OTC Oral Contraceptive Coming in 2024

Oral contraceptives are a safe, affordable, and effective way of preventing pregnancy.

In July 2023, the FDA approved Opill (norgestrel) tablet, the first daily oral contraceptive that will be available for sale in the United States without a prescription. Opill is a new option for individuals who do not have access to a physician and may be the first of many over-the-counter oral contraceptives approved. HRA Pharma, the manufacturer of Opill, is expecting it to be available in the United States in early 2024. Opill, a progestin-only oral contraceptive, will be available over the counter in stores and online. Progestin-only pills, also known as mini-pills, have very few contraindications compared to the majority of oral contraceptives that contain both estrogen and progestin. Opill, when used properly, is safe and effective.

Almost half of all pregnancies in the United States each year are unintended, which have been linked to negative maternal and perinatal outcomes. Research suggests that OTC access would increase the use of contraception, lowering the number of unintended pregnancies. This approval may reduce barriers to access previously seen with prescription-only oral contraceptives. Research also shows that oral contraception generally meets the requirements for the conversion from Rx to OTC:

  • Easily diagnosed
  • Ability to monitor use without clinician screening
  • Low toxicity if overdosed
  • Low potential for abuse or interaction
  • Properties that make it practical for over-the-counter use

HRA Pharma has not released a price and it is unsure if insurance companies will be covering Opill.  According to an article from Planned Parenthood, the typical cost for prescription birth control pills is $0-$50 a month. Insurance plans are not required to cover Opill, and there may be a charge for patients, especially when it is first released. The potential cost of Opill may be a barrier to access for patients, but advocates are pushing the federal government to update the Women’s Preventative Services Guidelines to make all OTC contraceptives available to patients at no charge.

The Affordable Care Act (ACA) requires most private health insurers to provide coverage of women’s preventive services without charging a copayment, including FDA-approved contraceptive methods prescribed by a health care provider. More specifically, 12 states and DC require coverage of methods received over the counter, but the insurer may still require the enrollee to obtain a prescription. Since legislation currently requires coverage for prescription contraceptives at no cost, changes would still be needed to have non-prescribed contraceptives available at no cost.

Because there may be an increased risk of breast cancer or other progestin-sensitive cancers, patients who have or have ever had breast cancer should not use Opill. Currently, Plan B emergency contraception is available OTC. Opill is not intended for use as an emergency contraceptive. Instead, patients should take Opill at the same time every day for pregnancy prevention. It is important for patients to understand this information before purchasing the drug.


Posted January 2024

Gene Therapy Challenges and Compendia Implications

Gene therapy is an emerging topic in the medical field with new innovations and successes documented daily. The FDA shared their prediction that, based on the current pipeline, they expect to approve anywhere from 10-20 gene and cellular therapy products each year beginning in 2025.

Gene therapy works by replacing a disease-causing gene, inactivating genes that are not functioning correctly, or adding genes to treat a disease. This is often confused with cellular therapy, which administers living cells to trigger an anti-tumor response of the patients’ own cells. Unlike most medications, which manage or prevent diseases, gene therapies can be curative.

Challenges arise in various stages of gene therapy development and marketing. One of the challenges is manufacturing related; after testing in a lab, these processes are being pushed into large scale manufacturing. Robust and reproducible technique is vital for efficient and accurate data during the development of these drugs. Manufacturers may struggle with the space and investment needed for the development of these therapies. Current gene therapies are often indicated for rare and underserved indications, potentially creating a less attractive investment in expensive equipment needed for large-scale production.  An additional challenge includes finding qualifying patients for clinical trials, since the target population is often very small. Patients are often required to travel frequently for their treatments and follow-ups.

In addition to manufacturing and patient obstacles with gene therapy, insurance companies are providing push back as well. In the United States, the average person changes insurers every 3-5 years. In most cases, gene therapy is a one-time infusion that is accompanied by a large cost. Insurance companies may not see the cost benefit until years later, during which time they may have lost that patient. Reform is being proposed to offer insurance companies options on the payment timing, spreading payments out over a period of time, for gene therapy.

One challenge PHSL has focused on is the inclusion of gene therapy products in the drug compendia. Gene therapies have unique strengths, dosing, and mechanisms of action that can be interpreted differently in their listings. The strengths of current genetic therapies use measurements such as genome copies (GC), vector genomes (VG), viral particles (VP), or plaque forming units (PFU). Due to the high number of units being delivered, the strength of gene therapy agents may be displayed using scientific notation. For products with weight-based dosing, multiple NDCs may be available for a gene therapy agent to meet the needs of each patient. Compendia often differentiate between NDCs of the same product by including the number of milliliters contained in the package. Both the number of units and the number of vials for these products may be variable from package to package.  See the below table reviewing how key factors can differ for various gene therapy agents.


There is a need for these products to be classified separately from other products treating similar disease states. Fortunately, compendia have included “Gene Therapy” and “Cellular Therapy” within therapeutic classification descriptions, though the format is not always consistent.  PHSL anticipates that the compendia will continue to refine their process for listing gene therapy agents as new therapies are developed. If you have a new gene therapy in development, contact PHSL to learn how we can use our knowledge and experience to assist in preparation for compendia submission.


Posted January 2024

FDA NDC Final Rule Timing

Patricia Milazzo, RPh and Dave Schuetz, RPh, Senior Consultants at PHSL, wrote an article featured in the Viewpoint column of the September/October 2022 edition of ComputerTalk for the Pharmacist.  Their article focuses on the FDA’s plans for the National Drug Code (NDC).  At the time the article was published, the authors expected the FDA would publish the Final Rule for NDC expansion by the end of 2023 or very early 2024.  However, the expected date of the Final Rule has been deferred.

According to the latest Unified Agenda of Regulatory and Deregulatory Actions posted by the OMB Office of Information and Regulatory Affairs, the Final Rule for “Revising the National Drug Code Format and Drug Labeling Barcode Requirements” is not expected to be published by HHS/FDA until August 2024.

PHSL continues to monitor for information regarding this important change to the NDC and will post more news as it becomes available.


Posted January 2024

Verified by GS1

GS1 is the standards organization behind the product identification numbers used for bar codes seen on products from most industries. GS1 launched a new website offering the ability to validate product and company information.  In the healthcare industry, this is important for validating the identification of medical devices that have been assigned a GTIN-14 as the Device Identifier.

The new website, called Verified by GS1, is available to view now and replaces the old GEPIR website as of December 31, 2023.  The enhanced database of GS1 identifiers provides a better user experience searching for product, location, and company information and provides more accurate and complete data than that available in GEPIR.

Verified by GS1 provides the ability to verify products by searching a product’s GTIN (Global Trade Item Number) in various formats, such as the GTIN-12 (normally associated with a bar code) and the GTIN-14 (an identification number that may be embedded in the UDI (Unique Device Identifier)).  This verification process requires the barcode number or the GTIN to search the GS1 database.  In some cases, the results provide exact product information and in other cases, the results provide only the company information that indicates the number is registered with a GS1 licensed company.  In the latter case, the user will be provided with the manufacturer’s GS1 Company Prefix (license type) along with other company information.

Verified by GS1 can also be used to validate a manufacturer’s GS1 Company Prefix, which is included in the GTIN.  The verification process requires the manufacturer’s name and country to find the company.  If there is a match, the user will be provided with the manufacturer’s GS1 Company Prefix (license type) along with other information verifying the company’s identity.

Verified by GS1 can also be used to verify location information to help support supply chain tracking.

Using the GTIN-14 embedded in the UDI, Verified by GS1 will be an important tool in the verification process of product identification numbers assigned to medical devices.  You do not need to be a member of GS1 to use Verified by GS1. PHSL recommends looking at the website and entering known information such as a GTIN-14 or a company name and country to see how they are listed in the GS1 database.  PHSL can assist medical device manufacturers in obtaining a GS1 identifier needed to list their products in pricing compendia.


Posted: December 2023

USP 2024 Draft Drug Classification Released

On September 1, 2023, U.S. Pharmacopeia (USP) Healthcare Quality and Safety Expert Committee announced the release of the Draft USP Drug Classification 2024 (USP DC 2024) which was open for public comment from September 1 to September 29, 2023. The anticipated publication date for USP DC 2024 is December 15, 2023.[1] A full copy of the USP DC with proposed changed may be obtained at

The USP is responsible for the USP Drug Classification (USP DC), an independent drug classification system, and the Medicare Part D Medicare Model Guidelines (MMG). The USP classification system is designed to assist with formulary support outside of Medicare Part D. The goal of the Healthcare Safety & Quality Expert Committee is the creation of a comprehensive classification system for use in drug formulary development or review in non-acute or outpatient care settings with the intent of providing guidance toward the design and comparison of balanced formularies. Per the USP, “USP DC is not intended for review of medical benefit drug coverage, since USP DC does not include all drugs administered in a clinical setting.”[1] In contrast to the USP Medicare Model Guidelines, the USP Drug Classification is not part of regulatory governance of Medicare or Medicaid.

The 2024 DC proposal includes new FDA approved drugs from November 2022-July 2023. Drugs approved from August 2023 through September 2023 will be considered for inclusion in the final version issued in December 2023. Drug products approved by the FDA after September 30, 2023, will be considered in the following publication. In general, the Subcommittee excludes most medications used in hospital-only settings, over the counter (OTC) drugs, and medications that are not FDA approved.

USP Drug Classification Hierarchy
The Drug Classification structure is a hierarchical therapeutic classification system with five levels moving from broad therapeutic category to example drug entities. Combination products are identified within the structure.

  • USP Category
    • USP Class
      • Example Drugs
        • Pharmacotherapeutic Group (information-in development)
          • Combination Drug Product Identification (yes/no)

2024 Example

  • Antibacterials (USP Category)
    • Beta-lactam, Penicillin (USP Class)
      • Amoxicillin/Clavulanate Potassium (Example Drugs)
        • Null value (Pharmacotherapeutic Group [information])
          • Yes (Combination Drug Product)

Proposed 2024 Changes
USP Categories, the highest level of the hierarchy, remain unchanged. Two (2) new USP Classes were added to address the first FDA approved therapies to treat COVID-19 and ALS with accompanying drug examples as shown below. The majority of the 2024 changes are forty-three (43) new Example Drugs approved between September 2022 and July 2023, which are available on the USP Drug Classification 2024 Draft.[2] One drug entity, hydroxyprogesterone caproate, was removed because the FDA approval was withdrawn for the product, and one drug entity was edited, methamphetamine hydrochloride, as the indication for obesity was removed.

2024 Draft New USP Classes

USP Draft September 2023

PHSL anticipates further changes may occur between now and the final 2024 DC, including September 2023 FDA approvals, new USP classes for first-in-therapy approval, or example drug removals if FDA withdraws the product’s approval.

What impact may the 2024 DC have on your business, your formulary design, or customer expectations? PHSL can provide analysis and assessment of your current and future formularies considering the 2024 USP DC and prepare communications to USP addressing your concerns and recommendations. Please contact us to discuss your needs.





Posted November 2023

FDA’s “Labeling for Biosimilar and Interchangeable Biosimilar Products; Draft Guidance for Industry: Availability“

On September 18, 2023, the FDA (Food and Drug Administration) announced the availability of a draft guidance for industry entitled “Labeling for Biosimilar and Interchangeable Biosimilar Products.” This draft guidance is intended to describe proposed labeling requirements for biosimilar and interchangeable biosimilar products. Per the FDA, “the recommendations for biosimilar and interchangeable biosimilar product labeling in this draft guidance pertain only to the prescribing information, except for certain recommendations pertaining to FDA-approved patient labeling (e.g., Patient Information, Medication Guide, Instructions for Use). When finalized, this draft guidance will revise and replace the guidance for industry entitled “Labeling for Biosimilar Products.”[1]

Our first post reviewed the FDA’s proposed recommendations regarding the inclusion or exclusion of FDA’s Purple Book assignments for biologicals within product’s Prescribing Information (PI). This post will provide a general description of the remaining recommended changes to biosimilars’ PI. The important date to remember is November 17, 2023, which is the last day the FDA will receive comments concerning the recommendations. PHSL is providing a summary of the FDA’s proposal and strongly recommends reading the entire publication to accurately evaluate the impact to biosimilar labeling for existing products and for those products anticipating FDA approval in the near future.

PHSL assists companies in staying up to date on the inherent complexity of the Purple Book and biologicals, which includes biological naming conventions and their impact on prescribing and dispensing. PHSL can provide an independent evaluation of the FDA’s proposal on biological products PI and can assist in crafting a company’s response to the proposed guidelines with the November 17 deadline in sight.

Major Proposed Changes

The FDA identified four significant changes from the previous July 2018 Guidance “Labeling for Biosimilar Products”.[2]

  • “Labeling for interchangeable biosimilar products
  • Product identification when the reference product labeling describes a clinical study conducted with a non-U.S.-approved biological product.
  • Pediatric use statements
  • Incorporating relevant immunogenicity data and information from the reference product labeling in the biosimilar or interchangeable biosimilar product labeling.”


Key Sections

PHSL has summarized key sections of the FDA’s proposals on biosimilar product labeling, as follows:


  1. Recommended Approaches to Product Identification

PHSL Summary: This section identifies when and where in the PI each of the following may be used: product name, biosimilar name, or a core name + products.  Each section includes a sample, using a hypothetical drug product and its biosimilar:

  • “When to Use the Biosimilar or Interchangeable Biosimilar Product Name
  • When to Use the Reference Product Name
  • When to Use the Core Name Followed by the Word ‘Products’
  • When to Use More Than One Product Identification Approach
  • When the Reference Product Labeling Describes a Clinical Study Conducted With a Non-U.S.-Approved Biological Product”[3]

 To recap, the following example contained in the draft guidance helps illustrate these naming conventions.

Key (hypothetical product)

Reference Product Name: JUMEXANT (replicamab-hjxf)

Biosimilar Product Name: NEXSYMEO (replicamab-cznm)

Core Name + Products: replicamab products

  1. Recommended Approaches to Content Presentation

PHSL Summary: The FDA describes proposed guidance to address complex situations surrounding biosimilars, such as shared clinical studies or approvals for different indications. This guidance covers several aspects of the content of the PI, including Boxed Warnings, Contraindications, Warnings and Precautions, Adverse Reactions, Drug Interactions, and Use in Specific Populations. The FDA provides multiple examples for each issue. For manufacturers, PHSL recommends your organization conduct a thorough review to determine the potential impact on your products’ labeling.

  1. Recommended Approaches to Specific Sections of Biosimilar and Interchangeable Biosimilar Product Labeling (covered in previous blog post)

PHSL Summary: The FDA wants to have a consistent approach with all biosimilar and interchangeable biosimilar product labeling. The proposed guidance details the FDA recommendations on how a biosimilar or interchangeable is described in the PI, including the naming conventions and how approval for different indications will impact the language contained in the PI. This section covers the Highlights section of the PI, including a Biosimilarity statement, Indications and Usage, Use in Specific Populations (specifically Pediatric Use Subsection), and Clinical Pharmacology/Immunogenicity.

Section V FDA-Approved Patient Labeling of Biosimilar and Interchangeable Biosimilar Products.

PHSL Summary: This section covers recommended changes to patient labeling including Medication Guides, Patient Information, and Instructions for Use.  The changes are specific to the terminology used to describe the reference product and the biosimilar within patient-centric sections of the PI.

Section VI and VII are specific guidelines for when and how the FDA requires revisions of the PI. This section is important to review. as it describes the FDA’s approach to the PI when a biosimilar obtains different indications than the reference product.


Contact PHSL to discuss how these changes impact your organization and to prepare a response to share your input with the FDA during this critical time period.



Posted: October 2023

[1] Federal Register: Labeling for Biosimilar and Interchangeable Products; Draft Guidance for Industry; Availability. 9/15/2023

[2]Email 9/18/2023: FDA Releases a New Draft Guidance on Labeling for Biosimilar and Interchangeable Biosimilar Products – Drug Information Update

[3] Federal Register: Labeling for Biosimilar and Interchangeable Products; Draft Guidance for Industry; Availability. 9/15/2023


Introduction: FDA Draft Guidance “Labeling for Biosimilar and Interchangeable Biosimilar Products”

In September 2023, the FDA released draft guidance detailing the proposed changes in biosimilar and interchangeable labeling, replacing the 2018 Guidance. The FDA identified four significant changes:

  • Labeling for interchangeable biosimilar products
  • Product identification when the reference product labeling describes a clinical study conducted with a non-US-approved biological product
  • Pediatric use statements
  • Incorporating relevant immunogenicity data and information from the reference product labeling into the biosimilar or interchangeable biosimilar product labeling

Although four major changes have been identified, this post will focus only on the proposed labeling change for biosimilars.  The proposed labeling changes include where and how within the labeling to use proprietary names, generic names, and molecule names. They also include a recommendation to require a uniform biosimilarity statement in the label that does not distinguish between biosimilar and interchangeable products. Although the Purple Book identifies a product as biosimilar or interchangeable according to the FDA approval requirements, state pharmacy practice laws use the Purple Book assignments as guidance for drug substitution laws and regulations, like they do with the FDA Orange Book in state laws and regulations governing the substitution of non-biological drug products.

The current inclusion of the Purple Book biosimilar or interchangeable assignment in the labeling introduced an additional level of detail in the product label that is not provided in small molecule prescription drug labels.  It allowed healthcare professionals to utilize the label itself, instead of the FDA Purple Book, to determine the biosimilar and interchangeable status for a product. The same healthcare professionals currently utilize the FDA Orange Book codes to determine the therapeutic equivalence rating for small molecules instead of product labels.

The draft guidance will more closely align with the current labeling practice for small molecules. Therapeutic equivalence ratings (A- and B- ratings) for non-biological drugs are absent from labeling and instead found in the FDA Orange Book. The proposed guidance recommends all biosimilars, including interchangeable products, use the same statement of biosimilarity in the product label, with the expectation that users will utilize the FDA Purple Book to determine whether a product is simply biosimilar, or whether it has interchangeable identification. This eliminates the risk of using outdated product labeling to determine FDA Purple Book codes.

The FDA requests comments on this draft guidance in order to increase clarity and understanding before it officially rolls out. These comments are due by November 17, 2023. The change to the biosimilarity statement in the label will more closely align with small molecule labels in that substitutability cannot be determined simply by reviewing the product’s labeling. Pharmacists, prescribers, and pharmacy system developers will need to rely on the FDA Purple Book to determine the interchangeability designation for specific products, similar to the FDA Orange Book for small molecule therapeutic equivalence. What impacts do you see with the proposed guidance on FDA labeling statements for biosimilars and interchangeable biosimilars?



Labeling for Biosimilar and Interchangeable Biosimilar Products | FDA


Posted: October 2023

Beers List Drug on Medicare Negotiated Price List

Xarelto® (rivaroxaban) is a direct oral anticoagulant (DOAC), specifically, a selective inhibitor of factor Xa, that helps prevent blood clots. A recent sequence of events led to an interesting scenario regarding the coverage of Xarelto for a specific population.

2023 Beers Criteria

Xarelto was mentioned in the 2019 Beers Criteria to “use with caution for treatment of VTE or atrial fibrillation in adults ≥75 years.” In 2023, the recommendation in the Beers Criteria update was modified to “avoid for long-term treatment of atrial fibrillation or VTE in favor of safer anticoagulant alternatives.” This change applies to all people ages 65 and older. Based on data from observational studies and meta-analyses, Xarelto was found to have a higher risk of major and gastrointestinal bleeding in older adults compared to other DOACs, Eliquis® (apixaban) in particular. However, the 2023 Beers Criteria update also notes that Xarelto may be appropriate in certain situations, such as when once daily dosing is preferred to ensure medication adherence. Additionally, DOACs were found to have a lower risk for intracranial hemorrhage than warfarin. Eliquis does not appear on the Beers List, but for Pradaxa® (dabigatran), it is recommended to “use caution [when selected] over other DOACs (e.g., apixaban) for long-term treatment of nonvalvular atrial fibrillation or VTE.”  The updated Beers Criteria does not eliminate the use of Xarelto in patients older than 65 years but adds a point to consider for patients, providers, and caregivers.

Medicare Pricing Negotiations

In August 2022, the Inflation Reduction Act was signed into law providing the opportunity for Medicare to negotiate prices of high expenditure medications that do not have generic or biosimilar competition. Xarelto is one of the ten drugs selected for negotiation, applicable for 2026. The Medicare Drug Price Negotiation Program shared information that 1.34 million Medicare Part D enrollees used Xarelto from June 2022 to May 2023, resulting in $6.03 billion of gross covered prescription drug costs. Eliquis is also included on the Medicare negotiation list, while Pradaxa is not. This list of drugs was announced by the Centers for Medicare and Medicaid Services (CMS) on August 29, 2023, months after the 2023 Beers Criteria update was released on May 4, 2023.


The 2023 Beers Criteria includes an update indicating cautionary use of Xarelto in adults older than 65 but does not always necessitate therapy discontinuation.  CMS selected Xarelto, months after the Beers update, as one of the 10 drugs subject to negotiation.  Did CMS consider the impact of selecting a drug for negotiation that recently experienced a cautionary use consideration in the primary population that is covered by Medicare?  Including Xarelto on the Medicare Drug Price Negotiation list for 2026 guarantees that Medicare Part D programs will cover this medication, along with the other drugs on the list at the negotiated prices. This is a potential concern as Medicare beneficiaries, or their providers, may turn to Xarelto as their preferred DOAC if this negotiated price is lower than the cost of other DOACs.  Could there be short-term financial savings but long-term increased costs due to adverse effects from the use of Xarelto in the Medicare population? Healthcare providers should continue to evaluate situations that are medically appropriate for the use of Xarelto on a case-by-case basis, while considering the Beers Criteria recommendations to provide individualized and holistic patient care.

Posted: October 2023

Who Assigns Labeler Codes?

Prescription Drug Labeler Code

Confusion often arises when evaluating what the labeler code is and who assigns it. When drugs are labeled, the first section of the NDC (National Drug Code) number is classified as the labeler code. Labeler codes are requested by the manufacturer and are required for any manufacturer or distributor who lists NDCs with the FDA. A Labeler Code Request SPL file must be sent to the FDA, where it will then be reviewed, and a labeler code will be sent within 10 business days. This code is assigned by the FDA and identifies the firm who manufactures or markets the drug. This code is required before the drug listing can be submitted. In the event that the code has not been used in a listing for 24 months, the code will become inactivated following notification from the FDA.

Labeler Code Example

Medical Device Labeler Code

For the labeling of medical devices, per FDA rules, Unique Device Identifiers (UDI) are now to be used instead of NDCs or NHRICs (National Health Related Item Code). The FDA accredited three organizations as UDI issuing agencies: GS1, Health Industry Business Communications Council (HIBCC), and International Council for Commonality in Blood Banking Automation (ICCBBA). Each issuing agency has a unique UDI format that was reviewed and approved by FDA as part of its process for accrediting issuing agencies.

Medical devices are to be assigned a UDI, which identifies devices from the manufacturing process through distribution and patient use. To acquire this code, the device manufacturer must contact one of the UDI issuing agencies accredited with the FDA to generate an identifier, which is then submitted, along with the device information, to the Global Unique Device Identification Database (GUDID) for approval. The UDI consists of a device identifier (DI) and a production identifier (PI).

The PI portion of the UDI includes information such as lot numbers, serial numbers, and expiration dates. The main purpose for this code is to improve patient safety, increase post market surveillance, and facilitate medical device innovations. A major benefit to the UDI is identifying medical devices in the event of recalls. These unambiguously facilitate the traceability through the supply and market chains. The UDI is found on the device label, packages, or on the device itself. For most nonsterile devices, the UDI will be found on the device itself. Sterile devices must consult the FDA for alternatives.


This section of the article focuses on the DI portion of the UDI created using the standard developed by GS1, an information standards organization. The DI identifies the labeler and the specific version or model of a device. GS1 developed a suite of standards that provide information regarding the identification of the product, services, logical matters (such as service relations), and even physical locations. Companies can utilize the GS1 system to create an identifier and obtain a barcode label for their medical device.

Companies first apply for a GS1 company prefix code. This prefix code will recognize the company’s ownership of the identifier and the product to which the identifier is attached. For pharmaceutical manufacturers or repackagers also selling devices, companies may request that their assigned NDC Labeler code be incorporated into their GS1 Company Prefix, if available.  To acquire the prefix, the company must purchase the membership from GS1 and declare the number of products that will use the prefix. The length of the prefix is dependent upon the number of products the company plans to identify using the prefix.

Each product from a given company will possess a global trade identification number (GTIN) beginning with the company’s prefix code. The GTIN is assigned by the manufacturer, who must follow the rules outlined by GS1 to ensure it is unique and correctly formatted. The GTIN serves to identify trade names of a company. This includes any products or services that exist to be priced, ordered, or invoiced at any point within the supply chain as they move toward the ultimate end user. This number is used to identify various packaging levels for a product, such as the quantity of items in the box or the quantity of boxes within the carton.

For the purposes of the UDI, when the GS1 standard is used to create the DI portion the identifier, the GTIN-14 format is utilized.  Compendia then reformat the GTIN-14 into an 11-digit product identifier that can be used for billing claims for medical devices or digital therapeutics.

In the example below, the entire identifier is the UDI.  Within the identifier, the numbers in parentheses are known as Application Identifiers (AI), which specify what the values in the four sections shown in the example represent. The DI portion of the UDI is the 14-digit number, or the GTIN-14, that follows the AI labeled (01).  The rest of the UDI is the PI portion.  The first digit of the GTIN-14 identifies the packaging level and the last digit is the check digit.  The 12 digits in the middle consist of the variable length GS1 Company Prefix and the variable length item identifier.

GS1 Barcode Example


A manufacturer may choose to use Health Industry Business Communications Council (HIBCC), another of the FDA accredited organizations, as a UDI issuing agency.  Companies must first obtain a company prefix from HIBCC, which is called a Labeler Identification Code (LIC).  HIBCC assigns a four-character alphanumeric LIC to the company for use in the UDI.  The assigned LIC identifies the registered company, not an individual product or device.  The LIC can be used across multiple product lines.  Once assigned an LIC, the company can begin to create identifiers at multiple packaging levels, depending upon the required granularity of identification necessary.

Since the manufacturer’s LIC and the product’s DI contain alpha characters, the DI cannot be reformatted into an 11-digit numeric identifier that can be listed in pricing compendia or used for data transactions and claims. Currently, only 11-digit product identifiers can be used universally for transactions and claims.  Pending new government rules for the National Drug Code and new mandated standards for claims submission, the industry will be evaluating the use of each identifier in their native form, without reformatting.  However, implementation of new processes allowing for this is still more than two years in the future.

Navigating these codes and labeling processes can be confusing and difficult. Pharmacy Healthcare Solutions offers the knowledge and experience to ensure accurate knowledge is conveyed while following respective guidelines. Contact PHSL for assistance with questions related to labeler code assignment or help with listing these products in the leading drug pricing compendia.


Posted September 2023 and Updated October 2023 with HIBCC details

Medical Devices and Digital Therapeutics: Many Ways to Get to Market

Most people know that for a prescription drug to be on the market, it must receive approval from the United States Food and Drug Administration (FDA). Did you know that many medical devices and Digital Therapeutics (DTx) are also approved and regulated by the FDA?

What are medical devices and how are they different from DTx?

Medical devices are defined by the FDA as “an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including a component part or accessory which is: recognized in the official National Formulary, or the United States Pharmacopoeia, or any supplement to them, intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, in man or other animals, or intended to affect the structure or any function of the body of man or other animals.” Some examples of medical devices include blood glucose monitors, insulin pumps, and heart monitors.

The Digital Therapeutics Alliance defines digital therapeutics as “a subset of digital health, evidence-based therapeutic interventions driven by high quality software programs to prevent, manage, or treat a medical disorder or disease.” To read more on digital therapeutics, click here for a previous PHSL blog post on the topic. While medical devices have been around for quite some time, digital therapeutics are a more recent development in the medical world. Some examples of digital therapeutics include reSET (a 90-day program for adults with substance use disorders), Somryst (an application for adults with depression and insomnia), and EndeavorRx (a video game for children with ADHD).

With hundreds of thousands of smart phone applications offering health-related functions, it is important to note that most of these digital health tools do not require FDA approval, since they are deemed relatively low-risk. As the name implies, Prescription Digital Therapeutics (PDTs), on the other hand, require a prescription and may come to the market in one of several ways.

The FDA segments devices into three classes, with “computerized behavioral therapy devices” (i.e., digital therapeutics) being listed as a Class II device. FDA guidance on the classification of medical devices is as follows:

  • Class I- low risk. Class I devices pose almost no risk to patient safety and require the least regulatory control.
  • Class II- moderate risk. Class II devices require regular assessment or premarket notification to prove safety and effectiveness.
  • Class III- high risk. Class III devices are vital to health maintenance and even survival of patients. They are the most tightly regulated class of devices and require premarket approval.

For DTx products seeking to come to market, several pathways may be followed.  If a device manufacturer can show that their product is substantially equivalent to an existing product and demonstrates benefit, the manufacturer may be able to submit for 510(k) clearance, also known as premarket notification, or PMN.  For newer low to moderate risk devices where no existing device exists for comparison and a PMN is not an option, manufacturers may seek to be approved as de novo.  For these products, manufacturers will need to provide clinical data to show that the digital therapeutic is both safe and effective.  For newer devices that fall into the high risk, class III category, manufacturers will need to submit for premarket approval, or PMA.  For these products, manufacturers will need to provide clinical data showing that the product is both safe and effective for its intended use.

Before sending an application to the FDA, sponsors must also pay medical device establishment user fees and provide various other documentation, including eCopy (electronic copies of FDA device submissions), eSTAR (electronic submission template and resources), and an outline of small business determination program highlighting price reduction in user fees. When preparing applications, sponsors should consider important aspects of regulation including design controls, nonclinical testing, consensus standards, clinical evidence, and labeling requirements.

What happens after the FDA receives the application?

The FDA will perform a series of reviews. An administrative review will be conducted to ensure that the submission is sufficiently complete to FDA standards. After the administrative review, device submissions will then undergo an interactive review. During the interactive review, the FDA will contact applicants and efficiently move through the review. Sponsors are also able to track their submissions through an online portal provided by the FDA.

After the FDA reviews the device and decides that it can be brought to market, a series of steps must be taken before the device is available to patients.  Note that all of the step components may not be applicable for DTx products, as a physical product is not created.

  1. Sponsors must register their organization, their location, and list the medical device(s) they market with the FDA.
  2. Sponsors must practice Good Manufacturing Practices when producing the device
  3. Sponsors must follow labeling requirements and follow regulations established by the FDA.
  4. Sponsors must ensure that their devices are not misbranded or adulterated.

Is there any way to expedite this process?

Yes, the FDA established a new program in 2017 called the Breakthrough Devices Program which expedites the process, allows sponsors to receive feedback more quickly, design flexible clinical trials, and ultimately get the device to market quicker. As of 2021, 617 medical devices qualified for the program. For example, EndeavorRX, the video game for children with ADHD, took this route. By expediting the approval process, digital therapeutics are made available faster to help more people.

Similarly, the FDA developed the Safer Technologies Program (STeP) to expedite the approval of devices for less serious conditions.

Finally, the FDA implemented a precertification pilot program consisting of nine volunteer companies with the goal of developing a new regulatory framework focusing on medical devices and technology. While the pilot program is still in progress, it was designed to be adaptive to fix medical software glitches as quickly as possible. Interestingly, the FDA regulates the companies rather than the devices themselves under this model.

Where do digital therapeutics fit in?

As of now, digital therapeutics follow the same pathways as other devices in the market.  Do you think that a new regulatory framework designed specifically for digital therapeutics will come into effect as a subset of medical devices? How do you think this will impact the market?


Posted August 2023