Infectious Disease Control Law of Japan and Biorisk management in NIID July 10, 2008, Seoul, Korea NIID 国立感染症研究所 Kazuyoshi SUGIYAMA National Institute of Infectious Diseases Division of Biosafety Control and Research
Historical Background for Establishment of Countermeasure for Biohazard(Biosafety)in Japan NIH (NIID) 1975 Biohazard committee 1976 Classification of pathogen by risk factor 1976 Biohazard material 1978 Biohazard material 1981 Regulations 1976 International Infectious disease research work (Ministry of Health) 1976 Overseas investigation 1979 Maximum containment hospital 1981 Maximum Safety Lab.(NIH) 1979 Recombinant DNA experiment guide line 1993 Biosafety Guideline (Virology Society, Japan) 1993 Regulations for handling pathogen (Animal Health, Ministry of Agriculture) 1998 Safety manual for micro-organism research in universities (M. Education and Science) 1999 Biosafety Guideline (Bacteriology Society, Japan), Enforcement of Infectious Disease Control Law (IDCL) 2002 Japanese Biological Safety Association (JBSA) established 2004 Legislation regarding recombinant DNA experiment 2006 Legislation for handling, possession of pathogens (select agents) 2007 Enforcement from June 1
Laboratory Security and Emergency Response
Outline of the Subway Sarin Attack Known at - 8 : 09 a.m on March 20, 1995 (1st 119 call) Where occurred: Within the premises of the subway in Tokyo Method employed in the crime: To prick a bag containing sarin liquid (about 900ml) with the tip of an umbrella Number of deaths -12 Number of injured -5,501 *Indiscriminate terrorist attack, using sarin gas, a deadly poison *Occurred within the premises of the subway, a closed space *Sarin gas was dispersed in multiple terrorist attacks
US Laws and Regulations 1996 - Antiterrorism Act Called for a list of select agents from Department of Health and Human Services (HHS) Imposed controls on transport of select agents CDC s first list included 42 pathogens 2001 - PATRIOT Act Possession and transport of select agents regulated (Certain individuals can t handle hazardous materials) 2002 - Bioterrorism Prevention Act Gave regulatory authority to both HHS and USDA Select agent list expanded to include animal and plant pathogens Required reporting of all possession and transfer of select agents 2002-2005 HHS/USDA Interim Final Rule and Final Rule Select agent provisions developed and implemented in stages from December 2002 to April 2005. All individuals with access to select agents must be approved by HHS Current select agent list contains 81 pathogens / toxins (50 from HHS, 51 from USDA, with 20 pathogens / toxins appearing on both lists) http://www.selectagents.gov/programbackground.htm http://www.biosecurity.sandia.gov/main.html?subpages/legislation.html http://www.hhs.gov/asl/testify/2007/10/t20071004b.html
Roles and Responsibilities Maintain select agent list Inspection of facilities Track transport and possession of agents Department of Health and Human Services (HHS) & Department of Agriculture (USDA) Background checks of individuals and institutions Department of Justice (DOJ)
I. Law for pathogen control in Japan Communicable disease prevention law for domestic animals :Ministry of Agriculture, Forestry and Fisheries laws regarding prohibition of import of pathogens for enzootic, communicable diseases Trade control law : Ministry of Economy, Trade and Industry laws regarding prohibition of export of pathogens and toxins
Handling of pathogens in Japan RI experiment:enacted in 1957 The law concerning prevention of radiation hazards due to radioisotopes, etc. Recombinant DNA experiment: law enacted in 19th February 2004 to secure biological diversity Pathogen experiment: except select agents by Infectious disease control law (2007), self- control by individual institutes (hospitals, universities, governmental institutes, companies) is conducted under the regulations for handling pathogenic agents
Laws Concerning Infectious Disease Surveillance Infectious Disease Control Law (IDCL) Law Concerning the Prevention of Infectious Diseases and Medical Care for Patients of Infections enacted in April 1999, abrogating the Communicable Disease Prevention Law, the Venereal Disease Prevention Law and the AIDS Prevention Law, this law was amended in November 2003 and December 2006 various infectious diseases Tuberculosis Prevention Law enacted in 1951, - tuberculosis By the revision of IDCL in 2006, this law was abrogated and integrated to IDCL and enacted in April 2007 Food Hygiene Law enacted in 1948, - food poisonings
Novel Concepts of the Infectious Disease Control Law (April 1999) Health administrations that implement measures in advance Categorizing target infectious diseases Reconstructing medical management and medical expense payment systems Hospitalization procedures in accordance with human rights Reconsidering measures against the spread of infectious diseases Strengthening measures against infectious diseases of animal origin Promoting international cooperation
Categorization of Infectious diseases: April 1999 Cat. Infectious disease (Infect. dis.) Definition Measures I II 5:Ebola HF, Crimea Congo HF, Marburg disease, Lassa F, Plague 6:Poliomyelitis, Diphtheria, Cholera, Dysentery, Typhoid fever, Paratyphoid fever From total point of view, extremely high risk, human to human infection High risk, human to human infection III 1:Enterohaemorrhagic E. coli infection Not high risk, potential mass epidemic, human to human infection IV V VI 33:All case report;amoeba dysentery, Q fever, Cryptosporidium infection, AIDS, Syphilis, Tetanus, Anthrax, Botulism, Brucellosis, and others 28:Fixed point observation;influenza, Measles, Genital chlamidiosis and Pharyngoconjunctival fever and others Infect. dis. designated with Government ordinance designation is limited within one year Infect. dis. Conducted with emergency treatment by Governor according to the technical direction by minister Infect. Dis. prevented outbreak/expansion by provide information to Medical person Potentially affect human health Known infect. Dis., Equivalent risk of Cat.I to Cat. III Un-known infect. Dis., Extremely high risk Hospitalization (As a rule), Treatments for disinfection Hospitalization (Case by case), Treatments for disinfection Restriction for specific work, Treatments for disinfection Collection, analysis, announcement of information According to Cat.I to Cat.III According to Cat.I
Revision of the Infectious Disease Control Law (Nov. 2003) Strengthening the role of the national government in an emergency, enabling it to conduct active investigation Strengthening control strategies against infectious diseases of animal origin Reconsidering target diseases of the Infectious Disease Control Law and their categories Closer cooperation with the quarantine system
Notifiable Diseases (category, hospitalization) (Nov. 2003) Cat. No. Diseases Transmission Hospital I 7 II 6 VHFs (4), plague, SARS, smallpox Bact. Enterocolitis (4); Cholera, Dysentery, Typhoid fever, Paratyphoid fever, Diphtheria, Polio Class I If symptomatic, Class II III 1 EHEC infection If necessary, ordinary IV (IV IV) V (IV V) 30 Various (zoonosis, food/water-borne) If necessary, ordinary 42 Various If necessary, ordinary V VI, VI VII
Revision of the Infectious Disease Control Law (2006) Integrated Infectious Disease Control to cope with deliberate infection including bio-terrorism.(a kind of Select Agents Law was prepared within framework of IDCL) Consideration for repeal of Tuberculosis Control Law (Integration into IDCL) Select agents are divided into four Classes; Class1, 2, 3 and 4 Addition or reconsideration of Categories for several diseases 1) Addition to Cat. I infectious disease; South American VHF 2) From Cat. I to Cat.II infectious disease; SARS 3) Addition to Cat. II infectious disease; TB 4) From Cat. II to Cat.III infectious disease; cholera, dysentery, typhoid fever, paratyphoid fever 5) Addition to Cat. IV infectious disease; glanders, melioidosis, EEE, WEE, Tick-borne E, Rift valley fever, AI and others.
Notifiable Diseases (category, hospitalization) (Nov. 2006) Cat. No. Diseases Transmission Hospital I 7 VHFs (5); South Africa VHF, plague, smallpox Class I II 4 Diphtheria, Polio, Tuberculosis SARS, If symptomatic, Class II III 5 IV 41 EHEC infection, Bact. Enterocolitis (4); Cholera, Dysentery, Typhoid fever, Paratyphoid fever Various (zoonosis, food/water-borne) EEE, WEE, Tick-borne E, Avian influenza, Glanders, Melioidosis, Rift valley F etc. If necessary, ordinary If necessary, ordinary V 42 Various If necessary, ordinary
Class 1 Prohibition of possession Class 2 Permission for possession Class 3 Notification of possession Class 4 Observance of standard Ebola, Small pox etc. Prohibition of production, import, possession, transfer (except institute by government ordinance) Regulations/train. Periodical report Transfer control Measure against damage in outbreak Botulinum toxin, F. tularensis, Y. pestis, SARScorona, B. anthrasis, C. botulinum Requirement of permission for production, import, possession, transfer by minister of MHLW) Regulations/train. Periodical report Transfer control Measure against damage in outbreak M. tuberculosis ( multi-anti drugs-r), C. burnetii, HFRS, Nipa, Rabies, etc. Notification to minister of MHLW) Periodical report Transfer control Polio, M. tuberculosis ( except multianti drugs-r), WN, YF, A. Inf., JE, etc. Observation of the regulation
For all Class 1, 2, 3, 4 Observance of standards by the MHLW ordinance for facility, keeping, usage, transport and sterilization Collection of report, inspection on the spot by a minister of the MHLW Order for improvement by a minister of the MHLW Penal regulation for disobedience against order of improvement
Classification of select agents by IDCL and Object pathogens Class 1 Class 2 Class 3 Class 4 6 Ebola virus Crimea Congo HF Virus Small pox virus South America HF virus Marburg virus Lassa virus 6 SARS-corona virus Bacillus anthracis Francisella tularensis Yersinia pestis Clostridium botulinum botulinum toxin 23 Coxiella burneti, Rabies v., M. tuberculosis (multi-drug resistance ) Government order: Coccidioides, Monkey pox v., HFRS v., WEE v., Tickborne encephalitis v., Omsk HF v., Kyasanur Forest disease v., EEE v., Nipah v., Rickettsia japonica, Rickettsia prowazekii, HPS v., B v., Burkholderia mallei, Brucella genus, VEE v., Hendra v., Rift Valley fever v., Burkholderia pseudomallei, Rickettsia rickettsii 16 Influenza v.(h2n2), ( H5N1 or H7N7), Yellow fever v., Cryptosporidium parvum, M. tuberculosis (except multi-drug resistance), Vibrio cholere, Shiga toxin, Shigella genus, Salmonella Typhi, Escherichia coli (intestinal hemorrhagic), Salmonella Paratyphi A, Polio v. Government order: West Nile v., Chlamydophila psittaci, Deng v., Japanese encephalitis v.
Class/Infectious disease category & Class/BSL Category I II III IV V Class 1 Class 2 Class 3 Class 4 BSL4 BSL3 BSL2 BSL1 Class 1 Class 2 Class 3 Class 4
Obligation by the law for person possesses Class 1 to 4 agents Class 1 Class 2 Class 3 Class 4 Regulation for prohibition of infect. dis. Responsible person for paths. handling Training Sterilization/distribution Entry (Record) Facility standards Keeping standards Transfer standards (Public Safety Commission) Notification of accident Emergency measure for calamity
Technical standards for location, structure, facility Class 1 Class 2 Class 2 Class 3 Class 3 Class 4 Class 4 Pathogen A B C D E F G Land collapse Fireproof Earthquake p. Restriction area Supportive facility Survey room for restriction area Facility for Protect intrusion Access control to lab. Storage fac., key Lab anteroom Inside lab, safety cabinet Air supply, HEPA Air exhaust, HEPA Water exhaust facility Animal facility, keeping facility Sterilization facility Maintenance, once a year
Technical standards for storage, use, sterilization Class 1 Class 2 Class 2 Class 3 Class 3 Class 4 Class 4 Pathogen A B C D E F G Storage with sealed container Storage lock Deposit with plural person Sign of biohazard in storage room Work with plural person Handling in safety cabinet Prohibition of eating, smoking PPE Decontamination leaving lab. Sterilization for contaminated material Access control to restricted area Restriction of taking out of infected animal Measure for infect. animal escape Sign of biohazard in storage room Sterilization of contaminated material Sterilization of waste water
II. MHLW: Organization related to Infectious Disease Control NIID: http://www.nih.go.jp/niid/index.html MHLW Sec. Health Science Sec. Food safety Sec. Infectious Dis. Sec. City water Sec. National Hospital NIID N.I. of Public Health N.I. of Health Sciences N. Special Medical Centers Quarantine Office Basic and applied Research on infect. Dis. Infect. Dis. Surveillance program (Field investigation ) Diagnosis National control on QC of biological products Reference services International cooperation activities International Medical Center of Japan National Cancer Center
National Institute of Infectious Diseases Tatsuo Miyamura, Director-General, Deputy Director-General Administration Dep. Planning and Coordination Dep. Virology I Dep. Virology II Dep. Virology III Dep. Bacteriology Dep. Bacterial Pathogenesis and Infection Control Dep. Parasitology Dep. Pathology Dep. Immunology Dep. Bioactive Molecules Dep. Biochemistry and Cell Biology Dep. Medical Entomology Dep. Veterinary Science Dep. Safety Research on Blood and Biological Products Div. International Cooperation Div. Biosafety Control and Research Div. Radiological Protection and Biology Div. Experimental Animal Research Infectious Diseases Surveillance Center AIDS Research Center Center for Pathogen Genomics Library Leprosy Research Center Dep. Microbiology Dep. Bioregulation
Regulations on the safety control of labs handling pathogenic agents, NIID Management for all pathogens including animal experiments Biorisk management committee BSL classification list Handling of pathogens, Distribution/acceptance Biosafety/security lecture Health management (There is another regulation for animal experiments.) Biosafety/Bio security 2007 June
Regulations on the safety control of labs handling pathogenic agents, NIID (from 1981) ( 2007 revised) Purpose: Safety handling and keeping of pathogen in NIID 1)Safety management system Biorisk management committee, Biorisk management sub-committee, Observation committee Div. Biosafety Cont. and Res. BSL2 lab. Supervisor for biosafety Chief of BSL2 pathogens handling Chief of BSL2 select agents handling BSL3 lab. Supervisor for biosafety Chief of BSL3 pathogens handling
Continue 2)Safety management standard Standards for lab. safety design and operation Classification of BSL for pathogen operation (management) Procedure for handling pathogens (includes select agents) Transportation (acceptance, distribution) Handling of BSL1,2,3 pathogen (notification or application) Information control Countermeasure for exposure, accident (theft), disaster and emergency Biosafety lecture 3)Health management Periodical health check Preservation of sera Issue of safe information card 4)Others observance of regulation and penal code
BSL3 Classification of BSL for pathogen in NIID virus: Chikungunya, Colorado tick.f., EEE, Hantaan, Herpes B*, HIV1,2, Influenza (highly pathogenic avian), Kyasanur F.f., Mayaro, Murray Valley E., Negishi, Powassan, Rabies(street strain), Rift V.f., RSSE, Semliki forest, SARS Co-V, St. Louis e., T-B E, VEE, West N f., WEE, Yellow f.* * small culture only for diagnosis rickettsia: Coxiella burnetii, O. tsutsugamushi bacteria: B. anthracis, Burucella, Burkholderia mallei, B. pseudomallei, F. tularensis, M. africanum, M. bovis, M. tuberculosis, S. Paratyphi A, S. typhi,y.pestis
Safety management system for handling of pathogens in NIID Biorisk management committee Director Gen. Biorisk management sub-committee Dep. Director Observation committee BSL3 laboratory supervisor Chief of BSL3 pathogens handling BSL3,(4) Laboratory BSL2 laboratory supervisor Chief of BSL2 pathogens handlng, Chief of BSL2 select agents handling BSL2 Laboratory Div. Biosafety
Implementing Infectious Disease Research and Strengthening Countermeasures against Infectious Diseases Ministry of Health, Labour and Welfare (MHLW) Quarantine stations MHLW National Institute of Infectious Diseases (NIID) Outbreak containment N. I. of B.Med. Innovation Preventive measures Infect. Dis. information International Medical Center of Japan (IMCJ) Research Institute of Tuberculosis
Popularization of idea of Biosafety and Biosecurity, Practice according to international standards -Symposium, Training course- 1st Asia-Pacific Symposium (2006) NIID, Japan Tranportation training course
III.1. Construction of BSL3 facility in NIID To cope with highly pathogenic agents -H5N1 avian influenza etc. BSL3 lab. according to GMP (three in vitro labs) to produce genetically engineered attenuated H5N1 IFN virus by introducing mutations within HA cleavage site to produce vaccine candidates; Another three animal labs; GLP A new building with 5 floors, about 4,000m 2 is under construction and will be completed in 2008.
NIID Bld-9 at Murayama Branch BSL2 for Centre for pathogen genomics - Illumina (Solexa): Genome Analyser II - Roche (454 Lifesciences): GS FLX Illumina Roche BSL3: 47.35m 2 x 3 labo ABSL3: 94.5m 2 x 3 labo - ABSL3-1: suit labo - ABSL3-2: suit labo - ABSL3-3: GBL labo
ABSL3-1 (suit labo) in NIID Bld-9 Bio-seal door Dissecting SC 94.5 sq-m suit (Delta) Ferret keeping chambers
ABSL3-3 (GBL labo) in NIID Bld-9 exit entry 94.5 sq-m
2. Renovation of BSL4 facility in NIID Glove-box line: 1 in vitro lab, 1 for animal lab including monkey
NIID BSL4 before renovation in 2007
Microscope before after (CCD camera / without eyepiece)
Ultracentrifuge / high speed centrifuge before (centrifuge was a part of GBL) after (centrifuge is installed in GBL)
Further development International co-operation for Infectious Disease Control, Biosafety, Biosecurity (ABSA, A-PBA, WPRO, JICA etc.) G7 Global Health Security Action Group Laboratory Network(GHSAGLN) Standardization of diagnosis for small pox, B. anthrasis etc. Biosafety/Biosecurity information exchange WHO biosafety program
The Japanese Biological Safety Association (JBSA) 2002 Jan. Foundation 2007 Nov.16,17 The seventh Annual Conference of the Japanese Biological Safety Association 2008 Dec.11, 12 The eighth Annual Conference in Osaka www.nih.go.jp/niid/meetings/jbsa
Conclusion 1. Under the framework of IDCL, control of select agents started June 1, 2007. Select agents are classified into four classes. Obligation by the law for pathogen possession, technical standards are introduced. Although the law is useful to strengthen biosafety and biosecurity, many steps are needed to perform this law effectively. 2. Biorisk management in NIID is carried out under the Regulations on the safety control of labs. handling pathogenic agents, NIID. 3. NIID biosafety group is contributing to developing the prevalence of biosafety in Japan by cooperation with other organizations. 4. To cope with highly pathogenic agents -H5N1 avian influenza etc., new BSL3 facility has been completed in NIID. 5. Renovation of BSL4 facility is proceeding in NIID. 6. It is required to promote biosafety system to perform according to international harmonization now.