The most widespread shortage identified in the new survey involves ifosfamide, a generic chemotherapy drug that 94 percent of responding centers reported as being in short supply. Ifosfamide is far from a niche product: it is a workhorse alkylating agent deployed in treatment regimens for bladder, ovarian, testicular, and uterine cancers, as well as soft tissue sarcoma, osteosarcoma, and several adult and pediatric leukemias and lymphomas. Its inclusion among pediatric and adolescent cancer protocols makes the shortage particularly consequential, because clinicians managing young patients with limited therapeutic alternatives have fewer options to substitute when a foundational drug becomes scarce. The breadth of ifosfamide’s use across tumor types means that a single manufacturing failure can touch nearly every subspecialty within a comprehensive cancer center at once, from sarcoma clinics to hematology wards.

Platinum-based chemotherapy agents, which form the backbone of curative and palliative regimens for numerous tumor types, are also under strain once again. Seventy-one percent of surveyed centers reported a current shortage of carboplatin, a striking return of the supply crisis that first drew national attention in 2023, while 16 percent reported shortages of cisplatin. These two drugs are among the most widely used cytotoxic agents in modern medicine, appearing in protocols for lung, ovarian, testicular, head and neck, and many other cancers. In addition, more than half of respondents reported ongoing shortages of Bacillus Calmette-Guérin, or BCG, the immunotherapy instilled directly into the bladder to treat non-muscle-invasive bladder cancer, a therapy for which there is no simple pharmacologic equivalent. The recurrence of carboplatin shortages, after an intense period of public attention and federal response in 2023, suggests that the underlying vulnerabilities in the generic injectable drug supply chain have not been resolved.

NCCN first began surveying its Member Institutions about drug shortages in June 2023, when an abrupt collapse in the supply of carboplatin and cisplatin, traced in part to quality problems at overseas manufacturing facilities, forced oncologists across the country to ration doses and delay treatments. The fact that the network has continued to measure the problem for more than three years provides a rare longitudinal view of a persistent public health failure. When the latest survey asked pharmacy directors whether national or state policies had made the shortage situation better or worse since 2023, only 4 percent said conditions had improved, while 96 percent felt the situation had stayed the same. That near-unanimous assessment of policy stagnation is perhaps the most politically significant finding in the dataset, indicating that legislative and regulatory efforts to date have not yet altered the economic dynamics that produce recurring shortages.

Crystal S. Denlinger, MD, Chief Executive Officer of NCCN, described the persistence of the problem as disheartening, noting that recurring or continued shortages of some drugs have continued despite years of raising the alarm and providing insight about what she characterized as a disruptive and dangerous issue for cancer care in America. Denlinger emphasized that the cancer centers in the network have developed internal strategies, task forces, and communications plans to keep patient care and clinical trials on track. The good news, she noted, is that those mechanisms exist; the bad news is that managing shortages consumes time and attention that could otherwise be spent improving patient experiences and outcomes, and it adds additional stress to an already burdened system. Her comments capture a paradox familiar to hospital pharmacists nationwide: the institutions best equipped to absorb supply shocks are also the ones expending enormous invisible labor to do so.

The operational toll of shortages is quantified elsewhere in the survey. Sixty-one percent of responding centers reported that they required pharmacy and physician-led mitigation strategies to keep all of their patients on a recommended dose and schedule. The majority of those centers implemented waste management strategies, which can include conserving vials, sharing partially used vials across patients under strict sterility protocols, and adjusting compounding practices to extract every usable dose from limited inventory. Others explored alternative recommended regimens, drawing on the NCCN Clinical Practice Guidelines in Oncology to identify evidence-based substitutions that preserve guideline-recommended care when a preferred agent is unavailable. These workarounds are clinically defensible, but they represent a continuous, resource-intensive improvisation that would be unnecessary in a functioning market.

When treatment plans did have to be modified because of shortages, 90 percent of centers reported a need for repeat prior authorization of the revised plan. That administrative requirement significantly increases the amount of work per patient and introduces the potential for delays in care continuity, since insurers must re-approve altered regimens before treatment can proceed. For patients, the consequence can be a gap between the decision to change therapy and the ability to actually receive it, a window in which aggressive cancers do not pause. For clinical staff, prior authorization rework compounds the pharmacy labor already consumed by shortage mitigation, illustrating how a supply chain failure upstream cascades into administrative burden downstream, multiplying the true cost of each shortage far beyond the price of the missing drug itself.

On the question of solutions, the survey revealed a strong consensus among pharmacy leadership. Alyssa Schatz, DrPh, MSW, Vice President of Policy and Advocacy at NCCN, noted that nearly every pharmacy director who responded would like to see economic incentives put in place to encourage high-quality manufacturing for generic cancer medications, something advocates have been requesting for years. One survey respondent summarized the core problem in stark terms: many oncology generics are clinically indispensable but economically unattractive, and without correcting that economic imbalance, shortages are likely to recur. The structural logic is well understood in health policy circles. Generic injectable drugs are cheap, which benefits payers and patients, but rock-bottom prices leave manufacturers with thin margins, little incentive to invest in quality infrastructure or redundancy, and every reason to exit the market when problems arise. The survey also illuminated a desire for better information about generic suppliers and for earlier notifications by manufacturers to the US Food and Drug Administration, which would give hospitals more lead time to prepare mitigation plans before shelves empty.

NCCN is part of the End Cancer Drug Shortages Coalition, a group that brings together more than a dozen hematology and oncology nonprofits to address the issue and propose long-term solutions. In May 2026, the coalition issued a consensus statement offering a big-picture assessment of the ongoing problem and a list of policy proposals for the future, ranging from payment and purchasing reforms to manufacturing quality incentives. The coalition’s work reflects a growing recognition among oncology professional societies that shortage response cannot remain the province of individual hospital task forces indefinitely, and that durable fixes must operate at the level of the market itself, where the pricing of essential generic medicines currently fails to reward reliability.

For patients and clinicians, the practical meaning of the 2026 survey is sobering: three years of advocacy, congressional hearings, and federal attention have produced internal resilience but not external change. Every comprehensive cancer center surveyed is still managing around at least one missing chemotherapy agent, and a substantial fraction is juggling five or more at once. The network’s findings, available through NCCN’s drug shortage resources, will continue to serve as a benchmark for measuring whether the economic incentives, supplier transparency measures, and early notification requirements that pharmacy leaders overwhelmingly support are eventually translated into policy. Until then, the quiet work of vial conservation, regimen substitution, and reauthorization paperwork will remain an unheralded but essential layer of cancer care in the United States, holding the system together one shortage at a time.

Subject of Research: Persistent generic cancer medication shortages reported by United States comprehensive cancer centers

Article Title: New NCCN survey highlights persistent cancer medication shortages across United States

Article References: New NCCN survey highlights persistent cancer medication shortages across United States. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: NCCN, drug shortages, cancer medication, ifosfamide, carboplatin, cisplatin, BCG, generic drugs, oncology, pharmacy, health policy, supply chain

The drug at the center of the study, roxithromycin, is a macrolide antibiotic related to erythromycin, used against respiratory tract and other bacterial infections. Like many macrolides, it is given orally and its absorption into the bloodstream depends on a chain of events that includes dissolution of the tablet in the gastrointestinal tract, permeation across the intestinal wall, and distribution into tissues. Any change in the formulation, the manufacturing process, or even the excipients used to bind and coat the tablet can in principle alter how quickly and completely the drug reaches the circulation. That is why regulators require bioequivalence testing whenever a generic version or a modified formulation is brought to market. The standard metrics are the area under the concentration-time curve, which reflects total drug exposure, the maximum plasma concentration, which reflects peak exposure, and the time at which that maximum occurs. If the ratios of these parameters between test and reference products fall within a ninety percent confidence interval of eighty to one hundred twenty-five percent, the products are considered bioequivalent.

Conducting such trials in humans is expensive, slow, and ethically burdensome, since volunteers are exposed to a drug without any personal therapeutic benefit. This is where physiologically based pharmacokinetic modeling, or PBPK, enters the picture. Unlike simpler empirical models that treat the body as a set of mathematical compartments with fitted parameters, a PBPK model attempts to represent the actual anatomy and physiology of the body: organs and tissues are connected by blood flows, and drug movement between them is governed by physicochemical properties such as solubility, permeability, lipophilicity, and protein binding, together with physiological parameters like organ volumes, blood flow rates, and enzyme abundances. Because the underlying structure reflects real biology, a well-constructed PBPK model can be adapted to different populations, doses, and even formulations simply by swapping in the relevant inputs, making it a powerful tool for predicting drug behavior in scenarios that have never been tested clinically.

The research team, led by Danfeng Yu, Qin Li, and colleagues including corresponding authors Jiyu Chen and Yan He, assembled roxithromycin’s physicochemical, in vitro, and in vivo parameters from established databases and the published literature, and constructed an adult PBPK model using the open-source software platform PK-Sim. The initial model was developed and calibrated against clinical pharmacokinetic data from a 150 milligram dose of the reference formulation. The critical test of any model, however, is not how well it fits the data used to build it, but how well it predicts data it has never seen. To address this, the researchers performed a comparative evaluation using clinical data from the test formulation, checking whether the model could reproduce concentration-time profiles for a product whose behavior had not informed the model’s construction.

To quantify the agreement between prediction and observation, the team applied the mean fold error approach, a standard metric in pharmacokinetic modeling that measures the ratio of predicted to observed values. For the three key parameters, the area under the curve from zero to the last measurable time point, the maximum concentration, and the time to maximum concentration, more than ninety percent of the mean fold error ratios fell within the range of 0.5 to 2. This means that for the overwhelming majority of comparisons, the model’s predictions were within a factor of two of the measured values, and in most cases considerably closer. With the model thus validated, the researchers imported formulation-specific in vitro dissolution data for both products, allowing the simulations to distinguish between the two tablets based on how rapidly each released its drug payload in the digestive tract.

The virtual bioequivalence trial itself was conducted in a simulated cohort of ninety-nine East Asian subjects, a population chosen to match the demographic context in which the formulations are intended to be used. Virtual subjects in PBPK platforms are not identical clones; the software samples from realistic distributions of physiological parameters such as body weight, gastric emptying time, and intestinal transit, so that the simulated population exhibits the same variability that a real trial population would. Each virtual subject received both formulations, and the resulting pharmacokinetic profiles were analyzed exactly as they would be in a conventional bioequivalence study. The outcome was unambiguous: the ninety percent confidence intervals for the geometric mean ratios of the primary pharmacokinetic parameters all fell within the regulatory acceptance range of eighty to one hundred twenty-five percent, indicating that the two formulations would be judged bioequivalent.

The implications of this result extend well beyond a single antibiotic. Bioequivalence studies are among the most numerous clinical trials conducted worldwide, required for every generic approval and for many post-approval manufacturing changes. If validated PBPK models can reliably substitute for some of these trials, the savings in cost, time, and human exposure could be substantial. Regulators, including the United States Food and Drug Administration and the European Medicines Agency, have already issued guidance on when modeling and simulation can support or replace certain clinical studies, and virtual bioequivalence is an active area of regulatory science. The present study adds to a growing body of evidence that, for drugs with well-characterized pharmacokinetics and formulations whose dissolution behavior can be measured reliably in vitro, a computer can indeed stand in for the clinic.

The study also illustrates the methodological discipline that makes such virtual trials credible. The researchers did not simply assume the model was correct; they built it from one dataset, tested it against an independent dataset from a different formulation, and reported a formal quantitative measure of predictive performance before trusting it for the bioequivalence question. The work was registered retrospectively at ClinicalTrials.gov under number NCT06798051, the underlying clinical study was approved by the Medical Ethics Committee of the Affiliated Hospital of Guizhou Medical University, and all participants in the source trials provided informed consent. The modeling was funded by the Science and Technology Planning Project of Guizhou Province and related institutional programs, and the authors declared no competing interests.

Certain caveats remain. A virtual trial is only as good as its underlying model, and PBPK predictions for drugs with complex metabolism, food effects, or narrow therapeutic windows demand even more extensive validation than was possible here. The ninety-nine subject cohort, while adequate for this comparison, is a simulation of a specific population rather than a demonstration across all patient groups. Nevertheless, the study offers a concrete template for how virtual bioequivalence can be conducted and documented: assemble the drug’s parameters, build and validate the model against real data, import formulation-specific dissolution profiles, and simulate a demographically realistic cohort under the same statistical criteria that govern human studies. As more models of this kind accumulate and are independently verified, the day when a generic drug can win approval on the strength of a computer trial, with human studies reserved for cases the models cannot yet handle, moves measurably closer.

Subject of Research: Virtual bioequivalence assessment of two roxithromycin formulations using a physiologically based pharmacokinetic model

Article Title: Virtual bioequivalence assessment for two roxithromycin formulations using a physiologically based pharmacokinetic model

Article References: Yu, D., Li, Q., Zeng, L., Liao, M., Lu, X., Chen, J., & He, Y. (2026). Virtual bioequivalence assessment for two roxithromycin formulations using a physiologically based pharmacokinetic model. BMC Pharmacology and Toxicology. https://doi.org/10.1186/s40360-026-01244-7

Image Credits: AI Generated

DOI: 10.1186/s40360-026-01244-7

Keywords: roxithromycin, PBPK modeling, virtual bioequivalence, PK-Sim, pharmacokinetics, generic drugs, drug dissolution, macrolide antibiotics, clinical trial simulation, regulatory science, East Asian population, BMC Pharmacology and Toxicology

Teneligliptin belongs to a family of medicines known as dipeptidyl peptidase-4, or DPP-4, inhibitors. These drugs work by blocking an enzyme that normally degrades incretin hormones, the gut-derived chemical messengers that prompt the pancreas to release insulin after a meal and to suppress glucagon when blood sugar is already adequate. By preserving incretin activity, DPP-4 inhibitors produce a glucose-dependent enhancement of insulin secretion, which gives them a comparatively favorable safety profile relative to some older antidiabetic agents. Teneligliptin in particular has gained a substantial foothold in Asian markets, where it is prescribed for adults with type 2 diabetes whose glycemic control is inadequate through diet and exercise alone.

The scientific rationale for the new study rests on a fundamental principle of generic drug approval: before a copycat tablet can be substituted for the branded original, regulators demand quantitative proof that the two formulations behave identically inside the body. This property, called bioequivalence, is assessed by comparing how much drug reaches the bloodstream, how quickly it gets there, and how long it lingers. The standard benchmarks are the area under the plasma concentration-time curve, abbreviated AUC, which captures total systemic exposure, and the maximum observed plasma concentration, known as Cmax, which reflects the peak level achieved after a dose. Because a generic can be manufactured and sold at a fraction of the brand-name price, demonstrating bioequivalence is the gateway to cost savings that can ripple across entire health systems, a consideration that is especially acute in countries with large diabetic populations and constrained drug budgets.

To generate that proof, the researchers recruited 52 healthy Chinese adults and enrolled them in a randomized, open-label, single-dose, two-sequence, two-period crossover trial, with 26 participants assigned to each treatment sequence. In a crossover design, every volunteer eventually receives both formulations, with the order of administration randomized; this arrangement is prized in bioequivalence work because each participant serves as his or her own control, stripping away much of the noise introduced by individual differences in metabolism, body composition, and physiology. The washout interval between the two doses was set at seven days, long enough for the first dose to be fully eliminated before the second was taken, ensuring that lingering drug from one period could not contaminate measurements in the other.

The trial was conducted twice under deliberately different dietary conditions, once in the fasting state and once after food. This dual design matters because meals can alter gastric emptying, bile flow, and the solubility of orally administered compounds, sometimes shifting absorption in ways that change both the speed and the extent of drug uptake. Regulatory agencies typically require bioequivalence testing under fasting conditions, and add a fed arm when a drug is likely to be taken with meals or when food effects are anticipated. A single 40 mg dose of either the test generic or the reference Tenelia was administered in each condition, allowing the investigators to establish that the two tablets perform equivalently regardless of whether a patient swallows the pill before breakfast or alongside it.

Measuring the drug in plasma demanded a highly sensitive analytical technique. The team used liquid chromatography-tandem mass spectrometry, or LC-MS/MS, a method that first separates teneligliptin from the other components of blood plasma and then fragments the molecules in a way that allows precise quantification even at very low concentrations. The assay was validated before use, and the accuracy of the measurements was verified through incurred sample reanalysis, in which selected patient samples are tested a second time to confirm that the original results are reproducible. Such quality-control steps are indispensable, because a bioequivalence verdict is only as trustworthy as the concentration data on which the entire statistical comparison is built.

The statistical framework for the comparison follows internationally harmonized regulatory conventions. For each pharmacokinetic parameter, the researchers calculated the geometric mean ratio between the generic and the branded product, then determined the 90 percent confidence interval around that ratio after logarithmic transformation of the data. Equivalence is declared only when the entire confidence interval falls within the predefined acceptance boundaries of 80 to 125 percent for the parameters AUC from time zero to the last measurable concentration, AUC extrapolated to infinity, and Cmax. The analysis of variance, or ANOVA, framework used for this purpose formally accounts for the crossover structure of the trial, testing whether formulation, period, and sequence effects influence the observed differences. In both the fasting and the fed studies, every confidence interval landed squarely inside the acceptance window, satisfying the regulatory criterion for bioequivalence in full.

Safety was monitored alongside the pharmacokinetic measurements, with adverse events graded according to the Common Terminology Criteria for Adverse Events, version 5.0. No serious adverse events occurred during the trial, an outcome consistent with the generally well-tolerated character of DPP-4 inhibitors at single therapeutic doses in healthy volunteers. While a small crossover study in healthy adults cannot substitute for the broader safety record accumulated through post-marketing surveillance, the absence of serious events provides reassurance that the generic formulation introduces no novel tolerability concerns relative to the established product.

The study was carried out from April through September 2025 at The Affiliated Panyu Central Hospital of Guangzhou Medical University, conducted in accordance with the Declaration of Helsinki and approved in advance by the institution’s Drug Clinical Trial Ethics Committee. Each volunteer provided written informed consent before screening began, and the trial was registered in the Chinese Clinical Trial Registry under identifier ChiCTR2500112749, registered retrospectively on November 19, 2025, with an earlier entry on the Drug Clinical Trial Registration and Information Publicity Platform under CTR20252533. The conduct of the trial and the preparation of the manuscript adhered to the CONSORT 2025 reporting guidelines and their applicable bioequivalence extensions, reflecting the transparency standards now expected of clinical research.

The broader significance of the result extends well beyond a single tablet. Bioequivalence studies of this kind form the backbone of generic substitution policies worldwide, allowing pharmacists and physicians to swap in lower-cost alternatives with confidence that patients will experience the same therapeutic effect. For teneligliptin specifically, the availability of a demonstrated equivalent generic in China could ease the financial burden of long-term diabetes therapy for a patient population that continues to grow. The authors conclude that the pharmacokinetic comparison supports the generic product as an equivalent alternative to Tenelia under both fasting and fed conditions, and that the evidence should help inform the product’s acceptance in clinical practice. The study was funded entirely without external grants, and the authors declare no competing interests, with the article published open access under a Creative Commons license so that clinicians, regulators, and patients can examine the full data for themselves.

Subject of Research: Bioequivalence evaluation of generic teneligliptin hydrobromide tablets in healthy Chinese volunteers

Article Title: Pharmacokinetic and bioequivalence evaluation of teneligliptin hydrobromide tablets following single-dose administration in healthy Chinese volunteers under fasting and fed conditions

Article References: Guan, Z., Chen, M., Wei, B., Su, J., Tan, D., Ke, J., & Huang, G. (2026). Pharmacokinetic and bioequivalence evaluation of teneligliptin hydrobromide tablets following single-dose administration in healthy Chinese volunteers under fasting and fed conditions. BMC Pharmacology and Toxicology. https://doi.org/10.1186/s40360-026-01234-9

Image Credits: AI Generated

DOI: 10.1186/s40360-026-01234-9

Keywords: teneligliptin, bioequivalence, pharmacokinetics, type 2 diabetes, DPP-4 inhibitor, generic drugs, LC-MS/MS, clinical trial, Chinese volunteers, drug safety, crossover study, BMC Pharmacology and Toxicology