Benzocaine: Summary Report Item Type Report Authors Yuen, Melissa V.; Gianturco, Stephanie L.; Pavlech, Laura L.; Storm, Kathena D.; Yoon, SeJeong; Mattingly, Ashlee N. Publication Date 2020-02 Keywords Compounding; Food, Drug and Cosmetic Act, Section 503B; Food and Drug Administration; Outsourcing facility; Benzocaine; Drug compounding; Legislation, Drug; United States Food and Drug Administration Rights Attribution-NonCommercial-NoDerivatives 4.0 International Download date 03/10/2021 00:27:38 Item License http://creativecommons.org/licenses/by-nc-nd/4.0/ Link to Item http://hdl.handle.net/10713/12049 Summary Report Benzocaine Prepared for: Food and Drug Administration Clinical use of bulk drug substances nominated for inclusion on the 503B Bulks List Grant number: 2U01FD005946 Prepared by: University of Maryland Center of Excellence in Regulatory Science and Innovation (M-CERSI) University of Maryland School of Pharmacy February 2020 This report was supported by the Food and Drug Administration (FDA) of the U.S. Department of Health and Human Services (HHS) as part of a financial assistance award (U01FD005946) totaling $2,342,364, with 100 percent funded by the FDA/HHS. The contents are those of the authors and do not necessarily represent the official views of, nor an endorsement by, the FDA/HHS or the U.S. Government. 1 Table of Contents REVIEW OF NOMINATIONS ............................................................................................................... 4 METHODOLOGY .................................................................................................................................. 5 Background information ...................................................................................................................... 5 Systematic literature review ................................................................................................................. 5 Outreach to medical specialists and specialty organizations.................................................................. 8 Survey ................................................................................................................................................. 8 CURRENT AND HISTORIC USE ........................................................................................................ 10 Summary of background information ................................................................................................. 10 Summary of literature review ............................................................................................................. 11 Summary of focus groups/interviews of medical experts and specialty organizations.......................... 19 Summary of survey results ................................................................................................................. 21 CONCLUSION ..................................................................................................................................... 22 APPENDICES ...................................................................................................................................... 23 Appendix 1. References ..................................................................................................................... 23 Appendix 2. Survey instrument .......................................................................................................... 32 2 Table of Tables Table 1. Participating associations ........................................................................................................... 9 Table 2. Associations that declined participation ...................................................................................... 9 Table 3. Currently approved products – US ........................................................................................... 10 Table 4. Currently approved products–select non-US countries and regions ........................................... 10 Table 5. Types of studies ....................................................................................................................... 11 Table 6. Number of studies by country .................................................................................................. 11 Table 7. Number of studies by combinations.......................................................................................... 13 Table 8. Dosage by indication – US ....................................................................................................... 14 Table 9. Dosage by indication – non-US countries ................................................................................. 16 Table 10. Compounded products – US ................................................................................................... 17 Table 11. Compounded products – non-US countries ............................................................................. 18 Table 12. Overview of interviewees ....................................................................................................... 19 Table 13. Characteristics of survey respondents ..................................................................................... 21 Table 14. Types of products used, prescribed, or recommended ............................................................. 21 Table 15. Compounded use of benzocaine in practice ............................................................................ 21 Table 16. Indications for which benzocaine is considered a standard therapy ......................................... 21 Table 17. Reasons for using a compounded product instead of any FDA-approved product .................... 21 Table 18. Change in frequency of compounded benzocaine usage over the past 5 years ......................... 21 Table 19. Do you stock non-patient specific compounded benzocaine in your practice? ......................... 21 Table 20. Questions related to stocking non-patient specific compounded benzocaine ............................ 21 3 REVIEW OF NOMINATIONS Benzocaine (UNII codes: U3RSY48JW5 and 41KZS5432U) was nominated for inclusion on the 503B Bulks List by Sincerus Florida, LLC, David Smith, AnazaoHealth Corporation, the Outsourcing Facilities Association (OFA), Triangle Compounding Pharmacy, the Specialty Sterile Pharmaceutical Society (SSPS), and Pine Pharmaceuticals. Benzocaine was nominated for various indications: While the exact medical condition for which the compounded product is being requested is generally unknown, benzocaine is generally used as a local anesthetic. Benzocaine will be compounded as various topical dosage forms and strengths based on the prescriber’s request; the therapeutic dose is 20%. Benzocaine will also be compounded as a topical oral gel in concentrations ranging from 5-20% for use as a numbing agent for local pain relief. Additionally, benzocaine will be compounded as a 20% topical cream for use as a topical anesthetic prior to painful skin procedures. Benzocaine will also be compounded in various dosage forms for topical, vaginal, rectal, oral, and otic use in concentrations ranging from 0.47%-30% to reduce pain caused by minor skin irritations, sore throat, sunburn, teething pain, vaginal or rectal irritation, ingrown toenails, hemorrhoids, ear pain, and other sources of minor pain on a surface of the body. Lastly, benzocaine will be compounded as a topical 20% solution for use as a local anesthetic. Benzocaine was recommended for combination use with lidocaine, prilocaine, and tetracaine, refer to Table 7 for the nominated combination formulations. Reasons provided for nomination to the 503B Bulks List include: • Commercially available medications may contain excipients such as fillers and preservatives that patients may not be able to tolerate due to allergies or sensitivities. Compounding from bulk allows using only the necessary ingredients to achieve the desired clinical outcome ensuring that no irritating, hazardous, or allergenic ingredients are included. • The dosage form, strength, or flavor of commercially available products may be inappropriate for the patient. • Compounded products are requested by prescribers to treat the individual needs of the prescriber’s patients. As a result, these may be the only formulations to effectively treat the intended indication. • Commercially available finished products have an inherent variance in potency creating an uncertain final concentration for the new product. • There are no FDA-approved drug products containing benzocaine. • There are no commercially available products that combine benzocaine with lidocaine and tetracaine. • There are no commercially available products that combine benzocaine with prilocaine, and lidocaine into a topical oral gel. • Prescriber and hospital preferences for varying concentrations, dosage forms, volumes, or final product containers. • It is relatively unsafe to expose the direct compounding area to hundreds of vials or ampules and hundreds of aseptic manipulations during the compounding of a typical batch size for an outsourcing facility; compounding from bulk is safer and more efficient and reduces sterility risk. • Use of state-of-the-art equipment, like the SKAN isolator technology, requires the use of bulk starting materials. • Benzocaine is shorter acting than other topical anesthetics. 4 METHODOLOGY Background information The national medicine registers of 13 countries and regions were searched to establish the availability of benzocaine