A couple weeks ago following an inspection by the Food and Drug Administration (FDA) of Front Range Laboratories, Leiter’s Compounding Pharmacy issued a nationwide recall of a non-sterile injectable product that exposes patients to the risk of contracting serious life-threatening injuries. This incident is just a latest among a string of episodes not even a year after 700 people fell ill after receiving tainted steroid injections from the New England Compounding Center (NECC) resulting in a nationwide outbreak of fungal meningitis. Back in 2005, the Centers for Disease Control and Prevention (CDC) responded to a multistate outbreak of Serratia marcescens bloodstream infection , which was linked to contaminated intravenous magnesium sulfate, again from a compounding pharmacy. At present, the regulatory landscape remains grossly inadequate to conduct effective surveillance and monitoring, but that may soon change upon passage of the federal Pharmaceutical Compounding Quality and Accountability Act (PCQAA).
Historically, compounding manufacturers have evaded federal oversight because they are not registered with the FDA as drug manufacturers. They do not have to report adverse events and the FDA does not approve prescriptions before they are marketed to the general public. Common sense would dictate that the consequences of such lax oversight would give way to unpredictable and, at times, deadly incidents that would beg the question as to why more was not done in anticipation of such events. The PCQAA attempts to fill those gaps.
Key features of the act, which replaces section 503A of the current Federal Food, Drug, and Cosmetic Act (FFDCA), establish clear boundaries between traditional compounders and compounding manufacturers who sell products across state lines. While preserving states’ authority to regulate pharmacies, the federal legislation is intended to contain the potentially widespread impact of unregulated practices that have given way to a series of tragic outbreaks. Compounding manufacturers would be defined as those entities that compound a sterile drug prior to or without receiving a prescription and introduces such drug into interstate commerce, i.e. across state lines (with the exception that the shipment within a hospital system will not result in the hospital pharmacy being labeled a compounding pharmacy). Moreover, a corporation that repackages sterile, “preservative-free” vials would also be considered a compounding manufacturer. This latter provision is in direct response to the NCCC, whose tainted injections led to the outbreak of fungal meningitis, because their version of methylprednisolone acetate did not contain preservatives. Since it was commercially available from an FDA-regulated facility, the law enabled NCCC to evade the regulatory process.
Under the PCQAA, compounding manufacturers must: (1) ensure that a pharmacist licensed in the State where the compounding manufacturers is located exercises direct supervision over its operations; (2) register with the Secretary its name, place of business, unique facility identifier, and point of contact e-mail address; (3) submit twice during the year a report identifying the drugs that it compounded over the previous 6-month period and provide the active ingredient, source of the ingredient, the National Drug Code number, the strength of the ingredient per unit, the dosage form and route of administration, the package description, and the number of individuals units produced, (4) be subject to inspection in accordance with a risk-based schedule established by the Secretary based on the compliance history of the manufacturer, the record and nature of recalls linked to the manufacturer, the inherent risk of the drug compounded, and a host of other factors; (5) report adverse events to the Secretary of each instance as soon as practicable but no later than 15 days after the initial receipt of the applicable information; and (6) adhere to drug labeling requirements, including an explicit statement that ‘This is a compounded drug’ or a reasonably comparable alternative statement.
Absent from the PCQAA is a former provision that sought to regulate the advertising of compounded drugs. This was not an oversight on the part of the Senate, but was in response to a ruling by the U.S. Supreme Court. In 2002, in Thompson v. Western States Medical Center (535 U.S. 357 (2002)), a number of licensed pharmacies brought suit after provisions of the Food and Drug Administration Act prohibited advertising and promotion of their products. The Court held that the prohibitions were unconstitutional restrictions on commercial speech. Under the 1st Amendment, compounding manufacturers have a right to advertise their products.
Nonetheless, the PCQAA is far more stringent than a status quo that represents a hodgepodge of state laws that to date have been simply ineffective in responding to severe outbreaks. At the very least, passage of the act may be an example of cooperative federalism whereby states and the federal government may work together to improve surveillance and monitoring, which in turn may strengthen efforts to mitigate widespread errors.
Historically, compounding manufacturers have evaded federal oversight because they are not registered with the FDA as drug manufacturers. They do not have to report adverse events and the FDA does not approve prescriptions before they are marketed to the general public. Common sense would dictate that the consequences of such lax oversight would give way to unpredictable and, at times, deadly incidents that would beg the question as to why more was not done in anticipation of such events. The PCQAA attempts to fill those gaps.
Key features of the act, which replaces section 503A of the current Federal Food, Drug, and Cosmetic Act (FFDCA), establish clear boundaries between traditional compounders and compounding manufacturers who sell products across state lines. While preserving states’ authority to regulate pharmacies, the federal legislation is intended to contain the potentially widespread impact of unregulated practices that have given way to a series of tragic outbreaks. Compounding manufacturers would be defined as those entities that compound a sterile drug prior to or without receiving a prescription and introduces such drug into interstate commerce, i.e. across state lines (with the exception that the shipment within a hospital system will not result in the hospital pharmacy being labeled a compounding pharmacy). Moreover, a corporation that repackages sterile, “preservative-free” vials would also be considered a compounding manufacturer. This latter provision is in direct response to the NCCC, whose tainted injections led to the outbreak of fungal meningitis, because their version of methylprednisolone acetate did not contain preservatives. Since it was commercially available from an FDA-regulated facility, the law enabled NCCC to evade the regulatory process.
Under the PCQAA, compounding manufacturers must: (1) ensure that a pharmacist licensed in the State where the compounding manufacturers is located exercises direct supervision over its operations; (2) register with the Secretary its name, place of business, unique facility identifier, and point of contact e-mail address; (3) submit twice during the year a report identifying the drugs that it compounded over the previous 6-month period and provide the active ingredient, source of the ingredient, the National Drug Code number, the strength of the ingredient per unit, the dosage form and route of administration, the package description, and the number of individuals units produced, (4) be subject to inspection in accordance with a risk-based schedule established by the Secretary based on the compliance history of the manufacturer, the record and nature of recalls linked to the manufacturer, the inherent risk of the drug compounded, and a host of other factors; (5) report adverse events to the Secretary of each instance as soon as practicable but no later than 15 days after the initial receipt of the applicable information; and (6) adhere to drug labeling requirements, including an explicit statement that ‘This is a compounded drug’ or a reasonably comparable alternative statement.
Absent from the PCQAA is a former provision that sought to regulate the advertising of compounded drugs. This was not an oversight on the part of the Senate, but was in response to a ruling by the U.S. Supreme Court. In 2002, in Thompson v. Western States Medical Center (535 U.S. 357 (2002)), a number of licensed pharmacies brought suit after provisions of the Food and Drug Administration Act prohibited advertising and promotion of their products. The Court held that the prohibitions were unconstitutional restrictions on commercial speech. Under the 1st Amendment, compounding manufacturers have a right to advertise their products.
Nonetheless, the PCQAA is far more stringent than a status quo that represents a hodgepodge of state laws that to date have been simply ineffective in responding to severe outbreaks. At the very least, passage of the act may be an example of cooperative federalism whereby states and the federal government may work together to improve surveillance and monitoring, which in turn may strengthen efforts to mitigate widespread errors.
