The Antibiotic Development to Advance Patient Treatment (ADAPT) Act () was introduced in the U.S. Congress on December 12, 2013 by Representative Phil Gingrey of Georgia and fifty-two cosponsors. Responding to the lack of financial incentives for drug manufacturers to innovate new antibiotics and antifungals and the regulatory barriers to their doing so, it proposed an expedited pathway for testing drugs intended for diseases for which no cure yet existed. After it died in committee, a similar version of the Act was re-introduced by Representative John Shimkus of Illinois and his cosponsor Representative Gene Green of Texas. Though this Act likewise failed to make it out of committee, several of its provisions were codified in the 21st Century Cures Act, which was signed into law on December 13, 2016. These include the expedited testing pathway for new antibiotics and a similar provision for antimicrobial susceptibility tests.
Background
Antibiotic resistance and the barriers to new treatments The cost of antibiotic resistance, in dollars and in lives, motivated the Act’s sponsors and the community stakeholders that supported its passage. In September 2014, the Subcommittee on Health of the House Committee on Energy and Commerce held a hearing at which officials from the Food and Drug Administration (FDA), Pew Charitable Trusts, and other organizations testified in favor of the ADAPT and 21st Century Cures Acts.21st Century Cures: Examining Ways to Combat Antibiotic Resistance and Foster New Drug Development; Hearing Before the Subcommittee. on Health of the Comm. on Energy and Commerce, 113th Cong. (2014) [hereinafter Hearing Before Health Comm.]. Opening the hearing, Subcommittee Chairman Joseph R. Pitts (R-PA) quoted then-Prime Minister David Cameron’s recent admonition that failure to “confront the threat of antibiotic resistance” could “cast [humanity] back into the dark ages.”Hearing Before Health Comm., supra, at 1 (statement of Joseph R. Pitts, Pennsylvania Rep. and Chairman of the Subcomm. on Health). Speaking at this same hearing, Representative Phil Gingrey (R-GA) (the 2013 Act’s principal sponsor) referenced Centers for Disease Control (CDC) statistics, which placed the number of Americans who die from drug-resistant infections each year at around 23,000.Hearing Before Health Comm., supra, at 5 (statement of Phil Gingrey, Georgia Rep.). Representative Gingrey asserted that the financial losses from such infections amount to $55 billion annually. Representative John Shimkus (R-IL) would later note these same figures in a House debate over the Acts in July 2015.Press Release, Congressman John Shimkus, With Over 10,000 Diseases and Only 500 Treatments--Shimkus Votes for Cures (July 10, 2015) ("Each year in the United States, at least 2 million people are infected with an antibiotic-resistant bacteria and at least 23,000 of them die as a direct result of those infections, according to the CDC.").
Equally worrisome to the ADAPT Act’s proponents were the economic and regulatory impediments to developing new treatments for drug-resistant illnesses. Citing the FDA, Representative Gingrey lamented during the 2014 hearing that “new antibiotic approval ha[d] decreased by 70 percent since the mid 1980s.” Representative Michael C. Burgess (R-TX) likewise took issue with the “lack of a pipeline of new drugs” to respond to the threat of super bugs.Hearing Before Health Comm., supra, at 3 (statement of Michael C. Burgess, Texas Rep.). Several blamed inadequate market incentives for this paucity of remedies. As Dr. Barbara E. Murray, then-President of the Infectious Diseases Society of America, observed, “Antibiotics are typically priced low [and] used for a short duration.”Hearing Before Health Comm., supra, at 60 (statement of Barbara E. Murray, MD, President of the Infectious Disease Society of America.). Pharmaceutical companies can reap greater returns in other areas of research; hence, the development of new antibiotics flounders.See Hearing Before Health Comm., supra, at 4 (statement of Frank Pallone, New Jersey Rep.).
Compounding the scant financial motives for drug development, creators of new treatments were made to contend with "serious regulatory barriers".Hearing Before Health Comm., supra, at 61 (statement of Barbara E. Murray, MD, President of the Infectious Disease Society of America.). Dr. Murray observed that the small number of patients infected by novel diseases made it difficult for manufacturers to find enough test subjects in order to comply with federal agencies’ n-count requirements. The unavailability of diagnostic tests for these new infectious agents also demanded a large investment to find eligible study participants, while generating little information about drug effectiveness. Stagnant innovation becomes self-perpetuating. The more antibiotics to which a pathogen becomes resistant, the fewer controls there are against which to measure an experimental treatment.
The GAIN Act In 2012, one of Congress’s earliest attempts at rectifying these barriers to new drug-resistant antibiotics came in the form of the Generating Antibiotics Now (GAIN) Act.See Kevin Khachatryan, Note, Incentivizing Drug Development: Novel Reforms of Pharmaceutical Innovation, 18 COLUM. SCI. & TECH. L. REV. 139, 156-57 (2016). GAIN was passed as an amendment to the Federal Food, Drug, and Cosmetic (FD&C) Act. Its strategy for generating new antibiotics is to offer manufacturers an artificial monopoly on any qualifying drugs that they produce. Such drugs must treat illnesses with “the potential to pose a serious threat to the public health.” However, beyond this blanket criterion, GAIN gave significant deference to the Secretary of the Department of Health and Human Services (the Secretary). This latitude was subject only to the requirements that she consider a given pathogen’s “impact on public health” and “morbidity and mortality rates” and consult with the CDC, FDA, and the medical community. Manufacturers who satisfied GAIN’s conditions were guaranteed five years of market exclusivity over the pertinent drug. These years could stack with the drug’s “five year exclusivity as a new chemical entity (NCE), three year clinical investigation exclusivity, and seven-year orphan drug exclusivity.” Moreover, any qualifying drugs were eligible for fast-track review.See Kevin Khachatryan, Note, Incentivizing Drug Development: Novel Reforms of Pharmaceutical Innovation, 18 COLUM. SCI. & TECH. L. REV. 139, 157-58 (2016).
GAIN’s value proposition proved to be an effective one. As Representative Frank Pallone (D-NJ) commented during the 2014 ADAPT Act hearing, within two years, GAIN had led to FDA approval of numerous new antibiotics.Hearing Before Health Comm., supra, at 4 (statement of Frank Pallone, New Jersey Rep.). The expedited review procedure further ensured that these drugs would be “able to combat an imminent infectious disease threat and reach patients at an accelerated pace". At the same time, Representative Pallone and others were concerned about the consumer harms that these decades of exclusivity might yield. Representative Henry A. Waxman (D-CA) warned that exclusivity “allow[s drug companies] to charge higher prices,” which “imposes a significant burden on patients and on the healthcare system overall.”Hearing Before Health Comm., supra, at 8 (statement of Henry A. Waxman, California Rep.). To justify “the carrot of marketing and regulatory exclusivities,” Representative Pallone exhorted his fellow members of Congress to ensure that their efforts “achieve[] the necessary impact on the pipeline of new drugs.”
Provisions
Purpose and Scope The ADAPT Act complemented GAIN. Representative Gingrey introduced it to the House as the “logical next step to the GAIN Act.”Hearing Before Health Comm., supra, at 6 (statement of Phil Gingrey, Georgia Rep.). To that end, it did not merely render the development of new treatments more lucrative but more feasible as well. The centerpiece of this proposal was ADAPT’s creation of a Limited Population Antibacterial Drug (LPAD) approval pathway for certain antibiotics.Donna Hanrahan, Federal Efforts to Reduce Overuse, Curb Misuse, and Incentivize the Development of Antibiotic Drugs, 26 ANNALS HEALTH L. 67, 85-86 (2017) Faced with a disease of sufficient severity for which alternatives do not yet exist, ADAPT would empower the Secretary to dispense with the usual testing requirements and allow manufacturers to go to market based on more limited efficacy tests.See id. As Allan Coukell, Director of Drug, Medical Device, and Food Programs at the Pew Charitable Trusts, observed, a patient with multi-drug-resistant pneumonia will likely die without access to a new antibiotic.Hearing Before Health Comm., supra, at 113 (statement of Allan Coukell, Director of Drug, Medical Device, and Food Programs, Pew Charitable Trusts). In that case, the uncertainty of an unproven remedy was preferable to the near certainty of death. In conducting such a risk-benefit assessment, ADAPT allowed the FDA to “accept less data” in approving a lifesaving drug.Id. As Representative Shimkus later commended, this “new, streamlined pathway” saved “thousands of lives” by making experimental drugs available to those who would otherwise have no cure.Press Release, supra
Given the uncertainty inherent in drugs approved via LPAD, ADAPT’s advocates were careful to constrain its reach to “high-need populations” suffering from the gravest threats. Dr. Janet Woodcock, Director of the FDA Center for Drug Evaluation and Research, claimed that ADAPT would be restricted to “rare resistant organisms where there are really very few treatment options available.”Hearing Before Health Comm., supra, at 37 (statement of Janet Woodcock, Director of the Food & Drug Administration Center for Drug Evaluation and Research). Within the population of patients affected by these diseases, the Act’s application would be further constrained to “the limited population in most need of the therapy, as opposed to all patients.”Hearing Before Health Comm., supra, at 62 (statement of Barbara E. Murray, MD, President of the Infectious Disease Society of America.). As such, ADAPT would not lower the federal review standard for new drugs, but merely contour it to the needs of “a specific population that is different from the general population.”
Relationship Between the 2013 and 2015 Acts The two versions of the ADAPT Act—H.R. 3742 (2013)Antibiotic Development to Advance Patient Treatment (ADAPT) Act of 2013, H.R. 3742, 113th Cong. (2013). and H.R. 2629 (2015)Antibiotic Development to Advance Patient Treatment (ADAPT) Act of 2015, H.R. 2629, 114th Cong. (2015).—contain the same three overriding provisions discussed above. Both would amend Section 505 of FD&C (21 U.S.C. § 355) to formally include the expedited testing pathway.H.R. 3742, § 2(a); H.R. 2629, § 2(b). Each prescribes certain labeling requirements for manufacturersH.R. 3742, § 2 (x)(C); H.R. 2629, § 2(b)(x)(3). and charges the Secretary of Health and Human Services with conducting the aforementioned breakpoint review.H.R. 3742 § 3(a); H.R. 2629 § 3(a). Under a modification to Title III of the Public Health Service Act (42 U.S.C. § 247b-22), the Secretary is also to monitor “the use of antibacterial and antifungal drugs” as well as “[c]hanges in bacterial and fungal resistance to drugs.”H.R. 3742 § 2(c); H.R. 2629 § 2(g). This new responsibility of the Secretary encompasses drugs approved both through LPAD as well as the standard procedure. The results of the Secretary’s resistance analysis, like the breakpoint research, are to be made public.