Today, we're taking a key step forward in implementing the Drug Quality and Security Act (DQSA) and section 503B of the Federal Food, Drug, and Cosmetic Act. Among other things, these provisions limit the bulk drug substances that outsourcing facilities can use in compounding. It directs the FDA to develop a list of bulk drug substances for which there is a clinical need - the 503B bulks list.

Today, we're issuing a critical policy document that addresses how that list will be formulated, and what bulk drug substances the outsourcing facilities can use to compound from drugs.

Compounding can be critical for advancing the health of patients who have specific medical needs that cannot be met by FDA-approved drugs. However, because compounded drugs are not FDA-approved and do not undergo premarket review by the FDA for safety, effectiveness and quality; they also present a greater risk to patients than FDA-approved drugs. This was illustrated by the 2012 nationwide fungal meningitis outbreak. This tragic outbreak led to more than 750 cases of illness and the deaths of 64 individuals who had used a compounded drug for injection that was supposed to be sterile, but became contaminated.

In response to that public health tragedy, Congress enacted the DQSA in 2013 to enhance the safety and quality of these medicines. Advancing the FDA's compounding program is a high priority for the agency. We're fully committed to implementing the DQSA requirements in a way that preserves access to compounded drugs for patients who have a medical need for them, while protecting patients from poor quality or otherwise unsafe compounded drugs that could cause them serious harm.

The draft guidance we're releasing today is one part of a comprehensive policy framework. In January, we released our compounding policy priorities plan, which lays out how the agency will implement, over the course of 2018, certain key provisions of DQSA and other requirements of the law relevant to compounders. The plan is comprised of a series of draft and final guidance documents, proposed and final rules, and a revised draft memorandum of understanding (MOU) between the FDA and states.

Today's draft guidance is a significant milestone in our work to implement that compounding priorities plan. The new draft guidance ("Evaluation of Bulk Drug Substances Nominated for Use in Compounding Under Section 503B of the Federal Food, Drug, and Cosmetic Act"), issued for public comment, discusses the FDA's interpretation of the statutory phrase "bulk drug substances for which there is a clinical need," as well as the factors and processes that the FDA proposes to use when evaluating whether to include a bulk drug substance on the list of bulk drug substances that outsourcing facilities may use in compounding drugs.

Outsourcing facilities are subject to more stringent FDA oversight than traditional pharmacy compounders and can compound drugs in one of two ways. First, by starting from an FDA-approved drug product, the outsourcing facilities may prepare compounded drugs by altering the FDA-approved drug. This can be done, for example, by diluting the FDA-approved drug or changing the dosage form, perhaps by crushing an approved tablet to make an oral solution. The second way outsourcing facilities compound drugs is by starting from a bulk drug substance. An outsourcing facility may do this because an attribute of the alternative, FDA-approved drug product makes it inappropriate or unsafe for the patient.

However, as our draft guidance explains, compounding from bulk drug substances generally presents greater risk to patients than compounding from FDA-approved drugs. There are fewer assurances of safety and quality associated with a bulk drug substance than with an FDA-approved drug. Compounding from bulk drug substances also involves more numerous and complex steps than compounding from approved drugs. This process can introduce increased risk for compounding errors or contamination.

Further, compounding drugs using bulk drug substances, when the use of an FDA-approved drug or a drug compounded using an FDA-approved drug would meet patients' medical needs, can undermine the drug approval process by reducing the incentive for drug manufacturers to seek approval of brand or generic drugs. These issues have informed our views on how we treat bulk drug compounding.

First, we're proposing to interpret the statutory language "bulk drug substances for which there is a clinical need" to mean there is a clinical need, or reason, for an outsourcing facility to compound a drug product using a bulk drug substance (instead of the FDA-approved drug as the source). Secondly, we're outlining factors we propose to use to evaluate the bulk drug substances, in a two-part analysis.

In many cases, a bulk drug substance is a component of an FDA-approved drug product. In assessing the clinical need for a drug to be compounded from bulk substance in these circumstances, the first step of the FDA's analysis involves the agency considering whether attributes of the approved drug may make it unsuitable to treat certain patients for particular conditions - and whether the compounded drug is intended to address that attribute. The FDA also intends to consider whether the drug product to be compounded must be produced from a bulk drug substance rather than an approved drug.

For example, if an approved drug contains peanut oil, the FDA would consider whether there was information indicating that patients with a peanut allergy need a drug product compounded without the allergen. The FDA would further consider whether there was information suggesting that the drug product needs to be compounded using a bulk drug substance, rather than the approved drug, because the type and number of manipulations necessary to remove the peanut oil from the approved product would adversely impact the overall quality of the drug.

The draft guidance then describes a second step of the clinical-need analysis, which would apply to any bulk drug substances that are components of FDA-approved drugs that proceed through the first step, and to bulk drug substances that are notcomponents of FDA-approved drugs. This analysis consists of a balancing test under which the FDA would weigh certain factors for each substance being proposed for use in a compounded drug product - specifically, its physical and chemical characterization, possible or known safety issues, evidence or lack of thereof of effectiveness, and historical use.

As the agency further refines what we intend our policies to be on this important topic, we know that stakeholders will, through the public comment process, bring competing concerns to our attention. We look forward to engaging stakeholders during this process. Our decisions related to the finalization of this guidance and the 503B bulks list will be guided by the law that Congress established to meet patient medical needs, and our mission to protect consumers and promote opportunities to improve health.

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