Department of Health and Human Services
OFFICE OF 
   
INSPECTOR GENERAL 
 
 
 
 
 
 
 
 
 
CDC CHEMPACK P : 
  S    ROJECT
 
N A  A S  
ERVE  GENT  NTIDOTE  TORAGE
 
 
 
 
 
 
 
Daniel R. Levinson  
Inspector General 
 
December 2009 
OEI-04-08-00040   
Office of Inspector General 
http://oig.hhs.gov 
 
The mission of the Office of Inspector General (OIG), as mandated by Public Law 95-452, as 
amended, is to protect the integrity of the Department of Health and Human Services 
(HHS) programs, as well as the health and welfare of beneficiaries served by those 
programs.  This statutory mission is carried out through a nationwide network of audits, 
investigations, and inspections conducted by the following operating components: 
Office of Audit Services 
The Office of Audit Services (OAS) provides auditing services for HHS, either by conducting 
audits with its own audit resources or by overseeing audit work done by others.  Audits 
examine the performance of HHS programs and/or its grantees and contractors in carrying 
out their respective responsibilities and are intended to provide independent assessments of 
HHS programs and operations.  These assessments help reduce waste, abuse, and 
mismanagement and promote economy and efficiency throughout HHS. 
Office of Evaluation and Inspections 
The Office of Evaluation and Inspections (OEI) conducts national evaluations to provide 
HHS, Congress, and the public with timely, useful, and reliable information on significant 
issues.  These evaluations focus on preventing fraud, waste, or abuse and promoting 
economy, efficiency, and effectiveness of departmental programs.  To promote impact, OEI 
reports also present practical recommendations for improving program operations.  
Office of Investigations 
The Office of Investigations (OI) conducts criminal, civil, and administrative investigations 
of fraud and misconduct related to HHS programs, operations, and beneficiaries.  With 
investigators working in all 50 States and the District of Columbia, OI utilizes its resources 
by actively coordinating with the Department of Justice and other Federal, State, and local 
law enforcement authorities.  The investigative efforts of OI often lead to criminal 
convictions, administrative sanctions, and/or civil monetary penalties. 
Office of Counsel to the Inspector General 
The Office of Counsel to the Inspector General (OCIG) provides general legal services to 
OIG, rendering advice and opinions on HHS programs and operations and providing all 
legal support for OIGs internal operations.  OCIG represents OIG in all civil and 
administrative fraud and abuse cases involving HHS programs, including False Claims Act, 
program exclusion, and civil monetary penalty cases.  In connection with these cases, OCIG 
also negotiates and monitors corporate integrity agreements.  OCIG renders advisory 
opinions, issues compliance program guidance, publishes fraud alerts, and provides other 
guidance to the health care industry concerning the anti-kickback statute and other OIG 
enforcement authorities.   
   
 E X E C U T I V E   S U M M A R Y  
OBJECTIVES 
To determine the extent to which: 
1.  nerve agent antidotes in the CHEMPACK project were stored at 
temperatures required by the Food and Drug Administration 
(FDA), 
2.  the Centers for Disease Control and Prevention (CDC) 
implemented procedures to ensure the quality of nerve agent 
antidotes in the CHEMPACK project, and   
3.  nerve agent antidotes in the CHEMPACK project appropriately 
received extended expiration dates under the Shelf Life Extension 
Program (SLEP). 
BACKGROUND 
In 2004, CDC established the CHEMPACK project as part of an 
approximately $3.5-billion Federal Strategic National Stockpile of 
drugs and medical supplies to assist States in protecting communities 
against the potentially deadly effects of chemical agents that attack 
the human nervous system (i.e., nerve agents).  While nerve agent 
antidotes in the CHEMPACK project (hereinafter referred to as 
CHEMPACK drugs) are part of the Strategic National Stockpile, they 
are not located with other federally stockpiled drugs.  Through the 
voluntary CHEMPACK project, CDC has placed over 1,900 containers 
stocked with CHEMPACK drugs in multiple locations in participating 
States, thereby allowing States to quickly respond to a nerve agent 
release.  Each container is stocked with CHEMPACK drugs to treat 
454 or 1,000 people, depending on the containers configuration.    
When States elect to participate in the CHEMPACK project, they sign 
a memorandum of agreement with CDC that outlines Federal and 
State roles and responsibilities.  For example, States are responsible 
for CHEMPACK drugs security, storage, and distribution in the 
event of a nerve agent release.  CDC retains ownership of 
CHEMPACK drugs and is responsible for their quality assurance, 
which includes temperature monitoring.  To ensure that CHEMPACK 
drugs are stored within the temperature range required by FDA, CDC 
remotely monitors containers stocked with CHEMPACK drugs using 
temperature-recording devices called Sensaphones and notifies States 
when temperatures need to be corrected.   
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E X E C U T I V E   S U M M A R Y  
As a holder of CHEMPACK drugs, CDC is subject to current good 
manufacturing practice (CGMP) provisions in the Food, Drug, and 
Cosmetic Act (the Act).  FDA considers CGMP provisions of the Act to 
be met if drugs are stored under temperatures required by their  
FDA-approved label.  CHEMPACK drugs must be stored according to 
the definition of controlled room temperature.  The definition requires 
a storage range of 68 degrees Fahrenheit (68F)77F with brief 
excursions (i.e., temperature fluctuations) permitted provided the 
calculated mean kinetic temperature (i.e., a fixed temperature that 
simulates the effect of temperature variation over a period of time) 
does not exceed 77F.  FDA requires entities that hold drugs with 
controlled room temperature storage requirements to calculate mean 
kinetic temperature but allows for flexibility in establishing the most 
appropriate method of performing the calculation.  FDA also requires 
entities that perform activities regulated by CGMP to establish and 
maintain a system to ensure the quality of their products.  FDA 
provides broad quality system guidance, but the entities have the 
flexibility to develop and implement procedures that best attain their 
quality objectives while still meeting FDA requirements.   
Finally, CDC participates in FDAs SLEP for selected Strategic 
National Stockpile drugs, including drugs in the CHEMPACK project.  
SLEP defers drug replacement costs by extending expiration dates.  
SLEP potency testing is conducted on a sample of drugs from one lot, 
or batch.  Based on the results, the expiration dates of other drugs 
from the same lot may be extended, provided that they were stored 
according to FDAs requirements.   
We reviewed CDC and FDA documents and interviewed CDC and 
FDA officials to assess the extent to which CDCs procedures met 
requirements for (1) CHEMPACK drug storage; (2) maintaining a 
system to ensure the quality of all Strategic National Stockpile drugs, 
including CHEMPACK drugs; and (3) SLEP.  We focused our review 
on the 1-year period from December 1, 2006, to November 30, 2007. 
FINDINGS 
Almost one-quarter of CHEMPACK containers did not have at 
least three daily temperature readings in accordance with CDC 
procedures.  Of the 1,255 CHEMPACK containers that were in State 
storage sites for the 1-year period we reviewed, 23 percent (288 of 
1,255) did not have the minimum number of CDC-established 
Sensaphone temperature readings for the full year.  Further, CDC did 
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E X E C U T I V E   S U M M A R Y  
not investigate and document most of the missing temperature 
readings. 
CDCs storage requirements for CHEMPACK drugs were not 
consistent with FDAs storage requirements.  CDCs procedures 
permitted CHEMPACK drugs to be stored between 59F and 86F.  
The storage temperature range required by FDA is 6877F with brief 
excursions permitted up to 86F and down to 59F, provided that the 
calculated mean kinetic temperature does not exceed 77F.  However, 
CDC did not calculate the mean kinetic temperature of CHEMPACK 
containers to demonstrate that their storage environment did not 
exceed a calculated mean kinetic temperature of 77F. 
Nine percent of selected CHEMPACK containers were not stored 
according to FDAs storage requirements for at least 1 month.  
Almost half of the 967 CHEMPACK containers that had at least three 
daily Sensaphone temperature readings for the 1-year period we 
reviewed experienced temperatures above 77F for varying amounts 
of time.  Using average temperature as a substitute for mean kinetic 
temperature, we determined that 9 percent (91 of 967) of selected 
containers had an average monthly temperature 1F or more above 
the mean kinetic temperature permitted by FDA (i.e., at or above 
78F) for at least 1 month.  In addition, 1 percent (12 of 967) of 
selected containers had an average temperature at or above 78F for 
at least 6 months.   
CDC did not consistently implement quality system procedures in 
the CHEMPACK project.  Although CDC had established a system to 
ensure the quality of all Strategic National Stockpile drugs, including 
CHEMPACK drugs, the system was not consistently implemented.  
Further, the quality system lacked the procedures necessary to 
ensure that CHEMPACK drugs were stored under conditions that 
would result in their highest possible level of quality and were 
maintained according to CGMP.   
CDCs procedures allowed CHEMPACK drugs to inappropriately 
receive extended expiration dates under SLEP.  Our findings 
demonstrate variability in CHEMPACK drug storage conditions.  
CDC procedures permit the comingling of drugs that were stored 
under these variable conditions with no means to link the drugs to 
records of their storage temperatures.  This process allowed drugs 
that were not stored according to FDAs requirements to receive 
extended expiration dates based on the potency testing results of 
drugs in the same lot that were stored as required by FDA.  Further, 
  OEI-04-08-00040  CDCS CHEMPACK PROJECT:  NERVE AGENT ANTIDOTE STORAGE 
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E X E C U T I V E   S U M M A R Y  
a similar process is also used to extend the expiration dates of       
non-CHEMPACK drugs in the $3.5-billion Strategic National 
Stockpile managed by CDC. 
RECOMMENDATIONS 
Surviving nerve agent exposure requires rapid treatment with nerve 
agent antidotes.  CDC has distributed over 1,900 CHEMPACK 
containers to participating States to allow quick response to a nerve 
agent release.  Each container is stocked with CHEMPACK drugs to 
treat 454 or 1,000 people, depending on the containers configuration.  
FDA has established minimum storage requirements to ensure that 
drugs are safe and effective.  However, CDC procedures did not 
ensure that CHEMPACK drugs stockpiled in States were stored 
according to these requirements.   
For example, CDC requirements allowed CHEMPACK drugs to be 
consistently stored under conditions that did not meet FDA storage 
temperature requirements and CGMP.  In addition, CDCs SLEP 
procedures do not comply with FDAs requirements for drugs to 
receive extended expiration dates.  These findings raise concerns 
about whether similar vulnerabilities also apply to other stockpiled 
CDC assets, i.e., non-CHEMPACK drugs in the $3.5-billion Strategic 
National Stockpile, because all assets share the same quality system 
and SLEP procedures. 
To address our findings, we recommend that CDC: 
Seek FDA guidance on whether CHEMPACK drugs that have 
received extended expiration dates under SLEP are appropriate 
for use. 
Revise its CHEMPACK project SLEP procedures to comply with 
FDA requirements. 
Revise its CHEMPACK drug storage temperature requirements to 
comply with FDA requirements.  
Ensure that the CHEMPACK projects quality system meets CGMP 
requirements for drug storage.    
 
 
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E X E C U T I V E   S U M M A R Y  
AGENCY COMMENTS AND OFFICE OF INSPECTOR GENERAL 
RESPONSE 
CDC concurred with all four of our recommendations.  CDC noted 
several actions it has taken or plans to take to address our findings and 
recommendations.  For example, CDC has retroactively calculated mean 
kinetic temperature for the same period as our evaluation and identified 
three CHEMPACK containers that FDA suggests may require 
additional testing to assure potency.  However, it is unclear from CDCs 
comments how it accounted for CHEMPACK containers that were 
missing temperature readings and documentation of temperature-
recording device calibrations. 
Finally, CDC stated that our report did not evaluate the overall 
Strategic National Stockpile program and therefore should not imply 
that problems exist with Strategic National Stockpile non-CHEMPACK 
assets.  Nevertheless, CDC has begun an assessment of how best to 
initiate an independent review of its quality system and other 
procedures relative to CHEMPACK containers, and the rest of the 
Strategic National Stockpile assets, to ensure compliance with FDA 
requirements.   
We support CDCs efforts to address these findings and encourage it to 
continue making progress in these areas.  We made technical changes to 
the report based on CDCs comments.     
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 T A B L E   O F   C O N T E N T S  
EXECUTIVE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . i
 
 
I N T RO DUC T IO N . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 
 
 
F I N D IN G S . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 
  Almost one-quarter of CHEMPACK containers did not have 
         at least three daily temperature readings in accordance 
         with CDC procedures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 
  CDCs storage requirements for CHEMPACK drugs were not  
          consistent with FDAs storage requirements . . . . . . . . . . . . . . . . 13 
  Nine percent of selected CHEMPACK containers were not  
         stored according to FDAs storage requirements for at least  
         1 month . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 
  CDC did not consistently implement quality system  
         procedures in the CHEMPACK project . . . . . . . . . . . . . . . . . . . . . 15 
  CDCs procedures allowed CHEMPACK drugs to inappropriately 
         receive extended expiration dates under SLEP. . . . . . . . . . . . . . . 17 
 
 
R E C O MMEN D A T ION S . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 
Agency Comments and Office of Inspector General Response . . . 21 
 
 
APPENDIXES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23 
 
  A:  The United States Pharmacopeia Definition of 
        Controlled Room Temperature. . . . . . . . . . . . . . . . . . . . . . . . . 23 
         B:  Methodology for Calculating Average Temperature. . . . . . . . . 24   
  C:  Cumulative Time CHEMPACK Containers Were  
               Maintained Above 77F. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 
  D:  Agency Comments. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26 
 
 
A C K NO WL E D G M E N T S . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31   
   
 I N T R O D U C T I O N  
OBJECTIVES 
To determine the extent to which: 
1.  nerve agent antidotes in the CHEMPACK project were stored at 
temperatures required by the Food and Drug Administration 
(FDA), 
2.  the Centers for Disease Control and Prevention (CDC) 
implemented procedures to ensure the quality of nerve agent 
antidotes in the CHEMPACK project, and   
3.  nerve agent antidotes in the CHEMPACK project appropriately 
received extended expiration dates under the Shelf Life Extension 
Program (SLEP). 
BACKGROUND 
The CDC Division of Strategic National Stockpile (DSNS) maintains 
an approximately $3.5-billion stockpile of federally owned drugs and 
medical supplies to assist State and local health departments in the 
event of a large-scale public health emergency.1, 2  This stockpile 
includes antidotes to treat people exposed to nerve agents.  
Nerve agents have been used to commit acts of terrorism.  For 
example, in 1995, the Aum Shinrikyo cult released the nerve agent 
sarin in five Tokyo subways, killing 12 people and injuring more than 
5,000 others.  Depending on the dose, nerve agents can cause 
immediate nervous system failure and death.  Surviving nerve agent 
exposure requires rapid treatment with nerve agent antidotes.  
In 2004, CDC established the CHEMPACK project as part of the 
Strategic National Stockpile to assist the 62 Bioterrorism Cooperative 
Agreement Project Areasthe 50 States, the District of Columbia, the 
cities of Chicago and New York, Los Angeles County, Puerto Rico, the 
U.S. Virgin Islands, and the 6 Pacific Basin jurisdictions (hereinafter 
referred to as States)to protect communities against the potentially 
 
1 The initial authorization to create and maintain special pharmaceutical stockpiles as a 
national resource is described in the Fiscal Year 1999 Omnibus Appropriations Act. 
2 CDC, Strategic National Stockpile (SNS).  Available online at 
http://emergency.cdc.gov/coca/ppt/DSNS_Piester_July12008_CE.ppt#303,1,Slide 1.  
Accessed on March 19, 2009.  
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I N T R O D U C T I O N  
deadly effects of nerve agents.3  Cumulative funding for the 
CHEMPACK project is estimated to exceed $100 million during fiscal 
years 20092013.4    
While nerve agent antidotes in the CHEMPACK project (hereinafter 
referred to as CHEMPACK drugs) are part of the Strategic National 
Stockpile, they are not located with other federally stockpiled drugs 
and medical supplies.  Through the voluntary CHEMPACK project, 
CDC places CHEMPACK drugs in multiple locations in participating 
States, thereby allowing States to quickly respond to a nerve agent 
release.5  As of January 2009, more than 92 percent of the United 
States population lived within a 1-hour distance of CHEMPACK 
drugs, according to CDC.6   
When States elect to participate in the CHEMPACK project, they sign 
a memorandum of agreement with CDC that outlines Federal and 
State roles and responsibilities.  For example, States are responsible 
for CHEMPACK drugs security, storage, and distribution in the 
event of a nerve agent release.  CDC retains ownership of 
CHEMPACK drugs and is responsible for their quality assurance, 
which includes temperature monitoring. 
CHEMPACK Drug Storage Containers 
CDC assembles containers stocked with CHEMPACK drugs  
(i.e., atropine, pralidoxime, and diazepam) and distributes the 
containers to CDC-approved State storage sites.  Each container is 
stocked with CHEMPACK drugs to treat 454 or 1,000 people, 
depending on the containers configuration.  As of January 2009, CDC 
had distributed over 1,900 CHEMPACK containers to States.7   
 
3 CHEMPACK Program Description (June 14, 2004).  Available online at 
http://www.bt.cdc.gov/planning/continuationguidance/pdf/chempack-attachj.pdf.  Accessed 
on October 1, 2007. 
4 Implementation Plan for Chemical, Biological, Radiological and Nuclear Threats,  
p. 13.  Health and Human Services Public Health Emergency Medical Countermeasures 
Enterprise, 2007.   
5 As of January 2009, 54 of the 62 States were participating in the CHEMPACK project. 
6 CDC, Public Health Preparedness:  Strengthening CDCs Emergency Response.  
Available online at http://emergency.cdc.gov/publications/jan09phprep/.  Accessed on 
February 15, 2009. 
7 Written CDC responses to OIG questions about the CHEMPACK project,              
August 20, 2009. 
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I N T R O D U C T I O N  
These stocked containers cost at least $83 millionapproximately 
$43,000 per container.8  CHEMPACK containers are monitored by 
temperature-recording devices called Sensaphones.  CDC programs 
each Sensaphone to take one temperature reading at least every  
8 hours, for a minimum of three daily temperature readings.9  A 
Sensaphone uses a telephone line to send the temperature readings to 
a CDC computer that retains the readings.  CDC personnel monitor 
the temperature readings and notify States when action is required to 
correct CHEMPACK drug storage temperatures.  
CHEMPACK Drug Storage Requirements  
FDA has established minimum requirements, known as current good 
manufacturing practices (CGMP), for drug manufacturers, processors, 
packers, and holders to ensure that drugs are safe and effective.10  As 
a holder of CHEMPACK drugs, CDC is subject to statutory CGMP 
provisions in section 501(a)(2)(B) of the Food, Drug, and Cosmetic Act 
(the Act).11, 12  FDA considers CGMP provisions of the Act to be met if 
drugs are stored according to FDA-approved requirements as 
specified on the drug labels.13   
CHEMPACK drug labeling requires that the drugs be stored in 
accordance with the United States Pharmacopeia definition of 
controlled room temperature.14  This definition establishes a storage 
 
8 CDC documentation of CHEMPACK container costs, dated December 20, 2007.  There 
are two types of CHEMPACK containers, each with a different configuration and cost.  To 
be conservative, we used the cost of the less-expensive container when calculating the total 
cost of the 1,937 containers. 
9 CDC has established Sensaphone alarm temperature settings.  When temperatures fall 
outside of range, a Sensaphone may take a temperature reading more frequently than every 
8 hours until the containers temperature returns within range. 
10 21 CFR  211. 
11 Written FDA response to Office of Inspector General (OIG) questions on CHEMPACK 
drug storage requirements, March 13, 2008. 
12 The Act requires that drugs be maintained to conform with CGMP, but does not 
specifically address what constitutes CGMP.  For guidance on good practices for holders of 
drugs, FDA refers to 21 CFR  205 and 211.  Specifically, FDA refers to holding provisions 
in the CGMP regulations and Guidelines for State Licensing of Wholesale Prescription 
Drug Distributors in 21 CFR  205.50.  The sections of the CGMP regulations in  
21 CFR  211 that are the most applicable as guidance for the holding of drug products 
include subparts B (Organization and Personnel), C (Buildings and Facilities), and              
H (Holding and Distribution). 
13 FDA Memorandum, Clarification Regarding SNS Medical Product Temperature 
Excursions.  May 18, 2005. 
14 The United States Pharmacopeia is an official public standards-setting authority for 
all prescription and over-the-counter medicines and other health care products 
manufactured or sold in the United States. 
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I N T R O D U C T I O N  
temperature range of 68 degrees Fahrenheit (68F) to 77F.  However, 
the controlled room temperature definition also recognizes that 
temperature excursions (i.e., fluctuations) can occur in typical drug 
storage warehouses.  As a result, drugs with controlled room 
temperature storage requirements are permitted to experience brief 
excursions as low as 59F and as high as 86F, provided that the 
calculated mean kinetic temperature (i.e., a fixed temperature that 
simulates the effect of temperature variation over a period of time) 
does not exceed 77F.  See Appendix A for the full definition of 
controlled room temperature. 
FDA officials provided further guidance on the definition of controlled 
room temperature, noting that it intends for drugs to be stored 
primarily within the 6877F range.  Further, FDA officials noted 
that drugs labeled for controlled room temperature storage should not 
be stored constantly at the upper excursion range because they may 
be exposed to a mean kinetic temperature exceeding 77F over time.  
FDA does not dictate how frequently drug storage temperatures must 
be recorded or the length of time over which mean kinetic 
temperature must be calculated.  However, FDA recommends that 
entities follow the instructions in United States Pharmacopeia 
General Information Chapter 1150 for collecting temperature 
monitoring data and for calculating mean kinetic temperature.  
General Information Chapter 1150 states that temperatures for 
calculating mean kinetic temperature can be conveniently collected 
using electronic devices that measure temperatures at frequent 
intervals (e.g., every 15 minutes). 
Finally, FDA does not require CHEMPACK drugs to be stored under 
controlled humidity, although CDC requires States to maintain the 
humidity level in CHEMPACK drug storage sites below 60 percent.15  
According to CDC personnel, this requirement was established based 
on input from the FDA, with legal oversight by the Office of the 
General Counsel at both the Departments of Homeland Security and 
Health and Human Services.16  
 
15 Memorandum of agreement between CDC and each participating State. 
16 Written CDC responses to OIG questions on the roles and responsibilities of the DSNS 
Quality Control Unit, March 25, 2008.   
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The Quality System for the CHEMPACK Project 
FDA requires entities that perform activities regulated by CGMP to 
establish and maintain a system to ensure the quality of their 
products.  FDA provides broad quality system guidance, but entities 
have the flexibility to develop and implement procedures that attain 
their quality objectives while still meeting FDA requirements. 
CDCs Strategic National Stockpile quality system applies to the 
CHEMPACK project, as well as other stockpiled CDC assets, i.e.,  
non-CHEMPACK drugs in the $3.5-billion Strategic National 
Stockpile.  For the CHEMPACK project, in particular, the quality 
system includes procedures to ensure that (1) Sensaphones take 
accurate temperature readings, (2) storage temperatures are 
monitored to maintain CHEMPACK drugs within a CDC-established 
temperature range, and (3) the temperature readings are accurately 
retained.17  In addition, the quality system includes procedures to 
correct and document out-of-range drug storage temperatures.  
Finally, the DSNS Quality Control Unit provides oversight of all 
Strategic National Stockpile drugs, including those in the 
CHEMPACK project, to ensure that the quality system is 
implemented as intended.  
Ensuring accurate temperature readings.  CDC procedures for the 
CHEMPACK project require CDC personnel to calibrate Sensaphones 
annually to ensure that the temperature recorded by the device 
reflects the actual storage environment.18  Further, according to CDC 
procedures for the CHEMPACK project, CDC personnel sign and date 
all calibration reports before placing them on file.   
Monitoring and retaining temperature readings.  To ensure that 
CHEMPACK drugs are stored within the CDC-established 
temperature range, CDC personnel monitor Sensaphone temperature 
readings for all CHEMPACK drug storage sites.  CDC also retains 
electronic records of Sensaphone temperature readings to document 
CHEMPACK drug storage conditions.  
Correcting and documenting out-of-range temperatures.  CDC 
procedures require CDC personnel to notify States when action is 
 
17 CDC has established a temperature range for CHEMPACK storage that is different 
from the temperature range required by FDA.  This will be discussed in detail later in this 
report. 
18 Calibration is a process during which a measuring instrument is adjusted to an 
acceptable level of accuracy. 
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required to return CHEMPACK drug storage temperatures to the 
CDC-established range. 
When CHEMPACK drug storage temperatures fall outside of the  
CDC-established range for less than 24 hours, CDC procedures for the 
CHEMPACK project require CDC personnel to create an incident 
ticket.  In general, an incident ticket documents the steps that States 
have taken to correct CHEMPACK drug storage temperatures, and 
what may have led to the out-of-range temperatures.19    
If CHEMPACK drug storage temperatures fall outside of the  
CDC-established range for longer than 24 hours, CDC personnel must 
create a corrective and preventive action report.  A corrective and 
preventive action report documents the steps that State and/or CDC 
personnel have taken to correct temperatures outside of the 
established range.  It also documents what may have led to the  
out-of-range temperatures and potential impact to the affected 
CHEMPACK drugs.  
Overseeing quality procedures.  The DSNS Quality Control Unit is 
responsible for overseeing the quality system for storing and 
monitoring all Strategic National Stockpile drugs, including 
CHEMPACK drugs.20  The Quality Control Unit reports directly to 
the DSNS Office of the Director and its responsibilities include: 
  ensuring that CDC and States comply with applicable CGMP 
regulations;   
  conducting regularly scheduled evaluations of all CHEMPACK 
drug storage sites, applicable policies, and standard operating 
procedures;    
  verifying appropriate investigation and resolution of situations and 
actions that do not adhere to CHEMPACK policies and standard 
operating procedures, e.g., out-of-range CHEMPACK drug storage 
temperatures; and 
  ensuring that all CHEMPACK CGMP documents, e.g., Sensaphone 
calibration reports, records of Sensaphone temperature readings, 
 
19 CDC personnel also develop incident tickets to document occurrences other than   
out-of-range storage temperatures, such as power outages and lack of Sensaphone 
connectivity. 
20 CDC, Establishment of an Independent Division of Strategic National Stockpile 
(DSNS) Quality Control Unit for the Storage and Movement of Finished Pharmaceuticals.  
December 15, 2005.   
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incident tickets, and corrective and preventive action reports, are 
appropriately maintained.21 
Shelf Life Extension Program  
CDC participates in SLEP for selected Strategic National Stockpile 
drugs, including CHEMPACK drugs.  SLEP is an FDA program that 
defers drug replacement costs by extending drug expiration dates.22   
Under SLEP, the shelf life of a drug may be doubled if the drug 
passes FDA potency testing.  CDC has reported that for every dollar 
spent on SLEP costs (e.g., shipping drugs, potency testing) in 2007, it 
saved $13 by deferring the purchase of new drugs.23, 24     
CDC provides FDA with a list of all lot numbers of CHEMPACK 
drugs that are approaching expiration.25  From this list, FDA 
determines which drugs will be potency tested and requests that CDC 
submit samples to be tested from each selected lot of the drugs.  CDC 
recalls, from State storage sites, the remaining drugs from each 
selected lot to central CDC storage, where they are held pending FDA 
potency test results.   
CHEMPACK drugs from one lot may have been stored in multiple 
locations.  According to FDA officials, SLEP potency testing results 
may be used to extend the expiration dates of drugs with the same lot 
number that were stored under appropriate conditions, i.e., according 
to FDA-approved labeling requirements.  When a drug fails potency 
testing, all drugs with that lot number must be destroyed.  Further, if 
drugs with any lot number were stored under conditions outside of 
FDA-approved labeling requirements, they should be potency tested 
separately or destroyed upon expiration.   
As of January 2009, samples of the CHEMPACK drugs atropine, 
pralidoxime, and diazepam have undergone FDA potency testing and 
received extended expiration dates.   
 
21 Ibid.   
22 FDA/DoD [Department of Defense] Shelf Life Extension Program.  Available online at 
https://slep.dmsbfda.army.mil/slep/slep_infor_paper_JAN_2006.doc.  Accessed on July 29, 
2008. 
23 CDC SLEP cost avoidance includes both CHEMPACK and non-CHEMPACK drugs. 
24 CDC, Online Performance Appendix, p. 120.  Available online at 
http://www.cdc.gov/FMO/PDFs/FY09_CDC_Online_Performance_Appendix.pdf.  Accessed 
on April 13, 2009. 
25 A lot number identifies a particular batch, or lot, of drug product from a manufacturer.  
  OEI-04-08-00040  CDCS CHEMPACK PROJECT:  NERVE AGENT ANTIDOTE STORAGE  7  
   
I N T R O D U C T I O N  
Related Work 
In 2006, OIG issued a report on early CHEMPACK project 
implementation and determined that CDC had opportunities to 
strengthen CHEMPACK deployment.  OIG recommended that CDC 
assist States in deployment testing, develop CHEMPACK 
performance goals and training materials, and provide medical 
expertise on CHEMPACK drugs.  In its comments to our report, CDC 
stated that it had addressed, or begun to address, OIGs 
recommendations. 
METHODOLOGY 
Scope 
We determined the extent to which CHEMPACK drugs were stored at 
the temperatures required by FDA during the 1-year period from 
December 1, 2006, to November 30, 2007.26   We also determined the 
extent to which CDC ensured that CHEMPACK drugs, as well as 
non-CHEMPACK drugs in the $3.5-billion Strategic National 
Stockpile, were maintained under a system to ensure their quality 
and appropriately received extended expiration dates under SLEP.   
We did not analyze the viability of CHEMPACK drugs that were 
stored outside FDA-required temperatures.  We also did not directly 
assess storage conditions for non-CHEMPACK drugs.   
Data Collection 
We requested that CDC provide a listing of all CHEMPACK 
containers that were in State storage sites for the entire year we 
reviewed.27  Of the over 1,900 containers that CDC had distributed as 
of January 2009, 1,262 met this criterion. 
In addition, we obtained written CDC policies, procedures, and 
records related to storing CHEMPACK drugs as well as the Strategic 
National Stockpile quality system and SLEP.  We also obtained 
written FDA requirements for CDC participation in SLEP. 
 
26 We used Sensaphone data to determine CHEMPACK drug storage temperatures.  The 
most recent 12-month period of Sensaphone data available at the time of our review was 
from December 1, 2006, to November 30, 2007.   
27 The containers were stored in 51 of the 54 States participating in the CHEMPACK 
project.  Three States had not yet received CHEMPACK containers when we began our 
review.  
  OEI-04-08-00040  CDCS CHEMPACK PROJECT:  NERVE AGENT ANTIDOTE STORAGE  8  
   
I N T R O D U C T I O N  
Further, we interviewed CDC officials about their policies and 
procedures for CHEMPACK drug storage and Strategic National 
Stockpile participation in SLEP.  Finally, we interviewed FDA 
officials on Federal storage requirements for CHEMPACK drugs and 
Strategic National Stockpile SLEP participation.  
Data Analysis 
We reviewed Sensaphone temperature records for 1,255 CHEMPACK 
containers that were in State storage sites for the entire 1-year period 
we reviewed.28  We reviewed the Sensaphone records to determine the 
extent to which the 1,255 containers had at least three temperature 
readings for each day of the 1-year period, in accordance with CDC 
procedures.29  For the containers that did not have at least three daily 
temperature readings for the year, we determined the total number of 
temperature readings that were missing.  We also reviewed CDC 
incident reports to determine the extent to which CDC investigated 
and documented the missing temperature readings.  
We selected the containers that had at least three daily temperature 
readings for the entire 1-year period for further analysis.  First, using 
Sensaphone temperature readings, we determined the cumulative 
time the containers were maintained above the 6877F storage range 
for CHEMPACK drugs.30, 31  We focused our analysis on 
temperatures above the storage range because they present the 
greatest risk of increasing a containers mean kinetic temperature 
above the 77F limit specified by FDA.  
Second, we calculated average temperature for the selected containers 
as a substitute for mean kinetic temperature for each month of the   
 
28 We excluded seven containers from our analysis because CDC did not provide their 
corresponding Sensaphone records. 
29 Sensaphones take temperature readings more frequently than every 8 hours when a 
containers storage temperature falls outside of the CDC-established storage range.  
30 We define cumulative time as the aggregate time that CHEMPACK containers were 
maintained above 77F over the course of the entire 1-year period we reviewed.  
31 To be conservative, we did not include periods of time when a containers temperature 
was above 110F because these temperature readings were questionable and/or we received 
CDC documentation explaining that they were not valid.   
  OEI-04-08-00040  CDCS CHEMPACK PROJECT:  NERVE AGENT ANTIDOTE STORAGE  9  
   
I N T R O D U C T I O N  
1-year period we reviewed.32, 33  We then counted the number of 
months that each container had an average temperature of 78F or 
higher, i.e., 1 degree or more above the mean kinetic temperature 
limit of 77F permitted by FDA.  See Appendix B for a description of 
the methodology we used to calculate average temperature.  
Next, we reviewed CDC documentation to determine the extent to 
which CDC personnel implemented Strategic National Stockpile 
quality system procedures for the CHEMPACK project by developing 
required incident tickets and corrective and preventive action reports.  
First, we selected CHEMPACK containers that had at least three 
daily temperature readings for the entire 1-year period we reviewed.  
Next, we used Sensaphone records to determine the number of 
occurrences that each selected containers temperature was outside of 
the CDC-established range.34  Finally, we reviewed CDC 
documentation to determine the extent to which CDC personnel 
developed incident tickets and corrective and preventive action 
reports for out-of-range temperatures lasting less than 24 hours and 
over 24 hours, respectively.  
We reviewed CDC documentation to determine the extent to which 
CDC personnel filed a signed and dated annual Sensaphone 
calibration report, as required by CDC procedures for the 
CHEMPACK project, for all 1,255 containers that were in State 
storage for the entire year we reviewed.35  We also reviewed the 
calibration reports to determine the extent to which CDC met CGMP 
standards when documenting the calibration procedures and results.   
Finally, we determined the extent to which CDC procedures ensured 
that CHEMPACK drugs appropriately received extended expiration 
dates.  We performed this analysis by comparing CDC SLEP 
 
32 We did not calculate mean kinetic temperature because we did not have the energy of 
activation, a variable required for calculation, for each CHEMPACK drug. 
33 According to FDA, the calculated mean kinetic temperature is higher than the average 
temperature.  FDA, Guidance for Industry:  Q1A(R2) Stability Testing of New Drug 
Substances and Products, November 2003, p. 18.  Available online at 
http://www.fda.gov/downloads/RegulatoryInformation/Guidances/ucm128204.pdf.  Accessed 
on November 13, 2009.    
34 We define occurrences as each time a containers temperature left and then returned 
within range.  
35 We performed this analysis on calibration records CDC personnel developed during 
the period from January to December 2007. 
  OEI-04-08-00040  CDCS CHEMPACK PROJECT:  NERVE AGENT ANTIDOTE STORAGE  10  
   
I N T R O D U C T I O N  
procedures to FDA SLEP requirements, and by reviewing transcripts 
of interviews we conducted with CDC and FDA officials about SLEP.  
Limitations 
We reviewed Sensaphone temperature readings for 1,255 CHEMPACK 
containers that were in State storage sites during the year from 
December 1, 2006, to November 30, 2007.  As of January 2009, there 
were over 1,900 containers stored in States.  
We reviewed the storage temperatures of CHEMPACK drugs during a 
1-year period.  However, many of the drugs had been stored for periods 
longer than 1 year.  The cumulative amount of time these drugs may 
have been stored outside their required storage range is unknown. 
We calculated average temperature as a substitute for mean kinetic 
temperature because we did not have the energy of activation, a 
variable necessary to calculate mean kinetic temperature, for each 
CHEMPACK drug.   
Further, FDA does not dictate how frequently drug storage 
temperatures must be recorded or the length of time over which mean 
kinetic temperature must be calculated.  However, FDA does note 
that more frequent measurements will provide a more precise mean 
kinetic temperature.  We calculated average temperature, as a 
substitute for mean kinetic temperature, for each month of the 1-year 
period we reviewed using all recorded temperatures for each 
container.  Other methods may also be appropriate.   
Standards 
This study was conducted in accordance with the Quality Standards for 
Inspections approved by the Council of the Inspectors General on 
Integrity and Efficiency.
  OEI-04-08-00040  CDCS CHEMPACK PROJECT:  NERVE AGENT ANTIDOTE STORAGE  11  
   
 F I N D I N G S  
 
Almost one-quarter of CHEMPACK containers  Twenty-three percent (288 of 
did not have at least three daily temperature  1,255) of the CHEMPACK 
containers in State storage sites 
readings in accordance with CDC procedures 
for the entire year we reviewed 
did not have the three required daily temperature readings for the    
1-year period we reviewed.36  The other 967 of 1,255 containers had at 
least three daily temperature readings for the full year. 
In most cases, the CHEMPACK containers that did not have at least 
three daily temperature readings were missing 1 percent or less of the 
required temperature readings (i.e., 11 readings or less).  These 
missing readings represent a cumulative maximum time of 
approximately 3.5 days of the 1-year period we reviewed.  
In some cases, these CHEMPACK containers were missing a 
significant number of temperature readings.  For example, 2 percent 
of containers (23 of 1,255) were missing more than one-quarter of the 
required temperature readings (i.e., over 247 readings).  These 
missing readings represent a cumulative minimum time of over 90 
days of the 1-year period we reviewed.  
Table 1 (on the next page) provides the number and percentage of 
CHEMPACK containers we determined were missing temperature 
readings during the 1-year period. 
  Table 1:  CHEMPACK Containers With Missing Temperature Readings 
Percentage of Missing Daily Temperature  Number of Containers  Percentage of 
Readings in a 1-Year Period*  Containers (n=1,255)** 
0.11%  248  20% 
Over 15%  6  0% 
Over 510%  4  0% 
Over 1025%  7  1% 
Over 2550%  13  1% 
Over 5075%  5  0% 
Over 75%  5  0% 
   Total  288  23%*** 
  * Ranges calculated out of 1,095 expected readings in a 1-year period. 
** Percentages are rounded to the closest whole number. 
*** Percentages do not add to total because of rounding. 
Source:  OIG analysis of Sensaphone temperature readings of CHEMPACK containers. 
 
36 We reviewed the 1-year period from December 1, 2006, to November 30, 2007. 
  OEI-04-08-00040  CDCS CHEMPACK PROJECT:  NERVE AGENT ANTIDOTE STORAGE  12  
   
F I N D I N G S  
CDC did not investigate and document most of the missing 
temperature readings  
CDC documented missing temperature readings for three 
CHEMPACK storage sites for the 1-year period we reviewed.  These 
sites corresponded to only 4 of the 288 containers that lacked 
temperature readings. 
 
CDCs storage requirements for CHEMPACK   FDA requires CHEMPACK 
drugs to be stored primarily 
drugs were not consistent with FDAs  
within the 6877F range, with 
storage requirements 
excursions permitted down to 
59F and up to 86F provided that the calculated mean kinetic 
temperature does not exceed 77F.37  
CDC requires CHEMPACK drugs to be stored in a 5986F range.  
This requirement allows States to indefinitely store CHEMPACK 
drugs in temperature ranges (i.e., 5967F and 7886F) that, 
according to FDA requirements, are permitted for brief excursion 
periods only.  FDA officials further noted that CHEMPACK drugs 
should not be constantly stored under temperatures in the upper 
excursion range.  
CDC did not calculate the mean kinetic temperature of CHEMPACK 
containers  
CHEMPACK drugs should not be stored under conditions that result 
in a calculated mean kinetic temperature that exceeds 77F.  
However, CDC did not calculate the mean kinetic temperature of 
CHEMPACK containers during the time of our review.  Without this 
calculation, CDC could not demonstrate that CHEMPACK drugs that 
experienced temperature excursions above 77F were held according 
to FDA requirements. 
 
Nine percent of selected CHEMPACK containers   We analyzed the temperature 
were not stored according to FDAs storage  readings of the 967 
requirements for at least 1 month  CHEMPACK containers that 
had at least three daily 
Sensaphone temperature readings for the 1-year period we reviewed 
 
37 Written FDA response to OIG questions on CHEMPACK drug storage requirements,  
March 13, 2008. 
 
  OEI-04-08-00040  CDCS CHEMPACK PROJECT:  NERVE AGENT ANTIDOTE STORAGE  13  
   
F I N D I N G S  
and determined that over one-third of these containers experienced 
temperatures above 77F for varying amounts of time.38  Specifically, 
36 percent (351 of 967) of these containers experienced temperatures 
above 77F for a cumulative period ranging from 8 hours to over 6 
months.  See Appendix C for further details on this analysis.  
Using average temperature as a substitute for mean kinetic 
temperature, we determined that 9 percent (91 of 967) of the selected 
containers had an average monthly temperature 1 degree or more 
above the maximum mean kinetic temperature permitted by FDA 
(i.e., at or above 78F) for at least 1 month.39  In addition,  
1 percent (12 of 967) of the selected containers had an average 
temperature at or above 78F for at least 6 months.  Three of these 
containers had an average monthly temperature at or above 78F for 
the entire 1-year period we reviewed.    
Table 2 provides the number of months that the selected CHEMPACK 
containers had an average temperature at or above 78F and the 
corresponding number and percentage of containers. 
  Table 2:  CHEMPACK Containers With a Monthly Average 
Temperature At or Above 78F 
Number of Months at or           Percentage of Selected 
Above 78F  Number of Containers  Containers (n=967)* 
1  35  4% 
2  19  2% 
3  14  1% 
4  8  1% 
5  3  0% 
6  2  0% 
7  3  0% 
8  4  0% 
11  1  0% 
12  2  0% 
   Total  91  9%** 
  * Percentages rounded to the closest whole number.  
** Percentages do not add to total because of rounding. 
Source:  OIG analysis of Sensaphone temperature readings of CHEMPACK containers. 
 
38 Approximately 44 percent (425 of 967) of these containers had at least one 
temperature reading above 77F 
39 Monthly average temperatures did not exceed 84F. 
  OEI-04-08-00040  CDCS CHEMPACK PROJECT:  NERVE AGENT ANTIDOTE STORAGE  14  
   
F I N D I N G S  
CDC did not consistently implement quality  Although CDC had established a 
system to ensure the quality of all 
system procedures in the CHEMPACK project 
Strategic National Stockpile 
drugs, including CHEMPACK drugs, the system was not consistently 
implemented.  Further, the quality system lacked procedures 
necessary to ensure that CHEMPACK drugs were stored under 
conditions that would maintain their highest level of quality and were 
maintained according to CGMP. 
CDC did not validate the computer that stores Sensaphone temperature 
readings 
CDC did not validate the computer that stores Sensaphone 
temperature readings to ensure that the stored temperatures were 
identical to the temperatures recorded by the Sensaphone.  In 
addition, CDC did not validate the computer system to ensure that 
controls were in place to prevent the loss of temperature readings, or 
unauthorized access or changes to those readings.  
CDC did not adequately document Sensaphone calibrations 
According to CDC procedures, Sensaphones must be calibrated 
annually to ensure that the temperatures recorded by the devices 
reflect the actual storage environment.  A calibration report must be 
signed and dated to document that the procedure was performed.  
However, 39 percent of the CHEMPACK containers (486 of 1,255) did 
not have a Sensaphone calibration report that was signed and dated 
by CDC personnel during the 1-year period of our review.  Therefore, 
we could not determine whether the calibration had been performed 
annually according to CDC procedures.   
The 769 calibration reports that were signed and dated contained the 
initials of the signatory but did not indicate whether that person had 
performed the calibration or was a reviewing official.  In addition, 
these calibration reports were not signed by a second person to 
demonstrate that they had been independently reviewed.  Further, 
none of the calibration reports contained necessary CGMP 
information about the calibration process.  For example, they all 
lacked clearly marked precalibration and postcalibration Sensaphone 
readings, as well as details about adjustments made to bring the 
Sensaphone to an acceptable level of accuracy.  In addition, none of 
the calibration reports documented that the Sensaphone alarm 
settings had been checked and were functioning as intended.   
  OEI-04-08-00040  CDCS CHEMPACK PROJECT:  NERVE AGENT ANTIDOTE STORAGE  15  
   
F I N D I N G S  
CDC did not consistently develop incident tickets and corrective and 
preventive action reports for CHEMPACK drug storage temperatures 
outside of the CDC-established range 
CDC must document deviations from written CDC procedures for the 
CHEMPACK project to be in compliance with these procedures and 
CGMP.  However, CDC personnel did not consistently develop 
incident tickets or corrective and preventive action reports to 
document CHEMPACK drug storage temperatures outside of the 
CDC-established temperature range (i.e., 5986F), in accordance 
with CDC procedures.  
For all 967 containers that had at least three daily temperature 
readings for the 1-year period of our review, there were  
6,438 occurrences when the containers temperatures fell outside of 
the CDC-established temperature range and returned to that range.  
According to CDC procedures, CDC personnel should have developed 
an incident ticket or corrective and preventive action report for each 
of these 6,438 occurrences.  However, CDC completed documentation 
for only 65 of these occurrences. 
We performed further analysis on the occurrences when the 
containers temperatures were continuously outside of the CDC-
established range for at least 1 hour.  Based on this analysis, there 
were 201 occurrences that should have been reported on an incident 
ticket because a containers temperature reading was outside of the 
CDC-established temperature range for at least one hour but less 
than 24 hours.  However, CDC completed an incident ticket for only 
32 percent (64 of 201) of these occurrences.    
Similarly, CDC personnel did not develop a corrective and preventive 
action report each time a container experienced temperatures outside 
of the CDC-established temperature range for longer than 24 hours.  
For all 967 containers that had at least three daily temperature 
readings for the 1-year period of our review, there were  
39 occurrences that should have led to a corrective and preventive 
action report.  However, CDC completed a corrective and preventive 
action report for only 1 of these 39 occurrences.  
CDC did not monitor humidity at CHEMPACK drug storage sites 
As outlined in the CHEMPACK memorandum of agreement, States 
must maintain the humidity level of CHEMPACK drug storage sites 
below 60 percent.  However, CDC did not monitor humidity in 
CHEMPACK storage sites and therefore did not notify States when 
  OEI-04-08-00040  CDCS CHEMPACK PROJECT:  NERVE AGENT ANTIDOTE STORAGE  16  
   
F I N D I N G S  
action was required to bring drug storage conditions back into the 
required humidity range. 
CDC did not ensure that the CHEMPACK project was reviewed as 
required by a quality control unit 
DSNS policy requires its Quality Control Unit to regularly inspect all 
Strategic National Stockpile storage sites, including those in the 
CHEMPACK project.  However, the DSNS Quality Control Unit had 
not inspected any CHEMPACK drug storage sites since the 
CHEMPACK projects inception in 2004.  In addition, DSNSs Quality 
Control Unit staff had not reviewed Sensaphone calibration reports, 
Sensaphone temperature records, or incident tickets and corrective 
and preventive action reports in accordance with CDC procedures.  
These reviews are necessary to ensure appropriate storage of 
CHEMPACK drugs as well as investigation and resolution of drug 
storage temperatures that did not adhere to CDC procedures and 
CGMP.   
 
CDCs procedures allowed CHEMPACK drugs      CDC procedures do not 
to inappropriately receive extended      ensure that CHEMPACK 
drugs stored outside of 
expiration dates under SLEP 
FDAs temperature 
requirements are destroyed or potency tested separately from drugs 
that meet those requirements, as required by FDA SLEP policy.   
When CHEMPACK drugs approach expiration, they are returned 
from State storage sites to a central CDC location and sorted by their 
manufacturer lot numbers.  However, according to CDC 
documentation, . . . product is not sorted or sortable by its history, so 
the container that it came out of cannot be determined once it is  
comingled with other [CHEMPACK drugs] of the same lot.  
Therefore, once CHEMPACK drugs are returned to central storage, 
CDC personnel cannot determine which drugs were stored under 
conditions required by FDA and which were not.  
Our findings demonstrate that almost one-quarter of CHEMPACK 
containers were missing temperature readings to document their 
storage conditions.  Further, there was variability in CHEMPACK 
drug storage conditions for the containers that had the minimum 
number of CDC-required temperature readings.  For example,  
36 percent (351 of 967) of containers were maintained above the 77F 
upper storage limit required by FDA for cumulative periods of 
  OEI-04-08-00040  CDCS CHEMPACK PROJECT:  NERVE AGENT ANTIDOTE STORAGE  17  
   
F I N D I N G S  
between 8 hours and more than 6 months.  Further, 9 percent  
(91 of 967) of the selected containers had an average monthly 
temperature 1 degree or more above the mean kinetic temperature 
permitted by FDA (i.e., at or above 78F) for at least 1 month.40  
CDC procedures allowed CHEMPACK drugs in containers that were 
not maintained within the FDA required temperature range to be 
mixed with drugs from containers that were maintained as required.  
These procedures allowed CDC to extend the expiration dates of 
CHEMPACK drugs that were not stored according to FDAs 
requirements based on the potency testing results of drugs in the 
same lot that were stored as required.  A similar process is used to 
extend the expiration dates of non-CHEMPACK drugs in the        
$3.5-billion Strategic National Stockpile managed by CDC. 
 
40 We calculated average temperature as a substitute for mean kinetic temperature.  
  OEI-04-08-00040  CDCS CHEMPACK PROJECT:  NERVE AGENT ANTIDOTE STORAGE  18  
   
 R E C O M M E N D A T I O N S  
 
 
Surviving nerve agent exposure requires rapid treatment with nerve 
agent antidotes.  CDC has distributed over 1,900 CHEMPACK 
containers to participating States to allow quick response to a nerve 
agent release.  Each container is stocked with CHEMPACK drugs to 
treat 454 or 1,000 people, depending on the containers configuration.  
FDA has established minimum storage requirements to ensure that 
drugs are safe and effective.  However, CDC procedures did not 
ensure that CHEMPACK drugs stockpiled in States were stored 
according to these requirements.   
For example, CDCs CHEMPACK drug storage temperature 
requirement allows the drugs to be consistently stored under 
conditions that do not meet FDAs storage temperature requirements 
and CGMP.  In addition, CDC did not consistently implement a 
quality system to ensure that procedures necessary to store 
CHEMPACK drugs according to FDAs requirements were followed.  
Further, CDC procedures allow CHEMPACK drugs to inappropriately 
receive extended expiration dates under SLEP.   
Although we did not assess non-CHEMPACK assets directly, we did 
review CDC procedures that pertain to other assets managed by the 
Strategic National Stockpile.  These findings raise concerns about 
whether similar vulnerabilities also apply to other stockpiled CDC 
assets, i.e., non-CHEMPACK drugs in the $3.5-billion Strategic 
National Stockpile, because all assets share the same quality system 
and similar SLEP procedures. 
To address our findings, we recommend that CDC: 
Seek FDA guidance on whether CHEMPACK drugs that have received 
extended expiration dates under SLEP are appropriate for use 
CDC cannot demonstrate that all CHEMPACK drugs that have 
received extended expiration dates were stored under the conditions 
required by FDA.  For this reason, CDC should provide the necessary 
drug storage information to FDA officials so that they can determine 
whether the drugs are appropriate for use, should be destroyed, or 
should undergo additional potency testing.  
 
  OEI-04-08-00040  CDCS CHEMPACK PROJECT:  NERVE AGENT ANTIDOTE STORAGE  19  
   
R E C O M M E N D A T I O N S  
Revise its CHEMPACK project SLEP procedures to comply with FDA 
requirements 
CDC should coordinate with FDA to revise its SLEP procedures for 
the CHEMPACK project so that they comply with program 
requirements.  CDC should also consider reviewing the SLEP 
procedures for other CDC drugs under SLEP, i.e.,  
non-CHEMPACK drugs included in the Strategic National Stockpile 
managed by CDC.  This will ensure that only drugs that are stored 
according to FDAs requirements receive extended expiration dates.  
Revise its CHEMPACK drug storage temperature requirements to 
comply with FDA requirements  
CDC should change its storage temperature requirements for 
CHEMPACK drugs to 6877F with excursions permitted up to 86F 
and down to 59F provided that the calculated mean kinetic 
temperature does not exceed 77F.  This change would also require 
CDC to develop a method for calculating and regularly monitoring the 
mean kinetic temperature of CHEMPACK drug containers.  CDC 
should seek FDA guidance to ensure that the method used to 
calculate mean kinetic temperature is appropriate for the long-term 
storage of CHEMPACK drugs. 
Ensure that the CHEMPACK projects quality system meets CGMP 
requirements for drug storage 
CDC should conduct a complete review of its Strategic National 
Stockpile quality system and coordinate with FDA or other CGMP 
experts to ensure that CHEMPACK drugs are stored under conditions 
that will maintain their highest level of quality.  According to FDA, 
the CGMP provisions most applicable to the CHEMPACK project are 
included in 21 CFR  211 and 205.50.  At a minimum, CDC should 
adhere to its procedures of taking at least three daily temperature 
readings for each CHEMPACK container, monitor Sensaphone 
records for missing temperature readings and anomalies, and 
investigate the causes when they occur.  In addition, CDC could 
consider seeking guidance from FDA as to whether taking a minimum 
of three daily temperature readings is sufficient.  CDC should also 
implement quality system procedures that include maintaining 
complete and accurate temperature records.  This would include 
validating the computer that stores Sensaphone readings and 
conducting fully documented Sensaphone calibrations.  Further, 
DSNSs Quality Control Unit should evaluate selected CHEMPACK 
drug storage sites and review CHEMPACK-related documents such 
  OEI-04-08-00040  CDCS CHEMPACK PROJECT:  NERVE AGENT ANTIDOTE STORAGE  20  
   
R E C O M M E N D A T I O N S  
as Sensaphone calibration records, incident tickets, and corrective 
and preventive action reports.  Finally, CDC should coordinate with 
FDA to review the requirement for States to maintain the humidity 
level of CHEMPACK drug storage sites below 60 percent.  If this 
review determines that such a requirement is necessary, CDC should 
start monitoring humidity in CHEMPACK drug storage sites.  If the 
requirement is not necessary, CDC should remove it from the 
CHEMPACK memorandum of agreement. 
AGENCY COMMENTS AND OFFICE OF INSPECTOR GENERAL 
RESPONSE 
CDC concurred with all four of our recommendations and stated that 
the reports findings provide important information regarding the 
adequacy of quality systems and procedures and CDC adherence to 
them at the time of the evaluation.  However, CDC noted that we did 
not evaluate the quality of CHEMPACK drugs and that our findings do 
not address the viability of these drugs.  CDC also noted that it has 
instituted a corrective action program to address our findings and 
recommendations and described actions it has taken.  That is, CDC 
stated that as of September 2008, it had instituted the calculation of 
mean kinetic temperature using an FDA-approved methodology for all 
CHEMPACK containers to ensure that the product is stored under the 
correct temperature conditions.  Additionally, CDC has retroactively 
calculated mean kinetic temperature for the same period as our 
evaluation and identified three CHEMPACK containers that FDA 
suggests may require additional testing to assure potency.  However, it 
is unclear from CDCs comments how it accounted for CHEMPACK 
containers that were missing temperature readings and documentation 
of temperature-recording device calibrations.   
In addition, CDC indicated that it plans to take other actions to address 
our findings and recommendations.  For example, CDC will develop a 
plan to sequester CHEMPACK drugs if their storage temperatures 
exceed allowable mean kinetic temperature values and seek FDA 
testing and guidance for these drugs.  Further, CDC is evaluating the 
feasibility of increasing the number of temperature readings taken to 
increase the confidence in fielded products.  CDC is also outlining steps 
to retrospectively validate the Sensaphone computer system. 
Finally, CDC stated that our report did not evaluate the overall 
Strategic National Stockpile program and therefore should not imply 
that problems exist with Strategic National Stockpile non-CHEMPACK 
  OEI-04-08-00040  CDCS CHEMPACK PROJECT:  NERVE AGENT ANTIDOTE STORAGE  21  
   
R E C O M M E N D A T I O N S  
assets.  Nevertheless, CDC has begun an assessment of how best to 
initiate an independent review of its quality system and other 
procedures relative to CHEMPACK containers, and the rest of the 
Strategic National Stockpile assets, to ensure compliance with FDA 
requirements.   
We support CDCs efforts to address these findings and encourage it to 
continue making progress in these areas.  We made technical changes to 
the report based on CDCs comments.  For the full text of CDCs 
comments, see Appendix D.   
  OEI-04-08-00040  CDCS CHEMPACK PROJECT:  NERVE AGENT ANTIDOTE STORAGE  22  
   
 A P P E N D I X   A  
 
 
The United States Pharmacopeia Definition of Controlled Room 
Temperature 
 
  A temperature maintained thermostatically that encompasses the 
usual and customary working environment of 68 degrees Fahrenheit 
(68F) to 77F that results in a mean kinetic temperature calculated 
to be not more than 77F and that allows for excursions between 59F 
and 86F that are experienced in pharmacies, hospitals, and 
warehouses.  Provided the mean kinetic temperature remains in the 
allowed range, transient spikes up to 104F are permitted as long as 
they do not exceed 24 hours.  Spikes above 104F may be permitted if 
the manufacturer so instructs.  Articles may be labeled for storage at 
controlled room temperature or at up to 77F, or other wording 
based on the same mean kinetic temperature.  The mean kinetic 
temperature is a calculated value that may be used as an isothermal 
storage temperature that simulates the nonisothermal effects of 
storage temperature variations. 
An article for which storage at controlled room temperature is 
directed may, alternatively, be stored and distributed in a cool place, 
unless otherwise specified in the individual monograph or on the 
label.41, 42 
 
41 Cool temperatures are those between 59F and 68F. 
42 This definition is reproduced verbatim with the exception that the temperatures in the 
original version are in Celsius.  
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 A P P E N D I X   B  
 
 
Methodology for Calculating Average Temperature 
 
To calculate average temperature of the 967 CHEMPACK containers 
that had at least three daily temperature readings, we performed the 
following calculation for each container: 
 
1. for each sequential pair of temperature readings, we multiplied 
the duration of time between readings by the average of the two 
temperatures;43 
2. added all of the values from step one; and 
3. divided the sum from step two by the total duration of time the 
container was in storage. 
 
For example, if a container was stored at 74 degrees Fahrenheit (F) 
at 12 a.m. day 1, 76F at 8 a.m. day 1, 84F at 4 p.m. day 1, and 74F 
at 12 a.m. day 2, the average temperature using our methodology 
equals 78F, i.e., (75F x 8 hours) + (80 x 8 hours) + (79F x 8 hours) 
= 1872 / 24 hours = 78F. 
 
 
43 Not all containers had the same number of temperature readings because 
Sensaphones take temperature readings more frequently than every 8 hours when a 
containers storage temperature falls outside of the CDC-established storage range. 
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 A P P E N D I X   C  
 
 
Cumulative Time CHEMPACK Containers Were Maintained 
Above 77F 
 
The table below shows the cumulative time that all 967 selected 
containers that had at least three daily Sensaphone readings, in 
accordance with Centers for Disease Control and Prevention 
procedures, for the 1-year period we reviewed were maintained above 
the storage range of 68 degrees Fahrenheit (68F) to 77F for 
CHEMPACK drugs, and the corresponding number and percentage of 
containers. 
 
 
CHEMPACK Containers Maintained Above the Storage 
 
Temperature Range  
 
Cumulative Time Above 77F  Number of  Percentage of Selected 
Containers  Containers (n=967)** 
 
8 hours to 1 day  52  5% 
 
Over 1 day to 1 week  114  12% 
  Over 1 week to 1 month*  78  8% 
Over 1 month to 3 months  70  7% 
 
Over 3 months to 6 months  25  3% 
  Over 6 months  12  1% 
   Total  351  36% 
 
* We define a month as a total of 30 days. 
  ** Percentages are rounded to the closest whole number.  
Source:  Office of Inspector General analysis of Sensaphone temperature readings of CHEMPACK 
 
containers. 
 
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 A P P E N D I X ~ D  
 
          AGENCY COMMENTS 
 
 
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A P P E N D I X ~ D  
 
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Page 5-Daniel R. Levinson 
 	 DSNS 110] Equipment Services and Preventive Maintenance Standard Operating 
Procedures (SOP) outlines the Sensaphone and equipment preventive maintenance 
progrmn which includes calibration and documentation through service records. This 
SOP is currcntly being revised to require the review ofcalibration records by the SNS 
Quality Control Unit. 
 	 Based on dialogue with FDA, CDC will determine if any further modifications to Project 
Area MOAs related to temperature controls are needed.  CDC will modify SOPs and 
adjust monitoring systems to ensure CHEMPACK is compliant with any new 
temperature monitoring requirements. 
We appreciate your consideration ofthe comments contained in this memo as you develop the 
final report. We are happy to discuss any of these comments with you.  Please direct any 
questions regarding these comments to Mr. Shaun Ratliff by telephone at (404) 639-2809, or by 
e-mail at iggao@cdc.gov. 
Thomas R. Frieden, M.D.,M.P.H. 
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 A C K N O W L E D G M E N T S  
 
 
This report was prepared under the direction of Dwayne F. Grant, 
Regional Inspector General for Evaluation and Inspections in the 
Atlanta regional office.  Mary-Elizabeth Harmon served as the team 
leader for this study, and Gerius Patterson served as the Lead Analyst.  
Other principal Office of Evaluation and Inspections staff from the 
Atlanta regional office who contributed to the report include Peggy 
Daniel, Jaime Durley, and Sarah Glowa-Kollisch; central office staff 
who contributed include Talisha Searcy.   
 
  OEI-04-08-00040  CDCS CHEMPACK PROJECT:  NERVE AGENT ANTIDOTE STORAGE  31