Drugs
Tamiflu and Relenza Emergency Use Authorization Disposition Letters and Question and Answer Attachments
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
Silver Spring MD 20993
June 22, 2010
Thomas R. Frieden, MD, MPH
Director
Centers for Disease Control and Prevention
1600 Clifton Rd., MS D-14
Atlanta, GA 30333
Re: Disposition of Certain Antiviral Drugs—Zanamivir and Oseltamivir Phosphate
Dear Dr. Frieden:
This letter responds to your request regarding the disposition of certain zanamivir and oseltamivir phosphate drugs upon termination of the authorization of emergency use that was issued on April 27, 2009, pursuant to section 564(b)(1) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. § 360bbb-3.
Attachment 1 provides Questions and Answers Regarding Terminating Certain Emergency Uses of Tamiflu and Relenza.
Attachment 2 provides Update Regarding Stockpiled Antivirals at or Nearing Expiration.
Sincerely,
_____________________________
Margaret Hamburg, M.D.
Commissioner of Food and Drugs
ATTACHMENT 1:
Questions and Answers Regarding Termination of the Emergency Use Authorizations (EUAs) for Tamiflu (oseltamivir) and Relenza (zanamivir)
During the 2009 H1N1 influenza public health emergency, FDA issued Emergency Use Authorizations (EUAs) that authorized certain unapproved uses of Tamiflu and Relenza.
On June 21, 2010, the U.S. Food and Drug Administration (FDA) notified the Centers for Disease Control and Prevention (CDC) that these EUAs will terminate when the Public Health Emergency determination for 2009 H1N1 Influenza expires on June 23, 2010. Therefore, after June 23, 2010, the EUAs authorizing the unapproved uses of Tamiflu and Relenza will no longer be in effect.
Q1. What is an EUA?
A. An EUA may be issued by FDA to allow either the use of an unapproved medical product or an unapproved use of an approved medical product during certain types of emergencies with specified agents.
Section 564 of the Federal Food, Drug, and Cosmetic Act (the Act), amended by the Project BioShield Act of 2004, permits authorization of such products for use in diagnosing, treating, or preventing serious or life-threatening diseases or conditions caused by biological, chemical, radiological, or nuclear agents, if certain statutory criteria are met.
Q2. What unapproved uses for Tamiflu and Relenza were authorized under the 2009 H1N1 influenza public health emergency EUAs?
A. Under the EUA, Tamiflu was authorized:
- To treat and prevent influenza in children under 1 year of age. Due to limited experience in infants less than 3 months of age, use of Tamiflu for prevention of 2009 H1N1 flu in this age group was not routinely recommended, but Tamiflu could have been used if the need was considered critical, e.g., if exposure was significant, if risk of severe illness was considered high.
- With dosing recommendations for children under the age of 1 year
Under the EUAs, Tamiflu and Relenza were authorized:
- For use at later time points after onset of symptoms. For example, for use in patients who were symptomatic for more than 2 days or in patients sick enough to require hospitalization ( i.e., patients with complicated influenza)
- To be distributed or dispensed by public health authorities without all of the FDA-required prescription label information
- To be accompanied by certain written emergency use information (Fact Sheets)
- To be distributed by public health officials or other volunteers to recipients in accordance with applicable state and local law and/or in accordance with the public health and medical emergency response of the Authority Having Jurisdiction
- For certain lots of Tamiflu for Oral Suspension, Tamiflu Capsules, and Relenza Inhalation Powder, for use beyond their labeled expiration dates
Q3. After the termination of the EUAs, what are FDA's recommendations regarding the previously-authorized, unapproved uses of Tamiflu and Relenza?
A. After June 23, 2010, Tamiflu and Relenza should be distributed and dispensed in compliance with FDA regulations and State laws, and in accordance with FDA-approved product labeling.
Tamiflu is approved by the FDA for the following indications:
- Treatment of uncomplicated acute illness due to influenza A and B virus infection in patients 1 year and older who have been symptomatic for no more than two days.
- Prophylaxis (prevention) of influenza A and B virus in patients 1 year and older.
Relenza is approved by the FDA for the following indications:
- Treatment of uncomplicated acute illness due to influenza A and B virus in adults and pediatric patients 7 years of age and older who have been symptomatic for no more than two days.
- Prophylaxis (prevention) of influenza A and B virus in adults and pediatric patients 5 years of age and older.
Q4. The EUA for Tamiflu provided dosing recommendations for Tamiflu in children less than 1 year of age. Has this dosing regimen been approved by FDA?
A. No. Tamiflu is approved for patients 1 year and older, and FDA has not approved dosing for children less than 1 year of age.
ATTACHMENT 2
Update Regarding Stockpiled Antivirals at or Nearing Expiration
During the 2009 H1N1 influenza public health emergency, the FDA issued Emergency Use Authorizations (EUAs) authorizing the emergency use of certain expired lots of Tamiflu (oseltamivir phosphate) and Relenza (zanamivir) based on scientific review and analysis that found the drugs could be used beyond their labeled expiration dates.
On June 21, 2010, the U.S. Food and Drug Administration (FDA) notified the Centers for Disease Control and Prevention (CDC) that these EUAs for Tamiflu and Relenza will terminate when the Public Health Emergency determination for 2009 H1N1 Influenza expires on June 23, 2010. Therefore, after June 23, 2010, the emergency use of certain expired lots of Tamiflu and Relenza will no longer be authorized under the EUAs.
This statement provides CDC updated information regarding these identified lots for purposes of informing public health authorities. This statement is not directed to individual patients who already have Tamiflu and/or Relenza in their homes. If they have Tamiflu or Relenza in their homes with expired date, they should discard the product.
For additional information, contact FDA's Division of Drug Information at 1-888-463-6332
Storage of Tamiflu and Relenza
If Tamiflu and/or Relenza is retained, it must be maintained and monitored under the product's labeled storage conditions. Tamiflu and Relenza should be stored at controlled room temperature.The United States Pharmacopeia (USP) defines controlled room temperature as a temperature that is maintained by thermostat and is between 20 and 25˚C (68 to 77˚ F).
Disposition of Identified Lots of Tamiflu and Relenza
Tamiflu Capsules and Relenza Inhalation Powder
FDA approved supplemental New Drug Applications for Relenza Inhalation Powder and Tamiflu Capsules that provided an expiration dating period of seven years. Approvals of new drug applications are generally prospective. FDA is aware that the following lots of Relenza Inhalation Powder and Tamiflu Capsules are currently packaged with an expiration date less than seven years. Provided that the products have been stored under the labeled storage conditions, FDA believes it would be scientifically supportable for the expiry extension (for a maximum of seven years) to apply to these lots that have already been manufactured. Thus FDA does not intend to take an enforcement action with regard to the following lots of Relenza Inhalation Powder and Tamiflu Capsules that are retained for potential use in future emergencies, provided that the products have been stored under the labeled storage conditions.
To minimize confusion on the part of healthcare professionals and patients, FDA recommends, prior to dispensing, that the identified lots be relabeled/repackaged by an FDA registered firm in accordance with applicable Current Good Manufacturing Practice (CGMP) requirements under 21 CFR 210, 211. (A relabeling/repackager firm's registration status can be confirmed/verified at the following website: http://www.fda.gov/Drugs/InformationOnDrugs/ucm135778.htm).
For Tamiflu Capsule blister packages and Relenza Diskhalers:
The registered relabeler/repackager should place the product in a sleeve and include the following printed statement with the product:
"FDA has determined that it is scientifically supportable to use this product beyond the printed expiration date that is on original label and internal components until [Enter 7 Year Expiry Date from Tables below]"
Tamiflu Capsules 75mg Blister Package
| Lot Number | Unit (10 capsules per blister package) |
Manufacturer's original expiry date | 7 Year Expiry Date |
|---|---|---|---|
| B1060 | Blister package | November 30, 2007 | November 03, 2010 |
| B1061-01 | Blister package | November 30, 2007 | November 04, 2010 |
| B1061-02 | Blister package | November 30, 2007 | November 04, 2010 |
| B1062 | Blister package | December 31, 2007 | December 08, 2010 |
| B1063 | Blister package | December 31, 2008 | December 11, 2010 |
| B1079 | Blister package | October 31, 2009 | October 31, 2011 |
| B1080 | Blister package | October 31, 2009 | October 31, 2011 |
| B1081 | Blister package | October 31, 2009 | October 31, 2011 |
| B1082 | Blister package | October 31, 2009 | October 31, 2011 |
| B1082-01 | Blister package | October 31, 2009 | October 31, 2011 |
| B1082-02 | Blister package | October 31, 2009 | October 18, 2011 |
| B1086 | Blister package | November 30, 2009 | November 30, 2011 |
| B1093 | Blister package | November 30, 2009 | November 26, 2011 |
| B1094 | Blister package | November 30, 2009 | November 29, 2011 |
Relenza Inhalation Powder Diskhaler
| Lot Number | Manufacturer's original expiry date | 7 Year Expiry Date |
|---|---|---|
| 153 | November 30, 2009 | November 30, 2011 |
| 154 | November 30, 2009 | November 30, 2011 |
| 154A | November 30, 2009 | November 30, 2011 |
| 237 | July 31, 2011 | July 31, 2013 |
| 238 | July 31, 2011 | July 31, 2013 |
| 270 | September 30, 2011 | September 30, 2013 |
| 271 | September 30, 2011 | September 30, 2013 |
| 273 | September 30, 2011 | September 30, 2013 |
| 274 | September 30, 2011 | September 30, 2013 |
| 275 | September 30, 2011 | September 30, 2013 |
| 276 | September 30, 2011 | September 30, 2013 |
| 277 | September 30, 2011 | September 30, 2013 |
| 279 | September 30, 2011 | September 30, 2013 |
| 280 | September 30, 2011 | September 30, 2013 |
| 281 | September 30, 2011 | September 30, 2013 |
| 282 | September 30, 2011 | September 30, 2013 |
| 287 | September 30, 2011 | September 30, 2013 |
| 292 | October 31, 2011 | October 31, 2013 |
| 293 | October 31, 2011 | October 31, 2013 |
| 294 | October 31, 2011 | October 31, 2013 |
| 305 | October 31, 2011 | October 31, 2013 |
| 306 | October 31, 2011 | October 31, 2013 |
| 307 | October 31, 2011 | October 31, 2013 |
| 308 | October 31, 2011 | October 31, 2013 |
| 374 | January 31, 2012 | January 31, 2014 |
| 518 | August 31, 2012 | August 31, 2014 |
| 519 | August 31, 2012 | August 31, 2014 |
| 521 | September 30, 2012 | September 30, 2014 |
| 522 | October 31, 2012 | October 31, 2014 |
| 523 | October 31, 2012 | October 31, 2014 |
| 524 | October 31, 2012 | October 31, 2014 |
| 525 | October 31, 2012 | October 31, 2014 |
| 526 | October 31, 2012 | October 31, 2014 |
| 7ZP0106 | November 30, 2012 | November 30, 2014 |
| 7ZP0862 | November 30, 2012 | November 30, 2014 |
| 7ZP1431 | November 30, 2012 | November 30, 2014 |
| 7ZP3799 | July 31, 2012 | July 31, 2014 |
| 7ZP3990 | August 31, 2012 | August 31, 2014 |
| 7ZP4325 | August 31, 2012 | August 31, 2014 |
| 7ZP5504 | August 31, 2012 | August 31, 2014 |
| 7ZP7104 | May 31, 2012 | May 31, 2014 |
| 7ZP8530 | October 31, 2012 | October 31, 2014 |
| 7ZP8753 | October 31, 2012 | October 31, 2014 |
| 7ZP8870 | October 31, 2012 | October 31, 2014 |
| 8ZP3152 | December 31, 2012 | December 31, 2014 |
Tamiflu Capsules bottles:
The registered relabeler/repackager should place a sticker over the old expiry date that does not obstruct any of the other label information with the appropriate 7 Year Expiry Date from the table below and the following statement:
"FDA has determined that it is scientifically supportable to use this product until [Enter 7 Year Expiry Date from Tables below]"
Tamiflu Capsule 75 mg Bottles
| Lot Number | Unit (10 capsules per bottle) |
Manufacturer's original expiry date | 7 Year Expiry Date |
|---|---|---|---|
| B1090 | Bottles | November 30, 2009 | November 30, 2011 |
| B1100 | Bottles | December 31, 2009 | December 31, 2011 |
| B1100-01 | Bottles | December 31, 2009 | December 31, 2011 |
| B1109 | Bottles | January 31, 2010 | January 31, 2012 |
| B1118 | Bottles | April 30, 2010 | April 30, 2012 |
| B1122 | Bottles | May 31, 2010 | May 31, 2012 |
| B1148 | Bottles | July 31, 2010 | July 31, 2012 |
| B1149 | Bottles | July 31, 2010 | July 31, 2012 |
| U2011 | Bottles | September 30, 2010 | September 30, 2012 |
| U2012 | Bottles | September 30, 2010 | September 30, 2012 |
| U2013 | Bottles | September 30, 2010 | September 30, 2012 |
| U2017 | Bottles | January 31, 2011 | January 31, 2013 |
| U2021 | Bottles | March 31, 2011 | March 31, 2013 |
| U2051 | Bottles | August 31, 2011 | August 31, 2013 |
| U400050 | Bottles | May 31, 2011 | May 31, 2013 |
| U400150 | Bottles | May 31, 2011 | May 31, 2013 |
| U400250 | Bottles | May 31, 2011 | May 31, 2013 |
| U4008-10 | Bottles | August 31, 2011 | August 31, 2013 |
| U4030-02 | Bottles | October 31, 2011 | October 31, 2013 |
| U4031-01 | Bottles | October 31, 2011 | October 31, 2013 |
| U4032-01 | Bottles | October 31, 2011 | October 31, 2013 |
| U4033-01 | Bottles | October 31, 2011 | October 31, 2013 |
| U4034-01 | Bottles | October 31, 2011 | October 31, 2013 |
| U4037-01 | Bottles | October 31, 2011 | October 31, 2013 |
The following lots of Tamiflu Capsules already have an expiration dating period of 7 years. Therefore these lots can be retained only until their manufacturer's original expiry date on the label.
Tamiflu 30 mg Capsules
| Lot Number | Unit (10 caps per bottle) |
Manufacturer's original expiry date |
|---|---|---|
| B1003-50 | Bottles | November 30, 2014 |
| B1004-50 | Bottles | November 30, 2014 |
| B1005 | Bottles | November 30, 2014 |
Tamiflu 45 mg Capsules
| Lot Number | Unit (10 caps per bottle) |
Manufacturer's original expiry date |
|---|---|---|
| B1003-50 | Bottles | November 30, 2014 |
| B1004 | Bottles | November 30, 2014 |
Tamiflu 75 mg Capsules
| Lot Number | Unit (10 caps per bottle) |
Manufacturer's original expiry date |
|---|---|---|
| U4067 | Bottles | August 31, 2014 |
| U4069 | Bottles | September 30, 2014 |
| U4070 | Bottles | September 30, 2014 |
| U4075 | Bottles | November 30, 2014 |
| U4078 | Bottles | November 30, 2014 |
Tamiflu for Oral Suspension
Unlike Tamiflu Capsules and Relenza Inhalation Powder, FDA has not approved an expiration dating period of seven years for Tamiflu for Oral Suspension. Therefore, the following lots of Tamiflu for Oral Suspension that were authorized for use under the EUA should be destroyed utilizing the facilities' pharmaceutical disposal procedures and in compliance with all applicable laws.
Lot Number |
Manufacturer's original expiry date |
|---|---|
| B1042 | January 31, 2005 |
| B1045 | May 31, 2005 |
| B1046 | November 30, 2005 |
| B1047 | November 30, 2005 |
| B1048 | January 31, 2006 |
| B1050 | January 31, 2006 |
| B1051 | January 31, 2006 |
| B1052 | January 31, 2006 |
| B1053 | January 31, 2006 |
| B1054 | January 31, 2006 |
| B1055 | January 31, 2006 |
| B1065 | June 30, 2006 |
| B1082 | May 31, 2007 |
| B1184 | June 30, 2009 |
| B1185 | June 30, 2009 |
| B1186 | June 30, 2009 |
| B1187 | June 30, 2009 |
| B1188 | June 30, 2009 |
| B1189 | June 30, 2009 |
| B1097 | June 30, 2007 |
| B1098 | June 30, 2007 |
| B1213 | November 1, 2009 |
| B1214 | November 1, 2009 |
| B1216 | November 1, 2009 |
| B120553 | August 8, 2009 |
| B120650 | August 8, 2009 |
