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A '''generic drug''' (pl. generic drugs, short: generics) is a [[medication|drug]] which is [[bioequivalence|bioequivalent]] to a [[brand]] name drug with respect to [[pharmacokinetics|pharmacokinetic]] and [[pharmacodynamics|pharmacodynamic]] properties. These drugs are usually sold at a lower price than the brand name drug. 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 [[pharmacopoeia|pharmacopoeial]] requirements for the preparation. By extension, therefore, generics are assumed to be identical in dose, strength, route of administration, safety, efficacy, and intended use.
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In [[medicine]] and [[pharmacology]], '''generic drugs''' are "drugs whose drug name is not protected by a trademark. They may be manufactured by several companies." <ref>{{MeSH}}</ref> Government agencies determine whether a generic drug is [[bioequivalence|bioequivalent]] to a [[brand]] name drug with respect to [[pharmacokinetics|pharmacokinetic]] and [[pharmacodynamics|pharmacodynamic]] properties. [[Vancomycin]] may be an example where pharmagological bioequivalence does not predict therapeutic bioequivalence.<ref name="pmid20547818">{{cite journal| author=Vesga O, Agudelo M, Salazar BE, Rodriguez CA, Zuluaga AF| title=Generic vancomycin products fail in vivo despite being pharmaceutical equivalents of the innovator. | journal=Antimicrob Agents Chemother | year= 2010 | volume= 54 | issue= 8 | pages= 3271-9 | pmid=20547818 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20547818 | doi=10.1128/AAC.01044-09 }} </ref>
 
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."<ref name="urlGeneric Drug Prices in the U.S. Are Lower Than Drug Prices in Canada">{{cite web |url=http://www.fda.gov/oc/whitepapers/drugprices.html |title=Generic Drug Prices in the U.S. Are Lower Than Drug Prices in Canada |author=Anonymous |authorlink= |coauthors= |date=November, 2003 |format= |work= |publisher=Food and Drug Administration |pages= |language= |archiveurl= |archivedate= |quote= |accessdate=2009-02-01}}</ref> A branded generic may be an authorized generic (see description of authorized generic drug below).
 
Generic drugs are underutilized.<ref name="pmid15941695">{{cite journal |author=Haas JS, Phillips KA, Gerstenberger EP, Seger AC |title=Potential savings from substituting generic drugs for brand-name drugs: medical expenditure panel survey, 1997-2000 |journal=Ann. Intern. Med. |volume=142 |issue=11 |pages=891–7 |year=2005 |month=June |pmid=15941695 |doi= |url= |issn=}}</ref><ref name="pmid17102189">{{cite journal |author=Kesselheim AS, Fischer MA, Avorn J |title=Extensions of intellectual property rights and delayed adoption of generic drugs: effects on medicaid spending |journal=Health Aff (Millwood) |volume=25 |issue=6 |pages=1637–47 |year=2006 |pmid=17102189 |doi=10.1377/hlthaff.25.6.1637 |url=http://content.healthaffairs.org/cgi/pmidlookup?view=long&pmid=17102189 |issn=}}</ref>  Generics may not always be exactly equivalent to the brand-name drug they are allowed to replace; they may, for example, contain more active ingredients, or completely different ingredients, than the original drug.  In some conditions where changes in blood factors can be detected only after weeks on the different drug (e.g., in thyroiditis), switching to a generic can cause the patient to have to work with doctors to adjust dosage.  The cost, discomfort and inconvenience of the adjustment/testing process may lead patients to have their doctors mark prescriptions as "non-generic".
 
"Dispense as written requests were common and associated with decreased rates of prescription filling".<ref name="pmid21435421">{{cite journal| author=Shrank WH, Liberman JN, Fischer MA, Avorn J, Kilabuk E, Chang A et al.| title=The consequences of requesting "dispense as written". | journal=Am J Med | year= 2011 | volume= 124 | issue= 4 | pages= 309-17 | pmid=21435421 | doi=10.1016/j.amjmed.2010.11.020 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21435421  }} </ref>


== Reasons for cheaper price ==
== Reasons for cheaper price ==
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.  
{{Image|Competition.gif|right|350px|Generic competition and drug prices.}}
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 <ref name="pmid12606142">{{cite journal |author=DiMasi JA, Hansen RW, Grabowski HG |title=The price of innovation: new estimates of drug development costs |journal=J Health Econ |volume=22 |issue=2 |pages=151–85 |year=2003 |month=March |pmid=12606142 |doi=10.1016/S0167-6296(02)00126-1 |url=http://linkinghub.elsevier.com/retrieve/pii/S0167-6296(02)00126-1 |issn=}}</ref>


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.  
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.
First, generic manufacturers do not incur the cost of drug discovery and instead reverse-engineer existing brand name drugs to allow them to manufacture [[bioequivalence|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.   
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. The significant research and development and marketing costs incurred by the large pharmaceutical companies in bringing a new drug to the market is often cited as the reason for the high cost of new agents - they wish to recover these costs before the patent expires. Generic manufacturers do not incur these costs, with bioequivalence testing and the actual manufacturing process costing relatively little, and are able to charge significantly less than the "innovator" brand.
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 [http://www.tevapharm.com/ Teva], [http://www.sandoz.com/ Sandoz], [http://www.ethex.com Ethex], and [http://www.ranbaxy.com/ Ranbaxy] specialize in generic drugs.


== When can a generic drug be produced? ==
== 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. The expiration of a patent removes the monopoly of the patent holder on drug sales licensing. 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.
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 of America]], the duration of a patent is 20 years.<ref name="urlPatent Term Restoration">{{cite web |url=http://www.fda.gov/Drugs/DevelopmentApprovalProcess/SmallBusinessAssistance/ucm069959.htm |title=Frequently Asked Questions on the Patent Term Restoration Program|author=Anonymous |authorlink= |coauthors= |date=May 12, 2008 |format= |work= |publisher=US Food and Drug Administration |pages= |language= |archiveurl= |archivedate= |quote= |accessdate=2009-01-11}}</ref> However, in the [[United States of America]], 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. "<ref name="urlPatent Term Restoration"/><ref name="urlwww.fda.gov">{{cite web |url=http://www.fda.gov/bbs/topics/speech/spe00001.htm |title= 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  |author=Nightingale, S |authorlink= |coauthors= |date=August 1, 1991 |format= |work= |publisher=US Food and Drug Administration |pages= |language= |archiveurl= |archivedate= |quote= |accessdate=2009-01-11}}</ref>
 
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."


Enacted in 1984, the U.S. [[Drug Price Competition and Patent Term Restoration Act]], 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 [http://www.fda.gov/cder/ob/ "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 [http://www.fda.gov/cder/ob/docs/preface/ecpreface.htm#Therapeutic%20Equivalence-Related%20Terms "Approved Drug Products with Therapeutic Equivalence Evaluations, Preface."]
=== Abbreviated New Drug Application ===
Enacted in 1984, the U.S. Drug Price Competition and Patent Term Restoration Act<ref name="urlSearch Results - THOMAS (Library of Congress)">{{cite web |url=http://thomas.loc.gov/cgi-bin/bdquery/z?d098:SN01538:@@@D |title=A bill to amend the patent laws of the United States |author= |authorlink= |coauthors= |date=9/24/1984 |format= |work= |publisher=Library of Congress |pages= |language=English |archiveurl= |archivedate= |quote= |accessdate=2009-02-01}}</ref>, informally known as the "Hatch-Waxman Act", standardized U.S. procedures for recognition of generic drugs. An applicant files an [http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/AbbreviatedNewDrugApplicationANDAGenerics/default.htm 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 [http://www.fda.gov/cder/ob/ "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 [http://www.fda.gov/cder/ob/docs/preface/ecpreface.htm#Therapeutic%20Equivalence-Related%20Terms "Approved Drug Products with Therapeutic Equivalence Evaluations, Preface."]


== Patent lifetime and research cost issues ==
====Establishing bioequivalence====
{{main|Bioequivalence}}
Assurance of [[bioequivalence]] may be regulated by governmental agencies such as the [[Food and Drug Administration]] in the [[United States of America]].


Pharmaceutical companies may produce a generic drug when the patent expires on the innovator drug. [[Patent]] lifetime differs from country to country. 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. Usually, generic drugs are much less expensive than the [[brand-name]] product. Some patients and physicians will hesitate to select these medications because of concerns about the quality of generic drugs. When a pharmaceutical company first markets a drug, it is usually under a patent that allows only the pharmaceutical company that developed the drug to sell it. This allows the company to recoup the cost of developing that particular drug. It costs on average around $800,000,000 <ref> DiMasi J.A. et al.: "The price of innovation: new estimates of drug development cost", Journal of Health Economics 22(2003), 151-185.</ref> to develop and test a new drug before it is approved for use. After the patent on a drug expires, any pharmaceutical company can manufacture and sell that drug. Since the drug has already been tested and approved, the cost of simply manufacturing the drug will be a fraction of the original cost of testing and developing that particular 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."
The FDA requires that the following tests be within 80% to 125% of the reference drug.<ref name="urlOrange Book Annual Preface">{{cite web |url=http://www.fda.gov/cder/ob/docs/preface/ecpreface.htm |title=Orange Book Annual Preface: Statistical Criteria for Bioequivalence |author=Anonymous |authorlink= |coauthors= |date=2008 |format= |work= |publisher=Food and Drug Administration |pages= |language= |archiveurl= |archivedate= |quote= |accessdate=2009-02-02}}</ref> In practice, the results are typically within 3%.<ref>{{Cite journal | doi = 10.1001/jama.282.21.1995-a | volume = 282 | issue = 21 | pages = 1995-a | last = Henney | first = Jane E. | title = Review of Generic Bioequivalence Studies | journal = JAMA | accessdate = 2009-02-03 | date = 1999-12-01 | url = http://jama.ama-assn.org }}</ref> The FDA typically tests 24 to 36 healthy human volunteers.<ref name="pmid12405134">{{cite journal |author= |title=Generic Drugs |journal=Med Lett Drugs Ther |volume=44 |issue=1141 |pages=89–90 |year=2002 |month=October |pmid=12405134 |doi= |url=http://www.medicalletter.org/scripts/articlefind.cgi?issue=1141&page=89 |issn=}} [http://www.medletter.com/freedocs/gendrugs.pdf Free access]</ref>
* Area under the plasma concentration-time curve (AUC) for extent of absorption
** Calculated to the last measured concentration (AUC<sub>(0-t)</sub>)
** Extrapolated to infinity (AUC<sub>(0-inf)</sub>)
* The maximum or peak drug concentrations (Cmax), for rate of absorption


==Ensuring bioequivalence==
After testing, the FDA assigns "[[Food_and_Drug_Administration/Therapeutic_Equivalence_Code|Therapeutic Equivalence Evaluations Codes]]", or AB ratings.<ref name="urlOrange Book Annual Preface"/><ref name="pmid12405134">{{cite journal |author= |title=Generic Drugs |journal=Med Lett Drugs Ther |volume=44 |issue=1141 |pages=89–90 |year=2002 |month=October |pmid=12405134 |doi= |url=http://www.medicalletter.org/scripts/articlefind.cgi?issue=1141&page=89 |issn=}} [http://www.medletter.com/freedocs/gendrugs.pdf Free access]</ref> Drugs considered therapeutically equivalent are given a rating of AB, AA, AN, AO, AP, or AT.
In the [[USA]] the [[Food and Drug Administration]] (FDA) is responsible for making sure that generic drugs are "safe and effective." The approval process for generic drugs began in the late 1960s. Generic drug manufacturers were required to prove that their formulation exhibits [[bioequivalence]] to the innovator product. Over the past several years there have been studies that have shown the effectivness and safety of some generic drugs. Generic drugs are always less expensive and can save patients and insurance companies thousands of dollars supposedly without compromising the quality of care.  The FDA must approve generic drugs just as innovator drugs must be approved.  Bioequivalence, however, does not mean that generic drugs are exactly the same as their innovator product counterparts, as chemical differences do exist.  Some doctors and patients emphatically believe that certain generic drugs are not as effective as the products they are meant to replace (ie. Prozac, Oxycontin), and consumers would undoubtedly benefit from more clinical studies done on drug by drug basis. Generic drugs start out at first being fairly expensive, however the price of the generic product decreases as the rate of production increases.


As an interesting case study in the use of generic equivalents of name-brand agents, [[warfarin]] has been only available under the trade name [[Coumadin]] in North America until recently. Warfarin (either under the trade name or the generic equivalent) has a narrow therapeutic window and requires frequent blood tests to make sure patients do not have a subtherapeutic or a toxic level.  A study performed in the [[Canada|Canadian]] province of [[Ontario]] showed that replacing Coumadin with generic warfarin was considered safe.<ref name="Pereira-2005">{{cite journal | author=Pereira JA, Holbrook AM, Dolovich L, Goldsmith C, Thabane L, Douketis JD, Crowther MA, Bates SM, Ginsberg JS. | title=Are brand-name and generic warfarin interchangeable? Multiple n-of-1 randomized, crossover trials. | journal=Ann Pharmacother | year=2005 | volume=39 | issue=7-8 | pages=1188-93 | id=PMID 15914517 | url=http://www.theannals.com/cgi/content/full/39/7/1188}}</ref>  In spite of the study, many physicians are not comfortable in allowing their patients to take the branded generic equivalent agents.<ref name="Pereira-2005-1">{{cite journal | author=Pereira JA, Holbrook AM, Dolovich L, Goldsmith C, Thabane L, Douketis JD, Crowther M, Bates SM, Ginsberg JS. | title=Are brand-name and generic warfarin interchangeable? A survey of Ontario patients and physicians. | journal=Can J Clin Pharmacol | year=2005 | volume=12 | issue=3 | pages=e229-39 | id=PMID 16278495 | url=http://www.cjcp.ca/pdf/CJCP_04-043_e229.pdf}}</ref>
=== 180 Day Generic Drug Exclusivity===
In the [[United States of America]], 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.


== 180 Day Generic Drug Exclusivity==
====Authorized generics====
The US FDA 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.
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.


Large pharmaceutical companies often spend thousands of dollars protecting their patents from generic competition. Apart from litigation, companies use other methods such as reformulation or licensing 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'''; they are not affected by the 180 day exclusivity period as they fall under the patent holder's original drug application.
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''';<ref name="pmid18003956">{{cite journal |author=Frank RG |title=The ongoing regulation of generic drugs |journal=N. Engl. J. Med. |volume=357 |issue=20 |pages=1993–6 |year=2007 |month=November |pmid=18003956 |doi=10.1056/NEJMp078193 |url=http://content.nejm.org/cgi/content/full/357/20/1993 |issn=}}</ref> 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<ref name="urlH.R. 573: To amend the Federal Food, Drug, and Cosmetic Act to prohibit the marketing of authorized generic drugs (GovTrack.us)">{{cite web |url=http://www.govtrack.us/congress/bill.xpd?bill=h111-573 |title=H.R. 573: To amend the Federal Food, Drug, and Cosmetic Act to prohibit the marketing of authorized generic drugs (GovTrack.us) |author= |authorlink= |coauthors= |date= |format= |work= |publisher= |pages= |language= |archiveurl= |archivedate= |quote= |accessdate=2009-02-01}}</ref>


A prime 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.
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]].


== See also ==
==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.


* [[Generic-brand]]
Independent organizations such as [http://www.consumerlab.com/ ConsumerLab.com] and [http://www.consumersunion.org/ Consumers Union] (publisher of [http://www.consumerreports.org/ Consumer Reports] and [http://www.consumerreportshealth.org/ Consumer Reports Health] promote generic drugs.
* [[Research exemption]] (in patent law)
* [[Clinical Trials Budgeting]]
* [[Clinical research]]
* [[Clinical monitoring]]
* [[Clinical protocol]]
* [[ANDA|Approval process for generic drugs]]


==Further reading==
Prescribers underutilize generic medications.<ref name="pmid15941695"/>
Fighting generic competition: strategies for research-based companies, ''Urch Publishing''[http://www.urchpublishing.com/resources/generics.html]


==References==
A minority of patients prefer generic medications.<ref name="pmid19276015">{{cite journal| author=Shrank WH, Cox ER, Fischer MA, Mehta J, Choudhry NK| title=Patients' perceptions of generic medications. | journal=Health Aff (Millwood) | year= 2009 | volume= 28 | issue= 2 | pages= 546-56 | pmid=19276015 | doi=10.1377/hlthaff.28.2.546 | pmc=PMC2748784 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19276015  }} </ref>
<div class="references-small">
<references /></div>


== External links ==
==Attribution==
* [http://www.fda.gov/cder/ogd/ USFDA, Office of Generic Drugs]
{{WPAttribution}}
* [http://www.dh.gov.uk/PolicyAndGuidance/MedicinesPharmacyAndIndustry/GenericMedicines/fs/en UK Department of Health, generic drugs]
* [http://www.fact-sheets.com/health/generic_drugs/ Generic Drug Fact Sheet]
* [http://www.ama-assn.org/ama1/pub/upload/mm/365/usanstmlist_10_19_05.doc USAN stem name list]
* [http://www.rossinc.com/generics Generic Pharmaceutical Manufacturers Resource Center]


==Footnotes==
<small>
<references>


[[Category:CZ Live]]
</references>
[[Category:Health Sciences Workgroup]]
</small>

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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] Government agencies determine whether a generic drug is bioequivalent to a brand name drug with respect to pharmacokinetic and pharmacodynamic properties. Vancomycin may be an example where pharmagological bioequivalence does not predict therapeutic bioequivalence.[2]

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."[3] A branded generic may be an authorized generic (see description of authorized generic drug below).

Generic drugs are underutilized.[4][5] Generics may not always be exactly equivalent to the brand-name drug they are allowed to replace; they may, for example, contain more active ingredients, or completely different ingredients, than the original drug. In some conditions where changes in blood factors can be detected only after weeks on the different drug (e.g., in thyroiditis), switching to a generic can cause the patient to have to work with doctors to adjust dosage. The cost, discomfort and inconvenience of the adjustment/testing process may lead patients to have their doctors mark prescriptions as "non-generic".

"Dispense as written requests were common and associated with decreased rates of prescription filling".[6]

Reasons for cheaper price

Generic competition and drug prices.

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 [7]

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 of America, the duration of a patent is 20 years.[8] However, in the United States of America, 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. "[8][9]

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[10], 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

For more information, see: Bioequivalence.

Assurance of bioequivalence may be regulated by governmental agencies such as the Food and Drug Administration in the United States of America.

The FDA requires that the following tests be within 80% to 125% of the reference drug.[11] In practice, the results are typically within 3%.[12] The FDA typically tests 24 to 36 healthy human volunteers.[13]

  • 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.[11][13] 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 of America, 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;[14] 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[15]

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.

Prescribers underutilize generic medications.[4]

A minority of patients prefer generic medications.[16]

Attribution

Some content on this page may previously have appeared on Wikipedia.

Footnotes

  1. ↑ Anonymous (2024), Generic drug (English). Medical Subject Headings. U.S. National Library of Medicine.
  2. ↑ Vesga O, Agudelo M, Salazar BE, Rodriguez CA, Zuluaga AF (2010). "Generic vancomycin products fail in vivo despite being pharmaceutical equivalents of the innovator.". Antimicrob Agents Chemother 54 (8): 3271-9. DOI:10.1128/AAC.01044-09. PMID 20547818. Research Blogging.
  3. ↑ 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.
  4. ↑ 4.0 4.1 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]
  5. ↑ 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.
  6. ↑ Shrank WH, Liberman JN, Fischer MA, Avorn J, Kilabuk E, Chang A et al. (2011). "The consequences of requesting "dispense as written".". Am J Med 124 (4): 309-17. DOI:10.1016/j.amjmed.2010.11.020. PMID 21435421. Research Blogging.
  7. ↑ 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.
  8. ↑ 8.0 8.1 Anonymous (May 12, 2008). Frequently Asked Questions on the Patent Term Restoration Program. US Food and Drug Administration. Retrieved on 2009-01-11.
  9. ↑ 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.
  10. ↑ A bill to amend the patent laws of the United States (English). Library of Congress (9/24/1984). Retrieved on 2009-02-01.
  11. ↑ 11.0 11.1 Anonymous (2008). Orange Book Annual Preface: Statistical Criteria for Bioequivalence. Food and Drug Administration. Retrieved on 2009-02-02.
  12. ↑ 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.
  13. ↑ 13.0 13.1 (October 2002) "Generic Drugs". Med Lett Drugs Ther 44 (1141): 89–90. PMID 12405134. [e] Free access
  14. ↑ 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.
  15. ↑ H.R. 573: To amend the Federal Food, Drug, and Cosmetic Act to prohibit the marketing of authorized generic drugs (GovTrack.us). Retrieved on 2009-02-01.
  16. ↑ Shrank WH, Cox ER, Fischer MA, Mehta J, Choudhry NK (2009). "Patients' perceptions of generic medications.". Health Aff (Millwood) 28 (2): 546-56. DOI:10.1377/hlthaff.28.2.546. PMID 19276015. PMC PMC2748784. Research Blogging.

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