Jay Campbell Executive Director North Carolina Board of Pharmacy

Jay Campbell Executive Director North Carolina Board of Pharmacy

I have no relationships with commercial interests related to the content of my presentation.

Assessment Questions TRUE or FALSE: The federal Drug Quality and Security Act places pharmacy compounding under the exclusive jurisdiction of the FDA. TRUE or FALSE: The federal Drug Quality and Security Act exempts pharmacies from FD&C Act requirements for labeling, cgmp compliance, and new drug approval when the pharmacy compounds products for office use. TRUE or FALSE: The federal Drug Quality and Security Act exempts outsourcing facilities from FD&C Act requirements for cgmp compliance when preparing sterile products for office use.

DQSA s Focus Further refinement of the intersection between state and federal regulation of compounding pharmacy practices. Creation and implementation of a national track and trace program intended to ensure the integrity of the prescription drug supply chain.

Reaffirmation of FD&C Act Section 503A Section 503A added to the FD&C Act in 1995. Pharmacies successfully challenged the advertising and promotion restrictions in Section 503A. The U.S. Supreme Court struck them down as violating the First Amendment. Persistent debate continued as to whether the remaining provisions of Section 503A remained in force (one federal court of appeals said yes; another said no ). That debate has been resolved. Congress has removed the advertising and promotion restrictions and reaffirmed the remaining provisions of Section 503A.

Section 503A Exempts Certain Compounded Drugs from Federal Requirements A pharmacy is exempted from FD&C Act requirements governing adequate labeling directions, cgmp compliance, and the new drug approval process if certain conditions are met. A drug is compounded on the prescription order for... an individual patient. A drug is compounded in limited quantities before the receipt of a valid prescription order based on a history of receiving valid prescription orders for the compound, and the drug is not dispensed to a patient until a prescription order is received.

Section 503A and Office Use Compounding Section 503A does not grant an exemption from FD&C Act requirements for office use compounds. Outsourcing facilities under Section 503B (discussed shortly) may compound office use products. Compounded positron emission tomography drugs and radiopharmaceuticals are exempted from Section 503A. FDA has stated that Section 503A applies nationally and immediately. FDA promises additional guidance on Section 503A interpretation at a later date.

Section 503A and Office Use Compounding From a January 17, 2014 FDA warning letter to a compounding pharmacy: Since the FDA inspected your facility, Congress enacted and the President signed into law the Compounding Quality Act (CQA), which amended FDCA section 503A by eliminating the advertising restrictions that had been the basis for conflicting judicial decisions. The CQA otherwise left section 503A intact, and so clarified that the remainder of section 503A, including the requirement of valid prescriptions for individually-identified patients, is applicable in every federal judicial circuit. Accordingly, the drugs you compound without valid prescriptions for individually-identified patients are not entitled to the exemptions in section 503A.

Individual Senators Statements on Office Use Compounding Senator Boozman (R-Ark.): The practice of pharmacy, including pharmacy compounding, is a state issue. Nothing in this law changes that. Compounded drugs for office-use is a state issue. Nothing in this law changes that. Senator Coburn (R-Okla.): The issue of office use, indeed all of pharmacy practice regulation, is best left to the states. So the omission of office use from 503(a) should not signal to the FDA that it has the authority to encroach upon State authority to regulate office use.

Individual Senators Statements on Office Use Compounding Such statements are likely to be of limited utility: They would only be probative (if at all) should the statutory language of the DQSA on this topic be deemed ambiguous. E.g., United States v. Rojas-Contreras, 474 U.S. 231, 235 (1985). Even when interpreting ambiguous statutory language, courts generally give little, if any, weight to individual floor statements by members of Congress. E.g., Consumer Prod. Saf. Comm n v. GTE Sylvania, Inc., 447 U.S. 102, 118 (1980). At least one other compounding bill expressly preserved an ability for pharmacies to engage in office compounding insofar as consistent with the law of the pharmacy s state of domicile. H.R. 3089, 113 th Cong. 2(a)(1)(C) (2013). The DQSA as enacted contains no such preservation clause.

Section 503A and USP Standards Section 503A provides that compounded products must comply with the United States Pharmacopeia chapter on pharmacy compounding. Some read this provision as requiring USP compliance only with respect to selection of ingredients for compounding. FDA interprets the provision as applying to the entire process of compounding and its draft guidance specifically notes that compliance with USP chapters <795> and <797> is required.

Other Conditions on Section 503A Exemptions for Compounded Products Compounded product does not appear on an FDAestablished list of products withdrawn from the market for safety or efficacy reasons. Compounded product is not essentially a copy of a commercially available drug product. Compounded product is not identified by FDA as presenting demonstrable difficulties for compounding that reasonably demonstrate an adverse effect on the safety or effectiveness of that drug product.

Pharmacy Compounding Advisory Committee Section 503A directs the creation of a Pharmacy Compounding Advisory Committee to: Advise on a list of drugs with "demonstrable difficulties for compounding", which may not be compounded either by pharmacies (under Section 503A) or outsourcing facilities (under Section 503B). Advise on a list of drugs that lack a USP monograph and are "not a component of a drug approved by [FDA]", but that can nonetheless be compounded (Section 503A). Advise on a list of drug that may not be compounded because they "have been withdrawn or removed from the market because such drug products or components of such products have been found to be unsafe or not effective" (Section 503A).

Pharmacy Compounding Advisory Committee The committee shall include representatives from the National Association of Boards of Pharmacy, United States Pharmacopeia, and pharmacists with current experience and expertise in compounding. FDA has received nominations. At a March 20, 2014 meeting, FDA officials said the number of nominees was large and the process for selecting members was underway. No timeline for completion was communicated.

Section 503A and Interstate Shipment Section 503A limits the ability of compounding pharmacies to ship products interstate. A state may enter into a memorandum of understanding with FDA to police the distribution of inordinate amounts of compounded products interstate. Section 503A charges NABP and FDA to work together on a proposed MOU. If a state does not enter into an MOU with FDA, compounding pharmacies in that state may not cause more than 5% of their total compounded products to be distributed interstate.

Cooperative Monitoring of Section 503A Compliance DQSA requires FDA to immediately notify a state board of pharmacy if it makes a determination that a pharmacy is acting contrary to section 503A. DQSA requires FDA to receive reports from state boards of pharmacy expressing concerns that a pharmacy may be acting contrary to section 503A.

Section 503B and Outsourcing Facilities DQSA provides a specific pathway for office use compounding. An outsourcing facility is a facility that is engaged in the compounding of sterile drugs, has elected to register with FDA as an outsourcing facility, and complies with Section 503B requirements. Section 503B exempts an outsourcing facility from certain FD&C Act requirements: adequate labeling directions and new drug approval process. Section 503B does not exempt outsourcing facilities from cgmp compliance.

Compliance Standards for Outsourcing Facilities Drugs must be compounded by or under the direct supervision of a licensed pharmacist in the outsourcing facility. Must meet cgmp standards. May not compound drugs that are essentially a copy of a commercially available product unless the drug appears on FDA s drug shortage list. May not engage in wholesale distribution of compounded products.

Compliance Standards for Outsourcing Facilities May not compound drugs that present demonstrable difficulties for compounding (same as in Section 503A). For any product compounded from a REMS drug, the outsourcing facility must, in advance, demonstrate to FDA that it has in place a comparable REMS strategy. Adverse events involving compounded drugs must be reported to FDA. Specific labeling requirements: This is a compounded drug; Not for resale; and Office Use Only Facilities must make twice-annual reports to FDA identifying all drugs compounded and various information about each compounded product.

Cooperative Enforcement FDA is required to receive reports from state boards of pharmacy expressing concerns that a compounding pharmacy may be acting contrary to section 503A. FDA is required to immediately notify state boards of pharmacy if it makes a determination that a pharmacy is acting contrary to section 503A. Much discussion at the March 20-21, 2014 intergovernmental meeting at FDA focused on the what and how of information sharing.

Next Steps State boards are awaiting FDA s promised interpretive guidance on Section 503A. State boards of pharmacy will have to consider how to deal with office use provisions in their practice acts or rules. State boards are awaiting a draft MOU for consideration. State boards will have to further address specific USP chapter <795> and <797> requirements in their practice acts or rules.

Assessment Questions FALSE. The federal Drug Quality and Security Act places pharmacy compounding under the exclusive jurisdiction of the FDA. FALSE. The federal Drug Quality and Security Act exempts pharmacies from FD&C Act requirements for labeling, cgmp compliance, and new drug approval when the pharmacy compounds products for office use. FALSE. The federal Drug Quality and Security Act exempts outsourcing facilities from FD&C Act requirements for cgmp compliance when preparing sterile products for office use.