Generic drug
In medicine and pharmacology, generic drugs are "drugs whose drug name is not protected by a trademark. They may be manufactured by several companies." [1] In addition, government agencies determine whether a generic drug is bioequivalent to a brand name drug with respect to pharmacokinetic and pharmacodynamic properties. Generic medicines must contain the same active ingredient at the same strength as the "innovator" brand, be bioequivalent, and are required to meet the same pharmacopoeial requirements for the preparation. Thus, generics should be identical in dose, strength, route of administration, safety, efficacy, and intended use. Generic drugs are usually sold at a lower price than the brand name drug.
A "branded generic" is "any product marketed by a multinational drug company (or it’s subsidiary) other than the innovator product and sold under a trade name other than the products generic approved name."[2] A branded generic may be an authorized generic (see description of authorized generic drug below).
Generic drugs are underutilized.[3][4]
Reasons for cheaper price
Usually, generic drugs are much less expensive than the brand-name product. The principal reason for the reduced price of generic medicines is that these companies incur less costs in creating the generic drug and are therefore able to offer a lower price and still maintain profitability. In 2003, was estimated that these costs average around $800,000,000 [5]
Manufacturers of generic drugs are mainly able to avoid the following three costs that brand name pharmaceutical companies incur: (1) costs associated with the research and development of the drug; (2) costs associated obtaining regulatory approval (i.e. proving safety and efficacy of a drug); and (3) marketing costs.
First, generic manufacturers do not incur the cost of drug discovery and instead reverse-engineer existing brand name drugs to allow them to manufacture bioequivalent versions.
Second, generic manufacturers do not bear the burden of proving the safety and efficacy of the drugs through clinical trials - rather, generic manufacturers must prove the bioequivalance to the existing drug.
Third, these companies receive the large benefit of the marketing that goes into pushing the innovator drug. The drugs that generic manufacturers are selling have been on the market for usually a decade or more and do not need additional advertising. For the same reason, generic manufacturers also do not give away sample doses to promote their products.
Companies such as Teva, Sandoz, Ethex, and Ranbaxy specialize in generic drugs.
When can a generic drug be produced?
Generic drugs can be legally produced for drugs where: 1) the patent has expired, 2) the generic company certifies the brand company's patents are either invalid, unenforceable or will not be infringed, 3) for drugs which have never held patents, or 4) in countries where a patent(s) is/are not in force.
Patent lifetime
Pharmaceutical companies may produce a generic drug when the patent expires on the innovator drug. The expiration of a patent removes the monopoly of the patent holder on drug sales licensing. Patent lifetime differs from country to country.
United States
In the United States, the duration of a patent is 20 years.[6] However, in the United States, patents for products such as food additives and drugs that require approval by federal entities such as the US Food and Drug Administration prior to marketing, can have a maximum of 5 years extended to the patent to compensate for marketing time lost while waiting for approval." In all cases, the total patent life for the product with the patent extension cannot exceed 14 years from the product’s approval date, or in other words, 14 years of potential marketing time. "[6][7]
The length of time before a patent expires varies for different drugs. Usually, there is no way to renew a patent after it expires. A new version of the drug with significant changes to the compound could be patented but this will require new clinical trials and will not prevent the generic versions of the original drug.
The brand-name drug companies have tended to litigate aggressively to extend patent protection on their medicines and keep generic versions off the market, a process referred to by critics as "evergreening."
Abbreviated New Drug Application
Enacted in 1984, the U.S. Drug Price Competition and Patent Term Restoration Act[8], informally known as the "Hatch-Waxman Act", standardized U.S. procedures for recognition of generic drugs. An applicant files an Abbreviated New Drug Application (or "ANDA") with the Food and Drug Administration (FDA) and seeks to demonstrate therapeutic equivalence to a specified, previously approved "reference listed drug." When an ANDA is approved, the FDA adds the drug to its Approved Drug Products list, also known as the "Orange Book", and annotates the list to show equivalence between the reference listed drug and the approved generic. The FDA also recognizes drugs using the same ingredients with different bioavailability and divides them into therapeutic equivalence groups. For example, as of 2006 diltiazem hydrochloride had four equivalence groups all using the same active ingredient but considered equivalent only within a group. For an explanation of FDA terms and procedures, see "Approved Drug Products with Therapeutic Equivalence Evaluations, Preface."
Establishing bioequivalence
Assurance of bioequivalence may be regulated by governmental agencies such as the Food and Drug Administration in the United States.
The FDA requires that the following tests be within 80% to 125% of the reference drug.[9] In practice, the results are typically within 3%.[10] The FDA typically tests 24 to 36 healthy human volunteers.[11]
- Area under the plasma concentration-time curve (AUC) for extent of absorption
- Calculated to the last measured concentration (AUC(0-t))
- Extrapolated to infinity (AUC(0-inf))
- The maximum or peak drug concentrations (Cmax), for rate of absorption
After testing, the FDA assigns "Therapeutic Equivalence Evaluations Codes", or AB ratings.[9][11] Drugs considered therapeutically equivalent are given a rating of AB, AA, AN, AO, AP, or AT.
180 Day Generic Drug Exclusivity
In the United States, the Food and Drug Administration offers a 180 day exclusivity period to generic drug manufacturers in specific cases. During this period only one (or sometimes a few) generic manufacturers can produce the generic version of a drug. This exclusivity period is only used when a generic manufacturer argues that a patent is invalid or is not violated in the generic production of a drug, and the period acts as a reward for the generic manufacturer who is willing to risk liability in court and the cost of patent court litigation. There is often contention around these 180 day exclusivity periods because a generic producer does not have to produce the drug during this period and can file an application first to prevent other generic producers from selling the drug.
Authorized generics
It is also becoming popular for the large pharmaceutical companies to preempt the expiry of their patent by producing their own generic product, or license their own product to be branded by generic companies. Thus, in some cases, the "generic" product is actually the brand product but inside a different box.
To combat the exclusivity period, license a subsidiary (or another company) to sell generics under the original patent. Generics sold under license from the patent holder are known as authorized generics;[12] they are not affected by the 180 day exclusivity period as they fall under the patent holder's original drug application. A list of authorized generics is maintained by the FDA at http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm126391.htm. In January, 2009 Representative Jo Ann Emerson (R-MO) introduced H.R. 573 that would prohibit the marketing of an authorized generic during the 180-day generic exclusivity period following a patent challenge[13]
An example of how this works is simvastatin (Zocor), a popular drug created and manufactured by U.S. based pharmaceutical Merck & Co., which lost its US patent protection on June 23, 2006. India-based Ranbaxy Laboratories (at the 80-mg strength) and Israel-based Teva Pharmaceutical Industries (at all other strengths) received 180 day exclusivity periods for simvastatin; due to Zocor's popularity, both companies began marketing their products immediately after the patent expired. However, Dr. Reddy's Laboratories also markets an authorized generic version of simvastatin under license from Zocor's manufacturer, Merck & Co.; some packages of Dr. Reddy's simvastatin even show Merck as the actual manufacturer and have Merck's logo on the bottom. Another example of an authorized generic is azithromycin.
Promotion of generic drugs
Although manufacturers of generic drugs do not promote generic drugs to health care providers and patients, generic drugs are promoted to hospitals and other purchasers of large amounts of drugs.
Independent organizations such as ConsumerLab.com and Consumers Union (publisher of Consumer Reports and Consumer Reports Health promote generic drugs.
References
- ↑ Anonymous (2024), Generic drug (English). Medical Subject Headings. U.S. National Library of Medicine.
- ↑ Anonymous (November, 2003). Generic Drug Prices in the U.S. Are Lower Than Drug Prices in Canada. Food and Drug Administration. Retrieved on 2009-02-01.
- ↑ Haas JS, Phillips KA, Gerstenberger EP, Seger AC (June 2005). "Potential savings from substituting generic drugs for brand-name drugs: medical expenditure panel survey, 1997-2000". Ann. Intern. Med. 142 (11): 891–7. PMID 15941695. [e]
- ↑ Kesselheim AS, Fischer MA, Avorn J (2006). "Extensions of intellectual property rights and delayed adoption of generic drugs: effects on medicaid spending". Health Aff (Millwood) 25 (6): 1637–47. DOI:10.1377/hlthaff.25.6.1637. PMID 17102189. Research Blogging.
- ↑ DiMasi JA, Hansen RW, Grabowski HG (March 2003). "The price of innovation: new estimates of drug development costs". J Health Econ 22 (2): 151–85. DOI:10.1016/S0167-6296(02)00126-1. PMID 12606142. Research Blogging.
- ↑ 6.0 6.1 Anonymous (May 12, 2008). Frequently Asked Questions on the Patent Term Restoration Program. US Food and Drug Administration. Retrieved on 2009-01-11.
- ↑ Nightingale, S (August 1, 1991). Statement by Stuart Nightingale, M.D. Associate Commissioner For Health Affairs U.S. Food and Drug Administration Public Health Service Department Of Health And Human Services Before the Subcommittee on Patents, Copyrights and Trademarks Committee on the Judiciary United States Senate. US Food and Drug Administration. Retrieved on 2009-01-11.
- ↑ A bill to amend the patent laws of the United States (English). Library of Congress (9/24/1984). Retrieved on 2009-02-01.
- ↑ 9.0 9.1 Anonymous (2008). Orange Book Annual Preface: Statistical Criteria for Bioequivalence. Food and Drug Administration. Retrieved on 2009-02-02. Cite error: Invalid
<ref>tag; name "urlOrange Book Annual Preface" defined multiple times with different content - ↑ Henney, Jane E. (1999-12-01). "Review of Generic Bioequivalence Studies". JAMA 282 (21): 1995-a. DOI:10.1001/jama.282.21.1995-a. Retrieved on 2009-02-03. Research Blogging.
- ↑ 11.0 11.1 (October 2002) "Generic Drugs". Med Lett Drugs Ther 44 (1141): 89–90. PMID 12405134. [e] Free access
- ↑ Frank RG (November 2007). "The ongoing regulation of generic drugs". N. Engl. J. Med. 357 (20): 1993–6. DOI:10.1056/NEJMp078193. PMID 18003956. Research Blogging.