Brand-Name Drugs vs Generic Drugs
Updated: March, 2016
Generic medications help to save significant sums of money. But are they as effective and safe as brand-name medications?
What is a brand-name drug?
An innovator pharmaceutical company originally discovers and develops a brand-name drug. The research and development process for novel medications is lengthy and requires billions of dollars. Before FDA will approve the drug for the market the innovator company undergoes New Drug Application (NDA) process.
Newly invented drug is granted a 20-year patent (after the drug is invented), which protects the innovator company and doesn't allow anyone else to produce and market the drug. When the patent of a brand name medication expires, other companies may produce and sell a generic version of the drug.
What is a generic drug?
In short, generic medication is a copy of a brand-name counterpart, produced after the patent on original product expires. It is relatively inexpensive for a generic company to make a copy once an innovative drug has been created.
Generic name is the established common name of the active drug in the drug product.
Generic medications are marketed after the patent expiration date of the innovator product.
1 Active pharmaceutical ingredient
Generic drug has the same active ingredient (the chemical that makes the drug work) as original brand product. Therefore it works the same way in the body as the brand-name drug. Generic drug is also required to have the same amount of active ingredient in the same dosage formulation.
2 Bioavailability and Bioequivalence
The most important characteristics of a generic drug are bioavailability and bioequivalence.
Generic drug is considered to be bioequivalent to the pioneer product if it contains an active ingredient that is chemically identical and is delivered to the site of action at the same rate and extent as original brand drug.
Bioavailability means the rate and extent to which the active ingredient is absorbed from a drug product and becomes available at the site of drug action.
Thus bioequivalent drug products have comparable bioavailability.
Can the bioavailability of the generic and brand-name drugs differ by up to 20%?
The key parameters for bioequivalence are the area under the blood concentration versus time curve (AUC) and maximum concentration of a drug (Cmax). The AUC and Cmax of a generic product must be no less than 80% or no more than 125% of the original brand name product. More importantly, the 90% confidence interval for each parameter (Cmax and AUC) must also lie within the 80-125% boundary. In that way, for the entire confidence interval to fall within the 80% to 125% range, the variance is generally less than 5%.
A generic product that actually differs by 20% or more from the innovator product in one or several of its pharmacokinetic parameters would have less than 5% chance of being approved.
In reality, the actual difference in bioavailability between generic and innovator products is typically no more than 5 -7%.
Biowaivers - bioequivalence studies are NOT required for:
- Aqueous solutions for parenteral use containing the same active ingredient in the same concentration.
- Solution for oral use containing the same active ingredient with same concentration, and excipients not affecting gastrointestinal absorption and transit.
- Powder for reconstitution as solution.
- Otic, ophthalmic, and topical solutions containing the same active ingredient in the same concentration, and same excipients in comparable concentrations.
- Inhalational product or nasal spray in form of an aqueous solution.
Generic drug that contains identical dose of the same active ingredient as the brand name comparator and has been shown to be bioequivalent to the reference product is considered to be therapeutically equivalent.
There is a good evidence for equivalent efficacy of the following brand-name and generic medications:
- calcium channel blockers
- antiplatelet agents
- angiotensin-converting enzyme inhibitors
- antibiotics (amoxicillin, amoxicillin clavulanate, clarithromycin, and cefaclor)
- lamotrigine[7, 8]
Generic and brand-name antihypertensive drugs are similarly effective for preventing the onset of cardiovascular disease.
4 Quality & FDA requirements
Generic and brand-name drugs must meet the exact same standards for effectiveness, safety and quality:
- Data showing the drug is bioequivalent to the one used in the original safety and efficacy investigation.
- FDA evaluates the manufacturer's adherence to good manufacturing practices as well as the active and inactive ingredients of the formulation before the drug enters the market.
- FDA examines the actual drug product.
- FDA reviews the drug's labeling.
- FDA periodically inspects manufacturing plants (e.g. manufacturing steps, quality control measures).
- Manufacturer has to get FDA approval before making major manufacturing changes or reformulating the drug.
- Manufacturer must report adverse reactions and serious side effects to the FDA.
1 Inactive ingredients (excipients)
Generic drugs are allowed to have different inactive (inert) ingredients, e.g. binders, fillers, coloring, and flavoring.
It is possible that the inactive ingredients can affect the bioavailability of the medication, but that is why the bioequivalence studies are required.
Some persons may have allergies to inactive ingredients such as lactose, gluten, or sulfites. Also, certain excipients can change gut motility and as a result affect drug absorption in sensitive patients.
2 Therapeutic efficacy
There are lots of reports on various medications describing variability in therapeutic efficacy and side effects when switching from an innovator to a generic medication or vice versa.
Bioequivalence doesn't always translate into therapeutic equivalence (the same clinical effect and the same safety profile). Sometimes these minimal allowable variations are clinically significant for certain patients. So individual differences raise the issue of average bioequivalence versus individual bioequivalence.
There are generic medications whose therapeutic effect is not equal to that of the brand-name original medication:
- Some of the generic antibiotics have less antibacterial potency or solubility than the brand name products.
- Meropenem[5, 18]
- Antiepileptic drugs: carbamazepine, levetiracetam [19, 20]. Several studies showed a recurrence of convulsions after the shift to generic antiepileptic drugs.
- Alendronate: several differences between generic alendronate and brand-name Fosamax® have been reported, including disintegration time, patient persistence to therapy, side effects and tolerability, clinical efficacy.
- Equivalence is particularly difficult to obtain for extended-release or delayed-release formulations, e.g. verapamil, bupropion, methylphenidate.
Generic medications do not undergo the rigorous approval process required for novel medications. The generic drug approval process does not require the manufacturer to repeat costly animal testing and Phase I-III clinical trials on active ingredients or dosage forms already approved by the US Food and Drug Administration.
A generic manufacturer needs to demonstrate that the product:
- contains the same active ingredients as the innovator drug product
- is identical in strength, dosage formulation, and route of administration to the innovator drug product
- is bioequivalent to the innovator drug product
- has the same clinical indications
- meets the same batch requirements for identity, strength, purity, and quality
- is manufactured according to the same FDA regulations.
The generic drug approval process usually lasts for about 2-4 years, while the approval process for the brand name drug may require from 10 to 14 years. Also, generic bioequivalence studies are performed in healthy volunteers.
The main advantage of generic medications is lower cost. The Tufts Center for the Study of Drug Development estimates that the rough cost to develop and gain marketing approval for a new drug is $2.6 billion. Generic drug manufacturers don't have to carry expenses on researching and developing a new pharmaceutical substance.
Moreover, many successful brand medications became well-established and widely used and so generic companies do not need to bear the costs of promotion and advertising.
Competition among generic drug companies further facilitates sharp price decline.
5 Negative perceptions about generics
Many doctors and patients have very negative biases about quality and efficacy of generic medications.
If a person has a very strong feeling that brand-name drug works perfectly or the belief is that generics are not as good as brand-name medications, than a negative bias about switching drugs can lead a patient to get worse or develop side effects.
Harmful influence of patient's negative expectations is called "nocebo effect", which is an opposite to placebo effect.
Patient's negative expectations lead to harmful results opposite to placebo effect.
- 1. Generic medications allow for significant savings and increased affordability and accessibility of medications.
- 2. Bioequivalence testing for generics has been in place in most countries for more than 20 years with an established track record of therapeutic equivalence.
- 3. There are rare cases when generic drugs fail to produce equal therapeutic effect.
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Last updated: March 21, 2016
Created: March 21, 2016
- Generic drugs are sometimes manufactured by brand name companies. These drugs may be called ultragenerics or pseudogenerics.
- Generic drugs bioequivalent to the same innovative product may not be bioequivalent to one another.