Statement from FDA Commissioner Scott Gottlieb, M.D. and Deputy Commissioner Anna Abram on new efforts to assure the quality of compounded drugs

FDA Statement

• For Immediate Release: December 10, 2018

As we continue to implement our 2018 Compounding Priorities Plan, our mission is to preserve patient access to compounded drugs to meet patients’ individual medical needs while also protecting patients from the risks of contaminated or otherwise harmful products. We’re especially focused on the importance of ensuring compounded product quality. Through enforcement actions, we’ve been addressing insanitary conditions and manufacturing quality issues at compounders’ facilities across the country. More activities are planned, and we’ve stepped up our collaborative work with the Department of Justice. But preventing problems before they put patient safety at risk is our key objective to protect consumers.

Although compounded drugs can serve an important role for certain patients whose medical needs cannot be met by an FDA-approved drug product, it’s important to understand that compounded drug products haven’t undergone FDA premarket review for safety and effectiveness. Compounders who are uniquely permitted under law to compound and distribute certain compounded drugs without receiving patient-specific prescriptions are referred to as outsourcing facilities. There has been a lot of discussion around the issue of “office stock” – the drugs that doctors may keep on hand for certain procedures. If certain conditions are met, the law allows outsourcing facilities to provide hospitals, physicians’ offices, and other health care facilities with supplies of compounded drugs to keep on hand as “office stock” for their patients, who may need quick or emergency medication upon diagnosis.

While this practice is permitted, outsourcing facilities must comply with certain requirements, including current good manufacturing practice (CGMP) requirements, and FDA routinely inspects outsourcing facilities to determine whether their products are manufactured appropriately. Today we’re updating some of our proposed policies related to these outsourcing facilities. Among our goals is to make it more feasible for compounding pharmacies to become outsourcing facilities.

Our principal focus remains patient safety.

Compliance with CGMP is particularly important in outsourcing facilities, as they often operate on a larger scale than other compounders and their compounded drug products may reach many patients across the country. As such, ensuring that their products are not contaminated, contain the right amount of each component, and maintain quality while stored on the shelf for a period of time are critical for office stock production. By adhering to CGMP requirements, such product quality problems and potential patient harm are more likely to be avoided. But, unfortunately, we continue to find concerning conditions and practices that can lead to contaminated, super or sub-potent, or mislabeled products. This is especially true when the compounder does not adhere to CGMP requirements, which we often observe in compounding pharmacies not registered as outsourcing facilities that are subject to CGMP and other requirements because they continue to engage in activities such as providing office stock.

Our aim is to protect patients and see more of the activity that creates the greatest potential for risk be done by compounders that meet CGMP requirements rather than by those that do not. Some of these higher risk activities include compounding done on a large scale, for drugs that must be sterile, and made using many manual manipulations.

That is why today we’re releasing a revised draft guidance with recommendations for protecting patients from the risk of contaminated or otherwise substandard products produced by outsourcing facilities. The aim is to outline practices for drugs produced under CGMP requirements by outsourcing facilities.

Maintaining the necessary standards to protect patients from contaminated or otherwise substandard products is of utmost importance. Quality is best assured by implementing appropriate controls throughout the manufacturing process, with end-product testing providing additional assurance. Through our efforts to develop guidelines that are applicable to and reflect outsourcing facility compounding operations, our aim for this guidance is to recognize the differences in drug production between outsourcing facilities and conventional drug manufacturers. The guidance is intended to provide clarity on quality assurance, maintaining suitable facilities, sterility, stability testing and beyond-use or expiration dates for products that don’t go through the FDA drug approval process.

We’ve heard the feedback from stakeholders to our proposed 2014 draft guidance that certain CGMP policies would have made it difficult for outsourcing facilities to fill smaller orders and that some compounded drug products that practitioners requested for office stock were not available from outsourcing facilities due to those policies. We want to advance policies that make it more feasible for outsourcing facilities to fulfill requests for office stock while maintaining product quality. This revised draft guidance includes changes intended to help achieve this goal, particularly through revisions related to release testing, stability testing and beyond-use dating, as well as policies that differentiate between production of sterile and non-sterile drug products.

In addition to the revised draft guidance that we’re releasing today, we’ll also be holding a public meeting in May to solicit comments on the potential impact of the policies, if finalized as described in the updated draft guidance, on outsourcing facilities supplying compounded drugs for office stock. Health care professionals, outsourcing facilities, entities considering becoming outsourcing facilities, and other interested parties will have the opportunity to present to FDA their perspectives concerning how the draft guidance revisions may impact them. We hope to gain additional clarity from stakeholders on outsourcing facility production of office stock products, the fulfillment of smaller orders of these office stock products, and the production of products with beyond-use-dating desired by providers, among other topics.

Effectively providing patients and clinicians with access to compounded products made under appropriate production standards is key to helping mitigate risk and assure quality for patients. In implementing the new law, we’re seeking to strike a balance that helps ensure compounded products are accessible to patients that need them and that they meet appropriate quality standards. The FDA is still concerned that we see far too much unsafe activity in the compounding sector, including at facilities that have not registered with FDA as outsourcing facilities but continue to distribute office stock products. And we’re concerned that patients still face too many risks. We’re seeking to focus on supervision of this sector and appropriate enforcement activities. And we’ll advance other new efforts to promote our oversight in this sector, to make it more feasible for compounding pharmacies to become outsourcing facilities, and for outsourcing facilities to meet provider requests. We’ll also continue to conduct risk-based inspection and enforcement efforts with respect to compounders not registered as outsourcing facilities, especially if they appear to be distributing compounded sterile drugs nationwide without valid patient-specific prescriptions. Our goal is to ensure industry compliance. And the FDA will take action against facilities with deficient practices to try and stop issues before they lead to patient harm.

Soon we’ll also be taking action to further define what substances can be used in compounded products by traditional compounders. We’ll be issuing a final rule that identifies the criteria we are using to evaluate bulk drug substances for the list of bulk drug substances that may be used in compounding under section 503A (503A bulks list). This final rule will also identify bulk substances the agency has evaluated and will or will not place on the 503A bulks list. It’s key to balancing access to appropriately compounded drugs and protecting patients from compounded products that could cause harm. We’ll continue our rulemaking effort and plan to seek public comment on additional bulk drug substances for the 503A bulks list.

As part of this effort, today we’re also adding two new entries to the “withdrawn or removed” list of drug products that cannot be compounded because they’ve been found to be unsafe or ineffective.

Compounded drug products play an important role for many patients, and we have made meaningful progress throughout 2018 on our compounding policy priorities and the implementation of the Drug Quality Security Act. We remain committed to this critical public health effort and look forward to continuing this important work next year, including laying out new compounding priorities in 2019.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.