5 CCR 1005-7
DEPARTMENT OF PUBLIC HEALTH AND ENVIRONMENT NATURAL MEDICINE TESTING FACILITY CERTIFICATION AND TESTING 5 CCR 1005-7 [Editor’s Notes follow the text of the rules at the end of this CCR Document.] _________________________________________________________________________ Adopted by the Board of Health on November 20, 2024.
Rule 1: Authority and Definitions
1.1 Authority
This regulation is established under the authority contained in sections 25-1.5-120(1) and 25- 1.5- 101(1)(f), C.R.S.
1.2 Scope and Purpose
The purpose of this rule is to establish criteria for natural medicine and natural medicine product testing and the certification of Natural Medicine Testing Facilities to perform this testing.
1.3 Definitions
The following terms, whenever used in or referred to in these regulations, shall have the following respective meanings:
1.3.1 “Acceptability Criteria” means the specified limits placed on the characteristics of an item or method that are used to determine data quality.
1.3.2 “Accreditation” means approval by an impartial non-profit organization that operates in conformance with the International Organization for Standardization (ISO) / International Electrotechnical Commission (IEC) standard 17011 and is a signatory to the International Laboratory Accreditation Cooperation (ILAC) Mutual Recognition Arrangement (MRA) for Testing.
1.3.3 “Action Level” means the threshold value that provides the criterion for determining whether a Sample passes or fails an analytical test.
1.3.4 “Analyte” means the substance of interest in the analysis.
1.3.5 “Chain of Custody” (COC) means the chronological documentation that records the sequence of custody, control, transfer, analysis, and disposal of a Sample.
1.3.6 “Corrective Action” means a reactive action implemented to eliminate the root cause of a Nonconformance and to prevent recurrence.
1.3.7 “Certificate of Analysis” (COA) means an official document issued by a certified Natural Medicine Testing Facility that shows results of scientific tests performed on a product.
1.3.8 “Certified Reference Material” (CRM) means a material characterized by a metrologically valid procedure for one or more specified properties, accompanied by a certificate issued by an authoritative body that provides the value of the specified property, its associated uncertainty, and a statement of metrological traceability.
1.3.9 “Department” means the Colorado Department of Public Health and Environment.
1.3.10 “Exclusivity” means the specificity of the test method for validating microbial and speciation testing methods. It evaluates the ability of the method to distinguish the Target Organisms from similar but genetically distinct non-target organisms.
1.3.11 “Facilitator” means a natural person who is 21 years of age or older, has the necessary qualifications, training, experience, and knowledge to perform and supervise natural medicine services for a participant, and is licensed by the director of the division of professions and occupations to engage in the practice of facilitation.
1.3.12 “Fruiting Body(ies)” means the spore producing organs of the fungi Psilocybe cubensis.
1.3.13 “Harvest Lot” means a specifically identified quantity of Fruiting Bodies that is cultivated from the same inoculation, and dried under the same conditions and harvested in the same area within the licensed premises, that may be partially harvested; and, may use the substrate material for multiple harvests. A Harvest Lot must not contain more than
1.000 kilogram by dry weight.
1.3.14 “Healing Center” means a facility where an entity is licensed by the State Licensing Authority pursuant to article 50 of title 44 that permits a Facilitator to provide and supervise natural medicine services for a participant.
1.3.15 “Inclusivity” means, related to microbiological and speciation method validation, the sensitivity of the test method. Inclusivity evaluates the ability of the test method to detect a wide range of Target Organisms by a defined relatedness.
1.3.16 “Instrument Detection Limit” (IDL) is the concentration equivalent of a signal, due to the Analyte of interest, which is the smallest signal that can be distinguished from background noise by a particular instrument. The IDL should always be below the method detection limit and is not used for compliance data reporting, but may be used for statistical data analysis and comparing the attributes of different instruments. The IDL is similar to the “critical level” and “criterion of detection” as defined in the literature.
1.3.17 “Limit of Detection” (LOD) or detection limit, is the lowest concentration level that can be determined to be statistically different from a blank (99% confidence). The LOD is typically determined to be in the region where the signal to noise ratio is greater than 5. Limits of detection are matrix, method, and Analyte specific. Note: For the purposes of Natural Medicine Testing Facility certification, the LOD is approximately equal to the Method Detection Limit (MDL) for those tests in which the MDL can be calculated.
1.3.18 “Limit of Quantitation” (LOQ), or lower limit of quantitation (LOQ), is the level above which quantitative results may be obtained with a specified degree of confidence. The LOQ is mathematically defined as equal to 10 times the standard deviation of the results for a series of replicates used to determine a justifiable limit of detection. Limits of quantitation are matrix, method, and Analyte specific.
1.3.19 “Matrix” means the components of a Sample other than the Analyte(s) of interest (i.e., Sample type).
1.3.20 “Measurement Uncertainty” is defined as a parameter, associated with the result of a measurement, which characterizes the dispersion of the values that could reasonably be attributed to the measurand. The following equation is recommended: Equation:
Where, And:
standard uncertainty (standard deviation)
uncertainty due to repeatability uncertainty due to reproducibility uncertainty due to accuracy (bias)
combined standard uncertainty Expanded uncertainty = coverage factor, use 2 for 95% confidence level
1.3.21 “Moisture Content” means the percentage of water in a Sample, by weight.
1.3.22 “Mycelium” means the fungal threads or hyphae of Psilocybe cubensis.
1.3.23 “Natural Medicine Business” means any of the following entities licensed pursuant to the Natural Medicine Code:
a. A Healing Center;
b. A Natural Medicine Cultivation Facility;
c. A Natural Medicine Products Manufacturer; and d. A Natural Medicine Testing Facility.
1.3.24 “Natural Medicine Code” means article 50 of title 55 of the Colorado Revised Statutes.
1.3.25 “Natural Medicine Cultivation Facility” means a location where Regulated Natural Medicine is grown, harvested, and prepared in order to be transferred to either a Healing Center, Facilitator, Natural Medicine Products Manufacturer, or to another Natural Medicine Cultivation Facility.
1.3.26 “Natural Medicine Products Manufacturer” means a person who manufactures Regulated Natural Medicine Products for transfer to a Healing Center, Facilitator, or to another Natural Medicine Products Manufacturer.
1.3.27 “Natural Medicine Testing Facility” means a public or private laboratory licensed or approved by the Colorado Department of Revenue and certified by the Department to perform testing and research on Regulated Natural Medicine and Regulated Natural Medicine Product.
1.3.28 “Nonconformance” means a non-fulfillment of a requirement or departure from written procedures, work instructions, or quality system, as defined by the Natural Medicine Testing Facility’s written Corrective Action and Preventive Action (CAPA) procedures.
1.3.29 “Person” means a natural person, an estate, a trust, an Entity, or a state or other jurisdiction.
1.3.30 “Preventive Action” means a proactive action implemented to eliminate or minimize the cause of a potential Nonconformance or other quality problem before it occurs.
1.3.31 “Production Lot” means psilocybin pressed tablets, tea bags, chocolate, gelatin- or agar- based gummies, or powdered capsules of the same type that were manufactured under the same conditions at the same time using the same manufacturing method, ingredients, and standard operating procedures.
1.3.32 “Proficiency Testing” means an assessment of the performance of a Natural Medicine Testing Facility’s methodology and processes. Proficiency Testing is also known as inter laboratory comparison. The goal of Proficiency Testing is to ensure results are accurate, reproducible, and consistent.
1.3.33 “Quality Control” means the set of measures implemented within an analytical procedure to ensure that the measurement system is operating in a state of statistical control for which errors have been reduced to acceptable levels.
1.3.34 “Regulated Natural Medicine” means natural medicine that is cultivated, manufactured, tested, stored, distributed, transported, transferred, or dispensed pursuant to the Natural Medicine Code. Regulated Natural Medicine includes:
a. Psilocybin; or b. Psilocin.
1.3.35 “Regulated Natural Medicine Product” means a natural medicine product that is cultivated, manufactured, tested, stored, distributed, transported, or dispensed pursuant to the Natural Medicine Code.
1.3.36 “Reference Material” means material containing a known concentration of an Analyte of interest that is in solution or in a homogeneous Matrix.
1.3.37 “Reference Method” means the method by which the performance of an alternate method is measured or evaluated.
1.3.38 “Sample” means a composite of Sample Increments collected from the same Harvest Lot or Production Lot and submitted for testing.
1.3.39 “Sample Increment” means a portion of Regulated Natural Medicine that is removed from a Harvest Lot or Regulated Natural Medicine Product that is removed from a Production Lot and combined into a Sample for required testing.
1.3.40 “Scope of Accreditation” means the tests or types of tests performed, materials or products tested, and the methods used for testing Regulated Natural Medicine or Regulated Natural Medicine Products for which the Accreditation has been granted.
1.3.41 “Standard Operating Procedure” (SOP) means a written document detailing instructions for the methods required to be followed for the routine performance of operations, analysis, or tasks. A SOP must include a clear and unique title, a purpose explaining the reason for the SOP and its scope. It must list all materials and equipment required to complete the procedure and provide definitions for any ambiguous, unclear or abbreviated terms. It must also delegate responsibilities by specifying individuals or job titles responsible for overseeing and completing the procedure. The procedure section must be a detailed step-by-step instruction dictating how and when an operation is routinely performed. Health and safety guidelines or protocols must be outlined. Any additional documents, forms, or references needed to complete the task or used to create the task must be included in an appendix or reference section. The SOP must also document all revisions and updates.
1.3.42 “Target Organism” means an organism that is being tested for in an analytical procedure or test method.
1.3.43 “Total psilocin” means psilocybin multiplied by 0.719 plus psilocin. Total Psilocin shall be expressed as a weight (i.e. mg Total Psilocin = (mg psilocybin x 0.719) + mg psilocin) or weight percent (i.e. % Total Psilocin = (% psilocybin x 0.719) + % psilocin). Rule 2: Natural Medicine Testing Facility Certification Authorizations 2.1 Testing of Natural Medicine Authorized. A Natural Medicine Testing Facility may accept Samples of Regulated Natural Medicine and Regulated Natural Medicine Product from Natural Medicine Businesses for testing and research purposes only.
2.2 A Natural Medicine Testing Facility shall be permitted to test Samples of Regulated Natural Medicine and Regulated Natural Medicine Product for required tests pursuant to 1 CCR 213-1 only in the category(ies) that the Natural Medicine Testing Facility is certified to perform testing in pursuant to Rule 4.1 – Natural Medicine Testing Facility: Certification Requirements.
2.3 Transferring Samples to another Certified Natural Medicine Testing Facility. A Natural Medicine Testing Facility may transfer Samples to another certified Natural Medicine Testing Facility for testing. All laboratory reports provided to a Natural Medicine Business must identify the Natural Medicine Testing Facility that actually conducted the test.
2.4 A Natural Medicine Testing Facility shall provide the results of any required compliance testing performed on a Sample of Regulated Natural Medicine or Regulated Natural Medicine Product to the Person submitting the Sample. Quality Control data associated with the Sample shall be provided when requested by the Person submitting the Sample. Rule 3: Natural Medicine Testing Facilities: General Limitations or Prohibited Acts 3.1 Conflicts of Interest. A Natural Medicine Testing Facility shall establish policies to prevent the existence or appearance of undue commercial, financial, or other influences that may diminish the competency, impartiality, and integrity of the Natural Medicine Testing Facility’s testing processes or results, or that may diminish public confidence in the competency, impartiality and integrity of the Natural Medicine Testing Facility’s testing processes or results. At a minimum, employees, owners or agents of a Natural Medicine Testing Facility who participate in any aspect of the analysis, resulting, and/or reporting of a Sample are prohibited from improperly influencing the testing process, improperly manipulating data, or improperly benefiting from any on-going financial, employment, personal or business relationship with the Natural Medicine Cultivator or Natural Medicine Manufacturer that provided the Sample.
3.2 Transfer to Unlicensed Persons Prohibited. A Natural Medicine Testing Facility shall not transfer any Regulated Natural Medicine or Regulated Natural Medicine Product to a Person who does not hold a Natural Medicine Testing Facility License or a Facilitator licensed by the Department of Regulatory Agencies under article 170 of title 12.
3.3 Destruction of Received Samples. A Natural Medicine Testing Facility shall properly dispose of all Samples it receives, that are not transferred to another Natural Medicine Testing Facility, after all requested tests have been completed and any sample retention period has elapsed. See Rule 14 – Waste Disposal.
3.4 Sample Rejection. A Natural Medicine Testing Facility shall reject any Sample where:
3.4.1 The condition of the Sample at receipt indicates that the Sample may have been tampered with or could have become contaminated as a result of damaged or improper packaging; OR 3.4.2 The Sample of Natural Medicine has not been collected in accordance with 1 CCR 213-1. Rule 4: Natural Medicine Testing Facilities: Certification Requirements 4.1 Certification Category. For required tests, the Natural Medicine Testing Facility must be certified by the Department in the category in order to perform that type of testing.
4.1.1 Microbials;
4.1.2 Tryptamine content; and
4.1.3 Homogeneity.
4.2 Certification Procedures and Principles. The Natural Medicine Testing Facility certification program is contingent upon successful on-site inspection, successful participation in proficiency testing, and ongoing compliance with the requirements in this Rule.
4.2.1 Certification Inspection. A Natural Medicine Testing Facility must be inspected prior to initial certification and annually thereafter by the Department.
4.2.2 Standards for Certification. A Natural Medicine Testing Facility must meet standards of performance, as established by these rules, in order to obtain and maintain certification. Standards of performance include but are not limited to: Personnel Qualifications, Standard Operating Procedures, analytical processes, Proficiency Testing, Quality Control, quality assurance, security, Chain of Custody, Sample retention, Sample disposal, space, records, and results reporting.
4.2.2.1 A Natural Medicine Testing Facility must be accredited under the International Organization for Standardization/International Electrotechnical Commission 17025:2017 Standard (ISO/IEC 17025), or any subsequent superseding ISO/IEC 17025 standard, by an Accreditation body that conforms to ISO/IEC 17011:2017 and is a signatory to the International Laboratory Accreditation Cooperation
4.2.2.2 Certification will be granted when facilities have met all certification requirements, including ISO/IEC 17025 Accreditation.
4.2.2.3 The Department may grant provisional certification for a testing category if the Natural Medicine Testing Facility has not yet obtained ISO/IEC 17025 Accreditation, but meets all other certification requirements. Such provisional certification shall be for a period not to exceed twelve months.
4.2.3 Disclosure of Certification. Prior to performing non-required testing on Regulated Natural Medicine or Regulated Natural Medicine Product, the Natural Medicine Testing Facility must notify the Natural Medicine Business that the Natural Medicine Testing Facility is not certified to perform non-required tests and that such test results have not been certified or subject to state regulator oversight and disclose this on the certificate of analysis
4.2.4 Personnel Qualifications.
4.2.4.1 Natural Medicine Testing Facility Director. A Natural Medicine Testing Facility must employ, at a minimum, a Natural Medicine Testing Facility director with sufficient education and experience in a regulated laboratory environment in order to obtain and maintain certification. See Rule 5 – Natural Medicine Testing Facilities: Personnel.
4.2.4.2 Employee Competency. A Natural Medicine Testing Facility must evaluate and document that employees are competent to perform all aspects of laboratory work for which the employee is responsible.
4.2.5 Standard Operating Procedures. A Natural Medicine Testing Facility must have written Standard Operating Procedures meeting the minimum standards set forth in these rules detailing the performance of all methods employed by the facility used to test the Analytes it reports that are available for testing analysts to follow at all times.
4.2.5.1 The current Natural Medicine Testing Facility director must approve, sign and date each procedure. If any modifications are made to those procedures, the Natural Medicine Testing Facility director must approve, sign, and date the revised version prior to use.
4.2.5.2 A Natural Medicine Testing Facility must maintain a copy of all Standard Operating Procedures to include any revised copies for a minimum of three years. See Rule 12 – Natural Medicine Testing Facilities: Records Retention and Rule 13 – Natural Medicine Testing Facilities: Business Records Required.
4.2.5.3 A Natural Medicine Testing Facility must inform the Department of any major method changes to Standard Operating Procedures pertaining to certified analytical methods, prior to implementing the changes. Major method changes include, but are not limited to: modifications to Sample preparation, changes in column type, enrichment media, solvent(s) used, instrumentation or instrumentation parameters.
4.2.6 Analytical Processes. A Natural Medicine Testing Facility must maintain a listing of all analytical methods used and all Analytes tested and reported. The Natural Medicine Testing Facility must provide this listing to the Department upon request.
4.2.7 Proficiency Testing. A Natural Medicine Testing Facility must successfully participate in a Department approved Proficiency Testing program in order to obtain and maintain certification.
4.2.8 Quality Assurance and Quality Control. A Natural Medicine Testing Facility must establish and follow a quality assurance and Quality Control program to ensure sufficient monitoring of Natural Medicine Testing Facility processes and quality of results reported.
4.2.9 Security. A Natural Medicine Testing Facility must be located in a secure setting to prevent unauthorized persons from gaining access to the testing and storage areas of the Natural Medicine Testing Facility.
4.2.10 Chain of Custody. A Natural Medicine Testing Facility must establish a system to document the complete Chain of Custody for Samples from receipt through disposal.
4.2.11 Space. A Natural Medicine Testing Facility must be located in a fixed structure that provides adequate infrastructure to perform analysis in a safe and compliant manner consistent with federal, state, and local requirements.
4.2.12 Records. A Natural Medicine Testing Facility must establish a system to retain and maintain records for a period not less than three years. See Rules 12 – Natural Medicine Testing Facility: Records Retention and Rule 13 – Natural Medicine Testing Facilities: Business Records Required.
4.2.13 Results Reporting. A Natural Medicine Testing Facility must establish processes to ensure results are reported in a timely and accurate manner. A Natural Medicine Testing Facility’s process may require that the Natural Medicine Cultivator or Natural Medicine Product Manufacturer remit payment for any test conducted by the Natural Medicine Testing Facility prior to reporting results. A Natural Medicine Testing Facility’s process established under this subparagraph (12) must be maintained on the premises of the Natural Medicine Testing Facility.
4.2.14 Conduct While Seeking Certification. A Natural Medicine Testing Facility, and its agents and employees, shall provide all documents and information required or requested by the Department and its employees in a full, faithful, truthful, and fair manner. Rule 5: Natural Medicine Testing Facilities: Personnel 5.1 Natural Medicine Testing Facility Director. The laboratory director is ultimately responsible for the overall analytical operation and quality of the results reported by the Natural Medicine Testing Facility, including the employment and supervision of personnel who are competent to perform test procedures and record and report test results promptly, accurately, and proficiently, and for assuring compliance with the standards set forth in this Rule.
5.1.1 The Natural Medicine Testing Facility director may also serve as a supervisory analyst, quality assurance manager, or testing analyst, or a combination of these roles for a Natural Medicine Testing Facility. If the laboratory director is serving as a combination of roles, a secondary review of data and quality documentation must be performed by qualified personnel that did not generate the data, report, or quality documentation.
5.1.2 The Natural Medicine Testing Facility director for a Natural Medicine Testing Facility must meet one of the following qualification requirements:
5.1.2.1 Be a Medical Doctor (M.D.) licensed to practice medicine in Colorado and have at least three years of full-time laboratory experience in a regulated laboratory environment performing analytical scientific testing in which the testing methods were recognized by an accrediting body;
5.1.2.2 Hold a doctoral degree in one of the natural sciences and have at least three years of full-time laboratory experience in a regulated laboratory environment performing analytical scientific testing in which the testing methods were recognized by an accrediting body;
5.1.2.3 Hold a master’s degree in one of the natural sciences and have at least five years of full-time laboratory experience in a regulated laboratory environment performing analytical scientific testing in which the testing methods were recognized by an accrediting body; OR 5.1.2.4 Hold a bachelor’s degree in one of the natural sciences and have at least seven years of full-time laboratory experience in a regulated laboratory environment performing analytical scientific testing in which the testing methods were recognized by an accrediting body.
5.2 What the Natural Medicine Testing Facility Director May Delegate. The Natural Medicine Testing Facility director may delegate the responsibilities assigned under this Rule to a qualified supervisory analyst or quality assurance manager, provided that such delegation is made in writing and a record of the delegation is maintained. See Rule 13 - Business Records Required. Despite the designation of a responsibility, the Natural Medicine Testing Facility director remains responsible for ensuring that all duties are properly performed.
5.3 Responsibilities of the Natural Medicine Testing Facility Director. The Natural Medicine Testing Facility director must:
5.3.1 Ensure that the Natural Medicine Testing Facility has adequate space, equipment, materials, and controls available to perform the tests reported;
5.3.2 Establish and ensure adherence to written Standard Operating Procedures used to perform the tests reported;
5.3.3 Ensure that testing systems developed and used for each of the tests performed in the Natural Medicine Testing Facility provide quality laboratory services for all aspects of test performance, which includes the preanalytic, analytic, and postanalytic phases of testing;
5.3.4 Ensure that the physical location and environmental conditions of the Natural Medicine Testing Facility are appropriate for the testing performed and provide a safe environment in which employees are protected from physical, chemical, and biological hazards;
5.3.5 Ensure that the test methodologies selected are fit-for-purpose and appropriate to ensure the quality of results required for the level of testing the Natural Medicine Testing Facility is certified to perform;
5.3.6 Ensure that validation and verification test methods used are adequate to determine the accuracy, precision, and other pertinent performance characteristics of the method;
5.3.7 Ensure that testing analysts perform the test methods as required for accurate and reliable results;
5.3.8 Ensure that the Natural Medicine Testing Facility is enrolled in and successfully participates in a Department approved Proficiency Testing program;
5.3.9 Ensure that the Quality Control and quality assessment programs are established and maintained to assure the quality of laboratory services provided and to identify failures in quality as they occur;
5.3.10 Ensure the establishment and maintenance of acceptable levels of analytical performance for each test system;
5.3.11 Ensure that all necessary remedial actions are taken and documented whenever significant deviations from the Natural Medicine Testing Facility’s established performance specifications are identified, and that test results are reported only when the system is functioning properly;
5.3.12 Ensure that reports of test results include pertinent information required for interpretation;
5.3.13 Ensure that consultation is available to the Natural Medicine Testing Facility's clients on matters relating to the quality of the test results reported and their interpretation of said results;
5.3.14 Employ a sufficient number of Natural Medicine Testing Facility personnel who meet the qualification requirements and provide appropriate consultation, properly supervise, and ensure accurate performance of tests and reporting of test results;
5.3.15 Ensure that prior to testing any Samples, all testing analysts receive the appropriate training for the type and complexity of tests performed, and have demonstrated and documented that they can perform all testing operations reliably to provide and report accurate results;
5.3.16 Ensure that policies and procedures are established for monitoring individuals who conduct preanalytical, analytical, and postanalytical phases of testing to assure that they are competent and maintain their competency to process Samples, perform test procedures and report test results promptly and proficiently, avoid actual and apparent conflicts of interests, and whenever necessary, identify needs for remedial training or continuing education to improve skills;
5.3.17 Ensure that an approved Standard Operating Procedure manual is available to all personnel responsible for any aspect of the testing process; and 5.3.18 Specify, in writing, the responsibilities and duties of each person engaged in the performance of the preanalytic, analytic, and postanalytic phases of testing, that identifies which examinations and procedures each individual is authorized to perform, whether supervision is required for Sample processing, test performance or results reporting, and whether consultant or Natural Medicine Testing Facility director review is required prior to reporting test results.
5.3.19 Ensure internal and vendor audits are completed regularly at a frequency established by the Natural Medicine Testing Facility; and 5.3.20 Ensure that quality anomalies and Nonconformances are regularly reviewed and documented as open or completed. Open Nonconformances should be reviewed at least annually, and high impact Nonconformances must be reviewed at least monthly.
5.4 Change in Natural Medicine Testing Facility Director. In the event that the Natural Medicine Testing Facility director leaves employment at the Natural Medicine Testing Facility, the Natural Medicine Testing Facility shall:
5.4.1 Provide written notice to the Department within seven days of the Natural Medicine Testing Facility’s director’s departure;
5.4.2 Designate an interim Natural Medicine Testing Facility director within seven days of the Natural Medicine Testing Facility director’s departure. At a minimum, the interim Natural Medicine Testing Facility director must meet the qualifications of a supervisory analyst; and 5.4.3 Hire a permanent Natural Medicine Testing Facility director within 60 days from the date of the previous Natural Medicine Testing Facility director’s departure.
5.4.3.1 The Natural Medicine Testing Facility may submit a waiver request to the Department to receive an additional 60 days to hire a permanent Natural Medicine Testing Facility director provided that the Natural Medicine Testing Facility submits a detailed oversight plan along with the waiver request. 5.5. Supervisory Analyst. Supervisory analysts must meet one of the qualifications for a Natural Medicine Testing Facility director or have at least a bachelor’s degree in one of the natural sciences and two years of full time laboratory experience in a regulated laboratory environment performing analytical scientific testing in which the testing methods were recognized by an accrediting body. A combination of education and experience may substitute for the two years of full-time laboratory experience.
5.6 Quality Assurance Manager. Quality Assurance Managers must meet one of the qualifications for Natural Medicine Testing Facility director or have at least a bachelor’s degree in one of the natural sciences and two years of full-time laboratory experience in a regulated laboratory environment performing analytical scientific testing in which the testing methods were recognized by an accrediting body. A combination of education and experience may substitute for the two years of full-time laboratory experience.
5.7. Natural Medicine Testing Facility Testing Analyst.
5.7.1 Educational Requirements. An individual designated as a testing analyst must meet one of the qualifications for a Natural Medicine Testing Facility director or supervisory analyst; OR
5.7.1.1 Have at least a bachelor’s degree in one of the natural sciences;
5.7.1.2 Have earned an associate degree in a laboratory science from an accredited institution;
5.7.1.3 Have education and training equivalent to that specified in 5.7.1.2 of this section that includes at least 60 semester hours, or equivalent, from an accredited institution that, at a minimum, include:
5.7.1.4 Have at least 5 years of full time experience in laboratory testing and have laboratory training that includes at least 3 months documented laboratory training in each testing category in which the individual performs testing.
5.7.2 Responsibilities. In order to independently perform any test for a Natural Medicine Testing Facility, an individual must at least meet the educational requirements for a testing analyst.
Rule 6: Natural Medicine Testing Facilities: Standard Operating Procedures 6.1 Standard Operating Procedures must include, but need not be limited to, procedures for:
6.1.1 Sample receiving;
6.1.2 Sample accessioning;
6.1.3 Sample storage;
6.1.4 Identifying, rejecting, and reporting unacceptable Samples;
6.1.5 Recording and reporting discrepancies during Sample receiving and accessioning;
6.1.6 Security and stability of Samples, aliquots and extracts and records;
6.1.7 Sample archive retention to assure stability, as follows:
6.1.7.1 For Samples submitted for testing, Sample archive retention for 14 days;
6.1.8 Validating a new or revised method prior to testing Samples to include the performance criteria as stated in Rule 7.1.5;
6.1.9 Sample preparation, including but not limited to, sub-sampling for testing, homogenization, and aliquoting Samples to avoid contamination and carry-over;
6.1.10 Disposal of Samples;
6.1.11 The theory and principles behind each assay;
6.1.12 Preparation and identification of reagents, standards, calibrators and controls and ensure all standards are traceable to a certified vendor that meets the accreditation requirements of the laboratory, such as National Institute of Standards of Technology (NIST), ISO 17034, or other similar entities;
6.1.13 Preparation and verification of internally developed Reference Materials, in the event that a suitable traceable CRM is not available;
6.1.14 Special requirements and safety precautions involved in performing assays;
6.1.15 Frequency and number of control and calibration materials;
6.1.16 Recording and reporting assay results;
6.1.17 Protocol and criteria for accepting or rejecting analytical procedure to verify the accuracy of the final report;
6.1.18 Pertinent literature references for each method;
6.1.19 Current step-by-step instructions with sufficient detail to perform the assay to include equipment operation and any abbreviated versions used by a testing analyst;
6.1.20 Acceptability Criteria for the results of calibration standards and controls as well as between two aliquots, Sample duplicates, new standard lots, or columns;
6.1.21 A documented system for reviewing the results of testing calibrators, controls, standards, and Sample test results, as well as reviewing for clerical errors, analytical errors and any unusual analytical results; and 6.1.22 A documented system for investigating existing or potential Nonconformances and implementing, and monitoring Corrective Actions and/or Preventative Actions, including instructions for the Natural Medicine Testing Facility to contact the requesting entity, when required;
6.1.23 Policies and procedures to follow when Samples are requested for referral and testing by another certified Natural Medicine Testing Facility or an approved local or state agency’s laboratory;
6.1.24 Protocol and criteria for calculating and applying Measurement Uncertainty;
6.1.25 Policies and procedures including the titles and required training of individuals responsible for the transport of biohazardous materials;
6.1.26 Procedures and/or protocols for general laboratory upkeep and cleaning, including specific procedures to eliminate or avoid cross-contamination;
6.1.27 Retesting or additional analyses of Samples, including but not limited to, when it is appropriate to retest or perform an additional analysis of the Sample, when it is appropriate for the requesting entity to request retesting (e.g., after failing microbial contaminant testing on Regulated Natural Medicine); and 6.1.28 Policies to follow for internal audits, including the frequency of internal audits and the documentation of the results of audits. Audit reports must include, but need not be limited to: audit title, scope, name(s) of personnel and auditors, audit date, introduction, problems noted, findings, observations/opportunities noted, date issued. Rule 7: Natural Medicine Testing Facilities: Analytical Processes 7.1 Method Validation and Verification. Analytical method selection, validation, and verification must ensure that the test method used is fit-for-purpose and that the Natural Medicine Testing Facility can successfully perform the testing.
7.1.1 The demonstration of testing validity must ensure consistent, accurate and reproducible analytical performance in the matrices tested by the laboratory.
7.1.2 Method performance specifications must ensure analytical tests are sufficiently sensitive for the purposes of the detectability requirements of Natural Medicine Division Rules, 1 CCR 213-1.
7.1.3 A Natural Medicine Testing Facility must validate new methodology and revalidate any changes to approved methodology prior to analyzing samples.
7.1.4 The Natural Medicine Testing Facility must implement a performance-based
measurement system for the selected methodology and validate the method following good laboratory practices in accordance with AOAC International, United States Pharmacopeia (USP), United States Food and Drug Administration (FDA), United States Department of Agriculture (USDA), or other reputable validation guidelines and methodology prior to reporting results. Validation, verification, or matrix extension of other or new methodology must include when applicable, but is not limited to:
7.1.4.1 Verification of Accuracy
7.1.4.2 Verification of Precision
7.1.4.3 Verification of Analytical Sensitivity
7.1.4.4 Verification of Analytical Specificity
7.1.4.5 Verification of the LOD
7.1.4.6 Verification of the LOQ
7.1.4.7 Verification of the Reportable Range
7.1.4.8 Identification of Interfering Substances
7.1.4.9 Exclusivity, which means the specificity of the test method for validating microbial testing methods. It evaluates the ability of the method to distinguish the target organisms from similar but genetically distinct non-target organisms;
7.1.4.10 Inclusivity, which means, related to microbiological method validation, the sensitivity of the test method. It evaluates the ability of the test method to detect a wide range of target organisms by a defined relatedness;
7.1.4.11 Verification of Recovery. The laboratory shall take action to remediate recovery issues where Matrix effects affect recovery at greater than plus or minus 20% of the theoretical value;
7.1.4.12 Measurement Uncertainty.
7.1.5 For qualitative methods, a minimum of three spiking/naturally occurring levels of target Analyte must be included assessing accuracy, precision and specificity per each matrix validated (microbiological methods shall be considered accurate/precise if fractional results are obtained when limits are <1 CFU preanalytical portion): one negative level in which no Analyte is present, one low level at which Analyte is present at the regulatory limit and one high level at which the Analyte is present at 10x the regulatory limit.
7.1.6 For qualitative methods, at least two levels must be included for the negative and high level spikes - at least ten replicates must be included at the fractional level, per Analyte, per matrix.
7.1.7 For quantitative methods, laboratories must include a minimum of four spiked levels or more, covering the analytical range must be included assessing accuracy, precision and specificity per each matrix validated: one negative level in which no Analyte is present, one low level at which Analyte is present at the regulatory limit, one medium level for which the Analyte is present at a concentration close to the middle calibrator and one high level at which the Analyte is present at the upper level of the calibration.
7.1.8 For quantitative methods, at least two replicates must be performed at each spiked level per each matrix validated.
7.1.9 Validation or verification of methodology must be documented in a validation report. The validation report shall include, but is not limited to, the following:
7.1.9.1 Validation plan;
7.1.9.2 Introduction and summary;
7.1.9.3 Materials, to include identification of Certified Reference Materials, and preparation methods;
7.1.9.4 Method parameters;
7.1.9.5 Raw data, including instrument raw data such as chromatograms, for each test method and each instrument, if any;
7.1.9.6 Instrument calibration data, if any;
7.1.9.7 Data, calculations, and results;
7.1.9.8 Method Acceptability Criteria performance data;
7.1.9.9 Interlaboratory Comparison
7.1.9.10 Verification of spreadsheets and/or laboratory information management
7.1.9.11 Conclusion and discussion; and
7.1.9.12 References.
7.1.10 Natural Medicine Testing Facilities must validate or verify instrumentation and methodology immediately and prior to use following a change in location.
7.1.11 Any changes to the approved other or new methodology must be revalidated and documented prior to testing samples.
7.1.12 Testing and Validation of Complex Matrices. A Natural Medicine Testing Facility must include a variety of matrices as part of the validation/verification process. During method validation/verification, a Natural Medicine Testing Facility must:
7.1.12.1 Select matrices which best represent each category of products to be
7.1.12.2 Perform a new Matrix validation, prior to reporting results, on matrices which are either a new category of Matrix or are considerably different from the original matrix validated within the category.
7.1.12.3 Perform a Matrix verification (a client Matrix spike or similar consisting of the target Analyte(s) at the time of analysis) on matrices submitted for testing which differ slightly from those initially validated but which fall within a category already validated.
7.1.13 Software must be validated prior to testing samples, including but not limited to: analytical software, application programming interface(s) (APIs), laboratory information management systems (LIMS), etc., to include any calculations performed by the software.
7.1.14 Prior to use, methodology must have a Standard Operating Procedure approved and signed by the laboratory director.
7.1.15 Testing analysts must have documentation of competency assessment prior to testing Samples.
7.1.16 Any changes to the approved methodology must be revalidated and documented prior to testing Samples. The documentation of changes and revalidation must be provided to the Department prior to implementation.
7.2 General Laboratory Equipment. A Natural Medicine Testing Facility must:
7.2.1 Track, verify and apply correction factors where applicable;
7.2.2 Perform annual calibration, monthly spore ampule checks and daily temperature checks of autoclaves;
7.2.3 Verify pipette calibration on a monthly basis across the volume range the pipette is used;
7.2.4 Perform annual calibration of balances and analytical weights. Balances must be verified across the appropriate mass range on each day of use;
7.2.5 Perform verification of laboratory dispensers on each day of use;
7.2.6 Perform annual gravimetric verification of volumetric glassware;
7.2.7 Calibrate pH meters on each day of use with buffers across the analytical range (i.e., 4, 7, 10);
7.2.8 Perform annual calibration of thermometers to a NIST traceable reference thermometer. Correction factors must be applied when such a factor could impact the final result;
7.2.9 Calibrate analytical timers annually.
7.3 Gas Chromatography (GC). A Natural Medicine Testing Facility using GC must:
7.3.1 Document the conditions of the gas chromatograph, including the detector response;
7.3.2 Perform and document preventive maintenance as required by the manufacturer and SOPs;
7.3.3 Ensure that records are maintained and readily available to the staff operating the equipment;
7.3.4 Document the performance of new columns before use;
7.3.5 Use an internal standard for each qualitative and quantitative analysis that has similar chemical and physical properties to that of the compound identified;
7.3.6 Establish Acceptability Criteria for variances between different aliquots and different columns;
7.3.7 Document the monitoring of the response (area or peak height) of the internal standard to ensure consistency over time of the analytical system;
7.3.8 Evaluate the performance of the instrument after routine and preventive maintenance prior to analyzing subject Samples; and 7.3.9 Monitor and document the performance of the instrument each day of testing.
7.4 Gas Chromatography Mass Spectrometry (GC/MS). A Natural Medicine Testing Facility using GC/MS must:
7.4.1 Perform and document preventive maintenance as required by the manufacturer and SOPs;
7.4.2 Document and maintain records when cleaning or changes in source, source conditions, column, or other routine maintenance are made to the instrument;
7.4.3 Ensure that records are maintained and readily available to the staff operating the equipment;
7.4.4 Maintain records of mass spectrometric tuning;
7.4.5 Establish written criteria for acceptable mass-spectrometric tuning parameters;
7.4.6 Document corrective actions if a mass-spectrometric tune is unacceptable;
7.4.7 Monitor analytic analyses to check for contamination and carry-over;
7.4.8 Use selected ion monitoring within each run to assure that the Natural Medicine Testing Facility compares ion ratios and retention times between calibrators, controls and Samples for identification of an Analyte;
7.4.9 Use an internal standard for qualitative and quantitative analysis that has similar chemical and physical properties to that of the compound identified and is isotopically labeled when available or appropriate for the assay;
7.4.10 Document the monitoring of the response (area or peak height) for the internal standard to ensure consistency over time of the analytical system;
7.4.11 Define the criteria for designating qualitative results as positive;
7.4.12 When a library is used to qualitatively identify an Analyte, the identity of the Analyte must be confirmed before reporting results by comparing the relative retention time and mass spectrum to that of a known standard or control run on the same system;
7.4.13 Evaluate the performance of the instrument after routine and preventive maintenance (e.g. clipping or replacing the column or cleaning the source) prior to analyzing subject Samples; and 7.4.14 Monitor and document the performance of the instrument each day of testing.
7.4.15 Monitor gas phase standards frequently by comparison to the initial calibration curve. Fresh standards must be prepared if this check exceeds 20% drift. Gas standards must be replaced after one week or as recommended by the standard manufacturer. Alternatively, standards must be replaced after an established period of time for which the Natural Medicine Testing Facility has demonstrated the stability of the standard..
7.4.16 Monitor non-gas standards frequently by comparison to the initial calibration. Fresh standards must be prepared if this check exceeds 20% drift. Non-gas standards must be replaced after one month for working standards and three months for opened stocks or as recommended by the standard manufacturer. Alternatively, standards must be replaced after an established period of time for which the Natural Medicine Testing Facility has demonstrated the stability of the standard; and 7.4.17 Monitor and document the performance of the instrument each day of testing.
7.5 Immunoassays. A Natural Medicine Testing Facility using Immunoassays must:
7.5.1 Perform and document preventive maintenance as required by the manufacturer and SOPs;
7.5.2 Ensure that records are maintained and readily available to the staff operating the equipment;
7.5.3 Validate any changes or modifications to a manufacturer’s approved assays or testing methods when a Sample is not included within the types of Samples approved by the manufacturer; and 7.5.4 Define acceptable separation or measurement units (absorbance intensity or counts per minute) for each assay, which must be consistent with manufacturer’s instructions.
7.6 High Performance Liquid Chromatography (HPLC). A Natural Medicine Testing Facility using HPLC must:
7.6.1 Perform and document preventive maintenance as required by the manufacturer and SOPs;
7.6.2 Ensure that records are maintained and readily available to the staff operating the equipment;
7.6.3 Monitor and document the performance of the HPLC instrument each day of testing;
7.6.4 Evaluate the performance of new columns before use;
7.6.5 Create written standards for acceptability when eluting solvents are recycled;
7.6.6 Use an internal standard for each qualitative and quantitative analysis that has similar chemical and physical properties to that of the compound identified when available or appropriate for the assay;
7.6.7 Document the monitoring of the response (area or peak height) of the internal standard to ensure consistency over time of the analytical system;
7.6.8 Evaluate the performance of the instrument after routine and preventive maintenance prior to analyzing subject Samples; and 7.6.9 Monitor and document the performance of the instrument each day of testing.
7.7 Liquid Chromatography Mass Spectrometry (LC/MS). A Natural Medicine Testing Facility using LC/MS must:
7.7.1 Perform and document preventive maintenance as required by the manufacturer and SOPs;
7.7.2 Ensure that records are maintained and readily available to the staff operating the equipment;
7.7.3 Establish written criteria for an acceptable mass-spectrometric tune;
7.7.4 Maintain records of mass spectrometric tuning;
7.7.5 Document Corrective Actions if a mass-spectrometric tune is unacceptable;
7.7.6 Use an internal standard with each qualitative and quantitative analysis that has similar chemical and physical properties to that of the compound identified and is isotopically labeled when available or appropriate for the assay;
7.7.7 Document the monitoring of the response (area or peak height) of the internal standard to ensure consistency over time of the analytical system;
7.7.8 Compare two transitions and retention times between calibrators, controls and Samples within each run;
7.7.9 Ensure ion ratios do not exceed +/- 30% relative to the average of calibration standards from the same sequence.
7.7.10 Document and maintain records when changes or cleaning in source, source conditions, eluent, or column are made to the instrument;
7.7.11 Evaluate and document the performance of the instrument after routine and preventative maintenance and when changes in: source, source conditions, eluent, or column are made prior to reporting test results; and 7.7.12 Monitor and document the performance of the instrument each day of testing.
7.8 Inductively Coupled Plasma Mass Spectrometry (ICP/MS). A Natural Medicine Testing Facility using ICP must:
7.8.1 Perform and document preventive maintenance as required by the manufacturer and SOPs;
7.8.2 Ensure that records are maintained and readily available to the staff operating the equipment;
7.8.3 Establish written criteria for an acceptable mass-spectrometric tune;
7.8.4 Maintain records of mass spectrometric tuning;
7.8.5 Document Corrective Actions if a mass-spectrometric tune is unacceptable;
7.8.6 Use an internal standard with each qualitative and quantitative analysis that has similar chemical and physical properties to that of the compound identified and is isotopically labeled when available or appropriate for the assay;
7.8.7 Document the monitoring of the response (counts per second) of the internal standard to ensure consistency over time of the analytical system;
7.8.8 Compare mass-to-charge ratios between calibrators, controls and Samples within each run;
7.8.9 Monitor analyses to check for contamination and carry-over;
7.8.10 Evaluate and document the performance of the instrument after routine and preventative maintenance and when changes in: source, conditions, or detector are made prior to reporting test results; and 7.8.11 Monitor and document the performance of the instrument each day of testing.
7.9 Microbial Assays. A Natural Medicine Testing Facility using microbial assays must:
7.9.1 Perform and document preventive maintenance as required by the manufacturer and SOPs;
7.9.2 Ensure that records are maintained and readily available to the staff operating the equipment;
7.9.3 Validate any changes or modifications to a manufacturer’s approved assays or testing methods when a Sample is not included within the types of Samples approved by the manufacturer;
7.9.4 Verify the method at the Action Levels for each Analyte. Verification at the qualitative presence/absence limit shall include a fractional recovery study;
7.9.5 The Natural Medicine Testing Facility shall include controls for each set of Samples. Quantitative microbial methods shall use controls of a specific known value or set of values that lies within the quantifiable range of the method;
7.9.6 For molecular methods, the Natural Medicine Testing Facility shall include controls for each individual analytical run. Quantitative molecular methods shall use controls of a specific known value or set of values that lies within the quantifiable range of the method;
7.9.7 PCR-based and qPCR-based methods must include validated internal amplification controls; and 7.9.8 Microbial methods must include steps to confirm presumptive positive results; confirmation methods may be molecular or cultural or both. Where applicable, confirmation of viability must be performed.
7.9.9 Verify the stated Limit of Detection of qualitative assays through “dilution to extinction” studies in which the calculated extinction dilution is corroborated with cultural data.
7.10 Other Analytical Methodology. A Natural Medicine Testing Facility using any other analytical methodology must:
7.10.1 Perform and document preventive maintenance as required by the manufacturer or SOP;
7.10.2 Ensure that records are maintained and readily available to the staff operating the equipment;
7.10.3 Ensure that appropriate quality assurance and Quality Control measures are performed and documented as necessary for the specific methodology; and 7.10.4 Evaluate the performance of the instrument after routine and preventive maintenance prior to analyzing subject Samples.
7.11 General Quantitative Quality Parameters: A Natural Medicine Testing Facility must meet the following criteria for quantitative method controls.
7.11.1 Chemical Quality Controls must not exceed plus or minus 10% recovery of the target value when Analytes are greater than or equal to 100 parts per million (ppm).
7.11.2 Chemical Quality Controls must not exceed plus or minus 20% recovery of the target value when Analytes are greater than or equal to 10 ppm.
7.11.3 Chemical Quality Controls must not exceed plus or minus 20% recovery of the target value > when Analytes are greater than or equal to 1 ppm.
7.11.4 Chemical Quality Controls must not exceed plus or minus 20% recovery of the target value when Analytes are greater than or equal to 100 parts per billion (ppb).
7.11.5 Chemical Quality Controls must not exceed plus or minus 40% recovery of the target value when Analytes are greater than or equal to 10 ppb.
7.11.6 Chemical Quality Controls must not exceed plus or minus 60% recovery of the target value when Analytes are greater than or equal to 1 ppb.
7.11.7 Microbiology Quality Controls must not exceed plus or minus 20% recovery of the target value.
Rule 8: Natural Medicine Testing Facilities: Proficiency Testing 8.1. Participation in Proficiency Testing. If required by the Department as part of certification, the Natural Medicine Testing Facility must have successfully participated in Proficiency Testing in the category for which it seeks certification, within the preceding 12 months.
8.1.1 The Natural Medicine Testing Facility shall request the proficiency testing provider to send results concurrently to the Department, if available, or the Natural Medicine Testing Facility shall provide the proficiency testing results to the Department within 3 business days after the Natural Medicine Testing Facility receives notification of their results.
8.1.2 The Department may designate proficiency testing providers which meet, at minimum, the following criteria:
8.1.2.1 are ISO 17043 accredited organizations or state or federal government agencies, 8.1.2.2 offer proficiency testing in relevant matrices and which includes the Analytes for which the Natural Medicine Testing Facility is certified, and
8.1.2.3 offer proficiency testing which challenges the analytical method.
8.2 Continued Certification. To maintain continued certification, a Natural Medicine Testing Facility must participate twice per calendar year in a designated Proficiency Testing program with continued satisfactory performance as determined by the Department as part of certification. The Department may designate a local agency, state agency, or independent third-party to provide Proficiency Testing.
8.3 Analyzing Proficiency Testing Samples. A Natural Medicine Testing Facility must analyze Proficiency Test Samples using the same procedures with the same number of replicate analyses, standards, testing analysts, equipment, and data review processes as used in its Standard Operating Procedures.
8.4 Proficiency Testing Attestation. The Natural Medicine Testing Facility director and all testing analysts who participated in Proficiency Testing must sign corresponding attestation statements.
8.5 Natural Medicine Testing Facility Director Must Review Results. The Natural Medicine Testing Facility director must review and evaluate all Proficiency Testing results after receiving them from the proficiency testing provider.
8.6 Remedial Action. A Natural Medicine Testing Facility must take and document remedial action when a score of less than 100% is achieved on any test during Proficiency Testing. Remedial action documentation must include a review of Samples tested and results reported since the last successful Proficiency Testing event. A requirement to take remedial action does not necessarily indicate unsatisfactory participation in a Proficiency Testing event.
8.7 Unsatisfactory Participation in a Proficiency Testing Event. Unless the Natural Medicine Testing Facility positively identifies at least 80% of the target Analytes tested, participation in the Proficiency Testing event will be considered unsatisfactory. A positive identification must include accurate quantitative and qualitative results as applicable. Any false positive result reported will be considered unsatisfactory participation in the Proficiency Testing event.
8.8 Consequence of Unsatisfactory Participation in Proficiency Testing Event. Unsatisfactory participation in a Proficiency Testing event may result in limitation, suspension or revocation of certification. A Natural Medicine Testing Facility’s certification will be suspended for the relevant testing category if two consecutive unsatisfactory Proficiency Testing events occur, or if two out of three consecutive unsatisfactory Proficiency Testing events occur. Certification may be reinstated after successful participation in the next Proficiency Testing event. Failure to achieve a satisfactory score in the next test event will result in the revocation of the certification and will require two successful consecutive Proficiency Testing events before the Natural Medicine Testing Facility may be eligible to reapply for certification. Any limitation, suspension or revocation of certification must be disclosed to clients. Rule 9: Natural Medicine Testing Facilities: Quality Assurance and Quality Control 9.1 Quality Assurance Program Required. A Natural Medicine Testing Facility must establish, monitor, and document the ongoing review of a quality assurance program that is sufficient to identify problems in the laboratory preanalytic, analytic and postanalytic systems when they occur and must include, but is not limited to:
9.1.1 Review of instrument preventive maintenance, repair, and troubleshooting; Corrective Actions documentation must be performed by the laboratory director or designated quality assurance manager on an ongoing basis to ensure the effectiveness of actions taken over time;
9.1.2 Review by the Natural Medicine Testing Facility director or designated quality assurance manager of all ongoing quality assurance; and 9.1.3 Review of the performance of validated methods used by the Natural Medicine Testing Facility to include calibration standards, controls and the Standard Operating Procedures used for analysis on an ongoing basis to ensure quality improvements are made when problems are identified or as needed.
9.1.4 Review of Nonconformance reports at an appropriate specified frequency.
Nonconforming work which is deemed high impact must be reviewed at least monthly until a resolution is reached and a root cause identified. High impact nonconforming work may include, but is not limited to, any situation in which the laboratory is in violation of the rules outlined herein or where the quality of the data released is impacted..
9.2 Quality Control Measures Required. A Natural Medicine Testing Facility must establish, monitor and document on an ongoing basis the Quality Control measures taken by the Natural Medicine Testing Facility to ensure the proper functioning of equipment, validity of Standard Operating Procedures and accuracy of results reported. The Natural Medicine Testing Facility must ensure that appropriate quality assurance and Quality Control measures are performed and documented as necessary for the specific methodology. Such Quality Control measures must include, but shall not be limited to:
9.2.1 Documentation of instrument preventive maintenance, repair, troubleshooting and Corrective Actions taken when performance does not meet established levels of quality;
9.2.2 Review and documentation of the accuracy of automatic and adjustable pipettes and other measuring devices when placed into service and annually thereafter;
9.2.3 Cleaning, maintaining, verifying, and calibrating as needed the analytical balances and in addition, verifying the performance of the balance annually using certified weights to include three or more weights bracketing the ranges of measurement used by the Natural Medicine Testing Facility;
9.2.4 Annually verifying working thermometers against a certified reference thermometer. Certified reference thermometers shall be calibrated traceable to the SI (International System of Units) through NIST, or equivalent by an ISO/IEC 17025 accredited calibration laboratory with a listed certification date;
9.2.5 Recording temperatures on all equipment when in use where temperature control is specified in the Standard Operating Procedures, such as water baths, heating blocks, incubators, ovens, refrigerators, and freezers;
9.2.6 Properly labeling reagents as to the identity, the concentration, date of preparation, storage conditions, lot number tracking, expiration date and the identity of the preparer;
9.2.7 Avoiding mixing different lots of reagents in the same analytical run;
9.2.8 Performing and documenting a calibration curve with each analysis using at minimum five calibrators throughout the reporting range;
9.2.8.1 The laboratory shall not remove data points from within a calibration range while still retaining the extreme ends of the calibration range. If a calibration point fails, the laboratory must re-prepare and re-analyze the calibration standard;
9.2.8.2 The laboratory must use an appropriate curve-fitting algorithm (e.g. linear, quadratic, with or without weighing.) The acceptance criteria for concentrations of the calibration standards shall adhere to the recovery requirements outlined in Rule 7.10; and 9.2.8.3 The lowest calibration level shall not be greater than the applicable regulatory limit.
9.2.9 For qualitative analyses, analyzing, at minimum, a negative and a positive control with each batch of Samples analyzed;
9.2.10 For quantitative analyses, analyzing, at minimum, a negative and two levels of controls that challenge the linearity of the entire curve;
9.2.11 Using a control material or materials that differ in either source or, lot number, or concentration from the calibration material used with each analytical run;
9.2.12 For multi-Analyte assays, performing and documenting calibration curves and controls specific to each Analyte, or at minimum, one with similar chemical properties as reported in the analytical run;
9.2.13 Analyzing an appropriate Matrix blank and control with each analytical run, when available;
9.2.14 Analyzing calibrators and controls in the same manner as unknowns;
9.2.15 Documenting the performance of calibration standards and controls for each analytical run to ensure the Acceptability Criteria as defined in the Standard Operating Procedure is met;
9.2.16 Documenting all Corrective Actions taken when unacceptable calibration, control, and standard or instrument performance does not meet Acceptability Criteria as defined in the Standard Operating Procedure;
9.2.17 Maintaining records of validation data for any new or modified methods to include; accuracy, precision, analytical specificity (interferences), LOD, LOQ, and verification of the linear range;
9.2.18 Performing testing that follows the current Standard Operating Procedures for the test or tests to be performed;
9.2.19. The LOQ must be 50% of the limit or less for all Analytes within all assays; 9.2.20. Duplicate Sample results shall not exceed 30% relative percent difference (RPD); and 9.2.21. LOD and LOQ must be scientifically valid and experimentally determined.
9.3 Nonconforming Work: A Natural Medicine Testing Facility shall have a documented system by which it investigates Nonconformances within its quality management system. This system must include a standardized process for documenting Nonconformances which must include, but shall not be limited to, the following items:
9.3.1 A detailed description of what occurred to include, as appropriate, instrument ID, sample ID, batch ID, SOP number or title, Quality Control failure, client complaint, and date of occurrence;
9.3.2 An estimate of the severity of the consequences of the Nonconformance;
9.3.3 The impact of the Nonconformance;
9.3.4 Persons responsible for any part of the generation or review of the nonconforming work;
9.3.5 A thorough investigation to determine a root cause of the Nonconformance by a prescribed analysis process, to include the person(s) assigned to the root cause investigation and associated deadlines for completion;
9.3.6 A list of any analytical batches that were impacted and a list of Sample results recalled;
9.3.7 Whether or not work was stopped;
9.3.8 Corrective and/or Preventative Actions identified to include deadlines and the person(s) assigned to implement the action and actual dates of implementation;
9.3.9 The Nonconformance report must not be closed until all identified Corrective and Preventative Actions are implemented. The closed report shall be reviewed, signed, and dated by the Natural Medicine Testing Facility director or delegated quality assurance manager; and 9.3.10 An assigned deadline for future review to evaluate the effectiveness of Corrective and Preventative Actions.
9.4 Laboratory Reanalysis. A Natural Medicine Testing Facility must establish a policy regarding the retesting of client Samples. For the purposes of this rule, retesting does not include reanalysis of samples performed because quality control requirements were not met as described in the applicable standard operating procedure.
9.4.1 Reanalysis policies must specify the laboratory testing must be performed on the same homogenized Sample submitted to the Natural Medicine Testing Facility and include criteria by which the original result is confirmed or invalidated. The Natural Medicine Testing Facility must contact the submitting client when reanalysis is performed. A Natural Medicine Testing Facility shall follow the Nonconforming work process outlined in Rule 9.3 for every reanalysis.
9.4.1.1 Prior to reporting a result that differs from the original data point, a Nonconformance for retests outlined in Rule 9.3 must be submitted to the Department and the Colorado Department of Revenue.
9.4.1.2 Failure to do a scientifically valid investigation, a root cause analysis, or monthly review of open Nonconformances where no root cause has been determined will be considered a violation of rule.
9.4.3 Multiple amended test results for the same cause or same test type may indicate that test results are not accurate, precise, or scientifically valid. In the event of three or more invalidated results within a six month period, the Natural Medicine Testing Facility shall evaluate all relevant aspects of the pre-analytic, analytic, and post-analytic systems to determine the source of the error and implement Corrective Actions.
9.4.4 Failure to complete the Nonconforming work process outlined in Rule 9.3 in a manner that is sufficient to identify and prevent the recurrence of analytical errors is cause for suspension or revocation of certification for the affected test category. Rule 10: Natural Medicine Testing Facilities: Certificate of Analysis (COA) 10.1 The Natural Medicine Testing Facility shall generate a Certificate of Analysis (COA) for each Sample that the laboratory analyzes.
10.2 The Natural Medicine Testing Facility shall ensure that the COA contains the results of all requested analyses performed for the Sample.
10.3 The Natural Medicine Testing Facility shall, within 1 business day of completing analysis of a Sample, provide a copy of the COA to the submitting Natural Medicine Business and the Colorado Department of Revenue Natural Medicine Division.
10.3.1 The Natural Medicine Testing Facility shall indicate that a test result is for official compliance purposes on the COA for Samples of Natural Medicine when applicable.
10.4 The COA shall contain, at minimum, the following information:
10.4.1 Natural Medicine Testing Facility’s name, address, and contact information;
10.4.2 Natural Medicine Cultivator’s or Natural Medicine Manufacturer’s name, address, and DOR licensee number;
10.4.3 Sample identification;
10.4.4 Sample identifying information, including Matrix type and unique Sample identifiers, including lot identification number when applicable;
10.4.5 Sample received date, and the date(s) of Sample analyses and corresponding testing results;
10.4.6 Units of measure;
10.4.7 The analytical methods, analytical instrumentation used, and corresponding Limits of Detection (LOD) and Limits of Quantitation (LOQ);
10.4.8 Reported results must include the range of estimated uncertainty which shall be reported as a ± value in the same units of measure as the test result, following best practices for significant figures and rounding; and 10.4.9 For Samples of Natural Medicine, reported tryptamine content results must provide a calculated Total Psilocin value, in addition to psilocybin and psilocin values.
10.4.9.1 A dedicated area to include any qualifiers or comments needed for
10.4.10 The COA may contain additional information at the discretion of the Natural Medicine Testing Facility and submitting client.
10.5 The Natural Medicine Testing Facility shall report test results for each representative Sample on the COA as follows:
10.5.1 When reporting qualitative results for each Analyte, the Natural Medicine Testing Facility shall indicate presence or absence;
10.5.2 When reporting quantitative results for each Analyte, the Natural Medicine Testing Facility shall only report results that are above the lowest concentration of calibrator or standard used in the analytical run;
10.5.3 When reporting results for any Analytes that were detected below the analytical method LOQ and above the LOD, indicate “<LOQ”;
10.5.4 When reporting results for any Analytes that were not detected or detected below the LOD, indicate “ND” or “<LOD”; and 10.6 The Natural Medicine Testing Facility director or supervisory analyst shall validate the accuracy of the information contained on the COA.
Rule 11: Natural Medicine Testing Facilities: Chain of Custody 11.1 General Requirements. A Natural Medicine Testing Facility must establish an adequate Chain of Custody for handling Samples. Instructions that must include, but are not limited to:
11.1.1 Issue instructions for the minimum Sample requirements and storage requirements;
11.1.1.1 Separate Sample into a test and a retain Sample;
11.1.2 Document identifying information of the submitting Natural Medicine Business, including Harvest Lot or Production Lot identification;
11.1.3 Assign and document a unique Sample identifier;
11.1.4 Document the condition of the external package and integrity seals utilized to prevent contamination of, or tampering with, the Sample;
11.1.5 Document the condition, temperature, Matrix, and amount of Sample provided at the time of receipt;
11.1.6 Document all persons handling the original Samples, aliquots, and extracts;
11.1.7 Document all Transfers of Samples, aliquots, and extracts referred to another certified Natural Medicine Testing Facility for additional testing or whenever requested by a client;
11.1.8 Maintain a current list of authorized personnel and restrict entry to the Natural Medicine Testing Facility to only those authorized;
11.1.9 Secure the Natural Medicine Testing Facility during non-working hours;
11.1.10 Secure short and long-term storage areas when not in use;
11.1.11 Utilize a secured area to log-in and aliquot Samples;
11.1.12 Ensure Samples are stored appropriately as defined in the written SOP; and
11.1.13 Document the disposal of Samples, aliquots, and extracts; and
11.1.14 Document the license number, inventory tracking number, photograph(s), and the reason for rejection of Samples that were rejected and notify the Colorado Department of Revenue within 7 days of Sample submission.
Rule 12: Natural Medicine Testing Facilities: Records Retention 12.1 General Requirements. A Natural Medicine Testing Facility must maintain all required business records. See Rule 13 - Business Records Required.
12.2 Specific Business Records Required Record Retention. A Natural Medicine Testing Facility must establish processes to preserve records in accordance with Rule 13 that includes, but is not limited to;
12.2.1 Test Results, including final and amended reports, and identification of analyst and date of analysis;
12.2.2 Quality Control and quality assurance Records, including Nonconformance reports, accession numbers, Sample type, and acceptable reference range parameters;
12.2.3 Standard Operating Procedures;
12.2.4 Personnel Records;
12.2.5 Chain of Custody Records;
12.2.6 Proficiency Testing Records; and
12.2.7 Analytical Data to include data generated by the instrumentation, raw data of calibration standards and curves.
Rule 13: Natural Medicine Testing Facilities: Business Records Required
13.1 General Requirements.
13.1.1 A Natural Medicine Testing Facility shall retain all records required by this rule for the current year and three preceding calendar years.
13.1.1.1 On premises records: The Natural Medicine Testing Facility records for
13.1.1.2 On- or off-premises records: Records associated with older periods may
13.1.2 The records must include, but shall not be limited to:
13.1.2.1 Current Employee List – This list must provide the full name and job title of each employee who works at the Natural Medicine Testing Facility;
13.1.2.2 Visitor Log – List of all visitors entering any limited or restricted access areas as defined by the Natural Medicine Testing Facility;
13.1.2.3 Waste Log – Comprehensive records regarding all waste that accounts
13.1.2.4 Testing Records – The Natural Medicine Testing Facility must maintain
13.1.2.5 Standard Operating Procedures – All Standard Operating Procedures as
13.1.2.6 Corrective Action and Preventive Action records;
13.1.2.7 Chain of Custody records; and
13.1.2.8 All other records required by these Rules.
13.1.3 Loss of Records and Data. Any loss of electronically-maintained records shall not be considered a mitigating factor for violations of this Rule. Natural Medicine Testing Facilities are required to exercise due diligence in preserving and maintaining all required records.
13.1.4 Provision of Any Requested Record to the Department. A Natural Medicine Testing Facility must provide on-demand access to on-premises records following a request from the Department during normal business hours or hours of apparent operation, and must provide access to off-premises records within three business days following a request from the Department.
Rule 14: Waste Disposal 14.1 All Applicable Laws Apply. All waste must be stored, secured, and managed in accordance with all applicable federal, state, local, and Tribal statutes, regulations, ordinances, or other requirements, including but not limited to the “Regulations Pertaining to Solid Waste Sites and Facilities” (6 CCR 1007-2, Part 1) and “Regulation No. 100 – Water and Wastewater Facility Operations Certification Requirements” (5 CCR 1003-2).
14.2 Liquid Waste. Liquid waste from Natural Medicine Testing Facilities must be disposed of in compliance with all applicable federal, state, local, and Tribal laws, regulations, rules, and other requirements.
14.3 Chemical, Dangerous and Hazardous Waste. Disposal of chemical, dangerous, and hazardous waste must be conducted in a manner consistent with federal, state, local, and Tribal laws, statutes, regulations, rules, and other requirements.
14.4 Regulated Natural Medicine Waste. Disposal of Regulated Natural Medicine Waste containing psilocybin or psilocin must be disposed of in accordance with 1 CCR 213-1, 3120 “Waste Disposal”.
_________________________________________________________________________ Editor’s Notes History New rule eff. 01/14/2025.