Interim Guidance for Coding, Coverage, and Reimbursement For

Interim Guidance for Coding, Coverage, and Reimbursement

Please see Important Safety Information on pages 14 to 15 and refer to accompanying full Prescribing Information for XEMBIFY. Table of contents

INTRODUCTION 4

CODING FOR XEMBIFY

HEALTHCARE COMMON PROCEDURE CODING SYSTEM (HCPCS) CODES 5

NATIONAL DRUG CODES (NDCs) 5

INTERNATIONAL CLASSIFICATION OF DISEASES (ICD-10-CM) CODES 6

CURRENT PROCEDURAL TERMINOLOGY (CPT) CODES 7

HOME INFUSION SERVICES 8

DURABLE MEDICAL EQUIPMENT (DME) CODES 8

BILLING MEDICARE DME MAC’S 9

HOSPITAL REVENUE CODE 9

SAMPLE CLAIM FORMS 10-11

XEMBIFY SUPPORT PROGRAM 13

IMPORTANT SAFETY INFORMATION 14-15

The information contained in this guide is provided for informational purposes only and is subject to change. Providers are encouraged to contact their payers for specific information. Coding rules and guidelines are subject to payer discretion and should always be verified by the paying entity. Healthcare providers make the ultimate determination as to when to use a specific product, based on clinical appropriateness for a patient. This guide is not intended to provide specific guidance on how to use, code, bill, or charge for any product or service. Third-party payment for medical products and services is affected by numerous factors, and Grifols cannot make any representation or guarantee concerning reimbursement or coverage for any service or item. The Guide will be revised upon assignment of a permanent HCPCS code for XEMBIFY.

Please see Important Safety Information on pages 14 to 15 and refer to the accompanying full Prescribing Information for XEMBIFY.

3 Introduction Coding for XEMBIFY Grifols is pleased to announce the FDA approval of XEMBIFY for subcutaneous use, and to provide customers with this This section describes the types of codes that are likely to be most relevant to provider claims for XEMBIFY. guide to coverage and reimbursement. The guide is intended to assist customers in understanding third-party payment XEMBIFY is administered subcutaneously via an external subcutaneous infusion pump. The most common setting of care is for XEMBIFY. the patient’s home; however, there may be some use in the physician office or Hospital Outpatient Department (HOPD), for XEMBIFY (immune globulin subcutaneous, human- klhw) is a 20% immune globulin solution for subcutaneous injection example, for training and instructional purposes. indicated for treatment of Primary Humoral Immunodeficiency (PIDD) in patients 2 years of age and older. This includes, 1 but is not limited to congenital agammaglobulinemia, common variable immunodeficiency, X-linked agammaglobulinemia, HEALTHCARE COMMON PROCEDURE CODING SYSTEM (HCPCS) CODES Wiskott-Aldrich syndrome, and severe combined immunodeficiencies. Presently, there is no specific, permanent HCPCS code for XEMBIFY. Grifols will apply for a permanent code at the end of 2019 with the Centers for Medicare and Medicaid Services (CMS). The code will be available for use beginning calendar year XEMBIFY is contraindicated in patients who have had an anaphylactic or severe systemic reaction to human 2021. Until a permanent code is assigned, payers may require one of the following codes for XEMBIFY. immunoglobulin or inactive ingredients of XEMBIFY such as polysorbate 80. It is contraindicated in IgA-deficient patients with antibodies against IgA and history of hypersensitivity. HCPCS CODE DESCRIPTION PLEASE NOTE: J3590* Unclassified biologics These codes are not all-inclusive; appropriate codes can vary by patient, setting of care, and payer. Correct coding is the responsibility of the provider submitting the claim for the item or service. Please check with NOC drugs, other than inhalation drugs, administered J7799* the payer to verify codes and special billing requirements. Grifols does not make any representation or through DME guarantee concerning reimbursement or coverage for any service or item. *Select the code recommended by the payer to which you are submitting claims.

DOSING AND ADMINISTRATION FOR XEMBIFY When using an unclassified or Not Otherwise Classified (NOC) code, claims should include a concise description of the drug administered in Item 19 of the CMS-1500 claim form or its electronic equivalent (see sample claim form on page 10): XEMBIFY is approved for subcutaneous infusion only. Before switching to XEMBIFY, healthcare professionals should obtain a patient’s serum IgG trough level to guide subsequent dose adjustments. •Drug name: The full description is “XEMBIFY (immune globulin subcutaneous, human —klhw) 20% solution” When switching from an IVIG to XEMBIFY: calculate the dose by using a dose adjustment factor of 1.37. Begin XEMBIFY •Total dosage: Grams administered one week after the last IVIG infusion. •Method of administration: Subcutaneous infusion Establish initial; weekly dose by converting the monthly (or every 3 weeks) IVIG dose into an equivalent weekly dose and The quantity-billed field must be entered as “1” which will alert claims processors to refer to Item 19 for specific details increase it by the dose adjustment factor 1.37. regarding the drug and dosage administered2 (see sample claim form on page 10).

For frequent dosing (2-7 times per week) you divide the calculated weekly dose by the desired number of times per week. 1Centers for Medicare and Medicaid Services (CMS). HCPCS file located at: http://www.cms.gov/Medicare/Coding/HCPCSReleaseCodeSets/ Alpha-Numeric-HCPCS.html. When switching from immune globulin subcutaneous (human) treatment (IGSC), the weekly dose (grams) should be the 2Noridian (a Medicare Administrative Contractor). Instructions located at: https://med.noridianmedicare.com/web/jeb/topics/claim-submission/submission-errors-solutions/ same as the weekly dose prior IGSC treatment (grams). unlisted-procedure-and-noc-codes Administration of XEMBIFY may occur in up to 6 infusion sites simultaneously, with at least 2 inches (5 cm) between sites avoiding bony prominences. Rotate sites for each administration. NATIONAL DRUG CODES (NDCs) NDCs are typically used for billing drugs and biologicals provided by pharmacies and by some home infusion providers. On some claims, certain payers may require NDCs in addition to HCPCS codes. XEMBIFY has the following NDCs:

NDC* SIZE GRAM PROTEIN

13533-0810-05 5 mL 1

13533-0810-10 10 mL 2

13533-0810-20 20 mL 4

13533-0810-50 50 mL 10

*The 10-digit NDC appears on the product packaging and the Product Information. For reimbursement purposes, an 11-digit NDC is required. This is achieved by adding a leading “0” to the second section of the 10-digit NDC (see bold in table).

Please see Important Safety Information on pages 14 to 15 and refer to the accompanying full Prescribing Information for XEMBIFY.

4 5 INTERNATIONAL CLASSIFICATION OF DISEASES, 10TH REVISION, CLINICAL MODIFICATION (ICD-10-CM) CODES3 ICD-10-CM diagnosis codes describe the patient’s condition requiring treatment. Please select the code(s) that accurately identify the patient’s diagnosis.

IMMUNODEFICIENCY COMMON VARIABLE IMMUNODEFICIENCY WITH D82 ASSOCIATED WITH OTHER D83 COMBINED IMMUNODEFICIENCY D80 PREDOMINANTLY ANTIBODY D81 MAJOR DEFECTS IMMUNODEFICIENCIES DEFECTS Common variable immunodeficiency Wiskott-Aldrich syndrome D83.0 with predominant abnormalities of Severe combined immunodeficiency D82.0 Immunodeficiency with B-cell numbers and function Hereditary hypogammaglobulinemia D81.0 Autosomal recessive (SCID) with reticular dysgenesis thrombocytopenia and eczema D80.0 agammaglobulinemia (Swiss type) Common variable immunodeficiency X-linked agammaglobulinemia [Bruton] D83.1 with predominant immunoregulatory (with growth hormone deficiency) Severe combined immunodeficiency T-cell disorders D81.1 (SCID) with low T- and B-cell numbers Di George’s syndrome Pharyngeal pouch syndrome D82.1 Thymic alymphoplasia Common variable immunodeficiency D83.2 with autoantibodies to B- or T-cells Nonfamilial hypogammaglobulinemia Severe combined immunodeficiency Thymic aplasia or hypoplasia with Agammaglobulinemia with D81.2 (SCID) with low or normal B-cell immunodeficiency immunoglobulin-bearing numbers Other common variable D80.1 B-lymphocytes D83.8 Hyperimmunoglobulin E [IgE] immunodeficiencies Common variable D82.4 agammaglobulinemia [CVAgamma] D81.4 Nezelof’s syndrome syndrome Hypogammaglobulinemia NOS Common variable immunodeficiency, Immunodeficiency associated with D83.9 Purine nucleoside phosphorylase D82.9 unspecified D81.5 major defect, unspecified Selective deficiency of [PNP] deficiency D80.2 immunoglobulin A (IgA) Major histocompatibility complex D81.6 Selective deficiency of class I deficiencey D80.3 immunoglobulin G (IgG) subclasses CURRENT PROCEDURAL TERMINOLOGY (CPT®) CODES4 Major histocompatibility complex D81.7 XEMBIFY is intended for subcutaneous infusion only. Selective deficiency of class II deficiencey D80.4 immunoglobulin M (IgM) D81.89 Other combined immunodeficiencies Immunodeficiency with increased CPT CODE DESCRIPTION D80.5 immunoglobulin M (IgM) Combined immunodeficiency, unspecified Severe combined D81.9 Subcutaneous infusion for therapy or prophylaxis (specify substance or drug); initial, up to 1 Antibody deficiency with near- immunodeficiency disorder [SCID] 96369 hour, including pump set-up and establishment of subcutaneous infusion site(s) D80.6 normal immunoglobulins or with NOS hyperimmunoglobulinemia Subcutaneous infusion for therapy or prophylaxis (specify substance or drug); each additional 96370 hour (list separately in addition to code for primary procedure) Transient hypogammaglobulinemia of D80.7 infancy Subcutaneous infusion for therapy or prophylaxis (specify substance or drug); additional pump 96371 set-up with establishment of new subcutaneous infusion site(s) (list separately in addition to Other immunodeficiencies with code for primary procedure) D80.8 predominantly antibody defects 3Optum, ICD-10-CM for Hospitals and Payers, Volumes 1, 2, and 3, publisher of the official code set issued by the Department of Health and Human Services Kappa light chain deficiency 4CPT 5-digit codes, nomenclature, and other data are ©2018 American Medical Association (AMA). No fee schedules, basic units, relative units, or related listings are included in CPT. The AMA assumes no liability for the data contained herein. Immunodeficiency with predominantly D80.9 antibody defects, unspecified

Please see Important Safety Information on pages 14 to 15 and refer to the accompanying full Prescribing Information for XEMBIFY.

6 7 HOME INFUSION SERVICES BILLING MEDICARE DME MACS5 The Medicare Part B Durable Medical Equipment (DME) benefit covers subcutaneously infused drugs requiring an HCPCS / CPT DESCRIPTION external infusion pump for administration. Suppliers submit Part B DME claims to the appropriate DME Medicare Administrative Contractor (MAC) using the electronic version of the CMS-1500 claim form (see sample claim form on Home infusion therapy, immunotherapy, administrative services, professional page 10). References to the CMS-1500 claim form use the paper format’s identifiers but will guide electronic claims * S9338 pharmacy services, care coordination, and all necessary supplies and submissions as well. equipment (drugs and nursing visits coded separately), per diem Professional services for the administration of subcutaneous immunotherapy G0069† for each infusion drug administration calendar day in the individual’s home, HCPCS CODE6 DESCRIPTION each 15 minutes. J3590-JB* Unclassified biologics 99601* Home infusion/specialty drug administration, per visit (up to 2 hours)

* Home infusion/specialty drug administration, per visit (up to 2 hours); each J7799-JB NOC drugs, other than inhalation drugs, administered through DME 99602* additional hour *To specify SC administration, Medicare requires that modifier –JB accompany the HCPCS code J3590 or J7799 on claims billed to the DME Medicare Administrative Contractors (MACs). *This code is not for use on Medicare claims, but may be covered by payers other than Medicare.

†This code represents a new Medicare temporary transitional payment for home infusion therapy services for calendar years 2019 and 2020. The payment is made to qualified specialty pharmacy providers for items and services necessary for the home infusion of drugs infused via durable medical equipment, including subcutaneous immune globulin. HOSPITAL REVENUE CODE For reimbursement to be provided, a skilled professional must be present in the home for the infusion. For hospital claims, most public and private payers require providers to use revenue codes. Revenue codes are 4-digit codes that identify the general types of services or products under broad revenue centers. DURABLE MEDICAL EQUIPMENT (DME) CODES The following revenue code most commonly applies to drug and biological products such as XEMBIFY: HCPCS CODE DESCRIPTION REVENUE CODE7 DESCRIPTION HCPCS Code Description EXTERNAL INFUSION PUMP CODES Pharmacy, drugs requiring Unclassified drugs 0636 C9399 E0779 Ambulatory infusion pump, mechanical, reusable for infusion 8 hours or greater detailed coding or biologicals

E0780 Ambulatory infusion pump, mechanical, reusable, for infusion less than 8 hours When using unclassified drugs or biological code C9399, the unit value entered in Form Locater (FL) 46 is always “1”, Ambulatory infusion pump, single or multiple channels, electric or battery operated, with E0781 regardless of the actual quantity administered. The unit value of “1” directs the (MAC) to the “Remarks” section of the administrative equipment, worn by patient CMS-1450 or its electronic equivalent, where the hospital should report: E0791 Parenteral infusion pump, stationary, single, or multichannel •The National Drug Code (NDC) for the drug;

EXTERNAL INFUSION PUMP SUPPLIES •The quantity that was administered;

Supplies for maintenance of non-insulin drug infusion catheter, per week (list drugs •The unit of measure applicable (e.g., grams or mg); and A4221 separately) •The date the drug was furnished to the beneficiary Infusion supplies for external drug infusion pump, per cassette or bag A4222 (list drugs separately) See sample claim form on page 11.

K0552 Supplies for external non-insulin drug infusion pump, syringe type cartridge, sterile, each

5Palmetto GBA (a Medicare Administrative Contractor). Instructions located at: https://palmettogba.com/palmetto/providers.nsf/DocsCat/Providers~JM%20Part%20 A~Resources~FAQs~Claims~8BFR455541?open&navmenu=%7C%7C

6Centers for Medicare and Medicaid Services (CMS). HCPCS file located at: http://www.cms.gov/Medicare/Coding/HCPCSReleaseCodeSets/Alpha-Numeric-HCPCS.html.

7National Uniform Billing Committee (NUBC) guidance located at: http://www.nubc.org/.

Please see Important Safety Information on pages 14 to 15 and refer to the accompanying full Prescribing Information for XEMBIFY.

8 9 Sample CMS-1500 for XEMBIFY Sample CMS-1450/UB-04 Uniform Bill for XEMBIFY

BOX 21: Insert the appropriate ICD- 10 CM code(s) Form Locator that reflect(s) the (FL) 42 &43: condition for which 0636 - Pharmacy the patient is being requiring detailed treated coding

BOX 19: • Drug name: “XEMBIFY solution for Form Locator subcutaneous use” (FL) 44: • Total dosage: Unclassified drugs or biologicals • Method of administration: Form Locator subcutaneous (FL) 46: infusion Unit value for C9399 = 1

BOX 24G: Form Locator Unit value for NOC (FL) 67: codes = 1 Insert the appropriate ICD- 10 CM code(s) BOX 24D: that reflect(s) the Insert the condition for which MM DD YYYY MM DD YYYY unclassified or the patient is being NOC HCPCS code MM DD YYYY MM DD YYYY treated accepted by the MM DD YYYY MM DD YYYY payer. Be sure to append modifier REMARKS: -JB on claims Insert the submitted to the appropriate the DME MACs. NDC for the Insert the vial of XEMBIFY appropriate administered along subcutaneous with the dosage as administration stated on the vial PLEASE PRINT OR TYPE APPROVED OMB-0938-1197 FORM 1500 (02-12) code according to label and carton.; payer requirements MM/DD/YYYY

Please see Important Safety Information on pages 14 to 15 and refer to the accompanying full Prescribing Information for XEMBIFY.

10 11 A partnership with dedicated support SUPPORTING PATIENTS THROUGHOUT THEIR TREATMENT

Copay Dedicated Access to assistance support program XEMBIFY

Patients may save up to Partnering with you and Call XEMBIFY Connexions $5000 over 12 months your PIDD patients to at 1-888-MYXEMBIFY to on their prescription for ensure ongoing access access XEMBIFY through XEMBIFY. and continuity of care. our distribution patners.

ACCESS TO XEMBIFY Coding and reimbursement information Benefits investigation

FINANCIAL ASSISTANCE Up to $5000 in copay assistance for PIDD patient Patient assistance program (PAP)

DEDICATED PATIENT SUPPORT PROGRAM Patient starter kit PIDD education materials

UP TO $5000 in Copay Assistance

1-844-MYXEMBIFY 1-844-699-3624 XEMBIFY.com

Please see Important Safety Information on pages 14 to 15 and refer Please see Important Safety Information on pages 14 to 15 and refer to the accompanying full Prescribing Information for XEMBIFY. to the accompanying full Prescribing Information for XEMBIFY.

12 13 INDICATION Transfusion-related acute lung injury (TRALI). Noncardiogenic pulmonary edema may occur in patients following treatment with immune globulin products, including XEMBIFY. Monitor patients for pulmonary adverse reactions. If TRALI XEMBIFY™ (immune globulin subcutaneous human–klhw) is a 20% immune globulin indicated for treatment of is suspected, perform appropriate tests for the presence of antineutrophil and anti-HLA antibodies in both the product primary humoral immunodeficiency disease (PIDD) in patients 2 years of age and older. XEMBIFY is for subcutaneous and patient serum. TRALI may be managed using oxygen therapy with adequate ventilatory support. administration only. Transmissible infectious agents. Because XEMBIFY is made from human blood, it may carry a risk of transmitting IMPORTANT SAFETY INFORMATION infectious agents, eg, viruses, the variant Creutzfeldt-Jakob disease (vCJD) agent, and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent. No cases of transmission of viral diseases, vCJD, or CJD have ever been associated with the use of WARNING: THROMBOSIS XEMBIFY. •Thrombosis may occur with immune globulin products, including XEMBIFY. Risk factors may include: Interference with lab tests. After infusion of XEMBIFY, passively transferred antibodies in the patient’s blood may yield advanced age, prolonged immobilization, estrogens, indwelling vascular catheters, hyperviscosity, and positive serological testing results, with the potential for misleading interpretation. cardiovascular risk factors. Thrombosis may occur in the absence of known risk factors.

•For patients at risk of thrombosis, administer XEMBIFY at the minimum dose and infusion rate Adverse Reactions practicable. Ensure adequate hydration in patients before administration. Monitor for signs and The most common adverse reactions in ≥ 5% of subjects in the clinical trial were local adverse reactions, including symptoms of thrombosis and assess blood viscosity in patients at risk of hyperviscosity. infusion-site erythema (redness), infusion-site pain, infusion-site swelling (puffiness), infusion-site bruising, infusion-site nodule, infusion-site pruritus (itching), infusion-site induration (firmness), infusion-site scab, infusion-site edema, and Contraindications systemic reactions including cough and diarrhea. XEMBIFY is contraindicated in patients who have had an anaphylactic or severe systemic reaction to the administration of human immune globulin. It is contraindicated in IgA-deficient patients with antibodies against IgA and a history of Drug Interactions hypersensitivity. Passive transfer of antibodies may transiently interfere with the immune responses to live attenuated virus vaccines (eg, measles, mumps, rubella, and varicella). Warnings and Precautions Hypersensitivity. Severe hypersensitivity reactions may occur with immune globulin products, including XEMBIFY. In Please see accompanying full prescribing information for XEMBIFY. case of hypersensitivity, discontinue infusion immediately and institute appropriate treatment. XEMBIFY contains IgA. Patients with known antibodies to IgA may have a greater risk of developing potentially severe hypersensitivity and anaphylactic reactions.

Thrombosis. Thrombosis may occur following treatment with immune globulin products, including XEMBIFY. Thrombosis may occur in the absence of known risk factors. In patients at risk, administer at the minimum dose and infusion rate practicable. Ensure adequate hydration before administration. Monitor for signs and symptoms of thrombosis and assess blood viscosity in patients at risk of hyperviscosity.

Aseptic meningitis syndrome (AMS). AMS may occur with human immune globulin treatment, including XEMBIFY. Conduct a thorough neurological exam on patients exhibiting signs and symptoms to rule out other causes of meningitis. Discontinuation of treatment has resulted in remission within several days without sequelae.

Renal dysfunction/failure. Acute renal dysfunction/failure, acute tubular necrosis, proximal tubular nephropathy, osmotic nephrosis, and death may occur with use of human immune globulin products, especially those containing sucrose. XEMBIFY does not contain sucrose. Ensure patients are not volume-depleted prior to starting infusion. In patients at risk due to preexisting renal insufficiency or predisposition to acute renal failure, assess renal function prior to the initial infusion of XEMBIFY and again at appropriate intervals thereafter. If renal function deteriorates, consider discontinuation.

Hemolysis. XEMBIFY may contain blood group antibodies that may cause a positive direct antiglobulin reaction and hemolysis. Monitor patients for clinical signs and symptoms of hemolysis. If signs and symptoms are present after infusion, perform confirmatory lab testing.

14 15 Go to www.xembify.com for additional resources and updates. Please contact XEMBIFY Connexions at 1-844-MYXEMBIFY (1-844-699-3624) for more information about financial support for patients with PIDD

Please see Important Safety Information on pages 14 to 15 and refer to the accompanying full Prescribing Information for XEMBIFY.