FDA issues draft guidance to ensure safety of compounded drugs
In an effort to assure the quality of compounded drugs, The Food and Drug Administration issued a revised draft guidance with recommendations for protecting patients from the risk of contaminated or otherwise substandard products produced by outsourcing facilities.
“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,” FDA Commissioner Scott Gottlieb said. “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.”
Gottlieb emphasized that 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 healthcare 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,” Gottlieb said.
Gottlieb continued, “While this practice is permitted, outsourcing facilities must comply with certain requirements, including current good manufacturing practice, or 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.”
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.
Gottlieb also said that 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," Gottlieb said.
Gottlieb said the FDA's 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.
"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 the production of sterile and non-sterile drug products," Gottlieb said.
The FDA also will 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.
The FDA plans to advance other new efforts to promote 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 a 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," Gottllieb said.
The agency also will 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, or 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," Gottlieb said.
The FDA today also added 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.
“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,” FDA Commissioner Scott Gottlieb said. “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.”
Gottlieb emphasized that 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 healthcare 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,” Gottlieb said.
Gottlieb continued, “While this practice is permitted, outsourcing facilities must comply with certain requirements, including current good manufacturing practice, or 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.”
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.
Gottlieb also said that 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," Gottlieb said.
Gottlieb said the FDA's 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.
"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 the production of sterile and non-sterile drug products," Gottlieb said.
The FDA also will 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.
The FDA plans to advance other new efforts to promote 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 a 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," Gottllieb said.
The agency also will 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, or 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," Gottlieb said.
The FDA today also added 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.