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Before the first generic version of a drug is marketed, patent litigation often occurs. The process begins when generic manufacturers notify the US Food and Drug Administration (FDA) of their intent to market a generic copy of a brand‐name drug protected by patents, which they allege to be invalid or not infringed (called a Paragraph IV certification). Assuming the brand‐name manufacturer responds with litigation within 45 days, a 30‐month stay period is triggered, which bars the FDA from authorizing generic entry until the stay period expires or litigation is resolved in favor of the generic manufacturer. To understand whether 30‐month stays delay generic entry, we examined the timing of major legal events leading to generic entry for a cohort of 46 generic drugs, including the timing of Paragraph IV certification filings, stay period expirations, the FDA approvals of generics, and generic product launches. We found Paragraph IV certifications were filed a median of 5.2 years after the brand drug’s FDA approval. There was a median of 3.2 years between the stay period expiration and subsequent generic launch. Because stay periods generally expire well in advance of when generic entry typically occurs, 30‐month stays are unlikely to delay the timing of generic entry. Patent litigation could begin even earlier, however, if litigation was allowed to start immediately following a brand‐name drug’s FDA approval; but by law currently, the soonest this can begin is 4 years after the brand drug’s FDA approval. Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? Before generic versions of new drugs reach the market, patent litigation often occurs. Once litigation has been initiated, a 30‐month regulatory stay period is triggered that bars the US Food and Drug Administration (FDA) from approving the generic application until litigation resolves or the stay period expires. WHAT QUESTION DID THIS STUDY ADDRESS? What is the timing of key legal events in the regulatory approval process for generic drugs in relation to the eventual launch of the generic product? WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? We identified the typical timing of the initiation of patent litigation and expiration of the 30‐month stay period prior to the eventual launch of generic products. Litigation is often initiated as soon as legally possible (i.e., 4 years after the launch of the brand product), and stay periods typically expire well before generic entry occurs. HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE? Stay periods are unlikely to delay generic entry directly because stay expirations often occur well before the time of generic launch. Allowing the submission of generic drug applications immediately following a brand drug’s FDA approval would facilitate earlier patent dispute resolution and prevent unnecessary delays in the anticipated generic product launch date.

PURPOSE: To determine how commonly pre-approval clinical trials could potentially be replicated using real-world data from insurance claims databases. METHODS: We conducted a cross-sectional study of medications approved by the FDA in 2011. For each medication, we reviewed the drug's label and the details of the pivotal clinical trials supporting its approval. We assessed whether each clinical trial could be replicated using an insurance claims databases by determining whether the following pivotal trial features could be reliably captured in claims data: study outcome, inclusion criteria, exclusion criteria, and the presence of an appropriate active comparator. RESULTS: In 2011, 28 new medications were approved. The most common disease areas were oncology (N = 8, 29%), infectious disease (N = 5, 18%), and neurology (N = 4, 14%). The primary outcome of pre-approval clinical trials was identifiable in claims databases for six (21%) of the medications. Two (ticagrelor and linagliptin) had at least 80% of inclusion and exclusion criteria that could be identified in claims databases and had an available active comparator. The non-identifiable primary outcomes were related to patient-reported symptoms (N = 9, 32%), imaging findings (N = 5, 18%), laboratory values (N = 5, 18%), or other measurements (eg, blood pressure) not typically available in insurance claims databases (N = 4, 14%). CONCLUSIONS: Among drugs FDA-approved in 2011, two (7%) had a pre-approval trial that could be replicated using insurance claims databases. In such qualifying trials, replication using claims databases could be useful in assessing whether they provide concordant results.

Prescription drugs and medical devices are increasingly coming to market through expedited US Food and Drug Administration (FDA) pathways that require only limited evidence of safety and efficacy, such as nonrandomized, unblinded trial data in small numbers of patients, or the use of surrogate end points. Reliance on more limited evidence means that there is often greater uncertainty about risks and benefits. Using a modified Delphi process, we sought to identify promising policy approaches that address physician-patient decision-making needs about the use of such drugs and medical devices. We convened 13 national leaders from academia, government, nonprofits, payors, and industry who had expertise in medical product regulation, payor policymaking, bioethics, physician practice, patient advocacy, public health expertise/advocacy, clinical trials, the pharmaceutical and device industry, institutional review board oversight, and real-world evidence. Through multiple rounds of voting and meetings focused on evaluating the feasibility and impact of various interventions, the 13 participants reached the broadest consensus on 4 interventions: strengthening FDA post-approval study requirements to ensure postmarket evidence is generated in a timely manner, better informing patients about the risks and benefits and level of evidence supporting therapies via simplified and patient-centered product information "boxes" modeled on nutrition labels, limiting prices for drugs and medical devices approved based on surrogate end point data until confirmatory clinical evidence is generated, and improving health professional education about FDA regulation to better support clinician use of drugs and devices as well as communication with patients.

Drugs and high-risk medical devices are increasingly likely to receive Food and Drug Administration (FDA) approval through expedited pathways, which has implications for informed treatment consent (i.e., consent in clinical practice).To obtain expert opinion about the clinical and ethical implications of the increasing availability of new drugs and devices approved through expedited development and regulatory review pathways.Qualitative study using individual semi-structured videoconference interviews.National leaders in medicine, ethics, and law (n=12) with expertise in medical product regulation, payor policymaking, bioethics, physician practice, patient advocacy, public health expertise/advocacy, clinical trials, the pharmaceutical and device industry, institutional review board oversight, and real-world evidence.Principal themes in 3 domains: expedited regulatory pathways, physician and patient understanding of and reliance on FDA approval, and informed treatment consent.Respondents pointed out that more common use of expedited pathways translates to increased reliance on surrogate measures, some with uncertain clinical significance. While expedited development and review can have advantages, participants expressed worry that physicians were unaware when medical products were expedited and did not communicate about uncertainties in knowledge about new drug or device approvals effectively with patients. Many participants felt that informed treatment consent discussions about new drugs or devices should include some explanations of expedited pathways and use of surrogate measures.Experts identified advantages of expediting development and of FDA flexibility in applying its standards to new drugs and medical devices, but highlighted concerns that patients may not be adequately informed about the risks of shorter review times or about uncertainties in the evidence that result. There is a need to identify approaches to ensure effective clinical use of drugs and devices when approved through expedited pathways.

Objectives To develop and test a method for approximating generic entry of top-selling drugs. Methods The procedure involved 1) identifying products' key patents as those with a patent term restoration extension (whenever relevant) or otherwise as the first expiring patent listed in the US Food and Drug Administration's patent register, 2) determining whether the key patent had been extended through an associated pediatric extension, 3) identifying other regulatory exclusivities associated with the drug, and 4) categorizing key patents as active ingredient (or extended) patents versus secondary patents. The accuracy and precision of the procedure's predictions were then tested against a database containing the timing of generic entry for 170 top-selling drugs that lost market exclusivity between 2000 and 2012, on the basis of Medicaid data. Results Overall, the procedure predicted a median market exclusivity period of 12.5 years (interquartile range [IQR] 7.25–14.5) compared with the median actual period of 12.5 years (IQR 8.5–14.75 years). Among the 131 drugs (77%) with active ingredient patents, the median predicted market exclusivity was 12.25 years (IQR 7.5–14.5) compared with a median actual period of 13.0 years (IQR 10.0–14.75). Among the 38 (22%) drugs protected only by secondary patents, the median predicted market exclusivity was 16.0 years (IQR 6.75–19.5), but the median actual market exclusivity was only 8.25 years (IQR 6.25–13.5). Conclusions The procedure approximated median actual exclusivity with reasonable accuracy and precision for drugs with active ingredient patents, but substantially overestimated exclusivity for drugs with only secondary patents.

The US Congress created the Breakthrough Therapy designation in 2012 to expedite drug development and review through efficient clinical trial design and intensive interaction with US Food and Drug Administration (FDA) reviewers. Yet, of the 116 pivotal trials supporting Breakthrough-designated drugs approved 2013–2018, 96 (83%) were already underway or completed when the designation was granted, limiting the potential of the designation to influence trial design. We found no difference between these trials and the 20 (17%) that had not yet begun when the designation was granted (which had greater potential to be impacted by the designation) with respect to phase, size, intervention model (single-arm vs. multi-arm), or use of surrogate end points under the Accelerated Approval (AA) pathway. This finding suggests that, in contrast to previous studies, observed trial characteristics were not likely attributable to the designation, and instead other factors such as disease category (e.g., oncology) may be driving both trial design and Breakthrough designation. The 20 trials in our sample that began after designation was granted were, however, over 8 months shorter than trials of nondesignated drugs. This suggests that designations granted early in clinical development may reduce trial time by influencing aspects of clinical programs other than design characteristics, such as timelines for FDA responses. Alternately, certain drugs may be more likely to both receive an early designation and have a shorter trial duration, for example, because of therapeutic category or large effect size.

The Food and Drug Administration (FDA) approves vaccines when their benefits outweigh the risks for their intended use. In this article we review the standard FDA approach to vaccine evaluation, which underpins its current approaches to assessment of vaccines to prevent coronavirus disease 2019 (COVID-19). The FDA has established pathways to accelerate vaccine availability before approval, such as Emergency Use Authorization, and to channel resources to high-priority products and allow more flexibility in the evidence required for approval, including accelerated approval based on surrogate markers of effectiveness. Among the thirty-five new vaccines approved in the US from 2006 through October 2020, about two-thirds of their pivotal trials used the surrogate outcome of immune system response, and only one-third evaluated actual disease incidence. Postapproval safety surveillance of new vaccines, and particularly vaccines receiving expedited approval, is crucial. This has generally been accomplished through such mechanisms as the Centers for Disease Control and Prevention (CDC) and FDA Vaccine Adverse Event Reporting System, the CDC Vaccine Safety Datalink, and the CDC Clinical Immunization Safety Assessment Project. Adverse events detected in this way may lead to changes in a vaccine's recommended use or withdrawal from the market. Regulatory oversight of new vaccines must balance speed with rigor to effectively address the pandemic.

Our objective was to compare expected and observed biosimilar and generic entry dates for a recent cohort of brand-name drugs. Therefore, we estimated expected biosimilar and generic entry dates for all 328 new drugs approved by the Food and Drug Administration (FDA) between 2000-2012, which we defined as the later of the expiration of the key patent term or statutory exclusivity (12 years for biologics, 5 years for small-molecule drugs not indicated for a rare disease, and 7 years for small-molecule drugs indicated for a rare disease (plus 6 months if a pediatric extension had been granted). For drugs with expected entry prior to 2019, we calculated the proportion with observed biosimilar or generic entry. The expected biosimilar entry dates were estimated to be a median of 12.3 years (interquartile range [IQR]: 12.0-14.0, n=60) after FDA approval. The 12-year biologic statutory exclusivity period comprised 98% of the median expected protection period. By contrast, expected generic entry was estimated to be a median of 12.2 years (IQR: 8.4-14.0, n=268), or 7.2 years after the 5-year small-molecule statutory exclusivity (59% of the total expected market protection period). By 2019, observed biosimilar entry occurred in 12% of cases (3/25) and observed generic entry in 65% (101/155). We concluded that expected US market exclusivity periods are similar for biologic and small-molecule drugs. Statutory exclusivity plays a more substantial role in market exclusivity protection for biologics. Biosimilar competition, currently lagging far behind generic competition, will likely increase as the biosimilar market becomes established.

Importance US law requires testing of new drugs before approval to ensure that they provide a well-defined benefit that is commensurate with their risks. A major challenge for the US Food and Drug Administration (FDA) is to achieve an appropriate balance between rigorous testing and the need for timely approval of drugs that have benefits that outweigh their risks. Objective To describe the evolution of laws and standards affecting drug testing, the use of new approval programs and standards, expansions of the role and authority of the FDA, and changes in the number of drugs approved from the 1980s to 2018. Evidence Sources of evidence included principal federal laws and FDA regulations (1962-2018) and FDA databases of approved new drugs (1984-2018), generic drugs (1970-2018), biologics (1984-2018), and vaccines (1998-2018); special development and approval programs (Orphan drug [1984-2018], Fast-Track [1988-2018], Priority Review and its predecessors [1984-2018], Accelerated Approval [1992-2018], and Breakthrough Therapy [2012-2018]); expanded access (2010-2017) and Risk Evaluation and Mitigation Strategies (2008-2018); and user fees paid to the FDA by industry (1993-2018). Findings From 1983 to 2018, legislation and regulatory initiatives have substantially changed drug approval at the FDA. The mean annual number of new drug approvals, including biologics, was 34 from 1990-1999, 25 from 2000-2009, and 41 from 2010-2018. New biologic product approvals increased from a median of 2.5 from 1990-1999, to 5 from 2000-2013, to 12 from 2014-2018. The median annual number of generic drugs approved was 136 from 1970 to the enactment of the Hatch-Waxman Act in 1984; 284 from 1985 to the enactment of the Generic Drug User Fee Act in 2012; and 588 from 2013-2018. Prescription drug user fee funding expanded from new drugs and biologics in 1992 to generic and biosimilar drugs in 2012. The amount of Prescription Drug User Fee Act fees collected from industry increased from an annual mean of $66 million in 1993-1997 to $820 million in 2013-2017, and in 2018, user fees accounted for approximately 80% of the salaries of review personnel responsible for the approval of new drugs. The proportion of drugs approved with an Orphan Drug Act designation increased from 18% (55/304) in 1984-1995, to 22% (82/379) in 1996-2007, to 41% (154/380) in 2008-2018. Use of Accelerated Approval, Fast-Track, and Priority Review for new drugs has increased over time, with 81% (48/59) of new drugs benefiting from at least 1 such expedited program in 2018. The proportion of new approvals supported by at least 2 pivotal trials decreased from 80.6% in 1995-1997 to 52.8% in 2015-2017, based on 124 and 106 approvals, respectively, while the median number of patients studied did not change significantly (774 vs 816). FDA drug review times declined from more than 3 years in 1983 to less than 1 year in 2017, but total time from the authorization of clinical testing to approval has remained at approximately 8 years over that period. Conclusions and Relevance Over the last 4 decades, the approval and regulation processes for pharmaceutical agents have evolved and increased in complexity as special programs have been added and as the use of surrogate measures has been encouraged. The FDA funding needed to implement and manage these programs has been addressed by expanding industry-paid user fees. The FDA has increasingly accepted less data and more surrogate measures, and has shortened its review times.

The FDA Breakthrough-Drug Designation In 2012, Congress created the breakthrough-therapy designation to expedite the testing and approval by the FDA of medications with potential to provide substan...

Importance US law generally requires testing of high-risk medical devices prior to approval, as well as premarket evaluation of moderate-risk medical devices, with the goal of ensuring that the benefits of these products exceed their risks. The US Food and Drug Administration (FDA) attempts to balance the need for evidence generation with an approval process that facilitates access and encourages innovation. Objective To review the development of laws and standards affecting the evaluation and oversight of medical devices by the US regulatory system and the outcomes of this system from 1976 to 2020. Evidence Review Laws enacted by US Congress and regulations promulgated by the FDA through 2020; databases maintained by the FDA of device authorizations from 1976 to 2020; and annual reports of user fees paid to the FDA by industry. Findings Since Congress and the FDA initiated premarket review of medical devices in 1976, some fundamental innovations in the device regulation system have included special pathways to accelerate availability of investigational devices, more flexible evidence and review requirements, and increased funding to the FDA through industry-paid user fees. From 1987 to 2020, the annual number of novel devices granted premarket approval (which excludes supplements) ranged from 8 to 56 (median, 32), and the number of clearances for 510(k) devices (those that are “substantially equivalent” to marketed devices) ranged from 2804 to 5762 (median, 3404). User fee funding for devices was established in 2002 and annual fees collected increased from $30 million in 2003 (in 2019 dollars) to more than $208 million in 2019; this represented 43% of FDA funding related to the review of medical devices. Although many new devices have led to considerable patient benefit, such as hypodermic needles and magnetic resonance imaging machines, important adverse events caused by some devices, such as an implanted device for birth control and a surgical mesh implant for pelvic organ prolapse, have led to calls to reexamine the regulatory system for such products. Conclusions and Relevance Over the last 45 years, medical device regulation has become more complex, with more regulatory pathways and greater variations in the evidence and controls required for authorization. Increased FDA support from industry and concern about flexible authorization requirements reflect the tension between efficient access and the need for assurances that products will safely benefit patients.

Antimicrobial resistance is of growing concern. To encourage development of new treatments, some commentators have suggested regulators exercise increased flexibility on the clinical evidence required for approval. We examined all 1065 new drugs and biologics approved by the US Food and Drug Administration between 1984 and 2018 and recorded each drug's use of the Orphan Drug Act, fast-track, priority review, accelerated approval, and breakthrough therapy programmes, as well as dates of investigational new drug application, new drug application, and new drug approval, which were used to calculate clinical development and review times. There were 178 (17%) antimicrobial products, which were more likely than non-antimicrobial products to benefit from priority review (103 [58%] of 178 vs 402 [45%] of 887, p=0·0023), fast-track designation (58 [37%] of 157 vs 151 [19%] of 814], p

In 2017, the US Food and Drug Administration (FDA) approved voretigene neparvovec-rzyl (Luxturna), a gene therapy used to treat a rare form of inherited blindness. Widely described by the media as a curative treatment that 'restores vision', it was priced at US$850000. Although voretigene neparvovec-rzyl represents a substantial therapeutic advance, most reports have failed to adequately describe study outcomes as documented by FDA reviewers. These documents reveal that the drug is not expected to restore normal vision, that only about half of treated patients met the FDA's threshold for minimally meaningful improvement, that improvements might not persist long-term, that the most common measure of visual function was rejected as a primary endpoint after yielding mixed results, and that two patients experienced permanent vision loss. Over US$100 million of additional publicly-funded costs are not evident from the US$850000 figure.

In 2010, Congress created an abbreviated application pathway for biosimilars, versions of approved biologics made by different manufacturers. However, as of November 1, 2018, the US Food and Drug Administration (FDA) had approved only 13 biosimilars under this pathway, of which just 6 were available for patients to use. We review the history of US regulation of biologics and identify manufacturing, regulatory, and marketing issues that have limited biosimilar market entry and uptake, concluding with recommendations for reform.

Precision medicines can benefit patients by increasing the probability of a successful treatment response in selected patient populations. The potential for more immediate signals of efficacy during clinical trials suggests such medicines will reach the market more rapidly than traditional drugs will. Using data from the Food and Drug Administration (FDA), we examined the regulatory review and pivotal trial characteristics of precision medicines. We found that in the period January 2013-June 2017, precision medicines were developed and reviewed almost two years faster than nonprecision medicines. In addition, approximately 48 percent of the precision medicines in our study qualified for the FDA's breakthrough therapy designation. Precision medicines were also approved based on fewer pivotal trials with fewer patients, and the trials were less likely to be randomized, blinded, or controlled with either an active or placebo comparator.

Purpose The breakthrough therapy program was established in 2012 to expedite the development and review of new medicines. We evaluated the times to approval, efficacy, and safety of breakthrough-designated versus non–breakthrough-designated cancer drugs approved by the US Food and Drug Administration (FDA). Methods We studied all new cancer drugs approved by the FDA between January 2012 and December 2017. Regulatory and therapeutic characteristics (time to FDA approval, pivotal trial efficacy end point, novelty of mechanism of action) were compared between breakthrough-designated and non–breakthrough-designated cancer drugs. Random-effects meta-regression was used to assess the association between breakthrough therapy designation and hazard ratios for progression-free survival (PFS), response rates (RRs) for solid tumors, serious adverse events, and deaths not attributed to disease progression. Results Between 2012 and 2017, the FDA approved 58 new cancer drugs, 25 (43%) of which received breakthrough therapy designation. The median time to first FDA approval was 5.2 years for breakthrough-designated drugs versus 7.1 years for non–breakthrough-designated drugs (difference, 1.9 years; P = .01). There were no statistically significant differences between breakthrough-designated and non–breakthrough-designated drugs in median PFS gains (8.6 v 4.0 months; P = .11), hazard ratios for PFS (0.43 v 0.51; P = .28), or RRs for solid tumors (37% v 39%; P = .74). Breakthrough therapy–designated drugs were not more likely to act via a novel mechanism of action (36% v 39%; P = 1.00). Rates of deaths (6% v 4%; P = .99) and serious adverse events (38% v 36%; P = 0.93) were also similar in breakthrough-designated and non–breakthrough-designated drugs. Conclusion Breakthrough-designated cancer drugs were associated with faster times to approval, but there was no evidence that these drugs provide improvements in safety or novelty; nor was there a statistically significant efficacy advantage when compared with non–breakthrough-designated drugs.

The Regulatory Accountability Act of 2017 The Regulatory Accountability Act has been described by its proponents as a way to reverse the increasing volume of regulatory requirements. But it could h...

The FDA Reauthorization Act of 2017 includes the sixth version of the Prescription Drug User Fee Act. User fees have accelerated drug approvals in the context of inadequate funding of the FDA, and industry now pays 75% of the costs of the scientific review of drugs.

This study uses the Drugs@FDA database to analyze clinical development times for drugs to treat serious diseases within the 4 FDA expedited programs intended to speed drug review and approval.

The authors review the FDA policies and procedures that permit some patients with serious conditions to receive investigational drugs before formal product approval and examine the legal and ethical issues associated with expanded access.

New prescription drugs receive approval from the US Food and Drug Administration (FDA) based on tests establishing safety and adequate and well-controlled trials demonstrating "substantial evidence" of efficacy. However, a number of legislative and regulatory initiatives, the most recent being the breakthrough therapy designation created in 2012, give the FDA flexibility to approve drugs on the basis of less rigorous data in situations of greater clinical need. These expedited development and review pathways now contribute to a majority of all new drug approvals and have important benefits in encouraging efficient availability of transformative drugs. They also have a number of risks, including a heightened possibility that the drugs will be discovered to be ineffective or unsafe after widespread use, and confusion by patients and physicians over what it means for a product to be "FDA approved."

Objective To evaluate the use of special expedited development and review pathways at the US Food and Drug Administration over the past two decades. Design Cohort study. Setting FDA approved novel therapeutics between 1987 and 2014. Population Publicly available sources provided each drug’s year of approval, their innovativeness (first in class versus not first in class), World Health Organization Anatomic Therapeutic Classification, and which (if any) of the FDA’s four primary expedited development and review programs or designations were associated with each drug: orphan drug, fast track, accelerated approval, and priority review. Main outcome measures Logistic regression models evaluated trends in the proportion of drugs associated with each of the four expedited development and review programs. To evaluate the number of programs associated with each approved drug over time, Poisson models were employed, with the number of programs as the dependent variable and a linear term for year of approval. The difference in trends was compared between drugs that were first in class and those that were not. Results The FDA approved 774 drugs during the study period, with one third representing first in class agents. Priority review (43%) was the most prevalent of the four programs, with accelerated approval (9%) the least common. There was a significant increase of 2.6% per year in the number of expedited review and approval programs granted to each newly approved agent (incidence rate ratio 1.026, 95% confidence interval 1.017 to 1.035, P

In 1984, Congress passed the Hatch-Waxman Act, which catalyzed the creation of the modem generic drug industry. Generic drugs today account for eighty-four percent of all prescriptions dispensed, but less than twenty percent of drug costs. Despite this success, numerous problems in the generic drug market have emerged. Some involve the deliberate manipulation of the Hatch-Waxman system, while others have arisen more unexpectedly, such as the Supreme Court's 2011 decision in Pliva v. Mensing that could undermine consumer confidence in generic drugs. We discuss these emerging challenges and propose updates to the Hatch-Waxman Act to continue support for the timely emergence of safe generic drugs.

Vaccines represent one of the greatest achievements of medicine, dramatically reducing the incidence of serious or life-threatening infectious diseases and allowing people to live longer, healthier lives. As life expectancy has increased, however, the burden of non-communicable diseases (NCDs) such as cancer, hypertension, atherosclerosis, and diabetes has increased. This shifting burden of disease has heightened the already urgent need for therapies that treat or prevent NCDs, a need that is now being met with increased efforts to develop NCD vaccines. Like traditional vaccines, NCD vaccines work by modulating the human immune system, but target cells, proteins or other molecules that are associated with the NCD in question rather than pathogens or pathogen-infected cells. Efforts are underway to develop NCD vaccines to address not only cancer and hypertension, but also addiction, obesity, asthma, arthritis, psoriasis, multiple sclerosis, and Crohn's disease, among others. NCD vaccines present an interesting challenge for the U.S. Food and Drug Administration (FDA), which is tasked with approving new treatments on the basis of efficacy and safety. Should NCD vaccines be evaluated under the same analytic frame as traditional vaccines, or that of biologic drugs? Despite the borrowed nomenclature, NCD vaccines differ in important ways from infectious disease vaccines. Because infectious disease vaccines are generally administered to healthy individuals, often children, tolerance for adverse events is low and willingness to pay is limited. It is important to have infectious disease vaccines even for rare or eradicated disease (e.g., smallpox), in the event of an outbreak. The efficacy of infectious disease vaccines is generally high, and the vaccines convey population level benefits associated with herd immunity and potential eradication. The combination of substantial population-level benefits, low willingness to pay, and low tolerance for adverse events explains the need for the federal National Childhood Vaccine Injury Compensation Act, which encourages production and uptake by providing immunity from liability to industry and compensation to injured patients. These characteristics and considerations contrast sharply with those of NCD vaccines, raising the question of whether the term "vaccine" is appropriate for this new category of drugs. The article explores the emerging class of NCD vaccines, explains how they differ from traditional vaccines, and describes some regulatory implications of this innovative type of therapeutic.

Specialty drugs are notable among prescription drugs in that they offer the possibility of substantial clinical improvement, come with important risks of adverse events and mortality, can be complex to manufacture or administer, and are usually extremely costly. The Food and Drug Administration (FDA) plays a critical role in ensuring that patients who could benefit from specialty drugs have access to them in a timely fashion. In this article we review the different strategies that the FDA can use to approve and influence the post-approval prescribing of specialty drugs. When specialty drugs show promise in early clinical trials, the FDA can expedite the drugs' availability to patients through expanded access programs and expedited approval pathways that speed regulatory authorization. After approval, to ensure that specialty drugs are directed to the patients who are most likely to benefit from them, the FDA can limit the scope of the drugs' indications, encourage the development of companion diagnostic tests to indicate which patients should receive the drugs, or require that manufacturers subject them to Risk Evaluation and Mitigation Strategies to ensure that their use is appropriately limited to a restricted population that is aware of the drugs' risks and benefits. Implementing these existing regulatory approaches can promote timely patient access to specialty drugs while preventing expensive and potentially inappropriate overuse.

In July 2012, the FDA Safety and Innovation Act created the “breakthrough therapy” designation to expedite development of therapies for serious diseases when evidence suggests substantial superiority over existing options. The authors discuss implications of the new designation.

This interactive graphic shows major legislative and regulatory events related to approval of new drugs by the Food and Drug Administration (FDA), drug approvals by year and by therapeutic category, and trends in the use of the FDAs various programs for expedited approval.