Generic medication now comprise roughly 90 p.c of all prescription drug purchases in the US, whereas accounting for less than 20 p.c of all prescription drug spending.1 These statistics end result from the statutory, regulatory, and biomedical analysis efforts of numerous stakeholders. For its half, the FDA has streamlined its oversight of generic drug improvement via modernized processes associated to bioequivalence examine design and information overview. As well as, the company’s analysis capabilities have been broadened to advance the requirements upon which generic drug merchandise may be assessed for efficacy, security, and high quality. Collaboration with business, lawmakers, and affected person advocacy organizations has been important to enhancing advertising and marketing practices and competitiveness in generic manufacturing.2

The advantages of a sturdy nationwide generic drug program are clear, each by way of affected person well being and the financial sustainability of our nationwide healthcare system extra broadly. Nonetheless, we proceed to face challenges specific to the generic drug panorama. A few of these come up from the scientific and regulatory complexities important to the merchandise themselves, whereas others seem to stem from societal perceptions of drug improvement and regulation that we’re nonetheless working to understand.3 We now have discovered, for instance, that variations within the look of generic capsule merchandise, regardless of their established bioequivalence, could also be related to the failure of sure sufferers to stick to evidence-based therapeutic regimens.4 We even have seen, significantly for medication that manifest a slender therapeutic window (i.e., medication the place small variations in dose or blood focus could result in severe therapeutic failures or antagonistic drug reactions), that physicians could also be extra prone to prescribe brand-name merchandise over authorized generic merchandise.5

On this Highlight on CDER Science, we overview current FDA-sponsored analysis that appears retrospectively on the medical dynamics associated to the therapeutic use of levothyroxine, a drug that not solely has a slender therapeutic window, however that additionally is without doubt one of the most generally prescription drugs in the US. The analysis, revealed in JAMA Inner Medication,6 capitalizes on using well being data to determine sufferers (anonymously) who’ve switched of their use of generic manufactured thyroxine merchandise whereas being monitored for thyroid perform over time. The deal with levothyroxine allowed the researchers, first, to execute a real-world medical overview (inside limitations dictated by out there claims information) of an FDA-approved therapeutic out there from a number of different generic producers. Second, the investigators’ evaluation extends to a consideration of whether or not social or institutional considerations, somewhat than potential evidence-based points associated to generic product efficiency, could finally place limitations on the uptake and prescribing practices of authorized generic drug merchandise.

Another excuse for specializing in levothyroxine is that the generic prescription price noticed for the drug, relative to brand-name prescription price, is way decrease than the worth of 90% cited for authorized prescribed drugs basically.6 Previous to initiating their examine, the researchers had famous, actually, that the American Thyroid Affiliation (ATA) had questioned the FDA’s strategies for figuring out bioequivalence between levothyroxine merchandise,6 which measured ranges of thyroid hormones instantly and in contrast them amongst volunteers taking totally different levothyroxine merchandise. The ATA pointers really useful utilizing thyrotropin ranges because the biomarkers for analysis of therapeutic equivalence. Within the absence of such proof, the ATA really useful that prescribers keep away from switching between levothyroxine merchandise within the remedy of hypothyroid sufferers. On account of that suggestion, brand-name levothyroxine was preferentially prescribed over generic levothyroxine merchandise.

The FDA-sponsored examine discovered that, for a inhabitants of sufferers (N > 15,000) present process correctly monitored levothyroxine remedy over time, those that switched amongst generic drug merchandise maintained the identical degree of thyroid perform (as indicated by common serum thyrotropin degree) as those that persistently used a single levothyroxine product. These outcomes set up proof that ought to mitigate considerations akin to these raised by the ATA over levothyroxine product switching.

The researchers had been cautious to level out that their examine was not designed to evaluate the therapeutic equivalence of levothyroxine merchandise. Slightly, by meticulously culling via a nationwide administrative claims database that linked laboratory check measures of thyroid perform of sufferers present process remedy with levothyroxine merchandise, the investigators recognized and matched two affected person populations to check the results of product switching to single-product use over the course of remedy. Their conclusion is that switching amongst totally different generic levothyroxine merchandise was not related to clinically vital modifications in thyroid perform (as indicated by subgroup common serum thyrotropin degree). The researchers’ conclusion—though totally according to FDA precepts of bioequivalence and, on the pharmacy degree, product interchangeability itself—conflicts with present ATA guideline suggestions that warn clinicians about potential modifications in thyroid perform related to levothyroxine product switching.

The impression of our nation’s generic drug program has been immense, with generic medication having saved our healthcare system upwards of $2.44 trillion {dollars} up to now decade. Bettering drug competitors and boosting affected person entry to revolutionary and inexpensive remedies stays a precedence for the FDA. As science and evidentiary requirements are strengthened to additional this success, it turns into equally necessary to determine elements—scientific or in any other case—that will restrict our full potential to comprehend advantages within the generic/interchangeable product area. The CDER-sponsored analysis mentioned right here means that there could also be institutional resistance amongst some stakeholders that will not be supported by real-world proof.


1Affiliation for Accessible Medicines. The U.S. Generic & Biosimilar Medicines Financial savings Report. October 2021. https://accessiblemeds.org/websites/default/information/2021-10/AAM-2021-US-Generic-Biosimilar-Medicines-Financial savings-Report-web.pdf. Accessed April 22, 2022.
2US FDA. FDA drug competitors motion plan. https://www.fda.gov/medication/guidance-compliance-regulatory-information/fda-drug-competition-action-plan. Accessed April 22, 2022.
3Deloitte. Will extra generic drug approvals push costs down, or push producers away? https://www2.deloitte.com/us/en/weblog/health-care-blog/2020/will-more-generic-drug-approvals-push-prices-down.html. Accessed April 22, 2022.
4US FDA. From our perspective: The significance of the bodily traits of generic medication. https://www.fda.gov/medication/news-events-human-drugs/our-perspective-importance-physical-characteristics-generic-drugs. Accessed April 22, 2022.
5Kesselheim AS, Misono AS, Lee JL, et al. Medical Equivalence of Generic and Model-Title Medication Utilized in Cardiovascular Illness: A Systematic Overview and Meta-analysis. JAMA. 2008;300(21):2514–2526. doi:10.1001/jama.2008.758.
6Brito JP, Deng Y, Ross JS, Choi NH, Graham DJ, Qiang Y, Rantou E, Wang Z, Zhao L, Shah ND, Lipska KJ. Affiliation Between Generic-to-Generic Levothyroxine Switching and Thyrotropin Ranges Amongst US Adults. JAMA Intern Med. 2022 Apr 1;182(4):418-425. doi: 10.1001/jamainternmed.2022.0045. PMID: 35226058; PMCID: PMC8886450.