Access Barriers to Specialty Medications

The limited availability of drug products has been a national concern for many years. Specialty medications have some unique concerns when considering patient access during times of product unavailability, but there are several reasons why a specialty drug may not be available for patients in need of treatment.

Product Shortages

There are times when a drug product is unavailable due to a supply shortage. In most cases, this shortage is the result of quality or production issues during the manufacturing process. Occasionally, shortages may result from changes in clinical practice guidelines or FDA approval of a new indication.

In 2012, the United States experienced a drug shortage crisis, with more than 300 shorted products. Today, the number is much lower with 170 reported shortages, but health care providers continue to experience the challenges associated with a shortage event.

Since specialty medications do not often have a variety of generic manufacturers to substitute during these times, product shortages can become a difficult challenge for patients and their health care providers. Clinicians may be required to locate an existing supply, compound the product, or substitute with an alternative therapy, if one is available.

Depending on the specialty drug product, this situation can result in additional counseling, laboratory monitoring, or therapy failure for patients.

Recalls

Medications are sometimes recalled by the FDA or manufacturer, depending on the circumstances. As Cardinal Health explains, “a recall is an action taken when a product is found to be in violation of laws and regulations administered by the FDA. Medications may be recalled for a variety of reasons including safety, mislabeling, contamination, and deviations in strength or potency.”

The FDA is responsible for classifying a drug recall, which leads to removal of the defective drug product from the market. There are 3 classifications:

• Class I: A dangerous or defective product that could cause serious health problems or death.
• Class II: A product that might cause a temporary health problem or pose slight threat of a serious nature.
• Class III: A product that is unlikely to cause any adverse health reaction, but that violates FDA labeling or manufacturing laws.

Like product shortages, if a drug recall is issued for a specialty medication, patients and clinicians may find themselves in a similar situation with limited or no therapy alternatives. A unique product recall example involved Triad alcohol prep pads in 2011.

Although the recall did not affect a pharmaceutical drug product, it did indirectly result in a recall of several specialty drug products that contained the prep pads within their packaging. Some examples included Betaseron, Copaxone, Xtavia, Boniva, Fusion, Nutropin AQ, and Pegasys.

Product Discontinuation

According to the definition provided by the FDA, “[products listed] as ‘discontinued’ are approved products that have never been marketed, have been discontinued from marketing, are for military use, are for export only, or have had their approvals withdrawn for reasons other than safety or efficacy after being discontinued from marketing.”

In the case of specialty drug products, initial approvals are sometimes granted with programs such as Elements to Assure Safe Use or Risk Evaluation and Mitigation Strategies (REMS). These programs mitigate risk to ensure that the benefits of a medication outweigh the risks.

An example of such a product is Zinbryta, a specialty drug product used to treat multiple sclerosis. Due to the risks of hepatic injury, including autoimmune hepatitis and other immune-mediated disorders, it was made available only through a REMS program that required prescriber and pharmacy certification, as well as patient enrollment.

In March 2018, Biogen and AbbVie announced a decision to withdraw the global marketing application for Zinbryta due to the adverse reactions being reported by patients on therapy. As a result, patients and prescribers were required to find alternative therapies for the disease state.

This was devastating for some patients who were experiencing successful outcomes with Zinbryta after failed attempts on other therapies. Another specialty drug product that was discontinued was Zecuity, a transdermal migraine therapy.

In June 2016, Teva announced the discontinuation of their product due to reports of application site reactions. Ultimately, patient safety must come first, but this scenario does result in accessibility issues for patients and prescribers when it comes to drug product availability.

Delivery Requirements

Several specialty medications belong to an exclusive or limited distribution network. This model restricts the distribution channel for a pharmaceutical product to 1 (exclusive) or a few (limited distribution) network of pharmacies. There are several reasons why a pharmaceutical manufacturer may choose this type of distribution model.

First, it can ensure safe distribution of high-risk medications to small patient populations. Second, it allows the manufacturer to have added control over the patient’s experience with their product.

Pharmacies who agree to the limited distribution network make promises to follow specific procedures outlined by the manufacturer to aid in patient safety, adherence, and outcomes. Examples of this may include how often outreach is made for counseling and/or order scheduling, patient education provided by the pharmacy, the type of information collected from the patient and/or prescriber, or financial assistance programs offered.

This information may be useful for manufacturers to evaluate the collected data for trends, which is made possible by working with a smaller number of pharmacies. Although there are benefits associated with this type of limited access distribution model, we should recognize that the same inherent features that make this model desirable can also lead to potential access issues.

For example, if a drug product is exclusively provided by a pharmacy that is affected by an event that causes them to be incapacitated, how will medications be distributed to patients? This is a decision that manufacturers must consider when establishing their product launch.

In most instances, having a pharmacy in-network with contingency plans, such as an alternate location, or a limited distribution model with a few various pharmacies in network will help to mitigate this access risk.

Natural Disasters

The FDA recommends that patients and pharmacies have an emergency plan ready and to take precautions during natural disasters, such as hurricanes, floods, fires, blizzards, and tornados. The 2017 hurricanes (Maria, Irma, and Harvey) reminded us of the importance of emergency preparedness and provided a platform to take action.

Specialty pharmacies play an important role in helping their patients during these times. Often, they can engage patients prior to an anticipated natural disaster to ensure delivery of medications before the necessary evacuation.

They can use this communication to remind them to plan ahead for potential disruptions. Pharmacies with digital technology may be able to communicate with patients to confirm their temporary locations for delivery.

Working with pharmacy benefit managers to apply medication overrides to allow for early filling of prescription medications is also a strategic mode for this type of scenario. Although most specialty products are not available at retail pharmacy locations, there are some, such as HIV and transplant medications.

Pharmacies can offer patients emergency supplies for their lifesaving medications, if available at a nearby pharmacy location. Additionally, mobile and pop-up pharmacies can be constructed at emergency shelters to provide care to patients.

If traditional shipping methods are unavailable, a private courier may be used to transport medication to a patient. In the event that the courier cannot access an area affected by an emergency disaster, the pharmacy may be able to work with the American Red Cross to assist in the delivery of the medication to the patient.

Puerto Rico was among the locations hit with a major hurricane in 2017. The region is responsible for the production of a significant amount of small-volume parenteral solution products, such as saline bags.

Since the disaster, supplies have been scarce. This is especially concerning since the parenteral solution is required for many compounding recipes and for dilution of concentrated drug products.

In November 2017, ASHP hosted a meeting of health care professional organizations for a roundtable on drug shortages. Suggestions outlined by the panel to mitigate drug shortage risks are listed below.

• Manufacturers providing the FDA with more information surrounding the causes of product shortages.
• Establishing best practices for high-alert drugs.
• Requiring manufacturers to establish contingency plans.
• Creating incentives through the FDA to manufacture shorted products.
• Provide more information on the quality of outsourcing facilities’ compounding.
• Evaluation of the purchasing process of sodium chloride.
• Requiring manufacturer transparency.
• Examining drug shortages as a national security initiative.
• Requesting vendors to provide easier solutions to allow for modifications of electronic health record systems.
• Establish a quality manufacturing initiative through the FDA.
• Include potential risk for drug shortages in the FTC’s review of drug company merger proposals.

In 2012, legislation was enacted requiring manufacturers to notify the FDA of changes in production that could lead to a reduction in the supply of a medication. This allows the FDA to explore alternative solutions during these times, such as working with alternative manufacturers to modify production rates, expediting review of abbreviated new drug applications, or establishing a controlled importation process to meet demand.

In a statement released by FDA commissioner Scott Gottlieb, MD, on May 31, 2018, he expressed the FDA’s commitment to “taking new steps to address the root cause of more of these shortage situations.”

Gottlieb also announced the FDA’s action plan to bring new technology to improve manufacturing, thereby reducing the chance for supply disruptions. The FDA has implemented an emerging technology program and established a team to carry out this initiative.

Additionally, they made a recent announcement of the formation of a Drug Shortages Task Force to find long-term solutions to the country’s drug shortages. It is clear that many circumstances can affect the availability of a specialty drug product for patient access.

With these initiatives underway, we should expect to see a positive impact to this universal concern within the health care industry.

About the Author

Michelle Byrne earned her Doctor of Pharmacy degree from Duquesne University and is currently enrolled in the Master of Science in Pharmacy Business Administration program at the University of Pittsburgh, a 12-month, executive-style graduate education program designed for working professionals striving to be tomorrow’s leaders in the business of medicines. She has worked in the specialty pharmacy industry for the past 9 years, starting as a clinical pharmacist and working in leadership roles within her organization. Her current role is pharmacy manager, quality and regulatory and pharmacist-in-charge for her site within the specialty operations division of her organization.