Clinical, Featured, Professional Advice / Opinions:

Brand Vs. Generic: What Every Prescriber Should Know

By: Marina Yermolayeva, PharmD Candidate c/o 2013

“I’m allergic to the generic; I need the brand name medication,” is a common claim heard by many health care providers.  Managed care organizations get numerous calls from doctors and patients requesting prior authorizations to approve brand name medications whilst there are generic alternatives available on formulary.  Much-needed healthcare resources, time, and money can be saved by investing some effort to educate people about the differences (or lack thereof) between brand and generic drugs.

Each medication available on the United States market today has been reviewed and approved by the U.S. Food and Drug Administration (FDA).  A company that has invented and synthesized a unique drug may designate this product with a “brand” name, which is usually catchy and easier to pronounce than the official, chemical name for the active ingredient.  The company then may legally claim exclusive rights to manufacture this product for up to 17 years from the time of discovery, which is known as a patent.1  Once this patent expires, other companies are allowed to manufacture the product using the same active ingredient but different fillers, coloring, and packaging; these multi-source products are known as “generics” and go by their chemical names.  To differentiate between the two, brand names are usually capitalized and generic names are not.

Generic products must meet stringent requirements set by the FDA.  The word “generic” is an adjective that refers to an entire class and is synonymous with “general.”  It just means that the generic is not unique and has the same characteristics as another item, in this case, the brand name medication.  Under the 1984 Drug Price Competition and Patent Term Restoration Act, generic medications must show the same active ingredient, strength, quality, purity, and potency as the brand name dosage form for entry into the U.S. market.2,3

Therapeutic equivalence must be proven via several tests.  If the generic and brand products show the same concentration profiles in the blood after administration, they are considered to be bioequivalent, and therefore therapeutically equivalent.  Bioequivalence studies typically involve studying the pharmacokinetics of the brand and generic formulations in healthy adults (in-vivo) in a randomized, crossover study design.4  While bioequivalence studies typically call for only 18—25 healthy volunteers, brand-name clinical trials are required to test hundreds to thousands of people to demonstrate safety and efficacy because virtually nothing is known about the pioneer drug.3  Once safety and efficacy is established for a brand medication, bioequivalence studies are considered sufficient evidence to validate a generic drug.  In order to meet bioequivalence requirements, certain criteria need to be met.  The total extent of absorption (AUC, area under the curve), maximum serum concentrations (Cmax), and the times to Cmax (tmax) should be neither statistically nor clinically significantly different from the standard formulation (in this case the brand medication). 4 The serum-concentration-versus-time curves for the two dosage forms should be identical.4  This data is published by the FDA in Approved Drug Products with Therapeutic Equivalence Evaluations (known as “the List”, or “Orange Book”, for short).There are some exceptions to the in-vivo bioequivalence requirements.  Bioequivalence of intravenous (IV) or oral solution dosage forms are inferred; and, some older drug formulations for which no bioequivalence issues are anticipated are only required to submit in-vitro dissolution tests to the FDA.3

According to the official FDA website, all generic manufacturing, packaging, and testing sites must pass the same quality standards as those of brand name drugs.  In fact, many generic drugs are made in the same manufacturing plants as brand name drug products.2  FDA inspectors evaluate each site to ascertain that Good Manufacturing Practice regulations are followed; samples of all drug products are randomly collected and sent to FDA laboratories for evaluation.3  Furthermore, the FDA imposes the same post-marketing surveillance tactics on generic products as it does on brands.  Programs such as MedWatch are in place for health care workers and patients to report adverse reactions.  These reports are investigated when necessary, and appropriate action is taken to ensure that only safe products are available on the U.S. market.  The FDA also encourages more extensive research to investigate which inactive ingredients are problematic among generics.2

If the regulations are not enough to convince health care professionals, there is published evidence of pharmacokinetic equivalence between brand and generic medications.  The FDA recently reviewed 2,070 human studies conducted between 1996 and 2007 to compare absorption of brand name and generic drugs by the human body.2  These studies were submitted to FDA to support approval of generics.  The average difference in absorption between the generic and brand name was 3.5 %.6  This amount is considered negligible and not expected to have clinical impact.  Even studies comparing batches of the same brand-name drug to itself, or to other brands, showed slight variability in absorption.  The difference for the generic-to-brand comparison was about the same as the brand-to-brand comparison in this analysis.  The FDA permits very small variations in purity, size, strength, and other parameters for mass-produced brand and generic products.2

Clinical benefit was evaluated by a retrospective meta-analysis of cardiovascular brand and generic drug outcomes published in the Journal of American Medical association.  The authors pooled articles from peer-reviewed health care–related journals between January 1984 and August 2008.7  In total, 47 articles [38 (81%) of which were randomized controlled trials (RCTs)], covering 9 subclasses of cardiovascular medications were identified and included in the analysis.  Clinical equivalence was found in RCTs of β-blockers (7/7 RCTs), diuretics (10/11 RCTs), calcium channel blockers (5/7 RCTs), antiplatelet agents (3/3 RCTs), statins (2/2 RCTs), angiotensin-converting enzyme inhibitors (1/1 RCT), and α-blockers (1/1 RCT).  Furthermore, clinical equivalence was also detected among narrow therapeutic index drugs [1/1 RCT of class 1 antiarrhythmic agents and 5/5 RCTs of warfarin].7  The overall data (n = 837) did not indicate a statistically significant difference between the effect of brand and generic drugs.  Despite these findings, the same study found that more than half of published editorials [23 of 43 (53%)] published during the same time period recommended against generic drug substitution.7

In addition, allergies to medication warrant special attention and avoidance of the offending drug.  However, identifying the causative agent as well as the type of allergy is key to determining how to manage each patient.  If the main pharmaceutical ingredient is causing a life-threatening reaction (anaphylaxis, toxic skin reactions, etc.), all brand and generic products with that ingredient are contraindicated.  If, however, the patient is found to be allergic to an inactive excipient, he or she may benefit from a different pharmaceutical formulation with different fillers and dyes.  Each generic company will have their own combinations and ratios of excipients, so being allergic to one company’s product does not warrant switching to a brand; instead, a different generic product from another manufacturer can be tried.  Health care practitioners should also differentiate between true allergies (immunologically mediated) and intolerances, or adverse reactions, to a drug product.  For example, if a patient has gastrointestinal upset or dyspepsia in response to a medication, these side effects can be managed (by taking the medication with food) rather than discontinuing or switching the medication.

As for patients that claim their generic medication is “not working” as well as the brand, there is no scientific evidence to support these claims based on the aforementioned FDA regulations and clinical studies.  Patients may extrapolate these theories from unfounded preconceived notions that generic drugs are inferior to brands.  If the patient is really not experiencing a clinical improvement, it is likely that the failure is due to the active ingredient and not the excipients.  Perhaps a different agent from the same therapeutic class should be tried, or even one from another class.  A patient may respond differently to certain drug characteristics unique to the active ingredient.  If the patient and doctor feel that the generic version of the medication is the underlying cause of treatment failure, a different generic manufacturer can be requested before resorting to a brand.

The lower price of generics only adds to the suspicion of their inferiority among patients, since a higher price is generally associated with greater benefit or safety.  In fact, while the original brand-name manufacturer spent millions of dollars on research, discovery, synthesis, and approval of the medication, the generic manufacturer skips these costs and must only ascertain that their drug is bioequivalent and comparable to the brand-name product for market approval.  This is the reason that generic companies are able to charge less for the same active medication and still make up their cost and accrue profit.  On average, the cost of a generic drug is 80—85 % lower than its brand counterpart.2

Finally, reluctance to use a generic product may result in therapy interruption.  Patients are often left without any medication in the time it takes to acquire authorization from a third party payer for a non-formulary brand name drug.  It is a time consuming process to get the prescription to the pharmacy, alert the doctor of an authorization block, have the doctor call the insurance plan and explain the situation, and ultimately allow the pharmacy to activate the authorization and dispense the drug.  This may take up to a few days, and the patient may not receive any medication in the meantime, not wanting to pay for it out of pocket.  If only the misconceptions about generic medications could be exposed and eradicated, this could be avoided.

In the majority of cases, substituting drugs within the same therapeutic class is reasonable and safe; the only exceptions are narrow therapeutic index drugs and antibiotics.  For example, some of the most popular formulary-exception and prior authorization requests are for brand-name proton pump inhibitors (PPIs).  There are currently six brand-name medications (Protonix® [pantoprazole], Nexium® [esomeprazole], Aciphex® [rabeprazole], Prevacid® [lansoprazole], Dexilant® [dexlansoprazole], Prilosec® [omeprazole]) and three generic medications (pantoprazole, omeprazole, lansoprazole) on the U.S. market.  These agents have the same mechanism of action and similar pharmacokinetic properties and side effect profiles.  Few head-to-head clinical trials have been executed comparing the effectiveness among these agents; therefore, it is difficult to judge which one will optimally benefit an individual patient.  If the patient’s formulary does not cover a drug prescribed by a clinician, it may be permissible to substitute not only with a generic product, but with any other PPI.  Clinical outcomes are expected to be the same among these agents, as long as adequate dosing is achieved and the patient is not subjected to undue interruptions in treatment.

In some clinical cases, it is preferred to use brand-name products or be consistent with the generic manufacturer of one’s medication.  Drugs with narrow therapeutic indices, such as Dilantin® (phenytoin), Lanoxin® (digoxin), Synthroid® (levothyroxine), and Coumadin® (warfarin) should not be substituted.1  Patients stabilized on one company’s formulation should remain on it for adequate therapeutic control.

As healthcare costs continue to skyrocket, managed care organizations are scrambling to cut down costs.  One cost-saving method is to substitute brand medications with their generic equivalents on formularies whenever possible.  In 2010 alone, the use of FDA-approved generics saved $158 billion, an average of $3 billion every week.3  Patients still benefit from the active ingredients, with significant decreases in insurance and co-payment costs.  Health care practitioners should take the time to educate patients on the concept of brand and generic medication to help develop an affordable, individualized, consistent therapy plan acceptable and beneficial to the patient.


  1. Maniscalco-Feichtl M, Whalen KL. Chapter 14. Community/Ambulatory Care. In: Kier KL, Nemire RE, eds. Pharmacy Student Survival Guide. 2nd ed. New York: McGraw-Hill; 2009. <>. Accessed June 26, 2012.
  2. “Facts about Generic Drugs.” U.S. Food and Drug Administration. 2012 Jun 6. <>. Accessed June 27, 2012.
  3. Nightingale SL, Morrison JC. “Generic Drugs and the Prescribing Physician.” JAMA. 1987 Sept 4, 258(9):1200-4. <>. Accessed June 27, 2012.
  4. Bauer LA. Chapter 8. Clinical Pharmacokinetics and Pharmacodynamics. In: Talbert RL, DiPiro JT, Matzke GR, Posey LM, Wells BG, Yee GC, eds. Pharmacotherapy: A Pathophysiologic Approach. 8th ed. New York: McGraw-Hill; 2011. <>. Accessed June 26, 2012.
  5. “Orange Book Preface.” U.S. Food and Drug Administration. 2012 Feb 3. <>. Accessed August 30, 2012.
  6. Davit BM, Nwakama PE, et al. “Comparing generic and innovator drugs: a review of 12 years of bioequivalence data from the United States Food and Drug Administration.” Ann Pharmacother. 2009 Oct; 43(10):1583-97.>. Accessed June 27, 2012.
  7. Kesselheim AS, Misono AS, et al. “Clinical equivalence of generic and brand name drugs used in cardiovascular disease: a systematic review and meta-analysis.” JAMA. 2008; 300(21): 2514—26. <>. Accessed June 27, 2012.
  8.  “Generics have the same quality as brand name drugs.” Image. U.S. Food and Drug Administration. 2012 Jun 6. <>. Accessed June 27, 2012.
Published by Rho Chi Post
Both comments and trackbacks are currently closed.