by Mary M. Bearden and Allison Shelton Brown & Fortunato, P.C.
On November 26, 2012, the U.S. Centers for Disease Control and Prevention (CDC) reported 510 cases of fungal meningitis infections or related conditions and a total of 36 deaths in 19 states. An infection involving fungi causes this rare form of meningitis. Inflaming the protective membranes surrounding the spinal cord and brain, meningitis can result in symptoms that include headaches, nausea, fever, and stiffness of the neck. Furthermore, fungal meningitis may result in stroke-like symptoms. Treatment of fungal meningitis is difficult; intravenous administration of anti-fungal drugs may be required for several months.
The recent fungal meningitis outbreak is linked to three contaminated lots of a steroid compounded by New England Compounding Center (NECC) in Framingham, Massachusetts. Generally, the compounded steroid is injected in an area adjacent to the spine in order to reduce pain and inflammation. Even though this drug is not approved by the U.S. Food and Drug Administration (FDA), the drug is widely prescribed for this off-label use and is also covered by several insurance plans. According to the CDC, approximately 14,000 patients received injections of the steroid from the three contaminated lots. In September, NECC recalled the steroid linked to the fungal meningitis outbreak. Then, on October 6, 2012, NECC voluntarily recalled all drugs compounded at the pharmacy in Framingham.
NECC is licensed as a compounding pharmacy in Massachusetts. Traditionally, compounding pharmacies prepare and package specific drugs for individual patients and for practitioners involved in research. Such compounded drugs are generally not commercially available; thus, compounding pharmacies play an important role in the health care environment. For example, if a patient cannot tolerate the tablet form of a commercially available medication, the patient’s physician can request that a compounding pharmacy prepare the medication in a form that is tolerable to the patient.
Because compounded drugs are not mass produced, they are not subject to the new drug approval process established by the FDA. Likewise, compounding pharmacies are not required to register with the FDA as manufacturers and follow the Current Good Manufacturing Practices. Instead, state agencies regulate compounding pharmacies. States generally authorize compounding pharmacies to compound drugs pursuant to valid prescriptions or in limited quantities that are based on historic prescriptions. Other practices, such as preparation of large batches of compounded drugs, are generally beyond the scope of a pharmacy’s state license. In a press release on October 11, 2012, Massachusetts Governor Deval Patrick alleged that NECC had acted outside the scope of its license. NECC had distributed approximately 17,500 vials to 75 facilities throughout 23 states.
As a result of the contamination linked to NECC’s compounds, the FDA and Massachusetts launched investigations of NECC. The investigations uncovered bacteria and mold in not only the pharmacy’s facility but also the vials of steroids. Furthermore, investigators found that NECC had improper and insufficient sterility testing. In the preliminary report, the Massachusetts Department of Health indicated that NECC violated its license because “NECC distributed large batches of compounded sterile products to facilities apparently for general use rather than requiring a prescription.” In addition to the governmental investigations and enforcement actions, several civil law suits have been filed against NECC, and criminal charges may be on the horizon.
The federal and state governments are focused on implementing not only responsive disciplinary actions against NECC but also preventative action that will affect the entire industry. On November 1, 2012, the Massachusetts Board of Registration in Pharmacy issued draft emergency rules that will require pharmacies engaged in sterile compounding to periodically report the states to which the pharmacy ships, the number of prescriptions dispensed, and the states in which the pharmacy is licensed. Changes in the role of the federal government in the regulation of pharmacies may be forthcoming as well.
Currently, the FDA regulates drug manufacturers, whereas regulation of compounding pharmacies generally falls within the purview of the state’s authority. With the growth of compounding pharmacies, however, the defining line between manufacturer and compounding pharmacy is not clear. Moreover, many states do not have the resources to implement robust oversight and enforcement programs. Therefore, on November 2, 2012, Representative Edward Markey (D-MA) and eight cosponsors introduced House Bill 6584 entitled, “Verifying Authority and Legality In Drug (VALID) Compounding Act of 2012.” The House Committee on Energy and Commerce is currently reviewing the bill.
Under the proposed legislation, the FDA will obtain more authority to oversee, regulate, and investigate compounding pharmacies. As long as compounding pharmacies meet certain criteria established in the VALID Compounding Act, the pharmacies will be exempt from FDA requirements for Current Good Manufacturing Practices and for approval of new drugs. Conditions for the exemption include: (1) licensed pharmacists compound drugs only pursuant to valid prescriptions for identified patients; (2) drugs are compounded from safe and approved products; (3) the pharmacy follows the applicable standards established by the U.S. Pharmacopeial Convention; (4) the compounded drugs are not commercially available; and (5) the drugs bear labels informing patients that the drug is not approved by the FDA and has not been tested for safety and effectiveness. In the event a pharmacy does not meet these criteria, the FDA may treat the pharmacy as a manufacturer. In bureaucratic terms, the exemption will not apply to a pharmacy that is, “in effect, manufacturing such drugs, as determined by the Secretary, taking into consideration the extent to which such pharmacy sells the drugs across state lines, the quantity of the drugs sold, and any other factors determined appropriate by the Secretary.”
Some of the conditions for the exemption may be waived in accordance with provisions in the VALID Compounding Act. For example, in cases of drug shortages or to protect public health and well-being, the Secretary may grant one year waivers of the condition that the pharmacy compound pursuant to a prescription for an identified patient. Likewise, the Secretary may waive the requirement that the drug is not commercially available in order to protect the health and well-being of the public. Finally, the VALID Compounding Act will authorize the Secretary and, at the delegation of the Secretary, state agencies to grant to certain pharmacies waivers of the requirement for compounding only pursuant to a prescription for an identified patient. Hospital pharmacies and retail pharmacies that compound limited quantities based on historic prescriptions may seek such waivers.
While many in the industry support the federal government’s initiative, the VAID Compounding Act, in its current form, may result in some negative and costly consequences for legitimate compounding pharmacies. First, the vague factorial test dividing compounding pharmacies from manufacturers will leave many pharmacies in an uncertain and potentially risky no man’s land. These pharmacies need a bright line test that clearly distinguishes the practice of pharmacy from drug manufacturing. Second, the requirement that pharmacies must obtain a waiver to compound limited quantities of a product will disrupt a common and accepted practice of compounding pharmacies. Compounding pharmacies generally prepare small batches of a product based on historic prescriptions in order to decrease waste and errors and in order to perform quality testing in advance. If the VALID Compounding Act is implemented before the process for the necessary waivers is established and available, many compounding pharmacies will have to either cease operations or encounter the risks associated with noncompliance.
The fungal meningitis outbreak clearly demonstrates a need for change; however, lawmakers should take time to ensure that legitimate compounding pharmacies may continue to provide needed services to the public. The VALID Compounding Act, in its current form, will likely have a negative impact on pharmacies engaged in legitimate compounding practices..