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CERTIFIED MAIL - RETURN RECEI PT REQUESTED 

Teva Pharmaceuticals 4/19/201 6 

Attention: Barinder Sandhu 

Senior Director, Regulatory Affairs, US Generics 

425 Privet Road 

Horsham, PA 19044 

Dear Madam: 

This letter is being sent under Section 506C(f) of the Federal Food, Drug, and 

Cosmetic Act (FD&C Act) for the reasons set forth below. 

Section 506C of the FD&C Act requires a manufacturer o f a drug product that is 

"life -supporting, life-sustaining, 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 of the drug; or (2) an interruption of the manufacture of the drug that 

is likely to lead to a meaningful disruption1 in the supply of that drug in the 

United States; and (3) the reason(s) for such discontinuance or interruption of 

manufacturing (FD&C Act§ 506C(a)) . The notification must be submitted at least 6 

months prior to the date of the discontinuance or interruption of ma nufacturing, or 

as soon as practicabl e (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 o f critical 

drugs for patients. 

If a person fails to submit this required notification within the required 

timeframe, FDA must issue a letter to that person informing the person of the 

failure to comply with the FD&C Act (FD&C Act§ 506C(f)). 

Tr etinoin capsules are a product t h at is "life-supporting, life-sustaining, or 

intended for use in the prevention or treatment o f a debilitating disease or 

condition ." This product has an approved indication for the induction of remission 

in patients with acute promyelocytic leukemia (APL) , French- American-British (FAB) 

c lassification M3 (including the M3 variant), characterized by the presence of the 

t(15 ; 17) translocation and/or the presence of the PML/RARQ gene who are refractory 

to, or who have relapsed from, anthracycline chemotherapy, or for whom 

anthracycline-based chemotherapy is contraindicated. It is our understanding that 

sometime between January and February 2016, there was an interruption in the 

manufacture of tretinoin capsules. This interruption was likely to lead to a 

meaningful disruption in the s upply of this drug product in the United States. The 

Agency learned of the disruption from outside stakeholders in February 2016, and 

tretinoin capsules were determined to be in shortage soon thereafter, on February 

19, 2016. Our records indicate that Teva Pharmaceuticals did not notify FDA of the 

interruption in manufacture of this 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 of the 

manufacturer to fill orders o r meet expected demand for t he 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 of this 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 

tretinoin capsules in February 2016. 

No later t han forty-five calendar days after the issuance of this letter, FDA will 

make this let ter and your response t o the letter available to the public on FDA' s 

Drug Shortage website, unless the Agency determines that this letter was i ssued 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. 

If you have further questions, please contact the Drug Shortage Staff at (301) 796­

1300 . 

Please submit all communicati ons regarding this drug product to the following 

address: 

Drug Shortage Staff 


Food and Drug Administration 


wo 22, Room 6204 


10903 New Hampshire Avenue 


Silver Spring, MD 20993 


s~ 

CAPT Valerie Jensen 

Associate Director 

Drug Shortage Staff 

Center for Drug Evaluation and Research