_,, ....,.,., ~ 

( ..tf..DEPARTMENT OF HEALTH AND HUMAN SERVICES 

...~~\. Food and Drug Administration 

Silver Spring MD 20993 

CERTIFIED MAIL-RETURN RECEIPT REQUESTED 

Teva Pharmaceuticals 9/14/2018 

Attention: Jill Pastore 

Senior Director, Regulatory Affairs, NA Generics 

425 Privet Road 

Horsham, PA 19044 

DearMadam: 

This letter is being sent under Section 506C(f) ofthe Federal Food, Drug, and Cosmetic Act (FD&C 

Act) for the reasons set forth below. 

Section 506C ofthe FD&C Act requires a manufacturer ofa drug product that is "life-supporting, lifesustaining, or intended for use in the prevention or treatment of a debilitating disease or condition" to 

notify the Food and Drug Administration (FDA or the Agency) of: (1) a permanent discontinuance in 

the manufacture ofthe drug; or (2) an interruption ofthe manufacture ofthe drug that is likely to lead to 

a meaningful disruption' in the supply of that drug in the United States; and (3) the reason(s) for such 

discontinuance or interruption ofmanufacturing (FD&C Act § 506C(a)). The notification must be 

submitted at least 6 months prior to the date ofthe discontinuance or interruption ofmanufacturing, or 

as soon as practicable (FD&C Act § 506C(b)). Compliance with this notification requirement is 

essential to facilitating the mitigation and/or prevention of a shortage or potential shortage, and 

ultimately may ensure availability of critical drugs for patients. 

Ifa person fails to submit this required notification within the required timeframe, FDA must issue a 

letter to that person informing the person ofthe failure to comply with the FD&C Act (FD&C Act § 

506C(f)). 

Etoposide injection is a product that is "life-supporting, life-sustaining, or intended for use in the 

prevention or treatment of a debilitating diseaS'e or condition." This product has approved indications 

for the management ofrefractory testicular tumors and small cell lung cancer. It is our understanding 

that sometime between November and December 2017, there was an interruption in the manufacture of 

etoposide injection. This interruption was likely to lead to a meaningful disruption in the supply of this 

drug product in the United States. The Agency learned ofthe disruption from outside stakeholders in 

December 2017, and etoposide injection was determined to be in shortage soon thereafter, on January 

24, 2018. Our records indicate that Teva Pharmaceuticals did not notify FDA of the interruption in 

supply ofthis product. Accordingly, we are issuing you this letter to notify you of your noncompliance 

with the FD&C Act. . 

1 The statute defines "meaningful disruption" to mean "a change in production that is reasonably likely to lead to a reduction 

in the supply of a drug by a manufacturer that is more than negligible and affects the ability ofthe manufacturer to fill orders 

or meet expected demand for the product," and "does not include interruptions in manufacturing due to matters such as 

routine maintenance or insignificant changes in manufacturing so long as the manufacturer expects to resume operations in a 

short period of time." Section 506C(h)(3). 
No later than thirty calendar days after the issuance ofthis letter, you must submit to the Agency a 

written response setting forth the basis for noncompliance with Section 506C and providing the required 

notification, including the reason(s) for the interruption in manufacturing that led to a disruption in the 

supply of etoposide injection in November and December 2017. 

No later than forty-five calendar days after the issuance ofthis letter, FDA will make this letter and your 

response to the letter available to the public on FDA's Drug Shortage website, unless the Agency 

determines that this letter was issued in error, or, after review of your response, determines that there 

was a reasonable basis for noncompliance. In posting the letter and your response on the Drug Shortage 

website, FDA would protect confidential commercial information and trade secrets, if any, as required 

by applicable law. 

Ifyou have further questions, please contact the Drug Shortage Staff at (240) 402-7770. 

Please submit all communications regarding this drug product to the following address: 

Drug Shortage Staff 


Food and Drug Administration 


WO 22, Room 6204 


10903 New Hampshire A venue 


Silver Spring, MD 20993 


Sincerely, 

CAPT Valerie Jensen 

Associate Director 

Drug Shortage Staff 

Center for Drug Evaluation and Research