Tamu Fall From Grace


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Discussion of Texas A&M Select Agent Program compliance issues

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Tamu Fall From Grace

  1. 1. Fall From Grace Texas A&M University’s Biodefense & Infectious Disease Research Labs Presented By Malcolm Smith November 1 st 2007
  2. 2. Presentation Outline <ul><li>Select Agents: characteristics and Select </li></ul><ul><li>Agent Rule </li></ul><ul><li>US High Containment Suites </li></ul><ul><li>Discussion of BSL-3 design and practices </li></ul><ul><li>Biodefense Lab watchdog organization: </li></ul><ul><li>Sunshine Project, Freedom of Information </li></ul><ul><li>Act </li></ul><ul><li>Texas A & M University (TAMU): location, background and biodefense efforts </li></ul><ul><li>Brucella exposure </li></ul><ul><li>Coxiella exposure </li></ul><ul><li>CDC Inspections </li></ul><ul><li>Timeline of events </li></ul>
  3. 3. Characteristics of a Select Agent <ul><ul><li>Long Term effects </li></ul></ul><ul><ul><li>Route of exposure </li></ul></ul><ul><ul><li>Degree of pathogenicity </li></ul></ul><ul><ul><li>Acute morbidity </li></ul></ul><ul><ul><li>Acute mortality </li></ul></ul><ul><ul><li>Communicability </li></ul></ul><ul><ul><li>Developed for use as a bioweapon </li></ul></ul><ul><ul><li>Ability to genetically manipulate </li></ul></ul><ul><ul><li>Available treatments </li></ul></ul><ul><ul><li>Vulnerable populations </li></ul></ul><ul><ul><li>Status of immunity </li></ul></ul><ul><ul><li>Ease of production </li></ul></ul>Why are they considered dangerous
  4. 4. Select Agent Rule <ul><li>42 CFR 73 Possession, Use and Transfer of Select Agents and Toxins, December 13, 2002 </li></ul><ul><ul><li>Requires USDA and HHS to work together and </li></ul></ul><ul><ul><li>consolidate regulations </li></ul></ul><ul><ul><li>Requires a Risk Assessment to be performed by </li></ul></ul><ul><ul><li>DOJ on all Select Agent Users </li></ul></ul><ul><ul><li>Requires the development of a biosecurity plan </li></ul></ul><ul><ul><li>Requires training to be provided to all Select </li></ul></ul><ul><ul><li>Agent users and non-users </li></ul></ul><ul><li>http://www.cdc.gov/od/sap/docs/42cfr73.pdf </li></ul>Explanation
  5. 5. Security Risk Assessment (SRA) <ul><li>Requirements : </li></ul><ul><ul><li>Has authority from entity to conduct select agent work </li></ul></ul><ul><ul><ul><li>Completes Patriot Act </li></ul></ul></ul><ul><ul><ul><li>Has a need to access select agents (i.e. is listed </li></ul></ul></ul><ul><ul><ul><li>on a Institutional Biosafety Committee approved </li></ul></ul></ul><ul><ul><ul><li>protocol) </li></ul></ul></ul><ul><ul><ul><li>Files fingerprint paperwork with FBI </li></ul></ul></ul><ul><ul><ul><li>Granted a SRA approval (5 years) thru the FBI </li></ul></ul></ul><ul><ul><ul><li>with CDC/USDA concurrence </li></ul></ul></ul>How is this obtained?
  6. 6. Components of a Select Agent Program <ul><li>Responsible Official (RO) / </li></ul><ul><li>Alternate Responsible Official </li></ul><ul><li>Biosecurity Plan </li></ul><ul><ul><li>Incident Control Plan/IT Security </li></ul></ul><ul><li>Biosafety Manual </li></ul><ul><li>Inventory Control Methods </li></ul><ul><li>Physical Security </li></ul><ul><li>Documentation </li></ul><ul><li>Tracking </li></ul><ul><li>Training </li></ul>Key Elements
  7. 7. Bio-Safety Level The biosafety level assigned to an agent is based on the activities typically associated with the growth and manipulation of the quantities and concentrations of infectious agents required to accomplish identification or typing. If activities with clinical materials pose a lesser risk to personnel than those activities associated with manipulation of cultures, a lower biosafety level is recommended. On the other hand, if the activities involve large volumes and/or concentrated preparations (&quot;production quantities&quot;), or manipulations which are likely to produce aerosols or which are otherwise intrinsically hazardous , additional personnel precautions and increased levels of primary and secondary containment may be indicated. BMBL 4 th Edition Explanation
  8. 8. High Containment Lab Locations Locations of Major BSL-3 and Known BSL-4 Labs
  9. 9. Bio-Safety Level 3 <ul><li>The design shall incorporate the following engineering elements: </li></ul><ul><ul><li>Facility must have effectively gas-tight walls, ceilings </li></ul></ul><ul><ul><li>and floors (i.e. capable of containing decontamination </li></ul></ul><ul><ul><li>gas during decontamination process for a period </li></ul></ul><ul><ul><li>according to EH&S specifications) </li></ul></ul><ul><ul><li>Air balance shall be set so air from low hazard rooms </li></ul></ul><ul><ul><li>flow into rooms with higher hazard </li></ul></ul><ul><ul><li>Room construction shall be high quality with special </li></ul></ul><ul><ul><li>consideration given to joints, finishes and penetrations </li></ul></ul><ul><ul><li>Work surfaces, floors, walls and ceilings shall be </li></ul></ul><ul><ul><li>designed, constructed, and finished to facilitate easy </li></ul></ul><ul><ul><li>cleaning and decontamination </li></ul></ul><ul><ul><li>Enhanced Security shall be provided </li></ul></ul><ul><ul><li>UC Environmental Health and Safety; Laboratory Safety Design Guide </li></ul></ul>Basic Laboratory Design
  10. 10. Bio-Safety Level 3 <ul><li>Access to the laboratory is limited or restricted at the discretion of the laboratory director </li></ul><ul><li>Persons wash hands after handling infectious materials, after removing gloves </li></ul><ul><li>Eating, drinking, smoking, handling contact lenses and applying cosmetics are not permitted in the laboratory </li></ul><ul><li>Mechanical pipetting devices are used </li></ul><ul><li>Safe handling of sharps are instituted </li></ul><ul><li>All procedures are performed carefully to minimize aerosols </li></ul><ul><li>Work surfaces are decontaminated at least once a day and after a spill of viable material </li></ul><ul><li>All cultures, stocks and other regulated wastes are decontaminated before disposal by an approved decontamination method, such as autoclaving </li></ul><ul><li>An insect and rodent control program is in effect </li></ul>Standard Microbiological Practices
  11. 11. Bio-Safety Level 3 <ul><li>Laboratory doors are kept closed when experiments are in progress </li></ul><ul><li>The laboratory director controls access to the laboratory and restricts access to persons whose presence is required for program and support purposes </li></ul><ul><li>When infectious materials are present in the laboratory, a hazard warning sign, incorporating the universal biohazard sign is posted on all laboratory access doors. The hazard sign identifies the agent, lists contact information for responsible persons, indicates special requirements for entering the lab and personal protective measures </li></ul><ul><li>A biosafety manual specific to the laboratory is prepared or adopted by the laboratory director </li></ul>Special Practices
  12. 12. Bio-Safety Level 3 <ul><li>Laboratory and support personnel receive appropriate training on the potential hazards associated with the work involved. Personnel receive annual updates or additional training as necessary for procedural changes </li></ul><ul><li>The laboratory director is responsible for ensuring that before working with BSL-3 type organisms, all personnel demonstrate proficiency in standard microbiological practices and techniques </li></ul><ul><li>Needles and syringes or other sharp instruments should be restricted in the laboratory for use only when there is no alternative </li></ul><ul><li>All open manipulations involving infectious materials are conducted in biological safety cabinets </li></ul><ul><li>Spills and accidents that result in overt or potential exposures to infectious materials are immediately reported to the laboratory director </li></ul>Special Practices
  13. 13. The Sunshine Project Biodefense Research Watchdog
  14. 14. The Sunshine Project The Sunshine Project is an international non-governmental organization dedicated to upholding prohibitions against biological warfare and, particularly, to preventing what it sees as military abuse of biotechnology . With offices in Austin, TX and Hamburg, Germany, the Sunshine Project works by exposing research on biological and chemical weapons . Typically, it accesses documents under the Freedom of Information Act and other open records laws, publishing reports and encouraging action to reduce the risk of biological warfare . It tracks the construction of high containment laboratory facilities and the dual-use activities of the U.S. biodefense program. http://www.sunshine-project.org/ Background
  15. 15. Noteworthy Individuals Director of the US Office of the Sunshine Project. Holds two Master's degrees from the University of Texas at Austin and worked on biotechnology-related policy since 1993. Hammond is a member of the Pugwash Study Group on the Chemical and Biological Weapons Conventions. Hammond directs the Sunshine Project in the US and manages its research program on biodefense, incapacitants, and other issues Edward Hammond
  16. 16. Freedom of Information Act <ul><ul><li>The Freedom of Information Act (FOIA), which can be found in Title 5 of the United States Code, section 552, was enacted in 1966 and generally provides that any person has the right to request access to federal agency records or information . All agencies of the Executive Branch of the United States Government are required to disclose records upon receiving a written request for them , except for those records (or portions of them) that are protected from disclosure by the nine exemptions and three exclusions of the FOIA. This right of access is enforceable in court, and it is supported at the administrative agency level by the &quot;citizen-centered and results-oriented approach&quot; of a presidential executive order (see below). </li></ul></ul><ul><ul><li>The FOIA does not, however, provide access to records held by Congress or the federal courts, by state or local government agencies, or by private businesses or individuals . </li></ul></ul><ul><ul><li>http://www.usdoj.gov/oip/referenceguidemay99.htm#intro </li></ul></ul>Definition
  17. 17. Texas A & M University <ul><li>College Station, and its sister city, Bryan, are located about 90 miles from Houston and Austin in the heart of the Brazos Valley in Central Texas </li></ul>Location
  18. 18. Texas A & M University <ul><li>373,000-square-foot facility </li></ul><ul><li>10,000 students on campus </li></ul><ul><li>150 fields of study </li></ul><ul><li>Research expenditures, as reported to the National Science </li></ul><ul><li>Foundation for fiscal year 2004 (the most recent reporting period), </li></ul><ul><li>totaled $520.9 million </li></ul><ul><li>2.5 million square feet of floor space used for research space and </li></ul><ul><li>supports 11,400 acres in the Research Valley </li></ul><ul><li>Ranked among the top 10 nationwide in number of science and </li></ul><ul><li>engineering doctoral degrees conferred annually </li></ul>Campus Information
  19. 19. Texas A & M University <ul><li>Biodefense focus areas will include </li></ul><ul><ul><li>epidemiologic modeling of infectious diseases </li></ul></ul><ul><ul><li>molecular epidemiology of infectious diseases </li></ul></ul><ul><ul><li>epidemiology of food-borne pathogens </li></ul></ul><ul><ul><li>bioinformatics/biostatistics </li></ul></ul><ul><ul><li>immunology and molecular biology/cell signaling </li></ul></ul><ul><li>Since 1998, infectious disease faculty have published 195 peer-reviewed manuscripts </li></ul><ul><li>Since 1998, more than 8 million in extramural grants on infectious diseases have been received by principal investigators </li></ul>Biodefense and Infectious Disease Department
  20. 20. Texas A & M University <ul><li>Research areas have included </li></ul><ul><ul><li>Spatial epidemiology of infectious diseases (Neospora </li></ul></ul><ul><ul><li>and Salmonella typhimurium ) </li></ul></ul><ul><ul><li>Field studies and bacterial molecular pathogenesis </li></ul></ul><ul><ul><li>( Salmonella typhimurium , Brucella spp ., Rhodococcus </li></ul></ul><ul><ul><li>equi , paratuberculosis), </li></ul></ul><ul><ul><li>Viral molecular pathogenesis (rotavirus, </li></ul></ul><ul><ul><li>coronaviruses, lentiviruses) </li></ul></ul><ul><ul><li>Molecular and genomic approaches to antimicrobial </li></ul></ul><ul><ul><li>resistance </li></ul></ul><ul><ul><li>Development and evaluation of diagnostic tests and </li></ul></ul><ul><ul><li>vaccines under field conditions. </li></ul></ul>Biodefense and Infectious Disease Department
  21. 21. The Incident
  22. 22. Brucellosis <ul><li>Acute form (<8 weeks from illness onset), </li></ul><ul><li>nonspecific and &quot;flu-like&quot; symptoms including </li></ul><ul><li>fever, sweats, malaise, anorexia, headache, </li></ul><ul><li>myalgia, and back pain </li></ul><ul><li>Undulant form (<1 year from illness onset), </li></ul><ul><li>symptoms include undulant fevers, arthritis, </li></ul><ul><li>and epididymo-orchitis in males; neurologic </li></ul><ul><li>symptoms may occur acutely in up to 5% of </li></ul><ul><li>cases </li></ul><ul><li>Chronic form (>1 year from onset), symptoms </li></ul><ul><li>may include chronic fatigue syndrome, </li></ul><ul><li>depression, and arthritis </li></ul>Clinical Features
  23. 23. Brucellosis <ul><li>Treatment can be difficult. </li></ul><ul><li>Doctors can prescribe effective antibiotics; </li></ul><ul><li>usually, doxycycline and rifampin are used in </li></ul><ul><li>combination for 6 weeks to prevent reoccuring </li></ul><ul><li>infection </li></ul><ul><li>Depending on the timing of treatment and </li></ul><ul><li>severity of illness, recovery may take a few </li></ul><ul><li>weeks to several months. </li></ul><ul><li>Mortality is low (<2%), and is usually </li></ul><ul><li>associated with endocarditis. </li></ul>Treatment
  24. 24. Brucella Exposure <ul><li>The infection incident occurred on 9 February 2006. </li></ul><ul><li>Several A&M researchers, were in a BSL-3 lab training in </li></ul><ul><li>the use of the Madison Aerosol Chamber. Supervising </li></ul><ul><li>the training was an A&M professor and inventor of the </li></ul><ul><li>chamber </li></ul><ul><li>Following a &quot;hot&quot; run that blew aerosolized brucella into </li></ul><ul><li>the chamber to expose mice, researchers began clean up </li></ul><ul><li>procedures </li></ul><ul><li>Following the stated protocol at the time, a researcher </li></ul><ul><li>&quot; cleaned the unit by climbing partially into the chamber </li></ul><ul><li>to disinfect it &quot; </li></ul><ul><li>A&M officials later concluded that the brucella bacteria </li></ul><ul><li>likely entered her body via her eyes as a result of this </li></ul><ul><li>improper procedure. </li></ul>What Happened
  25. 25. Brucella Exposure <ul><li>By April 2006, the researcher had &quot; been home sick </li></ul><ul><li>for several weeks. &quot; Nobody apparently suspected </li></ul><ul><li>brucellosis and eventually the researcher's personal </li></ul><ul><li>physician ordered blood tests and made the </li></ul><ul><li>diagnosis on about April 10 </li></ul><ul><li>On 15 April, the infected researcher began a heavy </li></ul><ul><li>treatment course including a week of intravenous </li></ul><ul><li>antibiotics followed by a 45-day course of two </li></ul><ul><li>additional antibiotic drugs </li></ul><ul><li>Just over a month later, new blood tests indicated </li></ul><ul><li>that the infection had passed. </li></ul>What Happened
  26. 26. Brucella Exposure <ul><li>Principal investigator communicates exposure to </li></ul><ul><li>TAMU officials ten days after communication with </li></ul><ul><li>researcher’s physician </li></ul><ul><li>Sunrise Project learns of exposure and asks TAMU </li></ul><ul><li>officials to release all paperwork on supposed </li></ul><ul><li>exposure in October of 2006 </li></ul><ul><li>TAMU officially reports exposure to CDC in April of </li></ul><ul><li>2007 </li></ul>What Happened
  27. 27. Madison Aerosol Chamber
  28. 28. Coxiella burnetii: Q-Fever <ul><li>Only about one-half of all people infected with </li></ul><ul><li>C. burnetii show signs of clinical illness </li></ul><ul><li>Two forms: Acute and Chronic </li></ul>
  29. 29. Coxiella burnetii: Q-Fever <ul><li>Acute cases of Q fever begin with sudden onset of one or more of the </li></ul><ul><li>following: </li></ul><ul><ul><li>High fevers (up to 104-105° F) </li></ul></ul><ul><ul><li>Severe headache, general malaise, myalgia, confusion, sore </li></ul></ul><ul><ul><li>throat, chills, sweats, non-productive cough, nausea, vomiting, </li></ul></ul><ul><ul><li>diarrhea, abdominal pain, and chest pain </li></ul></ul><ul><ul><li>Fever usually lasts for 1 to 2 weeks. </li></ul></ul><ul><ul><li>Weight loss can occur and persist for some time. </li></ul></ul><ul><ul><li>Thirty to fifty percent of patients with a symptomatic infection will </li></ul></ul><ul><ul><li>develop pneumonia. Additionally, a majority of patients have </li></ul></ul><ul><ul><li>abnormal results on liver function tests and some will develop </li></ul></ul><ul><ul><li>hepatitis </li></ul></ul><ul><ul><li>In general, most patients will recover to good health within </li></ul></ul><ul><ul><li>several months without any treatment </li></ul></ul><ul><ul><li>Only 1%-2% of people with acute Q fever die of the disease </li></ul></ul>Clinical Symptoms
  30. 30. Coxiella burnetii: Q-Fever <ul><li>Chronic Q fever is characterized by infection that persists for </li></ul><ul><li>more than 6 months </li></ul><ul><li>It’s uncommon but is a much more serious disease </li></ul><ul><li>Patients who have had acute Q fever may develop the chronic </li></ul><ul><li>form as soon as 1 year or as long as 20 years after initial </li></ul><ul><li>infection </li></ul><ul><li>A serious complication of chronic Q fever is endocarditis, </li></ul><ul><li>generally involving the aortic heart valves, less commonly the </li></ul><ul><li>mitral valve </li></ul><ul><li>Most patients who develop chronic Q fever have pre-existing </li></ul><ul><li>valvular heart disease or have a history of vascular graft </li></ul><ul><li>Transplant recipients, patients with cancer, and those with </li></ul><ul><li>chronic kidney disease are also at risk of developing chronic Q </li></ul><ul><li>fever </li></ul><ul><li>As many as 65% of persons with chronic Q fever may die of the </li></ul><ul><li>disease </li></ul>Clinical Symptoms
  31. 31. Coxiella Exposure <ul><li>Three researchers have blood titers analyzed for the </li></ul><ul><li>presence of Coxiella burnetii at University Occupational </li></ul><ul><li>Health Office in April of 2006 </li></ul><ul><li>All three researcher’s blood titers show high levels for </li></ul><ul><li>Coxiella burnetii </li></ul><ul><li>No clinical symptoms observed </li></ul><ul><li>Explanation of how researchers were exposed to </li></ul><ul><li>organism was never discovered </li></ul><ul><li>TAMU officials decide not to officially communicate to </li></ul><ul><li>CDC since they believed that high titers without </li></ul><ul><li>symptoms do not constitute a “release” of organism </li></ul><ul><li>TAMU officials decide to officially communicate to CDC </li></ul><ul><li>of high titer levels in April of 2007 </li></ul>What Happened
  32. 32. CDC Inspection Observations <ul><li>Major findings included: </li></ul><ul><li>TAMU performed unapproved Brucella work and unapproved Coxiella burnetii work in their laboratories (failure to submit amendments to CDC seeking permission) </li></ul><ul><li>All facility plans were in draft format and drills and exercises had not been conducted annually to test and evaluate effectiveness </li></ul><ul><li>RO did not conduct annual inspection of select agent rooms </li></ul><ul><li>Laboratory staff was noted wearing improper PPE </li></ul><ul><li>No evidence of baseline serum being collected </li></ul><ul><li>No effective medial surveillance program was established </li></ul><ul><li>Unauthorized access to select agents (non-SRA approved personnel) </li></ul><ul><li>No intra-entity procedure within security plan </li></ul><ul><li>No access records existed for room containing select access </li></ul><ul><li>Inventory discrepancies discovered, three missing vials of select agent </li></ul>
  33. 33. Incident Timeline <ul><li>February 9 th 2006 – Exposure to Brucella via cleaning of Madison Aerosol Chamber </li></ul><ul><li>April 10 th 2006 – PI informed by researcher of brucellosis disease </li></ul><ul><li>April 21 st 2006 – PI informs University of exposure </li></ul><ul><li>October 24 th 2006 – Sunshine Project files a Texas Public Information Act for release &quot; All records on possible or actual occupational exposures and/or laboratory-acquired infections with risk group 2 (RG2) or higher agents at TAMU, from 1 January 2000 through the present .“ </li></ul><ul><li>April 10 th 2006 – TAMU informs CDC of possible release of Select Agent (Form 3) </li></ul><ul><li>April 16 th 2007 – CDC meets with TAMU RO and ARO to review all documents, plans and training involved with Select Agent Program. They also conduct interviews and inspections of Select Agent rooms </li></ul><ul><li>April 20 th 2007 – CDC releases a “Cease and Desist Order” to TAMU relating to all experiments involving the room housing the aerosol chamber, all aerosol specific experimentations and all access of Select Agents to non-SRA approved individuals </li></ul><ul><li>May 4 th 2007 – CDC sends TAMU facility inspection report noting 21 observations during inspection </li></ul>
  34. 34. May 17 th 2007 – TAMU responds to CDC facility inspection report June July 18 th 2007 – Office of Inspector General notifies TAMU that they may be liable for civil penalties up to $750,000 for violating federal Select Agent Rule June 26 th 2007 – Sunshine Project Releases a report that three laboratorians were infected with Coxiella burnetti and noted high blood titers for the agent on April 3 rd 2006 June 30 th 2007 – CDC issues a “Cease and Desist Order” to TAMU for all Select Agent Work July 23 rd 2007 – CDC has a follow-up inspection of TAMU’s Select Agent Program August 17 th 2007 – TAMU proposes a settlement of $10,000 to the Office of the Inspector General for violation of Select Agent Rule August 31 st 2007 – CDC issues a Facility Inspection Report to TAMU citing 32 “observations” and asks TAMU to respond. Following TAMU response a follow-up inspection will be conducted to investigate facility Incident Timeline
  35. 35. Both the RO (August 2007) and the ARO/Biosafety Officer (September 2007) resign their post at TAMU Incident Timeline
  36. 36. Questions/Comments