REPORT OF VISIT TO THE BUREAU OF COSMETICS AND HAZARDOUS SUBSTANCES OF THAILAND, 4-6 DECEMBER 2012 TABLE OF CONTENTS Page 1. INTRODUCTION 2 2. OBJECTIVES OF THE VISIT 2 3. METHOD OF WORK 2 4. INSTITUTIONAL CAPACITY 3 4.1 4.2 4.3 4.4 4.5 3 4 5 5 6 Organization and management Documentation Laboratory facilities, equipment and materials Human resources Laboratory procedures 5. CONCLUSIONS AND RECOMMENDATIONS 6 6. PROPOSED ACTION PLAN 7 7. ACKNOWLEDGMENTS 7 ANNEX 1. ANNEX 2. LIST OF MAIN EQUIPMENT OF THE BUREAU FOR QUALITY CONTROL OF PESTICIDES 8 STAFF OF THE BUREAU OF COSMETICS AND HAZARDOUS SUBSTANCES THAT ARE INVOLVED IN PESTICIDE-RELATED WORK AND THEIR QUALIFICATIONS. 11 ANNEX 3. SCOPE OF ACCREDITATION 13 ANNEX 4. LIST OF VALIDATED METHODS FOR ANALYSIS OF PESTICIDES 15 1 1. INTRODUCTION The use of sub-standard public health pesticide products can have serious adverse effects on human health and the environment. It can also result in not only ineffective public health pest or vector control operations, thus leading to increasing application rates and cost, but also loss of human lives. It may increase the risk to users and the environment as substandard formulations may contain impurities which can increase the toxicity of the product to mammals and other non-target species. Noting the limited capacity of Member States in quality control of public health pesticides, designation of regional laboratories that can assist national programmes and other stakeholders in quality control of public health pesticides is of prime importance and of high priority. In Thailand, pesticides are regulated under the Hazardous Substances Act, B.E. 2535 (1992) (3rd Amendment, 2008). It is an umbrella Act that controls pesticides as well as other hazardous substances, e.g. radioactive substances and disinfectants. The regulations involving registration and licensing of pesticides are under purview of four department/agencies in Thailand, i.e. public health pesticides under the Thai Food and Drug Administration (FDA) while agricultural pesticides are under the Department of Agriculture (DOA), livestock pesticides are under the Department of Livestock Development (DLD) and pesticides used in fisheries are under the Department of Fisheries (DOF). Quality control of pesticides is conducted by different laboratories based on their area (sector) of use. The Bureau of Cosmetics and Hazardous Substances of the Department of Medical Sciences (DMSc) is the designated national reference laboratory for quality control of public health pesticides. Established in 1987, the Bureau supports enforcement of pesticide regulations and cooperates with the Thai FDA. 2. OBJECTIVES OF THE VISIT The objective of the visit was to assess the capacity of the Bureau of Cosmetics and Hazardous Substances of the Department of Medical Sciences, Ministry of Public Health, Thialand for quality control of public health pesticides and its potential for designation as a WHO Collaborating Centre. 3. METHOD OF WORK Dr Morteza Zaim, Coordinator, Vector Ecology and Management Unit of the World Health Organization (WHO) Department of Control of Neglected Tropical Diseases, and Dr Olivier Pigeon (Head of the WHO Collaborating Centre for Quality Control of Pesticides - CRA-W, Belgium), WHO Temporary Adviser, visited the Bureau of Cosmetics and Hazardous Substances, in Bangkok, from 4 to 6 December 2012. The assessment of the capacity included interviews and discussions with the Director of the Bureau, Ms Chaivanit Hansa, and with Ms Anantasinkul Nawaporn, Senior Medical Scientist and MS Siriwat Kultida , Risk Assessment Section Chief, Quality manager as well as other staff involved in quality control of pesticides. The assessment also included visit to the laboratory and other relevant facilities of the Bureau as well as direct observation and critical review of the organization and management of laboratory procedures. Dr Popattanachi 2 Niphon, Director-General of the Department of Medical Sciences was briefed on the mission objectives and observations. 4. INSTITUTIONAL CAPACITY 4.1 Organization and management The Bureau of Cosmetics and Hazardous Substances is one of the twenty-four bureaus/institutes/regional centres of the Department of Medical Sciences, located in the campus of the Ministry of Public Health in Muang District, Nonthaburi, Thailand. The Bureau is composed of four technical Sections (Quality and Technical Development; Risk Assessment; Quality and Safety Testing; and Standard Methods) and an administrative section, as presented in Figure 1. Ms Chaivanit Hansa, Director of the Bureau, is supported by a Senior Medical Scientist and four Section Chiefs. Ms Chaivanit has assumed the post of the Director of the Bureau since 2007. Figure 1. Organogram of the Bureau of Cosmetics and Hazardous Substances (December 2012) DIRECTOR-GENERAL (Dr P. Niphon) DEPARTMENT OF MEDICAL SCIENCES Deputy Director-General (Ms B. Juripom) Director (Ms H. Chaivanit) Bureau of Cosmetics and Hazardous Substances Senior Medical Scientist (Ms A. Nawaporn) Administrative Quality and Technical Development Standard Method Risk Assessment Quality and Safety Testing The activities of the four technical Sections are briefly as follows: o o o o Quality and Technical Development – development and maintenance of quality management system; conduct of proficiency testing. Risk Assessment – assessments for improving regulation of cosmetics and hazardous substances; development and evaluation of test kits in cosmetics and hazardous substances. Quality and Safety Testing – testing quality, safety and efficacy of cosmetics and hazardous substances for conformity to standards. Standard Method – development and validation of test methods; conducting training on test procedures. The Bureau of Cosmetics and Hazardous Substances serves as the national reference laboratory for research and development in cosmetics and hazardous substances, including 3 public health pesticides, in accordance with the Cosmetics Act 1992 and the Hazardous Substances Acts 1992 and 2008. The Bureau has established the quality management in the laboratories since 1992 and has been accredited according to ISO/IEC 17025 by the National Association of Testing Authorities of Australia (NATA) in medical devices testing in 1995. The scope of accreditation has been extended to hazardous substances and cosmetics testing. The Bureau has been also granted from accreditation body in Thailand, i.e., the Bureau of Laboratory Quality Standards (BLQS). The Bureau is mainly funded by the government (90% of the budget). Additional resources come from standard fees charged to manufacturers (10% of the budget) for the analysis of their products. The staff salaries are paid by the government. 4.2 Documentation The Bureau has set up a very good and detailed documentation system. A quality manual is available to describe the management of the laboratory according to the requirements of the ISO/IEC 17025 standard and of the accreditation bodies (NATA and BLQS). Standard Operating Procedures (SOP), work instructions and worksheets are available for the following activities: management, safety, waste treatment, test methods, calibration, reference materials and reference cultures, instruments and equipment, sample handling, cleaning, reagent / media preparation, standard solutions, training, audit, proficiency tests, method validation and verification and sample preparation. The Bureau has SOPs to guarantee the impartiality and prevention of conflict of interest and to protect the customer’s confidentiality and proprietary rights. The documents are prepared, reviewed and approved according to a well-established SOP. Testing service submission forms serve as contracts between the Bureau and customers before starting the analysis. The Bureau has SOPs for the resolution of complaints, corrective actions of nonconforming work and for preventive actions. The training of the staff is recorded in standard forms. Testing methods are fully described in SOPs. The Bureau has developed and validated analytical methods for 61 pesticides. These pesticides are those registered in Thailand for public health uses. The main methods for determination of active ingredient in pesticides are in-house validated methods. The analytical methods of the Collaborative International Pesticide Analytical Council (CIPAC) are used for some insecticides, namely allethrin isomers, deltamethrin, permethrin, piperonil butoxide, pyrethrins, temephos and cypermethrin. The Bureau plans to implement further CIPAC methods in the future. The test reports with raw data are archived for a period of at least 10 years after completion of the testing. After completion of the testing, the pesticide samples are stored as followings: samples submitted by government sectors ,exclusion of court case , and conform to the regulation, storage time of three months. samples submitted by government sectors and not conformed to the regulation, storage time of one year. samples for court case , store for at least ten years or until the course case end. samples submitted by private sectors, could be returned to the submittor or stored for one month. There is however no established system for collection and safe disposal of pesticide samples at the end of this period. 4 The Bureau conducts annual management reviews. The reviews take account of the following issues: suitability of policy and procedures, reports from section chiefs and laboratory supervisors, outcome of recent internal audits, corrective and preventive actions to improve quality of work, assessments from accreditation bodies, results of inter-laboratory comparisons, changes in the volume and type of work, results of customer satisfactory evaluations, complaints, recommendations for improvements, quality control of testing, resources such as personnel, equipment, needed convenient accessories and staff training. The Bureau performs also internal audits every year. 4.3 Laboratory facilities, equipment and materials The Bureau has all the necessary facilities and locals for receipt and preparation of pesticide samples as well as for their analysis. The Bureau also has all the materials (e.g. analytical standards and solvents) and equipment required to determine the active ingredient content and impurities in a pesticide product. However their experience has been limited to the determination of the former only. The main equipment of the Bureau for quality control of pesticides is listed in Annex 1. This includes gas chromatographs equipped with autosamplers and different detectors, flame ionization detectors (FID), electron capture detectors (ECD), mass spectrometry detectors (MS), nitrogen chemi-luminescence detector (NCD) and high-performance liquid chromatographs equipped with autosamplers and UV diode-array spectrometry detectors (DAD). The Bureau have some equipment to assess physical parameters of common public health pesticide formulations for some parameters, namely pH range, suspensibility, persistent foam, wettability, wet sieve test , emulsion characteristic and re-emulsion and water content (Karl Fischer method). However some equipment and materials are required to assess other chemical properties as well as physical parameters of common public health pesticide formulations. Such analysis is critical to safety and good performance of a pesticide formulation. All laboratories are equipped with appropriate working tables, fume hoods and ventilation systems. Most laboratories are equipped with air-conditioning. Locals for sample preparation and storage however need to be equipped with air-conditioning. The locals for storage of pesticide samples and solvents should be better ventilated and better secured against fire and for other safety aspects. The local for archiving of documentation and reports of the Bureau should be extended and properly secured, including against fire. 4.4 Human resources The list of the staff of the Bureau and their experience and qualifications is presented in Annex 2. The staff are well-trained for determination of active ingredient content in pesticide products. They however require further trainings on testing chemical and physical parameters of pesticides and in use of CIPAC methods. The motivation of staff in performing their duties was notable. 5 4.5 Laboratory procedures The main activities of the Bureau are focused on the analysis of cosmetics, disinfectants and pesticides. The Bureau is responsible for the chemical and microbiological testing of public health pesticides according to the Hazardous Substances Act. Chemical testing covers the active ingredient content in the formulated pesticide products. About 700 pesticide samples are analysed annually for active ingredient content. Average time for analysis and reporting is about one month. The Bureau does not sub-contract any testing. The source of samples analysed are mainly from the Thai FDA, in the framework of surveillance programmes, and also from pesticide manufacturers. The Bureau has in place appropriate standard operating procedures and manuals for receipt, registration, handing and analysis of pesticide samples. The sample preparation and their chromatographic analysis are performed according to well described analytical methods. However many such methods are in-house and not methods specified by WHO specifications (e.g. CIPAC) for wide acceptance. The list of analytical methods accredited according to ISO/IEC 17025 is given in Annex 3. Many analytical methods used by the Bureau for quality control of pesticides are validated for their linearity, precision, accuracy, and where relevant, their limit of detection and quantification. However validation has not been performed for all the methods used by the Bureau for quality control of pesticides and need to be addressed. The list of validated analytical methods for the analysis of pesticides is given in Annex 4. All major equipment are routinely calibrated in-house and or by external agents. Records of maintenance and calibration are available. In addition all laboratory operations are recorded in appropriate work sheets. All pesticide samples, analysis and reporting are identified by a unique bar code. There is however room for further computerization of the information/data throughout their chain of custody. Quality and accuracy of data is properly verified through appropriate laboratory measures including duplicate injections and analysis, analysis of blanks, check calibration solutions and spiked samples. The Bureau has participated in recent CIPAC collaborative trials of chlorfenapyr and piperonyl butoxide and has organized a national proficiency test on temephos granules in their attempts to further improve analysis of pesticides. 5. CONCLUSIONS AND RECOMMENDATIONS The Assessment Team has noted the excellent capacity of the staff of the Bureau of Cosmetics and Hazardous Substances in pesticide analytical methods and laboratory practices. The Team also noted the good procedures and practices in place to ensure quality of analysis and documentation. Quality control of pesticides by the Bureau, however, is largely limited to the determination of active ingredient which is not sufficient for full assessment of quality of pesticide products for their safety and good performance. In order to fulfil the two-year probationary period of satisfactory collaboration between the Bureau and WHO, which is a requirement for designation as a WHO Collaborating Centre, the following activities and actions are recommended: 6 o strengthen the capacity of the Bureau for testing of all physical and chemical properties of a public health pesticide product, including relevant impurities, as specified in the WHO specifications and as part of its quality control; promote and support conduct of such full testing as a policy for national regulation of public health pesticides; o use collaboratively tested analytical and other test methods as specified by WHO specifications (e.g. CIPAC), to ensure wide acceptability and application of results of quality assessment of public health pesticide; o Continue participation in proficiency tests and collaborative studies of international organizations, such as CIPAC, as a strategy for further strengthening the capacity of the Bureau for quality control of public health pesticides; and 6. PROPOSED ACTION PLAN 1. Develop, based on WHO specifications for public health pesticides (PHPs), the list of physical and chemical parameters and methods of analysis; 2. Develop the list and acquire materials and equipment required to perform the full physical and chemical testing of PHPs according to WHO specifications; 3. Acquire expertise on the conduct of physical and chemical analysis of public health pesticide products, including long-lasting insecticidal nets; a. Train 2 scientists/technicians in the WHO Collaborating Centre for Quality Control of Pesticides, Gembloux, Belgium; b. Conduct inter-laboratory comparison studies on selected physical and chemical tests between the Bureau and the above-mentioned WHO Collaborating Centre; c. Participate in CIPAC organized collaborative trials for pesticides; attend annual CIPAC Technical Meetings; 4. Organize visit of the Bureau by a WHO expert to assess implementation of physical and chemical testing of PHPs 5. Develop and submit to WHO a full report on implemented activities within the probationary period. 7. ACKNOWLEDGEMENTS The WHO Assessment Team wishes to thank the Director and the staff of the Bureau of Cosmetics and Hazardous Substances of the Department of Medical Sciences for their interest in and for their commitment to the work of WHO, and for their collaboration and support of this assessment. 7 ANNEX 1. LIST OF MAIN EQUIPMENT OF THE BUREAU FOR QUALITY CONTROL OF PESTICIDES No. Equipment Products / Models 1 Automatic titrator Metrohm / 702SM 2 Automatic titrator Metrohm / 751 Titrino 3 Automatic titrator Metrohm / 907 Titrino 4 Balance, electronic precision ( 0.001 g ) Precisa / XT 1220M 5 Balance, electronic analytical ( 0.0001 g ) Mettler / AT 200 5 Balance, electronic analytical ( 0.0001 g ) Sartorius / LA 230S 6 Balance, electronic analytical ( 0.0001 - 0.00001 g ) Mettler / AX 105 DR 7 Balance, electronic analytical ( 0.0001 - 0.00001 g ) Mettler / XP 205 DR 8 Bath, Cooling with external circulator LAUDA / E 100 9 Bath, Water with temperature control Memmert / EB 29 10 Deionizer Millipore / Milli-Q Plus 185 11 Deionizer, Mixed Bed Yamato / Autosil WA53-2 12 Deionizer, Mixed Bed Barnstead / D7033 13 Densitometer, TLC Scanner CAMAG / Scanner 3 14 Flashpoint tester SETAHOPE / SETAFLASH 15 Fume hood Easy lab / 200 16 Fume hood Easy lab / 200 17 Fume hood Easy lab / 150 18 Fume hood Easy lab / 200 19 Fume hood Easy lab / 150 20 Fume hood Easy lab / 150 21 Fume hood Easy lab / 150 8 22 Fume hood, Walk in Easy lab / 200 23 Fume hood, Walk in Easy lab / 200 24 Fume hood, Walk in Easy lab / 200 25 Gas Chromatograph (GC) Agilent / 6890N 26 Gas Chromatograph (GC) Agilent / 6890N 27 Gas Chromatograph (GC) Agilent / 7890 A 28 Gas Chromatograph (GC) Agilent / 7890 A 29 Gas Chromatograph (GC) Agilent / 7890 A 30 Gas Chromatograph-Mass Spectrometer (GCMS) Agilent / 6890N 31 HPLC WATERS 32 HPLC WATERS 33 HPLC WATERS 34 HPLC WATERS 35 HPLC WATERS / e2695 36 HPLC WATERS / e2695 37 LC/MS/MS WATERS / XEVO TQ-S 38 Incubator, aerobic WTB Binder / BED-115 39 Ion analyzer ORION / 930 40 Ion Chromatograph DIONEX/ICS-3000 series 41 Melting point Apparatus OPTIMELT / MPA 100 42 Oven , hot air WTB Binder / ED 531E 43 Oven , hot air Termaks / TS 8136 44 Polarimeter KRUSS / P 8000-T 45 Reference, weight (22 pieces) Masscal / F1 46 Reference, weight SARTORIUS / E2 (1 g) 47 Reference, weight SARTORIUS / E2 (10 g) 9 48 Reference, weight SARTORIUS / E2 (50 g) 49 Reference, weight SARTORIUS / E2 (100 g) 50 Reference, weight SARTORIUS / E2 (200 g) 51 Reference, weight LS/F1(2150207-1-1)(500 g) 52 Reference, weight LS/F1(2150207-2-1)(500 g) 53 Reference, weight (23 pieces) Hafner / E2 54 Refractometer, reflactive index KRUSS / DR 6100-T 55 Refrigerated centrifuge high speed (up to 26,000 rpm) Thermo / IEC B-22 M 56 Refrigerator Sanyo / SR-F380 57 Refrigerator Sanyo / SR-NF135 58 Refrigerator STRONGMAN 59 Refrigerator STRONGMAN 60 Refrigerator, T MITSUBISHI / MR-F56C-DS 61 Refrigerator, explosion proof HOTPACK / 825150 62 Thermometer PRECISION 63 Thermometer GOLD BRAND 64 Thermometer, Mercury Arno Amarell 65 Timer , Stopwatch Heathrow Scientific / HEA24490M 66 UV-VIS spectrophotometer SHIMADZU / UV-160A 67 UV-VIS spectrophotometer PERKIN-ELMER / Lambda 2S 10 ANNEX 2 . STAFF OF THE BUREAU OF COSMETICS AND HAZARDOUS SUBSTANCES THAT ARE INVOLVED IN PESTICIDERELATED WORK, AND THEIR QUALIFICATIONS. A. Senior scientists Name Anantasinkul Nawaporn Meesri Junya Siriwat Kultida Meethong Sudthida Tianungoon Suwunna Degree MSc.(Statistic); BSc.(Chemistry) BSc.(Chemistry) MSc.(Microbiology); BSc.(Biology) MSc.(Analytical Chemistry); BSc.(Chemistry) PhD.(Microbiology);MSc.(Toxicology); BSc.(Biology) # year 34 23 25 25 23 Section Senior Medical Scientist Quality and Technical Development Section Chief Risk Assessment Section Chief, Quality Manager Quality and Safety Testing Section Chief Standard Method Section Chief B. Junior scientists Name Nakniyom Wongdaun Nilmanee Laweng Vivon Menaka Nitchanpansri Jiraporn Suriyajun Woramon Chaichana Jatuporn Sangjarusvichai Haruthai Intharasamee Kamolluck Khejonnit Awiruth Kao-ian Chun-grida Noppkue Napaputch Degree MSc.(Analytical Chemistry); BSc.(Chemistry) MSc.(Medical Sciences); BSc.(Chemistry) MSc (Cosmetic Sciences); BSc.(Chemistry) MSc.(Analytical Chemistry); BSc.(Chemistry) BSc.(Pharmaceutical Sciences) MSc.(Analytical Chemistry); BSc.(Chemistry) MSc.(Analytical Chemistry); BSc.(Chemistry) BSc.(Chemistry) BSc.(Chemistry) BSc.(Pharmaceutical Sciences) MSc (Cosmetic Sciences); BSc.(Chemistry) 11 # year 20 15 12 3 3 1 1 17 18 2 5 Section Standard Method Supervisor Quality and Safety Testing Analyst Risk Assessment Analyst Quality and Safety Testing Analyst Standard Method Analyst Standard Method Analyst Quality and Safety Testing Analyst Quality and Safety Testing Analyst Risk Assessment Supervisor Quality and Safety Testing Analyst Standard Method Analyst C. Technicians (Temporary Staff, Medical Scientists) Name Suwannatrai Wadeelunate Santa Sumita Kompayak Preechaya # year 9 1 1 section Quality and Safety Testing Analyst Quality and Safety Testing Analyst Quality and Safety Testing Analyst D. Administration officer Name Sajjathanasakul Chommanee Boonyoung Prapaipak Wongkumjun Panrapeeput Deeying Jumpa Injai Jiravadee # year 1 30 18 25 20 12 section Administration Administration Section Chief and Document Control Officer Administration Sample Custodian Administration Administration Sample Custodian ANNEX 3. SCOPE OF ACCREDITATION National Association of Testing Authorities (NATA), Australia Accreditation No. 10627 of 08 June 2011 Type of sample Insecticide and acaricide formulations including insecticide treated nets Mosquito larvicides Compound Method Allethrin GC, SOP 06-02-264 Alpha-cypermethrin GC, SOP 06-02-264 Bifenthrin GC, SOP 06-02-264 Chlorpyrifos HPLC, SOP 06-02-263 Cyfluthrin GC, SOP 06-02-264 Cypermethrin GC, SOP 06-02-264 Deltamethrin GC, SOP 06-02-151 and SOP 06-02-264 Dichorvos GC, SOP 06-02-264 Fenvalerate GC, SOP 06-02-264 Fipronil HPLC, SOP 06-02-194(T) Imiprothrin GC, SOP 06-02-264 Permethrin GC, SOP 06-02-069 and SOP 06-02-264 Phenothrin GC, SOP 06-02-264 Piperonyl butoxide GC, SOP 06-02-264 Prallethrin GC, SOP 06-02-264 Tetramethrin GC, SOP 06-02-264 Temephos Normal phase HPLC, SOP 06-02-081 Temephos Reverse phase HPLC, SOP 06-02-201 13 ANNEX 3 continued. SCOPE OF ACCREDITATION Bureau of Laboratory Quality Standards (BLQS), Thailand Accreditation No. 4031/49 of 09 December 2011 Type of sample Insect repellents Compound Method Citronella GC, SOP 06-02-122 N,N-diethyl-m-toluamide HPLC, SOP 06-02-199 Dimethyl phthalate HPLC, SOP 06-02-199 Ethyl butylacetyl aminopropionate HPLC, SOP 06-02-199 N,N-diethyl-m-toluamide SOP 06-02-050 based on AOAC (2010) 985.03 d-Limonene HPLC, SOP 06-02-248 Permethrin SOP 06-02-191 based on AOAC (2010) 991.03 Cypermethrin SOP 06-02-191 based on AOAC (2010) 991.03 Pet shampoo Flumethrin HPLC, SOP 06-02-057 Insecticide chalk Cypermethrin SOP 06-02-275 based on AOAC (2010) 991.03 Deltamethrin SOP 06-02-275 based on AOAC (2010) 991.03 Insecticides 14 ANNEX 4. LIST OF VALIDATED METHODS FOR ANALYSIS OF PESTICIDES No Compound Technique* 1 2 3 N, N diethyl-m-toluamide flumethrin citronellal GC HPLC GC 4 5 6 7 8 9 10 11 12 13 Cypermethrin and permethrin Insect repellants :dimethyl phthalate , ethyl butylacetyl and N,N-diethyl-m-toluamide d-limonene Cypermethrin and deltamethrin permethrin temephos deltamethrin- bed net fipronil chlorpyrifos alphacypermethrin ,bifenthrin, cyfluthrin ,cypermethrin, deltamethrin, dichlorvos, fenvalerale, Imiprothrin, permethrin and phenothrin allethrin isomers HPLC HPLC HPLC HPLC GC HPLC GC HPLC HPLC GC 14 * GC = gas chromatography; HPLC = high-performance liquid chromatography 15 HPLC and GC