D

OFFICE OF 

INSPECTOR GENERAL 

epartment of Health and Human Services

 

Daniel R. Levinson 

Inspector General 

December 2009 

OEI-04-08-00040 

 

 CDC’S CHEMPACK PROJECT: 

NERVE AGENT ANTIDOTE STORAGE 
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 OIG’s 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. 
 

 EXECUTIVE SUMMARY 

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 container’s 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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EXECUTIVE SUMMARY 

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 (68°F)–77°F 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 77°F. 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 FDA’s 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 FDA’s requirements. 

We reviewed CDC and FDA documents and interviewed CDC and 

FDA officials to assess the extent to which CDC’s 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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EXECUTIVE SUMMARY 

not investigate and document most of the missing temperature 

readings. 

CDC’s storage requirements for CHEMPACK drugs were not 

consistent with FDA’s storage requirements. CDC’s procedures 

permitted CHEMPACK drugs to be stored between 59°F and 86°F. 

The storage temperature range required by FDA is 68–77°F with brief 

excursions permitted up to 86°F and down to 59°F, provided that the 

calculated mean kinetic temperature does not exceed 77°F. 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 77°F. 

Nine percent of selected CHEMPACK containers were not stored 

according to FDA’s 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 77°F 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 1°F or more above 

the mean kinetic temperature permitted by FDA (i.e., at or above 

78°F) for at least 1 month. In addition, 1 percent (12 of 967) of 

selected containers had an average temperature at or above 78°F 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. 

CDC’s 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 FDA’s 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, 

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EXECUTIVE SUMMARY 

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 container’s 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, CDC’s SLEP 

procedures do not comply with FDA’s 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 project’s quality system meets CGMP 

requirements for drug storage. 

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v

EXECUTIVE SUMMARY 

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 CDC’s 

comments how it accounted for CHEMPACK containers that were 

missing temperature readings and documentation of temperaturerecording 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 CDC’s efforts to address these findings and encourage it to 

continue making progress in these areas. We made technical changes to 

the report based on CDC’s comments. 
 TABLE OF CONTENTS 

EXECUTIVE SUMMARY .....................................i

INTRODUCTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 

FINDINGS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 

 Almost one-quarter of CHEMPACK containers did not have 

 at least three daily temperature readings in accordance 

 with CDC procedures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 

 CDC’s storage requirements for CHEMPACK drugs were not 

 consistent with FDA’s storage requirements . . . . . . . . . . . . . . . . 13 

 Nine percent of selected CHEMPACK containers were not 

 stored according to FDA’s storage requirements for at least 

 1 month . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 

 CDC did not consistently implement quality system 

 procedures in the CHEMPACK project . . . . . . . . . . . . . . . . . . . . . 15 

 CDC’s procedures allowed CHEMPACK drugs to inappropriately 

 receive extended expiration dates under SLEP . . . . . . . . . . . . . . . 17 

RECOMMENDATIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 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 77°F. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 

 D: Agency Comments. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26 

ACKNOWLEDGMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
 

 INTRODUCTION 

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 Areas—the 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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INTRODUCTION 

deadly effects of nerve agents.3 Cumulative funding for the 

CHEMPACK project is estimated to exceed $100 million during fiscal 

years 2009–2013.4 

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 container’s 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 CDC’s 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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INTRODUCTION 

These stocked containers cost at least $83 million—approximately 

$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 container’s 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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INTRODUCTION 

temperature range of 68 degrees Fahrenheit (68°F) to 77°F. 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 59°F and as high as 86°F, 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 77°F. 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 68–77°F 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 77°F 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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INTRODUCTION 

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. 

CDC’s 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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INTRODUCTION 

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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INTRODUCTION 

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. 

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INTRODUCTION 

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, OIG’s 

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. 

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INTRODUCTION 

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. 

ified by FDA. 

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 68–77°F 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 container’s mean kinetic temperature 

above the 77°F limit spec

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 

container’s 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 77°F over the course of the entire 1-year period we reviewed. 

31 To be conservative, we did not include periods of time when a container’s temperature 

was above 110°F because these temperature readings were questionable and/or we received 

CDC documentation explaining that they were not valid. 

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INTRODUCTION 

1-year period we reviewed.32, 33 We then counted the number of 

months that each container had an average temperature of 78°F or 

higher, i.e., 1 degree or more above the mean kinetic temperature 

limit of 77°F 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 container’s 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 container’s 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. 

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INTRODUCTION 

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.

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 FINDINGS 

Almost one-quarter of CHEMPACK containers 

did not have at least three daily temperature 

readings in accordance with CDC procedures 

Twenty-three percent (288 of 

1,255) of the CHEMPACK 

containers in State storage sites 

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 

Readings in a 1-Year Period* 

Number of Containers Percentage of 

Containers (n=1,255)** 

0.1–1% 248 20%

Over 1–5% 6 0% 

Over 5–10% 4 0% 

Over 10–25% 7 1% 

Over 25–50% 13 1% 

Over 50–75% 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. 

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FINDINGS 

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. 

CDC’s storage requirements for CHEMPACK 

drugs were not consistent with FDA’s 

storage requirements 

FDA requires CHEMPACK 

drugs to be stored primarily 

within the 68–77°F range, with 

excursions permitted down to 

59°F and up to 86°F provided that the calculated mean kinetic 

temperature does not exceed 77°F.37 

CDC requires CHEMPACK drugs to be stored in a 59–86°F range. 

This requirement allows States to indefinitely store CHEMPACK 

drugs in temperature ranges (i.e., 59–67°F and 78–86°F) 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 77°F. 

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 77°F were held according 

to FDA requirements. 

Nine percent of selected CHEMPACK containers 

were not stored according to FDA’s storage 

requirements for at least 1 month 

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We analyzed the temperature 

readings of the 967 

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. 
 

FINDINGS 

and determined that over one-third of these containers experienced 

temperatures above 77°F for varying amounts of time.38 Specifically, 

36 percent (351 of 967) of these containers experienced temperatures 

above 77°F 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 78°F) for at least 1 month.39 In addition, 

1 percent (12 of 967) of the selected containers had an average 

temperature at or above 78°F for at least 6 months. Three of these 

containers had an average monthly temperature at or above 78°F 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 78°F and the 

corresponding number and percentage of containers. 

Table 2: CHEMPACK Containers With a Monthly Average 

Temperature At or Above 78°F 

Number of Months at or 

Above 78°F Number of Containers 

Percentage of Selected 

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 77°F 

39 Monthly average temperatures did not exceed 84°F. 

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FINDINGS 

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 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. 

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FINDINGS 

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., 59–86°F), 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 CDCestablished 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 container’s 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 

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FINDINGS 

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 project’s inception in 2004. In addition, DSNS’s 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. 

CDC’s procedures allowed CHEMPACK drugs 

to inappropriately receive extended 

expiration dates under SLEP 

 

 

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CDC procedures do not 

ensure that CHEMPACK 

drugs stored outside of 

FDA’s 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 77°F 

upper storage limit required by FDA for cumulative periods of 
 

FINDINGS 

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 78°F) 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 FDA’s 

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. 

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 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 container’s 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’s CHEMPACK drug storage temperature 

requirement allows the drugs to be consistently stored under 

conditions that do not meet FDA’s 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 FDA’s 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. 

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RECOMMENDATIONS 

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 FDA’s 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 68–77°F with excursions permitted up to 86°F 

and down to 59°F provided that the calculated mean kinetic 

temperature does not exceed 77°F. 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 project’s 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, 

DSNS’s Quality Control Unit should evaluate selected CHEMPACK 

drug storage sites and review CHEMPACK-related documents such 

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RECOMMENDATIONS 

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 report’s 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 CDC’s 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 

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RECOMMENDATIONS 

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 CDC’s efforts to address these findings and encourage it to 

continue making progress in these areas. We made technical changes to 

the report based on CDC’s comments. For the full text of CDC’s 

comments, see Appendix D. 

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 APPENDIX 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 

(68°F) to 77°F that results in a mean kinetic temperature calculated 

to be not more than 77°F and that allows for excursions between 59°F 

and 86°F that are experienced in pharmacies, hospitals, and 

warehouses. Provided the mean kinetic temperature remains in the 

allowed range, transient spikes up to 104°F are permitted as long as 

they do not exceed 24 hours. Spikes above 104°F may be permitted if 

the manufacturer so instructs. Articles may be labeled for storage at 

“controlled room temperature” or at “up to 77°F,” 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 59°F and 68°F. 

42 This definition is reproduced verbatim with the exception that the temperatures in the 

original version are in Celsius. 

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 APPENDIX 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, 76°F at 8 a.m. day 1, 84°F at 4 p.m. day 1, and 74°F 

at 12 a.m. day 2, the average temperature using our methodology 

equals 78°F, i.e., (75°F x 8 hours) + (80° x 8 hours) + (79°F x 8 hours) 

= 1872 / 24 hours = 78°F. 

43 Not all containers had the same number of temperature readings because 

Sensaphones take temperature readings more frequently than every 8 hours when a 

container’s storage temperature falls outside of the CDC-established storage range. 

 O E I - 0 4 - 0 8 - 0 0 0 4 0 C D C ’ S CHEMPACK P ROJECT: NERVE A GENT ANTIDOTE S TORAGE 24
 

 APPENDIX C 

 O E I - 0 4 - 0 8 - 0 0 0 4 0 C D C ’ S CHEMPACK P ROJECT: NERVE A GENT ANTIDOTE S TORAGE 25

Cumulative Time CHEMPACK Containers Were Maintained 

Above 77°F 

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 (68°F) to 77°F for 

CHEMPACK drugs, and the corresponding number and percentage of 

containers. 

CHEMPACK Containers Maintained Above the Storage 

Temperature Range 

Cumulative Time Above 77°F Number of 

Containers 

Percentage of Selected 

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.
 

 APPENDIX~D 

 AGENCY COMMENTS

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APPENDIX~D 

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APPENDIX~D 

 O E I - 0 4 - 0 8 - 0 0 0 4 0 C D C ’ S CHEMPACK P ROJECT: NERVE A GENT ANTIDOTE S TORAGE 28
 

APPENDIX~D 

 O E I - 0 4 - 0 8 - 0 0 0 4 0 C D C ’ S CHEMPACK P ROJECT: NERVE A GENT ANTIDOTE S TORAGE 29
A P PEN 0 x D 

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 of calibration 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. 

OEI·04·08·00040 CDC's CHEMPACK PROJECT: NERVE AGENT ANTIDOTE STORAGE 30 
 

 O E I - 0 4 - 0 8 - 0 0 0 4 0 C D C ’ S CHEMPACK P ROJECT: NERVE A GENT ANTIDOTE S TORAGE 31

 ACKNOWLEDGMENTS 

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.