Pharmacy Practice FAQsCOMPOUNDING Statutes, Rules, and Standards Governing Compounding
A: Board Rule .2801 governs the preparation of compounded drug products. Compounding is also governed by the federal Drug Quality and Security Act and by applicable United States Pharmacopeia chapter standards, which are incorporated as a matter of federal and state law.
Q: What federal law governs the preparation of compounded drug products? A: The Drug Quality and Security Act of 2013 (“DQSA”) broadly governs the compounding of drug products by pharmacies. The Food and Drug Administration maintains comprehensive guidance on the DQSA’s provisions, associated guidance documents, and FDA policies here: FDA Human Drug Compounding Resource Page
Q: Does the federal Drug Quality and Security Act prohibit a pharmacy from compounding veterinary drugs for “office use”? A: No. The federal Drug Quality and Security Act speaks to compounding of human drug products. The FDA’s most current statement of regulatory policy governing veterinary compounding may be found here: FDA Regulation of Animal Drugs. Included in the resources at this link is FDA’s final Guidance for Industry #256, Compounding Animal Drugs from Bulk Drug Substances.
Q: My pharmacy engages in compounding. How should this be reported to the Board and what information should be provided? A: Pharmacies that hold a permit from the North Carolina Board of Pharmacy and that engage in any type of compounding are required to notify the Board. Such pharmacies must report (both on an initial permit application and as part of each annual renewal): (1) whether they compound; (2) whether the pharmacy engages in non-sterile compounding; and (3) whether the pharmacy engages in sterile compounding.
Q: Do United States Pharmacopeia (“USP”) chapter standards apply to drug product compounding as a matter of law? A: Yes. Both the federal DQSA and North Carolina Board of Pharmacy rule incorporate applicable USP chapter standards governing the preparation of non-sterile and sterile compounded drug products. USP chapter <825> governs compounding activities involving radiopharmaceuticals. It is incorporated into revised USP chapters <795> and <797> that became effective November 1, 2023, and therefore applies to compounding activities involving radiopharmaceuticals after that date: USP General Chapter <825>
Q: What are the USP<797> certification requirements for sterile compounding facilities? A: All certification testing and documentation must be compliant with USP Chapter <797>. See Board Rule .2801. The Pharmacy Manager and/or Designated Compounding Pharmacist should review certification and environmental sampling reports to ensure that appropriate tests are performed and are in compliance with USP Chapter <797> and that the results are compliant with the action levels set forth in USP Chapter <797>. This guidance discusses certification tests and required documentation for a sterile compounding facility and sterile compounding equipment. It also provides guidance on environmental sampling and documentation requirements.
Q: What are the compounding record and master formulation record requirements for sterile compounded products? A: USP Chapter <797> requires that a compounding record be created and maintained. Board rules have always required a compounding record and did so well before implementation and enforcement of USP standards for compounding: Guidance to Compounding Record and Master Formulation Record Requirements
Q: Does USP chapter <800> apply to non-compounding activities involving hazardous substances? A: Yes, but in North Carolina, USP chapter <800> is not enforceable under Board rule for non-compounding activities. The Board views compliance as a best practice for pharmacies who are doing non-compounding activities with hazardous medications. As pharmacists know, USP Chapter <800> standards are designed to protect pharmacists, pharmacy staff, patients, and the public from the harmful effects of exposure to hazardous medications. As USP Chapter <800> standards for non-compounding activities become commonly followed, North Carolina law is likely to reflect that doing so is considered standard of practice. In that case, failure to comply may be evidence of negligence. Therefore, you are encouraged to evaluate (and to continue to re-evaluate) to what extent compliance reflects the appropriate standard of care. Board staff will continue to make observations during inspections to help identify potential risk for handling Hazardous Medications and will provide education on how to comply with USP Chapter <800> standards to minimize risk to pharmacy staff, patients, and the public. These observations regarding USP Chapter <800> compliance in non-compounding activities involving Hazardous Medications will not, by themselves, serve as a basis for disciplinary action by the Board: Board Statement on USP Chapter <800> and Non-Compounding Activities Board Staff have created helpful educational information that addresses identification of Hazardous Drugs, instructions on conducting an Assessment of Risk, and templates for non-compounding pharmacies to develop Standard Operating Procedures (SOPs) addressed in USP<800>. This informational material is for pharmacies that DO NOT compound with hazardous medications: Guidance on USP <800> Assessment of Risk and Other Educational Information.
Specific Compounded Products
A: On April 28, 2023, FDA officials clarified semaglutide’s shortage status. This statement has been updated to reflect that FDA clarification. In response to several inquiries, Board staff have assembled a statement concerning if, when, and how semaglutide may be compounded: http://www.ncbop.org/PDF/SemaglutideCompounding.pdf.
Q: May I compound a copy of a commercially available product? A: In general, no. The federal Food Drug & Cosmetic Act prohibits pharmacies from compounding “drug products that are essentially copies of a commercially available drug product.” FD&C Act § 503A(b)(1)(D) FDA does not consider a drug to be “commercially available” if it appears in FDA's Shortage Database. On April 27, 2023, FDA officials clarified that a drug is considered in shortage by the FDA if it is listed in the database and its “status” is described as “currently in shortage.” When compounding any drug product, the substances used to compound must: (1) comply with the standards of an applicable United States Pharmacopeia (USP) or National Formulary (NF) monograph, if a monograph exists, and the USP chapter on pharmacy compounding; (2) if such a monograph does not exist, then the substances used must be components of drugs approved by the Secretary [of HHS]; or (3) if such a monograph does not exist and the drug substance is not a component of a drug approved by the Secretary [of HHS], appear on a list developed by the Secretary through regulation. FD&C Act § 503A(b)(1)(A)(i) The pharmacy must ensure that the API used in compounding is a pharmaceutical grade product, accompanied by a valid certificate of analysis, and is sourced from an establishment registered with FDA under Section 510 of the FD&C Act. FD&C Act § 503A(b)(1)(A)(ii) – (iii)
Q: Is adding flavoring to a conventionally manufactured product considered compounding? A: USP considers adding flavoring to a conventionally manufactured product to fall within the scope of compounding, because there are known instances when flavoring components have destabilized a product. If a pharmacy adds flavoring to a manufactured product it must take into account the manufacturer’s Beyond Use Date (BUD) and the effect on stability caused by adding flavoring. If a flavoring component is added to a manufactured product that does not contain a preservative (e.g., reconstitution of amoxicillin oral suspension) the BUD is 14 days refrigerated or shorter if indicated in the manufacturer’s labeling. If a flavoring component is added to a manufactured product that contains a preservative (e.g., pyridostigmine oral solution), then the BUD is 35 days in controlled room temperature or refrigerated or shorter if indicated in the manufacturer’s labeling. When adding flavoring the compounding record must include the flavor manufacturer or product, lot number, and expiration date. All of this information about the flavoring must be documented in the patient record notes for the prescription.
Q: Is it permissible to compound domperidone? A: Domperidone compounding is permissible only as part of an investigational new drug application (IND). Domperidone is not a drug approved for human use in the United States. Accordingly, any domperidone product dispensed in the United States outside of an IND is unapproved, adulterated, and misbranded under both federal and North Carolina law. Notwithstanding misleading Internet information to the contrary, it is not legal in the United States to acquire, compound, dispense, or administer domperidone outside of an IND. The FDA has long provided clear guidance on this point, which may be found here: How to Request Domperidone for Expanded Access Use As FDA’s information further states, “FDA has determined that domperidone should not be compounded or used to enhance breast milk production in lactating women.” Domperidone may be useful for “some patients with severe gastrointestinal disorders . . . that are refractory to standard therapy.” A physician who would like to prescribe domperidone for this indication may contact FDA to open an Investigational New Drug Application (IND). An FDA-authorized IND would “allow the importation, interstate shipment, and administration of the drug even though it is not approved for sale in the U.S.”
Q: What is the formulation for UNC Health Care’s Mucositis Mixture, also known as “Sleepy Butter”? A: UNC Health Care’s Mucositis Mixture is a part of the system’s formulary. The approved recipe by the Pharmacy and Therapeutics Committee is: Oral Formulation. USP <795> requires that water-containing oral formulations be assigned a BUD that is no longer than 14 days under refrigerated storage conditions. The directions for an oral formulation of Mucositis Mixture would be “swish and swallow” or similar. Mucosal Liquid Formulation. USP <795> requires that water-containing topical, dermal, and mucosal liquid and semisolid formulations be assigned a beyond used date (BUD) that is no longer than 30 days under room temperature storage. The directions for a mucosal liquid formulation of Mucositis Mixture would be “swish and spit” or similar. If a pharmacy compounds one batch of Mucositis Mixture to fulfil all Mucositis Mixture prescriptions – whether the directions are “swish and spit” mucosal formulation or “swish and swallow” oral formulations – the assigned beyond used date (BUD) must be the stricter one: no longer than 14 days under refrigerated storage. USP <795> allows for a longer BUD for Mucositis Mixture Mouthwash if the pharmacy has independent stability data justifying the extended BUD.
Q: How do I prepare “Duke’s Magic Mouthwash”? The appropriate USP <795> BUD for Magic Mouthwash depends on whether it is compounded and dispensed as an oral formulation or as a mucosal formulation. Oral Formulation. USP <795> requires that water-containing oral formulations be assigned a beyond used date (BUD) that is no longer than 14 days under refrigerated storage conditions. The directions for an oral formulation of Magic Mouthwash would be “swish and swallow” or similar. Mucosal Liquid Formulation. USP <795> requires that water-containing topical, dermal, and mucosal liquid and semisolid formulations be assigned a beyond used date BUD that is no longer than 30 days under room temperature storage. The directions for a mucosal liquid formulation of Magic Mouthwash would be “swish and spit” or similar. If a pharmacy compounds one batch of Magic Mouthwash to fulfil all Magic Mouthwash prescriptions – whether the directions are “swish and spit” mucosal formulation or “swish and swallow” oral formulations – the assigned beyond used date (BUD) must be the stricter one: no longer than 14 days under refrigerated storage. USP <795> allows for a longer BUD for Magic Mouthwash if the pharmacy has independent stability data justifying the extended BUD.
Q: Is it ok to use tap water to reconstitute medications? A: No, USP <795> states that Purified Water shall be used for compounding nonsterile drug preparations when formulations indicate the inclusion of water. This is also required when reconstituting medications such as antibiotics. Purified Water is different than Sterile water for irrigation. Sterile water for irrigation is not considered potable water and is not intended for oral administration.
|
