Clinical Policy: Skin and Soft Tissue Substitutes for Chronic Wounds Form

# Clinical Policy: Skin and Soft Tissue Substitutes for Chronic Wounds
Reference Number: CP.MP.185  
Date of Last Revision: 10/25  

[Coding Implications](Coding Implications)  
[Revision Log](Revision Log)  

See [Important Reminder](Important Reminder) at the end of this policy for important regulatory and legal information.  

## Description  
Patients receiving treatment with a skin substitute graft should be under the care of a wound care physician or surgeon and systemic disease should be monitored/treated to ensure adequate healing of the wound site. This policy addresses the medical necessity criteria for skin substitutes in the treatment of chronic wounds.  

Skin substitutes range widely in terms of origin, additives, and processing. Processing variations lead to broad differences between products within the same class, with a need for more comparative product studies. The result is that products within the same class vary significantly and the impact on the product’s function is indeterminant in many cases.³¹ A 2024 systematic review/meta-analysis concluded that “enough evidence is still lacking to determine a statistical difference between broad categories of CAMPs [cellular, acellular and matrix-like products]; hence decision-makers should consider published head-head comparative studies, real-world evidence, and cost-effectiveness evidence between individual CAMPs to decide on which to use in practice.”³²  

Medical necessity determinations regarding preferred products when deemed medically necessary are applicable to FDA-labeled indications. Preferred products are subject to change based on new product launches, product approvals, product withdrawals and other market changes.  

### Note:  
- For skin substitutes for burns, refer to CP.MP.186 Burn Surgery.  
- This policy only applies to skin and soft tissue substitute requests for diabetic foot ulcers and venous leg ulcers.  

## Policy/Criteria  
I. It is the policy of non-Medicare health plans affiliated with Centene Corporation® that up to four initial applications of skin and soft tissue substitutes/cellular and tissue-based products (CTPs) are **medically necessary** for diabetic foot ulcers (DFU) or venous leg ulcers (VLU) when all of the following criteria are met:  
A. Presence of a non-infected wound and one of the following:  
1. For patients with a DFU, documentation of all of the following:  
   a. Failure to achieve at least 50% ulcer area reduction, despite compliance with standard of care (SOC) wound treatment for a minimum of four weeks, as noted in I.C.;  
   b. Assessment of type 1 or type 2 diabetes and management history with attention to certain comorbidities (e.g., vascular disease, neuropathy, osteomyelitis);  
2. For patients with a VLU, documentation of all the following:  
   a. Failure to respond, despite compliance with SOC wound treatment for a minimum of four weeks, as noted in I.C.;  
   b. Assessment of clinical history (prior ulcers, body mass index, history of pulmonary embolism or superficial/deep venous thrombosis, number of pregnancies, and physical inactivity);  
   c. Updated medication history, including review of pertinent medical problems diagnosed since the previous ulcer evaluation;  
   d. Physical exam assessing for edema, skin changes and evaluation of vascular competence (including venous reflux and perforator incompetence) and venous thrombosis;  
   e. Documentation supporting the use of a firm strength compression garment (>20 mmHg) or multi-layered compressive dressing;  
B. Documentation that modifiable risk factors, such as diabetes, venous insufficiency, and neuropathy are being addressed adequately to improve likelihood of healing;  
C. Documentation of implemented SOC treatment plan demonstrating all the following:  
1. Debridement as appropriate to a clean granular base;  
2. Documented evidence of one of the following:  
   a. Offloading for DFUs;  
   b. Sustained compression dressings for VLUs;  
3. Infection control with removal of foreign body or nidus of infection;  
4. Management of exudate with maintenance of a moist environment;  
5. Documentation of smoking history, and counselling on the effect of smoking on wound healing, as well as treatment for smoking cessation and outcome of counselling (if applicable);  
D. Documentation to support failure to heal or stalled healing with SOC, including all the following:  
1. Measurements of the initial ulcer;  
2. Pre-SOC ulcer measurements;  
3. Weekly SOC ulcer measurements;  
4. Post-completion SOC ulcer measurements following at least four weeks of SOC treatment;  
5. Other interventions, as applicable;  
E. Request is for one of the following preferred products:  
1. TheraGenesis (A2008);  
2. Kerecis Omega3 Margen Shield (A2019);  
3. Apligraf (Q4101);  
4. Oasis Wound Matrix (Q4102);  
5. Integra Bilayer Matrix Wound Dressing (Q4104);  
6. Integra dermal regeneration template or Integra Omnigraft dermal regeneration matrix (Q4105);  

E. Request is for one of the following preferred products:  
7. Dermagraft (Q4106);  
8. Graftjacket (Q4107);  
9. Primatrix (Q4110);  
10. Gammagraft (Q4111);  
11. Alloskin (Q4115);  
12. Hyalomatrix (Q4117);  
13. Matristem micromatrix (Q4118);  
14. Theraskin (Q4121);  
15. Oasis ultra trilayer wound matrix (Q4124);  
16. Flex HD or Allopatch HD (Q4128);  
17. Grafix Core and Grafix PL Core (Q4132);  
18. Grafix PRIME, GrafixPL, PRIME, Stravix and Stravix PL (Q4133);  
19. Amnioexcel, amnioexcel plus or biodexcel (Q4137);  
20. Alloskin AC (Q4141);  
21. Tensix (Q4146);  
22. Neox cord 1K, Neox Cord RT or Clarix Cord 1K (Q4148);  
23. AmnioBand or Guardian (Q4151);  
24. DermaPure (Q4152);  
25. Biovance (Q4154);  
26. Neox 100 or Clarix 100 (Q4156);  
27. Kerecis Omega3 (Q4158);  
28. Affinity (Q4159);  
29. Nushield (Q4160);  
30. Cytal (Q4166);  
31. Cygnus (Q4170);  
32. Miroderm (Q4175);  
33. FlowerAmnioPatch (Q4178);  
34. Epifix (Q4186);  
35. Epicord (Q4187);  
36. AmnioArmor (Q4188);  
37. Puraply (Q4195);  
38. Puraply AM (Q4196);  
39. Puraply XT (Q4197);  
40. Matrion (Q4201);  
41. Derma-gide (Q4203);  
42. carePATCH (Q4236);  
43. Zenith amniotic membrane (Q4253);  
44. Dual Layer Impax Membrane (Q4262);  

F. Requested use complies with labeled indications;  
G. Only one skin substitute will be simultaneously in place per wound episode with the first skin substitute graft/CTP application beginning the episode of care. **Note:** Product change within the wound episode is allowed, with a total of up to four initially authorized and total applications not to exceed the eight-application limit per wound per 12–16-week episode of care;  
H. The graft will be applied in a single layer without overlay of product or adjacent skin in compliance with the correct label application techniques for the skin substitute graft/CTP;  
I. The following documentation requirements will be met for each application:  
1. Graphic evidence of ulcer size, depth, and characteristics of the ulcer or photo documentation of the ulcer at baseline and follow-up with measurements of wound including size and depth;  
2. A complete description of the procedure including product used (with identifying package label or National Drug Code (NDC) in the chart) and size of product used;  
3. If multiple sizes of a specific product are available, the size that best fits the wound is utilized, with the least amount of wastage;  
4. If a portion of a product is discarded, documentation includes all the following:  
   a. The amount administered and wasted;  
   b. The date, time, and amount of product wasted and the reason for the wastage.  

**Note:**  
- When a portion of a single use package must be discarded, payment will be made for the portion discarded along with the amount applied up to the amount of the product on the package label.  
- All documentation must be maintained in the member/enrollee’s medical record and made available upon request.  

II. It is the policy of non-Medicare health plans affiliated with Centene Corporation® that continued treatment beyond the initial four applications and up to a total of eight applications with skin and soft tissue substitutes/cellular and tissue-based products (CTPs) is **medically necessary** for diabetic foot ulcers (DFU) or venous leg ulcers (VLU) when all of the following criteria are met:  
A. Request is for one of the following preferred products:  
1. TheraGenesis (A2008);  
2. Kerecis Omega3 Margen Shield (A2019);  
3. Apligraf (Q4101);  
4. Oasis Wound Matrix (Q4102);  
5. Integra Bilayer Matrix Wound Dressing (Q4104);  
6. Integra dermal regeneration template or Integra Omnigraft dermal regeneration matrix (Q4105);  
7. Dermagraft (Q4106);  
8. Graftjacket (Q4107);  
9. Primatrix (Q4110);  
10. Gammagraft (Q4111);  
11. Alloskin (Q4115);  
12. Hyalomatrix (Q4117);  
13. Matristem micromatrix (Q4118);  
14. Theraskin (Q4121);  
15. Oasis ultra trilayer wound matrix (Q4124);  
16. Flex HD or Allopatch HD (Q4128);  
17. Grafix Core and Grafix PL Core (Q4132);  
18. Grafix PRIME, GrafixPL, PRIME, Stravix and Stravix PL (Q4133);  
19. Amnioexcel, amnioexcel plus or biodexcel (Q4137);  
20. Alloskin AC (Q4141);  
21. Tensix (Q4146);  
22. Neox cord 1K, Neox Cord RT or Clarix Cord 1K (Q4148);  
23. AmnioBand or Guardian (Q4151);  
24. DermaPure (Q4152);  
25. Biovance (Q4154);  
26. Neox 100 or Clarix 100 (Q4156);  
27. Kerecis Omega3 (Q4158);  
28. Affinity (Q4159);  
29. Nushield (Q4160);  
30. Cytal (Q4166);  
31. Cygnus (Q4170);  
32. Miroderm (Q4175);  
33. FlowerAmnioPatch (Q4178);  
34. Epifix (Q4186);  
35. Epicord (Q4187);  
36. AmnioArmor (Q4188);  
37. Puraply (Q4195);  
38. Puraply AM (Q4196);  
39. Puraply XT (Q4197);  
40. Matrion (Q4201);  
41. Derma-gide (Q4203)  
42. carePATCH (Q4236);  
43. Zenith amniotic membrane (Q4253);  
44. Dual Layer Impax Membrane (Q4262);  

B. Requested use complies with labeled indications;  
C. Documentation includes all the following:  

1. Explanation of why extended time or additional applications (beyond the initial four) are medically necessary for the specific member/enrollee’s wound;  
2. That the treatment plan regarding the initial four applications has resulted in wound healing and expectation that the wound will continue to heal with this plan;  
3. Estimated time for extended treatment, number of additional applications anticipated, and plan of care if healing is not achieved as planned;  
4. Modifiable risk factors, such as diabetes, venous insufficiency, and neuropathy, are being addressed adequately to improve likelihood of healing;  
5. For venous leg ulcers, appropriate consultation and management for the diagnosis and stabilization of any venous-related disease;  
6. Additional documentation from each of the initial four applications, and for all subsequent applications, includes all the following:  
   a. A complete description of the procedure including product used (with identifying package label or NDC in the chart) and size of product used;  
   b. Graphic evidence of ulcer size, depth, and characteristics of the ulcer or photo documentation of the ulcer at baseline and follow-up with measurements of wound including size and depth;  
   c. The skin substitute is applied in a single layer without overlay of product or adjacent skin in compliance with the correct label application techniques for the skin substitute graft/CTP;  
   d. When multiple sizes of a specific product are available, the size that best fits the wound with the least amount of wastage is utilized;  
D. Only one skin substitute will be simultaneously in place per wound episode with the first skin substitute graft/CTP application beginning the episode of care. **Note:** Product change within the wound episode is allowed; total applications not to exceed the eight-application limit per wound per 12–16-week episode of care;  
E. When a portion of a product is discarded, the medical record clearly demonstrates the amount administered and wasted, in addition to the date, time, amount of product wasted and the reason for the wastage.  

**Note:**  
- When a portion of a single use package must be discarded, payment will be made for the portion discarded along with the amount applied up to the amount of the product on the package label.  
- All documentation must be maintained in the member/enrollee’s medical record and made available upon request.  

III. It is the policy of non-Medicare health plans affiliated with Centene Corporation that skin and soft tissue substitutes are **not medically necessary** for the following indications or scenarios:  
A. Any usage not listed in section I. or II. of the policy;  
B. Greater than eight applications of a skin substitute graft/CTP within an episode of care (up to 16 weeks);  
C. Repeat applications of skin substitute grafts/CTP when a previous application was unsuccessful. Unsuccessful treatment is defined as increase in size or depth of an ulcer, no measurable change from baseline, and no sign of improvement or indication that  

improvement is likely (such as granulation, epithelialization, or progress towards closure);  
D. Inadequate control of underlying conditions or exacerbating factors, or other contraindications (e.g., active infection, progressive necrosis, active Charcot arthropathy of the ulcer extremity, active vasculitis, or ischemia);  
E. Use of surgical preparation services (e.g., debridement), with routine, simple, or repeat skin replacement surgery with a skin substitute graft/CTP for ulcer care;  
F. Use of liquid or gel skin substitute products/CTP for ulcer care;  
G. Placement of skin substitute grafts/CTP on an infected, ischemic, or necrotic wound bed.  

## Background  
Standard care for lower extremity wounds and ulcers includes infection control, management of edema, mechanical offloading of the affected limb, mechanical compression, limb elevation, debridement of necrotic tissue, management of systemic disease and counseling on the risk of continued tobacco use. Additionally, maintenance of a therapeutic wound environment with appropriate dressings can facilitate development of healthy granulation tissue and re-epithelialization. Dressings are essential to wound management because the appropriate dressing not only maintains the moisture balance within the wound, but the dressing also controls exudate, which protects the wound from additional trauma.¹⁻⁸  

The Centers for Medicare & Medicaid Services (CMS), define a chronic wound as a wound A wound that is physiologically impaired due to a disruption of the wound healing cycle because of impaired angiogenesis, innervation, or cellular migration, or other deficits for 4 weeks or longer. Even with advancements in standard wound care and synthetic occlusive dressings, some ulcers fail to heal and may benefit from a skin substitute.¹⁻⁸ The United Kingdom’s National Institute for Health and Care Excellence (NICE) recommends consideration of dermal or skin substitutes as an adjunct to standard care when treating diabetic wounds that are not healing.²⁹ Skin substitutes promote wound healing by replacing extracellular matrix.²⁰ Skin substitutes are categorized based on the composition of epidermal, dermal, and composite skin present.²⁰ They are heterogeneous and can be largely separated into two primary categories: cellular (comprised of living cells); or acellular (composed of synthetic materials or tissue from which living cells have been removed).²¹,²² The categories are further split based on composition and source of material, including xenograft, acellular allograft, cellular allograft, autograft and synthetic skin substitute choices.²⁰  

For VLU, an evaluation for the presence of saphenous vein reflux is essential prior to consideration of skin substitutes. If there is significant saphenous vein incompetence and reflux (valve closure time defined as > 500 milliseconds), or if ulcer bed veins are identified as contributory on ultrasound, a referral to a vascular surgeon or interventional radiologist is required. Endovascular laser or radiofrequency ablation can enhance rates of healing compared to other treatments for significant saphenous vein reflux. Without significant reflux, sclerotherapy may also be more beneficial.¹⁷  

According to a 2016 Cochrane review, the overall therapeutic outcome of skin grafts and tissue replacements used with standard wound care demonstrated an increase in the healing rate of foot  

ulcers and slightly fewer amputations in patients with diabetes compared with standard wound care alone.²³ The Wound Healing Society updated their guidelines in 2016, indicating that cellular and acellular skin equivalents positively affect healing in diabetic ulcers by “releasing therapeutic amounts of growth factors, cytokines, and other proteins that stimulate the wound bed.”²⁴ A health technology assessment of skin substitutes conducted for adults with neuropathic diabetic foot ulcers and venous leg ulcers found that adults with difficult to heal neuropathic diabetic ulcers and difficult to heal venous leg ulcers who used skin substitutes were more likely to experience complete wound healing than those who used standard care alone.²⁷ A systematic review of 17 trials using several skin substitutes to treat diabetic foot ulcers noted that completed closure of diabetic ulcers was significantly improved when compared to standard care alone.²⁶  

Outlined in a 2020 technical brief prepared for the Agency for Healthcare Research and Quality (AHRQ) are the various products commercially available in the United States that may be considered skin substitutes and identifies and assesses the clinical literature evaluating skin substitutes and their efficacy. Synder et al. (2020) conducted a systematic review of the published literature, grey literature and scientific packets received from manufacturers. The authors searched for systematic reviews/meta-analyses, randomized controlled trials (RCTs), and prospective nonrandomized comparative studies examining commercially available skin substitutes. The authors identified 76 commercially available skin substitutes and categorized them based on the Davisdon-Kotler classification system. Sixty-eight (89%) were categorized as acellular dermal substitutes, mostly replacements from human placental membranes and animal tissue sources. Three systematic reviews and 22 RCTs examined use of 16 distinct skin substitutes, including acellular dermal substitutes, cellular dermal substitutes, and cellular epidermal and dermal substitutes in diabetic foot ulcers, pressure ulcers, and venous leg ulcers. Of the 22 included RCTs, 16 studies compared a skin substitute with standard of care (e.g., debridement, glucose control, compression bandages for venous leg ulcers, daily dressing changes with moisture-retentive dressing, such as an alginate or hydrocolloid). Twenty-one ongoing clinical trials (all RCTs) examined an additional nine skin substitutes with similar classifications. The authors found that the studies rarely reported clinical outcomes, such as amputation, wound recurrence at least 2 weeks after treatment ended, or patient-related outcomes, such as return to function, pain, exudate, and odor. The authors concluded that there is a lack of studies examining the efficacy of most skin substitute products and the need for better-designed and -reported studies providing more clinically relevant outcomes. Before findings can be relied upon, more data are needed on hospitalization, pain reduction, need for amputation, exudate and odor control, and return to baseline activities of daily living and function.¹⁹  

## Coding Implications  
This clinical policy references Current Procedural Terminology (CPT®). CPT® is a registered trademark of the American Medical Association. All CPT codes and descriptions are copyrighted 2024, American Medical Association. All rights reserved. CPT codes and CPT descriptions are from the current manuals and those included herein are not intended to be all-inclusive and are included for informational purposes only. Codes referenced in this clinical policy are for informational purposes only. Inclusion or exclusion of any codes does not guarantee coverage. Providers should reference the most up-to-date sources of professional coding guidance prior to the submission of claims for reimbursement of covered services.  

| CPT Codes | Description |
|-----------|-------------|
| 15271 | Application of skin substitute graft to trunk, arms, legs, total wound surface area up to 100 sq cm; first 25 sq cm or less wound surface area |
| 15272 | Application of skin substitute graft to trunk, arms, legs, total wound surface area up to 100 sq cm; each additional 25 sq cm wound surface area, or part thereof (List separately in addition to code for primary procedure) |
| 15273 | Application of skin substitute graft to trunk, arms, legs, total wound surface area greater than or equal to 100 sq cm; first 100 sq cm wound surface area, or 1% of body area of infants and children |
| 15274 | Application of skin substitute graft to trunk, arms, legs, total wound surface area greater than or equal to 100 sq cm; each additional 100 sq cm wound surface area, or part thereof, or each additional 1% of body area of infants and children, or part thereof (List separately in addition to code for primary procedure) |
| 15275 | Application of skin substitute graft to face, scalp, eyelids, mouth, neck, ears, orbits, genitalia, hands, feet, and/or multiple digits, total wound surface area up to 100 sq cm; first 25 sq cm or less wound surface area |
| 15276 | Application of skin substitute graft to face, scalp, eyelids, mouth, neck, ears, orbits, genitalia, hands, feet, and/or multiple digits, total wound surface area up to 100 sq cm; each additional 25 sq cm wound surface area, or part thereof (List separately in addition to code for primary procedure) |
| 15277 | Application of skin substitute graft to face, scalp, eyelids, mouth, neck, ears, orbits, genitalia, hands, feet, and/or multiple digits, total wound surface area greater than or equal to 100 sq cm; first 100 sq cm wound surface area, or 1% of body area of infants and children |
| 15278 | Application of skin substitute graft to face, scalp, eyelids, mouth, neck, ears, orbits, genitalia, hands, feet, and/or multiple digits, total wound surface area greater than or equal to 100 sq cm; each additional 100 sq cm wound surface area, or part thereof, or each additional 1% of body area of infants and children, or part thereof (List separately in addition to code for primary procedure) |

### HCPCS codes that support medical necessity criteria
| HCPCS Codes | Description |
|-------------|-------------|
| A2008 | TheraGenesis, per sq cm |
| A2019 | Kerecis Omega3 MariGen Shield, per sq cm |
| Q4101 | Apligraf, per sq cm |
| Q4102 | Oasis wound matrix, per sq cm |
| Q4104 | Integra bilayer matrix wound dressing (BMWD), per sq cm |
| Q4105 | Integra dermal regeneration template (DRT) or Integra Omnigraft dermal regeneration matrix, per sq cm |
| Q4106 | Dermagraft, per sq cm |
| Q4107 | Graftjacket, per sq cm |
| Q4110 | PriMatrix, per sq cm |
| Q4111 | Gammagraft, per sq cm |
| Q4115 | Alloskin, per sq cm |

| HCPCS Codes | Description |
|-------------|-------------|
| Q4117 | Hyalomatrix, per sq cm |
| Q4118 | Matristem micromatrix, 1mg |
| Q4121 | TheraSkin, per sq cm |
| Q4124 | Oasis ultra tri-layer wound matrix, per sq cm |
| Q4128 | FlexHD, or AllopatchHD, per sq cm |
| Q4132 | Grafix Core and GrafixPL Core, per sq cm |
| Q4133 | Grafix PRIME, GrafixPL PRIME, Stravix and StravixPL, per sq cm |
| Q4137 | Amnioexcel, amnioexcel plus or biodexcel, per sq cm |
| Q4141 | AlloSkin AC, per sq cm |
| Q4146 | TENSIX, per sq cm |
| Q4148 | Neox Cord 1K, Neox Cord RT, or Clarix Cord 1K, per sq cm |
| Q4151 | AmnioBand or Guardian, per sq cm |
| Q4152 | DermaPure, per sq cm |
| Q4154 | Biovance, per sq cm |
| Q4156 | Neox 100 or Clarix 100, per sq cm |
| Q4158 | Kerecis Omega3, per sq cm |
| Q4159 | Affinity, per sq cm |
| Q4160 | Nushield, per sq cm |
| Q4166 | Cytal, per square centimeter |
| Q4170 | Cygnus, per sq cm |
| Q4175 | Miroderm, per sq cm |
| Q4178 | FlowerAmnioPatch, per sq cm |
| Q4186 | Epifix, per sq cm |
| Q4187 | Epicord, per sq cm |
| Q4188 | AmnioArmor, per sq cm |
| Q4195 | PuraPly, per square cm |
| Q4196 | PuraPly AM, per square cm |
| Q4197 | PuraPly XT, per square cm |
| Q4201 | Matrion, per sq cm |
| Q4203 | Derma-Gide, per sq cm |
| Q4236 | carePATCH, per sq cm |
| Q4253 | Zenith amniotic membrane, per sq cm |
| Q4262 | Dual Layer Impax Membrane, per sq cm |

### HCPCS codes that do not support medical necessity criteria
| HCPCS Codes | Description |
|-------------|-------------|
| A2001 | InnovaMatrix AC, per sq cm |
| A2002 | Mirragen Advanced Wound Matrix, per sq cm |
| A2005 | Microlyte Matrix, per sq cm |
| A2006 | NovoSorb SynPath dermal matrix, per sq cm |
| A2007 | Restrata, per sq cm |
| A2009 | Symphony, per sq cm |

| HCPCS Codes | Description |
|-------------|-------------|
| A2010 | Apis, per sq cm |
| A2011 | Supra SDRM, per sq cm |
| A2012 | Suprathel, per sq cm |
| A2013 | Innovamatrix FS, per sq cm |
| A2014 | Omeza Collagen Matrix, per 100 mg |
| A2015 | Phoenix Wound Matrix, per sq cm |
| A2016 | PermeaDerm B, per sq cm |
| A2017 | PermeaDerm Glove, each |
| A2018 | PermeaDerm C, per sq cm |
| A2020 | AC5 Advanced Wound System (AC5) |
| A2021 | NeoMatrix, per sq cm |
| A2022 | InnovaBurn or InnovaMatrix XL, per sq cm |
| A2023 | Innovamatrix PD, 1 mg |
| A2024 | Resolve Matrix or XenoPatch, per sq cm |
| A2025 | Miro3D, per cu cm |
| A2026 | Restrata MiniMatrix, 5 mg |
| A2027 | MatriDerm, per sq cm |
| A2028 | MicroMatrix Flex, per mg |
| A2029 | MiroTract Wound Matrix Sheet, per cc |
| A2030 | Miro3D fibers, per mg |
| A2031 | MiroDry Wound Matrix, per sq cm |
| A2032 | MiroMatrix, per sq cm |
| A2033 | Myriad Morcells, 4 mg |
| A2034 | Foundation DRS Solo, per sq cm |
| A2035 | Corplex P or Theracor P or Allacor P, per mg |
| A2036 | Cohealix Collagen Dermal Matrix, per sq cm |
| A2037 | G4Derm Plus, per ml |
| A2038 | MariGen Pacto, per sq cm |
| A2039 | Innovamatrix FD, per sq cm |
| C8002 | Preparation Skin Cell Susp Autograft, automated, including all enzymatic processing and device components |
| C9358 | Dermal substitute, native, nondenatured collagen, fetal bovine origin (SurgiMend Collagen Matrix), per 0.5 sq cm |
| C9360 | Dermal substitute, native, nondenatured collagen, neonatal bovine origin (SurgiMend Collagen Matrix), per 0.5 sq cm |
| C9363 | Skin substitute (Integra Meshed Bilayer Wound Matrix), per sq cm |
| C9364 | Porcine implant, Permacol, per sq cm |
| Q4100 | Skin substitute, not otherwise specified |
| Q4103 | Oasis burn matrix, per sq cm |
| Q4108 | Integra matrix, per sq cm |
| Q4112 | Cymetra, injectable, 1 cc |
| Q4113 | GRAFTJACKET XPRESS, injectable, 1 cc |
| Q4114 | Integra flowable wound matrix, injectable, 1 cc |

CLINICAL POLICY
Skin and Soft Tissue Substitutes for Chronic Wounds

| HCPCS Codes | Description |
|-------------|-------------|
| Q4116       | AlloDerm, per sq cm |
| Q4122       | DermaCELL, DermaCELL AWM or DermaCELL AWM Porous, per sq cm |
| Q4123       | AlloSkin RT, per sq cm |
| Q4125       | ArthroFlex, per sq cm |
| Q4126       | MemoDerm, DermaSpan, TranZgraft or Integuply, per sq cm |
| Q4127       | Talymed, per sq cm |
| Q4130       | Strattice TM, per sq cm |
| Q4134       | Hmatrix, per sq cm |
| Q4135       | Mediskin, per sq cm |
| Q4136       | E Z Derm, per sq cm |
| Q4138       | BioDFence DryFlex, per sq cm |
| Q4139       | AmnioMatrix or BioDMatrix, injectable, 1 cc |
| Q4140       | BioDFence, per sq cm |
| Q4142       | XCM biologic tissue matrix, per sq cm |
| Q4143       | Repriza, per sq cm |
| Q4145       | EpiFix, injectable, 1 mg |
| Q4147       | Architect, Architect PX, or Architect FX, extracellular matrix, per sq cm |
| Q4149       | Excellagen, 0.1 cc |
| Q4150       | AlloWrap DS or dry, per sq cm |
| Q4153       | Dermavest and Plurivest, per sq cm |
| Q4155       | Neox Flo or Clarix Flo 1 mg |
| Q4157       | Revitalon, per sq cm |
| Q4161       | Bio-connekt wound matrix, per sq cm |
| Q4162       | WoundEx Flow, BioSkin Flow, 0.5 cc |
| Q4163       | Woundex, bioskin, per sq cm |
| Q4164       | Helicoll, per sq cm |
| Q4165       | Keramatrix or Kerasorb, per sq cm |
| Q4167       | Truskin, per sq cm |
| Q4168       | AmnioBand, 1 mg |
| Q4169       | Artacent wound, per sq cm |
| Q4171       | Interfyl, 1 mg |
| Q4173       | Palingen or Palingen Xplus, per sq cm |
| Q4174       | PalinGen or ProMatrX, 0.36 mg per 0.25 cc |
| Q4176       | Neopatch or therion, per sq cm |
| Q4177       | FlowerAmnioFlo, 0.1 cc |
| Q4179       | FlowerDerm, per sq cm |
| Q4180       | Revita, per sq cm |
| Q4181       | Amnio Wound, per sq cm |
| Q4182       | Transcyte, per sq cm |
| Q4183       | Surgigraft, per sq cm |
| Q4184       | Celesta or Celesta Duo, per sq cm |
| Q4185       | Celesta Flowable Amnion (25 mg per cc); per 0.5 cc |
| Q4189       | Artacent AC, 1 mg |

Page 11 of 23

CLINICAL POLICY
Skin and Soft Tissue Substitutes for Chronic Wounds

| HCPCS Codes | Description |
|-------------|-------------|
| Q4190       | Artacent AC, per sq cm |
| Q4191       | Restorigin, per sq cm |
| Q4192       | Restorigin, 1 cc |
| Q4193       | Coll-e-Derm, per sq cm |
| Q4194       | Novachor, per sq cm |
| Q4198       | Genesis Amniotic Membrane, per sq cm |
| Q4199       | Cygnus matrix, per sq cm |
| Q4200       | SkinTE, per sq cm |
| Q4202       | Kerox (2.5 g/cc), 1 cc |
| Q4204       | XWRAP, per sq cm |
| Q4205       | Membrane Graft or Membrane Wrap, per sq cm |
| Q4206       | Fluid Flow or Fluid GF, 1 cc |
| Q4208       | Novafix, per sq cm |
| Q4209       | SurGraft, per sq cm |
| Q4210       | Axolotl Graft or Axolotl DualGraft, per sq cm |
| Q4211       | Amnion Bio or AxoBioMembrane, per sq cm |
| Q4212       | AlloGen, per cc |
| Q4214       | Celesta Cord, per sq cm |
| Q4215       | Axolotl Ambient or Axolotl Cryo, 0.1 mg |
| Q4216       | Artacent Cord, per sq cm |
| Q4217       | WoundFix, BioWound, WoundFix Plus, BioWound Plus, WoundFix Xplus or BioWound Xplus, per sq cm |
| Q4218       | SurgiCORD, per sq cm |
| Q4219       | SurgiGRAFT-DUAL, per sq cm |
| Q4220       | BellaCell HD or Surederm, per sq cm |
| Q4221       | Amnio Wrap2, per sq cm |
| Q4222       | ProgenaMatrix, per sq cm |
| Q4224       | Human Health Factor 10 Amniotic Patch (HHF10-P), per sq cm |
| Q4225       | AmnioBind or DermaBind TL, per sq cm |
| Q4226       | MyOwn Skin, includes harvesting and preparation procedures, per sq cm |
| Q4227       | AmnioCore TM, per sq cm |
| Q4229       | Cognex Amniotic Membrane, per sq cm |
| Q4230       | Cognex Flowable Amnion, per 0.5 cc |
| Q4231       | Corplex P, per cc |
| Q4232       | Corplex, per sq cm |
| Q4233       | SurFactor or NuDyn, per 0.5 cc |
| Q4234       | Xcellerate, per sq cm |
| Q4235       | AMNIOREPAIR or AltiPly, per sq cm |
| Q4237       | Cryo-Cord, per sq cm |
| Q4238       | Derm-Maxx, per sq cm |
| Q4239       | Amnio-Maxx or Amnio-Maxx Lite, per sq cm |
| Q4240       | CoreCyte, for topical use only, per 0.5 cc |
| Q4241       | PolyCyte, for topical use only, per 0.5 cc |

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CLINICAL POLICY
Skin and Soft Tissue Substitutes for Chronic Wounds

| HCPCS Codes | Description |
|-------------|-------------|
| Q4242       | AmnioCyte Plus, per 0.5 cc |
| Q4244       | Procenta, per 200 mg |
| Q4245       | AmnioText, per cc |
| Q4246       | CoreText or ProText, per cc |
| Q4247       | Amniotext patch, per sq cm |
| Q4248       | Dermacyte Amniotic Membrane Allograft, per sq cm |
| Q4249       | AMNIPLY, for topical use only, per sq cm |
| Q4250       | AmnioAmp-MP, per sq cm |
| Q4251       | Vim, per sq cm |
| Q4252       | Vendaje, per sq cm |
| Q4254       | Novafix, per sq cm |
| Q4255       | REGUARD, for topical use only, per sq cm |
| Q4256       | MLG-Complete, per sq cm |
| Q4257       | Relese, per sq cm |
| Q4258       | Enverse, per sq cm |
| Q4259       | Celera Dual Layer or Celera Dual Membrane, per sq cm |
| Q4260       | Signature Apatch, per sq cm |
| Q4261       | TAG, per sq cm |
| Q4263       | SurGraft TL, per sq cm |
| Q4264       | Cocoon Membrane, per sq cm |
| Q4265       | NeoStim TL, per sq cm |
| Q4266       | NeoStim Membrane, per sq cm |
| Q4267       | NeoStim DL, per sq cm |
| Q4268       | SurGraft FT, per sq cm |
| Q4269       | SurGraft XT, per sq cm |
| Q4270       | Complete SL, per sq cm |
| Q4271       | Complete FT, per sq cm |
| Q4272       | Esano A, per sq cm |
| Q4273       | Esano AAA, per sq cm |
| Q4274       | Esano AC, per sq cm |
| Q4275       | Esano ACA, per sq cm |
| Q4276       | ORION, per sq cm |
| Q4278       | EPIEFFECT, per sq cm |
| Q4279       | Vendaje AC, per sq cm |
| Q4280       | Xcell Amnio Matrix, per sq cm |
| Q4281       | Barrera SL or Barrera DL, per sq cm |
| Q4282       | Cygnus Dual, per sq cm |
| Q4283       | Biovance Tri-Layer or Biovance 3L, per sq cm |
| Q4284       | DermaBind SL, per sq cm |
| Q4285       | NuDYN DL or NuDYN DL MESH, per sq cm |
| Q4286       | NuDYN SL or NuDYN SLW, per sq cm |
| Q4287       | DermaBind DL, per sq cm |
| Q4288       | DermaBind CH, per sq cm |

Page 13 of 23

CLINICAL POLICY
Skin and Soft Tissue Substitutes for Chronic Wounds

| HCPCS Codes | Description |
|-------------|-------------|
| Q4289       | RevoShield+ Amniotic Barrier, per sq cm |
| Q4290       | Membrane Wrap-Hydro(TM), per sq cm |
| Q4291       | Lamellas XT, per sq cm |
| Q4292       | Lamellas, per sq cm |
| Q4293       | Acesso DL, per sq cm |
| Q4294       | Amnio Quad-Core, per sq cm |
| Q4295       | Amnio Tri-Core Amniotic, per sq cm |
| Q4296       | Rebound Matrix, per sq cm |
| Q4297       | Emerge Matrix, per sq cm |
| Q4298       | AmniCore Pro, per sq cm |
| Q4299       | AmniCore Pro+, per sq cm |
| Q4300       | Acesso TL, per sq cm |
| Q4301       | Activate Matrix, per sq cm |
| Q4302       | Complete ACA, per sq cm |
| Q4303       | Complete AA, per sq cm |
| Q4304       | GRAFIX PLUS, per sq cm |
| Q4305       | American Amnion AC Tri-Layer, per sq cm |
| Q4306       | American Amnion AC, per sq cm |
| Q4307       | American Amnion, per sq cm |
| Q4308       | Sanopellis, per sq cm |
| Q4309       | VIA Matrix, per sq cm |
| Q4310       | Procenta, per 100 mg |
| Q4311       | Acesso, per sq cm |
| Q4312       | Acesso AC, per sq cm |
| Q4313       | Dermabind Fm, per sq cm |
| Q4314       | Reeva Ft, per sq cm |
| Q4315       | Regenelink Amniotic Membrane Allograft, per sq cm |
| Q4316       | Amchoplast, per sq cm |
| Q4317       | Vitograft, per sq cm |
| Q4318       | E-Graft, per sq cm |
| Q4319       | Sanograft, per sq cm |
| Q4320       | Pelligraft, per sq cm |
| Q4321       | Renograft, per sq cm |
| Q4322       | Caregraft, per sq cm |
| Q4323       | Alloply, per sq cm |
| Q4324       | Amniotx, per sq cm |
| Q4325       | Acapatch, per sq cm |
| Q4326       | Woundplus, per sq cm |
| Q4327       | Duoamnion, per sq cm |
| Q4328       | MOST, per sq cm |
| Q4329       | Singlay, per sq cm |
| Q4330       | TOTAL, per sq cm |
| Q4331       | Axolotl Graft, per sq cm |

Page 14 of 23

CLINICAL POLICY
Skin and Soft Tissue Substitutes for Chronic Wounds

| HCPCS Codes | Description |
|-------------|-------------|
| Q4332       | Axolotl Dualgraft, per sq cm |
| Q4333       | Ardeograft, per sq cm |
| Q4334       | AmnioPlast 1, per sq cm |
| Q4335       | AmnioPlast 2, per sq cm |
| Q4336       | Artacent C, per sq cm |
| Q4337       | Artacent Trident, per sq cm |
| Q4338       | Artacent Velos, per sq cm |
| Q4339       | Artacent Vericlen, per sq cm |
| Q4340       | Simpligraft, per sq cm |
| Q4341       | Simplimax, per sq cm |
| Q4342       | Theramend, per sq cm |
| Q4343       | Dermacyte AC Matrix Amniotic Membrane Allograft, per sq cm |
| Q4344       | Tri-Membrane Wrap, per sq cm |
| Q4345       | Matrix Hd Allograft Dermis, per sq cm |
| Q4346       | Shelter DM Matrix, per sq cm |
| Q4347       | Rampart DL Matrix, per sq cm |
| Q4348       | Sentry SL Matrix, per sq cm |
| Q4349       | Mantle DL Matrix, per sq cm |
| Q4350       | Palisade DM Matrix, per sq cm |
| Q4351       | Enclose TL Matrix, per sq cm |
| Q4352       | Overlay SL Matrix, per sq cm |
| Q4353       | Xceed TL Matrix, per sq cm |
| Q4354       | PalinGen Dual-Layer Membrane, per sq cm |
| Q4355       | Abiomend Xplus Membrane and Abiomend Xplus Hydromembrane, per sq cm |
| Q4356       | Abiomend Membrane and Abiomend Hydromembrane, per sq cm |
| Q4357       | XWRAP Plus, per sq cm |
| Q4358       | XWRAP Dual, per sq cm |
| Q4359       | ChoriPly, per sq cm |
| Q4360       | AmchoPlast FD, per sq cm |
| Q4361       | EPIXPRESS, per sq cm |
| Q4362       | CYGNUS Disk, per sq cm |
| Q4363       | Amnio Burgeon Membrane and Hydromembrane, per sq cm |
| Q4364       | Amnio Burgeon Xplus Membrane and Xplus Hydromembrane, per sq cm |
| Q4365       | Amnio Burgeon Dual-Layer Membrane, per sq cm |
| Q4366       | Dual Layer Amnio Burgeon X-Membrane, per sq cm |
| Q4367       | AmnioCore SL, per sq cm |
| Q4368       | AmchoThick, per sq cm |
| Q4369       | AmnioPlast 3, per sq cm |
| Q4370       | AeroGuard, per sq cm |
| Q4371       | NeoGuard, per sq cm |
| Q4372       | AmchoPlast EXCEL, per sq cm |
| Q4373       | Membrane Wrap-Lite, per sq cm |
| Q4375       | DuoGRAFT AC, per sq cm |

Page 15 of 23

CLINICAL POLICY
Skin and Soft Tissue Substitutes for Chronic Wounds

| HCPCS Codes | Description |
|-------------|-------------|
| Q4376       | DuoGRAFT AA, per sq cm |
| Q4377       | TriGraft FT, per sq cm |
| Q4378       | Renew FT Matrix, per sq cm |
| Q4379       | AmnioDefend FT Matrix, per sq cm |
| Q4380       | AdvoGraft One, per sq cm |
| Q4382       | Advograft Dual, per sq cm |
| Q4383       | Axolotl Graft Ultra, per sq cm |
| Q4384       | Axolotl DualGraft Ultra, per sq cm |
| Q4385       | Apollo FT, per sq cm |
| Q4386       | Acesso TrifACA, per sq cm |
| Q4387       | NeoThelium FT, per sq cm |
| Q4388       | NeoThelium 4L, per sq cm |
| Q4389       | NeoThelium 4L Plus, per sq cm |
| Q4390       | Ascendion, per sq cm |
| Q4391       | AmnioPlast Double, per sq cm |
| Q4392       | GRAFIX Duo, per sq cm |
| Q4393       | SurGraft AC, per sq cm |
| Q4394       | SurGraft ACA, per sq cm |
| Q4395       | Acelagraft, per sq cm |
| Q4396       | Natalin, per sq cm |
| Q4397       | Summit AAA, per sq cm |

## Reviews, Revisions, and Approvals

| Reviews, Revisions, and Approvals | Revision Date | Approval Date |
|----------------------------------|--------------|--------------|
| Policy adapted from WellCare’s HS433 Skin Substitutes policy. Removed description information about identification of MD managing chronic conditions. Removed requirement for MD review of all requests. Rearranged some not medically necessary indications into the contraindications section. In I.D, changed requirement for no nicotine use for at least 4 weeks to documentation of effort to cease nicotine use, or no nicotine use for at least 4 weeks. In the diabetic foot ulcer criteria, removed requirement of neuropathy. In I.I.1, changed contraindication of “active Charcot arthropathy of the ulcer extremity” to “active Charcot arthropathy of the ulcer surface.” In DFU section, removed documentation of assessment of physical activity, nutrition, physical exam, check of prosthetics, and history of diabetes management, including comorbidities. Changed requirement of HbA1c ≤7% to ≤8%, or with documented improvement of blood glucose in last 4 weeks. Changed HbA1c contraindication to >8% or with no document improvement of blood glucose in last 4 weeks. Reworded some extraneous language with no clinical significance. Removed criteria stating that switching products during an episode of wound care is not allowed. Removed not medically necessary language about repeated | 04/20 | 04/20 |

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CLINICAL POLICY
Skin and Soft Tissue Substitutes for Chronic Wounds

## Reviews, Revisions, and Approvals

| Reviews, Revisions, and Approvals | Revision Date | Approval Date |
|----------------------------------|--------------|--------------|
| billing of surgical preparation services. Revised name of the policy to Skin Substitutes for Chronic Wounds. Added criteria of age ≥ 18 years, or type 1 diabetic. Added to the requirement for documentation of effort to cease nicotine use that this does not include nicotine replacement therapy. Added to section II that all indications not noted in section I are not medically necessary. Added CPT codes: 15271-15278; updated list of HCPCS codes of current products available, although not inclusive or guarantee of coverage. References reviewed and updated. All instances of “member” changed to “member/enrollee.” HCPCS codes removed as they are not included in Medicare Article A56696: Q4150, Q4183, Q4190, Q4208-Q4226. Q4210, Q4217, Q4219, and Q4220 removed. New codes added (from Article A56696): Q4176, Q4237, Q4238, and Q4239. | 05/20 | 06/20 |
| Annual review completed. References reviewed and updated. Changed “Review Date” in the header to “Date of Last Revision” and “Date” in the revision log header to “Revision Date.” Added “type 2 diabetes” to I.A. Reworded some extraneous language with no clinical significance. Added I.F.2. “unless Integra® is used per FDA guidelines”. Removed I.J.3. “Concurrent treatment with hyperbaric oxygen therapy”. Background section updated with no additional impact to criteria. Added the following HCPCS codes: A2001-A2010, Q4199, Q4201, Q4232 and Q4254. Removed Q4119, Q4174. Added reference CMS A56696. Specialist reviewed. | 04/21 | 04/21 |
| Updated description for code Q4128. | 10/22 |  |
| Annual review completed. Changed policy title and statements in 1. and II. to reflect the inclusion of soft tissue substitutes for chronic wounds. Added note specifying that requests for skin and soft tissue substitutes other than for the indications noted in the policy is outside of the scope of the policy. Updated policy statement I. to include full thickness skin-loss ulcers. Revised criteria I.G. In I.H clarified that the request complies with FDA-approved indications and application limits. Removed criteria I.IA. Reworded extraneous language and background updated with no clinical significance. Removed deleted HCPCS code A2003. Labeled HCPCS Table 1 to note support of medical necessity. Added HCPCS Table 2 of codes that do not support medical necessity. Moved the following codes from the previous code reference table to table 2, HCPCS codes that do not support medical necessity: A2002, A2005, A2006, A2007, A2009, A2010, Q4184, Q4199, Q4237, Q4238, Q4239, Q4262, Q4263 and Q4264 to HCPCS table 1. Added new codes Q4253, Q4262, Q4263 and Q4264 to HCPCS table 1. Added additional codes to not medically necessary table, Table 2. References reviewed and updated. | 04/23 | 04/23 |
| Annual review. In note and policy statements I and II, specified that this policy applies to non-Medicare plans. Removed language related to | 03/24 | 03/24 |

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CLINICAL POLICY
Skin and Soft Tissue Substitutes for Chronic Wounds

## Reviews, Revisions, and Approvals

| Reviews, Revisions, and Approvals | Revision Date | Approval Date |
|----------------------------------|--------------|--------------|
| venous stasis ulcers. Removed criteria I.A Age ≥ 18 years, or diabetic (Type 1 or Type 2). Removed “including silver dressings in C.1. Replaced C2 “wound has increased in size or depth or has not changed… with “Wound area has reduced <50% in four weeks”. Updated description for HCPCS code A4225. Removed the following codes from HCPCS codes that do not support medical necessity criteria and added to table for HCPCS codes that support medical necessity criteria: A2002, Q4236, and Q4262. Added HCPCS code Q4278 to table for HCPCS codes that support medical necessity criteria. Added the following codes to table for HCPCS codes that do not support medical necessity criteria: Q4279 and Q4287 through Q4304. Coding reviewed. References reviewed and updated. Reviewed by external specialist. | 03/25 | 03/25 |
| Annual review. Removed note under description to refer to MC.CP.MP.185 for Medicare plans. Updated and replaced previous criteria I.A. with new criteria I.A. through G. Also updated and replaced previous criteria IIA. through C. with new criteria I.A. through G. Description and Background reviewed and updated. Coding updated to reflect addition of preferred product list in criteria I.E. References reviewed and updated. Reviewed by external specialist. | 03/25 | 03/25 |
| Added the following codes to the “HCPCS that do not support medical necessity criteria” table: A2026, A2027, A2028, A2029, C8002, Q4280, Q4311, Q4312, Q4313, Q4314, Q4315, Q4316, Q4317, Q4318, Q4319, Q4320, Q4321, Q4322, Q4323, Q4324, Q4325, Q4326, Q4327, Q4328, Q4329, Q4330, Q4331, Q4332, Q4333, Q4334, Q4335, Q4336, Q4337, Q4338, Q4339, Q4340, Q4341, Q4342, Q4343, Q4344, Q4345, Q4346, Q4347, Q4348, Q4349, Q4350, Q4351, Q4352, Q4353, Q4368, Q4369, Q4370, Q4371, Q4372, Q4373, Q4375, Q4376, Q4377, Q4378, Q4379, Q4380, Q4382. | 06/25 | 06/25 |
| In policy statement 1., specified that criteria is applicable to “up to four initial applications.” Under criteria LF, removed “FDA approved” and replaced with “labeled”. Added criteria LG.-II. Created policy statement II. and criteria for “beyond the initial four applications and up to a total of eight …”. In III.A, added that non medically necessary indications include usage not listed in section II. of the policy. Added the following to the table of HCPCS codes that do not support medical necessity:A2036, A2037, A2038, A2039, Q4383, Q4384, Q4385, Q4386, Q4387, Q4388, Q4389, Q4390, Q4391, Q4392, Q4393, Q4394, Q4395, Q4396, Q4397. Removed Q4104 and Q4106 from list of codes not supported by medical necessity criteria, as they are on the preferred product list. | 10/25 | 10/25 |

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CLINICAL POLICY
Skin and Soft Tissue Substitutes for Chronic Wounds