The Truth About Generic Drugs

Physicians have an obligation first to do no harm to their patients, but the overall goals of providing care go far beyond that. They include treating disease, repairing damage, and alleviating pain. Often, medications are prescribed to achieve these objectives, and physicians must consider not only the appropriateness of a prescription for a particular condition but also the patient’s access to medications and therapies prescribed. Access and affordability influence patient adherence to physician orders. Generic equivalent medications are prescribed to ease the financial burden for the patient, but do these agents deliver the same therapeutic efficacy and safety as their brand-name siblings? Although FDA guidelines offer strict specifications for generic drugs, these products may not be entirely equal to their branded counterparts. This article examines some of the differences between the two.

THE BASICS

A brand-name drug is discovered or created by a pharmaceutical company. The drug is developed, put through clinical trials, and then submitted to the FDA for approval via a new drug application. Clinical safety and efficacy must be established in order to meet the FDA’s rigorous standards. Additional studies must demonstrate characteristics such as stability, solubility, purity, strength, and the use of quality manufacturing processes for a drug to receive FDA approval.

The pharmaceutical company’s patent on a newly created drug allows exclusivity to the formulation. The average lifespan of a drug patent is 10 years, with the exception of medications for orphan diseases. Drug sales not only provide a profit for the pharmaceutical company, but they also allow the company to recoup money spent on research and development.¹

A generic drug is defined by the FDA as “a medication created to be the same as an already marketed brand-name drug in dosage form, safety, strength, route of administration, quality, performance characteristics, and intended use.”² Generic drugs should have the same active ingredients, perform the same way, and carry the same risks and benefits as their brand-name counterparts, per the FDA.

DRAWING COMPARISONS

Generic medications have much in common with their equivalent brand-name drugs, but they are not identical products. For one thing, the appearance of generic drugs’ packaging (ie, color, shape, and markings) will differ from that of branded products due to trademarking. Except in the case of generic ophthalmic medications,³ the inactive ingredients of a generic equivalent drug may differ from those of the brand-name drug. The inactive ingredients in a generic formulation must be shown to have no effect on the function of the medication, all ingredients must be reviewed by the FDA and found to be acceptable.²

Bioequivalence

Additionally, brand-name and generic drugs must show bioequivalence, which is determined by a randomized, crossover trial of both drugs, with the branded drug serving as the control. These trials assess several pharmacokinetic factors.³ Bioequivalence between the two drugs occurs if the 90% confidence interval of the ratio of geometric means of the primary pharmacokinetic responses (after log-transformation) is within the bioequivalence limits of 80% and 125%.⁴ A common misinterpretation of the 80% to 125% bioequivalence rule holds that a generic drug must be only within a range of 45% of the active ingredient to be considered equivalent to its branded alternative.³

Calculation of bioequivalence requires statistical analysis and a comparison of generic and branded formulations with relation to the area under the curve and the maximum serum concentration to be determined. If a generic drug meets the standard of bioequivalence, then that drug can be considered not to be different from the branded drug. However, a generic drug is not necessarily defined as the same as a branded drug. Even branded drugs can have a variability of 10% between manufacturing lots.⁵ The active and inactive ingredients of generic medications should be within ±5% of those of their brand-name counterparts.⁵

Drop Volume, Viscosity, Surface Tension, and Shape of the Bottle Tip

Although many characteristics of branded drugs are mirrored by their generic equivalents per FDA guidelines, some features are not. A 2012 study evaluated American and Canadian brand-name versions of timolol maleate ophthalmic gel forming solution (Timoptic XE, Valeant Pharmaceucticals International) and found significant differences from the generic version with regard to drop volume, viscosity, surface tension, and shape of the bottles’ tips. The Canadian brand-name product provided a significantly smaller drop than did the generic product.⁶ Physicians should consider the delivery method of a generic drug in addition to its bioequivalence. Larger drop size could waste product at each administration. Additionally, bottle design may differ between brand-name and generic drugs. Ease of bottle use can be important for patients with functionality barriers such as arthritis or tremor.⁷

Performance

Despite the rigorous standards set by the FDA for drug composition and manufacturing, clinical practice and retrospective case reviews have shown variations in results with branded versus generic ophthalmic medications. Corticosteroids are a good example of generic drugs that do not perform the same as their branded alternatives.⁷ Patients may require additional follow-up visits to manage inflammation and, ultimately, have their medication switched to a branded drug to reach therapeutic effectiveness. In addition to inadequate performance, some generic drugs have been found to cause deleterious clinical results. For example, some generic nonsteroidal antiinflammatory drugs have been shown to put patients at risk for corneal melts relative to their brand-name competitors.⁶

THE LONG AND SHORT OF IT

Generic drugs make up approximately two-thirds of prescriptions written in the United States, but they represent only about 13% of the total cost.⁸ These cost savings are significant for both patients and the US health care system. An estimated 75% of insured patients have tiered drug coverage plans that require generic equivalent drugs to be prescribed in lieu of branded drugs and often require a higher copayment for branded products.⁹ Although the fulfillment rate of generic drugs is relatively high, that growth is stimulated in part by insurers rather than physician or patient preference.

Not only do physicians not want to inflict harm, but they also want to heal and benefit their patients. Consequently, doctors must consider the affordability of and patient access to various medications in order to offer cost-effective solutions and increase adherence to prescribed therapy. That said, therapeutic efficacy is essential, and it may be necessary in some cases to prescribe a brand-name drug to achieve a successful outcome.