US Food and Drug Administration (FDA) Commissioner Margaret Hamburg has called upon Congress to grant the agency new authorities to regulate and oversee pharmaceutical compounders with the help of a new regulatory paradigm, according to testimony scheduled to be delivered before a House subcommittee.
Hamburg is scheduled to appear at a 10 a.m. hearing before the House Energy and Commerce committee to discuss FDA's response to the meningitis outbreak which has resulted from improper practices at a Massachusetts pharmaceutical compounder, the New England Compounding Center (NECC).
One of the central issues being investigated by the committee is whether FDA has sufficient authority to regulate compounders. It does not, said Hamburg in her prepared remarks.
One of the most basic issues is the division of regulatory authority to oversee the facility between federal and state regulators. An October 2012 inspection of NECC's Framingham, MA facility, for instance, needed to be coordinated between FDA and the Massachusetts Board of Pharmacy.
"We coordinated closely with the State [of Massachusetts] on this adverse event inspection, because the State has authority to compel certain actions where our authority is more limited," explained Hamburg, referencing its inspection of NECC's facility.
"Throughout this time, NECC has repeatedly disputed FDA's jurisdiction over its facility," Hamburg observed.
A Changed Industry
But Hamburg made clear that the problem extends far beyond just any one company. Rather, it extends to the entire industry of compounding.
Pharmaceutical compounding began to morph into an altogether different entity in the 1990s, said Hamburg. Whereas traditional compounding focused on small-scale and personalized compounds, newer facilities have increasingly been working at huge scales and compounding in bulk amounts.
Though FDA would put into place its own compliance policy guide (CPG) to define traditional-and therefore exempt from FDA oversight-compounding, Hamburg noted that Congress had consistently weakened its authority through new legislation. The FDA Amendments Act (FDAAA) of 2007, for example, specifically exempted compounded products from FDA's authority so long as the compounding is conducted by a licensed physician, is for a valid prescription and is for an individual patient.
Provided those-and some other-provisions were met, compounders would be exempt from current good manufacturing (CGMP) regulations, labeling requirements and pre-market approval restrictions. Under FDAAA, FDA was allowed to restrict compounding of certain drug products through the rulemaking process and limit the amount of products a compounding pharmacy could ship across state lines, but the most critical regulations-CGMP-remained out of reach.
Though Hamburg's testimony doesn't specifically make note of the types of violations at both NECC's and Ameridose's facilities, both were primarily CGMP-based, with a litany of basic yet egregious violations including rampant microbial contamination, un-validated processes and improperly handled records.
A New Compounding Paradigm
In her testimony, Hamburg said FDA, "Look[s] forward to working with Congress to address these issues."
"FDA believes that there is a legitimate role for traditional compounding to provide needed drugs to patients that, for example, need a drug that is allergen free or have a medical need that cannot be met with an approved FDA product," explained Hamburg. "However, we have grown increasingly concerned about certain compounding practices, and we have seen an increasing number of incidents related to compounded drugs. The NECC/meningitis situation is the latest, and most serious, incident."
Hamburg presented what she called a "framework" for expanding FDA's regulatory authority, which calls for the segregation of compounding activities into one of two definitions: traditional compounding and non-traditional compounding.
Traditional compounding, Hamburg explained, "Would include the combining, mixing or altering of ingredients to create a customized medication for an individual patient with an individualized medical need for the compounded products, in response to a valid patient-specific prescription or order from a licensed practitioner documenting such medical need." Traditional compounding would remain under the regulatory oversight of state pharmacy boards, Hamburg said.
Non-Traditional Compounding More Tightly Regulated
Non-traditional compounding would still be for a patient's medical need, but would be regulated by FDA based on the presence of one or more mitigating factors, including the compounding of sterile products, the amount of the product being made, whether the compounding is done before or after the receipt of a valid prescription, and the supply chain of the product.
Hamburg said it is her recommendation that non-traditional compounding should be required to meet CGMP standards, and that FDA be allowed to ban the production of certain types of compounds that are not safe "under any circumstances." Those products would include copies of FDA-approved drugs-a major turnaround for FDA, which has maintained that compounders could create copies of KV Pharmaceuticals' Makena (hydroxyprogesterone caproate injection) so long as it was on a small scale and met quality standards. Exceptions would be made for drugs experiencing shortage situations or on a case-by-case basis as FDA finds appropriate.
"FDA would like to explore with Congress other authorities that would be important to support this new regulatory paradigm," added Hamburg, who added the agency would stand to benefit from "clear, full authority to collect and test samples of compounded drugs" and production records from compounding facilities. Those facilities engaged in non-traditional compounding should also be required to register with FDA, she said. Other requirements, such as special labeling and adverse event reporting requirements, would be welcome as well, she added.
"We look forward to working with Congress in striking the right balance," Hamburg concluded.