Epinephrine autoinjector

{{Infobox medical intervention

| image = File:Epi-Pen 2016.jpg| caption = Mylan 0.3 mg EpiPen, epinephrine autoinjector

| alt =

| pronounce =

| specialty =

| ICD10 =

| ICD9 =

| ICD9unlinked =

| CPT =

| MeshID =

| LOINC =

| other_codes =

| MedlinePlus =

| eMedicine =

|Speciality=|field=Emergency medicine|types={{Ublist|Standard: 0.3 mg|Junior size: 0.15 mg}}|Synonyms=|Synonym=EpiPen|Name=Epinephrine autoinjector|uses=Anaphylaxis}}

An epinephrine autoinjector (or adrenaline autoinjector, also known by the trademark EpiPen) is a medical device for injecting a measured dose or doses of epinephrine (adrenaline) by means of autoinjector technology. It is most often used for the treatment of anaphylaxis. The first epinephrine autoinjector was brought to market in 1983.

Medical uses

File:Intramuscular site of adrenaline.jpg

File:Jext300-Autoinjektor-02 (cropped).jpg

Epinephrine autoinjectors are hand-held devices carried by those who have severe allergies; the epinephrine delivered by the device is an emergency treatment for anaphylaxis.{{cite web|title=Anaphylaxis|url=https://www.niaid.nih.gov/topics/anaphylaxis/Pages/default.aspx|website=National Institute of Allergy and Infectious Diseases|access-date=4 February 2016|date=April 23, 2015|url-status=dead|archive-url=https://web.archive.org/web/20150504041904/http://www.niaid.nih.gov/topics/anaphylaxis/Pages/default.aspx|archive-date=4 May 2015}}{{cite journal|last1=Dinakar|first1=C|title=Anaphylaxis in children: current understanding and key issues in diagnosis and treatment.|journal=Current Allergy and Asthma Reports|date=December 2012|volume=12|issue=6|pages=641–9|pmid=22815131|pmc=3492692|doi=10.1007/s11882-012-0284-1}}

When anaphylaxis is suspected, epinephrine solution should be given as soon as possible as an intramuscular injection, in the middle of the outer side of the thigh, which corresponds to the location of the vastus lateralis muscle.{{cite web|url=https://medlineplus.gov/druginfo/meds/a603002.html|title=Epinephrine Injection|website=MedlinePlus}} Last revised 03/15/2017 The injection may be repeated every 5 to 15 minutes if there is insufficient response. A second dose is needed in 16–35% of episodes with more than two doses rarely required; in around 80% of the cases where a second dose is administered, it is by a medical professional. It is not clear which are the people who might need a second injection at the outset. The intramuscular route is preferred over subcutaneous administration because the latter may have delayed absorption.{{cite journal|last=Simons|first=KJ|author2=Simons, FE|title=Epinephrine and its use in anaphylaxis: current issues|journal=Current Opinion in Allergy and Clinical Immunology|date=August 2010|volume=10|issue=4|pages=354–61|pmid=20543673|doi=10.1097/ACI.0b013e32833bc670|s2cid=205435146}} Minor adverse effects from epinephrine include tremors, anxiety, headaches, and palpitations.

The epinephrine in autoinjectors expires after one year. A study in rabbits showed that intramuscular epinephrine has decreased effectiveness after it expires; that study also recommended that if the drug in an expired device has not started to precipitate (if the solution is not cloudy and has no particles in it) using the expired device is better than no injection at all in an emergency situation.

Design

File:Epipen design (cropped).jpg solution. 5. Outer body. When retracted upward (left) exposes the needle and triggers the latch mechanism. Later springs back to cover the needle after use. 6. Needle exits through a protective barrier when this is pressed against the skin.]]

The devices contain a fixed dose of epinephrine and a spring-loaded needle (or, in the case of AuviQ, a CO₂-driven needle) that exits the tip or edge of the device and penetrates the recipient's skin, to deliver the medication via intramuscular injection.

People to whom epinephrine autoinjectors are prescribed need to be trained how to use the specific device prescribed.{{cite journal|last1=Muraro|first1=A|display-authors=etal|last2=The EAACI Food Allergy and Anaphylaxis Guidelines Group|title=Anaphylaxis: guidelines from the European Academy of Allergy and Clinical Immunology.|journal=Allergy|date=August 2014|volume=69|issue=8|pages=1026–45|pmid=24909803|doi=10.1111/all.12437|s2cid=11054771}} The rate of unintentional injections using these devices is unknown but a 2009 review found that the rate is increasing. Unintentional injections are delivered to a finger or thumb around 90% of the time; they cause intense pain locally but usually completely resolve. The cause of unintentional injections has been attributed to design flaws, where the device is mistaken for a pen or the user mistakes which end of the device contains the needle.{{cite journal|last1=Simons|first1=FE|last2=Lieberman|first2=PL|last3=Read EJ|first3=Jr|last4=Edwards|first4=ES|title=Hazards of unintentional injection of epinephrine from autoinjectors: a systematic review.|journal=Annals of Allergy, Asthma & Immunology|date=April 2009|volume=102|issue=4|pages=282–7|pmid=19441598|doi=10.1016/s1081-1206(10)60332-8}}

The European Medicines Agency conducted a review of the safety of devices then on the market and found several factors that determine whether the devices successfully deliver drug into muscle, including "needle length, the thickness of fat under the skin, the way the auto-injector works (e.g., if it is spring loaded or not), the angle at which the device is placed on the skin and the force used to activate the device as well as how well the user follows the instructions for injection."{{cite news|last1=European Medicines Agency|title=Better training tools recommended to support patients using adrenaline auto-injectors|url=http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2015/06/news_detail_002351.jsp&mid=WC0b01ac058004d5c1|date=June 26, 2015|access-date=August 31, 2016|archive-date=September 10, 2016|archive-url=https://web.archive.org/web/20160910052959/http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2015/06/news_detail_002351.jsp&mid=WC0b01ac058004d5c1|url-status=dead}} It found that how well the user was trained was the most important factor determining successful delivery, and requested companies to develop better training materials for doctors and people to whom the devices are prescribed.

File:Auvi-Q Injection.webm

In 2013, emergency physician Seth C. Hawkins and coauthors published a technique for obtaining multiple additional doses of epinephrine from used, single dose autoinjectors EpiPen and Adrenaclick. It was emphasized this was an emergency adaptation of the intended design for austere environments when no additional epinephrine was available.{{cite journal|last1=Hawkins|first1=SC|last2=Weil|first2=C|last3=Baty|first3=F|last4=Fitzpatrick|first4=D|last5=Rowell|first5=B|title=Retrieval of Additional Epinephrine from Auto-Injectors|journal=Wilderness & Environmental Medicine|date=September 2013|volume=24|issue=4|pages=434–44|doi=10.1016/j.wem.2013.03.025|pmid=24041621|doi-access=free}} In 2016, Robinson and Lareau published a similar technique adapted to used AuviQ autoinjectors.{{cite journal|last1=Robinson|first1=P|last2=Lareau|first2=S|title=Novel Technique for Epinephrine Removal in New Generation Autoinjectors|journal=Wilderness & Environmental Medicine|date=April 2016|volume=27|issue=2|pages=252–5|doi=10.1016/j.wem.2016.02.005|pmid=27095540|doi-access=free}}

History

=Product introduction=

Autoinjectors were originally developed for the rapid administration of nerve gas antidotes in kits like the Mark I NAAK. The first modern epinephrine autoinjector, the EpiPen, was invented in the mid-1970s at Survival Technology in Bethesda, Maryland, US by Sheldon Kaplan{{cite web|url=http://www.tampabay.com/news/humaninterest/epipen-inventor-helped-millions-and-died-in-obscurity/1038756 |title=EpiPen inventor helped millions and died in obscurity |first=Kevin |last=Smetana |work=St. Petersburg Times |date=September 24, 2009 |access-date=2010-07-07 |url-status=dead |archive-url=https://web.archive.org/web/20130201055705/http://www.tampabay.com/news/humaninterest/epipen-inventor-helped-millions-and-died-in-obscurity/1038756 |archive-date=February 1, 2013 }}National Inventors Hall of Fame [http://invent.org/inductees/kaplan-sheldon/ Kaplan Sheldon] {{Webarchive|url=https://web.archive.org/web/20160131003008/http://invent.org/inductees/kaplan-sheldon/ |date=2016-01-31 }} and was first approved for marketing by the FDA in 1987.FDA [http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.Set_Current_Drug&ApplNo=019430&DrugName=EPI%20E%20Z%20PEN%20JR&ActiveIngred=EPINEPHRINE&SponsorApplicant=MYLAN%20SPECLT&ProductMktStatus=3&goto=Search.DrugDetails Approval history for NDA 019430 - EpiPen] Page accessed Aug 30, 2016

One of the people who helped in making the EpiPen was Richard B. Toren. He had the idea to use this technology for allergic reactions because his daughter was allergic to bees and had to carry around a complex kit if she was ever stung. He then helped to slightly alter the technology in order to create EpiPen's current design.{{Cite web|url=http://www.adeliberatepause.com/Rick_Toren_Videos.html|title=Rick Toren|website=www.adeliberatepause.com|access-date=2019-11-20|archive-date=2021-01-22|archive-url=https://web.archive.org/web/20210122125914/http://www.adeliberatepause.com/Rick_Toren_Videos.html|url-status=dead}}

In 1996, Survival Technology merged with a company called Brunswick Biomedical and the new company was called Meridian Medical Technologies.Meridian Medical Technologies [https://www.sec.gov/Archives/edgar/data/95676/0001024739-97-000670.txt 10-K Filing] For the fiscal year ended July 31, 1997 In 1997, Dey, a subsidiary of Merck KGaA, acquired the exclusive right to market and distribute the EpiPen.Dey, Inc. [http://www.nasdaq.com/markets/ipos/filing.ashx?filingid=901594 Amendment No. 3 to Form S-1] Registration Statement under The Securities Act Of 1933. Filed April 30, 1999King Pharmaceuticals Oct 21, 2002. [http://www.prnewswire.com/news-releases/king-pharmaceuticals-to-acquire-meridian-medical-technologies-76364227.html Press Release: King Pharmaceuticals to Acquire Meridian Medical Technologies] In 1998 there was a recall of one million EpiPens, the second such recall in a year.{{cite news|last1=Chase|first1=Marilyn|title=EpiPen Recall PointsTo Broader Concerns|url=https://www.wsj.com/articles/SB895440623631960000|work=Wall Street Journal|date=18 May 1998}}

In 2001 Meridian and Dey introduced a two-pack version of the EpiPen; at that time the device had $23.9 million in annual sales and accounted for 75% of the market in the United States.Meridian Medical Technologies, Merck KGaA. April 03, 2001 [http://www.evaluategroup.com/Universal/View.aspx?type=Story&id=33164§ionID=&isEPVantage=no Press Release: Meridian Announces Launch Of New EpiPen 2-Pak] In 2002 King Pharmaceuticals acquired Meridian for $247.8 million in cash; the deal was completed in January 2003.King Pharmaceuticals [https://www.sec.gov/Archives/edgar/data/1047699/000095014404006620/g89681e11vk.htm Form 11K] filed For the fiscal year ended December 31, 2003. Kaplan continued to improve his designs over the years, filing for example US Patent 6,767,336 in 2003.{{cite web|url=https://patents.google.com/patent/US6767336B1/en|title=Automatic injector|website=Patents.google.com|access-date=16 March 2019}}

In 2003, Hollister-Stier received approval from the FDA to market an epinephrine autoinjector called Twinject that could deliver two shots of epinephrine, which it had spent ten years developing.Jennifer Sudick for the Spokane Spokesman-Review. July 20, 2005 [http://www.spokesman.com/stories/2005/jul/20/spokane-firm-sells-rights-to-auto-injector/ Spokane firm sells rights to auto-injector]FDA [http://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/20-800_Twinject_approv.pdf Twinject Approval Package]FDA [http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.Set_Current_Drug&ApplNo=020800&DrugName=ADRENACLICK&ActiveIngred=EPINEPHRINE&SponsorApplicant=AMEDRA%20PHARMS&ProductMktStatus=1&goto=Search.DrugDetails Approval History NDA 020800 - Twinject and Adrenaclick] Page accessed August 25, 2016 In 2005, it sold the product to Verus Pharmaceuticals, which launched the product the same year.{{cite web|url=http://www.veruspharm.com/news_releases_08_16_2005.htm |title=Verus Pharmaceuticals Announces U.S. Launch of Twinject for Anaphylaxis |website=Veruspharm.com |url-status=bot: unknown |archive-url=https://web.archive.org/web/20051222104426/http://www.veruspharm.com/news_releases_08_16_2005.htm |archive-date=2005-12-22 }} In March 2008, Sciele Pharma acquired Twinject from VerusSciele Pharma. March 13, 2008. [http://www.businesswire.com/news/home/20080313005131/en/Sciele-Pharma-Acquires-Twinject-Epinephrine-Auto-Injector-Verus Press Release: Sciele Pharma Acquires Twinject® Epinephrine Auto-Injector from Verus Pharmaceuticals] and later that year, Sciele was acquired by Shionogi.Z+Kazuhiro Shimamua for The Wall Street Journal. Sept. 1, 2008 [https://www.wsj.com/articles/SB122025623886887159 Shionogi to Buy Sciele Pharma]

In 2007, Mylan acquired the right to market the EpiPen from Merck KGaA as part of a larger transaction.Tara Parker-Pope and Rachel Rabkin Peachman for the New York Times. Aug 22, 2016 [http://well.blogs.nytimes.com/2016/08/22/epipen-price-rise-sparks-concern-for-allergy-sufferers/?_r=1 EpiPen Price Rise Sparks Concern for Allergy Sufferers] At that time annual sales were around $200 million and the EpiPen had about 90% of the market.{{cite news|last1=Johnson|first1=Carolyn Y.|last2=Ho|first2=Catherine|title=How Mylan, the EpiPen company, maneuvered to create a virtual monopoly|url=http://www.chicagotribune.com/business/ct-mylan-epipen-monopoly-20160825-story.html|work=The Washington Post via The Chicago Tribune|date=August 25, 2016}}

In 2009, Mylan and King started marketing a new version of EpiPen with the same basic mechanism but a stronger spring, better safety features, and clearer markings and instructions; an expert for NBC News estimated that the cost to redesign the device and packaging may have been "several million dollars" and the cost to retool the manufacturing process may have "run into the double-digit millions."{{cite news|last1=Popken|first1=Ben|title=Upgraded EpiPens torn apart. Tech firm: "It's the same core device"|url=https://www.nbcnews.com/business/consumer/mylan-says-it-upgraded-epipen-2009-so-experts-looked-inside-n652651|work=NBC News|date=September 30, 2016}}

=Market development=

In 2009, Teva Pharmaceuticals filed an ANDA to market a generic EpiPen in collaboration with Antares Pharma Inc, a maker of injection systems; Pfizer and King sued them for infringing US Patent 7,449,012 that was due to expire in 2025;{{cite web|url=https://patents.google.com/patent/US7449012B2/en|title=Automatic injector|website=Patents.google.com|access-date=16 March 2019}} Pfizer, Mylan, and Teva settled in April 2012 in a deal that allowed Teva to start selling the device in mid-2015, pending FDA approval.Phil Milford for Bloomberg News April 26, 2012 [https://www.bloomberg.com/news/articles/2012-04-26/mylan-pfizer-announce-epinephrine-pen-settlement-with-teva-1- Mylan, Pfizer Reach Epinephrine-Pen Settlement With Teva]

In 2009, Intelliject, a US startup developing a new epinephrine autoinjector, licensed their product to Sanofi.Katie Thomas for the New York Times. Feb 1, 2013 [https://www.nytimes.com/2013/02/02/business/auvi-q-challenges-epipen-with-a-new-shape-and-size.html Brothers Develop New Device to Halt Allergy Attacks]

King was acquired by Pfizer in 2010 for $3.6 billion in cash.{{cite web |url=http://www.pfizer.com/news/press_releases/pfizer_press_release_archive.jsp?guid=20110301006102en&source=2011&page=14 |archive-url=https://archive.today/20130630050306/http://www.pfizer.com/news/press_releases/pfizer_press_release_archive.jsp?guid=20110301006102en&source=2011&page=14 |url-status=dead |archive-date=June 30, 2013 |title=Pfizer Completes Acquisition Of King Pharmaceuticals, Inc.; Pfizer and King begin joint operations on March 1, 2011 |date=March 1, 2011 |website=Pfizer.com |type=press release }}

In 2010, Sciele/Shionogi faced a recall of Twinject devicesRecalls.org [http://www.recalls.org/d2010-12.htm December 2010] {{Webarchive|url=https://web.archive.org/web/20160829013442/http://www.recalls.org/d2010-12.htm |date=2016-08-29 }} and launched Adrenaclick, a modified version of the Twinject that could deliver only one dose.Staff, Monthly Prescribing Reference. January 07, 2010 [http://www.empr.com/news/adrenaclick-auto-injector-launched-for-anaphylaxis/article/160817/ Adrenaclick Auto-injector launched for anaphylaxis]FDA/Shionogi [http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020800s018lbl.pdf Adrenaclick original label 2009]

In 2010, European regulators approved Twinject,Shionogi. August 31, 2010 [http://www.shionogi.co.jp/en/company/news/2010/pmrltj00000013em-att/Shionogi.pdf Press Release: Shionogi Announces Positive Outcome to the Decentralized Procedure For The European Approval Of Twinject (Epinephrine Auto-Injector)] and also approved a new epinephrine autoinjector made by ALK and sold under the brand name Jext.{{cite web|url=https://newsclient.omxgroup.com/cdsPublic/viewDisclosure.action?disclosureId=420528&messageId=508349|title=ALK media release (07 October 2010)|access-date=2014-04-08}}{{cite web|url=https://newsclient.omxgroup.com/cdsPublic/viewDisclosure.action?disclosureId=421242&messageId=509295|title=ALK media release (13 October 2010)|access-date=2014-04-08}} Jext was launched in the European Union in September 2011.{{cite web|url=https://newsclient.omxgroup.com/cdsPublic/viewDisclosure.action?disclosureId=468888&messageId=571948|title=ALK media release (06 September 2011)|access-date=2014-04-08}}

Also in 2010, Shionogi authorized Greenstone, the authorized generics division of Pfizer,{{cite news|last1=Staff|title=Greenstone LLC - A Successful Business Model|url=http://www.pharmacytimes.com/publications/supplement/2008/supp_2008-08/supp_2008-08_006|publisher=Pharmacy Times|date=August 1, 2008}}{{cite news|last1=Hensley|first1=Scott|title=Pfizer to Make Generic Version of Its Zoloft|url=https://www.wsj.com/articles/SB115154467879893805|work=Wall Street Journal|date=29 June 2006}} to begin selling an authorized generic of Adrenaclick.{{cite web|last1=Tucker|first1=Janna|title=Generic Epinephrine Injector May Cause Confusion|url=http://acaai.org/resources/connect/letters-editor/letters-to-web-editor-6|publisher=American College of Allergy, Asthma & Immunology|access-date=August 30, 2016|archive-url=https://web.archive.org/web/20160829121100/http://acaai.org/resources/connect/letters-editor/letters-to-web-editor-6|archive-date=August 29, 2016|url-status=dead}}{{cite web|title=EPINEPHRINE injection [Greenstone LLC] |url=http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=16934 |publisher=FDA via DailyMed |date=16 May 2010 |quote=Marketing Category: NDA Authorized Generic; Application Number Or Monograph: NDA020800; Marketing Start Date: 03/31/2010 |url-status=bot: unknown |archive-url=https://web.archive.org/web/20100516130646/http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=16934 |archive-date=2010-05-16 }} The media noted that Pfizer, through Greenstone, was marketing a generic epinephrine autoinjector when Pfizer acquired King later that year.{{cite news|last1=Edwards|first1=Jim|title=In $3.6B King Deal, Pfizer Gets a Small but Important EpiPen Monopoly|url=http://www.cbsnews.com/news/in-36b-king-deal-pfizer-gets-a-small-but-important-epipen-monopoly/|agency=CBS MoneyWatch|date=Oct 12, 2010}} At that time, King and Mylan's EpiPen had 91% of the global market share for epinephrine autoinjectors and 96% of the US market.

In 2010, Pfizer and King sued Novartis' Sandoz generic unit for patent infringement after Sandoz submitted an ANDA to sell a generic EpiPen.Julie Zeveloff for Law360. July 16, 2010. [http://www.law360.com/articles/181459/king-pharma-sues-sandoz-over-generic-epipen King Pharma Sues Sandoz Over Generic EpiPen] In response, Sandoz challenged the validity of the patents, and as of July 2016 this litigation was ongoing.Pfizer [https://www.sec.gov/Archives/edgar/data/78003/000007800316000105/pfe-7032016x10q.htm Quarterly Report (Form 10-Q) for the quarterly period ended July 3, 2016]

In 2011, Pfizer and King sued Intelliject and Sanofi after the companies filed a 505(b)(2)Note - a "505(b)(2)" is a kind of new drug application that allows the applicant to rely in part on someone else's drug approval data - this pathway is used for example to get approval for an existing drug for a new indication. The information about the drug itself is someone else's, but the applicant has to generate the data showing the drug works for the new indication. In the case of Intelliject, it is the generic drug in a new device. For an explanation see Kenneth V. Phelps for Drug Discovery & Development Magazine. Aug 9, 2012 [http://www.dddmag.com/article/2012/08/taking-505b2-route Taking the 505(b)(2) Route] New Drug Application for the product, then known as "e-cue";Sherri Oslick for PatentDocs. [http://www.patentdocs.org/2011/week4/ Court Report January 23, 2011] Pfizer, Mylan and Sanofi settled in 2012 under a deal that allowed the device to enter the market no earlier than November 2012, pending FDA approval.Mylan. Feb 16, 2012 [http://www.prnewswire.com/news-releases/mylan-and-pfizer-announce-epinephrine-auto-injector-settlement-agreement-139440018.html Press Release: Mylan and Pfizer Announce Epinephrine Auto-injector Settlement Agreement] In August 2012, the FDA approved the autoinjector, called "Auvi-Q" after the FDA required a name change from "e-cue".John Reid Blackwell for the Richmond Times-Dispatch. August 14, 2012 [http://www.richmond.com/business/article_88a7cbb3-2f92-551e-a8c2-33c8512be1eb.html FDA approves Intelliject's life-saving device for allergy sufferers] The device is equipped with a sound chip to provide electronic voice instructions to guide the user in the proper use of the device.{{cite web|title=Auvi-Q Fact Sheet|url=http://www.multivu.com/assets/57459/documents/Auvi-Q-Fact-Sheet-original.pdf|access-date=18 August 2012}}Sanofi August 13, 2012 [http://en.sanofi.com/Images/30999_20120813_EAI_FDA_APPROVAL_en.pdf Press Release: Sanofi Announces FDA Approval for Auvi-Q] {{Webarchive|url=https://web.archive.org/web/20170131211920/http://en.sanofi.com/Images/30999_20120813_EAI_FDA_APPROVAL_en.pdf |date=2017-01-31 }}

In 2012, Mylan launched a program called EpiPen4Schools to sell EpiPens in bulk and with discounts to schools; to participate in the program schools had to agree not to buy epinephrine autoinjectors from any other company for a year.{{cite news|last1=Swetlitz|first1=Ike|last2=Silverman|first2=Ed|title=Mylan may have violated antitrust law in its EpiPen sales to schools|url=https://www.pbs.org/newshour/rundown/mylan-may-violated-antitrust-law-epipen-sales-schools-legal-experts-say/|work=PBS Newshour|date=August 26, 2016}}

In December 2012, the National Association of State Boards of Education launched a policy initiative designed to "help state boards of education as they develop student health policies regarding anaphylaxis and epinephrine auto-injector access and use", and advocated for state laws protecting school from legal liability for stocking and using epinephrine autoinjectors. Gayle Conelly Manchin, mother of Mylan's CEO, Heather Bresch, had become president of the association in 2010, and shortly after had discussed donations from her "daughter's company" to the association. Manchin had been appointed to the West Virginia state school board by her husband Joe Manchin, then-governor of the state, in 2012.{{cite news|last1=O'Donnell|first1=Jayne|title=Family matters: EpiPens had high-level help getting into schools|url=https://www.usatoday.com/story/news/politics/2016/09/20/family-matters-epipens-had-help-getting-schools-manchin-bresch/90435218/|work=USA Today|date=September 21, 2016}}

In 2012, Shionogi, the manufacturer of Adrenaclick and Twinject, announced it would stop making them; it had sold the rights to the NDA to a company called Amedra Pharmaceuticals.National Council for Prescription Drug Programs May 2013 [https://www.ncpdp.org/standards/standards-quic-forms.aspx?ID=12 QUIC FORM 201313 Adrenaclick Auto-Injector, NDC 59630-0803-02 And 59630-0804-02 Resolution] {{Webarchive|url=https://web.archive.org/web/20160914024059/https://www.ncpdp.org/standards/standards-quic-forms.aspx?ID=12 |date=2016-09-14 }}. Indexed [https://www.ncpdp.org/standards/standards-quic-forms.aspx?word=adrenaclick here] {{Webarchive|url=https://web.archive.org/web/20170802114230/https://www.ncpdp.org/standards/standards-quic-forms.aspx?word=adrenaclick |date=2017-08-02 }}Shionogi [http://www.shionogi.co.jp/en/ir/pdf/sup12_05.pdf FY2011 Financial Results: Supplement] See note in the margin of page 6

In June 2013, Amedra relaunched Adrenaclick.Amedra Pharmaceutical June 14th, 2013 [http://www.firstwordpharma.com/node/1108790?tsid=17#axzz4IQ7wEMc1 Press Release: Amedra Pharmaceuticals Markets Adrenaclick Auto-Injector] and at the same time, Lineage Therapeutics launched its authorized generic version of Adrenaclick.Lineage Therapeutics. Jun 14, 2013 [http://www.prnewswire.com/news-releases/lineage-therapeutics-markets-authorized-generic-epinephrine-auto-injector-211585371.html Press Release: Lineage Therapeutics Markets Authorized Generic Epinephrine Auto-Injector] Lineage was a wholly owned subsidiary of Amedra that had acquired the rights to the Adrenaclick authorized generic from Greenstone/Pfizer.{{cite news|title=Clinical Alert|url=https://www.magellanmedicaid.com/news/ClinicalAlerts/CA_2013-07.pdf|publisher=Magellan Medical|date=July 2013|archive-url=https://web.archive.org/web/20160909230123/https://www.magellanmedicaid.com/news/ClinicalAlerts/CA_2013-07.pdf|archive-date=September 9, 2016}}

After successful lobbying from Mylan, in 2013, the "School Access to Emergency Epinephrine Act" became law after passing Congress with broad and bipartisan support; it protected anyone from liability if they administered epinephrine to a child in a school (previously, only trained professionals or the affected person were allowed to administer the drug, and were open to liability), and it provided some financial incentives for schools that didn't already stock epinephrine autoinjector to start stocking them.{{cite news|last1=Novak|first1=Matt|title=How Congress, the FDA, and Sarah Jessica Parker Helped EpiPen Become a $1 Billion Business|url=https://gizmodo.com/how-congress-the-fda-and-sarah-jessica-parker-helped-1785568792|website=Gizmodo.com|date=August 23, 2016}} Joe Manchin, the father of Mylan's CEO, was a senator at that time.

In January 2015 Mylan filed a citizen petition with the FDA raising concerns about TEVA's ANDA application to market a generic EpiPen and filed an additional supplement later in May; the FDA rejected the petition in June.{{cite news|last1=Gibney|first1=Michael|title=Could EpiPen's plastic cap be Mylan's secret weapon?|url=http://www.fiercepharma.com/drug-delivery/could-a-plastic-cap-epipen-have-given-mylan-its-market-dominance|work=FiercePharma|date=September 1, 2016}}{{cite web|title=FDA-2015-P-0181: Requests that the FDA take certain actions with respect to abbreviated new drug application (ANDA) 90-589, submitted by Teva Pharmaceuticals (Teva), for an epinephrine auto-injector.|url=http://www.regulations.gov/docket?D=FDA-2015-P-0181|publisher=US Government Dockets Repository|access-date=September 10, 2016}}

In March 2015, Impax Laboratories acquired the parent company of Amedra and Lineage, and placed Amedra and the Adrenaclick in its Impax Specialty Pharma division; at the same time it acquired Lineage, which it placed, along with its generic version of Adrenaclick, in its Impax Generics division.{{cite web | url = http://investors.impaxlabs.com/files/doc_financials/2015/2014-Annual-Report_v001_i3ejq8.pdf | title = Impax 2014 Annual Report | access-date = 2016-08-26 | archive-url = https://web.archive.org/web/20151023074926/http://investors.impaxlabs.com/files/doc_financials/2015/2014-Annual-Report_v001_i3ejq8.pdf | archive-date = 2015-10-23 | url-status = dead }}Impax March 10, 2015 [http://investors.impaxlabs.com/Media-Center/Press-Releases/Press-Release-Details/2015/Impax-Completes-Acquisition-Of-Tower-Holdings-Inc-And-Lineage-Therapeutics-Inc/ Press Release: Impax Completes Acquisition Of Tower Holdings, Inc. And Lineage Therapeutics Inc.] {{Webarchive|url=https://web.archive.org/web/20160827154040/http://investors.impaxlabs.com/Media-Center/Press-Releases/Press-Release-Details/2015/Impax-Completes-Acquisition-Of-Tower-Holdings-Inc-And-Lineage-Therapeutics-Inc/ |date=2016-08-27 }}

In May 2015, the Emerade epinephrine autoinjector developed by the Swedish company Medeca was approved in Sweden and Germany;{{cite web|title=Epinephrine self-injectable - Medeca Pharma AB - AdisInsight|url=http://adisinsight.springer.com/drugs/800043402|publisher=Adis Insight|access-date=3 October 2016}} it had been approved in the UK in 2013.{{cite web|title=Emerade, 500 micrograms, solution for injection in pre-filled pen - Summary of Product Characteristics (SPC) - (eMC)|url=https://www.medicines.org.uk/emc/medicine/28631|publisher=UK Electronic Medicines Compendium|access-date=3 October 2016|archive-date=3 October 2016|archive-url=https://web.archive.org/web/20161003193436/https://www.medicines.org.uk/emc/medicine/28631|url-status=dead}} Also in 2015 Valeant, which had licensed the rights from Medeca, abandoned its efforts to get Emerade approved in the US.{{cite web|title=Valeant Form 10-K For the fiscal year ended December 31, 2015|url=https://www.sec.gov/Archives/edgar/data/885590/000088559016000101/valeant2015form10-k.htm|publisher=SEC Edgar}}

In October 2015, Auvi-Q and Allerject devices were voluntarily recalled by Sanofi in North America.{{cite web|url=http://www.richmond.com/business/article_73687f17-3be1-5c9f-a66d-443dd8ee9804.html|title=Auvi-Q auto injector being recalled|work=Richmond Times-Dispatch|date=October 29, 2015|author=Tammie Smith}}{{cite web|url=http://www.cbc.ca/news/health/allerject-epinephrine-auto-injectors-recalled-by-drugmaker-sanofi-1.3293765|title=Allerject epinephrine auto-injectors recalled by drugmaker Sanofi|date=30 October 2015|agency=Associated Press|publisher=Canadian Broadcasting Company}} The reason stated by Sanofi was that the products had been found to potentially have inaccurate dosage delivery, which may include failure to deliver drug.{{cite web|url=https://www.fda.gov/Safety/Recalls/ucm469980.htm|title=Updated: Sanofi US Issues Voluntary Nationwide Recall of All Auvi-Q® Due to Potential Inaccurate Dosage Delivery|website=Fda.gov}} In February 2016, Sanofi terminated its license to manufacture and market the Auvi-Q, leaving Kaléo (Intelliject was renamed) to consider how and whether to re-introduce the device.{{cite news|last1=Spiers|first1=Jonathan|title=French pharma giant vacates deal with Shockoe Slip firm|url=http://richmondbizsense.com/2016/03/21/french-pharma-giant-vacates-deal-with-shockoe-slip-firm/|work=Richmond BizSense|date=21 March 2016}}{{cite news|last1=Stanton|first1=Dan|title=Sanofi abandoning Auvi-Q after dosage problems led to total recall|url=http://www.in-pharmatechnologist.com/Processing/Sanofi-abandoning-Auvi-Q-after-dosage-problems-led-to-total-recall|work=in-Pharma Technologist|date=February 26, 2016}}

The EpiPen had 89% of the market for epinephrine autoinjectors in 2015; in the first half of the year it had about 85% share and Auvi-Q had about 10% share.

In March 2016, Teva's ANDA for a generic EpiPen, which had already faced several delays, was rejected by the FDA.Staff, The Pharma Letter. 3 March 2016 [http://www.thepharmaletter.com/article/teva-suffers-setback-over-epipen-generic Teva suffers setback over EpiPen generic]

In 2015 Mylan had about $1.5 billion in sales of EpiPens, which accounted for 40% of Mylan's profit. Mylan had maintained about a 90% market share since it had acquired the product, and had continually raised the price of EpiPens starting in 2009: in 2009, the wholesale price of two EpiPens was about $100; by July 2013, the price was about $265; in May 2015, it was around $461; and in May 2016, the price rose again to around $609, around a 500% jump from the price in 2009. The cost of the drug and device to Mylan as of 2016 was about $35. In the summer of 2016, as parents prepared to send their children back to school and went to pharmacies to get new EpiPens, people began to express outrage at the cost of the EpiPen and Mylan was widely and harshly criticized. In September 2016, the New York State Attorney General began an investigation into Mylan's EpiPen4Schools program in New York to determine if the program's contracts violated antitrust law{{cite news|last1=Larson|first1=Erik|last2=Hopkins|first2=Jared S.|title=Mylan's EpiPen School Sales Trigger N.Y. Antitrust Probe|url=https://www.bloomberg.com/news/articles/2016-09-06/n-y-s-schneiderman-launches-probe-into-mylan-epipen-sales|access-date=September 7, 2016|publisher=Bloomberg|date=September 6, 2016}} and the West Virginia State Attorney General opened an investigation into whether Mylan had given the state the correct discount under the Medicaid Drug Rebate Program and subpoenaed the company when it refused to provide the documentation the state requested.{{cite news|last1=Feeley|first1=Jef|last2=Langreth|first2=Robert|title=Mylan Investigations Mount as West Virginia Opens Fraud Probe|url=https://www.bloomberg.com/news/articles/2016-09-20/mylan-epipen-files-sought-as-west-virginia-opens-fraud-probe|work=Bloomberg News|date=20 September 2016}} In October 2016, Mylan announced a $465M settlement with the US Department of Justice over rebates paid by Mylan to states under the Medicaid Drug Rebate Program.

On 5 September 2017, FDA posted a warning letter to the manufacturer, Meridian Medical Technologies. The agency warned Meridian Medical for failing to investigate problems with the devices, recall bad batches, and follow-up on problems found. According to the FDA, the manufacturer of EpiPen devices failed to address known malfunctions in its auto-injectors even as hundreds of customer complaints rolled in and failures were linked to deaths. During an inspection, Meridian employees told inspectors that they weren't allowed to disassemble and investigate complain samples, because they were allowed to do if only it was “approved by management”.{{Cite web|url=https://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2017/ucm574981.htm|title=2017 - Meridian Medical Technologies, Inc. a Pfizer Company 9/5/17|website=www.fda.gov|language=en|access-date=2017-09-10}}{{Cite news|url=https://arstechnica.com/science/2017/09/fda-slams-epipen-maker-for-doing-nothing-while-hundreds-failed-people-died/|title=FDA slams EpiPen maker for doing nothing while hundreds failed, people died|work=Ars Technica|access-date=2017-09-10|language=en-us}}

On 16 August 2018 the FDA approved the first generic EpiPen from Teva Pharmaceuticals.{{Cite web |url=https://www.investors.com/news/technology/teva-pharma-approved-to-make-generic-version-of-mylans-epipen/ |title=Teva Pharmaceutical Gains Approval for Generic EpiPen, Mylan Shares Flat |access-date=2018-08-17 |archive-url=https://web.archive.org/web/20180817193300/https://www.investors.com/news/technology/teva-pharma-approved-to-make-generic-version-of-mylans-epipen/ |archive-date=2018-08-17 |url-status=dead }}{{Cite web | url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm617173.htm | title=Press Announcements - FDA approves first generic version of EpiPen| website=Food and Drug Administration| date=20 February 2020}}

In an effort to address the supply shortage of EpiPens,{{cite web |last1=Novak |first1=Matt |title=EpiPen Expiration Dates Extended as Schools Face Shortage of Allergy Medicine |url=https://gizmodo.com/epipen-expiration-dates-extended-as-schools-face-shorta-1828491035 |website=Gizmodo |date=22 August 2018 |publisher=Gizmodo Media Group |access-date=22 August 2018}} on August 21, 2018 the FDA approved extending the expiration dates on some products by four months.{{cite web |title=Extended Use Dates Provided by Pfizer |url=https://www.fda.gov/Drugs/DrugSafety/DrugShortages/ucm563360.htm |website=FDA.GOV |publisher=United States Food and Drug Administration}}

The Sandoz division of Novartis announced on 9 July 2019 the availability of Symjepi, a manual epinephrine injection as an alternative to autoinjectors, in 0.3 mg and 0.15 mg versions.{{cite news|url=https://finance.yahoo.com/news/adamis-pharmaceuticals-provides-u-retail-123000215.html|title=Adamis Pharmaceuticals Provides Update on U.S. Retail Launch of SYMJEPI|publisher=GlobeNewswire|work=Yahoo Finance|date=2019-07-09|access-date=2019-08-08}}

Society and culture

=Brands=

As of 2015, the following epinephrine autoinjectors were available in various parts of Europe: Adrenalina WZF, Adrenaline (epinephrine) 1 in 1000 solution for injection BP auto-injector, Altellus, Anapen, Emerade, EpiPen, Fastjekt, FastPen, and Jext.EMA. [http://www.ema.europa.eu/docs/en_GB/document_library/Referrals_document/Adrenaline_31/WC500165691.pdf Annex I] {{Webarchive|url=https://web.archive.org/web/20180618222947/http://www.ema.europa.eu/docs/en_GB/document_library/Referrals_document/Adrenaline_31/WC500165691.pdf |date=2018-06-18 }}: List of the names, pharmaceutical form(s), strength(s) of the medicinal product(s), route(s) of administration, marketing authorisation holder(s) in the Member States. Published April 25, 2014; Updated August 26, 2015. See [http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/referrals/Adrenaline_auto_injectors/human_referral_000367.jsp&mid=WC0b01ac05805c516f Index page for EMA Review of Adrenaline auto-injectors] {{Webarchive|url=https://web.archive.org/web/20180710041425/http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/referrals/Adrenaline_auto_injectors/human_referral_000367.jsp&mid=WC0b01ac05805c516f |date=2018-07-10 }} As of 2018, three branded products were available in the United States: Adrenaclick, Auvi-Q, and EpiPen.{{cite journal|last1=Song|first1=TT|last2=Worm|first2=M|last3=Lieberman|first3=P|title=Anaphylaxis treatment: current barriers to adrenaline auto-injector use.|journal=Allergy|date=August 2014|volume=69|issue=8|pages=983–91|pmid=24835773|doi=10.1111/all.12387|s2cid=7156705|doi-access=free}}

As of 2020, three brands of autoinjectors are available in Canada: Allerject, Emerade, and EpiPen.{{cite web |title=Emerade epinephrine auto-injectors are now available in Canada |url=https://foodallergycanada.ca/emerade-epinephrine-auto-injectors-are-now-available-in-canada/ |website=Food Allergy Canada |access-date=8 January 2021 |date=20 October 2020}} One generic autoinjector has been approved by Health Canada but is not marketed.{{cite journal |title=Epinephrine autoinjectors available in Canada |journal=Therapeutics Letter |date=2019 |url=https://ti.ubc.ca/letter119 |publisher=Therapeutics Initiative, University of British Columbia |issn=2369-8683}} From 2015 to 2020 the only autoinjector marketed in Canada was EpiPen and production issues led to supply shortages during that period.{{cite news |last1=Young |first1=Leslie |title=EpiPen shortage may drag into next year: Health Canada |url=https://globalnews.ca/news/4367570/epipen-shortage-health-canada-supply/ |access-date=8 January 2021 |work=Global News |date=2 August 2018}}{{cite news |title=Epipen and EpiPen Jr. in short supply, no alternatives available |url=https://www.cbc.ca/news/health/epipen-supply-1.4616737 |access-date=June 9, 2019 |work=CBC News |date=April 12, 2018}}{{cite news |last1=Hyshka |first1=Ashley |last2=McLaughlin |first2=Ross |title=EpiPen shortage: What are your alternative epinephrine injector options? |url=https://bc.ctvnews.ca/epipen-shortage-what-are-your-alternative-epinephrine-injector-options-1.4569251 |access-date=8 January 2021 |work=CTV News |date=28 August 2019 |language=en}} During a 2018 shortage of EpiPens, Health Canada temporarily permitted the importation of Auvi-Q autoinjectors from the United States.{{cite news |title=Petitpas Taylor moves to make U.S. EpiPen alternative available in Canada |url=https://www.theglobeandmail.com/politics/article-petitpas-taylor-moves-to-make-us-epipen-alternative-available-in/ |access-date=June 9, 2019 |work=The Globe and Mail |agency=The Canadian Press |date=August 9, 2018}}

As of 2005, epinephrine autoinjectors were not available in most of the developing world.

=Price=

==Canada==

{{As of|May 2019}}, in Canada the wholesale cost of a single EpiPen is approximately {{CAD|95.00}}.

==Europe==

{{As of|September 2016}}, two EpiPens cost around $100 in France and at maximum 10€ for members of the statutory health insurance in Germany.{{cite news|last1=Paton|first1=James|last2=Kresge|first2=Naomi|title=Why the $600 EpiPen Costs $69 in Britain|url=https://www.bloomberg.com/news/articles/2016-09-29/epipen-s-69-cost-in-britain-shows-other-extreme-of-drug-pricing-itnvgvam|work=Bloomberg News|date=29 September 2016}}{{Cite web|date=2019-01-24|title=Allergien: Diese Kosten übernimmt die Krankenkasse|url=https://vorsorge.biallo.de/allergien-kosten-krankenkassen|access-date=2021-04-07|website=Biallo Versicherungen|language=de-DE|archive-date=2022-01-24|archive-url=https://web.archive.org/web/20220124171849/https://vorsorge.biallo.de/allergien-kosten-krankenkassen|url-status=dead}}

{{As of|September 2016}}, two Jext autoinjectors cost users about £8.50 (US${{To USD|8.50|GBR}}) in Britain, and the National Health Service pays around £48 (US${{To USD|48|GBR}}) in order to make them available; that price was about 17 percent less than 2013.

Supplies of 150 microgram adrenaline auto-injectors were said to be “critical” in the United Kingdom in October 2018. Community pharmacists were told to prioritise supplies for children weighing 25 kg or less. Mylan identified shortages because of manufacturing problems in May 2018.{{cite news |title=Small children prioritised under emergency protocol to tackle 'critical' EpiPen shortage |url=https://www.pharmaceutical-journal.com/20205615.article |access-date=2 December 2018 |publisher=Pharmaceutical Journal |date=18 October 2018 |archive-date=3 December 2018 |archive-url=https://web.archive.org/web/20181203055503/https://www.pharmaceutical-journal.com/20205615.article |url-status=dead }}

==United States==

In October 2016 the CEO of Mylan testified to Congress that Pfizer/King charged Mylan about $34.50 for one EpiPen. The devices deliver about $1 worth of drug.Cynthia Koons and Robert Langreth for Bloomberg Businessweek. September 23, 2015 [https://www.bloomberg.com/news/articles/2015-09-23/how-marketing-turned-the-epipen-into-a-billion-dollar-business How Marketing Turned the EpiPen Into a Billion-Dollar Business]{{clarify |date=November 2021 |reason=Unclear what $1 refers to; production cost, wholesale cost, cost in another delivery mechanism?}} In September 2016, a Silicon Valley engineering consultancy performed a teardown analysis of the EpiPen and estimated the manufacturing and packaging costs at about $10 for a two-pack.{{cite news|last1=Tracy|first1=Seipel|title=Silicon Valley engineers figure real cost to make lifesaving auto-injector two-pack|url=http://www.mercurynews.com/2016/10/01/epipen-outrage-silicon-valley-engineers-figure-true-cost-to-make-lifesaving-auto-injector-about-10/|access-date=1 October 2016|publisher=The Mercury News}}

The EpiPen, manufactured by Meridian Medical Technologies, and marketed by Mylan, has dominated the market. In 2007 when Mylan acquired the rights to market the product, annual sales of all epinephrine autoinjectors were about $200 million and EpiPen had around 90% of the market; in 2015 the market size was around $1.5 billion and Mylan still had about 90% of the market. Mylan raised the price from around $100 for a package of two EpiPens in 2007 to around $600 in 2016.{{Cite web|url=http://baltimore.cbslocal.com/2016/08/18/cost-jumps-nearly-500-percent-for-life-saving-epipens/|title=Cost Jumps Nearly 500-Percent For Life-Saving EpiPens|last=Bartolotta|first=Devin|date=18 August 2016|publisher=CBS Baltimore|access-date=19 August 2016}} In the United Kingdom, an EpiPen costs £26.45 as of 2015.{{cite book|title=British National Formulary (BNF) 69|date=2015|publisher=Joint Formulary Committee|isbn=9780857111562|page=215|edition=69}} In Canada they are about 120 CAD each.{{cite web|title=Canadians users of EpiPen not subject to price hike as U.S. consumers|url=https://toronto.citynews.ca/2016/08/25/canadians-users-of-epipen-not-subject-to-price-hike-as-u-s-consumers/|access-date=6 September 2016|date=Aug 26, 2016}}

Mylan acquired the right to market the EpiPen line of epinephrine autoinjector devices from Merck KGaA as part of their 2007 deal. Heather Bresch, Mylan's CEO, saw an opportunity to increase sales in the US through marketing and advocacy, and the company launched a marketing campaign to increase awareness of the dangers of anaphylaxis for people with severe allergies that made the EpiPen brand as identified with epinephrine autoinjectors as Kleenex is for facial tissue; the company also successfully lobbied the FDA to broaden the label to include risk of anaphylaxis and in parallel, successfully lobbied Congress to generate legislation making EpiPens available in public places like defibrillators are, and hired the same people that Medtronic had worked with on defibrillator legislation to do so.

Mylan's efforts to maintain its market dominance were aided when Sanofi's competing product was recalled in November 2015 and further when Teva's generic competitor was rejected by the FDA in March 2016.Carly Helfand for FiercePharma Mar 1, 2016 [http://www.fiercepharma.com/sales-and-marketing/fda-swats-down-teva-s-epipen-copy-putting-mylan-cruise-control FDA swats down Teva's EpiPen copy, putting Mylan in cruise control] By the first half of 2015, sales of EpiPen accounted for 40% of Mylan's profit. Those profits were also due in part to Mylan's continually raising the price of EpiPens starting in 2009: in 2007, the wholesale price of two EpiPens was about $100; the price was about the same in 2009; by July 2013, the price was about $265; in May 2015, it was around $461; and in May 2016, the price rose again to around $609, around a 500% jump from the price in 2009. The last price increase sparked widespread outrage in the late summer as parents prepared to send their children back to school and went to pharmacies to get new EpiPens.{{cite web|last1=Goldberg|first1=Kenny|title=People With Food Allergies Say Life-Saving Drug Too Expensive|url=http://www.kpbs.org/news/2016/feb/18/food-allergies-life-saving-drug-too-expensive/|website=KPBS Public Media|date=18 February 2016 |access-date=8 June 2016}}{{cite news|last1=Walker|first1=Joseph|last2=Winslow|first2=Ron|last3=Steele|first3=Anne|title=Mylan to Launch Cheaper Generic EpiPen Alternative|url=https://www.wsj.com/articles/mylan-to-launch-cheaper-generic-epipen-alternative-1472467730|work=Wall Street Journal|date=30 August 2016}} Some Americans responded to the high price by buying EpiPens online from pharmacies outside the US,{{cite news |last1=Tuttle |first1=Brad |date=Aug 22, 2016 |title=5 Signs That EpiPen Prices Are Completely Out of Control |work=Money.com |url=https://money.com/epipen-prices-mylan-out-of-control/ |url-status=live |archive-url=https://web.archive.org/web/20210119115859/https://money.com/epipen-prices-mylan-out-of-control/ |archive-date=January 19, 2021}}{{cite news|last1=Lamble|first1=Kate|title=Drug company stung by criticism of 'outrageous' EpiPen price rises|url=https://www.bbc.com/news/blogs-trending-37179158|work=BBC|date=25 August 2016}} forgoing new EpiPens and relying on their expired EpiPen, or forgoing an autoinjector altogether and having their children carry pre-loaded syringes.{{cite news|last1=Khazan|first1=Olga|title=Have You Ever Tried to Buy an EpiPen?|url=https://www.theatlantic.com/health/archive/2016/08/epi-pens/497126/|work=The Atlantic|date=August 24, 2016}} Former Mylan CEO, Heather Bresch testified before the U.S. Senate Special Committee on Aging to argue that the price change was "fair".{{Cite book |url=https://books.google.com/books?id=Q4OHtqPMjvYC |title=Mylan 50 Years of Unconventional Success |publisher=UPNE |language=en}}

In response to criticism, Mylan increased financial assistance available for some patients to purchase EpiPens,{{cite news |url=https://www.theguardian.com/business/2016/aug/25/epipen-price-hike-savings-card-mylan-heather-bresch-congress |title=Mylan to provide EpiPen cost assistance as CEO is asked to testify on price hike | Business | The Guardian |newspaper=The Guardian |date=2016-08-25 |last1=Kasperkevic |first1=Jana }} a gesture that was called a "classic public relations move" by Harvard Medical School professor Aaron Kesselheim.{{cite news|last1=Carolyn Y. Johnson|title=Why Mylan's 'savings card' won't make EpiPen cheaper for all patients|url=https://www.washingtonpost.com/news/wonk/wp/2016/08/25/under-pressure-mylan-will-expand-patient-assistance-for-epipen/|newspaper=Washington Post|date=August 25, 2016}} The up to $300 saving cards can be used only by a small number of people who need the drug, and no one on Medicaid. They do nothing about the high price which is still being paid by insurers, who ultimately pass the cost on to consumers. In October 2016, Mylan announced a settlement with the US Department of Justice over rebates paid by Mylan to states under the Medicaid Drug Rebate Program.{{cite news|last1=Thomas|first1=Katie|title=Mylan to Settle EpiPen Overpricing Case for $465 Million|url=https://www.nytimes.com/2016/10/08/business/epipen-mylan-justice-department-settlement.html?ref=topics&_r=0|work=The New York Times|date=7 October 2016}} Questions had been raised by Congress and others about why EpiPen had been classified as a generic rather a proprietary product in the program since 1997; generic drugs have lower rebates (13%) than proprietary drugs (23%), and price hikes for generic drugs cannot be passed onto states, and a common form of pharmaceutical fraud involves misclassifying proprietary drugs as generic under the program.{{cite news|last1=Thomas|first1=Katie|title=Is EpiPen a Brand-Name or a Generic Drug? Mylan Casts It Both Ways|url=https://www.nytimes.com/2016/09/03/business/is-epipen-a-brand-name-or-a-generic-drug-mylan-casts-it-both-ways.html|work=The New York Times|date=2 September 2016}} Under the agreement, Mylan agreed to pay a $465 million payment and to a sign a corporate integrity agreement requiring it to perform better in the future; the settlement also resolved cases brought by states related to the rebates.{{cite news|last1=Mole|first1=Beth|title=For ripping off Medicaid, EpiPen maker Mylan pays Feds $465 million|url=https://arstechnica.com/science/2016/10/for-ripping-off-medicaid-epipen-maker-mylan-pays-feds-465-million/|access-date=8 October 2016|publisher=Ars Technica|date=7 October 2016}}

{{As of|August 2016}}, the authorized generic of Adrenaclick cost $142 at retail stores.{{cite web|url=http://www.consumerreports.org/drugs/can-you-get-a-cheaper-epipen/|title=Can You Get A Cheaper EpiPen?|author=Ginger Skinner|date=August 11, 2016|publisher=Consumer Reports}}[http://www.modernhealthcare.com/article/20160328/NEWS/160329971 Lack of competition leads to EpiPen pricing woes], Adam Rubenfire, Modern Healthcare, March 28, 2016

In September 2016, a group of hackers called the Four Thieves Vinegar published a video and documents describing what they call an EpiPencil, an autoinjector which can be built using off-the-shelf parts, for a claimed price tag of about $30. At its core is a repurposed insulin autoinjector.{{Cite web|last=Laufer|first=Dr. Mixæl S.|date=2016-09-19|title=Introducing the EpiPencil|url=https://fourthievesvinegar.org/?b=001|access-date=2021-11-03|website=fourthievesvinegar.org|publisher=Four Thieves Vinegar}} This device has not been subject to any validation by regulatory agencies.{{cite web| url=https://spectrum.ieee.org/hackers-offer-a-diy-alternative-to-the-600-epipen | publisher = IEEE Spectrum | title=Hackers Offer a DIY Alternative to the $600 EpiPen | author=Eliza Strickland|date= 19 September 2016 | access-date= 22 September 2016}}