Practice of Medicine or Drug Biologic Product—Regenerative Sciences, LLC

“Practice of Medicine” or FDA Authority to Regulate

The Food and Drug Administration and the Authority to Regulate

Regenerative Sciences, LLC vigorously defended its position that FDA could not regulate the practice of medicine in its Regenexx™ treatment or Regenexx-C™ cultured treatment which uses Mesenchymal adult stem cells (MSCs) that originate primarily from bone marrow. The company promotes the Regenexx™ treatment as a “non-surgical” treatment option for joint or bone pain in the hip, knee, shoulder, back or ankle as well as non-union fractures. The dispute with FDA has been ongoing since at least 2008 when FDA sent correspondence to Regenerative Sciences depicting the cell treatment as a drug or biologic. FDA conducted an inspection and found violations of current Good Manufacturing Practices (cGMPs). The United States Court of Appeals for the District of Columbia Circuit upheld the District Court and the United States Food and Drug Administration’s (FDA’s) argument that Regenerative Sciences “Cultured Regenexx Procedure” was a biological drug subject to FDA approval through the biologics licensing application (BLA) process. The court of appeals upheld the permanent injunction against the use of the biological drug without FDA approval. The issue focused on the practice of medicine versus the regulation by the United States Food and Drug Administration. This distinction has far reaching ramifications.

Issue the Court of Appeals Addressed

In the civil enforcement action, the court of appeals had to decide “whether the appellants—three individuals and a related corporate entity—violated federal laws regulating the manufacture and labeling of drugs and biological products by producing, as part of their medical practice, a substance consisting of a mixture of a patient’s stem cells and the antibiotic doxycycline.” The court of appeals determined that FDA had the authority to regulate the product and affirmed the district court’s judgment and the permanent injunction it entered against appellants.

What Regenerative Sciences, LLC Argued

Regenerative Sciences, LLC (Regenerative Sciences) alleged several arguments that their product did not fall within FDA regulatory authority; however, the court rejected all of the arguments. For example, Regenerative argued that the Federal Food, Drug, and Cosmetic Act (FDCA) did not apply because the product was a procedure overseen by state “practice of medicine”. Another argument advanced by Regenerative Sciences was that the product was exempt from FDA approval because it was a compounded product and further it was a minimally manipulated product. As mentioned, the court of appeals rejected all of the arguments advanced by Regenerative Sciences.

Looking Ahead

This was a long awaited decision. The future is uncertain in terms of how a court will rule about novel therapies such as the issue in this case. However, no doubt as more technological advances occur, FDA will again be challenged as to the agency’s authority to regulate such products and or procedures.The link to the full case is as follows:

USA v Regenerative Sciences

Top 5 Highlights of FDA Accomplishments in 2013—Snapshot Year in Review: Why the United States Needs a Food and Drug Administration.

Does the United States Needs a Food and Drug Administration? Year in Review—Top 5 Highlights of FDA Accomplishments in 2013

Does the United States even need a Food and Drug Administration (FDA)? The role and mission of FDA has been debated for years. The FDA role ranges from that of a regulator, watchdog and facilitator. Commentary ranges from overbearing federal regulation to lack of public protection. Yet, based on these selected accomplishments, FDA provides an important function in keeping with the mission of the Food, Drug and Cosmetic Act and the numerous amendments. Although the FDA has across the board accomplishments, the following are standouts and all involve safety—Food Safety Modernization, Drug Quality and Security, Tobacco Products, Antibiotic-Antimicrobials Use in Food Producing Animals and Dietary Supplement Enforcement.

DRUG SAFETY—DRUG QUALITY and SECURITY ACT

This necessary and milestone legislation (H.R. 3204) enacted towards the end of 2013, addresses federal regulatory authority over pharmacy compounding. Unfortunately, this legislation was enacted in response to the unnecessary deaths associated with large scale compounding. Additionally, this law contains “track and trace” provisions throughout the drug supply chain.

DIETARY SUPPLEMENT OVERSIGHT

Dimethylamylamine DMAA—Muscle Building and Performance Enhancement

Dimethylamylamine commonly known as (DMAA) provides an excellent illustration example of issues related to post-market enforcement. DMAA, a stimulant is used in supplements, promotes weight loss, muscle building and performance enhancement. DMAA, a stimulant is used in supplements, promotes weight loss, muscle building and performance enhancement. According to FDA, medical issues associated with DMAA include elevated blood pressure, potential cardiovascular problems such as heart attack, shortness of breath and tightening of the chest.

The following link contains the FDA warning letters. http://www.fda.gov/Food/DietarySupplements/QADietarySupplements/ucm346576.htm

The following link contains the response letter from FDA to USPlabs. http://1.usa.gov/1lcJC77

ANTIMICROBIAL RESISTENCE

At the end of 2013, FDA issued a guidance and proposed rule about a phase out of antimicrobial drugs in food animals for food production purposes. According to FDA, the agency issued voluntary guidance that promotes the judicious use of antibiotics in food animal production is preferable because of resource limitations; that is, according to FDA, the agency would use fewer resources compared to withdrawing the animal drugs on an individual basis

VETERINARY ACTION—ANTIMICROBIAL VOLUNTARY PHASE OUT

Final Guidance and Proposed Rulemaking Rx Status

http://1.usa.gov/1bHsi92

TOBACCO PRODUCTS REGULATION

Tobacco Product Marketing Orders

http://1.usa.gov/1kCu7aV

Tobacco products are regulated so differently than other FDA regulated products due to the fact they are: harmful yet still extensively used consumer products; and responsible for severe health problems in both users and non-users, including cancer, lung disease, and heart disease, which often lead to death. A company who desires to market a new tobacco product has the following options available.

There were 17 SE orders, 13, NSE orders and 162 Report Withdrawals from pre-June 2013-December. http://www.fda.gov/TobaccoProducts/Labeling/MarketingandAdvertising/ucm339928.htm

MODERNIZING FOOD SAFETY

Did you know that much of the food that Americans consume originate from countries outside of the United States? The Food Safety Modernization Act (FSMA), signed into law back in January 2011, addresses imported food as well as food produced in the United States. Major accomplishments include a final rule and five proposed rules.

Final Rule Administrative Detention of Food   Criteria Used to Order Administrative Detention of Food for Human or Animal Consumption which amended the criteria for administrative detention to prevent potentially unsafe food from reaching the marketplace. A guidance was issued as well titled: Guidance For Industry on Administrative Detention  was issued on March 7, 2013 FDA released revised guidance on administrative detention entitled “Guidance for Industry: What You Need to Know About Administrative Detention of Foods; Small Entity Compliance Guide.”

5 Proposed Food Safety Rules: Preventive Controls; Produce Safety; Foreign Supplier Verification, Third Party Accreditation and Intentional Adulteration Mitigation Strategies.

1. Proposed Rule: Preventive Controls for Human Food — The proposed rule issued January 2013 would implement the requirements of FSMA for covered facilities to establish and implement a food safety system that includes a hazard analysis and risk-based preventive controls.

http://www.regulations.gov/#!documentDetail;D=FDA-2011-N-0920-0001

2. Proposed Rule: Produce Safety— The proposed rule would establish science-based minimum standards for the safe growing, harvesting, packing, and holding of produce on farms. http://www.regulations.gov/#!documentDetail;D=FDA-2011-N-0921-0001

3. Proposed Rule: Foreign Supplier Verification Programs (FSVP) for Importers of Food for Humans and Animals— On July 26, 2013, FDA issued proposed regulations that would greatly strengthen the oversight of foods imported for U.S. consumers. http://1.usa.gov/1jEeD8l

4. Proposed Rule: Third Party Accreditation of Auditors or “Certification Bodies”— On July 26, 2013, the FDA published for public comment its proposed rule to establish a program for accreditation of third-party auditors, also known as certification bodies, to conduct food safety audits and issue certifications of foreign facilities and the foods for humans and animals they produce.

http://www.fda.gov/Food/GuidanceRegulation/FSMA/ucm361903.htm

5. Focused Mitigation Strategies to Protect Food Against Intentional Adulteration

This proposed rule would require the food businesses in the United States and abroad to take measures to prevent facilities from being the target of intentional attempts to contaminate the food supply. http://1.usa.gov/1fVCv2p

RECOMMENDATIONS

Despite the federal government shutdown, FDA did have major accomplishments as the above examples illustrate. They illustrate the necessity for “an FDA”. Hopefully though the proposed rules will be finalized shortly and hopefully Congress will revisit FDA regulatory authority for some products such as dietary supplements where FDA can only legally exercise post-enforcement. Stay tuned for more about the role of FDA and for more food and drug law updates in 2014.

The What and Why of Pharmacy Compounding

What is Pharmacy Compounding?

Pharmacy compounding usually involves a small quantity of custom made prescriptions. However, this has changed over the years to what some term large scale production. By way of illustration, in the later part of 2012, the United States Food and Drug Administration (FDA) was forced to confront the issue of pharmacy compounding on a large scale. This was due to several deaths associated with compounded drug products linked to fungal meningitis that involved the New England Compounding Center (NECC). FDA Commissioner Margaret Hamburg testified before Congress and specifically recommended that Congress enact legislation to provide authority FDA with enforcement authority. The NECC distributed contaminated pain injections that caused serious adverse events including approximately 32 deaths.

Why did this happen?

Well back in 2002, an FDA inspection revealed a contamination issue with the same steroid; however, FDA had to defer to Massachusetts state authorities. Traditionally, with pharmacy compounding, state pharmacy boards maintain regulatory oversight. Further, as mentioned, traditionally compounding pharmacies fill special orders from physicians for an individual patient. Yet, over the years, this has changed dramatically from a small to large-scale operation and NECC is an illustration of where thousands of doses of drugs were shipped to several states.

What are the FDA Solutions?

Commissioner Hamburg proposed a two-tier system in which traditional compounding pharmacies continue to be regulated at the state level, and larger pharmacies would be subject to FDA oversight. According to Dr. Hamburg, these non-traditional pharmacies that operate on large-scale compounding would have to register with the FDA as well as undergo regular inspections. Further, these large-scale compounding pharmacies would be obligated to meet the more rigorous manufacturing standards required of pharmaceutical companies.
Previously, FDA attempts to regulate large scale operations have been stymied; however, that should change. For example, Ameridose LLC, managed by the same parties who managed NECC, voluntarily recalled all of its unexpired products in 2012 due to FDA sterility assurance concerns. The recall was conducted for preventive measures not because of reports of adverse events such as infections.

As background, when the United States Supreme Court decision of Thompson v. Western States, was decided back in 2002, FDA then clarified that the agency would continue to use enforcement action against those who compounded drugs that are actually attempts to illegally manufacture drugs. FDA released a Compliance Policy Guide (CPG) section 460.200 [Pharmacy Compounding] issued by FDA on May 29, 2002, following the Thompson Supreme Court decision. The CPG sets forth a list of factors that FDA considers in determining whether to take enforcement action when the scope and nature of a pharmacy’s activities raise the kind of concerns ordinarily associated with drug manufacturing. For example, FDA would consider enforcement action against pharmacists who compound medications that are commercially available in the marketplace or those that use bulk ingredients that are not components of FDA approved drugs or those pharmacists who use commercial scale manufacturing or testing equipment.

Recommendations

Here is what I propose. The tier proposal is a good start. Yet, what really needs to happen is communication on all levels. By that I mean communication with state and federal government agencies as well as communication between industry and the FDA as well as state pharmacies. Finally, the nature of pharmacy compounding has markedly changed from small to large scale manufacture. So, the time is ripe for Congress to address this issue legislatively.

Stay tuned for more on pharmacy compounding specific to veterinary products.