Over the past ten years, Butler Snow has stood alongside so many of you – our clients – as key FDA initiatives have been proposed and implemented. These efforts bring to mind the familiar phrase, “time flies when you’re having fun.” We’re not sure it would be fair (or accurate!) to characterize our collaborative work on FDA programs as “fun,” but we are honored to have been your legal counsel navigating the ins and outs of many FDA programs that impact the pharmaceutical industry. We hope you enjoy this “retrospective” piece, knowing that Pro Te: Solutio has been covering many of these topics along the way.
It’s been almost 80 years since passage of the Federal Food, Drug, and Cosmetic Act of 1938, which authorized the FDA to demand evidence of safety and effectiveness for new drugs, issue standards for food safety, and conduct factory inspections. Since that time, the FDA has grown into a comprehensive federal agency, regulating $1 trillion worth of products anually, from animal drugs and feed to human drugs and medical devices.
There can be no question that the FDA’s actions impact the consuming public – and necessarily the pharmaceutical industry – in myriad ways. What follows is a snapshot of ten initiatives over the past ten years that have had (or are having) a major impact in the world of drugs and devices. We start with laws signed in 2007 and move forward in time to fairly recent Congressional and FDA activity with a brief look at FDA’s priorities in the year to come.
1. 2007: Food and Drug Administration Amendments Act of 2007
President George W. Bush signed the Food and Drug Administration Amendments Act of 2007 (FDAAA) on September 27, 2007. The many aspects of this law included reauthorization and expansion of the Prescription Drug User Fee Act and the Medical Device User Fee and Modernization Act, which significantly raised the annual user fees paid by the industry to the FDA for new drug reviews. The amendments also reauthorized the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act, both directed at research and development of treatments for children. The law further contained amendments to the citizen petition process intended to prevent delay in the approval of pending ANDAs and 505(b)(2) applications.
One of the (many) parts of the 2007 amendments that impacted the pharmaceutical industry was the significant increase in the FDA’s responsibilities, requirements, authority, and resources regarding pre- and post-market drug safety. Together with a doubling of resources allocated to the FDA’s Office of Drug Safety, the amendments added to the FDA’s authority to require post-market studies and clinical trials, safety labeling changes, and Risk Evaluation and Mitigation Strategies (REMS). This included the addition of the FDA’s authority to require application holders to conduct post-marketing studies and clinical trials “to assess a known serious risk, assess signals of serious risk, or identify an unexpected serious risk related to the use of a drug product . . . . ” According to the FDA, as of fiscal year 2015, a total of 88 percent of post-marketing requirements overall and 89 percent of FDAAA post-marketing requirements were progressing according to their original schedules.
Not to be overlooked, the amendments in 2007 require the FDA to establish a database of post-marketing adverse drug reactions; more on that, below.
2. 2008: FDA’s Sentinel Initiative
In May 2008, the FDA launched its Sentinel Initiative in response to requirements of the FDAAA that the FDA work with public and private entities to coordinate a system for providing access to existing electronic healthcare information from across multiple sources. The FDA would then use this information to help monitor safety of regulated products and take actions such as issuing safety communications or warnings. After a pilot program (“Mini-Sentinel”), the Sentinel System officially launched in 2016.
For a look back at the impact of this program – including a discussion about how, in litigation, plaintiffs’ firms try to argue that pharmaceutical companies failed to timely report a key safety signal – we invite you to view the coverage of the Sentinel Initiative in the June 2014 issue of Pro Te: Solutio.
3. 2010: Patient Protection and Affordable Care Act/Healthcare and Education Reconciliation Act
The Patient Protection Affordable Care Act was a landmark piece of legislation affecting all levels of the healthcare industry. Passed in March 2010 along with the Healthcare and Education Reconciliation Act, the legislation changed the face of healthcare in the United States by, inter alia, imposing a regulatory overhaul and greatly expanding healthcare coverage to Americans.
With respect to the FDA in particular, the Affordable Care Act provided that manufactures and distributors must provide the FDA with specific information concerning drug samples that they distribute, including: (1) the identity and quantity of drug samples requested; (2) the identity and quantity of drug samples distributed; (3) the name, address, professional designation, and signature of any person who makes or signs such a request; and (4) any other category of information determined appropriate by the Secretary. The FDA has also issued a Draft Guidance explaining how these provisions work in conjunction with the existing provisions of the Prescription Drug Marketing Act.
Pro Te: Solutio devoted its February 2011 issue to this legislation, and tackled topics including how healthcare reform would affect tax and employee benefits; how governmental enforcement actions of fraud in the healthcare industry were ramping up; and how legal challenges to the Acts were shaping up. To fast-forward to today, the political landscape has changed in Washington, D.C., and, as with any change in administration, the priorities and laws themselves will change. Stay tuned to Butler Snow communications for coverage on developing aspects of this part of the healthcare and pharmaceutical industry.
4. 2012: Food and Drug Administration Safety and Innovation Act
The Food and Drug Administrative Safety and Innovation Act (FDASIA) was signed into law by President Obama in July of 2012. FDASIA consisted of 11 titles. The first five affected pediatric therapy development and drug and medical device user fees, establishing new fee statutes for generics and biosimilars. The next two titles concerned changes to medical device regulation and the FDA’s inspection authority and global drug supply chain safety. Title VIII created incentives for the development of products to treat antibiotic-resistant infections. Title IX created a “breakthrough therapy” designation intended to expedite development and review of such drugs and expanded the number of products subject to accelerated approval. Title X created new authority for the FDA to address drug shortages, and Title XI reauthorized provisions of the FDA Amendments Act of 2007, regulated medical gases, and included myriad other provisions such as a 180-day generic drug marketing exclusivity, additional regulations on citizen petitions, and nanotechnology provisions.
FDASIA’s user fee provisions are incredibly important to the FDA, as user fees have played an increasingly vital part of the agency’s budget. In 2017, user fees accounted for more than 40 percent of the FDA’s overall budget.
5. 2012: Medical Device User Fee and Modernization Act
The Medical Device User Fee and Modernization Act (MDUFMA III) was enacted in 2012 as part of FDASIA. User fees have been established and implemented in four parts. The Medical Device User Fee and Modernization Act (MDUFMA) first created device user fees in 2002. They were renewed in 2007 with MDUFMA II, again in 2012 with MDUFMA III, and finally in 2017 with MDUFMA IV. MDUFMA IV will be in effect from October 1, 2017, through September 30, 2022. These provisions authorize the FDA to collect fees from medical device companies at various stages in the regulatory process – for example, when they register their establishments, when they list their devices, when they submit applications or notifications to market new medical devices in the United States, and for other types of submissions.
The FDA issues annual performance reports to Congress under MDUFMA on its progress in the timely completion of application reviews and other items.
6. 2013: Pandemic and All-Hazards Preparedness Reauthorization Act
Enacted in 2013, the Pandemic and All-Hazards Preparedness Reauthorization Act (PAHPRA) establishes programs permitting the FDA to prepare for and respond to emergency situations, including chemical, biological, radiological, or nuclear crises, but also infectious diseases. PAHPRA reflects an amendment to the existing Emergency Use Authorization already granted the FDA.
Examples of acts permitted by PAHPRA are the authorization of emergency dispensation of products, extended expiration dating of products, and waiver of Current Good Manufacturing Practice and Risk Evaluation and Mitigation Strategies requirements.
7. 2013: Drug Quality and Security Act
Prompted by a fungal meningitis outbreak and covered in the November 2012 issue of Pro Te: Solutio, Congress enacted the Drug Quality and Security Act (DQSA) in 2013 to enhance the FDA’s ability to help protect consumers from exposure to counterfeit, stolen, contaminated, or otherwise harmful drugs.
The Act implemented greater regulatory oversight of drug compounding facilities. It also outlined steps for an electronic system to identify and trace certain prescription drugs throughout the United States to improve detection and removal of potentially dangerous drugs from the drug supply chain. Further, DQSA directed FDA to establish national licensure standards and reporting obligations for wholesale distributors and third-party logistics providers.
8. 2016: 21st Century Cures Act
One of the more recent initiatives – the 21st Century Cures Act (Cures Act), enacted on December 13, 2016 – seeks to accelerate medical product development, thereby bringing new innovations to patients faster and more efficiently. Among the Act’s objectives are to incorporate patient perspectives into the development and approval of pharmaceutical products; modernize clinical trial designs and clinical outcome assessments to speed development and review of novel medical products; coordinate activities in major disease areas between the drug, biologics, and device centers; improve the regulation of combination products; and provide FDA with authority to recruit and retain scientific, technical, and professional experts. Among others, new product development programs include:
- The Regenerative Medicine Advanced Therapy, which offers a new expedited option for certain eligible biologics products
- The Breakthrough Devices program, designed to speed review of certain innovative medical devices
In addition, the 21st Century Cures Act clarified FDA’s regulation of medical software; it also amended the definition of a “device” to exclude certain software functions.
To date, items completed on the Act’s “deliverables” list include issuance of Guidances and Draft Guidances, submission of Federal Register notices, submission of a work plan and funding allocation to Congress, and presentation of a meeting by NIH in August 2017 of the Task Force on research specific to pregnant and lactating women.
Pro Te: Solutio has worked diligently to cover this Act, with articles in Fall 2016 and Spring 2017 addressing everything from an overview of the Act to new clinical research tools.
9. 2017: Medical Device Reporting
This item is not about something the FDA has done, but about what it hasn’t done. In 2007, Congress amended 21 U.S.C. § 360i(a) to ease the burden of medical device reporting for manufacturers and other reporters for Class I and Class II medical devices. Specifically, rather than providing individual medical device reports within 30 days of each qualifying event, reporters would be permitted to file summary quarterly reports of medical device reports to the FDA. (Congress also gave the FDA authority to create exceptions for certain devices that would have to continue the usual 30-day reports.) But for unexplained reasons, more than a decade later, the FDA still has not implemented the statute.
In December 2017, the FDA announced a “proposed program for manufacturer reporting of certain device malfunction medical device reports (MDRs) in summary form.” This followed the FDA’s “Pilot Program for Medical Device Reporting on Malfunctions,” announced in 2015, which studied summary medical device reporting. Under the proposed program, reporters for certain products would be permitted to voluntarily opt-in to summary reporting. Though this may ease the reporting burden for some products, it does not reach the scope contemplated by Congress in 21 U.S.C. § 360i(a).
10. Ongoing: Significant Enforcement Actions
A look back at FDA initiatives over the past decade would not be complete without mention of the FDA’s efforts — conducted in conjunction with the Department of Health and Human Services and the Office of Inspector General – to investigate and prosecute fraud in the healthcare industry, including the pharmaceutical industry. Pro Te: Solutio has reported throughout the years on many different efforts by federal agencies under their respective jurisdictional domains, ranging from articles on Warning Letters, Whistleblower Actions, Healthcare Fraud, and the “Park Doctrine” involving prosecution of corporate executives, just to name a few. You can be sure we’ll cover developing trends in this important area of healthcare, moving forward.
WHAT LIES AHEAD?
We don’t have a crystal ball, and we cannot predict what lies ahead for the pharmaceutical industry or the FDA. But as a sneak peek, consider recent statements of FDA Commissioner, Scott Gottlieb, M.D., identifying these priorities for the FDA for 2018 :
- Addressing the Nicotine Addiction Crisis (e.g., proposed rulemaking regarding regulation of tobacco flavors and “premium cigars”)
- Advancing drug safety (e.g., issuance of regulations on drug compounding facilities, national standards for licensing of prescription drug wholesale distributors and third-party logistic providers: “track-and-trace” requirements)
- Promoting food safety
- Empowering consumers (e.g., new proposed patient medication document for drugs or biologics each time a patient receives a medication from the pharmacy and broadening access to non-prescription drugs)
- Modernizing standards (e.g., harmonizing global standards, modernizing mammography standards, and embracing electronic submissions)
- “Looking to the future” (e.g., reducing drug cost by encouraging competition, spurring innovation, creating regulatory efficiencies in bringing products to market, and addressing the opioid addiction crisis)
Butler Snow cherishes the
work we’ve done with clients on initiatives over the past ten years, and we
hope that this trip down memory lane together – with the articles we’ve shared
via Pro Te: Solutio reminds you of all that has flown by over the last decade.
We welcome the challenges yet to come, and we will be right there with you as
new issues arise. We look forward to the next decade and beyond.
 https://www.fda.gov/RegulatoryInformation/LawsEnforcedbyFDA/default.htm (last visited Jan. 5, 2018).
 https://www.fda.gov/RegulatoryInformation/LawsEnforcedbyFDA/default.htm (last visited Jan. 5, 2018).
 https://www.fda.gov/RegulatoryInformation/LawsEnforcedbyFDA/SignificantAmendmentstotheFDCAct/FoodandDrugAdministrationAmendmentsActof2007/default.htm (last visited Jan. 5, 2018).
 Report on the Performance of Drug and Biologics Firms in Conducting Postmarketing Requirements and Commitments; availability, FDA (Nov. 28, 2016), available at https://www.federalregister.gov/documents/2016/11/28/2016-28442/report-on-the-performance-of-drug-and-biologics-firms-inconducting-postmarketing-requirements-and (last visited Jan. 19, 2018).
 FDA Oversight of Postmarketing Studies, N. Engl. J. Med. 2017; 377:1201-1202 (Sept. 21, 2017), available at http://www.nejm.org/doi/full/10.1056/NEJMc1709185 (last visited Jan. 19, 2018).
 https://www.sentinelinitiative.org/ (last visited Jan. 5, 2018). See also The Sentinel Initiative: National Strategy for Monitoring Medical Product Safety, FDA (May 2008), available at https://www.fda.gov/downloads/Safety/FDAsSentinelInitiative/UCM124701.pdf (last visited Jan. 19, 2018).
 Jordan N. Walker, “There is an App for That: Adverse Event Reports and the Sentinel Initiative,” Pro Te: Solutio, Vol. 7. No. 2 (June 2014), available at https://3epjwm3sm3iv250i67219jho-wpengine.netdnassl.com/wp-content/uploads/2014/09/Pro-Te-Solutio-Vol-7-No-22.pdf (last visited Jan. 25, 2018).
 https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/ucm292040.htm (last visited Jan. 9, 2018).
 https://www.federalregister.gov/documents/2014/07/11/2014-16238/draft-guidance-for-industryon-reporting-drug-sample-information-under-section-6004-of-the (last visited Jan. 9, 2018).
 Pro Te: Solutio, Vol. 4 No. 1 (Feb. 2011), available at https://3epjwm3sm3iv250i67219jho-wpengine.netdna-ssl.com/wp-content/uploads/2014/08/Pro-Te-Solutio-February-2011.pdf (last visited Jan. 26, 2018).
 https://www.fda.gov/RegulatoryInformation/LawsEnforcedbyFDA/SignificantAmendmentstotheFDCAct/FDASIA/default.htm (last visited Jan. 6, 2018).
 https://www.fda.gov/AboutFDA/Transparency/track/ucm328907.htm (last visited Jan. 6, 2018).
 https://www.hhs.gov/about/budget/fy2017/budget-in-brief/fda/index.html (last visited Jan. 6, 2018).
 https://www.fda.gov/AboutFDA/ReportsManualsForms/Reports/UserFeeReports/PerformanceReports/ucm2007450.htm (last visited Jan. 5, 2018).
 https://www.fda.gov/emergencypreparedness/counterterrorism/medicalcountermeasures/mcmlegalregulatoryandpolicyframework/ucm359581.htm (last visited Jan. 6, 2018).
 “Will Compounding Pharmacies be Hit with Compounding Regulation in the Wake of Meningitis Outbreak?,” Jim Beakes, Pro Te: Solutio, Vol. 5 No. 4 (Nov. 2012), available at https://www.butlersnow.com/2012/11/pro-te-solutio-november-2012-issue/ (last visited Jan. 8, 2018).
 https://www.fda.gov/Drugs/DrugSafety/DrugIntegrityandSupplyChainSecurity/DrugSupplyChainSecurityAct/default.htm (last visited Jan. 5, 2018).
 https://www.fda.gov/MedicalDevices/DigitalHealth/default.htm (last visited Jan. 5, 2018).
 https://www.fda.gov/RegulatoryInformation/LawsEnforcedbyFDA/SignificantAmendmentstotheFDCAct/21stCenturyCuresAct/ucm562475.htm (last visited Jan. 5,2018).
 Kimberly S. Coggin, “The 21st Century Cures Act,” Pro Te: Solutio, Vol. 9 No. 3 (Fall 2016), available at https://3epjwm3sm3iv250i67219jho-wpengine.netdna-ssl.com/wp-content/uploads/2017/03/The-21st-Century-Cures-Act-%E2%80%93-Pro-Te-Fall-2016.pdf (last visited Jan. 25, 2018); Kimberly S. Coggin, “Introduction To The Cures Act,” Pro Te: Solutio, Vol. 10 No. 2 (Spring 2017), available at https://3epjwm3sm3iv250i67219jho-wpengine.netdna-ssl.com/wp-content/uploads/2017/07/Introduction-To-The-Cures-Act.pdf (last visited Jan. 25, 2018); Hollie A. Smith, “Health Information Technology (HIT) Inoperability Under the 21st Century Cures Act,” Pro Te Solutio, Vol. 10 No. 2 (Spring 2017), available at https://3epjwm3sm3iv250i67219jho-wpengine.netdna-ssl.com/wp-content/uploads/2017/07/Health-Information-Technology-HIT-Inoperability-Under-The-21st-Century-Cures-Act.pdf (last visited January 29, 2018); Virginia B. Wilson, “21st Century Cures Act: New Clinical Research Tools,” Pro Te: Solutio, Vol. 10 No. 2 (Spring 2017), available at https://3epjwm3sm3iv250i67219jho-wpengine.netdna-ssl.com/wp-content/uploads/2017/07/21st-Century-Cures-Act-New-Clinical-Research-Tools.pdf (last visited Jan. 25, 2018).
 82 Fed. Reg. 60922, 60922 (Dec. 26, 2017).
 Kimberly S. Coggin, “You’ve Been Warned: FDA Warning and Untitled Letters,” Pro Te: Solutio, Vol. 3 No. 4 (Oct. 2010), available at https://3epjwm3sm3iv250i67219jho-wpengine.netdna-ssl.com/wp-content/uploads/2014/08/PT_Vol3_No4.pdf (last visited Jan. 8, 2018); Laura Dixon, “FDA Warning Letters Through Finality and Beyond: Potential Evidentiary Effects of July 2012 FDA Regulatory Procedures Manual,” Pro Te: Solutio, Vol. 5 No. 4 (Nov. 2012), available at https://3epjwm3sm3iv250i67219jho-wpengine.netdna-ssl.com/wp-content/uploads/2014/08/PTVol5-No4.pdf (last visited Jan. 8, 2018).
 Todd P. Photopulos, “Whistleblower,” Pro Te: Solutio, Vol. 1 No. 2 (Apr. 2008), available at https://3epjwm3sm3iv250i67219jho-wpengine.netdna-ssl.com/wp-content/uploads/2014/08/ProTeVol1No2.pdf (last visited Jan. 8, 2018).
 Bob Anderson, “Turning Up the H.E.A.T. in Healthcare Fraud Enforcement,” Pro Te: Solutio, Vol. 4 No. 1 (Feb. 2011), available at https://3epjwm3sm3iv250i67219jho-wpengine.netdna-ssl.com/wp-content/uploads/pdfs/attorney_publications/turning-up-the-h-e-a-t-in-healthcarefraud-enforcement.pdf (last visited Jan. 8, 2018); Amanda B. Barbour, “Health Care Strike Force: Uncovering Fraud in the Healthcare Industry,” Pro Te: Solutio, Vol. 7 No. 1 (March 2014 ), available at https://3epjwm3sm3iv250i67219jho-wpengine.netdna-ssl.com/wp-content/uploads/2014/08/ProTe-March2014.pdf (last visited Jan. 8, 2018).
 Richelle W. Kidder, “Proof of Knowledge Not Required,” Pro Te: Solutio, Vol. 4 No. 2 (May 2011), available at https://3epjwm3sm3iv250i67219jho-wpengine.netdna-ssl.com/wp-content/uploads/2014/08/PT_Vol4_No2.pdf (last visited Jan. 8, 2018).
 “Looking ahead: Some of FDA’s major policy goals for 2018,” posted on Dec. 14, 2017, by FDA Voice, available at https://blogs.fda.gov/FDAvoice/index.php (last visited Dec. 15, 2017).