.

Regulatory statusIDRT/Omnigraft have PMA approval for specific indications; coverage aligns with labeled criteria and trial inclusion requirements.

Clinical evidenceSupported by randomized controlled trials for non-healing DFUs; most subjects required one application in trials.

Kerecis Omega3 (FSG) — product definition

ProductKerecis Omega3 (FSG): acellular processed fish dermal matrix containing omega-3 fatty acids, FDA 510(k) cleared for partial and full-thickness wounds with RCT evidence supporting DFU healing.

Trial eligibilityKerecis trials included DFUs with index ulcer sizes typically ≥1 cm² and ≤25 cm² and required adequate perfusion; SOC screening periods were used.

Clinical outcomesRCTs reported higher closure rates versus SOC or comparator dressings at 12–24 weeks in several studies; infection was a noted adverse event in some trials.

Oasis Wound Matrix — product definition

ProductOasis Wound Matrix: a porcine-derived, acellular collagen matrix (510[k] cleared) for management of partial and full-thickness wounds including pressure, venous, diabetic and chronic vascular ulcers.

Patient selectionOasis use requires chronic ulcer failing standard care, viable tissue at wound edges, A1C <12% for diabetic patients, and adequate arterial supply (palpable pedal pulse or ABI ≥ 0.70).

Application limitsPolicy limits initial applications and allows additional applications within a 12-week window when evidence of healing is present; beyond 12 weeks not medically necessary.

TransCyte — product definition

ProductTransCyte: a human bilaminate temporary skin substitute (PMA-approved) for full- or partial-thickness burns used as a temporary covering until autograft is possible.

IndicationUsed after surgical excision of burns as a temporary dressing; supported by RCTs and prospective series for burn care.

Regulatory notePMA-approved device with specified burn-related indications; not intended as permanent graft in these uses.

HCT/P — definition

DefinitionHCT/P: Human Cells, Tissues, and Cellular or Tissue-Based Products regulated under 21 CFR Part 1271 and Section 361 of the PHS Act.

Regulatory implicationProducts regulated as HCT/Ps may not require PMA/510(k) and are governed by tissue processing and donor screening rules; documentation of sourcing/processing may be needed for authorization.

ExamplesSeveral amniotic/placental-derived allografts (e.g., AmnioCore, Grafix variants) are regulated under HCT/P rules per policy descriptions.

PMA — definition and example

DefinitionPMA (Premarket Approval): FDA regulatory pathway requiring clinical data to support claims for high-risk devices; examples include Apligraf and Dermagraft.

Clinical implicationCoverage for PMA-labeled indications aligns with the strict labeled criteria (e.g., duration, perfusion, A1C) described in product labeling and policy.

DocumentationWhen requesting coverage for PMA-labeled uses, include documentation demonstrating all labeled inclusion criteria are met.

HCT/P — regulatory note (additional)

DefinitionHCT/P regulatory note: Human Cellular and Tissue-based Products are regulated under 21 CFR Part 1271; several products in the policy are described as HCT/Ps processed according to FDA requirements and AATB standards.

ImplicationHCT/P classification affects premarket review requirements and may influence documentation and coding expectations for authorization.

Provider actionConfirm current regulatory classification of the product (HCT/P vs device) when requesting coverage and include processing/accreditation details if available.

AATB-accredited — accreditation note

AccreditationAATB-accredited: accreditation by the American Association of Tissue Banks noted for multiple manufacturers as part of processing standards and expected documentation.

ImplicationProducts processed and distributed under AATB-accreditation should have sourcing and processing documentation available for authorization requests.

Provider actionInclude manufacturer accreditation or tissue bank registration details in prior authorization when applicable.

ECM matrix / graft — definition

DefinitionECM matrix / graft: a biologic extracellular matrix product derived from human or porcine tissues (e.g., dermis, amnion, small intestinal submucosa) intended to provide a scaffold for tissue remodeling and repair.

ExamplesProducts such as Cytal, CorMatrix, and various porcine or bovine-derived matrices are characterized as ECM grafts in the policy.

Clinical useUsed for wound coverage, soft tissue reinforcement, or as barriers depending on product-specific indications and evidence.

Amniotic membrane allograft — definition

DefinitionAmniotic membrane allograft: products derived from placental amniotic tissue (dehydrated, cryopreserved, or flowable) used for wound and soft tissue applications and containing growth factors and ECM proteins per manufacturer descriptions.

FormatsAvailable as membranes, micronized powders, flowable products; efficacy evidence varies by format and product.

Regulatory noteMany amniotic products are regulated as HCT/Ps under 21 CFR Part 1271; document processing and accreditation when submitting requests.

FDA 510(k) clearance — definition

DefinitionFDA 510(k) clearance: regulatory status indicating the device was reviewed by FDA as substantially equivalent to a legally marketed device for specific indications.

ImplicationProducts with 510(k) clearance (e.g., Oasis, GORE BIO-A, Kerecis variants) have indications defined by the clearance; prior authorization should reference the exact cleared indication when applicable.

DocumentationInclude FDA 510(k) number or product labeling when requesting coverage for a 510(k)-cleared device to support intended use.

HCT/P / Section 361 regulation — definition

DefinitionHCT/P / Section 361 regulation: products processed from human tissue regulated solely under section 361 of the Public Health Service Act and 21 CFR Part 1271 (e.g., many amniotic/umbilical products) not subject to FDA premarket device review.

ImplicationThese products rely on donor screening and processing standards; clinical effectiveness evidence varies and is often limited in peer-reviewed literature.

Provider actionWhen applicable, provide HCT/P processing and accreditation information with authorization requests to support safety considerations.

GORE BIO-A Fistula Plug — product definition

ProductGORE BIO-A Fistula Plug: synthetic bioabsorbable scaffold (PGA:TMC copolymer) supplied as a preformed 3D mesh intended for reinforcement of soft tissue in repair of anorectal fistulas; FDA 510(k) cleared.

EvidencePolicy notes insufficient peer-reviewed evidence to support safety and efficacy for this indication; manufacturer indicates product has been discontinued.

Coverage implicationRequests for this product should include clinical justification and supporting literature; absence of evidence may lead to denial.

Integra Flowable Wound Matrix — product definition

ProductIntegra Flowable Wound Matrix: granulated, acellular bovine tendon collagen and glycosaminoglycan device reconstituted into a gel for filling complex wounds; FDA 510(k) cleared for partial and full-thickness wounds.

Trial evidenceA randomized, placebo-controlled trial (small DFU population) exists; such trial-derived inclusion criteria may inform coverage decisions when matched to the patient.

DocumentationProvide trial-relevant details (wound type, Wagner grade, perfusion measures) when requesting coverage for uses aligned with trial populations.

Policy Revision History

2025-08-15focused_review

Added AlloMend and VNEW to the policy statement; clarified Phasix ST mesh as appropriate for paraesophageal/hiatal hernia repair.

2025-03-15annual_review

Added coverage statements for GalaFLEX in breast reconstruction, Actigraft and Kerecis for diabetic foot ulcers, multiple dural repair products, Phasix ST and GORE BIO-A for paraesophageal/hiatal hernia repair; added AlloDerm for parotidectomy; removed Symbotex and various other products; updated CPT listings and EIU product codes.

2025-03-15focused_review

Added noncoverage statement for XWrap.

2025-01-15focused_reviewLatest

Revised venous stasis ulcer initial application limits and added noncoverage statements for Membrane Wrap and Membrane Graft.

OpenPayer

Related Billing Codes

Tissue-engineered skin substitutes and related grafts (coverage criteria)

Coverage Criteria and Product-Specific Indications

Billing Codes, HCPCS and CPT Mapping

Prior Authorization, Documentation, and Practice Requirements

Background, Definitions and Evidence Context

Policy Revision History