505(b)(2) Drugs and HCPCS Codes

505(b)(2) Pathway Explained

The 505(b)(2) drug approval pathway is a regulatory pathway in the United States created by the Hatch-Waxman Amendments of 1984 and located under the Federal Food, Drug, and Cosmetic Act. The 505(b)(2) pathway allows for an abbreviated process for the approval of new drug applications (NDAs) that represent modifications to previously approved products. Below is a breakdown of the 505(b)(2) pathway compared to other prominent approval drug pathways: 

505(b)(2) Pathway: 

The 505(b)(2) approval process is designed for drugs that represent modifications of previously approved products. These modifications could include:

  • New Formulation
  • New Dosage Form
  • New Dosing Regime
  • New Route of Administration
  • Combination Product
  • New Indication for an Existing Product

During the approval process, the 505(b)(2) applicant can use the FDA’s previous findings of safety and efficacy for an existing drug, while providing new data to support the changes made to the original product. This leads to a shorter and less costly development/approval process compared to a traditional NDA. 

Traditional NDA (New Drug Application):

The traditional NDA, also known as the 505(b)(1) pathway is the standard approval pathway for entirely new drugs. The NDA requires extensive data from preclinical and clinical studies from the applicant in order demonstrate the safety and efficacy of the drug. Earning drug approval under the traditional NDA is a time-consuming and often very expensive process.

ANDA (Abbreviated New Drug Application) for Generics:

An ANDA, also known as the 505(j) pathway exists for generic version of previously-approved brand name drugs. Rather than demonstrating safety and efficacy through new clinical trials, the generic drug manufacturer must demonstrate bioequivalence to the reference listed drug (RLD). In other words, that the drug is the same in terms of quality, performance, and intended use. The provides a timely and efficient manner for generic drugs to gain approval and enter the market. 

The 505(b)(2) pathway provides an intriguing option for manufacturers seeking a hybrid between the traditional NDA process and the ANDA for generic products. 

What Types of Drugs Qualify for the 505(b)(2) Pathway?

The 505(b)(2) pathway is uniquely suited for drugs that aren’t completely new (which would generally go through the traditional NDA process) and aren’t generic replicas (which would go through the ANDA process). As explained previously, drugs that qualify for 505(b)(2) might involve changes in dosage form, strength, formulation, administration route, or indication. To delve a bit deeper into the modifications that might warrant a 505(b)(2) approval: 

  • New Formulation: If a manufacturer removed a certain preservative or chemical from a drug, to create a similar but mildly-different product. 

  • New Dosage Form: If a previously approved drug was in tablet form, and another company develops a liquid formulation or a controlled-release version.

  • New Dosing Regimen: If an approved drug is taken twice daily, and a new formulation allows for once-daily dosing.

  • New Route of Administration: If a drug was initially approved as an oral drug, and another company later develops an injectable form.

  • Combination Product: A manufacturer combines two or more previously approved drugs into a single new product.

  • New Indication for an Existing Product: If a drug was initially approved for depression and later is found to be effective for anxiety.

How Does the Current Application of 505(b)(2) impact Buy and Bill?

In the year of 2023, there has been a tremendous wave of new 505(b)(2) pathway drug approvals. Although 505(b)(2) has existed since 1984, it was not actively enforced and perpetuated by the Centers for Medicare & Medicaid Services until late 2022/early 2023.

During this period of time, the Centers for Medicare & Medicaid Services along with various pharma manufacturers have actively worked to achieve 505(b)(2) approvals and enforce 505(b)(2) status to certain drugs. More specifically, CMS has granted HCPCS codes to a very large number of drugs that had previously been approved under the 505(b)(2) pathway or qualified for 505(b)(2) status, but had not yet recieved their own distinct HCPCS codes. Many drugs and NDC codes previously mapped to generic or miscellenous HCPCS codes, recieved their own unique HCPCS during the year of 2023. 

This shift has created quite a few issues in the office-administered drug ‘Buy and Bill’ process: 

  • NDC-HCPCS mapping: The sudden surge of 505(b)(2) HCPCS codes has made the NDC to HCPCS cross-walking process exceedingly complex. Many 505(b)(2) HCPCS are not listed on the CMS HCPCS-NDC crosswalk file, leaving providers stranded when it comes to NDC-HCPCS mapping. 

  • Diminishing Importance of NOC: With the implementation of 505(b)(2) HCPCS codes, CMS has begun clearing out the various NOC (Not Otherwise Classified) files published on their site. A large number of NDCs previously linked to NOC codes no longer appear on the CMS database. This presents a confusing situation for providers using these NDCs. 

  • Exteme ASP Fluctuation: The administration of new HCPCS codes for NDCs that were previously aligned to a single HCPCS can create heavy quarter-to-quarter ASP price fluctuations. Providers must be keenly aware of the HCPCS code they are utilizing to track how its ASP might be changing every quarter. 

Luckily for healthcare providers, BuyandBill.com provides highly accurate NDC-HCPCS alignments and several ASP monitoring tools. Just Login or Register to access our advanced features. 

Below is a table containing all 505(b)(2) drugs and HCPCS codes as of October, 2023: 

HCPCS CodeHCPCS Code DescriptorManufacturerDrug Name505(b)(2) Drug Type
J0131Injection, acetaminophen, not otherwise specified,10 mgMYLAN INSTITUTIONAL LLCACETAMINOPHENACETAMINOPHEN 505(b)(2)
J0134Injection, acetaminophen (fresenius kabi) not therapeutically equivalent to j0131, 10 mgFRESENIUS KABIACETAMINOPHENACETAMINOPHEN 505(b)(2)
J0136Injection, acetaminophen (b braun) not therapeutically equivalent to j0131, 10 mgB. BRAUN MEDICAL INC.ACETAMINOPHENACETAMINOPHEN 505(b)(2)
J0137Injection, acetaminophen (hikma) not therapeutically equivalent to j0131, 10 mgHIKMA PHARMACEUTICALS USA INC.ACETAMINOPHENACETAMINOPHEN 505(b)(2)
J0171Injection, adrenalin, epinephrine, 0.1 mgPAR PHARMACEUTICAL, INCEPINEPHRINE HCLEPINEPHRINE 505(b)(2)
J0173Injection, epinephrine (belcher) not therapeutically equivalent to j0171, 0.1 mgBELCHEREPINEPHRINEEPINEPHRINE 505(b)(2)
J0612Injection, calcium gluconate (fresenius kabi), per 10 mgFRESENIUS KABICALCIUM GLUCONATECALCIUM GLUCONATE 505(b)(2)
J0613Injection, calcium gluconate (wg critical care), per 10 mgWG CRITICAL CARECALCIUM GLUCONATECALCIUM GLUCONATE 505(b)(2)
J0689Injection, cefazolin sodium (baxter), not therapeutically equivalent to j0690, 500 mgBAXTERCEFAZOLIN SODIUMCEFAZOLIN SODIUM 505(b)(2)
J0690Injection, cefazolin sodium, 500 mgFRESENIUS KABICEFAZOLINCEFAZOLIN SODIUM 505(b)(2)
J0692Injection, cefepime hydrochloride, 500 mgSAGENT PHARMACEUTICALS INCCEFEPIME HYDROCHLORIDECEFEPIME HCL 505(b)(2)
J0701Injection, cefepime hydrochloride (baxter), not therapeutically equivalent to maxipime, 500 mgBAXTERCEFEPIME HCLCEFEPIME HCL 505(b)(2)
J0703Injection, cefepime hydrochloride (b braun), not therapeutically equivalent to maxipime, 500 mgB. BRAUN MEDICAL INC.CEFEPIME HCL IN DEXTROSECEFEPIME HCL 505(b)(2)
J0737Injection, clindamycin phosphate (baxter), not therapeutically equivalent to j0736, 300 mgBAXTER HEALTHCARE CORPCLINDAMYCIN PHOSPHATE IN NACLCLINDAMYCIN PHOSPHATE 505(b)(2)
J0877Injection, daptomycin (hospira), not therapeutically equivalent to j0878, 1 mgPFIZER INC.DAPTOMYCINDAPTOMYCIN 505(b)(2)
J0883Injection, argatroban, 1 mg (for non-esrd use)SANDOZARGATROBANARGATROBAN 505(b)(2)
J0884Injection, argatroban, 1 mg (for esrd on dialysis)PAR PHARMACEUTICAL, INCARGATROBANARGATROBAN 505(b)(2)
J0891Injection, argatroban (accord), not therapeutically equivalent to j0883, 1 mg (for non-esrd use)ACCORD HEALTHCARE INC.ARGATROBANARGATROBAN 505(b)(2)
J0892Injection, argatroban (accord), not therapeutically equivalent to j0884, 1 mg (for esrd on dialysis)ACCORD HEALTHCARE INC.ARGATROBANARGATROBAN 505(b)(2)
J0893Injection, decitabine (sun pharma) not therapeutically equivalent to j0894, 1 mgSUN PHARMACEUTICAL GLOBAL FZE.DECITABINEDECITABINE 505(b)(2)
J0894Injection, decitabine, 1 mgSANDOZDECITABINEDECITABINE 505(b)(2)
J0898Injection, argatroban (auromedics), not therapeutically equivalent to j0883, 1 mg (for non-esrd use)AUROMEDICS PHARMA LLCARGATROBANARGATROBAN 505(b)(2)
J0899Injection, argatroban (auromedics), not therapeutically equivalent to j0884, 1 mg (for esrd on dialysis)AUROMEDICS PHARMA LLCARGATROBANARGATROBAN 505(b)(2)
J1456Injection, fosaprepitant (teva), not therapeutically equivalent to j1453, 1 mgACTAVIS PHARMA, INC.FOSAPREPITANT FOR INJECTION 150 MGFOSAPREPITANT 505(b)(2)
J1570Injection, ganciclovir sodium, 500 mgFRESENIUS KABIGANCICLOVIRGANCICLOVIR 505(b)(2)
J1574Injection, ganciclovir sodium (exela) not therapeutically equivalent to j1570, 500 mgEXELA PHARMA SCIENCESGANCICLOVIRGANCICLOVIR 505(b)(2)
J1576Injection, immune globulin (panzyga), intravenous, non-lyophilized (e.g., liquid), 500 mgPFIZER INC.PANZYGAPANZYGA 505(b)(2)
J1599Injection, immune globulin, intravenous, non-lyophilized (e.g., liquid), not otherwise specified, 500 mgPFIZER LABSPANZYGAPANZYGA 505(b)(2)
J1610Injection, glucagon hydrochloride, per 1 mgBOEHRINGER INGELHEIM PHARMACEUTICALS, INC.GVOKE KITGLUCAGON 505(b)(2)
J1611Injection, glucagon hydrochloride (fresenius kabi), not therapeutically equivalent to j1610, per 1 mgFRESENIUS KABI USA, LLCGLUCAGONGLUCAGON 505(b)(2)
J1642Injection, heparin sodium, (heparin lock flush), per 10 unitsMEDEFIL, INC.HEPARINHEPARIN SODIUM 505(b)(2)
J1643Injection, heparin sodium (pfizer), not therapeutically equivalent to j1644, per 1000 unitsPFIZER INC.HEPARIN SODIUM (PORCINE)HEPARIN SODIUM 505(b)(2)
J1644Injection, heparin sodium, per 1000 unitsFRESENIUS KABIHEPARIN SODIUMHEPARIN SODIUM 505(b)(2)
J1805Injection, esmolol hydrochloride, 10 mgMYLAN INSTITUTIONAL LLCESMOLOL HCLESMOLOL HYDROCHLORIDE 505(b)(2)
J1806Injection, esmolol hydrochloride (wg critical care) not therapeutically equivalent to j1805, 10 mgWG CRITICAL CAREESMOLOL HCLESMOLOL HYDROCHLORIDE 505(b)(2)
J1920Injection, labetalol hydrochloride, 5 mgAKORNLABETALOL HCLLABETALOL HCL 505(b)(2)
J1921Injection, labetalol hydrochloride (hikma) not therapeutically equivalent to j1920, 5 mgHIKMA PHARMACEUTICALS USA INC.LABETALOL HCLLABETALOL HCL 505(b)(2)
J1950Injection, leuprolide acetate (for depot suspension), per 3.75 mgABBVIE US, LLCLUPRON DEPOT-PED 11.25MGLEUPROLIDE DEPOT 505(b)(2)
J1951Injection, leuprolide acetate for depot suspension (fensolvi), 0.25 mgTOLMARFENSOLVILEUPROLIDE DEPOT 505(b)(2)
J1952Leuprolide injectable, camcevi, 1 mgACCORD BIOPHARMA INC.CAMCEVILEUPROLIDE DEPOT 505(b)(2)
J1954Injection, leuprolide acetate for depot suspension (cipla), 7.5 mgCIPLA USA, INC.LEUPROLLIDE DEPOTLEUPROLIDE DEPOT 505(b)(2)
J2021Injection, linezolid (hospira) not therapeutically equivalent to j2020, 200 mgPFIZER INC.LINEZOLIDLINEZOLID 505(b)(2)
J2184Injection, meropenem (b. braun) not therapeutically equivalent to j2185, 100 mgB. BRAUN MEDICAL INC.MEROPENEMMEROPENEM 505(b)(2)
J2185Injection, meropenem, 100 mgFRESENIUS KABIMEROPENEMMEROPENEM 505(b)(2)
J2186Injection, meropenem and vaborbactam, 10mg/10mg (20mg)MELINTA THERAPEUTICS, INC.VABOMEREMEROPENEM 505(b)(2)
J2250Injection, midazolam hydrochloride, per 1 mgFRESENIUS KABIMIDAZOLAM HCLMIDAZOLAM HCL 505(b)(2)
J2251Injection, midazolam hydrochloride (wg critical care) not therapeutically equivalent to j2250, per 1 mgWG CRITICAL CAREMIDAZOLAM HCLMIDAZOLAM HCL 505(b)(2)
J2270Injection, morphine sulfate, up to 10 mgFRESENIUS KABIMORPHINE SULFATEMORPHINE SULFATE 505(b)(2)
J2272Injection, morphine sulfate (fresenius kabi) not therapeutically equivalent to j2270, up to 10 mgFRESENIUS KABIMORPHINE SULFATEMORPHINE SULFATE 505(b)(2)
J2274Injection, morphine sulfate, preservative-free for epidural or intrathecal use, 10 mgHIKMA PHARMACEUTICALS USA INC.MITIGOMORPHINE SULFATE 505(b)(2)
J2281Injection, moxifloxacin (fresenius kabi) not therapeutically equivalent to j2280, 100 mgFRESENIUS KABIMOXIFLOXACIN HCLMOXIFLOXACIN HCL 505(b)(2)
J2599Injection, vasopressin (american regent) not therapeutically equivalent to j2598, 1 unitAMERICAN REGENTVASOPRESSIN (AMERICAN REGENT)VASOPRESSIN 505(b)(2)
J2805Injection, sincalide, 5 microgramsBRACCO DIAGNOSTICSSINCALIDE INJSINCALIDE 505(b)(2)
J2806Injection, sincalide (maia) not therapeutically equivalent to j2805, 5 microgramsFRESENIUS KABI USA, LLCSINCALIDESINCALIDE 505(b)(2)
J3243Injection, tigecycline, 1 mgFRESENIUS KABITIGECYCLINETIGECYCLINE 505(b)(2)
J3244Injection, tigecycline (accord) not therapeutically equivalent to j3243, 1 mgACCORD HEALTHCATIGECYCLINETIGECYCLINE 505(b)(2)
J3370Injection, vancomycin hcl, 500 mgFRESENIUS KABIVANCOMYCIN HCLVANCOMYCIN HCL 505(b)(2)
J3371Injection, vancomycin hcl (mylan) not therapeutically equivalent to j3370, 500 mgMYLAN INSTITUTIONAL LLCVANCOMYCIN HCLVANCOMYCIN HCL 505(b)(2)
J3372Injection, vancomycin hcl (xellia) not therapeutically equivalent to j3370, 500 mgXELLIA PHARMACEUTICALS USA, LLCVANCOMYCIN HYDROCHLORIDEVANCOMYCIN HCL 505(b)(2)
J9033Injection, bendamustine hcl (treanda), 1 mgCEPHALON INC.BENDAMUSTINE HYDROCHLORIDEBENDAMUSTINE 505(b)(2)
J9034Injection, bendamustine hcl (bendeka), 1 mgCEPHALON INC.BENDEKABENDAMUSTINE 505(b)(2)
J9036Injection, bendamustine hydrochloride, (belrapzo/bendamustine), 1 mgEAGLE PHARMACEUTICALS, INC.BELRAPZOBENDAMUSTINE 505(b)(2)
J9046Injection, bortezomib, (dr. reddy's), not therapeutically equivalent to j9041, 0.1 mgDR. REDDY'S LABORATORIES, INC.BORTEZOMIBBORTEZOMIB 505(b)(2)
J9048Injection, bortezomib (fresenius kabi), not therapeutically equivalent to j9041, 0.1 mgFRESENIUS KABIBORTEZOMIBBORTEZOMIB 505(b)(2)
J9049Injection, bortezomib (hospira), not therapeutically equivalent to j9041, 0.1 mgHOSPIRA, INC.BORTEZOMIBBORTEZOMIB 505(b)(2)
J9056Injection, bendamustine hydrochloride (vivimusta), 1 mgSLAYBACK PHARMAVIVIMUSTABENDAMUSTINE 505(b)(2)
J9058Injection, bendamustine hydrochloride (apotex), 1 mgAPOTEX CORPBENDAMUSTINE (APOTEX)BENDAMUSTINE 505(b)(2)
J9059Injection, bendamustine hydrochloride (baxter), 1 mgBAXTER HEALTHCARE CORP.BENDAMUSTINE HYDROCHLORIDEBENDAMUSTINE 505(b)(2)
J9196Injection, gemcitabine hydrochloride (accord), not therapeutically equivalent to j9201, 200 mgACCORD HEALTHCARE INC.GEMCITABINEGEMCITABINE 505(b)(2)
J9198Injection, gemcitabine hydrochloride, (infugem), 100 mgSUN PHARMACEUTICAL INDUSTRIES, LTD.INFUGEMGEMCITABINE 505(b)(2)
J9201Injection, gemcitabine hydrochloride, not otherwise specified, 200 mgSUN PHARMA GLOBGEMCITABINEGEMCITABINE 505(b)(2)
J9217Leuprolide acetate (for depot suspension), 7.5 mgTOLMARLUPRON DEPOT-3 MONTH 22.5MG KITLEUPROLIDE DEPOT 505(b)(2)
J9259Injection, paclitaxel protein-bound particles (american regent) not therapeutically equivalent to j9264, 1 mgAMERICAN REGENT, INC.PACLITAXEL PROTEIN-BOUND (AMERICAN REGENT)PACLITAXEL 505(b)(2)
J9264Injection, paclitaxel protein-bound particles, 1 mgCELGENE CORPORATIONABRAXANEPACLITAXEL 505(b)(2)
J9267Injection, paclitaxel, 1 mgFRESENIUS KABIPACLITAXELPACLITAXEL 505(b)(2)
J9294Injection, pemetrexed (hospira) not therapeutically equivalent to j9305, 10 mgHOSPIRA, INC.PEMETREXEDPEMETREXED 505(b)(2)
J9296Injection, pemetrexed (accord) not therapeutically equivalent to j9305, 10 mgACCORD HEALTHCARE INC.PEMETREXEDPEMETREXED 505(b)(2)
J9297Injection, pemetrexed (sandoz), not therapeutically equivalent to j9305, 10 mgSANDOZPEMETREXEDPEMETREXED 505(b)(2)
J9304Injection, pemetrexed (pemfexy), 10 mgEAGLE PHARMACEUTICALSPEMFEXYPEMETREXED 505(b)(2)
J9305Injection, pemetrexed, not otherwise specified, 10 mgFRESENIUS KABI USA, LLCPEMETREXEDPEMETREXED 505(b)(2)
J9314Injection, pemetrexed (teva) not therapeutically equivalent to j9305, 10 mgTEVA PHARMACEUTICALS USA, INC.PEMETREXEDPEMETREXED 505(b)(2)
J9322Injection, pemetrexed (bluepoint) not therapeutically equivalent to j9305, 10 mgBLUEPOINT LAB INJECTABLESPEMETREXED DISODIUMPEMETREXED 505(b)(2)
J9323Injection, pemetrexed ditromethamine, 10 mgHOSPIRA, INC.PEMETREXED (HOSPIRA)PEMETREXED 505(b)(2)
J9393Injection, fulvestrant (teva) not therapeutically equivalent to j9395, 25 mgACTAVIS PHARMA, INC.FULVESTRANTFULVESTRANT 505(b)(2)
J9394Injection, fulvestrant (fresenius kabi) not therapeutically equivalent to j9395, 25 mgFRESENIUS KABIFULVESTRANTFULVESTRANT 505(b)(2)
J9395Injection, fulvestrant, 25 mgASTRAZENECAFULVESTRANTFULVESTRANT 505(b)(2)