CurrentPremera BluecrossPolicy 2.01.543_PBC (11-11-2025)

Recombinant and Autologous Platelet-Derived Growth Factors for Wound Healing and Other Non-Orthopedic Conditions

Defines medical necessity and investigational indications for recombinant platelet-derived growth factor (becaplermin) and autologous platelet-rich plasma (PRP) for non-orthopedic wounds and other non-orthopedic conditions, including documentation, usage guidelines, coding, evidence summary, and referenced trials/guidelines.

Policy Summary

PayerPremera Bluecross

PolicyRecombinant and Autologous Platelet-Derived Growth Factors for Wound Healing and Other Non-Orthopedic Conditions

Policy CodePolicy 2.01.543_PBC (11-11-2025)

Change TypeRevised; coding updates; investigational additions

Effective DateDec 1, 2025

Next Review Date

Key ActionDocument oxygenation, wound stage, and participation in a wound management program to support becaplermin use and expect denials or need for justification for investigational PRP uses.

POLICY UPDATE CHANGES

Policy renumbered from 2.01.16 to 2.01.543 effective 01/01/25 and added that PRP for fat graft retention is considered investigational.

Added HCPCS G0465 and removed CPT 86999 on 04/01/22; minor coding updates historically.

April 2021 annual review noted CMS will cover autologous PRP for chronic non-healing diabetic wounds for 20 weeks when prepared by devices with FDA-cleared indications.

12/01/25 Interim Review: policy reviewed with literature update and additional conditions added for which PRP is investigational; otherwise policy statements unchanged.

2Covered Indications for Becaplermin

manyPRP investigational non-orthopedic indications

Typical max treatment duration with becaplermin

20CMS CED coverage duration (weeks)

presentFDA boxed warning status (historical)

ManyEvidence / references cited

Coverage Summary

Scope: This policy defines medical necessity and investigational indications for recombinant platelet-derived growth factor (becaplermin) and autologous platelet-rich plasma (PRP) for wound healing and other non-orthopedic conditions. Becaplermin (recombinant PDGF) may be considered medically necessary as an adjunct to standard wound management for neuropathic diabetic ulcers and pressure ulcers that extend into the subcutaneous tissue. Use of platelet-rich plasma (autologous PRP) is considered investigational for all non-orthopedic indications (listed in the policy).

Effective/last review dates: Effective 2025-12-01; Last review 2025-11-11.

Surface thresholds and quick facts

Transcutaneous pO2 threshold>= 30 mm Hg (foot dorsum or ulcer margin)

Albumin concentration> 2.5 dL

Total lymphocyte count> 1,000 / μL

Typical maximum becaplermin durationOnce daily for up to 20 weeks (typical)

CMS CED coverage duration noteCMS covers autologous PRP for chronic non-healing diabetic wounds for a duration of 20 weeks when prepared by devices with FDA-cleared indications; coverage beyond 20 weeks determined by local MACs

Effective CMS 2021 decision dateApril 2021 (CMS decision memo updating coverage to 20 weeks)

Becaplermin (recombinant PDGF) — Medical Necessity

Recombinant platelet-derived growth factor (becaplermin) - Medical Necessity

Becaplermin may be considered medically necessary as an adjunct to standard wound management for the following indications:

ANY of the following

Neuropathic diabetic ulcers extending into the subcutaneous tissue (see additional selection criteria below)
See Additional Guidelines for selection criteria
Pressure ulcers extending into the subcutaneous tissue (see additional selection criteria below)
See Additional Guidelines for selection criteria

ANY of the following

Ischemic ulcers
Investigational

Autologous Platelet-Rich Plasma (PRP) — Coverage and Investigational Criteria

Platelet-rich plasma (PRP) - Investigational

Use of platelet-rich plasma is considered investigational for all non-orthopedic indications, including but not limited to:

Investigational PRP indications (non-orthopedic)

Abnormal uterine bleeding
Investigational
Acne
Investigational
Alopecia areata
Investigational
Androgenetic alopecia
Investigational

Codes

PRP / Autologous PRP CPTCPT

0232T

Injection(s), platelet rich plasma, any site, including image guidance, harvesting and preparation when performed

PRP / Autologous PRP HCPCSHCPCS

G0460	Autologous platelet rich plasma for nondiabetic chronic wounds/ulcers, including phlebotomy, centrifugation, and all other preparatory procedures, administration and dressings, per treatment
G0465	Autologous platelet rich plasma (PRP) for diabetic chronic wounds/ulcers, using an FDA-cleared device (includes administration, dressings, phlebotomy, centrifugation, and all other preparatory procedures, per treatment)
P9020	Platelet rich plasma, each unit
S0157	Becaplermin gel 0.01%, 0.5 gm
S9055	Procuren or other growth factor preparation to promote wound healing

HCPCS/CPT/Other codes referenced historically (mentioned as added/removed in history)mixed

G0460	HCPCS code added to policy (updated code description noted historically)
G0465	HCPCS code added 04/01/22
0232T	CPT code added 12/27/2010 (historical)
86999	CPT code removed 04/01/22 (historical)
20926	CPT code removed 07/14/15; PRP not considered tissue graft (historical)
Q4102	Removed (do not apply to policy) (historical)
Q4103	Removed (do not apply to policy) (historical)

Provider Actions & Documentation Requirements

Documentation Required

Document oxygenation for diabetic ulcers

For neuropathic diabetic ulcers treated with becaplermin, document tissue oxygenation measured by transcutaneous partial pressure of oxygen (TcPO2) at the foot dorsum or ulcer margin of >= 30 mm Hg to support use.

Documentation Required

Document wound staging and program participation

Document that the ulcer is full-thickness (stage III or IV) and that the patient participates in a wound management program including sharp debridement, pressure relief (non-weight bearing/off-loading), and infection control as prerequisites for becaplermin therapy.

Full-thickness ulcer (stage III or IV)
Participation in wound management program: sharp debridement
Pressure relief/non-weight bearing (off-loading)

Background and Evidence Summary

Background: The policy discusses both recombinant (lab-made) platelet-derived growth factors (for example, becaplermin) and autologous platelet-derived preparations (platelet-rich plasma, PRP) derived from a patient's own blood. Recombinant PDGFs are produced in the laboratory, while autologous PRP is prepared from centrifuged autologous blood and may be activated (for example with thrombin and calcium) to form a platelet gel that releases growth factors and fibrin for application to wounds or as a surgical adjunct.

PRP preparation and variability: PRP is prepared using point-of-care concentration systems (centrifugation devices) and may be activated to release growth factors; numerous preparation systems exist and different devices/procedures produce variable platelet, protein, leukocyte, and red cell concentrations and activation methods, resulting in substantial variability between PRP products and studies.

Intended use: These growth factor products have been used to promote wound healing (diabetic ulcers, pressure ulcers, venous stasis ulcers, surgical and traumatic wounds) and have been proposed for many non-orthopedic conditions, but evidence and regulatory status differ between recombinant PDGF and autologous PRP.

Concise evidence summary

RCT / Systematic review evidence for becaplerminRandomized trials and systematic reviews show improved healing rates for diabetic neuropathic ulcers and pressure ulcers; sufficient evidence for net health benefit

PRP evidence summary for chronic wounds

Medicare National Coverage Determinations

Effective Year	Name	Number/ID	Type
2012	CMS national coverage decision on autologous blood-derived products for chronic non-healing wounds	NCD 270.3	NCD
2012 (version effective 2012-08-02) and updated 2021 (decision memo April 2021)	Autologous Blood-Derived Products for Chronic Non-Healing Wounds	270.3 / CAG-00190R4	NCD

Definitions

Definitions:

PRP (Platelet-rich plasma): Autologous platelet-rich plasma — an autologous platelet concentrate suspended in plasma prepared from centrifuged autologous blood; when activated (e.g., thrombin and calcium) it degranulates platelets and can form a platelet gel used to deliver growth factors to wounds or surgical sites.

PDGF (Platelet-derived growth factor): Platelet-derived growth factor — growth factor family that can be delivered as recombinant (lab-made) products (recombinant PDGF such as becaplermin) to promote wound healing.

Chronic non-healing wound: Wounds (diabetic, venous, pressure) that have not healed with standard care — the target population described in CMS National Coverage Determination for autologous PRP under Coverage with Evidence Development (CED).

CED (Coverage with Evidence Development): Coverage with Evidence Development — a CMS policy mechanism requiring enrollment in clinical studies meeting specified criteria (prospective assessment of outcomes like complete wound healing, return to function, or reduction in wound size/healing trajectory) as a condition of Medicare coverage for autologous PRP for chronic non-healing wounds.

Revision History

04/01/22coding update

Coding table updated: HCPCS G0465 added and CPT 86999 removed; coding section aligned with policy.

04/2021CMS coverage clarification

April 2021 CMS decision: will cover autologous PRP for chronic non-healing diabetic wounds for a duration of 20 weeks when prepared by devices with FDA-cleared indications; coverage beyond 20 weeks to be determined by local MACs.

12/10/2024policy approval / renumbering

Approved December 10, 2024; policy renumbered from 2.01.16 to 2.01.543 effective 01/01/25 and added that PRP for fat graft retention is considered investigational.

Policy Summary

PayerPremera Bluecross

PolicyRecombinant and Autologous Platelet-Derived Growth Factors for Wound Healing and Other Non-Orthopedic Conditions

Policy CodePolicy 2.01.543_PBC (11-11-2025)

Change TypeRevised; coding updates; investigational additions

Effective DateDec 1, 2025

Next Review Date

Key ActionDocument oxygenation, wound stage, and participation in a wound management program to support becaplermin use and expect denials or need for justification for investigational PRP uses.

On This Page

Venous stasis ulcers

Investigational

Superficial ulcers: Ulcers not extending through the dermis into the subcutaneous tissue

Investigational

(See Additional Guidelines for individual selection criteria)

Becaplermin - Appropriate candidate criteria for neuropathic diabetic ulcers

Appropriate candidates should meet ALL of the following criteria:

Neuropathic diabetic ulcers candidate criteria

tcPO2: Adequate tissue oxygenation as measured by a transcutaneous partial pressure of oxygen of 30 mm Hg or greater on the foot dorsum or at the margin of the ulcer>= 30 mm Hg
Measurement location: foot dorsum or at ulcer margin
Full-thickness ulcer (stage III or IV), extending through the dermis into subcutaneous tissues
Wound management program: Participation in a wound management program that includes sharp debridement, pressure relief (non-weight bearing), and infection control

Documentation: Required documentation: tcPO2 >= 30 mm Hg and documentation of full-thickness ulcer and wound management program participation

See Documentation Requirements

Becaplermin - Appropriate candidate criteria for pressure ulcers

Appropriate candidates should meet ALL of the following criteria:

Pressure ulcers candidate criteria

Full-thickness ulcer (stage III or IV), extending through the dermis into subcutaneous tissues
Off-loadable location: Ulcer is in an anatomic location that can be off-loaded for the duration of treatment
Albumin concentration is greater than 2.5 dL> 2.5 dL
Lab/clinical assessment required
Total lymphocyte count is greater than 1,000/μL> 1,000 / μL
Lab/clinical assessment required
Vitamins A and C: Normal values of vitamins A and C
Lab/clinical assessment required

Documentation: Required documentation: ulcer staging, off-loadability, albumin >2.5 dL, total lymphocyte count >1,000/μL, and normal vitamins A and C

See Documentation Requirements

Becaplermin - Treatment frequency and formulation guidance

Additional guidelines on treatment frequency, formulation, and application:

Treatment frequency: Individuals are typically treated once daily for up to 20 weeks or until completely healed

Application may be performed at home

Formulations and application: Becaplermin available in 2-g, 7.5-g, and 15-g tubes; applied in a thin continuous layer about 1/16th inch (1.6 mm) thick; amount depends on ulcer size in cm2

Example: average 3 cm2 ulcer treated 85 days requires a little more than one 15-g tube; 140 days requires ~1.75 of 15-g tubes

Application setting: Application may be performed by the individual at home

Anal fistula

Investigational

Assisted reproductive technology (including intrauterine injection for endometrium thickening, poor ovarian response, sperm quality)

Investigational

Fat graft retention

Investigational (added in 01/01/25 renumbering)

Many others: Includes numerous other non-orthopedic indications (e.g., erectile dysfunction, sexual dysfunction, skin rejuvenation, wounds - acute/chronic/non-healing, etc.)

See policy list

Clinical evidence limitations: Evidence for most non-orthopedic uses is limited by small, heterogeneous studies and variability in PRP preparation; therefore uses are investigational

Medicare National Coverage Conditions for Autologous PRP (as described)

CMS covers autologous PRP only when ALL of the following are met for chronic non-healing diabetic, pressure, and/or venous wounds:

CMS CED enrollment

Study outcomes: Study must address at least one outcome: complete wound healing; ability to return to previous function/resumption of normal activities; or reduction of wound size or healing trajectory leading to return to function

CMS 20-week limit for diabetic wounds: For chronic non-healing diabetic wounds, CMS will cover autologous PRP for a duration of 20 weeks when prepared by devices whose FDA-cleared indications include management of exuding cutaneous wounds such as diabetic ulcers20 weeks

Coverage beyond 20 weeks determined by local MACs

Local MAC determination: Coverage for other chronic non-healing wounds (non-diabetic) will be determined by local Medicare Administrative Contractors (MACs) under section 1862(a)(1)(A) of the Act

Becaplermin (Regranex) FDA Indication and Warnings

FDA-labeled indication and boxed warning details relevant to clinical decision-making:

FDA labeled indication: Indicated for treatment of lower extremity diabetic neuropathic ulcers that extend into the subcutaneous tissue or beyond and have an adequate blood supply, as an adjunct to good ulcer care (sharp debridement, pressure relief, infection control)

Regranex (becaplermin) labeled indication (1997)

Not evaluated uses: Not evaluated for diabetic neuropathic ulcers that do not extend through the dermis into subcutaneous tissue or for ischemic diabetic ulcers; not intended for wounds that close by primary intention

Boxed warning history: 2008 boxed warning: increased rate of mortality secondary to malignancy observed in patients treated with three or more tubes in a post-marketing retrospective cohort study; use only when benefits outweigh risks and use with caution in patients with known malignancy

2018 labeling changes removed language referencing 'increased rate of cancer mortality' from boxed warning and warnings

FDA / Regulatory Notes on PRP

Regulatory context and device variability considerations for PRP and PRP preparation systems:

FDA regulation context: FDA regulates human cells and tissues via CBER under 21 CFR parts 1270 and 1271; blood products such as PRP are included

Exemptions and activated PRP: Certain blood products including PRP are exempt from traditional FDA regulatory pathway; FDA has not attempted to regulate activated PRP

Device variability: Numerous PRP preparation systems have 510(k) clearance for concentrating patient plasma at point of care for bone grafting; different devices/procedures lead to variable platelet/protein concentrations and variability between studies

Infection control measures

Documentation Required

Laboratory documentation for pressure ulcers

For pressure ulcers, document that the ulcer can be off-loaded for duration of treatment and provide labs showing albumin > 2.5 dL, total lymphocyte count > 1,000/µL, and normal values of vitamins A and C to support use of becaplermin.

Ulcer in location that can be off-loaded
Albumin > 2.5 dL
Total lymphocyte count > 1,000/µL
Normal vitamins A and C

Billing Rule

Becaplermin dosing and tube use guidance

Becaplermin is typically applied once daily for up to 20 weeks (or until healed). Document the tube size formulation used (2 g, 7.5 g, or 15 g) and the ulcer surface area to justify the number of tubes billed and support expected quantity used.

S0157

Prior Authorization

Investigational PRP uses require coverage determination

PRP for non-orthopedic indications is considered investigational. Expect coverage denials or need for clinical justification for uses outside approved/covered conditions; relevant PRP procedure and supply codes include those listed below.

0232T
G0460
G0465
P9020

Prior Authorization

Clinical research enrollment requirement for Medicare coverage

Medicare covers autologous PRP for chronic non-healing diabetic, venous, and/or pressure wounds only when the patient is enrolled in a qualifying clinical research study that prospectively evaluates specified outcomes using validated and reliable methods; enrollment is a condition of coverage under CMS CED.

Documentation Required

Study endpoints and documentation

Clinical studies qualifying for coverage with evidence development must prospectively assess at least one predefined outcome: complete wound healing; ability to return to previous function and resumption of normal activities; or reduction of wound size/healing trajectory that results in functional return. Document these endpoints and that PRP was given in addition to well-defined optimal usual care versus usual care alone.

Complete wound healing
Return to previous function/resumption of normal activities
Reduction in wound size or improvement in healing trajectory leading to functional return

Billing Rule

Coverage duration limit

For chronic non-healing diabetic wounds, CMS covers autologous PRP prepared by devices with FDA-cleared indications for exuding cutaneous wounds for a duration limited to 20 weeks; coverage beyond 20 weeks is determined by local Medicare Administrative Contractors (MACs).

Denial Risk

Non-covered circumstances per CMS/NCD

Coverage may be denied or deferred to local MACs for autologous PRP uses outside the CMS-specified conditions (e.g., not enrolled in qualifying CED studies, non-diabetic wounds, or products/devices without the specified FDA-cleared indications). Expect denials or local determination for non-covered circumstances.

Meta-analyses of small trials show mixed results; imprecision and risk of bias make evidence insufficient to confirm net health outcome improvement

CMS NCD history (CED)2012 CMS NCD instituted Coverage with Evidence Development (CED) for autologous PRP for chronic non-healing wounds

CMS 2021 decision summaryApril 2021 decision: cover autologous PRP for chronic non-healing diabetic wounds for 20 weeks when prepared by FDA-cleared devices; other wound coverage by local MACs

Becaplermin FDA approval yearApproved 1997 for lower-extremity diabetic neuropathic ulcers extending into subcutaneous tissue

11/11/2025policy approval / interim reviewLatest

Approved November 11, 2025 (Interim Review dated 12/01/25): policy reviewed with literature update and additional conditions added for which PRP is investigational; otherwise policy statements unchanged.