Extending Expiration Dates 
of Doxycycline Tablets and 
Capsules in Strategic 
Stockpiles 
Guidance for Government Public Health 
and Emergency Response Stakeholders 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
 
April 2019 
Procedural 
 
   
Extending Expiration Dates 
of Doxycycline Tablets and 
Capsules in Strategic 
Stockpiles
 
Guidance for Government Public Health 
and Emergency Response Stakeholders 
 
 
Additional copies are available from: 
Office of Communications, Division of Drug Information  
Center for Drug Evaluation and Research 
Food and Drug Administration 
10001 New Hampshire Ave., Hillandale Bldg., 4th Floor  
Silver Spring, MD 20993-0002  
Phone: 855-543-3784 or 301-796-3400; Fax: 301-431-6353 
Email: druginfo@fda.hhs.gov  
https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
 
April 2019 
Procedural 
  Contains Nonbinding Recommendations 
TABLE OF CONTENTS 
 
 
 
I.  INTRODUCTION............................................................................................................. 1 
II.  BACKGROUND ............................................................................................................... 2 
A.  Doxycycline Drug Product ............................................................................................................ 2 
B.  FDA Information on the Safe and Effective Use of Doxycycline Tablets and Capsules for 
Inhalational Anthrax Post-Exposure Prophylaxis or Treatment ....................................................... 3 
C.  Approaches to Drug Product Expiration Date Changes and Extensions ................................. 3 
1. Expiration Date Changes Initiated by the Manufacturer ................................................................ 3 
2. Federal Shelf-Life Extension Program ............................................................................................ 4 
3. Section 564A(b) of the FD&C Act ................................................................................................... 4 
III.  DISCUSSION .................................................................................................................... 5 
A.  Doxycycline Tablet and Capsule Stability Based on Historical Data ........................................ 6 
B.  Bioavailability ................................................................................................................................. 6 
C.  Recommended Protocol for Shelf-Life Extension of Doxycycline Tablets and Capsules ........ 7 
1. Lots Stored According to Labeled Storage Conditions and Less Than 6 Years Beyond Their 
Labeled Expiration Dates (Including Lots That Are Nearing Their Labeled Expiration Dates) ......... 8 
2. Lots Not Stored According to Labeled Storage Conditions or 6 Years or More Beyond Their 
Labeled Expiration Dates ..................................................................................................................... 9 
D.  Identifying a Suitable Laboratory To Conduct Doxycycline Tablets and Capsules Testing 10 
E.  Process for Requesting and Receiving an Authorized Expiration Date Extension for an 
Identified Lot of Doxycycline Tablets or Capsules ............................................................................ 11 
1. Overview ........................................................................................................................................ 11 
2. Format of Submissions ................................................................................................................... 12 
3. Notification of Authorization Decision to Requesters and Public Notice of Extensions for 
Government Stakeholders To Apply an Authorization to Untested Lots ............................................ 13 
4. Other Requirements and Conditions Under Section 564A(b) of the FD&C Act ........................... 14 
IV.  REFERENCES ................................................................................................................ 16 
ATTACHMENT ......................................................................................................................... 18 
  Contains Nonbinding Recommendations 
Extending Expiration Dates of Doxycycline Tablets and Capsules in 
Strategic Stockpiles 
Guidance for Government Public Health and  
Emergency Response Stakeholders1 
 
 
This guidance represents the current thinking of the Food and Drug Administration (FDA or Agency) on 
this topic. It does not establish any rights for any person and is not binding on FDA or the public. You can 
use an alternative approach if it satisfies the requirements of the applicable statutes and regulations. To 
discuss an alternative approach, contact the FDA office responsible for this guidance as listed on the title 
page. 
 
 
 
 
I.  INTRODUCTION 
 
A number of government public health and emergency response stakeholders2 maintain 
stockpiles of doxycycline3 tablets or capsules for post-exposure prophylaxis (PEP) or treatment 
of inhalational anthrax in the event of an anthrax emergency. States have asked FDA what would 
be necessary to provide confidence that stockpiled doxycycline tablets and capsules have 
retained their original quality (i.e., purity and potency) beyond the manufacturers labeled 
expiration date so the replacement of stockpiled product could be deferred.4 
 
This document provides guidance to government stakeholders on testing to extend the expiration 
dateunder section 564A(b) of the Federal Food, Drug, and Cosmetic (FD&C) Act5of 
stockpiled doxycycline tablets and capsules for public health emergency preparedness and 
response purposes for an anthrax emergency.  
 
                                                 
1 This guidance has been prepared by the Office of Pharmaceutical Quality in the Center for Drug Evaluation and 
Research at the Food and Drug Administration.  
2 For purposes of this guidance, the term government stakeholders refers to the public health and/or emergency 
response agencies or their agents/delegates that have legal responsibility and authority for responding to an incident, 
based on political or geographical boundaries (e.g., city, county, tribal, territorial, State, or Federal), or functional 
range or sphere of authority (e.g., law enforcement, public health, military health) to prescribe, administer, deliver, 
distribute, hold, or dispense a medical product during an emergency situation. 
3 For the purposes of this guidance, doxycycline refers to both doxycycline monohydrate and doxycycline hyclate 
forms of the drug that are indicated for post-exposure prophylaxis or treatment of inhalational anthrax. 
4 This is, in part, based on guidance FDA issued in 2004 for Federal agencies and State and local governments to 
conduct shelf-life testing of stockpiled potassium iodide: Potassium Iodide Tablets Shelf Life Extension. FDA 
updates guidances periodically. For the most recent version of a guidance, check the FDA guidance web page at 
https://www.fda.gov/RegulatoryInformation/Guidances/default.htm. 
5 21 U.S.C. 360bbb-3a(b). 
1 
  Contains Nonbinding Recommendations 
This guidance applies to both doxycycline monohydrate and doxycycline hyclate tablets and 
capsules equivalent to 50 mg and 100 mg of doxycycline that are indicated for PEP or treatment 
of inhalational anthrax.  
 
This guidance provides background information on the doxycycline drug product, the 
recommended protocol to support extending the expiration dates of specific doxycycline lots, 
how to identify a suitable laboratory to conduct testing, and the process for requesting and 
receiving an authorized expiration date extension for an identified lot of doxycycline. The 
criteria for an authorized extension include the requirements and conditions under section 
564A(b) of the FD&C Act for any expiration date extensions authorized by FDA based on 
testing conducted following this guidance. 
 
This guidance and any resulting expiration date extensions authorized by FDA do not apply to 
doxycycline available commercially or otherwise held for any other nonemergency purpose. 
  
In general, FDAs guidance documents do not establish legally enforceable responsibilities. 
Instead, guidances describe the Agencys current thinking on a topic and should be viewed only 
as recommendations, unless specific regulatory or statutory requirements are cited. The use of 
the word should in Agency guidances means that something is suggested or recommended, but 
not required.  
 
 
II.  BACKGROUND 
 
A.  Doxycycline Drug Product 
 
Doxycycline is a bacteriostatic tetracycline antibiotic prescribed mainly for the treatment of 
zoonotic, respiratory, sexually transmitted, and other infections caused by gram-negative bacteria 
and also is approved for PEP and treatment of inhalational anthrax caused by Bacillus anthracis. 
 
Although doxycycline is available commercially by prescription as capsules, delayed-release 
capsules, tablets, delayed-release tablets, powder for oral suspension, oral suspension, 
periodontal systems, and injectable dosage forms with strengths ranging from 20 to 200 mg 
(equivalent to base doxycycline), this guidance is applicable only to tablets and capsules 
indicated for PEP or treatment of inhalational anthrax. FDA has approved multiple new drug 
applications (NDAs) and abbreviated NDAs (ANDAs) for doxycycline tablets and capsules.6 
 
The applicationscurrently provide for marketing of tablets or capsules by prescription.7  
 
                                                 
6 For an up-to-date listing of all approved doxycycline products, consult the online version of FDA's Approved Drug 
Products With Therapeutic Equivalence Evaluations (Orange Book) at 
http://www.accessdata.fda.gov/scripts/cder/ob/default.cfm. 
7 However, during an anthrax emergency and if appropriate, FDA may authorize dispensing without individual 
patient prescriptions to facilitate official public health responses. See section 564A(d) of the FD&C Act.  
2 
  Contains Nonbinding Recommendations 
B.  FDA Information on the Safe and Effective Use of Doxycycline Tablets and 
Capsules for Inhalational Anthrax Post-Exposure Prophylaxis or Treatment 
 
Among other things, doxycycline is approved by FDA for treatment of anthrax caused by 
B. anthracis; the approved indication also includes PEP to reduce the incidence or progression of 
disease following exposure.8 Based on national preparedness for chemical, biological, 
radiological, and nuclear (CBRN) emergencies and doxycyclines anthrax indication, a number 
of government stakeholders stockpile doxycycline tablets or capsules that are generally stored 
under controlled conditions. For example, the Strategic National Stockpile (SNS), which is 
managed by the U.S. Department of Health and Human Services Office of the Assistant 
Secretary for Preparedness and Response (ASPR), stockpiles doxycycline, among other medical 
countermeasures (MCMs), to distribute to states to rapidly dispense as PEP to impacted 
populations during an anthrax emergency. Also, some states and local jurisdictions stockpile 
doxycycline for PEP before arrival of SNS assets (e.g., as a quick strike force for protecting first 
responders and health care professionals) or if SNS assets are not provided. 
 
Additionally, to help facilitate anthrax preparedness and public health interest in the emergency 
use of doxycycline for anthrax responses, FDA has issued an emergency dispensing order9 and 
the Centers for Disease Control and Prevention (CDC) has issued Emergency Use Instructions 
(EUI) to facilitate doxycycline mass dispensing efforts by government stakeholders.10 FDA also 
coordinates with ASPR and CDC on clinical and scientific issues related to the use of 
doxycycline for anthrax preparedness, including conducting Shelf-Life Extension Program 
(SLEP) testing of doxycycline held in the SNS.  
 
C.  Approaches to Drug Product Expiration Date Changes and Extensions 
 
Although there are several possible approaches to changing or extending the expiration date for 
approved drugs, the most appropriate or feasible approach depends on factors such as whether 
the extension is initiated by the manufacturer, is for certain drugs held in critical Federal 
stockpiles, or is for certain MCMs under section 564A(b) of the FD&C Act. 
 
1.  Expiration Date Changes Initiated by the Manufacturer 
 
The manufacturer of an approved drug product may extend the expiration date for the drug 
product based on acceptable data from full, long-term stability studies on at least three pilot or 
production batches in accordance with a protocol approved in the NDA or ANDA. FDA should 
be notified of the extension of the expiration dating period. The data can be submitted in an 
                                                 
8 Labeling can be found by searching for doxycycline on the FDA Approved Drug Products website, 
http://www.accessdata.fda.gov/scripts/cder/daf. 
9 Available on FDAs Emergency Dispensing Orders web page at 
https://www.fda.gov/EmergencyPreparedness/Counterterrorism/MedicalCountermeasures/MCMLegalRegulatoryan
dPolicyFramework/ucm495126.htm. 
10 Available on CDCs Emergency Use Instructions (EUI) for Doxycycline and Ciprofloxacin for Post-exposure 
Prophylaxis (PEP) of Anthrax web page at https://www.cdc.gov/anthrax/medical-care/emergency-use-doxycycline-
ciprofloxacin.html. 
3 
  Contains Nonbinding Recommendations 
annual report to the NDA or ANDA if, after obtaining and analyzing the data in accordance with 
the protocol, the criteria set forth in the approved stability protocol are met.11 Such extended 
dating typically is applied prospectively to newly manufactured lots and generally not 
retrospectively applied to lots manufactured before the newly determined dating period.12 
 
2.  Federal Shelf-Life Extension Program  
 
SLEP is another approach, but it is limited to specific drug products. SLEP is the Federal, fee-
for-service program through which the labeled shelf life of certain federally stockpiled medical 
materiel (e.g., in the SNS) may be extended after select drug products undergo periodic stability 
testing conducted by FDA (Khan et al. 2014). The program, which is administered by the 
Department of Defense (DoD), was established in 1986 after it was recognized through testing 
that certain drug products remained stable beyond their labeled expiration dates when properly 
stored. Through expiration date extensions, SLEP helps to defer the replacement costs of certain 
drug products, including doxycycline, in critical Federal stockpiles. Testing under SLEP is 
limited to drug products in Federal stockpiles. 
 
3.  Section 564A(b) of the FD&C Act 
 
Under section 564A(b) of the FD&C Act, FDA has the authority to extend the manufacturer-
provided expiration date of eligible FDA-approved medical products stockpiled for use in CBRN 
emergencies if the extension is intended to help facilitate the Nations ability to protect the 
public health or military preparedness and effectiveness and is ensured by an appropriate 
scientific evaluation conducted or accepted by FDA.13,14,15,16 To be an eligible product under 
section 564A of the FD&C Act, a product must be an approved, cleared, or licensed medical 
                                                 
11 See the guidance for industry Changes to an Approved NDA or ANDA. 
12 However, in certain cases for emergency preparedness purposes, manufacturers may agree to permit the use of 
their stability data to permit FDA extensions of expiration dates for existing products, or FDA may rely on other 
data that will support extensions. 
13 In March 2013, the Pandemic and All-Hazards Preparedness Reauthorization Act of 2013 (PAHPRA) was enacted 
in part to develop new authorities to sustain and strengthen national preparedness for public health emergencies 
involving CBRN agents, including emerging infectious disease threats (e.g., pandemic influenza). Among its many 
provisions, PAHPRA gives FDA the authority to extend, based on an appropriate scientific evaluation, the 
expiration date of certain approved MCMs for emergency response purposes under section 564A(b) of the FD&C 
Act. See http://www.gpo.gov/fdsys/pkg/PLAW-113publ5/pdf/PLAW-113publ5.pdf. 
14 Under section 564A(b)(4) of the FD&C Act, expiration date is the date established through appropriate stability 
testing required by the regulations issued by FDA to ensure that the product meets applicable standards of identity, 
strength, quality, and purity at the time of use. 
15 See the guidance for industry and other stakeholders Emergency Use Authorization of Medical Products and 
Related Authorities.  
16 Before PAHPRAs enactment, for the distribution, dispensing, or use of products with extended expiration, and 
any related labeling adjustments, the only available mechanisms to allow for use beyond the labeled expiration date 
were under FDAs exercise of its enforcement discretion or through issuance of an emergency use authorization 
under section 564 of the FD&C Act. 
4 
  Contains Nonbinding Recommendations 
product; intended for use to prevent, diagnose, or treat a disease or condition involving a CBRN 
agent(s); and intended for use during certain emergency circumstances.17,18 
 
Under section 564A(b), FDA must identify specific lots/batches or other units of the product for 
which extended expiration is authorized and the duration of each extension. FDA also may 
identify any other requirements or conditions for an extension as FDA may deem appropriate for 
the protection of the public health. This may include requirements for, or conditions on, product 
sampling, storage, packaging or repackaging, transport, labeling, notice to product recipients, 
record keeping, periodic testing or retesting, or product disposition. Eligible products with 
authorized expiration date extensions may be introduced, or delivered for introduction, into 
interstate commerce after the expiration date provided by the manufacturer. These products will 
not be considered unapproved products (as defined in section 564(a)(2)(A)) or deemed 
adulterated or misbranded under the FD&C Act.  
 
The expiration date extension authority under section 564A(b) of the FD&C Act does not codify 
the existing SLEP program, extend SLEP to State or local MCM stockpiles, create a new SLEP 
program for non-Federal government stakeholders, or otherwise address programmatic elements 
of SLEP. It does not alter FDAs role with regard to SLEP. SLEP remains limited to Federal 
stockpiles at this time. However, section 564A(b) of the FD&C Act provides FDA with the 
authority to extend the expiration date(s) of certain eligible medical products, thereby 
eliminating any uncertainty about the legal status of such products when FDA authorizes an 
extended expiration date and helping to address MCM stockpiling challenges such as those faced 
by non-Federal government stakeholders. 
 
As noted earlier, the DoD SLEP program remains limited to Federal stockpiles, so non-federally 
stockpiled products are not eligible for testing under that program. To help address this public 
health need, FDA is providing this guidance on testing to support expiration date extensions 
under section 564A(b) of the FD&C Act of doxycycline tablets and capsules being stockpiled for 
emergency purposes usually under controlled conditions by government stakeholders. 
 
 
III.  DISCUSSION 
 
Studies conducted through SLEP on various drug products have shown that the expiration dates 
for many drug products can be extended. For certain products that are generally known to be 
stable, such as doxycycline tablets and capsules, test results may be extrapolated for emergency 
use. Government stakeholders are expected to store stockpiled products according to 
                                                 
17 This includes the circumstances under which a specific type of emergency or threat determination has been made 
by the Secretary of the Department of Homeland Security, DoD, or Health and Human Services under section 
564(b)(1) of the FD&C Act. See section 564A(a) of the FD&C Act.  
18 Eligible products authorized for emergency use under section 564A of the FD&C Act, including those with 
extended expiration dates under section 564A(b) of the FD&C Act, may be considered covered countermeasures for 
purposes of liability protection under the Public Readiness and Emergency Preparedness (PREP) Act. For additional 
information on the PREP Act and current PREP Act declarations, see 
http://www.phe.gov/Preparedness/legal/prepact/Pages/default.aspx.  
5 
  Contains Nonbinding Recommendations 
manufacturers labeled storage conditions (Kahn et al. 2014). However, if stockpiled 
doxycycline tablets and capsules have not been stored under storage conditions as specified in 
the products approved labeling or if storage conditions cannot be verified, suitability of 
stockpiled lots may be determined through accelerated studies19 that include confirmatory testing 
over the study period. 
 
A.  Doxycycline Tablet and Capsule Stability Based on Historical Data 
 
Doxycycline tablets and capsules are compendial drug products that are manufactured to meet 
the recommended tests and criteria of the United States Pharmacopeia (USP)/National Formulary 
(NF) monographs and FDA-approved specifications. Specification attributes include assay, 
dissolution, and degradant20 limits, which may be stability-indicating and relevant for stability 
studies. Stability studies reviewed by FDA over many years have confirmed that none of the 
components of approved doxycycline tablets and capsules, including the active ingredient, has 
significant potential for chemical degradation or interaction with other components in the 
formulation or with components of the container closure system when stored according to 
labeled directions. 
 
Based on historical data, doxycycline tablets and capsules are expected to remain within USP 
assay and dissolution acceptance criteria beyond their labeled expiration dates. Degradants are 
also expected to show minimal increase over time when stored according to the labeled storage 
conditions. From a pharmacology/toxicology perspective, the acceptable limits for degradants in 
doxycycline tablets and capsules should be restricted to the existing limits in the USP 
monographs. For purposes of this guidance, current USP monographs should be referenced for 
tablets and capsules.  
 
B.  Bioavailability 
 
Based on the available information on solubility, intrinsic dissolution, complete absorption of 
doxycycline in the GI tract, and published relative bioavailability studies in a small number of 
subjects, both forms of doxycycline, monohydrate and hyclate, have comparable bioavailability 
(Jantratid et al. 2010; Bogardus and Blackwood 1979; Kitzes-Cohen et al. 1998; Saux et al. 
1981; Malmborg 1984).21 Although there is a solubility difference between the two forms, both 
monohydrate and hyclate can be considered highly soluble according to the Biopharmaceutics 
Classification System.22 Even if formulation-related factors should result in dissolution and 
absorption rate differences, significant exposure differences between the two forms are not 
                                                 
19Accelerated studies are studies designed to increase the rate of chemical degradation or physical change of a drug 
substance or drug product by using exaggerated storage conditions as part of the formal stability studies. 
20 The term degradant is used to mean an impurity that may increase over shelf life. Impurity and related substance 
are terms sometimes used in USP monographs to denote degradants. Where degradant is used in this guidance, it 
should be considered to mean the same as impurity or related substance in a compendial monograph. 
21 See also doxycycline monohydrate properties on DrugBanks Doxycycline web page, 
http://www.drugbank.ca/drugs/DB00254. 
22 See the guidance for industry Waiver of In Vivo Bioavailability and Bioequivalence Studies for Immediate-Release 
Solid Oral Dosage Forms Based on a Biopharmaceutics Classification System. 
6 
  Contains Nonbinding Recommendations 
expected. Additionally, there have not been reports of absorption rate effects for any of the wide 
range of excipients used for doxycycline hyclate and monohydrate products. In conclusion, 
doxycycline monohydrate and hyclate are likely to provide similar systemic exposure based on 
FDAs current knowledge. Based on this evidence, the recommended acceptance criteria, 
analytical methods, and shelf-life extension procedures outlined in this guidance may be applied 
to either form of the drug.  
 
C.  Recommended Protocol for Shelf-Life Extension of Doxycycline Tablets and 
Capsules 
 
Before testing is conducted to extend expiration dates, government stakeholders should 
determine whether all stockpiled product for which they seek an expiration date extension and 
from which testing samples are selected has been and will continue to be stored under the 
manufacturers labeled storage conditions. If proper storage conditions have been maintained and 
lots are less than 6 years beyond the manufacturers original labeled expiration dates, then 
government stakeholders should follow the testing protocol described in Table 1 (see 
Attachment).  
 
If appropriate storage conditions of the stockpiled product have not been maintained or cannot be 
confirmed to have been maintained during any time the product has been stockpiled, accelerated 
stability testing should be performed following the testing protocol in Table 2 (see Attachment) 
to evaluate the continued suitability of the lot and its eligibility for expiration extension. 
Similarly, regardless of storage conditions, any lots that are 6 years or more beyond the 
manufacturers original labeled expiration dates should be placed on accelerated stability testing 
to extend their expiration dates following the testing protocol described in Table 2.  
 
After testing is completed, if government stakeholders would like to request an expiration date 
extension for tested lots, they must submit certain information, as described below in section 
III.E, to inform FDAs decision regarding whether to authorize an extension for the stakeholders 
tested drug products (section 564A(b) of the FD&C Act). Also as described in section III.E, FDA 
will identify on its website each lot of doxycycline for which it authorizes an extension, which 
will enable other government stakeholders who might stockpile the same lot to apply an existing 
extension to their lot if stored according to the drug products labeled storage conditions. 
Irrespective of whether an extension is authorized under the testing performed within sections 
III.C.1 or III.C.2, FDA expects that, moving forward, any lots for which an extension has been 
authorized will be stored according to the manufacturers labeled storage conditions. 
 
Stockpiles should be checked routinely for lots nearing their labeled expiration date. These lots 
should be tested within a reasonable time frame (e.g., 6 months) that allows government 
stakeholders to submit requests to FDA for consideration of an expiration date extension 
authorization before reaching the labeled expiration date. This will help to ensure that such 
stakeholders hold product that is authorized by FDA for use beyond its labeled expiration date 
during an anthrax emergency. For lots tested before their expiration dates that FDA has 
authorized for use beyond the labeled expiration date, the 2-year extension will begin from the 
labeled expiration date rather than from the date of testing.  
 
7 
  Contains Nonbinding Recommendations 
1.  Lots Stored According to Labeled Storage Conditions and Less Than 6 Years 
Beyond Their Labeled Expiration Dates (Including Lots That Are Nearing Their 
Labeled Expiration Dates) 
 
For lots that have been stored according to the manufacturers labeled storage conditions for the 
entire time they have been stockpiled and are less than 6 years beyond their manufacturers 
labeled expiration dates, including those lots that are approaching (i.e., have not yet reached) 
their labeled expiration dates, expiration dates may be extended for 2 years based on acceptable 
test results (see Table 1). If three or fewer lots are stockpiled from a single manufacturer, then 
every lot should be tested to extend the expiration date. If more than three stockpiled lots are 
supplied by a single manufacturer, then the three oldest lots should be tested to extend the 
expiration date of all lots held from that manufacturer. If any of the three lots fail, then all lots 
from that manufacturer should be tested and expiration dates should only be extended for those 
lots that pass all criteria. Testing of lots from one manufacturer may not be used to extend the 
expiration dates of lots from another manufacturer.  
 
The number of tablets or capsules withdrawn from each lot for testing should be sufficient to 
perform the test procedures described in the referenced monograph. Compliance with the USP 
criteria for assay, degradants, and dissolution should be confirmed by the designated laboratory. 
Additionally, the laboratory performing the testing should visually inspect the product to verify 
its integrity. Government stakeholders are encouraged to retain the manufacturers labeling (i.e., 
package insert) so that the product description and storage conditions are readily available. If, 
however, the label is unavailable at the time of testing, the National Institutes of Health (NIH) 
has links to most FDA-approved product labels for reference.23 
 
A 2-year extension of the expiration date may be approved upon receipt of acceptable test results 
as follows: 
 
  The Table 1 testing protocol should be followed for a 2-year extension of the expiration 
date for individual tested lots. If testing results are acceptable from individual tested lots, 
then those tested lots can be considered qualified for a 2-year extension of the expiration 
date. 
 
  The Table 1 testing protocol should be followed for a 2-year expiration extension for 
representative lots used to qualify multiple lots from the same supplier. If testing results 
are acceptable from at least the three oldest lots from the same manufacturer, then all of 
the same-manufacturer lots of doxycycline can qualify for a 2-year extension of the 
expiration date. 
 
  After this initial confirmation, additional 2-year extensions of the expiration date would 
be qualified by following the Table 1 testing protocol and obtaining passing test results. 
However, for product that is 6 years beyond the manufacturers labeled expiration date, 
                                                 
23 NIH, U.S. National Library of Medicine, DailyMed, http://dailymed.nlm.nih.gov/dailymed/index.cfm. 
8 
  Contains Nonbinding Recommendations 
continued 2-year extension of the expiration date must be determined by accelerated 
stability studies following the testing protocol described in Table 2. 
 
  For lots that have not yet reached but are nearing the manufacturers labeled expiration 
date, testing should be performed within a reasonable time frame (e.g., 6 months) before 
their labeled expiration dates to allow adequate time for conducting the testing and 
requesting an authorization of expiration date extension for lots that pass testing. If such 
lots pass testing before their labeled expiration date, then the initial 2-year extension 
time frame may begin on the labeled expiration date (i.e., rather than the date the 
testing was performed). Testing for all subsequent extension periods should also be 
performed within a reasonable time frame (e.g., 6 months before the extended lot reaches 
its new expiration date). The new expiration date for these subsequent extension periods 
will begin 2 years from the expiration date that was established for the previous extension 
period (i.e., rather than the date the testing was performed). 
 
  For lots that have reached the manufacturers labeled expiration date and have been 
stored according to labeled storage conditions and are less than 6 years beyond their 
labeled expiration dates, authorization of expiration date extension for lots that pass 
testing will begin 2 years from the date of testing. Subsequent expiration date 
extensions will begin on the expiration date associated with the initial 2-year extension 
only if subsequent stability testing is performed before lots have reached the expiration 
date of the initial 2-year extension. Otherwise, subsequent extension periods will begin 2 
years from the testing date of each subsequent extension. 
 
  As described below in section III.E, adequate records of all testing should be kept, even 
when a lot fails stability testing. For more information regarding the protocol to follow 
for disposition of drug product that fails stability testing, see section III.E.4. 
 
2.  Lots Not Stored According to Labeled Storage Conditions or 6 Years or More 
Beyond Their Labeled Expiration Dates 
 
If stockpiled lots have not been stored in accordance with the manufacturers labeled storage 
conditions or if the lots are 6 years or more beyond the manufacturers labeled expiration date, 
the expiration date may be extended only if the lots are shown to meet the acceptance criteria 
indicated in the testing protocol described in Table 2 after 3 months of storage at accelerated 
stability testing conditions. If three or fewer lots are from a single manufacturer, then every lot 
should be placed on accelerated stability testing to extend the expiration date. If more than three 
stockpiled lots are supplied by a single manufacturer, at least the three oldest lots should be 
placed in the accelerated stability study to extend the expiration dates of all lots held from that 
manufacturer. Testing lots from one manufacturer may not be used to extend the expiration date 
of lots from another manufacturer. 
 
Accelerated stability testing storage conditions are 40C  2C /75%  5% relative humidity. 
These conditions stress the product and are thought to be conservatively predictive of future 
stability for a period of time under room temperature conditions. The long-term stability data in 
conjunction with accelerated stability data are commonly used initially to establish tentative 
9 
  Contains Nonbinding Recommendations 
expiration dates for pharmaceuticals. The tentative expiration dates are confirmed with full, long-
term stability data after approval. For products in government stockpiles, performance of long-
term stability studies is not expected. However, accelerated studies should be performed for 
cases in which lots have not been stored according to manufacturers labeled storage conditions 
or when stockpiled lots are 6 years or more beyond the manufacturers labeled expiration date. 
 
For lots that have not been stored in accordance with the manufacturers labeled storage 
conditions or that are 6 years or more beyond the manufacturers labeled expiration date, results 
of these tests can qualify expiration date extensions as follows: 
 
  The Table 2 testing protocol should be followed for a 2-year expiration date extension for 
individual tested lots. If testing results are acceptable from individual tested lots after 3 
months of storage under accelerated storage conditions, then those tested lots can be 
considered qualified for a 2-year extension of the expiration date beyond the expiration 
date from the initial sampling point in the accelerated stability study (month 0) for the 
initial 2-year extension of the expiration date. 
 
  The Table 2 testing protocol should be followed for representative lots used to qualify 
multiple lots from the same manufacturer. If the testing results are acceptable after 3 
months of storage under accelerated storage conditions, then all lots of doxycycline 
tablets or capsules stockpiled from that manufacturer can be qualified for a 2-year 
extension of the expiration date from the initial sampling point in the accelerated 
stability study (month 0) for the initial 2-year expiration extension.  
 
  After this confirmation, additional 2-year extensions of the expiration date from the 
initial sampling point in the accelerated stability study (month 0) can be qualified 
through accelerated studies (i.e., 3 months storage at accelerated conditions). The 
additional 2-year extension of the expiration date qualified by an additional accelerated 
study would begin from the initial sampling point (month 0) of the additional study. 
 
  As described below in section III.E, adequate records of all testing should be kept, even 
when a lot fails stability testing. For more information regarding the protocol to follow 
for disposition of drug product that fails stability testing, see section III.E.4.  
 
D.  Identifying a Suitable Laboratory To Conduct Doxycycline Tablets and 
Capsules Testing  
 
Government stakeholders may conduct their own stability testing if they have labs that meet the 
elements of a suitable laboratory. Alternatively, if a government stakeholder chooses to have 
stability testing performed by a contractor, a suitable laboratory should be identified. Most 
suitable laboratories should be capable of performing the testing described in this guidance. A 
suitable laboratory for purposes of this guidance is one that follows relevant current good 
manufacturing practice (CGMP) requirements as cited in 21 CFR parts 210 and 211.24 In 
                                                 
24 For a laboratorys inspection classification, search FDAs Inspection Classification Database at 
https://www.accessdata.fda.gov/scripts/inspsearch/. 
10 
  Contains Nonbinding Recommendations 
addition, testing for assay, impurities (degradants), and dissolution should be performed using 
the methods and apparatus as described in USP. Because these are compendial tests, the testing 
laboratory should verify the methodology as described in USP General Chapter <1226> 
Verification of Compendial Procedures. 
 
E.  Process for Requesting and Receiving an Authorized Expiration Date 
Extension for an Identified Lot of Doxycycline Tablets or Capsules 
 
1.  Overview 
 
Based on FDAs understanding of the stability of doxycycline products and the testing 
methodology described in this guidance, when testing conducted by a suitable laboratory 
demonstrates the product is stable at the time of testing, FDA may accept these results as an 
appropriate scientific evaluation under section 564A(b) of the FD&C Act. In general, FDA will 
accept a government stakeholders self-certification that appropriate testing has been conducted 
on a specified lot of stockpiled doxycycline tablets or capsules. However, FDA reserves the right 
to deny a request for an expiration date extension of a specific lot for the protection of the public 
health. 
 
Each lot that has undergone testing in accordance with this guidance and is found to be stable at 
the time of testing may be eligible to be authorized by FDA for a 2-year expiration date 
extension each time the product is tested under section 564A(b) and other conditions under 
section 564A(b) are met.25 The doxycycline product tested must be FDA-approved and intended 
for use to prevent or treat a disease or condition involving B. anthracis during the circumstances 
under which (1) a determination under section 564(b)(1) of the FD&C Act has been made by the 
Secretary of DoD, Department of Homeland Security (DHS), or Department of Health and 
Human Services or (2) a Material Threat Determination (MTD) pursuant to section 319F-2 of the 
Public Health Service Act has been made by the Secretary of DHS.26 Furthermore, doxycycline 
tablets or capsules available commercially or stockpiled for other nonemergency purposes are 
not eligible for expiration date extensions under section 564A(b) of the FD&C Act or this 
guidance. 
  
As described in section III.E.2, before FDA may authorize an expiration date extension under 
section 564A(b), government stakeholders should submit certain information to enable FDA to 
identify each specific lot for which extended expiration is authorized. Before such stakeholders 
may use tested products for anthrax emergency purposes, they first must receive notification that 
FDA has authorized the expiration date extension of each lot. Certain requirements and 
conditions under section 564A(b) will apply to any extension FDA authorizes based on 
government stakeholder testing conducted in accordance with this guidance.  
 
                                                 
25 See sections III.C and III.D of this guidance. 
26 On September 23, 2008, pursuant to section 564(b)(1)(A) of the FD&C Act, in a memorandum to Michael O. 
Leavitt, the Secretary of DHS determined that there is a significant potential for a domestic emergency involving a 
heightened risk of attack with a specified CBRN agent or agentsin this case, B. anthracis 
(http://www.dhs.gov/xlibrary/assets/ofsec_signed_determination092308.pdf). 
11 
  Contains Nonbinding Recommendations 
2.  Format of Submissions  
 
Extension requests and questions about them should be emailed to 
DoxycyclineExpirationExtensionRequest@fda.hhs.gov, with a cc to CDEREUA@fda.hhs.gov 
and EUA.OCET@fda.hhs.gov. 
 
To facilitate timely consideration of requests, FDA strongly recommends that government 
stakeholders submit a cover letter and the following information in any request for a doxycycline 
expiration date extension based on testing conducted in accordance with this guidance: 
 
  Requesters name, title, affiliation, and contact information (i.e., mailing address, email 
address, telephone number, and fax number) and requesters preferred way to be 
contacted by FDA. 
 
  Date of request. 
 
  Statement of the request for an FDA expiration date extension for a specific lot of 
doxycycline tablets or capsules stockpiled for anthrax preparedness and tested under this 
guidance. A single request letter may include a government stakeholders request for 
extensions of more than one lot, including other lots (1) that the stakeholder has tested in 
accordance with this guidance or (2) to which the requesting stakeholder would like their 
test results to be extrapolated. 
  
  Statement that the government stakeholder certifies the test results and that resulting new 
expiration dates are based on testing conducted in accordance with the testing 
methodology and any other requirements or conditions described in this guidance. 
 
  Information about the tested doxycycline product:  
 
  Dosage form (e.g., tablets or capsules). 
o
 
  Strength (e.g., 100 mg). 
o
 
  Name(s) of manufacturer(s). 
o
 
  Lot numbers. 
o
 
  A photograph or digital image of the product label. 
o
 
  Manufacturers labeled expiration date (original and last extended dates, if 
o
applicable). 
 
  Quantity of lots and number of units of the product in each lot stockpiled. 
o
 
  Unit of product stockpiled (e.g., 20-count unit-of-use bottle (packaging 
o
configuration)). 
12 
  Contains Nonbinding Recommendations 
 
  Whether lots have undergone expiration date extension testing previously under this 
o
guidance (and, if so, a brief summary of the findings of the previous testing, including 
whether the product was found to be stable at the time of testing). 
 
  Past and current storage conditions (i.e., whether lots have been and continue to be 
o
properly stored according to the manufacturers labeled storage conditions). 
 
  The report from the laboratory that conducted the testing that includes the following 
information about the doxycycline testing: 
 
  Test methods and validation reports of the test methods. 
o
 
  Name and contact information of the laboratory.  
o
 
  Test dates. 
o
 
  Lots/batches tested. 
o
 
  Whether the tested product was found to be stable at the time of testing or failed 
o
specifications, and any observations that may have occurred while testing the product.  
 
  Proposed new expiration date based on the date of testing and criteria described in 
o
this guidance (if the laboratory report does not already include such information). 
 
  Other information the government stakeholder believes would be important to inform 
FDAs review.  
 
3.  Notification of Authorization Decision to Requesters and Public Notice of 
Extensions for Government Stakeholders To Apply an Authorization to Untested 
Lots 
 
After reviewing a government stakeholders request, consistent with section III.E.2, FDA will 
notify (e.g., by email) the requester of the expiration date extension decision (i.e., whether FDA 
authorizes the requested extension, the specific lot(s) for which an extended expiration date is 
authorized, and the new expiration period). FDA may decline to authorize the request based on a 
number of factors (e.g., if the doxycycline product fails to meet the necessary criteria identified 
in section 564A of the FD&C Act or as described in section III.E.4 of this guidance). FDA also 
will notify the requester when FDA declines to authorize the extension for the product, including 
whether or not the product should be properly disposed of.  
 
In addition, FDA will provide public notice (e.g., a memorandum posted on the FDA website) of 
each expiration date extension (e.g., manufacturer name, lot number, original manufacturers 
labeled expiration date, new expiration date) for which the product is authorized under section 
13 
  Contains Nonbinding Recommendations 
564A(b) of the FD&C Act and in accordance with this guidance.27 This notification will enable 
other government stakeholders holding the same lot(s) of the product to apply an applicable 
extension of shelf life to their own stockpiled lot(s) of doxycycline without testing such lot(s), as 
long as the stakeholders follow other applicable requirements and conditions described below in 
section III.E.4.28  
  
4.  Other Requirements and Conditions Under Section 564A(b) of the FD&C Act 
 
In addition to the identification of specific lots/batches or other units of the product for which 
extended expiration is authorized and the duration of such an extension, FDA may identify any 
other requirements or conditions as deemed appropriate for the protection of the public health, 
including related to product sampling, storage, packaging or repackaging, transport, labeling, 
notice to product recipients, record keeping, periodic testing or retesting, or product 
disposition.29  
 
The following is a list of other requirements and conditions that apply to any expiration date 
extensions FDA authorizes based on stockpiled doxycycline tablet or capsule testing conducted 
following this guidance: 
 
  Testing: Test results may be considered an appropriate scientific evaluation that may be 
accepted by FDA for purposes of an expiration date extension under section 564A(b) of 
the FD&C Act if government stakeholders ensure that the doxycycline testing is 
conducted by a suitable laboratory and in accordance with the testing methodology, as 
described in this guidance. FDA reserves the right to conduct inspections of laboratories 
conducting testing under this guidance. Government stakeholders must secure agreements 
from such laboratories that the laboratories will permit FDA inspection, as appropriate. 
 
  Periodic testing or retesting: Government stakeholders are not required to conduct 
periodic testing or retesting. However, if such stakeholders are interested in requesting an 
additional 2-year extension of the expiration date for a previously tested lot, such lot, if 
eligible for an additional 2-year extension of the expiration date, must be retested 
according to the testing protocol outlined in this guidance. In addition, the government 
stakeholder must submit a new 2-year extension of the expiration date request to FDA, 
and FDA must authorize the new 2-year extension of the expiration date (including for 
any lots to which test results are extrapolated).  
 
  Storage: Government stakeholders should have stored, and should continue to store, their 
stockpiled doxycycline tablets or capsules according to the manufacturers labeled 
                                                 
27 Section 564A(b)(2) of the FD&C Act. 
28 For a list of doxycycline expiration date extensions authorized by FDA under section 564A(b), see 
https://www.fda.gov/EmergencyPreparedness/Counterterrorism/MedicalCountermeasures/MCMLegalRegulatoryan
dPolicyFramework/ucm619289.htm.  
29 Section 564A(b)(2) of the FD&C Act. 
14 
  Contains Nonbinding Recommendations 
storage conditions until the time of emergency use.30 As described earlier in this 
guidance, testing may be permitted on certain lots that have not been stored according to 
their labeled storage conditions up to the time of testing. However, FDA expects that all 
such lots will, moving forward, be stored according to their labeled storage conditions if 
testing finds such product to be stable at the time of testing and if FDA authorizes an 
expiration date extension for such lots. If a government stakeholder does not test its lot(s) 
but rather extends its expiration date based on another stakeholders testing and 
authorized date extension, its untested lots must have been stored according to the 
manufacturers labeled storage conditions for the entire time the lots were stockpiled. 
FDA reserves the right to conduct audits or inspections of stockpiled product, as 
appropriate.  
 
  Record keeping: Government stakeholders should keep detailed records about storage 
and any testing they conduct or have conducted under this guidance (e.g., manufacturer 
name, lot number, and original manufacturers labeled expiration date; date of testing; 
any additional lots to which the test results apply; name and contact information of the 
laboratory that conducted the testing; results of the testing, including whether any lots 
failed testing and, if known, the reason why a specific lot failed testing; number of times 
each lot was tested; any correspondence from FDA). Through a process of inventory 
control, government stakeholders also should maintain records of emergency use of any 
doxycycline lots that have received an expiration date extension from FDA. All such 
records described in this paragraph will be made available to FDA for inspection or audit 
upon request. 
  
  Labeling: Although government stakeholders may choose to relabel each individual 
container (e.g., unit-of-use bottle, bulk bottle) of product that has been authorized for an 
expiration date extension, FDA is not recommending that each individual container be 
relabeled with the new expiration date. However, government stakeholders should 
distinguish the doxycycline tablet or capsule lots that have new expiration dates or that 
have undergone stability testing (e.g., by shrink wrapping a pallet and placing a single 
marking on a centrally stockpiled lot with the authorized extended expiration date). 
 
  Notice to product holders: Government stakeholders must inform product holders that 
the products labeled expiration date has been extended by FDA through appropriate 
scientific testing accepted by FDA (e.g., if the testing is conducted or supported by the 
State public health agency, the State will notify any applicable jurisdictions or other 
government stakeholders that stockpile the same lot(s) of doxycycline in the State of any 
applicable extension(s)).  
                                                 
30 However, under section 564 of the FD&C Act and section 564A(c) of the FD&C Act, FDA may, as appropriate 
and under certain circumstances, waive certain CGMP requirements (e.g., related to storage temperature) 
temporarily to facilitate an emergency response. Waivers of certain CGMP requirements for doxycycline during an 
anthrax emergency are included in the doxycycline emergency dispensing order. See FDAs Emergency Dispensing 
Orders web page at 
https://www.fda.gov/EmergencyPreparedness/Counterterrorism/MedicalCountermeasures/MCMLegalRegulatoryan
dPolicyFramework/ucm495126.htm. 
15 
  Contains Nonbinding Recommendations 
 
  Notice to product recipients: Government stakeholders must inform recipients (i.e., 
individuals in the impacted population to whom the drug is being dispensed) of such 
product at the time of dispensing (i.e., during or in anticipation of an anthrax emergency) 
that the products labeled expiration date has been extended through appropriate 
scientific testing accepted by FDA.31 
 
  Product disposition: If a government stakeholder submits to FDA test results that do not 
initially appear to be favorable for supporting an expiry date extension, it should continue 
to properly store the applicable lot(s) and should not dispose of such lot(s) until receiving 
notification from FDA. Government stakeholders who do not submit such data to FDA, 
or who otherwise receive notification from FDA to dispose of their lot(s) after FDA 
reviews their test data, should properly dispose of any such lot to prevent potential 
misuse, environmental contamination, or antimicrobial resistance. 
 
  Other: FDA may identify other requirements or conditions as FDA may deem 
appropriate for the protection of the public health. 
 
 
IV.  REFERENCES 
 
Bogardus, JB, and RK Blackwood, 1979, Dissolution Rates of Doxycycline Free Base and 
Hydrochloride Salts, J Pharm Sci, 68(9):11831184. 
 
Jantratid, E, S Strauch, C Becker, JB Dressman, GL Amidon, HE Junginger, S Kopp, KK Midha, 
VP Shah, S Stavchansky, and DM Barends, 2010, Biowaiver Monographs for Immediate Release 
Solid Oral Dosage Forms: Doxycycline Hyclate, J Pharm Sci, 99(4):16391653. 
 
Khan, SR, R Kona, PJ Faustino, A Gupta, JS Taylor, DA Porter, and M Khan, 2014, United 
States Food and Drug Administration and Department of Defense Shelf-Life Extension Program 
of Pharmaceutical Products: Progress and Promise, J Pharm Sci, 103(5):13311336. 
 
Kitzes-Cohen, R, D Farin, A Laor, G Piva, K Hazan, A Wasserman, and I Gozlan, 1998, 
Bioequivalence Study of Two Formulations of Doxycycline, Curr Ther Res, 59(5):315323. 
 
Malmborg, A-S, 1984, Bioavailability of Doxycycline MonohydrateA Comparison With 
Equivalent Doses of Doxycycline Hydrochloride, Chemotherapy, 30(2):7680. 
 
Saux, MC, J Mosser, H Pontagnier, and B Leng, 1981, Pharmacokinetic Study of Doxycycline 
Polyphosphate (PPD), Hydrochloride (CHD) and Base (DB), Eur J Drug Metab Pharmacokinet, 
6(1):310. 
  
                                                 
31 The recipient notice requirement may be met if applicable CDC-issued EUI under section 564A(e) of the FD&C 
Act for doxycycline address the use of such product beyond its labeled expiration date. See 
https://www.cdc.gov/anthrax/medical-care/doxy-eui-recipients.html. 
16 
  Contains Nonbinding Recommendations 
Guidances for Industry 
 
Guidance for industry Changes to an Approved NDA or ANDA (April 2004) 
 
Guidance for industry Waiver of In Vivo Bioavailability and Bioequivalence Studies for 
Immediate-Release Solid Oral Dosage Forms Based on a Biopharmaceutics Classification 
System (December 2017) 
 
Guidance for Federal agencies and State and local governments Potassium Iodide Tablets Shelf 
Life Extension (March 2004) 
 
Guidance for industry and other stakeholders Emergency Use Authorization of Medical Products 
and Related Authorities (January 2017)
17 
  Contains Nonbinding Recommendations 
ATTACHMENT  
 
Each table includes examples of how to present data as well as the protocol to follow as referenced in section III. This format should 
be followed for recording test results. The test results and specifications below are provided for illustration. Test methods and 
acceptance criteria should follow the appropriate monograph for each product as described in section III. 
 
Table 1. Testing Protocol for Expiration Date Extension of Doxycycline Tablets and Capsules Meeting Criteria Under III.C.1*  
Product  Lot  Storage**  Test Date   Specifications   Test Result  Manufacturers  Proposed 
Name and  Identification  [Y/N]     Labeled Expiration  New 
Strength  (number and  Date (original and last  Expiration 
manufacturer)  extended dates, if  Date 
applicable) 
Doxycycline  Lot #Abc0123  Y  1/01/2017  Assay: 90.0-120.0% labeled amount  100.0%  6/2017 manufacturers  6/2019 
Hyclate  AB  Dissolution: NLT 80%(Q) in 30 min.    labeled expiration date 
Capsules 100  Manufacturing  Mean:  99% 
mg, USP  High:  101% 
Low:  98% 
Degradants:    
4-Epidoxycycline: NMT 0.5%  0.10% 
Any other individual: NMT 0.5%  0.09% 
Total: NMT 2.0%  0.19% 
Appearance: Conforms with label  Conforms 
description and maintains integrity*** 
*Product has been continuously stored according to manufacturers labeled storage conditions and is less than 6 years beyond manufacturers labeled expiration date. 
** Has the product been stored continuously under manufacturers labeled storage conditions before testing? The response should be yes (Y) or no (N). If the response is no (N), 
then accelerated studies should be performed or an extension cannot be considered. Refer to Table 2. 
***Conformance to the product label description. Evaluation of the general integrity of the product should be made. This result can be denoted as conforms or does not conform. 
18 
  Contains Nonbinding Recommendations 
Table 2. Testing Protocol for Expiration Date Extension of Doxycycline Tablets and Capsules Under III.C.2 * 
Product Name  Lot  Storage**  Test  Specifications   Test Result   Manufacturers  Proposed 
and Strength  Identification  [Y/N]  Station    Labeled Expiration  New 
(number and  and Test    Date (original or last  Expiration 
manufacturer)  Date  extended)  Date 
Doxycycline  Lot #Abc0123  N  Month 0  Assay: 90.0-120.0% labeled amount  100.0%     
Hyclate  AB  1/01/2017  Dissolution: NLT 80%(Q) in 30 min.   
Capsules 100  Manufacturing    Mean:  99% 
mg, USP  High:  101% 
Low:  98% 
Degradants:    
4-Epidoxycycline: NMT 0.5%  0.10% 
Any other individual: NMT 0.5%  0.09% 
Total: NMT 2.0%  0.19% 
Appearance: Conforms with label  Conforms 
description and maintains integrity*** 
Month 1  Assay  97.0%     
2/01/2017  Dissolution  98%/ 100%/ 
Mean/High/Low  97% 
Degradants  0.10%/0.09%/
4-Epi/other/total  0.19% 
Appearance  Conforms 
Month 2  Assay  97.5%     
3/01/2017  Dissolution  98%/ 100%/ 
Mean/High/Low  97% 
Degradants  0.20%/0.09%/
4-Epi/other/total  0.29% 
Appearance  Conforms 
Month 3  Assay  95.0%  6/2017 Manufacturers  1/2019 
4/01/2017  Dissolution  97%/ 98%/  labeled expiration date 
  Mean/High/Low  95% 
Degradants  0.30%/0.10%/
4-Epi/other/total  0.40% 
Appearance  Conforms 
*Continuous storage according to manufacturers labeled storage conditions cannot be confirmed or lots are 6 years or more beyond the manufacturers labeled expiration date. 
Accelerated studies should be continued for at least 3 months or an extension cannot be considered. Testing under accelerated conditions (40C  C/75%  5% relative 
humidity). 
 2
** Has the product been stored continuously under manufacturers labeled storage conditions before testing? The response should be yes (Y) or no (N). If the response is no (N), 
then please explain.  
***Conformance to the product label description. Evaluation of the general integrity of the product should be made. This result can be denoted as conforms or does not conform. 
19