RECOMMENDATION 4

Additional federal and state-level oversight should be implemented to better address public health and clinical concerns regarding the safety and effectiveness of compounded bioidentical hormone therapy (cBHT).

The National Association of Boards of Pharmacy (NABP) and state boards of pharmacy should expand and improve their oversight and review of 503A compounding pharmacies to ensure that adequate quality standards are maintained and documented for every cBHT preparation dispensed. This increased oversight should include the following:

• All 503A compounding pharmacies should provide a standardized insert for dispensed cBHT preparations. The insert should:
  
  
  • Include a detailed description of the preparation's formulation, including all active pharmaceutical ingredients and the excipient(s) used, and use of the established name of the drug.
  • Clearly note that the preparation has not been FDA-approved for use and that rigorous bioavailability data, such as that available on FDA-approved products, are not available.
  • Include indications and guidance for use (administration), dosage strength and form, statement of compliance to current good manufacturing practices or U.S. Pharmacopeia (USP) standards, beyond-use date, contraindications, side effects, caution for potential adverse effects, and instructions on how to report adverse events.
  • Include information on the person responsible for the quality and safety of the dispensed cBHT preparation, such as the establishment's supervising pharmacist or other designated individual, and the name and contact information for the pharmacy.
  
  
  
• All cBHT preparations dispensed from 503A compounding pharmacies should include boxed warnings for potential adverse effects for compounded prescriptions that include estrogens (estradiol, estriol, estrone) and androgens (testosterone), like those used in FDA-approved drug products with boxed warnings to educate the user about potential health risks.
• All 503A compounding pharmacies should increase their surveillance capacity by monitoring, recording, and annually reporting the types, formulations, payer, and dispensing rates of cBHT preparations. Data on the volume and types of cBHT dispensed should be submitted annually to a central repository within NABP and made available for public access.
• All 503A compounding pharmacies should be required to monitor and report all adverse events of cBHT preparations to state boards of pharmacy and simultaneously to MedWatch and the FDA Adverse Event Reporting Systems (FAERS). Annual adverse events reports for non-severe and non-life-threatening events should also be submitted. These reports should include information on the frequency, type, and severity of adverse events related to the use of cBHT.
• All states should uniformly and immediately adopt USP and standards to ensure the quality of dispensed sterile and non-sterile cBHT preparations. USP and should be considered minimum standards and regulators should apply additional standards where needed to reduce patient risk.

FDA should continue to incorporate public health considerations into its regulation of the manufacturing, testing, and dispensing of cBHT by 503B outsourcing facilities. These considerations should include:

• Expand the requirement for 503B outsourcing facilities to provide information on the bioavailability and effectiveness of common cBHT preparations (e.g., Bi-est, Tri-est, all sterile preparations including pellets), in addition to their current focus on quality, purity, and sterility.
• All 503B outsourcing facilities should use a standardized insert for dispensed cBHT preparations. In addition to the current requirements, the insert should include:
  
  
  • A detailed description of the preparation's formulation, including all active pharmaceutical ingredients and inactive ingredients (e.g., excipients) used.
  • Clearly note that the preparation has not been FDA-approved for use, and that rigorous bioavailability data, such as that available on FDA-approved products, are not available.
  • Include indications and guidance for use (administration), dosage strength and form, statement of compliance to current good manufacturing practices or USP standards, beyond-use date, contraindications, side effects, caution for potential adverse effects, and instructions on how to report adverse events.
  
  
  
• All cBHT supplied by 503B outsourcing facilities should include boxed warnings for potential adverse effects for compounded prescriptions that include estrogens (estradiol, estriol, estrone) and androgens (testosterone), like those used in FDA-approved drug products with boxed warnings to educate the user about potential health risks.
• Modify the standard MedWatch form to adequately collect and track adverse events data related to cBHT use, including but not limited to:
  
  
  • All active pharmaceutical ingredients and excipients in the cBHT formulation
  • Potential drug-drug interactions