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.


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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.

What are the similarities?

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[11].

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[11].

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[13].

In reality, the actual difference in bioavailability between generic and innovator products is typically no more than 5 -7%[12].

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.
  • Gas.
  • 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.

3 Efficacy

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:

  • beta-blockers[3]
  • diuretics[3]
  • calcium channel blockers[3]
  • antiplatelet agents[3]
  • angiotensin-converting enzyme inhibitors[3]
  • statins[2]
  • antibiotics (amoxicillin, amoxicillin clavulanate, clarithromycin, and cefaclor)[6]
  • lamotrigine[7, 8]
  • clozapine[9]

Generic and brand-name antihypertensive drugs are similarly effective for preventing the onset of cardiovascular disease[1].

4 Quality & FDA requirements

Generic and brand-name drugs must meet the exact same standards for effectiveness, safety and quality[14]:

  • 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.

What are the differences?

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[5].
  • Meropenem[5, 18]
  • Teicoplanin[4]
  • Levothyroxine[10]
  • Clozapine[15]
  • Citalopram[23]
  • 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[21].
  • Equivalence is particularly difficult to obtain for extended-release or delayed-release formulations, e.g. verapamil[24], bupropion[25], methylphenidate[26].

3Approval process

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[22]:

  • 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.

4Cost

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[16]. 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[17].

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.

Bottom Line
  • 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.

References

  • 1. Corrao G, Soranna D, Merlino L, Mancia G. Similarity between generic and brand-name antihypertensive drugs for primary prevention of cardiovascular disease: evidence from a large population-based study. Eur J Clin Invest. 2014 Oct;44(10):933-9. PubMed
  • 2. Corrao G, Soranna D, Arfe A, Casula M, Tragni E, Merlino L, Mancia G, Catapano AL. Are generic and brand-name statins clinically equivalent? Evidence from a real data-base. Eur J Intern Med. 2014 Oct;25(8):745-50. PubMed
  • 3. Kesselheim AS, Misono AS, Lee JL, Stedman MR, Brookhart MA, Choudhry NK, Shrank WH. Clinical equivalence of generic and brand-name drugs used in cardiovascular disease: a systematic review and meta-analysis. JAMA. 2008 Dec 3;300(21):2514-26. PubMed
  • 4. Fujimura S1, Fuse K, Takane H, Nakano Y, Gomi K, Kikuchi T, Watanabe A. Antibacterial effects of brand-name teicoplanin and generic products against clinical isolates of methicillin-resistant Staphylococcus aureus. J Infect Chemother. 2011 Feb;17(1):30-3. PubMed
  • 5. Fujimura S1, Watanabe A. Generic antibiotics in Japan. J Infect Chemother. 2012 Aug;18(4):421-7. PubMed
  • 6. Piovani D, Clavenna A, Cartabia M, Bortolotti A, Fortino I, Merlino L, Bonati M. Comparing recurrent antibiotic prescriptions in children treated with a brand name or a generic formulation. Pharmacoepidemiol Drug Saf. 2015 Feb;24(2):121-8. PubMed
  • 7. Ting TY, Jiang W, Lionberger R, Wong J, Jones JW, Kane MA, Krumholz A, Temple R, Polli JE. Generic lamotrigine versus brand-name Lamictal bioequivalence in patients with epilepsy: A field test of the FDA bioequivalence standard. Epilepsia. 2015 Sep;56(9):1415-24. PubMed
  • 8. Privitera MD, Welty TE, Gidal BE, et al. Generic-to-generic lamotrigine switches in people with epilepsy: the randomised controlled EQUIGEN trial. Lancet Neurol. 2016 Feb 11. pii: S1474-4422(16)00014-4. PubMed
  • 9. Bobo WV, Stovall JA, Knostman M, Koestner J, Shelton RC. Converting from brand-name to generic clozapine: a review of effectiveness and tolerability data. Am J Health Syst Pharm. 2010 Jan 1;67(1):27-37. PubMed
  • 10. Carswell JM, Gordon JH, Popovsky E, Hale A, Brown RS. Generic and brand-name L-thyroxine are not bioequivalent for children with severe congenital hypothyroidism. J Clin Endocrinol Metab. 2013 Feb;98(2):610-7. PubMed
  • 11. Development & Approval Process (Drugs). Orange Book Preface. FDA
  • 12. Therapeutic equivalence of generic drugs: response to National Association of Boards of Pharmacy. April 16, 1997 FDA
  • 13. DB. Troy, P. Beringer. Remington: The Science and Practice of Pharmacy. 21st ed. Baltimore; Lippincott Williams& Wilkins; 2006. p. 1043
  • 14. FDA Ensures Equivalence of Generic Drugs. Available at FDA
  • 15. Lam YW, Ereshefsky L, Toney GB, Gonzales C. Branded versus generic clozapine: bioavailability comparison and interchangeability issues. J Clin Psychiatry. 2001;62 Suppl 5:18-22; PubMed
  • 16. Cost to Develop and Win Marketing Approval for a New Drug Is $2.6 Billion. CSDD
  • 17. Colgan S, Faasse K, Martin LR, Stephens MH, Grey A, Petrie KJ. Perceptions of generic medication in the general population, doctors and pharmacists: a systematic review. BMJ Open. 2015 Dec 15;5(12):e008915. PubMed
  • 18. Agudelo M, Rodriguez CA, Pelaez CA, Vesga O. Even apparently insignificant chemical deviations among bioequivalent generic antibiotics can lead to therapeutic nonequivalence: the case of meropenem. Antimicrob Agents Chemother. 2014;58(2):1005-18. PubMed
  • 19. Chaluvadi S, Chiang S, Tran L, Goldsmith CE, Friedman DE. Clinical experience with generic levetiracetam in people with epilepsy. Epilepsia. 2011 Apr;52(4):810-5. PubMed
  • 20. Fitzgerald CL, Jacobson MP. Generic substitution of levetiracetam resulting in increased incidence of breakthrough seizures. Ann Pharmacother. 2011 May;45(5):e27. PubMed
  • 21. van den Bergh JP, Bouts ME, van der Veer E, van der Velde RY, Janssen MJ, Geusens PP, Winkens B, Oldenhof NJ, van Geel TA. Comparing tolerability and efficacy of generic versus brand alendronate: a randomized clinical study in postmenopausal women with a recent fracture. PLoS One. 2013 Oct 21;8(10):e78153. PubMed
  • 22. U.S. Food and Drug Administration. Facts about Generic Drugs. Available at US FDA
  • 23. Van Ameringen M1, Mancini C, Patterson B, Bennett M. Symptom relapse following switch from Celexa to generic citalopram: an anxiety disorders case series. J Psychopharmacol. 2007 Jul;21(5):472-6 PubMed
  • 24. Waldman SA, Morganroth J. Effects of food on the bioequivalence of different verapamil sustained-release formulations. J Clin Pharmacol. 1995 Feb;35(2):163-9.
  • 25. Bupropion Hydrochloride Extended-Release 300 mg Bioequivalence Studies. Available at US FDA
  • 26. Methylphenidate Hydrochloride Extended Release Tablets (generic Concerta) made by Mallinckrodt and Kudco. Available at US FDA

Last updated: March 21, 2016
Created: March 21, 2016

Interesting facts

Generic drugs
  • 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.
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