TABLE OF CONTENTS PREFACE

CHAPTER ONE - INTRODUCTION AND QUALITY POLICY

1.1 Mission Statement1.2 Core Values1.3 Ethics Policy1.4 Debarment Certification1.5 Regulatory History1.6 Quality Management1.7 Risk Analysis1.8 Confidentiality

CHAPTER TWO - ORGANIZATION AND STRUCTURE

2.1 Organization Structure Figure 1 - Organizational Chart

2.2 Floor Plan Figure 2 - Floor Plan

2.3 Instrumental Services2.4 Testing Services2.5 Procedures

Table 1 - Standard Operating Procedures

CHAPTER THREE - LABORATORY QUALITY ASSURANCE

3.1 Role and Responsibilities of the Quality Unit3.2 Internal Quality Control3.3 Precision and Accuracy in Quality Control3.4 Control Charts3.5 Corrective Action3.6 Laboratory Control Standards - Reference Materials

Table 2 - Standard Reference Materials3.7 External Quality Control Programs3.8 Data Packages, Data Review and Audits3.9 Document Control3.10 Purchasing3.11 Change Control3.12 Customer Service and Client Audits3.13 Complaint Resolution3.14 Out-of-Specification Investigations3.15 Non-Conformances and Corrective/Preventative Actions3.16 Validation, Transfer, and Verification of Methods3.17 Facility and Environmental Controls3.18 Training and Qualification of Analysts3.19 Qualification of Equipment3.20 Software Validation3.21 Internal Audits3.22 Continuous Improvement3.23 Business Continuity Plan3.24 Management Review

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TABLE OF CONTENTS (cont.)

CHAPTER FOUR - OPERATIONAL PROCEDURES

4.1 Sample Receipt4.2 Review of Analytical Request Forms

Figure 3 - Chain of Custody Figure 4 - Analytical Request Form

4.3 Sample Receipt and Review of Contracts4.4 Job Envelope, Job Number, and Distribution4.5 Sample Analysis and Review4.6 Job Tracking4.7 Data Reporting4.8 Storage of Completed Samples, Reports, Data and Job Envelopes4.9 Sample Containers and Sampling Supplies4.10 Shipping and Receiving4.11 Subcontracting

CHAPTER FIVE - Specific Analytical Capabilities

5.1 Pharmaceuticals and Medical Devices5.2 Research and Methods Development5.3 Unique Applications of IC-ICPMS and LC-ICPMS5.4 California Proposition 65 - Lead in Supplements5.5 High Purity Reagents5.6 Polymers, Paints, Coatings, and Adhesives5.7 Product Composition and Contamination5.8 Pesticides5.9 Foods and Produce5.10 Drinking Water5.11 Wastewater and Hazardous Waste5.12 Risk Assessment5.13 Industrial Hygiene

APPENDIX A - Resumes APPENDIX B - Legal & Forensic Jobs APPENDIX C - Requirements for Special Projects APPENDIX D - Equipment Listing APPENDIX E - Confidentiality Agreement APPENDIX F - Terms & Conditions APPENDIX G - Quality Agreement for GMP APPENDIX G - Project Experience APPENDIX H - Certifications, Accreditations, Licenses, and Other Programs

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Preface Origination Date: 4/84

Revision 1/88

Figure 2-2 New floor plan includes all of buildingSection 5.1 Quality Assurance Coordinator descriptionSection 5.2 Expanded policy on treatment of QC data, warning limits, and control limitsAppendix D Requirements for Special Programs

Revision 3/88

Section 3.2 Chain of CustodyFigure 3-1 Chain of Custody Form

Revision 2/89 Minor revisions and updatingRevision 3/90 Minor revisions and updatingRevision 1/91 Minor revisions and updating

Revision 9/91

Section 1.0 Paragraph added on quality objectivesSection 2.5 ConfidentialitySection 5.7 Data Packages, Data Review, and Audit

Revision 1/92

Section 5.6 Corrective ActionAppendix B General revisions and updatingAppendix B Annual statistics updateAppendix B Refrigerators changed from 4-8C to 2-6CAppendix B Five place balance calibration changed to 2.0000 0.00009 g Table 1 QC frequency (new table)Table 2 Out of control (new table)

Revision 7/93

Figure 2-1 Updated organization chartAppendix E Job Descriptions addedAppendix B Minor updating

Revision 6/95

General updating to most sectionsSection 1.1 GLP, QA/QC separation, and SOP expansionSection 2.6 Complaint resolutionSection 3.2 Added internal CoC when necessaryAppendix B Deleted, placed in SOP #2210, Quality ControlAppendix E Deleted, job descriptions place in SOP #110

Revision 5/96

Minor revision and updating

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Revision 5/98

Minor revisions and updating Organization Chart, generalizing QAU functions

Revision 5/99

Minor revisions, updating resumes and Organization Chart

Revision 6/00

Updating of style, Organization Chart, Examples, Floor PlanTable 1: Personnel Policies deletedServices provided updatedExamples updatedJob Envelope, Job Number, and Distribution updated to reflect ongoing changes to Log-in.Mission Statement, Core Values, and Ethics Policy added.Statement of Qualifications discontinued and replaced with an expansion of this document.

Revision 10/01

Section 1.6 Changed permanent record kept by Laboratory Director to QA Coordinator.Table 1. Added SOPs 1530 and 2270. Deleted SOP 2150 (Retired).Section 2.1 Updated lab groups. Figure 1 Updated organizational chart to reflect current staffing.Section 2.2 Updated square footage for new building.Figure 2 Updated floor plan for new building.Section 2.3 Deleted chemical ionization; Added electrochemical statements.Section 2.4 Omitted Bioanalytical; Changed product to identification.Section 3.4 Sample storage time changed from two to four weeks; Omitted sentence referencing additional

storage time; Added general statement about test methods, data assembly, review and sign-off.Figure 5 Added signature Page for Data Package.Section 3.6 Changed lab secretaries to client services; Deleted statement of providing floppy disks and

custom computer data format.Section 3.7 Changed sample disposal time from 30 days to four weeks; Changed each job to many jobs;

Revised legal sample statement.Section 3.8 Deleted supplying of badges, sampling tubes, bags, etc. and SUMMA canisters. Section 4.2 Deleted NIOSH program.Section 5.8 Deleted AIHA accreditation statement.Appendix A Updated resumes to reflect current staff members.Appendix D Updated equipment listing.Appendix G.4 Updated to include Trace boron in biological samples.Appendix H Added USFDA registration number and attached current ELAP certificate.

Revision 10/03

Table of Contents Deleted 5.2 Nutraceuticals and renumbered appropriately.Chapter 1 Added XRF, Hg - CVAFS, and LCMS. Table 1, Section 1.4 Added SOPs 220 (Change Control) and 2280 (Chemical Inventory).Section 2.1 Updated organizational structure and chart.Figure 2 Updated floor plan. Section 2.3 Added XRF, Hg - CVAFS, and LCMS.Figure 3 Updated chain-of-custody to reflect new address.Section 4.4 Updated control chart.Table 2 Added USP and EP reference standards to list.

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Revision 10/03 (cont.)

Section 5.1 Added HPLC and LCMS.Section 5.2 Deleted Nutraceuticals and renumbered appropriately. Added Acrylamide by GCMS.Appendix A Updated resumes to reflect current staff members.Appendix D Updated equipment listing.Appendix F Updated to reflect current format.Appendix G Added Medical Devices and supplement sections.Appendix H Updated soils permit number. Added permit to import or transfer etiological agents and

vectors of human disease to list. Changed attached to linked on website for ELAP Certificate.

Revision 04/06

Chapter 1 Removed privately owned. Section 1.3 Replaced President and Lab Director with General Manager. Removed to the best of our

knowledge and added hereby certify to debarment statement.Section 1.4 Removed statement for added SOPs and analytical method SOPs. Section 1.5 Changed solely to only.Section 1.6 Changed President and Lab Director to Technical Director and General Manager.Table 1 Added SOP 2290 and changed title of SOP 2160 to (Quality Assurance). Section 2.1 Updated organizational structure.Figure 1 Updated organizational chart.Section 2.3 Added GC-MS/MS, GC-ICPMS, LC-ICPMS, reaction and collision cells, polarimetry,

CHN analysis, ES, and API. Changed qualified to recommended labs. RemovedElemental Analyses and Emission Spectroscopy (EMS) from list of subcontracted labs.

Section 2.4 Added RoHS testing.Figure 3 Updated chain-of-custody to reflect new form.Figure 4 Updated job envelope.Section 4.2 Changed PE to PT. Added Soil and UST to ERA tests. Added RTC for organic lead in

soil test.Section 4.7 Changed QA Action Form to QC Action Form.Table 2 Removed N and P series from USGS reference sample and added mercury. Chapter 5 Reworded to generalize and removed redundant statements.Section 5.1 Added LC-ICPMS and biological samples for residual drugs and metabolites. Changed

contaminant metals and anions to residual metals and anions, and additives in productsto additives. Removed bioanalytical methods.

Section 5.2 Added element speciation, perchlorate, lovastatin, and ultratrace lead. Removedsaccharides, protein analysis, separation of chiral drugs, and lead isotopes for identifyingsource of pollution.

Section 5.3 Removed example of isotope ratio.Section 5.12 Changed "many" to "some" regarding 500 series methods.Appendix A Updated resumes to reflect current staff members.Appendix D Updated equipment listing.Appendix E Updated Confidentiality AgreementAppendix F Updated Terms and Conditions FormAppendix G G.6 (Organic Lead Determination by ICPMS) - Added speciation by GC-ICPMS. G.5

(Data Package Deliverables) - Changed to G.7 for numbering consistency.Appendix H Added Soil and UST to ERA Studies. Changed USGS testing frequency from quarterly to

biannual. Updated radioactive materials license number. Removed permit to import ortransfer etiological agents and vectors of human disease from list.

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Revision 08/08Revised throughout to reflect acquisition by Exova and align with corporate documents

Sections 2.6,3.10-3.25 Added to better reflect compliance with ISO 17025 and CGMP. Table 1 Added SOP 240Section 2.1 and Fig. 1 Revised to reflect current organizational structure.Section 2.2 and Fig. 2 Revised to reflect expansion of laboratory.Section 2.3 GFAA deleted due to retirement of equipment.Section 3.2 Section renamed for clarity.Appendix A Updated resumes to reflect current staff members.Appendix D Updated equipment listing.Appendix E Updated Confidentiality AgreementAppendix F Updated Terms and Conditions Form

Revision 10/09Revised throughout to reflect name change to Exova. Resumes and organizational chartupdated.

Section 2.6 Moved to Section 4.8. Section 3.12 to 3.26 Moved to Section 4.9 to 4.23.

Revision 06/10Minor update - Resumes, organizational chart, and equipment list updated.

Revision 04/11Minor update - Resumes, organizational chart, and equipment list updated.

Sections 3 and 4 Switched to improve readability. Section 4.8 Document retention time changed from 5 years to 7 years. Section 1.5 Added. Appendix G Added.

Revision 07/12Minor update - Resumes, organizational chart, and equipment list updated. ISO 17025accreditation through A2LA added.

Table 1 Added SOP 2300 Section 2.3, Appendix D UPLC added Section 3.6 Expanded to reflect A2LA traceability policy.

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Chapter 1: Introduction and Quality Policy Exova Inc. of 9240 Santa Fe Springs Rd., Santa Fe Springs CA is a commercial testing laboratoryspecializing in trace chemical analysis using GC, GCMS, IC, LC, UPLC, FTIR, NMR, ICPOES, ICPMS,LC-ICPMS, GC-ICPMS, LCMS/MS, and other state-of-the-art analytical technology. Our technical staff iscomprised of well-trained, educated chemists. We encourage our staff to publish papers on some of theresearch and non-confidential methods development that is performed in-house. The laboratory wasestablished in 1983 as West Coast Analytical Services. On February 1, 2006, the laboratory was acquiredby Bodycote Materials Testing as part of their Bodycote Testing Group. This group was acquired by theprivate investment firm of Clayton, Dubilier and Rice in 2008 and rebranded Exova Inc. in June 2009. Thislaboratory is part of the Health Sciences and Analytical Division of Exova, headquartered in Mississauga,Ontario Canada.

ISO/IEC 17025 and NLLAP through A2LA, Certificate 3248.01FDA Establishment Identification (FEI): 3000203007DUNS number: 114257850CA DOHS ELAP, Certificate 2652

This laboratory is accredited to the ISO/IEC 17025 standard by the American Association of LaboratoryAccreditation (A2LA) for the tests included in the scope of certificate 3248.01. Additionally, our QualityAssurance program meets NELAP, 21CFR211 (Pharmaceutical GMP), 21CFR111 (Dietary SupplementGMP), 21CFR820 (Medical Device GMP), 21CFR58 (GLP), 40CFR160 and 40CFR792 (EnvironmentalGLP), ICH Q1-10, ISO 9001, and ISO 13485 standards. We participate in round-robin performanceevaluation and third-party proficiency testing studies. We consider ensuring the quality of work to be aprerequisite in serving our clients needs.

The Quality Assurance Manual (QAM) describes the procedures that are followed to ensure the quality ofwork.

Chapter 1: Introduction and Quality Policy - Includes Exova Mission Statement, Core Values, andEthics Statement.

Chapter 2: Organization and Services - Describes our organization, services offered, and the sourceof analytical procedures used in our work. Included is an organizational chart and floorplan of the laboratory.

Chapter 3: Laboratory Quality Control and Quality Assurance - Describes the procedures used tomonitor the precision and accuracy of data and ensure data quality.

Chapter 4: Operational Procedures - Describes the procedures that are used to review analyticalrequests; log, track, and store samples; and produce analytical data and reports.

Chapter 5: Specific Analytical Capabilities - Lists various analyses that Exova has performed in thepast and areas of expertise.

Appendix A: Key staff members resumes Appendix B: Legal and forensic job procedures Appendix C: Requirements for special projects Appendix D: Laboratory equipment list Appendix E: Confidentiality agreement Appendix F: Terms and conditions Appendix G: Quality Agreement for GMP Appendix H: Project experience Appendix I: Certifications, accreditations, licenses, and other programs

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1.1 Mission Statement

To provide world class companies with testing services that make a positive contribution to thesuccess of their business. To engage, develop, and retain competent people, harness theirenthusiasm, and inspire them to excel. To act as a good corporate citizen.

1.2 Core Values

At Exova we hold the following principles and values to be the most important, and we consider thesevalues in making decisions in our business:

We are honest and trustworthy in our dealings with our customers, colleagues, andcommunity

We value and protect the safety and health of our colleagues and work to minimizethe environmental impact of our activities

We value and practice good science We are fair to our customers and our colleagues We are committed to the constant improvement of the quality of our services

1.3 Ethics Policy

Ethics is a set of moral principles, a code for right and wrong, or behavior which conforms to acceptedprofessional practices.

Fraud is an intentional act of deceit that may result in legal prosecution. Unethical actions becomefraudulent when a law is violated. For example, it is unethical to change the acquisition date of a file for achromatogram to meet holding times. It becomes fraud when the results are mailed or faxed to the client(wire fraud or mail fraud).

All employees at all times shall conduct themselves in an honest and ethical manner. Compliancewith this policy will be strictly enforced. Unethical behavior is grounds for immediate termination.

Examples of unethical behavior include, but are not limited to the following:

Artificially fabricating results Misrepresenting data such as peak integration, calibration, tuning, or system suitability Improper representation of date or time to meet holding times Intentional deletion or obscuring of data Improper manipulation of data or software Improper handling of data errors, non-compliant data, or QC outliers Lack of reporting unethical behavior by others

An employee must report any suspected unethical behavior or fraudulent activities to the General Manager.If an employee wishes to remain anonymous, they may choose to describe the situation in a note withoutsigning the note, or leave a message on the General Managers home phone during the day(562-947-6173). If the facts of the case are not clear after an investigation, a committee of senioremployees may be asked to investigate the situation further and offer an opinion to the corporate officers.

Annually, employees are required to sign a statement attesting that no conflict of interest exists or appearsto exist between their private interests and official duties.

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1.4 Debarment Certification

We hereby certify that neither Exova Inc. nor its employees connected with the development or submissionof any drug application has been convicted of any crime described in Section 306 subsections (a) and (b)of the Generic Drug Enforcement Act of 1992. Exova Inc. does not and will not knowingly use, in anycapacity, the services of any person debarred under section 306 subsection (a) and (b) of the Generic DrugEnforcement Act of 1992. We have no convictions to report.

In addition none of our employees appear on the Health and Human Services/Office of the InspectorGeneral (HHS/OIG) List of Excluded Individuals/Entities (presently accessible athttp://oig.hhs.gov/fraud/exclusions.asp) or the Federal General Services Administrations List of PartiesExcluded from Federal Programs (presently accessible at http://epls.arnet.gov/)

1.5 Regulatory History

This site has been inspected by the US FDA in December 2010 (no Form 483 issued), June 2010 (no 483issued), June 2009 (483 and response available upon request), Sept. 2006 (no 483 issued), Sept. 2004,July 2002, Aug. 1999, and May 1996. No Warning Letters or Consent Decrees have been issued for thislaboratory. There are no unresolved FDA 483 observations and we are in good standing with the FDA.

This site has been inspected by California State Department of Public Health, for CA ELAP compliance, inApril 2003, September 2006, and April 2011. There are no outstanding issues from these inspections. 1.6 Quality Management

As part of the laboratory resources provided to our clients Quality Control Unit, we maintain appropriatelaboratory and record controls as described in NELAP, ISO 17025, 21CFR58, 21CFR211, 21CFR820,40CFR160, and 40CFR792. While Good Laboratory Practices (GLP) and Good Manufacturing Practices(GMP) regulations under FDA and EPA refer to specific regulated activities in support of applications fordevelopment or production of drugs or pesticides, Exova follows these practices as standard proceduresand is capable of full GLP compliance through pre-approved protocols for the regulated programs whenrequested. Quality Control (QC) refers to steps taken by the analysts to ensure and monitor data precisionand accuracy. Quality Assurance (QA) is an independent monitor of QC activities and specific studies. Thismanual provides a brief description of both.

Three levels of documentation define the Quality System of Exova Inc. The first tier is the Exova QualityManual, controlled at the corporate level. National and International standards are also considered first tierdocuments. The second tier is comprised of SOPs numbered Exova-SPxx, also controlled at the corporatelevel. The third tier consists of local SOPs with site specific procedures. For the Exova Inc., 9240 Santa FeSprings Road, Santa Fe Springs CA site (site 400), these are indicated as Exova SOP 101-19999. Allreferences to Exova SOPs or Exova procedures in this document refer to third tier documents.

This manual and Exova procedures detail the person responsible for carrying out quality related tasks. Inaccordance with normal management practice, it is acceptable for the designated person to delegate theactual performance of the task to another individual with the appropriate combination of education, training,or experience to perform that function. However, the responsibility for ensuring that the task is carried outcannot be delegated.

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1.7 Risk Mangement

Exova recognizes that through its technical activities it may influence the risk associated with the use of itscustomers materials, components, products, service or property. Frequently the end use of the material oritem under test may not be fully disclosed to Exova. All work is carried out on the basis that it has potentialsafety implications. No differentiation is made between safety critical and non-safety critical work.

1.8 Confidentiality

During the course of business, we are privy to data or information considered confidential or proprietary byour clients. This information includes test results, origin of samples, business relationship with client, anyprocedures and processes that they conduct or investigate, information about their business, our ownlaboratory procedures, and clients. All such information is kept strictly confidential and discussed only withthose designated as technical contacts, purchasing agents for the particular project or with corporateofficers for the clients company. The information will not be discussed with anyone, even those withinthe clients company not designated as a contact, without written permission from the client. Appendix Econtains an example of a Confidentiality Agreement.

Often we are contacted by government agencies or consultants hired by our clients. Without expresspermission, we only discuss the test methods or QC limits, and then only if it is obvious from theconversation that the caller has a copy of the original report. Any discussion of the information listed in theabove paragraph requires written permission from the designated contact. Permission by the designatedcontact may be granted by phone and should be followed in writing.

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Chapter 2: Organization and Services

2.1 Organization Structure

The laboratory is divided into eight (8) functional groups in the following manner:

Administrative, Human Resources, Accounting, PurchasingSupport Staff

Marketing, Business Development, Sales, Client Services, Sample Receivingand Control, Reporting.

Client Services

Regulatory compliance; hazardous waste and controlled substancesmanagement; facilities maintenance; metrology and equipment qualification;training and qualification of employees; materials receiving and release;laboratory investigations; change control; Deviations/NCRs andcorrective/preventative actions (CAPA); document approval and control,including test methods; quality trending and reporting to management;management of internal and third-party audits and regulatory inspections;facilitating continuous improvement of management systems.

HSEQ(Health, Safety, Environmental, andQuality)

NMR, FTIRSpectroscopy

Wet Chemistry, UV-Vis, Fluorometry, Karl-Fischer, Polarimetry,Refractometry, and CHN

Wet Chemistry

ICPMS, ICPOESInorganics

HPLC, IC, UPLCIC/LC

GC, GCMS, LCMSOrganics

ResponsibilitiesGroup

An organizational chart appears in Figure 1.

Group leaders are department managers responsible for administrative management of small groups oftwo or more staff members in a functional area. The group leaders assign work to individual members ofthe group, organize the work efforts, review data packages, and help solve analytical problems. The groupleader may be assisted with these duties by senior technical members of the group. Organizationalstructure is further defined in Exova SOPs 110 (Organization and Facilities) and 120 (Job Descriptions).

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Figure 1. Organizational Chart

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2.2 Floor Plan

A floor plan is given in Figure 2. The building is approximately 35,000 square feet (220 x 160). Laboratory floor space is assigned in the estimated manner:

Application Square Footage

GC/GCMS/LCMS 3,600ICPMS/ICPOES 6,500Wet Chemistry 2,400LC/IC 3,300NMR/FTIR 2,500Administrative, IT, and QA 2,800 Client services, Sample Receiving, Sample Storage 4,100

2.3 Instrumentation

Testing is performed using the following analytical instrumentation (See Appendix D for Equipment List)

Gas Chromatography (GC) - packed and capillary GC with flame ionization (FID), thermal conductivity(TC), electron capture (EC), Hall, thermionic N/P, flame photometric (FPD), and photo ionization (PID)detection.

Gas Chromatography-Mass Spectrometry (GCMS) - positive ion electron impact, quadrupole massfilter, capillary GCMS, positive and negative chemical ionization GC-MS/MS.

Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) with reaction and collision cells, GC-ICPMS,LC-ICPMS, and ICP-OES for elemental analysis.

Nuclear Magnetic Resonance (NMR), 500 MHz, for structural determination via proton (1H), carbon(13C), phosphorus (31P), nitrogen (15N), fluorine (19F), or silicon (29Si) spectral analysis.

Wet chemical analysis such as Karl Fischer, gravimetric, titrimetric, polarimetry, and spectrometricanalyses.

Elemental analysis: Carbon, Hydrogen, and Nitrogen (CHN) by combustion. Liquid Chromatography-Mass Spectrometry (LC-MS/MS), electrospray (ES) and atmospheric pressure

ionization (API) for both positive and negative ions. Ion and Liquid Chromatography (IC, LC, and UPLC) with UV-Vis, fluorescence, electrochemical,

refractive index and conductivity detection. Thin Layer Chromatography (TLC). Fourier Transform - Infrared Spectroscopy (FTIR) for identification of chemicals. Ultra violet and visible absorption spectroscopy (UV-Vis); Fluorometry. Refractometry.

The following analyses are subcontracted, following client approval. The client is responsible forqualifying any laboratory used for this work:

Microbiological Analyses Surface Analyses (SEM, ESCA etc.) - Subcontracted to other Exova labs. X-ray Diffraction and X-Ray Fluorescence - Subcontracted to other Exova labs.

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Figure 2. Floor Plan

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2.4 Testing Services

Testing services include, but are not limited to: Active Pharmaceutical Ingredient Characterization Air Pollution Analysis Aluminum in Adjuvanted Vaccines by ICPOES and EP (2.5.13) Anions and Cations by Ion Chromatography Arsenic (ultra trace and speciation) Boron (traces in biological samples) Cleaning Validation Studies Composition of Organic Mixtures Consulting and expert witness testimony. Contaminant Analysis - Organic or Inorganic Diet and Nutrition Studies Support Elemental Analysis (Carbon, Hydrogen, and Nitrogen by combustion) Elemental Impurities, including USP and ICH Q3D Environmental Analysis (drinking water, soil, wastewater, hazardous waste, ambient & air stack gas) Food and Flavor Analysis Gas Analysis (fixed gases and hydrocarbons) Hexavalent Chromium (ultra trace) Identification by FTIR; FTIR Microscopy Identification by NMR; Impurities by Quantitative NMR Identification of Unknown Chromatographic Peaks Industrial Hygiene Analyses (NIOSH & OSHA Methods) Impurities in Active Pharmaceutical Ingredients and Excipients, Organic and Inorganic Leachable Contaminants from Plastics (for pharmaceutical containers) Medical Device Testing (chemical contamination) Metabolite and Degradation Identification Metals Analysis (trace and ultra trace) Molecular Structure Elucidation Natural Gas and LPG Analysis Optical Rotation Perchlorates by IC-MS/MS Pesticide Residues Pharmaceuticals Analysis Pharmacokinetic Studies Support Phthalates by GCMS Polymer Additives; Polymers and Coatings Analysis Proposition 65 (California) - Toxic chemicals in products sold in California Raw Material Specifications (USP, NF, EP, JP, FCC, ACS, etc.) Registration, Evaluation, and Authorization of Chemical Substances (REACH) Restriction of Hazardous Substances (RoHS) Residual Solvent Analysis, including USP and ICH Q3C Risk Assessment Studies Support Semivolatile Organics by GC, GCMS, and LCMS. Solvent Composition Sterilant Residues Surfactant Identification USP/NF, EP, BP, JP and other Compendial Testing Volatile Organics by GC and GCMS

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2.5 Test methods

Routine methods and procedures are described in Exova Standard Operating Procedures (SOPs). A list ofSOPs is given in Table 1. Copies of our quality system and general laboratory SOPs may be found on ourwebsite: http://www.exovachemist.com.

The following references are used for analytical methods: American Chemical Society (ACS) Reagents American Society for Testing and Materials: Annual Standards (ASTM) U.S. Environmental Protection Agency (EPA): Manuals: EPA 600, SW846, etc. American Public Health Association American Water Works Association (AWWA) Water Pollution Control Federation: Standard Methods for the Examination of Water and Wastewater American Pharmaceutical Association: National Formulary (NF) The U.S. Pharmacopeial Convention, Inc.: The Pharmacopeia of the United States (USP) European Pharmacopoeia (EP) Japanese Pharmacopoeia (JP) FDA Pesticide Analytical Manual The Association of Official Analytical Chemists (AOAC): Official Methods of Analysis of the Association

of Official Analytical Chemists California Air Resources Board (CARB) and Air Quality Management Districts (AQMD) manuals State of California: LUFT Manual Military Specifications: (MIL-SPEC) NIOSH and OSHA Manuals of Analytical Methods Food Chemical Codex (FCC) Other government and private sector specifications

Table 1 Standard Operating Procedures

General SOPs

101 Control of SOPs and Test Methods110 Organization and Facilities120 Job Descriptions140 Documentation of Training and Employee Qualification170 Sample and Waste Disposal190 Complaint Resolution200 Radiation Safety210 Handling Controlled Substances220 Change Control240 Housekeeping, Pest Control, and Security250 Internal, Third Party, and Vendor Audits260 Vendor Qualification270 Laboratory Non-Conformances, Including Corrective and Preventative Actions280 Lock-out, Tag-out Program500 Good Laboratory Practices

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Manuals

900 Exova Safety Manual930 Quality Assurance Manual

Administrative and Clerical Procedures

1000 Record Retention1500 Sample Receipt and Review of Contracts1510 Temperature Monitoring 1520 Foreign Soil Documentation1530 Environmental Sample Preservation Checking1540 Importation or Transfer of Etiological Agents

Laboratory SOPs

2100 Solutions, Reagents and Standards Preparation2110 Calibration and Use of Analytical Balances2120 Data Management and Computing Systems2130 Network Backups and Maintenance2140 Thermometer Calibration2160 Laboratory Data Review and Generation of Reports2170 Selection, Maintenance, and Calibration of Volumetric Measurement Devices2180 Detection Limits2190 Significant Figures and Rounding2200 Water Purification2220 Method Validation and Verification2230 Out-of-Specification (OOS) Investigations2240 Good Documentation Practices2250 Instrument Qualification and Facility Equipment Maintenance2260 Control and Use of Laboratory Notebooks, Logbooks, and Worksheets2270 Data Archival and Retrieval2280 Control of Purchased Standards, Chemicals, and Reagents2290 Calibration and Use of pH Meters2300 General Chromatography2800 Glassware Cleaning

Test Methods and Instrumentation SOPs

3000-3999 (non-validated), 13000-13999 (validated) Gas Chromatography4000-4999 (non-validated), 14000-14999 (validated) Liquid Chromatography5000-5899 (non-validated), 15000-15899 (validated) Gas Chromatography-Mass Spectrometry5900-5899 (non-validated), 15900-15999 (validated) Elemental Analyzer6000-6999 (non-validated), 16000-16999 (validated) NMR and FTIR7000-7999 (non-validated), 17000-17999 (validated) ICPMS and ICPOES8000-8999 (non-validated), 18000-18999 (validated) Wet Chemistry9000-9999 Miscellaneous

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Chapter 3: Laboratory Quality Assurance

The responsibility for maintaining the laboratory quality assurance systems rests with the HSEQ Officer.Independent oversight and monitoring of laboratory quality control is performed by the Quality Unitcomposed of the HSEQ Officer and others, as assigned. Employees are trained in quality control,GMP/GLP, NELAP, and ISO/IEC 17025 during regularly scheduled training sessions that cover policies,SOPs, recent audit findings and other NCRs, and regulations.

3.1 Role and Responsibilities of the Quality Unit

The Quality Unit is responsible for assuring compliance with regulatory agency requirements, certifyingbody standards, corporate policies, and quality agreements with clients. HSEQ responsibilities includeensuring the health, welfare and safety of all employees and visitors; hazardous waste and controlledsubstances management; facilities maintenance;metrology and equipment qualification; training andqualification of employees; materials receiving and release; laboratory investigations; change control;corrective and preventative actions; document approval and control, including test methods; qualitytrending and reporting to management; management of internal and third-party audits and regulatoryinspections; and facilitating continuous improvement of management systems. The Quality Unit is headedby the HSEQ Officer, who also reports to the Exova corporate Quality Manager (however named). TheHSEQ Officer is responsible for the implementation and monitoring of the Exova management system andfulfills the Quality Manager function as defined in International Standards. The HSEQ Officer heads theQuality Unit, as defined in FDA GMP and GLP regulations. The HSEQ Officer has the authority to stopwork and withhold the issuance of reports and certificates where such activities compromise the integrity ofExova services, the validity of reported data, or management system requirements.

3.2 Internal Quality Control

For quantitative tests, a minimum of 5% of incoming samples are split and analyzed in duplicate (includingduplicate sample preparation) to yield data on the precision of the analysis. Results from the analysis ofduplicates are individually reported to the client. A minimum of 5% of incoming samples are spiked withknown amounts of the analyte to determine method accuracy. This is described in more detail below.Method blanks are prepared and analyzed with each batch of samples in order to identify potentialinterferences or contamination of samples. Standard Reference Materials (SRM) are routinely used asLaboratory Control Standards (LCS) or second source Initial Calibration Verification (ICV) samples. Whenlarge numbers of samples are included in an instrument run, the analysis of a midrange calibrationstandard is repeated at appropriate intervals to demonstrate that acceptable system suitability has beenmaintained.

In the statistical analysis of data precision and accuracy, control limits are set using 3 standard deviations(SD) from the mean. If the data shows that an out-of-control situation or uncertainty of measurement maycause an erroneous conclusion because of its proximity to a critical or regulatory limit, the source of errorshould be identified and corrected, the initial results invalidated, and the analysis repeated. The use of dataoutside control limits must be scientifically supported and shall be at the discretion of the group leader,Technical Director, or QAU (for GMP/GLP or ISO 17025 scope work) depending on the needs of the client.

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3.3 Precision and Accuracy in Quality Control

As a general QC procedure, replicate analyses are performed for determining precision and spikedsamples are analyzed to determine accuracy. Control limits are set at 3 SD (99% confidence limits). Theanalysis of standards is routinely repeated during the instrument run to ensure calibration and systemsuitability remains within set parameters. Initial Calibration Verification (ICV) standards, prepared from asecond source (preferred) or second weighing of a reference material, are used to demonstrate theaccuracy of the calibration curve. Midrange continuing calibration standards are analyzed at appropriateintervals throughout a run to demonstrate system suitability throughout the analysis.

Accuracy is a measure of the nearness of a result or the mean of a set of results to the true value. It isoften expressed as percent recovery from a spiked sample. If the native concentration of a target analyte ishigh relative to the spiking concentration, then this may contribute a significant uncertainty tothe recovery calculations; the MS recovery may not be representative of actual method performancefor the matrix. In the absence of other guidance, for instance that established through a method validation,the MS recovery is evaluated when the spiking concentration is greater than the native analyteconcentration. If the spiked amount is less than the amount in the unspiked sample, the percent recovery isreported as NR (not reported).

Recovery is calculated as:

SS - S Percent recovery = SA * 100% where SS = spiked sample S = original unspiked sample (the average of duplicate preparations is used,

if available) SA = spike amount

Precision is a measure of agreement between replicate determinations. It can be expressed as relativepercent difference (RPD) or relative standard deviation (RSD) from replicate analyses. Precision is onlymeaningful when the analytes are quantitated above the limit of quantitation. If the values are below theestimated LOQ, the precision is reported as NR (not reported).

Precision in the laboratory is commonly calculated as:

|( z - y )| RPD = ( z + y ) / 2 * 100%

where z = original result y = duplicate result

An example of how precision and accuracy data are used:

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A set of 15 water samples is submitted for routine analysis for an antioxidant. One sample from this setis selected for duplicate analysis. Two aliquots of this sample are analyzed. The results of this set ofduplicates are compared to previous laboratory data which shows that the relative standard deviationfor past replicates of this approximate concentration of analyte is 6%. If the relative percent difference(RPD) of the duplicates is larger than 18% (3 SD), the set of results are suspect. The method andresults are critically reviewed to determine if a problem was encountered which must be corrected. Thesample which has been analyzed in duplicate is also spiked with the analytes of interest. Previouslaboratory data has shown that mean recovery of the antioxidant from this type of sample is 95% with astandard deviation of 5%. The control limits are therefore 80-110%. The recovery of this particularsample is therefore used to judge the validity of the set of results as outlined above. If precision oraccuracy measurements are outside of the control limits, the group leader must be notified and theanalytical problem corrected.

The analyst is directly responsible for quality control during analysis. Many data reduction schemes involvevalidated Lotus 1-2-3 spreadsheets. Each of these incorporates forms for documenting QC results fromduplicates, spikes, and control samples in the final report. The forms compare the analytical results withcontrol limits, and flag the results if they are outside these limits.

The group leader or a second qualified analyst reviews these forms in the data packages (per SOP 2160).The analysts are responsible for alerting their supervisors of non-conformances (per SOP 270), finding andcorrecting any problems, obtaining authorization for a re-test (if an assignable cause is found to invalidatethe data, such as laboratory error), and reanalyzing samples. In this way, the QC program identifies andcorrects analytical problems as they arise.

3.4 Control Charts

Control charts are useful for monitoring trends in analytical precision, accuracy, and identifying problemoccurrences. In general, a parameter of known value is measured periodically during a sample set, and itsmeasured value is compared with its theoretical value. From a number of such measurements, the SD canbe calculated. Acceptance windows for this measurement can then be set, typically 3 SD. Data can thenbe plotted on a graph with the measured value on the Y-axis and the sample sequence on the X-axis. Theacceptance or warning limits are shown in the graph as dotted lines extending from the Y-axis representingY 3 SD, when Y is the mean of several measurements. EXAMPLE: The data set below was taken from the analysis of 100 biological samples for lead (Pb). Onesample out of every 10 was spiked with 10 g Pb and the percent recovery Calculated.

10 1019 1068 1047 1016 1005 1024 1003 962 1021 104Sample Pb % Recovery

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The mean and standard deviation were calculated and found to be: X = 101.6SD = 2.76

This data can then be used to prepare a graph showing the measurements and how they compare to thewarning limits ( 2 SD) and control limits ( 3 SD). If any of the data fall outside the control limits, this wouldmean that the analytical data may have abnormally large errors, and that some of the samples may need tobe reanalyzed. The control limits determined by this set of 10 spikes can then be used to judge theacceptance of future spiked samples by adding their results to the graph. When significantly more data isgathered, the control limits may be recalculated.

3.5 Correction

SOPs outline general steps and policies for individual test procedures. Whenever an out-of-control situationhas been detected, the analyst notifies a supervisor and, under their guidance, works to resolve the issue.After resolution, the analyst continues with appropriate actions to bring the analysis back in control.Repreparing and/or reanalyzing samples is only performed if previously acquired data is first invalidateddue to a documented laboratory error, instrumentation problem, or as part of a pre-approved investigationinto the cause of the out-of-control situation. When sample or time limitations (rush work) precludecorrecting the situation, the issue is discussed with the Quality Unit, the client is notified, and theout-of-control data is flagged on the report.

3.6 Laboratory Control Standards (Reference Materials)

Exova uses standard reference materials from NIST, EPA, USGS, USP, and other sources to check theaccuracy of analysis and to calibrate instruments. Some of the reference materials used are listed in Table2. These materials are used to routinely check analysis using control limits from historic or round-robindata. Certified Reference Materials (CRM), traceable to NIST or other primary standards, are purchasedfrom ISO Guide 34 and ISO 17025 accredited suppliers for use as standards, when available. If notavailable, consensus standards (USP or EP) or neat chemical standards with a purity documented to begreater than 96% may be used for analyses not requiring NIST traceability (e.g. not within the scope of thelaboratory's ISO 17025 certification). Clients may supply the laboratory with well-characterized materials touse as standards for analysis. If these are to be retained for further analyses, the client must providestorage conditions and an expiration date. Characterization and qualification of these standards is theresponsibility of the client.

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Table 2 Standard Reference Materials

NIST Standard Reference Materials (SRMs):

C241B Lead (Bullet) 1645 River Sediments (Trace Metals)600 Bauxite 1646 Estuarine Sediment (Trace Metals)679 Brick Clay (Trace Metals) 1845 Cholesterol in Whole Egg Powder887-9 Cemented Carbides 1889 Cement Composition951 Boric Acid (Isotopes) 2670 Toxic Metals in Freeze-dried Urine981-3 Lead Isotopes 2677a Beryllium & Arsenic on Filter Media987 Strontium Carbonate (isotopes) 2704 Buffalo River Sediment (Trace Metals)1084 Wear-Metals in Lubricating Oil 2713 Lead in Reference Fuel Oil1486 Bone Meal 2715 Lead in Reference Fuel1567 Wheat Flour 3087 Metals on Filter Media1572 Citrus Leaves 3126 Iron1577a Bovine Liver 3149 Selenium1588 Organics in Cod Liver Oil 3159 Thorium1549 Nonfat Milk Powder 3168 Zinc1583 Chlorinated Pesticides 3181 Sulfate1632b Trace Elements in Coal (bituminous) 3183 Fluoride1635 Trace Elements in Coal (sub bitum.) 3184 Bromide1633 Trace Elements in Coal Fly Ash 3186 Phosphate1634b Trace Elements in Residual Fuel 4350 River Sediment (Trace Metals)1640 Natural Water 4354 Lake Sediment (Trace Metals)1641b Mercury in Water 8407-8 Mercury in Sediment1643c Trace Metals in Water 8486-8 Portland Cement Clinker

National Research Council Canada:

Best -1 Marine SedimentBCSS-1 Marine SedimentCASS-2 Nearshore Seawater Reference Material for Trace MetalsDCSS-1 Marine SedimentDORM-1 Dogfish MuscleNASS-3 Open Ocean Seawater Reference Material for Trace MetalsPACS-1 Marine SedimentSLRS-1 River Water

Miscellaneous Reference Samples:

EPA WS and WP Samples EPA PCBs in OilEPA Trace Metals in FishNIOSH Past PE samples for IH reference samplesRestek SemivolatilesSupelco HerbicidesSupelco, RTC Volatile organicsCPI, SCP NIST traceable inorganic standardsUSGS Various T,M, and Hg Series samplesExova Volatile organics in gasUSP, EDQM Consensus Reference Standards for USP and EP monograph testing

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3.7 External Quality Control Programs

Accreditations, licenses, and certifications are listed in Appendix H. The laboratory regularly participates inproficiency testing (PT) round-robins, including the following:

American Industrtial Hygiene Association California Department of Health Services Environmental Laboratory Accreditation Programs

(ELAP, formerly the Approved Water and Hazardous Waste Testing Programs) Environmental Resource Associates (ERA) PT programs: Water Supply (WS), Water Pollution

(WP), and Soil. U.S Geological Survey (USGS) Resource Technology Corporation (RTC) PT programs, including organic lead and

pharmaceutical analyses Institute for Interlaboratory Studies (IIS): Metals in plastics, phthalates in plastics FAPAS PT programs: Food chemistry testing NIST - Quality Assurance PT program for Food Supplements

3.8 Data Packages, Data Review, and Data Audits

Raw data is assembled with the draft report and QC summaries into data packages by the analysts. Acover page summarizing the contents of the data package and any deviations is signed by the analyst anda supervisor or second qualified analyst after the data has been reviewed, per SOP 2160. The datapackage contains the face page; a copy of the instrument run log; QC summaries such as internal standardrecovery, calibration data, LCS summary, duplicate results, matrix spike/matrix spike duplicate (MS/MSD)recovery, and blank results; raw data; and Retest/Reanalysis or QC Action Forms (if required). The datapackages are then filed by date or job number within an analytical group.

All GLP and GMP data and at least 10% of all non-GLP/GMP data packages undergo an independent auditby the Quality Unit. In addition, clients may order a QA reviewed data package. This includes copies of allraw data and a documented audit of the data by a member of the Quality Unit. Following data audits, theQuality Unit will initiate any corrective action required to comply with Quality Standards (per SOP 270),generally involving the group leader, analysts, and the Technical Director (as needed).

The Quality Assurance system of QC procedures, preset QC limits, review of data packages, and approvalof reports is designed to catch errors and problems prior to data being reported to clients. However, whencorrective actions or investigations reveal a potential problem with previously reported data, the client isnotified within one business day.

3.9 Document Control

SOPs are reviewed and revised as needed, at a minimum once every two years. Revision or effectivedates, approval signatures, and a summary of changes are documented in the preface to each SOP.Document changes are approved by a technical reviewer and the Quality Unit (SOP 101). Original copiesand associated computer files are kept in a secured manner. The access of analysts to the current versionsof SOPs, validated spreadsheets, current compendia, and approved test methods is ensured through theuse of a password protected Intranet system with appropriate levels of access assigned to each employee.Obsolete versions of documents are archived and controlled by the Quality Unit. Bound laboratorynotebooks or controlled worksheets are used for the recording of original data and observations.

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3.10 Purchasing

Exova uses only suppliers from an approved supplier list maintained by our corporate entity to purchaseservices, equipment, and supplies for the laboratory (SOP 260). Upon receipt, materials and reagents areexamined by the Quality Unit for container integrity, labeled with the date received and an expiration date,and entered into the Chem Track module of Job Tracking following a review of the manufacturersCertificate of Analysis (SOP 2280). Materials and reagents are then stored in accordance withmanufacturers instructions to prevent deterioration. Critical reagents are analyzed for suitability prior to usewith each new vendor lot number.

3.11 Change Control

Significant changes to test procedures, controlled documents, materials, qualified equipment,management, or facilities are documented and approved by the Quality Unit (SOP 220). Our clients areinformed if there is any potential impact to the quality of a clients data.

3.12 Customer Service and Client Audits

Exova is committed to providing its customers with all reasonable cooperation in the performance of itsanalytical services in accordance with their needs. Exova will provide customers or their authorizedrepresentatives with access to witness work being performed and to audit our quality systems. Suchaccess will be controlled and arrangements will be made to ensure that the confidentiality, protection, andsecurity of other customers work is maintained. Exova reserves the right to charge an additional fee forthis service. Employees who deal with clients will behave with respect and integrity towards the customer.Customer feedback surveys are used to monitor customer satisfaction with our services.

3.13 Complaint Resolution

When a complaint is received, a permanent record is created, tracked to ensure resolution, and brought tothe attention of senior management (SOP 190). A complaint is a client contact that questions the quality orvalidity of our analytical work. The nature of the complaint is documented by opening an entry in theComplaints module of the Job Tracking database. A senior level employee is assigned to resolve theissues. The progress of the complaint resolution is discussed and tracked during weekly staff meetings.Finally, after resolution, the client is contacted for final comments, and the complaint form is signed off bythe General Manager or, in his absence, the Technical Director or HSEQ Officer. Opportunities forimprovement are entered into the CAPA program when applicable and trend reports are prepared andpresented to Corporate QA and the General Manager on a monthly basis.

3.14 Out-Of-Specification (OOS) Investigations

Whenever test results fall outside of the specifications or regulatory limits provided by our clients orout-of-trend results are noted by our clients, an OOS form is generated, an investigation is initiated, and theclient is notified within one business day of the completion of the intial investigation (SOP 2230). Retestingis not performed unless the investigation concludes that the original data is invalid due to a documentedlaboratory error or instrumentation problem. Reanalysis of sample preparations may also be performed aspart of the OOS investigation. Resampling or retesting, in the absence of an assignable cause, is onlyperformed under the direction of a client-approved retest plan, in accordance with our clients OOSprocedures

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3.15 Non-Conformances (Deviations) and CAPA

Metrology out-of-tolerance events, deviations from approved test procedures, vendor quality issues,sample storage condition excursions, laboratory errors, or other unexpected events that have the potentialto affect the quality of data are documented and investigated (SOP 270). When necessary, work is stoppedto prevent further adverse effects on the quality of data. The root cause is identified, where possible.Corrective and preventative actions are approved, tracked, and trended by the Quality Unit. Our clients areinformed if there is potential impact to the quality of their data.

3.16 Validation, Transfer, and Verification of Methods

Most standard and compendial methods are considered validated, however verification of their suitabilityunder actual conditions of use must be demonstrated. Exova accomplishes this through the analysis ofquality control samples, including positive and negative controls, matrix spike samples, and duplicateanalyses, as applicable. In addition, system suitability criteria for instrumentation provides assurance thatthe instrument conditions are appropriate for the analysis. Validation, verification, or transfer of testmethods for a specific client matrix, in accordance with USP , USP , and ICH Q2(R1)guidelines, may be performed upon request, per SOP 2220. The assessment of the regulatory requirementfor method validation, transfer, or verification is the responsibility of our clients. If analytical work isperformed on samples within the scope of FDA GMP (as indicated by our clients) and the method has notbeen validated for that matrix within our laboratory, the laboratory report will state this.

3.17 Facility and Environmental Controls

Prevention of contamination and preservation of the integrity of client samples is ensured throughcontrolled sample handling, including temperature monitoring of sample storage and laboratory testingareas. In addition, specific air handling or containment systems are in place for critical sample handling, asappropriate. A written program for housekeeping, security, and pest control is in place (SOP 240). Securityof the facility is maintained through locked doors to the facility, an alarm system, and monitored videosurveillance. No area of the laboratory is used in a manner that would adversely affect its primary functionas a controlled testing environment.

3.18 Training and Qualification of Analysts

We have in place a training program (refer to SOP 140). to ensure that our chemists are qualified and keptup-to-date on method changes (including compendial changes), SOP changes, instrument additions, andcGMP. New employees begin with an orientation program, complete an initial training period, and thenproceed to extended training. Documented reviews are conducted annually that include an evaluation ofefficacy of training, including a review of the analysts participation in proficiency testing programs. Jobtitles reflect progress in training, experience, and responsibilities (refer to SOP 120).

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3.19 Qualification of Equipment

A bound logbook is maintained for each analytical instrument. This logbook is used to document theanalysis of samples and to record calibration, qualification, and maintenance information. These logs arereviewed with each data package and periodically by the QAU (SOP 250).

Qualification and calibration of instrumentation is performed in accordance with written procedures (SOP2250). Equipment is qualified for use when first acquired (IQ/OQ) and when significant repairs or changesto the instrumentation occur. Performance verification (PQ) is documented for equipment at appropriateintervals. Analytical equipment is labeled with its calibration or qualification status. Equipment found to beout-of-tolerance is labeled "out of service" or removed from the area to prevent unauthorized use.Equipment which is beyond its calibration date, or has otherwise not been demonstrated as qualified for itsintended use, will not be used for commercial analytical work.

3.20 Software Validation

Computerized analytical instruments contain integrated chips with low-level software, known as firmware.Such instruments will not function without properly operating firmware, and users generally cannot alterfirmware design or function. Firmware is therefore considered a component of the instrument itself and thequalification of hardware is not possible without operating it via its firmware. Operational Qualification,which involves the entire instrument and software system, qualifies the firmware holistically. Themanufacturer performs Design Qualification, validates the software, and will provide a summary ofvalidation when the instrument is installed. Operational Qualification, which involves the entire instrumentand software system, qualifies the instrument control, data acquisition, and processing software holistically.Software associated with analytical instrumentation used for FDA GMP or GLP work is additionallychallenged to demonstrate the security of data storage, backup, archiving, and the presence of audit trails.This challenge is performed by executing a Data Integrity Protocol. This protocol is re-executed at aminimum of every three years or when a change in software is made that has the potential to affect dataintegrity.

3.21 Internal Audits

Scheduled internal audits are performed on a regular basis and cover all areas of activity on an annualbasis (SOP 250). Audits include quality system evaluations as well as data and logbook reviews. Forcause and follow-up audits are performed in response to non-conformance investigations and todetermine the effectiveness of preventative actions. Whenever an audit finding casts doubt on the validityof a clients data, the client will be immediately notified.

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3.22 Continuous Improvement

Exova is committed to continuous improvement. The effectiveness of quality systems, includingmanagement, is subject to ongoing assessment and review. Methods of identifying opportunities forimprovement include, but are not limited to, complaint trending, OOS trending, NCR/CAPA trending, clientaudit reports, regular management meetings, review of client surveys, review of proficiency testing data,and periodic review of the quality policy.

3.23 Business Continuity Plan

Exova has an on-site generator to provide power to critical electronic equipment in the case of anemergency. This system is challenged once a week. The computer archival system includes regular off-sitestorage of data. Our business continuity plan includes subcontracting work to other qualified Exovalaboratories to perform testing temporarily unavailable at this site.

If the laboratory goes out of business, clients will be notified at least 60 days in advance of the closure ofthe laboratory. Requests for data packages will be processed to ensure that clients are able to archive datarelated to their analyses in accordance with their internal record retention policy.

3.24 Management Review

The corporate entity of Exova Inc. conducts a management review of the management system and itsimplementation at each site annually. The review includes an assessment of the effectiveness of the Exovamanagement system. Recommendations for improvement across sites and plans for implementation arecoordinated by the Exova HSEQ Director or designated Quality Manager.

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Chapter 4: Operational Procedures 4.1 Sample Receipt

Samples are received in the Log-in area where lab personnel are responsible for logging in the samples,assigning them a unique identifier, entering them into the Job Tracking computer database, and securingthem in the appropriate storage area under the direction of the Client Services Manager.

4.2 Review of Analytical Request Forms

Chain-of-Custody (CoC) procedures are followed for almost all samples, but especially for environmental orindustrial hygiene samples because of their potential for litigation. All environmental samples delivered tothe lab should be accompanied by CoC forms. This is necessary to preserve the traceability and security ofsamples as evidence. Samples are considered secure for evidentiary purposes if they are in onespossession, within view, or in a secured area. The lab is considered secure because access duringworking hours is monitored and the lab is locked and armed with alarms (audible and silent) during nonworking hours. Cameras provide monitoring of the periphery of the building and points of entrance. TheCoC record is used to document the change in possession from sampling to delivery to receipt by thelaboratory. On the back of the Exova CoC are our Terms and Conditions (See Appendix F).

Clients may have forms of their own to use to request analytical work or they may use our CoC (Figure 3.)or Analytical Request Form (Figure 4.). When the samples are received by the laboratory, the analyticalrequest form is reviewed and the client contacted if any requirements are unclear. The Job Trackingdatabase is used to capture previous contact with the client to ensure analytical work proceeds inaccordance with the clients needs. Each sample must be uniquely identified or the client will be contactedfor clarification. The condition of the sample/container and the presence/absence of custody seals is noted.Signatures of parties changing custody, date and time is documented on the form.

In rare cases, some clients may require internal laboratory CoC procedures in addition to sample receipt. Inthis case, the samples are kept under lock by the Sample Custodian (Client Services Manager), and anadditional form documents the change of possession with each analyst who handles the samples.

4.3 Sample Receipt and Review of Contracts

A hardbound Master Job Logbook is maintained at the Log-in desk. The following information is enteredinto the log to initiate a job:

1. Initials of person receiving/logging in the job and the date received2. How samples were delivered to Exova (e.g. client, courier, U.S. Mail, UPS, FedEx)3. Assigned sequential job number (a number stamp is used)4. Customers company name5. Number of samples 6. Description of the work requested7. Group to which the work is assigned8. Indication that the job was reviewed and entered into the Job Tracking database9. Invoice date and number10. Disposition of samples after the analyses are completed, i.e., consumed in test, stored, returned to

customer via, etc.11. Remarks - for any other special entries.

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Figure 3: Chain-of-Custody Form

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Figure 4: Analytical Request Form

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4.4 Job Envelope, Job Number, and Distribution

Concurrent with entering the above information into the Master Job Log, a job envelope is prepared whichwill ultimately contain all correspondence, notes, and draft reports connected with this job. A copy of thefinal report is also filed in the job envelope.

A sequential, unique job number corresponding to the entry number in the Master Job Log is placed on thejob envelope and on each sample container associated with the job. At times, samples may be too delicateor small to accommodate a job number affixed to the container. In this case, a note is made on the jobenvelope indicating that individual samples have not been labeled with a job number and the samples areplaced in a secondary container which is labeled with the job number (e.g. a plastic bag). In the case ofbiological samples, the job number may be added at the time of sample prep/extraction. A note to thiseffect will also be made on the job envelope. Subsequent references to the sample are made using this jobnumber combined with the customer's sample identification. By using the clients sample identification, weminimize the possibility of sample switching or misidentification resulting from using two identifiers (clientand lab) for a particular sample. After checking in the samples, logging the job into the Job Trackingdatabase, preparing the job envelope, and tagging the samples, the samples are placed in the appropriatestorage location and the job envelope is placed in the Client Services office in the numerical job file. Exovaadheres to method or client specified storage parameters such as cold storage, controlled roomtemperature, protection from light, etc. Depending on the method requested, samples are either stored inrefrigerators, freezers, or on shelves in a cool and dry room. Samples are stored in this manner for aminimum of four weeks after the invoice date, after any investigations related to the analysis have beencompleted.

The jobs are assigned, at the time of sample log-in, to the group or groups that will be responsible for theanalytical work. If log-in personnel do not have adequate information to assign the group, then ClientServices assigns this when they receive the job sheet for review. Once the paperwork has been receivedby Client Services and submitted to the appropriate analytical group(s), a staff member from the group willcheck the samples and associated paperwork to ensure that all the information necessary for jobcompletion is present. If more information is needed, the analyst, group leader, or a Client Servicesrepresentative will contact the client.

Information from the Master Job Log is entered into a computerized, validated database (Job Tracking) andthen verified by a second employee. Designated group leaders schedule work for their groups and assignmembers of their groups to various analyses. Analysts and group leaders are able to access a listing ofoutstanding jobs from the Job Tracking database to plan their daily work schedule.

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4.5 Sample Analysis and Review

Analysts record their work in bound logbooks or on controlled worksheets specific to the instrument or typeof analysis. Sample, standard, and reagent preparation is documented in bound logbooks or on controlledworksheets. Each analytical instrument has a logbook used to record instrument activity, including eachsample analyzed or sample injection (standards, calibrations, blanks, test articles, etc.).

These logbooks or worksheets are used to record the following information about the analysis:

1. Instrument run number (if applicable)2. Analyst initials/Date3. Job number/Client4. Sample identification5. Other pertinent information, such as instrument conditions or method used6. Equipment and/or instrument used7. Standards, materials, and reagents used, including identification and expiration date

Analyses are generally conducted in compliance with Exova SOPs, compendial methods (USP, ACS, EPA,etc.), client provided methods, or published methods. When the analysis of samples is complete, theanalyst assembles the raw data, calculations, and QC information into a data package for review andsubsequent filing (refer to SOP 2160). The first page of the data package, signed by the analyst,summarizes the contents of the package, QC parameters, and any non-conformances. The data packagecover page is also signed by a supervisor or other senior analyst following a technical review of the datapackage (See section 4.7). Data packages associated with GMP/GLP work are also audited by the QAU.

4.6 Job Tracking

From the Exova Job Tracking computer database, periodic outstanding job lists are prepared and reviewedwith each group manager. An end-of-the-month reconciliation is done between the Exova Job Trackingcomputer network and the Master Job Log Book. Sample results files for inclusion in the final report areintegrated into this data base. A hierarchy of security measures is provided through password protection.Only select, qualified staff members are allowed access to make changes to or approve reports (per SOP2160 and 2240).

4.7 Data Reporting

After the analysis is complete, analysts prepare the draft report by creating a file using the Job Trackingdatabase. The raw data and the draft report are assembled by the analyst and reviewed by a supervisor orsenior analyst. The draft report and job envelope are forwarded to Client Services and the draft report isfaxed or emailed to the client. The reviewing analyst enters a status of complete into the Job Trackingdatabase.

The final report and invoice are prepared by Client Services. Each report is reviewed and signed by twoindividuals: a Senior Chemist (or higher) and the Technical Director or two Senior Chemists (or higher). ForGMP and GLP work, one of the signatories will be a member of the QAU. Depending on client preference,data can be reported in several different formats including hard copy, FAX, e-mail, CD, and custom agencyreport formats such as WIP, CLP, and others.

Raw data packages are available at an additional charge. GMP data packages may be ordered by theclient. This format includes documentation of a QA audit of the raw data.

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4.8 Storage of Completed Samples, Reports, Data and Job Envelopes

A copy of the signed final report is filed in the job envelope. Job envelopes are filed numerically. Datapackages are filed by date or job number within an analytical group. Hard copies of raw data are kept onsite for two years and stored off-site for an additional five years (total retention time = seven years).

Approximately four weeks after invoicing, samples are either disposed with other compatible lab waste (perSOP 170) or returned to the customer. For new clients, a card is sent with the final report requestingdirections for disposition of the samples. If this card is received back from the client, we will either returnthe samples or dispose of them according to the clients request. If the card is not received back from theclient, the client will be contacted only if the samples are extremely hazardous. If the samples are notextremely hazardous, the samples will be disposed of without contacting the client.

Samples are disposed of following all State and Federal regulations governing disposal. Exova utilizes anoutside service for shipping and disposing of our wastes.

For legal samples, the client will be contacted concerning disposition of their samples. Most legal sampleswill be returned to the client. All others will be disposed of after receiving the clients approval.

4.9 Sample Containers and Sampling Supplies

Sample bottles are supplied as a courtesy to our clients under the condition that the samples will bereturned to us for analysis. Sample bottles are pre-cleaned by the sample bottle supplier. We will alsosupply sample bottles that are certified clean to specified limits for a nominal fee.

4.10 Shipping and Receiving

We normally use UPS, FedEx, or equivalent to ship samples, sample containers, and supplies to clients. Ifan item is needed on an expedited basis, we will use a courier service or other premium service to ensurethat the client receives their requested items within the time frame needed. All items shipped from Exovawill meet DOT regulations. Shipping is provided either free of charge or for a nominal fee depending on thesituation and urgency.

Exova receives thousands of samples every year, day in, day out. All delivery services serving this areacan and do deliver to our facility. We are open for sample receiving from 7:00 a.m. to 5:00 p.m., Mondaythrough Friday. Late night, weekend, or holiday sample receipt can be arranged. For our employeessafety, we insist that any known sample hazards be explained in the paperwork sent with the samples.

4.11 Subcontracting

Exova may subcontract analytical work to outside laboratories or to other Exova testing facilities upon clientrequest. Client approval is obtained before any work is subcontracted. The certificate of analysis from thesubcontractor is forwarded to our client as received. Auditing and qualification of subcontract laboratories isthe responsibility of our clients.

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Chapter 5: Specific Analytical Capabilities With the professional staff and equipment that we have, our abilities to solve complex client problems havebeen proven time after time. Exova has pioneered the application of many of its instrumental techniques toproblems of trace analysis for many industries. The following sections give more information on ourexperience. Specific projects are described in Appendix G.

5.1 Pharmaceuticals and Medical Devices

Exova is expert at full monograph testing of most compounds and materials found in the USP, NF, EP, JP, andmany other compendia. Pharmaceuticals can be assayed using chromatographic (GC, HPLC, TLC, etc.) or wetchemical methods. Metabolites and contaminants have been identified and quantitated using HPLC, LCMS,GC, GCMS, and LC-ICPMS. For medical devices, our clients use our services for determining sterilantresidues, residual metals and anions, additives, contaminants in polymers, structural determination ofpolymers by NMR, and other analytical challenges.

5.2 Heavy Metals Testing: USP , ICH Q3, REACH, and California Proposition 65

As the first contract laboratory in the United States to offer commercial trace metals testing by ICPMS, we havean unmatched depth of experience to help companies transition from non-specific heavy metals methods, suchas USP , to the new USP Elemental Impurities General Chapter required to demonstratecompliance with USP , USP and ICH Q3D specifications for the control of inorganic impurities indrug products.

Interest in trace amounts of lead (Pb) in calcium based antacids and dietary supplements was initially fueled byCalifornia Proposition 65, which limits exposure to lead to 0.5 g/day. Testing has expanded from calciumbased products to practically all types of supplements, drug products, and herbal formulations.

Our test method involves dissolution or digestion of the product in acid, addition of an isotope dilution internalstandard, and analysis of the lead isotopes using ICPMS. To date, this procedure has been validated at thislaboratory on more than 50 products. The use of an isotope dilution technique makes the method very robustin a wide array of matrices, even in the presence of high concentrations of dissolved solids.

Other testing for California Proposition 65 (and its European counterpart, REACH) include testing fabrics andcoatings used on children's lunch boxes and backpacks, leachables from small kitchen appliances anddinnerware, testing for phthalates in plastic bottles, and many other analyses on consumer products offered forsale in California and around the world.

5.3 Unique Applications of IC-ICPMS and LC-ICPMS

ICPMS determines each isotope of an element, and therefore can perform isotope ratios and isotope dilutionanalyses producing highly accurate quantitative results. NIST and others use this technique for the analysisand certification of reference materials. By adding known amounts of an element enriched in one isotope to asample, then determining the isotope ratios, the amount of original, naturally occurring element can bedetermined by eliminating sample induced biases.

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5.4 Research and Methods Development

Research projects have been conducted identifying contaminants and byproducts in such things as siliconeimplants, intraocular products, developing new methods for drug analyses, and analysis of biological samplesfor residual drug and metabolites. Exova has a staff of professional scientists with experience in a wide varietyof industries as well as analytical chemistry such as: environmental, electronics and semiconductors,petroleum, catalysis, pharmaceutical, forensics, pesticides, photochemistry, foods and flavor chemistry,polymers, just to name a few. Their experience coupled with some of the best and latest analytical equipmentcan be put to work for you not only on routine tests, but in developing answers to difficult chemical problems.

Some of the most recent Research and Development projects include: Element Speciation using GC- and LC-ICPMS: As, Se, Fe, Hg, Sn, and Pb Perchlorate in environmental samples, food, and raw produce using IC-MS/MS. Lovastatin in Red Yeast Rice using LC-MS/MS. Polysorbate 80 in Drug Formulations using LC-MS/MS. Ultra trace iodine in body fluids by ICPMS. Ultra trace boron in body fluids and tissue by ICPMS. Ultra trace silver in body fluids and tissue by ICPMS. Silicone in tissue and body fluids by GC. Cyanide by Ion Chromatography Trace metal composition in ancient works of art by ICPMS. Vitamin and mineral analysis by ICPMS and LC. Antioxidants in polymers by LC. Ultratrace Lead in chemicals and raw materials using isotope dilution ICPMS.Ion Chromatography (IC) also has some unique capabilities. In addition to being able to determine all kinds ofcompounds and elements that exist in ionic forms, it can distinguish between valence or oxidation states insome cases. Different oxidation states of the same element can have quite different chemical and toxicologicalproperties with Hexavalent Chromium being a good example of this. IC and LC overlap considerably in theircapabilities and interfacing either of these to ICPMS gives a very powerful technique for speciating andquantitating trace amounts of organometallics and elements in different oxidation states.

5.5 High Purity Reagents

Many modern high-tech industries depend on the use of highly pure reagents. Monitoring the impurities inthese chemicals and products requires special approaches to many analyses. At Exova we have appliedtechnologies such as ICPMS, GCMS, GC, LC, and IC to electronic grade reagents, high purity acids,semiconductor dopants, synthetic organic chemicals, pharmaceuticals and others.

5.6 Polymers, Paints, Coatings, and Additives

Polymers are usually identified using IR. The samples may need to be prepared as KBr pellets, films from asuitable solvent, or pyrolysates. In some cases, additional information from NMR analysis may be valuable foradditional characterization. We also test for the volatile content of paints and coatings as well as contaminantsin all of the above matrices.

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5.7 Product Composition and Contamination

Product composition determinations require a variety of methods for analysis. Organic chemicals, solvents,polymers, additives, etc. can be identified using GC, GCMS, LC, and IR. Occasionally NMR, or othertechniques may be required, but generally most components in the percent to ppm range can be determined.Inorganic components are usually identified using emission spectroscopy and X-Ray diffraction. OccasionallyIC, LC, IR, and ICPMS are useful for some components.

The analysis of additives and contaminants can usually be achieved using these same techniques coupledwith different sample extraction, concentration, and/or cleanup techniques. For example, a residual monomerin a polyacrylamide gel inter ocular product is extracted with methanol, cleaned-up by passing the extractthrough a C18 solid phase extraction cartridge, then analyzed by LC or GC.

5.8 Pesticides

Exova can test for a variety of pesticides using traditional GC or GCMS and the latest in LC methods. Our labhas worked with several environmental groups doing pesticide contamination monitoring at very low levels infresh water, sea water, fish, and plant tissue. We have experience with many of the less common pesticidesincluding triazines, propargite, and picloram. We offer a pesticide screen by GCMS for many matrices.

5.9 Foods and Produce

As one of the first labs certified by CDFA for multi-pesticide residue analyses in produce and environmentalsamples, our lab handles many foods with suspected chemical contamination. Exova has determined solvents,metals, pesticides, melamine, cyanuric acid, etc. in foods, produce, tissues, and other types of biologicalsamples.

5.10 Drinking Water

Our lab is currently certified by the state California Department of Health Services for drinking water analyses.Exova is certified for some of the 500 series methods which enable us to achieve very low detection limits. Inaddition to the conventional methods for analyzing for metals, volatile/semi volatile organics, and pesticides,our laboratory is certified to perform tests for PNAs, carbamates, and many other less common analytes.

5.11 Wastewater and Hazardous Waste

Our lab is certified for wastewater and hazardous waste parameters. We were the first laboratory certified formetals using ICPMS. For one client, we developed methods for ppt levels of semivolatile organics inmonitoring wells. For another, we were able to determine uranium to less than 10 ppt in ground water usingICPMS.

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5.12 Risk Assessment

Risk Assessment studies often require extremely low detection limits to determine the risks of long term, lowlevel exposure. In one case Exova developed an extension of a method for hexavalent chromium in ambientair to measure down to 1 ng/m3. The method uses sodium bicarbonate impingers to trap and stabilize theCr(VI), ion chromatography to separate the chromate ion from sample interference's, and post columnderivatization and UV detection. As low as 0.01 g/L can be determined in water, and the samples inbicarbonate buffer have been shown to be stable for weeks. EPA and SCAQMD have published versions ofthis method claiming only 0.1 g/L detection limits.

Many of the other instruments such as GCMS and ICPMS also offer extremely low detection limits for riskassessment projects. If current published methods are not adequate for your purposes, call us to discussmethod enhancements or development of completely new methods.

5.13 Industrial Hygiene

To measure worker exposure or indoor air quality we follow OSHA and NIOSH methods. We pioneered theuse of ICPMS for metals analysis on IH filters and published a paper in the AIHA Journal. In addition to thetraditional metals and solvents, we perform many of the less common methods requiring derivatization GC orLC such as isocyanates, formaldehyde, maleic anhydride, and diamines. The Cr (VI) analysis described underRisk Assessment gives detection limits 1000 times lower than the NIOSH 7600 method.

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Appendix A:

RESUMES

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LOUIS R. ALBANESESenior Chemist

Client Services DirectorClient Services Group

Dept. of Molecular Biology and Biochemistry- UC Irvine, Irvine CAPerformed peptide synthesis and purification by HPLC. Prepared buffers and media for aresearch laboratory.

Laboratory Assistant1986-1988

Bachem, Inc., Torrance CA Conducted peptide synthesis and HF cleavage.

Production Chemist1988-1989

Tower Nursery Wholesale Growers, Los Angeles CA Responsible for sales, marketing, and shipping management. Supervised pesticide andherbicide applications.

Sales Manager1989

Curtis & Tompkins, Ltd., Irvine CA Responsible for VOC testing of drinking, ground and waste waters, soil and hazardouswaste samples using GC and GC/MS at an environmental testing facility.

Volatile Organics Group Leader1989-1997

STAR Biochemicals, Torrance CA Responsible for analytical testing of pharmaceutical-grade peptides and raw materialsusing IC, HPLC, and TLC.

Quality Control Supervisor1997-2001

Tracked progress of analyses. Resolved analytical and QA requirements with clients.Answered client questions. Conducted hexavalent chromium analysis by LC.

Business Development andClient Services Project ManagerChemist2001-2010

Exova Inc., Santa Fe Springs CA (fka West Coast Analytical Service, Inc.)Manages the Client Services group. Performs business development.

Client Services Director2011-present

EMPLOYMENT HISTORY

B.S., Chemistry, 1988 University of California, Irvine CA

EDUCATION

ADDITIONAL TRAINING

ISO 9001, 7.2 and 8.2: Contract Review, Paton Professional Webinar, June 2010.

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ALBERTO ALVAREZSenior Chemist

Client Services RepresentativeClient Services

LA Biomed. Harbor-UCLA Hospital, Torrance CA Assisted researchers in diabetes projects. Prepared and completed DNA allelefrequency project. Handled lab mice and extracted DNA samples.

Laboratory Student Intern2000

Department of Molecular Biology, UCLA, Los Angeles CA Assisted in HIV research projects. Performed PCR, plasmid preparations, gelelectrophoresis, and DNA quantification using dye-binding spectrophotometry, enzymeactivity assays, and pH titrations. Maintained lab reagents, sterilized glassware, andprepared stock solutions.

Laboratory Assistant2000-2004

Responsible for analyses in wet chemistry.Chemist2005-2011

Responsible for wet chemistry analyses, group productivity, and quality control.Group Leader2011-2012

Exova Inc., Santa Fe Springs CA (fka West Coast Analytical Service, Inc.)Tracks progress of analyses. Resolves analytical and QA requirements with clients.Answers client questions.

Client Services Representative2012-present

EMPLOYMENT HISTORY

B.S., Molecular, Cell, and Developmental Biology, 2004 University of California, Los Angeles CA

EDUCATION

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MATT BLABONHSE Coordinator

Quality Unit

Manufactured parts, tooling and drill fixtures.Machinist1981-1985

Managed tooling production and product flowMethods Foreman1985-1988

Scheduled workload, managed, and performed training for eight employees.Communicated with vendors to order tooling, materials, and to schedule machinemaintenance. Designed tooling.

Machine Shop Supervisor1988-1992

PTC Aerospace, Garden Grove CAReworked, modified, and prepared prototype seat assemblies per engineering drawings.

Engineering Lab Technician1992-1993

B/E Aerospace Service Group, Orange CAResponsible for all phases of quality control, including pre-inspection, in progress,shipping, first piece, tooling, receiving, and final inspection. Supervised field servicequality control. Developed inspection procedures and assisted in the authorship ofquality manual and other documents. Implemented vendor qualification program.

QC Inspector1993-2000

Responsible for facilities maintenance and environmental monitoring program. Performssample prep for environmental organic analyses. Biannually performs calibration ofthermometers and checks flow rate of hoods. Checks calibration of balances daily.Responsible for hazardous waste disposal.

Facilities/Sample Prep2000-2010

Exova Inc., Santa Fe Springs CA (fka West Coast Analytical Service, Inc.)Responsible for facilities maintenance, metrology, and environmental monitoringprogram. Coordinates health and safety program. Performs sample prep forenvironmental organic analyses. Responsible for hazardous waste disposal.

HSE CoordinatorMetrology and Extractions2000-Present

EMPLOYMENT HISTORY

Total Quality Management, SPC, Boeing DI-9000A Certificate, 1998Gle