Based on the premise that activity of an innovator drug prod- uct has already been established and documented in the NDA process, a more streamlined approach is used to approve ge- neric drugs. Submission of an abbreviated new drug application (ANDA) for approval to market a generic product was enabled by the Drug Price Competition and Patent Term Restoration Act of 1984 (also known as the Hatch-Waxman Amendments). This special form of NDA is “abbreviated” because in most cases, the sponsor is not required to conduct animal or clinical studies to es- tablish the generic drug’s safety and efficacy. Due to this regulato - ry shortcut, the sponsor is required only to demonstrate that their product performs the same as the innovator. It must contain the same amount of the same active ingredient and perform similarly to the innovator drug. Typically, this assessment is made by measuring the time that it takes for the drug to enter the bloodstream as well as the to- tal extent of absorption. Generally, this is accomplished using a clinical study where subjects receive both the branded innovator and the proposed generic drug. Data obtained from blood sam- ples is then compared statistically. If the generic is found to be statistically comparable to the brand-name product, it is said to be bioequivalent. On this basis, FDA may conclude that the prod- ucts can be used interchangeably. This process allows the gener- ic sponsor to avoid repeating expensive and duplicative clinical trials, resulting in their ability to offer their generic products at reduced cost relative to the innovator (FDA, 2022c) Every month, FDA issues an updated version of the Approved Drug Products with Therapeutic Equivalence Evaluations (the Or- ange Book). This publication identifies all FDA-approved drug products, as well as their patent and exclusivity status. Important- ly, this guide identifies generic drugs that have been shown to be therapeutically equivalent to the brand products. Therefore, this important book can serve as a critical pharmacist resource, use- ful for the selection of appropriate generic drug products (FDA, 2022d). Self-Assessment Quiz Question #5 While sponsors are required to provide documentation of every drug product’s safety and efficacy to FDA, there are differences between what evidence is usually required for brand-name and generic products. Which of the following is typically required for generics? a. Clinical studies to demonstrate efficacy. b. Clinical studies designed to show bioequivalence to the brand-name product. c. Animal studies to show that the proposed generic product is safe. d. A full NDA application. products: the Purple Book. Key elements of the Purple Book are listings of products that have been determined by the FDA to be biosimilar to other approved products. Like the Orange Book, it also includes information regarding patent and exclusivity status (FDA, n.d.). Self-Assessment Quiz Question #6 While biosimilars are conceptually similar to generic drug prod- ucts, there are differences. Which of the following distinguishes the two? a. Only generics are required to be safe. b. The review process for both types of products is similar in scope. c. Biosimilars are usually subject to an evaluation of safety and efficacy relative to the branded innovator product. d. Both biosimilars and generics drug products are typically synthesized from readily available chemical precursors.
Healthcare Professional Consideration: Patients receiving warfarin therapy may need to use a variety of dosage strengths to obtain and maintain therapeutic levels of coagulation. These changes may lead to confusion regarding the correct tablet to consume. Mistakes could lead to patient risk, either through sub- or super-therapeutic anticoagulation. Providers can par- tially mitigate this risk by ensuring that their patients are clear on the color of warfarin tablet that they should take. Self-Assessment Quiz Question #4 Although FDA requires that generics contain the same amount of active drug substance as their brand-name counterpart, there may be differences in the composition and appearance of the products. Name one consistent exception to this obser- vation. a. FDA requires that the shape of generic drugs be the same as their branded counterpart to assist patients in the identification of their medication. b. In order to maintain consistent performance, inactive ingredient profiles are identical in generic and brand-name products. c. Patients can expect that when interchanging warfarin generic products of the same dose for the color to remain relatively constant. d. The relative size of generic tablets is the same as the brand-name product. In addition to physical similarities and differences, the regulato- ry route to approval for branded and generic drugs is different. Brand-name, innovator drugs generally require more documenta- tion to support approval than generic drug products. Since 1938, every drug has been required to submit a satisfactory New Drug Application (NDA) to FDA prior to commercialization. The con- cept of the NDA is that the sponsor must generate a compre- hensive document designed to allow FDA reviewers to reach the following critical decisions: ● The new drug is safe and effective for its proposed use. In essence, proof must be provided demonstrating that the ben- efits of the medication outweigh the risks. ● The proposed package insert is appropriate, accurate, and contains all the information needed for a prescriber to safely use the medication. ● The manufacturing and control processes are adequate to en- sure the drug’s identity, strength, quality, and purity. The NDA, then, must tell the entire story of the drug, to include what it contains, how it is made and packaged, the results of ani- mal studies, and how it behaves in the body (FDA, 2022b). Biosimilars Conceptually, biosimilars are like generic drugs: alternative ver- sions that work like innovator products. The divergence is given away by their name. Unlike generic drugs whose active ingredi- ents are identical to the brand-name product, biosimilars are re- quired to be comparable to the predecessor product. The key difference is that biosimilars, made from natural sources, may be structurally complex, while generic drugs, synthesized from chemical sources are more easily characterized. Due to potential differences in biosimilars, inherent to their complicated compo- sition, FDA often requires more information for these products than they do for generic drugs. The comparability of biosimilars, relative to the brand-name product, is tested using clinical trials, evaluating safety and efficacy, and by undergoing an abbreviated FDA review process. These products must be shown to be safe and effective and may be less expensive than the brand-name medication. (NCI, 2020). Similar to the Orange Book, FDA maintains a database containing information on all FDA-licensed biological products, to include licensed biosimilar, interchangeable products, and their reference
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