Pharmacovigilance in the Age of the Specialty Pharmacy

Wednesday, September 30, 2015

Rutgers – The State University of New Jersey

It began with a notion. Concentrating the flow of specialized medicines through distinct channels maximized not only to the patient’s care but also the distribution of the specialty medicines. Specialty pharmacy, which once occupied only a small niche in the marketplace, has now become the largest growth area in the pharmacy industry¹. This new entity offers access to the latest injectable and biologic products and helps patients with treatments on complex disease states, such as cancer, multiple sclerosis, rheumatoid arthritis, as well as rare genetic disorders. But it does not come without controversy. One of the issues is that setting up a specialty pharmacy is a relatively simple process and does not have strict regulations. Neither the FDA or EMA, nor any other major regulatory body has designated guidelines on the setup and management of a specialty pharmacy. This lack of concrete governing parameters has helped these entities proliferate over the last decade. However, lack of parameters in an entity that has a direct correlation to patient safety is worrisome for pharmacovigilance professionals. In order to understand problem, it is necessary to examine the idea of a specialty pharmacy from its roots to its current role in the facilitation of drug distribution as well as its obstacles in meeting the pharmacovigilance demands placed upon by the manufacturers.

When medication requires special management or the local retail pharmacy does not have the proper resources, a specialty pharmacy needs to be employed. The medications available via a specialty pharmacy are usually higher-cost medications, drugs taken with a needle (injectables) at home, oral medications (oral cancer drugs), biologic products, medications that may require more patient support or counseling, medications that must be handled and/or stored carefully, and medications that may be used by a small percentage of the population². Similar to a local pharmacy, a specialty pharmacy can help review the medications and understand potential issues or drug interactions³. In 2005, 21% of new drug approvals by the Food and Drug Administration (FDA) were for specialty medications and these drugs are projected to hit 45% of US prescription sales volume by 2017⁴.

A specialty pharmacy is a unique business model, in that it caters to a narrow but concentrated patient population and the barriers to setting up this entity are few. Defining a specialty pharmacy isn't easy; there is no special licensure or accepted industry-wide definition to designate a specialty pharmacy. Specialty pharmacies began with pockets of independent pharmacies attempting to fill key voids in traditional pharmacy practice, such as the management of complex disease states, treatment regimens, and challenging reimbursement scenarios. Initially, the “customer” was simply the patient whose disease state required the use of specialized medications. However, as specialty pharmacies have evolved, the “customer” has also evolved to include not only the patient but also the manufacturer and has attracted the attention of MCOs, PBMs, employers, community pharmacy, distributors, and others seeking to manage costs or offer enhanced drug management services while providing an acceptable standard of care⁵. Adam Fein, PhD, president of Pembroke Consulting and chief executive officer of the Drug Channels Institute, described Specialty pharmacy as a “business strategy that can be adopted by any pharmacy with access to a drug through a legitimate distribution channel⁶.” Now that the definition of customer has been broadened to include manufacturers, some challenges are being identified, namely in the realm of pharmacovigilance that are becoming an additional criteria for the launch of such an entity.

Pharmaceutical manufacturers are accustomed to establishing robust procedures and systems to support compliance with the pharmacovigilance regulations set forth by regulatory bodies around the globe. On the other hand, pharmacies have traditionally followed local state pharmacy law as it relates to reporting adverse events⁷. Because the role of specialty pharmacies in patient support, medication monitoring, and disease management, compliance with the guidelines that exist for pharmacovigilance is necessary. Pharmacovigilance (PV) is defined as the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problem, with its core aims to enhance patient care and patient safety in relation to the use of medicines; and to support public health by providing reliable, balanced information for the effective assessment of the risk-benefit profile of medicines⁸. Both the FDA 21 CFR Part 314.80 and the European Medicines Agency (EMA) Module VI define an adverse reaction/adverse drug experience similarly as an unintended, untoward medical event associated with a medicinal product. Both FDA and EMA have similar provisions on the prompt reporting of such events by manufacturers. In order to ensure compliance and limit exposure to penalties, manufacturers are placing additional requirements on their specialty pharmacy partners and other health care service providers regarding staff training and implementation of processes for adverse event capture and reporting. These processes require careful consideration as manufacturers plan their resourcing and budget forecasts for patient support, reimbursement programs, and pharmacist interactions. Important factors in the resourcing and budgeting of these processes include: development and implementation of complex standard operating procedures, incremental staff training on product-specific adverseevent criteria and reporting procedures, extended call interaction time and post interaction follow-up activities, documentation of training and procedures, audit and inspection preparation and support, and enhancements to pharmacy database systems6.

The trend in pharmacovigilance and GCP audits of specialty pharmacies underlines the need for dialogue on quality directives and timely adverse event reporting. The major audit findings center on the inability of the specialty pharmacy to adhere to the FDA 21 CFR 314.80 and EMA Module VI guidelines on prompt reporting of adverse events. From an anecdotal history, specialty pharmacies are leanly operated, with little margin for extra overhead. And the burden of identifying and reporting unsolicited adverse events taps into this frail margin. The clinicians at the specialty pharmacy may not grasp the nature of why they must extend themselves further, in an already tight resource situation, to provide feedback to the manufacturer on what could be a possible adverse event with a patient. Often, when they do provide such information, it has been residing at the specialty pharmacy for some time and is included in a “batch update” or monthly status report to the manufacturer. This practice undermines the reconciliation of adverse events by the manufacturer and aids in creating a negative view of the specialty pharmacy. Not understanding the core requirement of timely pharmacovigilance reporting to the manufacturer is the crux of the impasse between these two parties.

The dilemma is the opposing viewpoints on what constitutes an adverse event and which interpretation takes the lead. Recall that in the specialty pharmacy domain, there is little regulation or enforcement of adverse event reporting, with just simple guidelines in place at the state level. In contrast, at the manufacturer level, there are harsh penalties for failure to report patient safety issues and strict global guidelines along with pharmacovigilance departments that are mandated to follow these guidelines. From a manufacturer point of view, the progression is simple: most specialty pharmacies already provide 24-hour support to the patient and it is feasible to assume that the patient would reach out to the specialty pharmacy when side effects occur, the clinicians at the specialty pharmacy are already engaged with the patients in providing disease state monitoring and education, and these additional communications with the specialty pharmacy staff may increase the likelihood of receiving an unsolicited adverse event from the patient.

Thus, the manufacturer expects the specialty pharmacy to comply with its adverse event report training and guidelines. From a specialty pharmacy viewpoint, the differences in standard interpretations are a challenge for both training and company resources. Each manufacturer’s adverse event reporting process can require manufacturer specific training materials, tracking documentation, and training sessions. Lily P. Duong, PharmD, Therigy’s Vice President of Outcomes and Reporting, states the dilemma as such: “When manufacturers approach a specialty pharmacy and award a purchasing contract, it usually includes language on adverse event reporting. As specialty pharmacies dispensing products on [a manufacturer’s] behalf, the pharmacies … are obligated to report those adverse events⁹.”

Typically, because of operational constraints, a specialty pharmacy is unable to complete all training requirements through the manufacturer provided sessions and must use a train-the-trainer method to avoid compromising the pharmacy’s workflow. The burden of training and tracking completion, therefore, falls onto the specialty pharmacy dispensing the manufacturer’s product¹⁰. By not having all of its members able to participate in the training program on pharmacovigilance and adverse event reporting, specialty pharmacy teams do not benefit from a pure source transfer of knowledge, instead relying on the depth of understanding by the second tier trainer to answer any questions or concerns they have about the AE requirements put into place. Another complicating factor for specialty pharmacies is that what comes naturally to pharmacovigilance professionals at the manufacturer is a learned mechanism for specialty pharmacy staff. For example, all pharmacovigilance professionals have learned about making an adverse event case when four identifiers (patient, product, event, and reporter) are identified, and are alert to when a patient reports a potential adverse event. Conversely, specialty pharmacies have been exempt from reporting all adverse events, and are required by respective state mandates to report only significant ones such as death.

To protect patient safety in the dispensing and utilization of specialized medications, a compromise needs to be put in place between the manufacturer and the specialty pharmacy concerning the need to perform timely pharmacovigilance reporting. This need not be viewed as a burden by either party. For the specialty pharmacy, having access to a diverse population within a local niche can offer great analytics on medication usage, adherence, and general patient issues. The appropriate and effective use of specialty pharmacy has the potential advantage of improving care for people… also, by the nature of their size and numbers of patients within their catchments, specialty pharmacies have access to data and information that could more quickly identify safety issues¹¹.

Manufacturers can participate in this discovery of analytics by fostering open dialogue at the contract stage. Essential training is an area where the manufacturer can leverage its expertise in pharmacovigilance and provide resources for the specialty pharmacy, by way of having access to internal persons for any issues that arise in the conduct of operations. By taking the onus on training away from the specialty pharmacy, the manufacturer can reinforce the proper adverse event training as well as ensure that the trained clinicians grasp the core requirements and understand the importance of why their adherence to reporting guidelines will save both parties much unnecessary effort expenditure in their ongoing business relationship. It will also deflect from the growing opinion that specialty pharmacies are providing such services “above normal expectations” and ought to be reimbursed for their labor and resource usage. By creating a forum that fosters open critiques of processes and conversation on even the most basic matters, both sides can also learn about each’s internal processes centered on patient safety.

As the number of patients using specialty pharmaceuticals continues to increase due to recent approvals or expanded indications, it is becoming even more important for the specialty pharmacy industry and manufacturers to create alignment on adverse event reporting10. As both sides understand each’s unique talents in upholding patient safety issues, the challenges faced by both sides dissipate. Specialty pharmacies have access to key patient data by nature of their business practices that if they were to leverage these data for tracking events and for outcomes research, patient safety could be significantly improved. Manufacturers have a firm grasp on federal and global patient safety regulations by way of their pharmacovigilance department, that if they were to include specialty pharmacies into their training activities and take a long form view of this business relationship, they could influence the practice of their respective business partner. The goal of this relationship between the manufacturer and the specialty pharmacy ought to be for creation of a less burdensome environment and more collaborative one, which in turn will facilitate the achievement of mutual pharmacovigilance goals.