teva

December 18, 2018

Drug Shortage Staff

Food and Drug Administration WO 22, Room 6204
10903 New Hampshire Avenue

Silver Spring, MD 20993

FDA DRUG SHORTAGE RESPONSE

ANDA # 074529
Toposar® (Etoposide Injection USP 20mg/mL)

Dear FDA Drug Shortage Staff:

Teva Pharmaceuticals USA, Inc. is hereby providing this letter in response to the Food and Drug
Administration (FDA) letter received on October 31, 2018, dated September 18, 2018 sent under
Section 506C (f) of the Federal Food, Drug, and Cosmetic Act concerning the failure to notify FDA of
interruption in manufacturing of Etoposide Inection{J@#mg (ANDA 074529).

Teva would like to provide the Agency with a chronology of events concerning the reason for the
interruption in manufacturing of this product along with the communication shared with the Agency.

On October 27, 2017, Teva inventory was below safety stock levels for Toposar® Injection on two out
of the three presentations; Toposar® Injection 20mg/mL 1x25mL and Toposar® Injection 20mg/mL
1x50mL while maintaining sufficient quantities of Toposar® Injection 20mg/mL IxSmL. New
production was being planned when the active pharmaceutical ingredient (API) manufacturer
experienced problems supplying their material. The API manufacturer subsequently commenced the
allocation of open orders. This issue resulted in delays in our scheduled production which in turn caused
a backorder by November of 2017 for the 20mg/mL 1x25mL and 20mg/mL 1x50mL presentations.
Throughout the process Teva worked closely with the API manufacturer who committed to delivering
additional supply of the API. By December 27, 2017 the inventory of Toposar® 20mg/mL 1 x5mL
presentation had also dropped below safety stock and on January 2, 2018 Teva notified FDA Drug
Shortage via NextGen. On the same day FDA contacted Teva and we confirmed the drug shortage was
expected to last until the first quarter of 2018.

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teva

The expectation was that the API manufacturer would deliver the API and it was not expected that our
temporary backorder would create a market drug shortage. Upon realizing that we would not have
sufficient product to supply the demand Teva notified FDA within 3 business days. It is our
understanding that this drug shortage was also attributed and further exasperated by other approved
manufacturers who also were experiencing difficulty in manufacturing and supplying the commercial
market.

On February 26, 2018, FDA contacted Teva to inquire about supply. Teva informed the Agency that
product was back in inventory and as long as the API supplier continues to supply without interruption
there should be no impact to the Teva product supply to the market. On April 4, 2018 Teva notified
FDA of limited quantities and product being allocated due to API shortage. Periodic backorders of
Toposar were anticipated until the API requirements could be fully obtained. On October 26, 2018
Teva informed FDA that as of October 25, 2018 all of the presentations of the product were available.

Teva is committed to the needs of our patients and we are committed to working diligently to assure
supplying the commercial market with Toposar and all medically necessary products.

We hope this written response appropriately satisfies the Agency 's request of noncompliance for the
interruption in manufacturing that led to an unforeseeable disruption in the supply of Toposar®
Injectable in 2017.

This letter may contain trade secrets and confidential commercial information (collectively, the
"Protected Information"). We request that the Protected Information not be disclosed outside of the
Government pursuant to FOIA Exemption 4 (5 U.S .C. section 552(b)(4)) and 18 U.S.C. section 1905,

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David R. Bonilla
Associate Director Commercial Quality USA
Teva Pharmaceuticals

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