Understanding Biologic Substitutions – New Tool Available!

Our PAAS National® analyst team developed a new tool to assist pharmacies with biologic substitutions. Understanding when to substitute and what to substitute with can be complicated. This new tool, Understanding Biologic Substitutions, will help you understand the biologic terminology and simplify the substitution process at your pharmacy. The resource also includes a chart (with reference NDCs) for the most confusing biologic substitution drug category – insulin.

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The FDA publishes two lists of approved drugs:

  • The Orange Book – Approved Drug Products with Therapeutic Equivalence Evaluations
  • The Purple Book – Approved Biological Products including Biosimilar and Interchangeable products

Biologic products are found in the Purple Book and are not described in familiar terms like “brand“, “generic”, or “AB rated” as found in the Orange Book. The FDA’s Purple Book lists each product as a Reference Product, Biosimilar, or Interchangeable. Review the Purple Book terminology below:

Reference Product is the original biological product approved through a 351(a) BLA (Biologic Licensing Application)

  • Think of these products like brand drugs in the FDA Orange Book
  • Cannot be substituted for other Reference Products without prescriber approval

Biosimilar products are approved through an abbreviated 351(k) BLA

  • Think of these products like B-rated generic drugs in the FDA Orange Book
  • Cannot be substituted for Reference Products without prescriber approval

Interchangeable products have been deemed interchangeable with a reference product after going through additional switching studies and approved under a 351(k) BLA

  • Think of these products like A-rated generic drugs in the Orange Book
  • CAN be substituted for respective Reference Products without contacting the prescriber if state law permits

Unbranded biologic products are approved under the Reference Product’s 351(a) BLA

  • Think of these products like authorized generics in the Orange Book
    • CAN be substituted for the Reference Product without prescriber approval or regard to state law
    • Considered by the FDA to be equivalent to its brand name biological product because it is the same product as the brand name under the same BLA, just with a different label
    • Is not different in strength, dosage form, route of administration, or presentation
    • NOT separately identified in the Purple Book

PAAS Tips:

  • Pharmacy level substitution of a reference product is only allowed if one of the following scenarios is applicable:
  • identified as interchangeable AND your state pharmacy practice law allows
    • Ex: Semglee® can be substituted for Lantus® due to 351k interchangeable status
  • an unbranded biologic with the same BLA number as the reference product
    • Ex: Semglee® (BLA 761201) can be freely substituted with its unbranded biologic Insulin glargine-yfgn (BLA 761201)
  • an unbranded biologic with the same BLA number as an interchangeable biosimilar
    • Ex: Insulin glargine-yfgn (BLA 761201), an unbranded biologic of Semglee® (BLA 761201), can be substituted for Lantus (BLA 021081) because Semglee® has 351(k) interchangeable status to Lantus and therefore its unbranded biologic (insulin glargine-yfgn) can also be freely substituted
  • See FDA Purple Book to determine interchangeability status of a particular biologic drug
    • FDA has more detailed definitions on the Purple Book website.
    • There is also a frequently asked question section that discusses unbranded biologics (FAQ #11).
  • State pharmacy laws may limit biologic interchangeability, but this does not apply to unbranded biologics. Review your state laws (reference) or  contact your state Board of Pharmacy.
  • If you are ever in doubt about whether products may be substituted
  • Review the September 2022 Newsline article, NCPDP Updates DAW Code Definitions to Encompass Interchangeable Biosimilars
  • Review the FDA’s Curriculum Materials for Health Care Degree Programs | Biosimilars

Boost Your Bottom Line with In-Home Preventative Vaccine Administration

As some may recall, the Centers for Medicare & Medicaid Services (CMS) rolled out a program back in 2021 where pharmacies were eligible to receive additional reimbursement for administering COVID-19 vaccinations to certain Medicare homebound patients (see October 2021 PAAS Newsline article, COVID-19 Vaccine Administration Audit Risk). As of January 2024, pharmacies can take advantage of a similar program where Medicare beneficiaries who meet the necessary criteria can be vaccinated for the other preventative vaccines covered under Medicare Part B – influenza, hepatitis B, and pneumococcal.

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As explained on CMS’s In-Home Vaccine Administration: Additional Payment website, Medicare beneficiaries who have “difficulty leaving the home or faces barriers to getting a vaccine in settings other than their home” would be considered eligible. Examples given by CMS include:

  • They have a condition, due to an illness or injury, that restricts their ability to leave home without a supportive device or help from a paid or unpaid caregiver
  • They have a condition that makes them more susceptible to contracting a disease
  • They’re generally unable to leave the home. If they do leave the home, it requires a considerable and taxing effort
  • The patient is hard-to-reach because they have a disability or face clinical, socioeconomic, or geographical barriers to getting a vaccine in settings other than their home. These patients face challenges that significantly reduce their ability to get vaccinated outside the home, such as challenges with transportation, communication, or caregiving.

As evident from this guidance, CMS leaves the standard to meet this requirement relatively open to interpretation. In addition, pharmacies do not need to certify that the Medicare beneficiary is homebound, which is a departure from the requirements under the Medicare home health benefit. However, PAAS National® recommends documenting the rationale for the patient qualification [for the vaccine administration at home] on the prescription.

As part of the program, pharmacies can earn an in-home vaccination payment of $38 in addition to the $30 standard administration amount, totaling $68 (subject to rate adjustments based on geographical location) per patient if the sole purpose of the visit is to administer vaccine(s). Visit the CMS website for more information on additional payment scenarios.

PAAS Tips:

  • Ensure appropriate CPT code use for vaccine administration: flu (G0008), hepatitis B (G0010), pneumococcal (G0009)
  • Utilize HCPCS Level II code M0201 to bill for the additional payment amount earned by administering the vaccination as part of the in-home program

U.S. Government Alleges Counterfeit HIV Drugs Hiding in Pharmacy-to-Pharmacy Purchases

PAAS National® previously alerted pharmacies to a large-scale counterfeit HIV medication scam in our April 2022 article Know Your Distributors: Gilead Confiscates Phony HIV Medication where criminal enterprises routed black market and counterfeit HIV medications through the secondary wholesaler market (the 2022 Gilead lawsuit is referred to as Gilead I).

In a new lawsuit filed by Gilead in June 2024 (referred to as Gilead II), the U.S. Government alleges that the criminals changed their strategy to route diverted medications through pharmacies that were “in on the conspiracy” who would then sell the counterfeit products to other, unsuspecting, pharmacies through “pharmacy to pharmacy” purchases. The scheme involves …

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criminals buying back empty manufacturer bottles from patients, removing pharmacy labels with lighter fluid, refilling the bottles with cheap medication or counterfeit tablets made to look like the real thing, and then selling them to cooperating pharmacies that are in on the scheme. The participating pharmacies then either dispensed the medications to patients (after billing insurance) or further distributed the drugs to unsuspecting pharmacies through online marketplaces where Drug Supply Chain Security Act (DSCSA) integrity can be compromised.

The DSCSA permits pharmacies (called “dispensers” under the law) to purchase drugs from other pharmacies – to conform to the law, these purchases must be accompanied by the pedigree to ensure that the “track and trace” paper trail remains intact. A notable exception to the DSCSA is that pharmacies may purchase drugs and do NOT have to obtain the pedigree IF the purchase is for a “specific patient need” (further discussed in December 2022 article Pharmacy to Pharmacy Inventory Transfers – Buyer Beware!)

Due to systemic underpayments by PBMs, many pharmacies have been forced to hunt for savings outside of their primary wholesaler agreement which has led to the proliferation of “pharmacy to pharmacy” purchases, resulting in routine purchases from marketplaces because products are cheaper than from regular wholesalers (despite widespread availability). The criminals know that pharmacies run on tight margins and are often desperate to find savings. These fraudsters are also smart enough to discount prices just enough to get pharmacies to buy the products, but not discount them too much as to tip off the fraud (i.e., a 5% discount is more believable than a 30% discount).

PAAS has worked with numerous pharmacies that have run into significant invoice audit problems based on large volumes of pharmacy-to-pharmacy purchases that occurred through online marketplaces. Due to these large volumes, the PBMs (mainly Caremark and OptumRx) are challenging the claim that the purchases fall under DSCSA exception and demand that pharmacies provide evidence of specific patient need, copies of selling pharmacy licenses, and copies of wholesaler invoices showing where the selling pharmacies obtained the drugs. Because of the arms-length transaction facilitated through the online marketplace, the selling pharmacies are typically not interested in getting involved. In the absence of these supporting documents to prove that the pharmacy is “innocent”, and the products are legitimate, the PBMs have presumed products are counterfeit or diverted, resulting in them seeking full recoupments (often 6- and 7-figures) from independent pharmacies!

Additionally, in the last few weeks, PAAS has seen several subpoenas being issued to independent pharmacies pursuant to Gilead II’s pending case in the U.S. District Court for the Eastern District of New York.

The DSCSA is designed to keep counterfeit and diverted medications out of the U.S. supply chain and keep patients safe. While the full implementation of electronic interoperability will not be enforced until November 27, 2026 (2 year exemption for “small dispensers”) pharmacies are still required to comply with many aspects of DSCSA including: ensuring that you purchase drugs from authorized trading partners, receive/store/provide product tracing information, and quarantine/investigate suspect and illegitimate drugs.

PAAS Tips:

  • Procuring medications outside of DSCSA “Authorized Trading Partners” puts pharmacies and patients at great risk
  • See this information sheet from the Partnership for Safe Medicines to help educate your staff
  • See Newsline article from April 2024, Caremark Invoice Audits – Purchases from Other Pharmacies for a list of data points to record if you purchase inventory from another pharmacy

Walgreens $107 Million Settlement for False Claims Act Violations

A recent Department of Justice press release outlined a settlement with Walgreens for nearly $107 million for False Claims Act violations related to claims billed to government programs that were never dispensed. The government alleges that from 2009-2020, Walgreens restocked thousands of prescriptions billed to Medicare and Medicaid and resold the same medication, effectively collecting payment twice on the same medications.

The underlying cause of the systematic overbilling was related to a feature in Walgreens’ pharmacy management software (Intercom Plus, IC+) where prescriptions which were billed but not sold were removed from the local IC+ servers after 29 days (to save space) and moved into an “Unaccounted-For Status” on the central IC+ server. Pharmacists in the stores could no longer see these prescriptions in the local IC+ work queue and there was no back-end process to reverse the paid claims that were moved into the Unaccounted-For Status. Essentially thousands of billed prescriptions “got lost” and Walgreens received payment for items never dispensed.

In January 2020, Walgreens self-disclosed the systematic error, began to implement corrective actions to resolve the problem, and fully cooperated with the government to settle the overpayments.

Two separate qui tam relators brought this systemic problem to the government’s attention and will receive $14.9 and $1.6 million dollars, respectively.

PAAS Tips:

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  • PAAS suggests that pharmacies perform Return to Stock for any claims not picked up within 10 days of billing
  • PAAS FWA and HIPAA Compliance members can find information about unclaimed prescriptions in section 4.1.1 of their Policy & Procedure Manual
  • Pharmacies with an integrated point-of-sale system should periodically run reports to looking for paid claims that have not been sold to ensure that there are no prescription claims that are “lost” and may result in inappropriate overpayments

Download PAAS’ Return to Stock Chart for detail on PBM specific requirements

FDA Proposed Guidance for Biosimilar Updates

Over the last 10 years, biologics have transformed the treatment of many illnesses like chronic bowel disease, kidney disease, arthritis and cancer and they are the fastest growing class of medications in the United States. The FDA has gained valuable scientific information in reviewing both biosimilar and interchangeable biosimilar medications. They both meet the same high FDA standards and are as safe and effective as the reference product. When the FDA designates a biosimilar product as “interchangeable,” a pharmacist may substitute that product for a biologic without contacting the physician (predicated on state law). This pharmacy-level substitution provides increased access to treatments and cost savings for patients.

However, many pharmacies struggle to understand which biosimilar products can be substituted for the reference product. Consider the following definitions from the FDA:

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  • A biosimilar is a biologic that is highly similar to and has no clinically meaningful difference from an existing FDA-approved biological medication, called a reference product.
  • A reference product is approved in a standalone application that must contain all data and information necessary to demonstrate the product’s safety and effectiveness.

Newly proposed FDA guidance may alleviate this confusion of biosimilar interchangeability.

On June 20, 2024, the FDA issued a draft guidance for industry Considerations for Demonstrating Interchangeability With a Reference Product: Update. The recommendations in the draft guidance would provide clarity and transparency regarding the FDA’s review and approval process for biosimilars. 

The draft guidance eliminates the requirement that biosimilars produce clinical data to show they are interchangeable with their reference product. These clinical trials (switching studies) add time and expense to the development of a biosimilar and delay them from reaching patients.

This update would allow manufacturers who are interested in obtaining a Biologic License Application (BLA) for a biosimilar with a review for interchangeability status to either:

  1. Submit clinical trial data or
  2. Provide a statement indicating why the data in the BLA already demonstrates switching safety
    1. Any other information relevant to support the risk, in terms of safety and diminished efficacy, from alternating or switching between the reference product and proposed biosimilar is not greater than the risk of using the reference product without a clinical trial

Companies with pending BLAs can also submit an amendment to their application including the above information.

While biologic substitution is regulated at the state level, the FDA could broadly increase the number of biologics categorized as interchangeable biosimilars with this draft guidance, making pharmacist driven substitutions more commonplace. PAAS will keep you informed as we await Final Guidance from the FDA.

Self-Audit Series #8: Compound Prescriptions

Compound prescriptions may not be a frequent occurrence for some pharmacies; however, those that do bill compounds must be aware of the audit risks. In addition to a valid prescription, the pharmacy must also have sufficient compound worksheets/logs, and ensure they are billing the claim accurately.

Here is a review what you will need for audit purposes for compound prescriptions:

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  1. Prescription
    1. Must have a valid prescription order that meets all state and federal requirementsMedication that is commercially available is generally prohibited from being compounded by the pharmacy. Be sure you have good documentation if there’s a clinical reason the patient cannot use a commercial product. Shortages can be verified on the FDA website: Drug ShortagesPrescription must clearly indicate each ingredient along with the final concentration prescriber is intending. Avoid using abbreviations or common nicknames (e.g., Magic Mouthwash)
    1. Pre-printed prescription forms are prohibited by many PBMs and should be avoided
  • Compound Worksheet/Log
    • At a minimum your worksheet/log should include:
      • Link to Rx number it was prepared for
      • Formula name, strength and dosage form
      • Date prepared and total quantity made
      • Beyond Use Date (BUD)
      • Each ingredient name, NDC, quantity, lot and expiration date
    • May also consider including:
      • Each ingredient cost (AWP or U&C)
      • Employee name that prepared and approved the compound
      • Documentation for quality control procedures
      • Certificate of Analysis for bulk powders
      • Specific instructions for the compound process
  • Billing for Compounds
    • NDCs billed on the claim must match the NDCs used to prepare the compoundAll ingredients must be included on the claim
      • Do not bypass plan rejects by omitting non-covered ingredientUtilize Submission Clarification Code 08 (Process Compound for Approved Ingredients) when appropriateDo not reduce quantity to bypass any plan rejects due to cost or prior authorization requirementsConfirm pharmacy software is billing accurate quantities for “QS”(quantity sufficient), if needed
      Compounds should only be billed and compounded using USP-NF (United States Pharmacopeia-National Formulary) pharmaceutical grade ingredientsRefer to each PBM Provider Manual for correct Level of Effort (LOE) billing codes
    • Bill an accurate days’ supply based off instructions for use

PAAS Tips:

Audit Risks: Medication Home Delivery

Many independent pharmacies offer unique services to their patients, such as house charge accounts and medication delivery, to provide a better customer experience. While these are convenient services to offer patients, they do bring audit risks if they are implemented without appropriate safeguards.

PAAS National® analyst have seen numerous PBM audit recoupments for insufficient deliveries and discrepancies linked to insufficient evidence of refill request, copay collection, or delivery. Additionally, we have seen audits where the prescriptions were billed for deceased patients.

Review the tips below to ensure that your pharmacy doesn’t incur unnecessary audit risks.

PAAS Tips:

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  • Home delivery tips
    • Require a dated signature from patient/caregiver at every delivery (pre-printed dates on delivery manifests are insufficient)Avoid leaving medications in the mailbox or at the door without evidence of delivery (geotagged photos from pharmacy staff are typically insufficient)Avoid “automatic refills” and instead implement a “medication synchronization” program that includes a telephone check-in prior to medication billing and delivery to ensure that patient is still alive, living at same address, has not been hospitalized since last delivery (or had medication therapy changes), and to confirm the needed medications prior to scheduled delivery date
    • Collect payment at the time of delivery, or implement a robust accounts receivable (“house charge”) process
  • Facility delivery tips
    • Coordinate with LTC facilities to understand if Medicare patients are in a “Part A” versus a “Private Pay” status as this will dictate whether pharmacy is to bill the facility (if Part A) or Medicare Part D (if private pay)
      • Develop written agreements in place that require facility cooperation with retroactive billing changes such as when claims are accidentally billed to Medicare Part D and then subsequently adjusted due to Part A status
    • Pre-printed dates on delivery manifests are insufficient, receiving individuals should handwrite the date received
  • Additional helpful information on house charge accounts can be found in the following Newsline articles:

California Pharmacy Charged in $300 Million Medicaid Fraud Scheme

The US Attorney’s Office for the Central District of California recently issued a press release outlining charges against a pharmacist for the submission of more than $300 million in fraudulent claims to the state Medicaid Program (Medi-Cal) for medications that were not medically necessary, where drugs were not dispensed to patients, and where prescriptions were obtained through illegal kickbacks.

Reportedly, the pharmacy exploited a loophole in Medi-Cal’s claim adjudication process starting in 2022 when Medi-Cal suspended Prior Authorization requirements during a transition to a new payment system. When the pharmacy found this loophole, they began billing for “tens of millions of dollars per month for dispensing high-reimbursement, non-contracted, generic drugs” through the pharmacy claim system. The pharmacy obtained prescriptions through illegal kickbacks and frequently did not even order or dispense the medications involved.

Consequently, it seems Medi-Cal has followed up on this fraudulent activity with more pharmacies receiving extensive invoice audit letters in late July 2024 requesting over three years of invoice records, in addition to dispensing history and financial records (e.g., income statements and balance sheets).

Fraudulent activity from one provider gives payors and PBMs justification to perform additional audits looking for other criminals. Invoice audits often uncover honest billing and documentation errors that can cost you big money – see the tips section below to protect yourself from losses in an invoice audit.

PAAS Tips:

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  • Only purchase drugs from authorized suppliers (Rx and OTC)
    • Remember that OptumRx® requires use of NABP Drug Distributor Accreditation wholesalers
  • Maintain a comprehensive list of your suppliers
  • Ensure that your staff is billing the correct NDC (all 11 digits matter)
  • Reverse prescriptions timely when they are not picked up (return to stock)

Is It Time to Purge? Understanding Record Retention Requirements

The majority of prescriptions filled by pharmacies are based off of an electronically-sent prescription, or “e-script” – 94% according to a 2021 Surescripts National Progress Report to be exact. However, physical hardcopies may still exist in the form of telephone orders, transfers, faxes and written hardcopies. In an effort to free up physical space, amongst other reasons, a common question PAAS National® analysts receive is in regard to how long pharmacies are obligated to retain physical hardcopies of prescriptions, in addition to other physical records. In essence, “PAAS, can I get rid of this yet?”.

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Unfortunately, there is not a straightforward answer. The pharmacy needs to consider a number of things in order to ensure they are in compliance.

Many regulations exist which impact how long records are maintained; inconveniently, they all differ. With that said, the pharmacy must maintain the records to accommodate the longest time period, relieving the pharmacy from memorizing specific regulations. According to 42 CFR §422.504(d) and 42 CFR §423.505(d), two federal regulations governing the CMS Medicare Part D Program, records must be retained for a period of ten (10) years in addition to the current contract year, which includes, but is not limited to, hardcopy prescriptions, signature logs, copay collection and invoices. Since Medicare Part D has the longest record retention requirement, it is PAAS’ recommendation to retain records for 11 years.

Pharmacies need to also consider in which format the records may be stored. As addressed above, electronic transmission is the primary origin of prescriptions. However, there still exists a fraction of prescriptions that pharmacies may have in a physical hardcopy form. It is common for states to have a requirement for hardcopies to be retained in their original form for a period of time before converting to an electronic format.

In the same vein as state-level original format requirements, the DEA has record retention requirements, including but not limited to controlled substance prescriptions, invoices, inventory counts. Controlled Substances must be kept in their original form for two (2) years from the written date. If a pharmacy opts to convert a physical hardcopy to an electronic copy thereafter, it needs to be an exact copy of the front and back of the prescription even if the back of the prescription is blank. 

In conclusion, PAAS urges members to be mindful of how they retain records, whether it is in electronic or physical format. In the case of software changes/crashes/etcetera, ensure there is a backup method to be able to access prescriptions (and other important documentation) in a “readily retrievable” manner. Regardless of the reason, pharmacies are still obligated to respond to audit requests.

PAAS Tips:

  • PAAS FWA/HIPAA Compliance Program members can refer to Section 4.3 of the Provider Manual to ensure that information conforms to your intended practices.
  • Medicaid record retention requirements may be more stringent than state regulations
  • For audit purposes, clinical notations must be retrievable for auditor’s review

How to Submit Your Audit Documents for an Effective Review

PAAS National® analysts continue to see an increasing amount of PBM audits demanding large audit volumes of documents for reviews. Our goal is to help pharmacies respond accurately and efficiently as you submit documentation.

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PAAS analysts review your documents as if we are performing remote pharmacist verification, so it is helpful if we can see both the prescription AND the billing information at the same time.

Upon receiving an audit notice, send it to PAAS. This allows for the analyst on your case to provide guidance from the very beginning of the audit process, which can result in you saving time gathering less paperwork. Additionally, it allows the analyst to provide guidance on what to look for as documents are pulled, such as any electronic clinical notes that need to be added to the hardcopy. This can result in a more efficient, and seamless, pre-audit consult after documents have been reviewed by your analyst, ensuring an effective review for your audit.

General

  • Organize documents in the same order as listed on audit letter
  • If prescriptions/signature logs are requested in two separate “lists”, then separate them in your response (rather than co-mingled)        
  • Include page numbers at the bottom of each page in sequence to ensure no pages are missing and to allow for easy reference if needing to refer an auditor to a contested aspect of your audit.

Prescription Hardcopies

  • Only produce one copy per unique Rx #
  • Only include back of prescription if it has information, otherwise write “back is blank” on the face of the

               hardcopy

  • Include “fill sticker/back slap/backtag” on the front side of the prescription, in the same orientation
  • Make sure clinical notes are visible to support claim as billed
  • Include Patient label (if requested)
  • If any DUR, SCC, DAW or Diagnosis code was submitted, then documentation should include both  the code used and a clinical note to justify its use   
  • Make sure to document on the hard copy if the prescription is a transfer or phoned in order              

Signature Log

  • Only provide for specific date(s) of service when requested
  • Must include at least 3 elements: Rx number, date of dispensing, signature or “COVID-19” (where applicable), some PBM’s require the fill date or refill #
  • Omit PHI for any Rx not subject to audit and be sure to point out the Rx number in question

 Copay Collection

  • Only provide for specific date(s) of service when requested
  • Point-of-Sale transaction receipts with Rx number, copay amount, and method of payment

PAAS Tips: