CurrentBlue Cross Blue Shield - Rhode IslandPolicy N/A

Digestive Enzyme Cartridges

Reimbursement and medical necessity criteria for in-line digestive enzyme cartridges used with enteral feeding (e.g., RELiZORB), applicable to Medicare Advantage and Commercial products offered by the payer.

Policy Summary

PayerBlue Cross Blue Shield - Rhode Island

PolicyDigestive Enzyme Cartridges

Policy CodePolicy N/A

Change TypeNo material changes

Effective DateAug 1, 2023

Next Review DateN/A

Key ActionPrior authorization is recommended for Commercial Products; document diagnosis, evidence of fat malabsorption despite optimized PERT, and continuous enteral feeding >=6 hours.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

B4105HCPCS code specified for cartridge

6hMinimum feeding duration

61%ASSURE improved weight

90dASSURE study duration

Coverage Criteria

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Initial approval criteria: 1) Individual has a diagnosis of cystic fibrosis AND confirmed exocrine pancreatic insufficiency; AND 2) Continued malabsorption of fats from enteral formula evidenced by insufficient weight gain or weight loss despite optimization with pancreatic enzyme replacement therapy (PERT) tablets or capsules (including administration via feeding tube where applicable); AND 3) Individual requires enteral tube nutrition for continuous durations of 6 hours or more.

Initial request criteria as stated in policy

Continuation therapy (Commercial Products)

Covered when ALL of the following are met for continuation requests (Commercial Products):

Continuation approval criteria: 1) Evidence of stable or increased weight from use of Relizorb; AND 2) Continued requirement for enteral tube nutrition for continuous durations of 6 hours or more.

Continuation request criteria as stated in policy

Medicare Advantage coverage

Medicare Advantage coverage stance:

Medicare Advantage: Digestive enzyme cartridges (in-line immobilized lipase cartridges) are covered when the medical criteria in this policy are met; they are not covered when those criteria are not met.

Medicare Advantage coverage is based on compliance with policy criteria

Evidence and indications outside CF

Evidence limits:

Evidence limitations: There is insufficient evidence to support effectiveness of in-line digestive enzyme cartridges for pancreatic insufficiency caused by conditions other than cystic fibrosis (examples include celiac disease, chronic pancreatitis, Crohn's disease, diabetes mellitus, pancreatic cancer, small bowel resection, and short bowel syndrome).

Policy cites limited evidence beyond cystic fibrosis; randomized trials for other causes are lacking

Use of in-line digestive enzyme cartridges (also called in-line immobilized lipase cartridges or ILCs) is intended to hydrolyze triglycerides in enteral formula for patients with exocrine pancreatic insufficiency (EPI). For Commercial Products, initial coverage is available when ALL of the following are documented: a diagnosis of cystic fibrosis with confirmed EPI; evidence of persistent fat malabsorption manifested by insufficient weight gain or weight loss despite optimization with pancreatic enzyme replacement therapy (PERT) (tablets or capsules, including administration via feeding tube when applicable); and a requirement for enteral tube nutrition delivered continuously for ≥ 6 hours per feeding episode. Continuation coverage for Commercial Products requires demonstration of stable or increased weight while using the cartridge and continued need for enteral nutrition delivered for ≥ 6 hours continuously.

Digestive enzyme cartridges are considered not medically necessary (or not covered) when the policy’s specified medical criteria are not met. This includes absence of the qualifying diagnosis (for Commercial Products the policy limits initial approval to cystic fibrosis with confirmed EPI), lack of documented persistent fat malabsorption despite optimization with PERT, failure to show the required enteral feeding pattern of ≥ 6 hours continuous feeding, or lack of evidence of benefit on continuation requests (no weight stabilization or gain). For Medicare Advantage members, cartridges are not covered when criteria are not satisfied; similarly, Commercial Product requests that do not meet the stated criteria will be considered not medically necessary.

Coding and Billing

Covered HCPCS Codes (Medicare Advantage)HCPCSCovered

B4105

In-line cartridge containing digestive enzyme(s) for enteral each feeding,

Covered HCPCS Codes (Commercial Products)HCPCSCovered

B4105

In-line cartridge containing digestive enzyme(s) for enteral feeding, each

inv-09: Minimum continuous enteral feeding duration

Minimum continuous enteral feeding duration>= 6 hours

Applies to initial and continuation requests (Commercial Products)Required for approval of both initial and continuation therapy per policy

Documentation expectationChart must show enteral tube nutrition delivered continuously for at least 6 hours

Provider Actions and Documentation

Prior Authorization

Prior authorization is not required for Medicare Advantage plans. Prior authorization is recommended for Commercial Products via the participating provider online tool.

Medicare Advantage: No prior authorization required.
Commercial Products: Prior authorization recommended via participating provider online tool.

Step Therapy

Optimization with PERT Required

Requests for an in-line digestive enzyme cartridge (eg, Relizorb™ immobilized lipase cartridge) require prior optimization with pancreatic enzyme replacement therapy (PERT) tablets or capsules, including administration via the feeding tube when applicable, before initial approval will be considered.

Optimize therapy with PERT tablets or capsules (oral or via feeding tube, capsules only when required) prior to requesting cartridge therapy.
Enteral tube nutrition should be required for continuous durations of 6 hours or more.

Documentation Required

Required Documentation for Medical Necessity

Documentation must demonstrate medical necessity for both initial and continuation requests. Include diagnostic evidence, clinical course, and response to therapy.

Diagnosis: documentation of cystic fibrosis with exocrine pancreatic insufficiency or other documented cause of exocrine pancreatic insufficiency.
Evidence of malabsorption of fats despite optimized PERT (eg, inadequate weight gain or weight loss, persistent signs of fat malabsorption).
For initial requests: documentation that the member requires enteral tube nutrition for continuous durations of 6 hours or more and that PERT optimization has been attempted.
For continuation requests: documentation of clinical benefit from cartridge use (eg, stable or increased weight) and continued requirement for enteral tube nutrition for continuous durations of 6 hours or more.
Provider should include relevant weight trends, nutrition assessments, and previous PERT dosing/administration details.

Denial Risk

Provider Actions

Requests that do not meet the above clinical criteria and documentation requirements will be considered not covered or not medically necessary.

Medicare Advantage: service is not covered when criteria are not met.
Commercial Products: service is not medically necessary when criteria are not met.
Covered code when criteria met: B4105 — In-line cartridge containing digestive enzyme(s) for enteral feeding, each.

Background

In-line immobilized lipase cartridges (for example, RELiZORB) contain immobilized pancreatic lipase and are used inline with enteral feeding tubing to hydrolyze fats in enteral formula into absorbable fatty acids and monoglycerides for patients with inadequate pancreatic lipase secretion. Clinical evidence supporting ILC use is strongest in cystic fibrosis populations: observational studies (for example, Sathe et al., 2021) reported improvements in weight and height z-scores over months of use. However, well-designed trials demonstrating effectiveness of ILCs for pancreatic insufficiency caused by conditions other than cystic fibrosis (such as chronic pancreatitis, celiac disease, diabetes, pancreatic cancer, short bowel syndrome, and others) are lacking, and the policy explicitly notes insufficient evidence to support use outside of CF.

Definitions

inv-15: In-line digestive enzyme cartridge (ILC)

Device definitionA single-use cartridge containing immobilized pancreatic lipase that connects in-line with enteral feeding tubing to hydrolyze fats in enteral formula.

Intended functionHydrolyzes triglycerides to free fatty acids and monoglycerides as formula flows through the cartridge

Example productRELiZORB (Alcresta Pharmaceuticals) is described as a single-use in-line digestive enzyme cartridge

inv-16: Exocrine pancreatic insufficiency (EPI)

DefinitionClinical condition in which the pancreas does not secrete sufficient digestive enzymes (notably lipase), leading to fat malabsorption and qualifying as a diagnosis for cartridge use.

Common qualifying diagnosisCystic fibrosis with confirmed exocrine pancreatic insufficiency is specified as an indication for cartridge use

Clinical evidence requirementPolicy requires continued fat malabsorption (insufficient weight or weight loss) despite optimization with pancreatic enzyme replacement therapy (PERT)