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 nonsevere 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 <795> and <797> standards to ensure the quality of dispensed sterile and non-sterile cBHT preparations. USP <795> and <797> 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.

EDITORIAL COMMENTS (Regarding 503A Compounding Pharmacies)
Of the 6 recommendations, this may be the most problematic of all, as it basically requires efforts that parallel an FDA-approved product for compounded preparations, which are for individual patients. Also, with an estimate of 10 to 100 individual patients daily with individualized prescriptions in a community pharmacy, this is an impossible task.

It is interesting that there are hundreds of individual drug products on the market that have never been individually FDA-approved (pre-1938 drugs, OTC drugs that are simply group-monographed) and do not have the statement "This specific product has not been FDA-approved" so why is this recommended for each and every compounded preparation? This is an iappropriate recommendation unless all non-FDA-approved drugs are required to do the same. One could also mention that mega-marketed dietary supplements have little or no oversight with no guarantee of safety, efficacy, or quality standards.

"Standardized inserts" were discussed 25 years ago and dropped because they are impractical due to the large variety of compounded preparations and potential liability concerns. It is not reasonable to develop standardized inserts to accompany the diverse array of individualized dosage forms, doses, formulations, and patient needs as per the prescriber.

The explanation in the Recommendation (Line 4) includes the phrase "...statement of compliance to good manufacturing practices or U.S. Pharmacopeia (USP) standards..." This is problematic because 503a pharmacies are exempt from cGMP and not all states require USP Standards but have developed and established their own state compounding standards to meet the specific requirements of the respective state. To place the non-governmental private organization, USP, in a position of establishing required national compounding standards (regulations) that must be enforced by the state is untenable (one size does not fit all!) as this should not be the role of the USP.

The discussion involving "surveillance capacity" is unreasonable and unnecessary, and the NABP should not be in the business of monitoring the volume and types of cBHT preparations compounded by pharmacies within their state. (Big Brother?)

Many of the items discussed in this recommendation would require hiring numerous additional personnel, add increased costs to the medication, and would serve no meaningful purpose other than generating additional paperwork and requirements for compounding pharmacies. The committee seems to have difficulty separating the purpose and practice of individualized medications for specific patients (i.e., compounding, from mass manufacturing of FDA-approved drug products). Much more harm can be caused by lack of patient access to individualized medications if these recommendations became reality.