5. Does compounding the drug product or category of drug products involve a complex compounding process that presents a demonstrable difficulty for compounding that is reasonably likely to lead to an adverse effect on the safety or effectiveness of the drug product?

RESPONSE

Commonly compounded formulations for bHRT preparations include capsules (powder-fill, semisolid-fill, oil-fill), oral solutions/suspensions, topical preparations (solutions/suspensions/emulsions/sprays/drops), creams, ointments, gels, suppositories/inserts, injections, pellets/implants and others.

6. Does compounding the drug product or category of drug products necessitate complex physicochemical or analytical testing that presents a demonstrable difficulty for compounding that is reasonably likely to lead to an adverse effect on the safety or effectiveness of the drug product?

RESPONSE

The microbiological, physicochemical, and analytical testing for compounded preparations is the same as for manufactured products. In addition to sterility testing, endotoxin testing, preservative effectiveness testing, etc., the following specific tests are listed in the USP for hormones and hormone products used in bHRT.

Estradiol USP Tests: IR and UV Spectroscopy, Melting Range, Specific Rotation, Water Determination, Chromatographic Purity.

Estradiol Cream Tests: Identification, HPLC Assay, Minimum Fill, Microbial Enumeration, and Tests for Specific Microorganisms.

Estradiol Vaginal Inserts Tests: Thin-Layer Chromatography Identification, HPLC Assay, Dissolution, Impurities (HPLC), Microbial Enumeration, and Tests for Specified Microorganisms.

Estriol USP Tests: Completeness of Solution, IR and UV Spectroscopy Identification, Specific Rotation, Residue on Ignition, Thin Layer Chromatography Purity, HPLC Assay.

Estrone USP Tests: IR and UV Spectroscopy, Clarity of Solution, Specific Rotation, Loss on Drying, Residue on Ignition, Visual Limits Color Tests, HPLC Assay.

Progesterone USP Tests: IR and UV Spectroscopy for Identification, Melting Range, Specific Rotation, Loss on Drying, HPLC Assay.

Progesterone Injection USP Tests: IR Spectroscopy, HPLC Assay. Also USP Chapter <1> for Injections.

Progesterone Compounded Vaginal Inserts USP: IR Spectroscopy for Identification, HPLC Assay, Uniformity of Dosage Units. (Note that this is an official compounded preparation monograph.)

Testosterone USP Tests: IR and UV Spectroscopy for Identification, Melting Range, Specific Rotation. Loss on Drying, HPLC Assay.

SUMMARY FOR QUESTIONS 5 AND 6

It is quite evident that a complex compounding process is NOT REQUIRED, as the procedures involved in compounding bHRT preparations are routine and practiced daily by thousands of compounding pharmacists.

It is also apparent that complex physicochemical or analytical testing is NOT REQUIRED but are tests commonly used for official hormones in the USP utilizing analytical and microbiological laboratories. Of note is that some laboratories used for analyzing compounded preparations are also utilized by major PHARMA companies and federal and other organizations.

Also, the compounding process and physicochemical and analytical testing is basically the same for all compounded preparations and manufactured preparations using the same analytical instrumentation, etc.

Next week, we will summarize the six questions.