Importance to FDA

Compounding is generally a practice in which a licensed pharmacist, a licensed healthcare professional, or, in the case of an outsourcing facility, a person under the supervision of a licensed pharmacist, combines, mixes, or alters ingredients of a drug to create a medication tailored to the needs of an individual patient. Although compounded drugs can serve an important medical need for certain patients, they also present special risks. Compounded drugs are not reviewed by FDA for safety, efficacy, or manufacturing quality before they are marketed.

In 2012, contaminated drugs compounded by a Massachusetts pharmacy led to more than 750 cases of serious infections and over 60 deaths in 20 states, resulting in the enactment of the Drug Quality and Security Act (DQSA, Public Law 113-54). The DQSA established a new category of compounders (outsourcing facilities), which are held to more stringent quality standards and are inspected by FDA according to a risk-based schedule. FDA’s compounding program aims to protect patients from unsafe, ineffective, and poor-quality compounded drugs, while preserving access to lawfully marketed compounded drugs for patients who have a medical need for them. FDA is engaged in efforts aimed to reduce risks related to compounded drugs, including research on bulk drug substances used in compounding and research, training, and educational initiatives through FDA’s Compounding Quality Center of Excellence.

Examples

• FDA engages in significant research and analysis on bulk drug substances (active pharmaceutical ingredients) that may be used in compounding under federal law. These ongoing initiatives involve dedicated efforts of numerous clinicians, scientists, and researchers to understand available information on clinical use, safety, and effectiveness for bulk drug substances used in compounded drugs. FDA also engaged with the following external research partners to inform these efforts and agency decision-making generally, as well as inform the public:
  • The National Academies of Science, Engineering & Medicine (NASEM) conducted research on the safety and effectiveness of multi-ingredient compounded topical pain creams and concluded, among other things, that there is limited evidence to support the use of compounded topical pain creams in the general adult population.
  • NASEM also conducted research to assess treating patients with compounded hormone therapy (HT) products and the availability of scientific evidence for their safety and efficacy. NASEM’s report found that there was a lack of rigorous evidence of safety and effectiveness from well-designed or properly controlled clinical studies.
  • The University of Maryland CERSI engaged in two research efforts: a three-year effort to examine the clinical use of drugs compounded from certain bulk drug substances, engaged in a three-year effort to examine the clinical use of drugs compounded from certain bulk drug substances and a two-year effort to obtain additional information about certain bulk drug substances.
  • The Johns Hopkins University CERSI conducted research to evaluate available evidence on the safety and effectiveness of each of six bulk drug substances used in compounded drugs for patients with autism spectrum disorder.
• FDA has advanced the Compounding Quality Center of Excellence to improve the quality of compounded drugs. This major initiative includes education, outreach, and research initiatives, including regulatory science projects involving multiple FDA labs:
  • FDA initiated a Landscape Study of the outsourcing facility sector to better understand barriers and opportunities encountered by outsourcing facilities in three major areas: compliance with current good manufacturing practice (CGMP)/good quality drug production, market and business viability, and interactions with FDA. The research provides insights that FDA can use to identify future FDA training topics, understand the effects of FDA policy on the sector, inform areas that FDA can increase engagement with outsourcing facilities, and enhance Compounding Quality Center of Excellence program areas.
  • As part of the Compounding Quality Center of Excellence’s focus on regulatory science, FDA has projects underway related to compounding operations, including a study that evaluates commercially obtained sporicidal disinfectants to strengthen the scientific framework by building an accurate efficacy database of these products, which will provide additional information regarding their use by compounders.