DATE

EVENT 

Pre 1785

Digitek® is a brand name for the heart drug, “digoxin” or “digitalis,” manufactured by the drug company, Actavis Totowa.  Digoxen is a purified “cardiac glycoside” extract from the foxglove plant, Digitalis lanata. (Wikipedia: Digoxen.)

Throughout history, plant extracts containing cardiac glycosides, (including what is now known as digoxin), have been used as both a medicine and a poison.  Native people in various parts of the world used the extracts as arrow and ordeal poisons. Ancient Egyptians used them as medicine. The Romans used them as a diuretic, heart tonic, emetic, and rat poison. (eMedicine: “Digitalis Toxicity,” last updated 05/26/06.)

1785

William Withering, an English botanist, geologist, chemist, and physician publishes, “An Account of the Foxglove and some of its Medical Uses", which describes clinical trials and notes on digitalis effects and toxicity. (Wikipedia: Willam Withering.)

1956

Pharmaco (later to become known as Actavis Totowa) is founded as a purchasing alliance by seven Icelandic pharmacists. (Actavis Website: Milestones & Company Profile.)

December, 2003

Charles Cullen admits to killing as many as 40 hospital patients with overdoses of heart medication—usually digoxin—at hospitals in New Jersey and Pennsylvania over his 16-year career as a nurse. (See Wikipedia: Charles Cullen.)

May 2004

Actavis becomes the new name for the Pharmaco Group. (Actavis Website: Milestones.)

01/10/06 – 02/08/06

The FDA conducts an inspection of Actavis’ facility located at 101 East Main Street , Little Falls, New Jersey .  (See FDA 08/15/06 Warning Letter to Actavis.)

02/08/06

The FDA issues Form FDA-483, List of Inspectional Observations, which found serious violations of laws requiring drug manufacturers to identify, investigate and report serious and unexpected adverse events for products including Digoxin, as well as other violations.  (FDA 08/15/06 Warning Letter to Actavis.)

02/28/06

Actavis responds to Form FDA-483. (However, as set forth the in the FDA’s subsequent Warning Letter on 08/15/06, this response was insufficient and did not fully address the FDA’s concerns.) (FDA 08/15/06 Warning Letter to Actavis.)

07/10/06 – 08/10/06

The FDA conducts another inspection of Actavis’ New Jersey facility. (See 02/01/07 FDA Revised Warning Letter Posted at: http://www.gmptrainingsystems.com/PDF/Actavis_WL.pdf)

08/10/06

The FDA presents another FDA-483, “List of Inspectional Observations,” to Actavis documenting significant deviations from the current Good Manufacturing Practice (cGMP) in conjunction with the company’s manufacture of prescription drug products. (02/01/07 FDA Revised Warning Letter Posted at: http://www.gmptrainingsystems.com/PDF/Actavis_WL.pdf)

08/15/06

The FDA issues a warning letter based on their finding during the 1/10/06-2/8/06 inspection.  The FDA again notes Actavis’ failure to comply with laws relating to the investigating and reporting of serious and unexpected adverse drug reactions.  (FDA 08/15/06 Warning Letter to Actavis.)

02/01/07

The FDA issues another warning letter based on their findings during the 07/10/06-08/10/07 inspection. The FDA again notes Actavis’ significant from the current Good Manufacturing Practice (cGMP) regulations and “that drug products manufactured in your facility are adulterated within the meaning of 21 U.S.C. § 351(a)(2)(B), Section 501(a)(2)(B) of the Federal Food Drug and cosmetic Act….” (02/01/07 FDA Revised Warning Letter Posted at: http://www.gmptrainingsystems.com/PDF/Actavis_WL.pdf)

04/25/08

Actavis initiates a Class 1 nationwide recall of Digitek (digoxin tablets, USP, all strengths) for oral use, as some tablets contained twice the approved level of active ingredient than was appropriate. The products were distributed by Mylan Pharmaceuticals, Inc. under a "Bertek" label and by UDL Laboratories, Inc. under a "UDL" label. (Actavis Website: 04/25/08 Press Release.)

08/02/08

Actavis announces a second recall at the retail level of all drug products manufactured at its Little Falls, New Jersey facility, as “a precautionary, voluntary action by Actavis following an inspection conducted by the Food and Drug Administration earlier this year.”  The company publicly admits that “the inspection at Little Falls revealed operations which did not meet the FDA’s or Actavis’ standards for good manufacturing practices.”  (Actavis Website: 08/02/08 Press Release.)