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Generic Pills From the Patient Perspective: Comment on “Variations in Pill Appearance of Antiepileptic Drugs and the Risk of Nonadherence”

Generic Pills From the Patient Perspective: Comment on “Variations in Pill Appearance of... Generic drug products are becoming increasingly important to health care. Nearly 80% of prescriptions filled in the United States are for generic drugs. At the US Food and Drug Administration (FDA), the Office of Generic Drugs (OGD) is responsible for the approval of generic drug products. The OGD assesses the safety, efficacy, and quality of generic drug products by making a finding of pharmaceutical equivalence and “bioequivalence.” A key principle is that generic drug products that reach health care providers and patients must be scientifically verified as appropriately substitutable for the brand-name products that are listed by the FDA as reference products. Beyond regulated standards of pharmaceutical equivalence, bioequivalence, and good manufacturing practices, drug manufacturers have been free to exercise certain rights common to manufacturers of nondrug products. The investigations and discussions of Kesselheim et al1 and Greene and Kesselheim2 touch on the trade dress rights of generic drug manufacturers. The authors' analysis suggests that physical appearance may have important consequences for patient adherence to prescribed drug regimens. As a science-based institution, the FDA is not charged to regulate products with regard for aesthetic factors such as pill color or shape. But the agency has long recognized the impact of physical attributes, such as color scheme, size, and shape, in affecting patient opinion of products. We will never know if “a little red pill” (rather than purple) could have had quite the same impact on pharmacological treatments of gastroesophageal reflux disease that we have witnessed in the past decade or so. But we do know, as Kesselheim et al1 show in their investigation, that switching from a brand-name product to a generic product with a significantly different appearance can be problematic for some patients. The authors reveal that medication regimens involving antiepileptic drugs (AEDs) can be adversely affected when patients encounter generic versions of an AED. The choice of AEDs as the basis of their analysis is interesting in that the substitutability of generic AEDs has been questioned by the American Academy of Neurology,3 the American Epilepsy Society,4 and the Epilepsy Foundation.5 The authors' intriguing finding—that changes in pill color in particular may undermine patient compliance—clearly speaks to the concerns of these organizations. The FDA applauds the authors' attention to the effect of physical characteristics of AEDs, and the OGD has, in fact, started to include in its reviews the visual dimensions of product presentation that could have an impact on patient compliance. It will be interesting to see how the results of the authors' study of AED adherence will compare with studies in other drug classes. As the development and use of generic drug products continue to expand, the issues raised by the authors, as well as countless other challenges, will become ever more urgent. The FDA is committed to partnering with other stakeholders in addressing these challenges. Generic drug manufacturers will be challenged to consider the patient's potential sensibility in their pharmaceutical development process, not to make all generic versions of a class to be physically identical but rather to consider pill size, shape, and color with more consistent regard, not only for proprietary issues but also for the information we are gaining concerning the realities of patient use. Health care providers will need to educate patients more effectively about generic drugs and must foresee possible patient concerns over product appearance. And increasingly, the role of patient self-education comes to bear on multiple aspects of generic drug use. Clearly, the FDA, too, can play roles in each of these arenas. With the commencement of the Generic Drug User Fee Act program, we expect the number of FDA staff dedicated to the review, approval, and continued safety monitoring of generic drugs to more than double in the next 3 years. The agency, along with many stakeholders in the health care arena, believes that such staff growth is essential in view of our nation's growing demand for generic drugs. We very much hope that work, such as that presented by Kesselheim et al,1 will continue to inform our appreciation for the great challenges that lie ahead in the development and approval of generic drugs. We believe that the nation's health care system can be greatly strengthened by such science-based approaches that so elegantly focus on the patients themselves who rely on that system. Back to top Article Information Correspondence: Dr Yu, Office of Generic Drugs, US Food and Drug Administration, 7519 Standish Pl, Rockville, MD 20855 (lawrence.yu@fda.hhs.gov). Published Online: December 31, 2012. doi:10.1001/jamainternmed.2013.2283 Conflict of Interest Disclosures: None reported. References 1. Kesselheim AS, Misono AS, Shrank WH, et al. Variations in pill appearance of antiepileptic drugs and the risk of nonadherence [published online December 31, 2012]. JAMA Intern Med. 2013;173(3):202-208Google Scholar 2. Greene JA, Kesselheim AS. Why do the same drugs look different? pills, trade dress, and public health. N Engl J Med. 2011;365(1):83-8921732842PubMedGoogle ScholarCrossref 3. American Academy of Neurology position statement, November 2, 2006. http://www.aan.com/globals/axon/assets/2323.pdf. Accessed October 8, 2012 4. The substitution of different formulations of antiepileptic drugs for the treatment of epilepsy, November 29, 2007. http://www.aesnet.org/go/press-room/consensus-statements/drug-substitution. Accessed October 8, 2012 5. Statement on substitution of generic antiepileptic drugs, May 2009. http://www.epilepsyfoundation.org/getinvolved/advocacy/positionstatements/genedrev.cfm. Accessed October 8, 2012 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png JAMA Internal Medicine American Medical Association

Generic Pills From the Patient Perspective: Comment on “Variations in Pill Appearance of Antiepileptic Drugs and the Risk of Nonadherence”

JAMA Internal Medicine , Volume 173 (3) – Feb 11, 2013

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Publisher
American Medical Association
Copyright
Copyright © 2013 American Medical Association. All Rights Reserved.
ISSN
2168-6106
eISSN
2168-6114
DOI
10.1001/jamainternmed.2013.2283
Publisher site
See Article on Publisher Site

Abstract

Generic drug products are becoming increasingly important to health care. Nearly 80% of prescriptions filled in the United States are for generic drugs. At the US Food and Drug Administration (FDA), the Office of Generic Drugs (OGD) is responsible for the approval of generic drug products. The OGD assesses the safety, efficacy, and quality of generic drug products by making a finding of pharmaceutical equivalence and “bioequivalence.” A key principle is that generic drug products that reach health care providers and patients must be scientifically verified as appropriately substitutable for the brand-name products that are listed by the FDA as reference products. Beyond regulated standards of pharmaceutical equivalence, bioequivalence, and good manufacturing practices, drug manufacturers have been free to exercise certain rights common to manufacturers of nondrug products. The investigations and discussions of Kesselheim et al1 and Greene and Kesselheim2 touch on the trade dress rights of generic drug manufacturers. The authors' analysis suggests that physical appearance may have important consequences for patient adherence to prescribed drug regimens. As a science-based institution, the FDA is not charged to regulate products with regard for aesthetic factors such as pill color or shape. But the agency has long recognized the impact of physical attributes, such as color scheme, size, and shape, in affecting patient opinion of products. We will never know if “a little red pill” (rather than purple) could have had quite the same impact on pharmacological treatments of gastroesophageal reflux disease that we have witnessed in the past decade or so. But we do know, as Kesselheim et al1 show in their investigation, that switching from a brand-name product to a generic product with a significantly different appearance can be problematic for some patients. The authors reveal that medication regimens involving antiepileptic drugs (AEDs) can be adversely affected when patients encounter generic versions of an AED. The choice of AEDs as the basis of their analysis is interesting in that the substitutability of generic AEDs has been questioned by the American Academy of Neurology,3 the American Epilepsy Society,4 and the Epilepsy Foundation.5 The authors' intriguing finding—that changes in pill color in particular may undermine patient compliance—clearly speaks to the concerns of these organizations. The FDA applauds the authors' attention to the effect of physical characteristics of AEDs, and the OGD has, in fact, started to include in its reviews the visual dimensions of product presentation that could have an impact on patient compliance. It will be interesting to see how the results of the authors' study of AED adherence will compare with studies in other drug classes. As the development and use of generic drug products continue to expand, the issues raised by the authors, as well as countless other challenges, will become ever more urgent. The FDA is committed to partnering with other stakeholders in addressing these challenges. Generic drug manufacturers will be challenged to consider the patient's potential sensibility in their pharmaceutical development process, not to make all generic versions of a class to be physically identical but rather to consider pill size, shape, and color with more consistent regard, not only for proprietary issues but also for the information we are gaining concerning the realities of patient use. Health care providers will need to educate patients more effectively about generic drugs and must foresee possible patient concerns over product appearance. And increasingly, the role of patient self-education comes to bear on multiple aspects of generic drug use. Clearly, the FDA, too, can play roles in each of these arenas. With the commencement of the Generic Drug User Fee Act program, we expect the number of FDA staff dedicated to the review, approval, and continued safety monitoring of generic drugs to more than double in the next 3 years. The agency, along with many stakeholders in the health care arena, believes that such staff growth is essential in view of our nation's growing demand for generic drugs. We very much hope that work, such as that presented by Kesselheim et al,1 will continue to inform our appreciation for the great challenges that lie ahead in the development and approval of generic drugs. We believe that the nation's health care system can be greatly strengthened by such science-based approaches that so elegantly focus on the patients themselves who rely on that system. Back to top Article Information Correspondence: Dr Yu, Office of Generic Drugs, US Food and Drug Administration, 7519 Standish Pl, Rockville, MD 20855 (lawrence.yu@fda.hhs.gov). Published Online: December 31, 2012. doi:10.1001/jamainternmed.2013.2283 Conflict of Interest Disclosures: None reported. References 1. Kesselheim AS, Misono AS, Shrank WH, et al. Variations in pill appearance of antiepileptic drugs and the risk of nonadherence [published online December 31, 2012]. JAMA Intern Med. 2013;173(3):202-208Google Scholar 2. Greene JA, Kesselheim AS. Why do the same drugs look different? pills, trade dress, and public health. N Engl J Med. 2011;365(1):83-8921732842PubMedGoogle ScholarCrossref 3. American Academy of Neurology position statement, November 2, 2006. http://www.aan.com/globals/axon/assets/2323.pdf. Accessed October 8, 2012 4. The substitution of different formulations of antiepileptic drugs for the treatment of epilepsy, November 29, 2007. http://www.aesnet.org/go/press-room/consensus-statements/drug-substitution. Accessed October 8, 2012 5. Statement on substitution of generic antiepileptic drugs, May 2009. http://www.epilepsyfoundation.org/getinvolved/advocacy/positionstatements/genedrev.cfm. Accessed October 8, 2012

Journal

JAMA Internal MedicineAmerican Medical Association

Published: Feb 11, 2013

Keywords: anticonvulsants

References