The History of the Legal And Regulatory Issues Surrounding Pharmacy Compounding

Transcription

1 The History of the Legal And Regulatory Issues Surrounding Pharmacy Compounding T.C. Spencer Pryor Partner, Alston & Bird LLP FDA & CDC: Collaboration & Challenges FSMA, Food Outbreaks, Pharmacy Compounding & Emerging Health Issues January 29, 2014 Emory University

2 Overview of Presentation The history of drug compounding. Regulation of drug compounding prior to the FDAMA. The new regulatory scheme post-fdama. The Supreme Court s decision in Western States Medical Center v. Thompson. The post-western States Circuit split and resulting regulatory confusion. Regulatory confusion leads to adverse events, such as the 2012 meningitis outbreak. Call to reform.

3 Origins of Use Medicinal practice that dates back to ancient times. Compounding was central to the medicines of the Ancient Egyptians, the cultures of Mesopotamia, Ancient Greece and Ancient Rome. The Papyrus Ebers, dating to 1500 B.C., is an Egyptian collection of nearly 800 prescriptions, many devised through compounding.

4 Advent in the United States Began widespread usage in the 1800s. As many as 80% all prescriptions were made using compounding up until the 1920s. Modern pharmaceutical manufacturing diminished the practice beginning in the 1950s and 1960s. The practice of compounding would drop to a low of less than 1% in the 1970s.

5 Modern Use Within the U.S. The trend toward natural and homeopathic medicines revitalized the industry in the 1990s. Now one of the fastest growing practices within the pharmaceutical industry. It is estimated that 1% to 10% of all prescriptions are compounded but producing and filling those prescriptions falls on a proportionally smaller number of pharmacists and pharmacies.

6 The Benefits of Drug Compounding Compounding can provide drugs that are: Tailored to the needs of the individual patient (e.g. a drug that a patient would not normally be able to take due to allergies, is now available to that patient through compounding). Useful but not commercially available due to FDA regulation, discontinuation or commercial shortages. Cheaper, at times, than commercial drugs. Easier to use. (e.g. flavoring a medication that a child would normally refuse.)

7 Potential Risk of Compounding Compounding poses many different risks: Not required to prove safety of drug through FDA New Drug Application. Between , at least 200 adverse events involving 71 compounded medicines. Many more have likely occurred but adverse events are rarely reported because there is no reporting requirement. Common issues include: Subpotency Superpotency Contamination Overmedication Medication Replacement

8 Regulatory Structure Regulation of drug compounding split between State and Federal regulation State: Boards of Pharmacy Federal: Food and Drug Administration ( FDA) At the Federal level, the Federal Food, Drug and Cosmetic Act ( FDCA ) is the operative regulatory statute, which was passed in The amendments relevant to drug compounding are: The Food And Drug Administration Modernization Act of 1997 The Drug Quality and Security Act of 2013

9 State Regulatory Structure States are the primary and front-line regulator of pharmacies, including their compounding practices. Usually a state Board of Pharmacy provides licensure that requires actions such as: secure storage, recordkeeping, forms of pads used for prescriptions, labeling, training of pharmacists and safety protocol to ensure the product s integrity. Increased ability to ship drugs from state-tostate, reduces the ability to control standards at the state level, arguably increasing the need for a federal structure.

10 Federal Regulatory Structure Compounded drugs do not go through the FDA New Drug Approval process. Generally, federal regulators defer to the state boards of pharmacy as long as the compounding pharmacies adhere to FDCA 503A and 503B. Outsourcing pharmacies are regulated by the FDA under FDCA 503B and can be subject to inspection. Those pharmacies are subject to the Current Good Manufacturing Practices ( cgmp) standards.

11 Food and Drug Administration Modernization Act Passed in 1997, the FDAMA exempted compounded drugs from FDCA requirements provided that they: 1. Are compounded for an individual patient or in quantities that anticipate certain types of orders; 2. Are made from approved ingredients; 3. Do not duplicate a drug previously removed from the market due to safety or effectiveness concerns; 4. Do not duplicate commercially available products; 5. Are not on FDA list of products demonstrating compounding difficulties; 6. Are not distributing compounded drugs out of state in quantities exceeding 5% of prescription orders; 7. Are not soliciting or advertising the compounded drugs.

12 Supreme Court Overturns 503A In the culmination of multiple legal challenges, the Supreme Court overturned portions of 503A on First Amendment grounds for being overly restrictive of free speech in Thompson v. Western States Medical Center. Specifically, the Court overturned the restriction on advertising and promotion of compounded drugs. It did not, however, rule on the severability of the unconstitutional provision from the rest of 503A, leading to confusion among the Circuits.

13 Circuit Split on the Continued Validity of 503A Ninth Circuit, the opinion out of which Western States arose, argued 503A was not severable. The FDA agreed with the Ninth Circuit, arguing that they considered 503A to be invalidated, and then reissued Compliance Policy Guide Pharmacy Compounding - to stand in its place. Confusion began with Medical Center Pharmacy v. Mukasey, when the Fifth Circuit ruled that the unconstitutional provision was severable. Also ruled that compounded drugs are exempted from new drug protocol as long as they comply with 503A

14 Regulatory Confusion The Fifth and Ninth Circuits created dueling regulatory schemes: 5 th Circuit: 503A is valid but for the restrictions on advertising. Compounded drugs are provided a narrow exception from having to follow the FDA new drug approval protocol. 9 th Circuit: 503A is completely overturned, and the FDA must regulate within a pre-fdama structure.

15 Regulatory Confusion (Cont.) As demonstrated by by CPG , FDA preferred the Ninth Circuit s regulatory scheme so the FDA followed the Fifth Circuit only in the states within the Fifth Circuit, operating under two different regulatory schemes. Widespread confusion over whether the FDA or states were the primary regulator. The confused regulatory scheme of the FDA, even prior to Mukasey, led to lackadaisical inspection and oversight over pharmacies the federal and state roles were unclear.

16 Meningitis Outbreak In September 2012, there was a widespread outbreak of fungal meningitis associated with compounded drugs manufactured by the New England Compounding Center. Outbreak led to 751 cases of meningitis resulting in 64 deaths and continuing complications. The compounded drug traced to the outbreak violated requirements under both 503A and FDA CPG, but no oversight was exercised due to the fragmented roles of the federal and state regulators.

17 Clamor for Reform Different constituencies began to call for reform that would provide a clear system of oversight. Pharmacists, such as the National Community Pharmacists Association, in support of drug compounding, even welcomed reform calling for legislation that: addresses the issues that led to the NECC tragedy, protects the physician-patient-pharmacist relationship, maintains critical patient access to compounded medications, and strengthens the pharmaceutical supply chain.

18 Congressional Reform The meningitis outbreak forced Congress hand to reform the regulation of compounded drugs to ensure better oversight. As Janet Woodcock, Director of the FDA s Center for Drug Evaluation Research testified before the House of Representative on July 16, 2013, the existing structure of regulatory ambiguity would continue to bring about adverse events unless a clear system was put in place.

19 Drug Quality and Security Act ( DQSA ) Signed into law on November 27, 2013, the Act seeks to clarify confusion regarding regulation of drug compounding. The requirements of 503A, but for the unconstitutional provision, are implemented for certain compounded drugs. In addition, 503B is added, which allows compounders not covered under 503A to become outsourcing facilities. Such a compounder may register with the FDA to become an outsourcing facility. Once registered, they are exempt from FDA approval requirements as long as they comply with compounding requirements.

20 Contact Information T. C. Spencer Pryor Partner Alston & Bird LLP (w) (fax)