US Pharm. 2018;43(6)(Generic Drugs suppl):6-8.
ABSTRACT: Patients may lack an understanding of generic drugs, which are determined to be equally as safe and effective as their branded counterparts by the FDA, as well in comparison studies. Because the FDA approval process for generic drugs requires fewer resources, generic drugs are less expensive and can help patients reduce prescription healthcare costs. Pharmacists are well positioned to guide both patients and clinicians in the appropriate use of generic drugs, and they therefore have the opportunity to address questions from their patients and enhance patients’ knowledge to encourage the use of generic drugs.
According to the U.S. Department of Health and Human Services, prescription-drug spending in the United States was estimated to be about $457 billion in 2015, and spending has continued to increase significantly since then.1 Kesselheim and colleagues attribute the exponential prescription-drug spending to increasingly high prices for brand-name drugs.2 Drug manufacturers can set prices based on market exclusivity granted by the FDA for a certain period of time following approval of the drug; this exclusivity ranges from 3 to 7 years. Generic-drug availability can be a means of reducing drug spending and overall healthcare costs. The influence of generic drugs in the market, however, realizes its potential only when the patent of a brand-name drug has ended and the generic drug is not inhibited by regulatory processes.2
FDA Approval of Brand-Name Versus Generic Drugs
A product is approved by the FDA as a brand-name drug after a lengthy process starting with research and development and ending with the completion of various applications. Before conducting large clinical trials to assess a drug’s efficacy and safety in humans, a drug company first investigates efficacy and safety through laboratory and animal tests. The company submits an Investigational New Drug application to the FDA’s Center for Drug Evaluation and Research before performing clinical trials in humans. Once approved, clinical trials are conducted in three phases, which, combined, can take several years to complete.3,4
Because the research and development stage of a new drug takes a long time and involves substantial resources, brand-name drugs command high prices in order to recover the costs over the course of an approved patent period.5 When the patent on an existing brand-name drug is nearing its end, a generic drug manufacturer may submit an Abbreviated New Drug Application (ANDA) to demonstrate the safety and effectiveness of its formulation of the drug conducting lengthy clinical trials.6 A drug is considered a generic substitute if the FDA has deemed it to be bioequivalent to the corresponding brand-name (or reference) drug.5 A bioequivalent substitute is a generic drug that exhibits bioavailability properties—such as rate and extent of absorption—similar to those of the reference drug.7
The Orange Book is the FDA’s repository and coding system for approved drugs and their bioequivalent products. If a drug is therapeutically equivalent to its reference drug, it receives the code “A” followed by another letter indicating its dosage form. This means that the drug exhibits properties meeting the necessary bioequivalence requirements and that it is expected to be as effective and safe as the reference drug. If a drug is not deemed therapeutically equivalent, it is given the code “B.” A drug is coded “AB” if any identified bioequivalence problems were resolved in order to render it bioequivalent.7
In addition to proving bioequivalence, a generic-drug manufacturer must provide the FDA with information about its processes for manufacturing the actual product to ensure its high quality. Multiple drug manufacturers can produce a generic product, leading to increased competition and a further reduction in overall drug prices.6
Even if a generic drug company submits an ANDA, FDA approval may be delayed if an application is incomplete or if the provided data are unsatisfactory or do not meet the aforementioned requirements.6
Studies Comparing Brand-Name Versus Generic Drugs
Many studies demonstrate the efficacy and safety of generic drugs compared with brand-name drugs. To take one example, cardiovascular disease comprises multiple conditions that contribute to high healthcare spending; therefore, it would be reasonable to develop and approve generic equivalents of therapeutic agents to curb such costs while maintaining positive health outcomes. A 2008 systematic review and meta-analysis examined studies comparing clinical outcomes between generic and brand-name drugs used to treat cardiovascular diseases.8 No difference in clinical outcomes was found between the bioequivalent drugs, even in drugs with narrow therapeutic indexes (i.e., warfarin vs. Coumadin). The one study that did demonstrate a difference in outcomes did not compare a bioequivalent formulation of warfarin with Coumadin.8
Shrank and colleagues found that medication adherence improved in patients with chronic conditions when they were prescribed generic drugs instead of brand-name drugs. Through an analysis of pharmacy claims data from a large health plan, the authors measured adherence—defined as the proportion of days covered in the first year of use—and determined how the health plan’s formulary affected adherence.9 It was concluded that adherence was greater when patients were prescribed generic or preferred drugs instead of nonpreferred drugs, which are often brand-name drugs that do not have generic equivalents.9
A systematic review and meta-analysis by Kesselheim and colleagues sought to determine whether generic substitutions for antiepileptic drugs resulted in loss of seizure control.10 Based on the randomized, controlled studies analyzed, it was found that generic substitutions did not differ from brand-name equivalents. However, the authors noted that in the observational studies analyzed, patients used more health services as a result of switching from a brand-name product to a generic drug, indicating a possible decrease in efficacy with the generic agents. As with any narrow-therapeutic-index drug, it is recommended that drug concentrations and/or relevant laboratory values be closely monitored when a patient is switched from one epileptic drug formulation to another.10
Educating Patients About Generic Drugs
Patients may have a poor understanding of generic drugs, which can affect their willingness to use these agents. Pharmacists have the opportunity to identify patient concerns by encouraging their patients to ask questions, and they can clarify potential misconceptions about generic drugs via patient education. With open communication, pharmacists can improve patients’ knowledge and help them become more comfortable with using generic drugs.11 See TABLE 1 for a listing of frequently asked patients’ questions about generic drugs, as well as suggested patient-friendly responses that the pharmacist can provide.
The availability of generic drugs allows patients to purchase cheaper equivalents of brand-name drugs without compromising efficacy, safety, or quality. Therefore, the use of generics can greatly reduce healthcare costs associated with prescription-drug spending. Pharmacists can encourage patients’ acceptance of generics and provide information that helps patients understand the similarities and differences between generic and brand-name drugs, as well as guide clinicians in the appropriate use of generic drugs.
1. ASPE Issue Brief. Observations on trends in prescription drug spending. https://aspe.hhs.gov/sites/default/files/pdf/187586/Drugspending.pdf. March 8, 2016. Accessed March 14, 2018.
2. Kesselheim AS, Avorn J, Sarpatwari A. The high cost of prescription drugs in the United States: origins and prospects for reform. JAMA. 2016;316:858-871.
3. FDA. Development & approval process (drugs). www.fda.gov/Drugs/DevelopmentApprovalProcess/default.htm#FDA. Accessed March 16, 2018.
4. FDA. How drugs are developed and approved. www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/default.htm. Accessed March 16, 2018.
5. FDA. Generic drugs: questions & answers. www.fda.gov/drugs/resourcesforyou/consumers/questionsanswers/ucm100100.htm#q1. Accessed March 15, 2018.
6. FDA. The generic drug approval process. www.fda.gov/Drugs/NewsEvents/ucm508150.htm. Accessed March 15, 2018.
7. U.S. Department of Health and Human Services. Approved Drug Products With Therapeutic Equivalence Evaluations, 38th ed. www.fda.gov/cder/orange/obannual.pdf. Accessed March 15, 2018.
8. Kesselheim AS, Misono AS, Lee JL, et al. Clinical equivalence of generic and brand-name drugs used in cardiovascular disease: a systematic review and meta-analysis. JAMA. 2008;300:2514-2526.
9. Shrank WH, Hoang T, Ettner SL, et al. The implications of choice: prescribing generic or preferred pharmaceuticals improves medication adherence for chronic conditions. Arch Intern Med. 2006;166:332-337.
10. Kesselheim AS, Stedman MR, Bubrick EJ, et al. Seizure outcomes following the use of generic versus brand-name antiepileptic drugs: a systematic review and meta-analysis. Drugs. 2010;70:605-621.
11. Sanchez CK, Zurek AM. Patient perceptions of generic drugs: dispelling misconceptions. US Pharm. 2016;41(6)(Generic Drug Review suppl):36-41.
12. Pope ND. Generic substitution of narrow therapeutic index drugs. US Pharm. 2009;34(6)(Generic Drug Review suppl):12-19.
13. Vivian JC. Generic-substitution laws. US Pharm. 2008;33(6)(Generic Drug Review suppl):30-34.
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