Disclosure 11/10/2015. Ethical and Legal Compounding Practices ASORN. Executive Vice President of Sales, Avella Specialty Pharmacy

Transcription

1 Ethical and Legal Compounding Practices ASORN Hamilton Baiden, Executive Vice President of Sales Avella Specialty Pharmacy Disclosure Executive Vice President of Sales, Avella Specialty Pharmacy 1

2 Agenda November 13th, 2015 Background: the road to the Drug Quality and Security Act The DQSA 503A 503B What is Next? Confidential and proprietary 5 The Road to DQSA Pharmacy compounding was widely practiced when the Federal Drug and Cosmetic Act was first enacted in 1938 The precise legal status of compounding under federal law was uncertain for many years FDA long acknowledged that extemporaneous compounding to address a specific patient need served the public health Confidential and proprietary 6 2

3 The 1992 Compliance Policy Guide: By the early 1990s, FDA became concerned that an increasing number of pharmacies were engaged in practices that more closely resembled large scale drug manufacturing than traditional compounding. FDA issued a Compliance Policy Guide (CPG) to address the issue in 1992 The stated purpose of the CPG was to differentiate between traditional compounders and those engaged in practices more akin to drug manufacturing Confidential and proprietary 7 The 1992 CPG: In fact, the CPG focused on a variety of factors not related to scope or volume, including: Quality of APIs Anticipatory Compounding Implicit Message: All compounded drugs fall under FDA s jurisdiction Compounded drugs are unapproved new drugs and thus technically illegal FDA will regulate through enforcement discretion This position troubled many pharmacists Many argued compounding was regulated by states How could a skill taught in pharmacy school be per se illegal under federal law? Confidential and proprietary 8 503A (Round 1) In 1997, Congress added section 503A to the FDCA Intended to clarify status of compounded drugs under federal law Compounded drugs that met the requirements in 503A were exempt from three key provisions of the FDCA: New drug approval requirements (section 505) Current Good Manufacturing Process (section 501(a)(2)) Adequate Directions for Use (section 502(f)(1)) The 1997 version also prohibited pharmacies from advertising the names of the drugs they compounded 503A verified that compounded drugs fall under FDA jurisdiction but gave them a safe harbor in certain circumstances Confidential and proprietary 9 3

4 Western States In the Western States case, several compounding pharmacies challenged 503A on the grounds that its prohibition on advertising violated the First Amendment. The 9 th Circuit agreed, ruling that the prohibition was unconstitutional and that all of 503A was invalid since the advertising provisions could not be severed from the rest of the section. See 228 F.3d 1090 (9 th Cir. 2001) In 2002, the Supreme Court upheld the First Amendment ruling but did not opine on the question of severability. See 535 U.S. 357 (2002) FDA thus followed the decision of the 9 th Circuit on severability and treated 503A as defunct nationwide Confidential and proprietary Compliance Policy Guide: To fill the void created by Western States, FDA issued a second CPG in May The 2002 CPG closely resembled the 1992 version FDA continued to regulate pharmacy compounding through the exercise of enforcement discretion The CPG listed multiple factors that FDA would consider in determining whether to initiate enforcement action against a compounding pharmacy As in 1992, FDA s stated purpose was to differentiate the line between traditional extemporaneous compounding and practice more akin to large scale drug manufacturing Confidential and proprietary 11 MedCenter Pharm and NECC Following Western States, several pharmacies sued FDA in federal court on the grounds that FDA lacked jurisdiction to regulate compounded drugs In 2005, the 5 th Circuit ruled that compounded drugs are new drugs under FDA s jurisdiction, but concluded also that the 9 th Circuit had incorrectly decided the severability issue on the old 503A. See 536 F.3d 383 (5 th Cir. 2005) This ruling meant that 503A was entirely defunct in the 9 th Circuit, alive in the 5 th Circuit except for the advertising restrictions, and of uncertain status everywhere else. This uncertainty created difficulties for both FDA and pharmacies in the years that followed Congress was called to action, however, by the serious injuries and deaths associated with products compounded and sold by the New England Compounding Center in 2012 Confidential and proprietary 12 4

5 A New Era: the DQSA In 2013 Congress Enacted the Drug Quality Security Act (DQSA) (Pub. L. No (2013) With respect to pharmacy compounding, the DQSA amends/adds two provisions to the FDCA: 503A 503B The new law removes from the old 503A the unconstitutional advertising prohibition, thus clarifying that the new 503A applies nationwide The new law also creates in 503B a category of compounding entity called an outsourcing facility. Confidential and proprietary 14 The DQSA: 503A The new 503A is identical to the old 503A except that the unconstitutional advertising restrictions have been removed As with the old 503A, the new 503A describes the conditions that must be met for drug products compounded by a licensed pharmacist or a licensed physician to be exempt from three key provisions of the FDCA: New drug approval requirements (section 505) Current Good Manufacturing Process (section 501(a)(2)) Adequate Directions for Use (section 502(f)(1)) Confidential and proprietary 15 5

6 503A: Requirements To qualify for the exemptions on the preceding slide, the following conditions must be met: 1. The drug must be compounded for an identified individual patient based on the receipt of a valid prescription order or notation on the order that a compounded product is necessary for the identified patient; 2. The drug must be compounded by a licensed pharmacist or licensed physician on the prescription order for the individual patient, or The drug may be compounded by a licensed pharmacist or licensed physician in limited quantities before the receipt of the valid prescription based on a history of having received valid orders for the compounding of the product where those orders have been generated solely within an established relationship between the compounder and the individual patient or the practitioner who will write the prescriptions Confidential and proprietary A: Bulk Substances 3. The bulk drug substances used to compound the drug must: Comply with the standards of an applicable USP or National Formulary Monograph, if a monograph exists, and the USP chapter on pharmacy compounding Be components of FDA-approved drugs if such a monograph does not exist, or Appear on a list published by FDA if neither of the preceding two conditions are met; 4. The bulk drug substances must be manufactured by an establishment that is registered with FDA; 5. The bulk drug substances must be accompanied by valid certificates of analysis Confidential and proprietary A: Prohibited Drugs 6. The ingredients other than bulk substances used in the compounded drug must meet an applicable USP or Formulary monograph if one exists; 7. The compounded drug cannot appear on a list published by FDA in the Federal Register of drugs that have been withdrawn or removed from the market for safety; 8. The licensed pharmacist or licensed physician cannot compound regularly or in inordinate amounts drug products that are essentially copies of commercially available drug products; and Confidential and proprietary 18 6

7 503A: Additional Prohibitions 9. The compounded drug cannot be one that is included in a final FDA rulemaking on drugs that present demonstrable difficulties for compounding; and 10. A compounder may not distribute compounded drugs out of state in quantities that exceed 5% of the total prescription orders dispensed by that pharmacy or physician unless the state in which the drug is compounded has entered into an MOU with FDA that provides differently. 11.FDA is required to issue regulations to implement 503A and, before doing so, is required to convene an advisory committee to address certain subsections Confidential and proprietary B: Outsourcing Facilities 503B creates the new outsourcing facility An outsourcing facility is one that Is engaged in compounding sterile drugs Has elected to register with FDA as an outsourcing facility; and Complies with the requirements in section 503B As with 503A, 503B describes the conditions that must be met for compounded drug products to be exempt from three key provisions of the FDCA: New drug approval requirements (section 505) Track and Trace Requirements (section 582) Adequate Directions for Use (section 502(f)(1)) Note: GMP exemption in 503A not included here Confidential and proprietary B: Similarities and Differences Outsourcing facilities are compounding specialists that can sell over 5% of their compounds out of state and/or specialize in compounding standardized sterile injectable drug products FDA is supposed to have primary jurisdiction over outsourcing facilities whereas the states will continue to exercise primary jurisdiction over 503A pharmacies There are several key similarities and differences between 503A pharmacies and 503B outsourcing facilities Confidential and proprietary 21 7

8 503A and 503B: Similarities Outsourcing facilities are subject to several of the same requirements as 503A pharmacies: Both are prohibited from compounding products that are essentially copies of FDA-approved drugs Both are subject to FDA s rulemaking on drugs that present demonstrable difficulties for compounding Both are subject to limitations on the use of bulk substances, including requirements related to compliance with an applicable UPS or National Formulary monograph, registration by bulk suppliers, and valid certificates of analysis Confidential and proprietary A and 503B: Differences There are, however, significant differences between 503A and 503B: The only bulk drugs an outsourcing facility can use are those identified on a list published by FDA or substances on FDA s drug shortage list Outsourcing facilities are not exempted from GMP requirements Outsourcing facilities must register with FDA Outsourcing facilities must comply with specific labeling requirements, including disclosure statements Outsourcing facilities must pay user fees to FDA Confidential and proprietary A and 503B: Differences Differences (continued): Outsourcing facilities must report adverse event Outsourcing facilities need not be licensed pharmacies, but compounding must be supervised by a licensed pharmacist Outsourcing facilities may or may not obtain prescriptions for identified patients - Allows for sale of office stock - Outsourcing facilities may compound a drug that is subject to a REMS with elements to assure safe use, but only if they can demonstrate use of controls comparable to the REMS - There is no limit on the volume of compounded product that outsourcing facilities may sell interstate Confidential and proprietary 24 8

9 FDA Implementation FDA has been implementing the new sections since enactment: Final Guidance on whether to register as an outsourcing facility Draft guidance for repackagers of human drugs and biologics FDA has held a number of public meeting on compounding by outsourcing facilities, including bulk drug substances Draft MOU to states Final guidance Adverse event reporting Confidential and proprietary 25 Recent Enforcement FDA has sent several Warning Letters since enactment Emphasis on contaminated products and health threats Other common citations: Insanitary conditions GMP violations (503Bs) Use of bulk substances not authorized under 503A Failure to tie compounded drugs to prescriptions FDA has not been as active in enforcing commercial copy language as it had pre-western States. This may signal FDA intends to clarify standard Confidential and proprietary 26 What is Next? There are a number of issues to watch for: Can 503B pharmacies compound for office stock? Will FDA modify GMP requirements for 503Bs? How will FDA interpret the definition of essentially a copy of a commercially available drug? What drugs (or categories of drugs) will be deemed demonstrably difficult to compound? What types of bulks will FDA authorize 503Bs to use? Who is liable for injuries associated with compounded drugs? States attempt to cope with new category of facility (outsourcing facilities) by creating licensing categories and specific statutes/regulations, but most haven t quite figured it out yet. Will FDA address anticipatory compounding? Follow-up action to FDA outsourcing facility inspections and Form-483s Confidential and proprietary 27 9

10 Questions? Optimizing patient health through a relentless devotion to clinical excellence. 10