Acceptance criteria: Predetermined limits (e.g., number, numerical ranges, or other suitable measures) for acceptance of examination or test results.
Adequate: Item/area/system/knowledge that meets basic minimum requirements that are needed to accomplish intended purpose.
Adulteration: A food shall be deemed to be adulterated if it contains any poisonous or deleterious substance as specified in 402(a)(1) and (a)(2) of the FFDCA: or if it consists of any filthy, putrid, or decomposed substance, or if it is otherwise unfit for food as specified in 402(a)(3) of the FFDCA; or if it has been prepared, packed or held under insanitary conditions as specified in 402(a)(4) of the FFDCA; or if its container is composed of any poisonous or deleterious substance which may render the contents injurious to health as specified in 402(a)(6) of the FFDCA; or if it has been intentionally subjected to radiation as specified in 402(a)(7) of the FFDCA; or if the contents have been altered, or if damage and or inferiority has been concealed as specified in 402(b)(1-4); or if it contains a color additive which is unsafe as specified in 402(c); or if it is a dietary supplement or contains a dietary ingredient that presents a significant or unreasonable risk of illness or injury as specified in 402(f)(1); or if it is a dietary supplement that has not been prepared, packed, or held under conditions that do not meet current good manufacturing practice regulations as specified in 402(g)(1); or if it has not been transported in compliance with regulations as specified in 402(i).
Adverse event: Any undesirable experience associated with the use of a dietary supplement in a person.
Adverse event report: A direct communication from an identifiable first-hand reporter of an adverse event that includes at least the following information: an identifiable reporter, an identifiable person(s) who experienced the adverse event(s), an identifiable dietary supplement, and one or more adverse events.
Allergen Cross-Contact: The unintentional incorporation of a food allergen into a dietary supplement.
Allergen: A major food allergen as defined in section 201(qq) of the FFDCA, means any of the following: (1) milk, egg, fish (e.g., bass, flounder, or cod), Crustacean shellfish (e.g., crab, lobster, or shrimp), tree nuts (e.g., almonds, pecans, or walnuts), wheat, peanuts, and soybeans; (2) a food ingredient that contains protein derived from a food specified in (1), except (A) any highly refined oil derived from a food specified in (1) and any ingredient derived from such highly refined oil, and (B) a food ingredient that is exempt under paragraph (6) and (7) of section 403(w) of the FFDCA.
Article: Includes substances (such as components, in-process material, dietary ingredients), products (such as dietary supplements), and materials (such as packaging containers and closures, and labels).
Audit: A planned, systematic, objective, independent, and documented examination (through observation, investigation, records review, discussions with employees of the audited firm, and, as appropriate, sampling and laboratory analysis) to assess whether agreed upon requirements are being met.
Batch: A specific quantity of a dietary supplement or other article that is intended to be uniform; that is intended to meet specifications for identity, purity, strength, and composition; and that is produced during a specified time period according to a single manufacturing record during the same cycle of manufacture.
Batch (or lot) number: Any distinctive group of letters, numbers, or symbols, or any combination of them, from which the complete history of the manufacturing, packaging, labeling , and/or holding of a batch or lot of dietary supplements can be determined.
Calibration: The demonstration that a particular instrument or device produces results within specified limits by comparison with those produced by a reference or traceable standard over an appropriate range of measurements.
Can: Used to indicate a possibility or a capability.
Certificate of Analysis (CoA): A document relating specifically to the results of testing a representative sample drawn from the batch of material. The CoA should list each test performed in accordance with compendial or manufacturer requirements, including reference to the test procedure, the acceptance limits, and the results obtained.
Code of Federal Regulations (CFR): The CFR annual edition is the codification of the general and permanent rules and regulations published in the Federal Register by the executive departments and agencies of the Federal Government of the United States. It is structured into 50 subject matter titles; title 1 applies to general provisions, and title 21 applies to food and drugs. Titles are broken down into parts, subparts, sections and paragraphs. For example, 21 CFR 11.10(k)(2) would be read as title 21, part 11 (subpart B, not specified here), section 10, paragraph (k)(2). The CFR annual edition is published by the Office of the Federal Register, National Archives and Records Administration and the Government Publishing Office. In addition to this annual edition, the CFR is published in an unofficial format on-line in electronic format (eCFR), which is updated daily.
Component: Any substance intended for use in the manufacture of a dietary supplement, including those that may not appear in the finished batch of the dietary supplement.
Composition: The specified mix of product and product-related substances, i.e., specified mix of food ingredients or excipients and dietary ingredients in a dietary supplement.
Contact Surface: Any surface that contacts a component, in-process material, or dietary supplement, and those surfaces from which drainage onto the component or dietary supplement, or onto the surfaces that contact the component or dietary supplement, occurs during the normal course of operations. Examples of contact surfaces include containers, utensils, tables, contact surface of equipment, and packaging.
Contamination: The undesired introduction of a chemical or microbiological nature, or of foreign matter, into or onto a component, in-process material, or dietary supplement during production, sampling, packaging, repackaging, storage or transport.
Contract manufacturer: A manufacturer performing some aspect of manufacturing on behalf of the original manufacturer.
Corrective Action: An action that is developed and implemented to ensure that any identified root cause of a nonconformity does not recur.
Critical: Describes a manufacturing process step, process condition, test requirement, or other relevant parameter or item that must be controlled within predetermined criteria to ensure the dietary supplement meets its specification.
Design qualification (DQ): DQ is the documented collection of activities that defined the functional and operational specifications and intended purpose of the equipment or instrument. DQ states what the user wants the equipment or instrument to do and shows that the selected equipment or instrument is suitable.
Defect action level: A level of a non-hazardous, naturally occurring, unavoidable defect at which FDA may regard a food product “unadulterated” and subject to enforcement action under section 402(a)(3) of the FFDCA.
Deviation: Departure from an approved instruction or procedure, or from an established standard (i.e., a failure, or an out of specification result). Deviations can be planned, or unplanned (i.e., a nonconformity).
Dietary ingredient: An ingredient intended for use or used in a dietary supplement that is: a vitamin; a mineral; an herb or other botanical; an amino acid; a dietary substance for use by man to supplement the diet by increasing the total dietary intake, or a concentrate, metabolite, constituent, extract; or a combination of the aforementioned ingredients.
Dietary supplement: A product (other than tobacco) intended to supplement the diet that bears or contains one or more of the following dietary ingredients: a vitamin; a mineral; an herb or other botanical; an amino acid; a dietary substance for use by man to supplement the diet by increasing the total daily intake; or a concentrate, metabolite, constituent, extract or combination of the aforementioned ingredients; that is intended for ingestion in a tablet, capsule, powder, softgel, gelcap, or liquid form; that is not represented for use as a conventional food or as a sole item of a meal or the diet; and is labeled as a dietary supplement; and does include an article approved as a new drug, certified antibiotic, or licensed biologic, and was prior to such approval, certification, or license, marketed as a dietary supplement or food unless the Secretary of Health and Human Services has issued a regulation finding that the article , when used as or in a dietary supplement under the conditions of use and dosages set forth in the labeling for such dietary supplement is unlawful.
Disposition decision: A decision to approve or reject material, quality control and manufacturing related processes or documents, based on a scientifically valid reason. Disposition decisions can be made regarding release of components, in-process materials, dietary supplements, packaging materials, labels, returned dietary supplements, based on a determination of whether or not established specifications are met; or regarding reprocessing treatments and in-process adjustments, master manufacturing records and batch production records, repackaging or relabeling, calibrations of an instrument or control, modification or deviations from standard procedures, and whether or not a deviation or unanticipated occurrence during the production and in-process control system could lead to addulteration of a dietary supplement.
Documentation: Written material related to the requirements of the quality system, including paper and electronic records, that consist of raw data, reports, protocols, and procedures related to manufacturing controls and laboratory testing. Official documents are records that support procedure, product, or the manufacturer’s quality systems (e.g., standard operating procedures, master batch records, material specifications, standard test procedures, protocols, reports). Source documents are records that contain original data or information (e.g., forms, notebooks, logbooks, instrument printouts).
Equipment: Devices used to manufacture, package or hold dietary supplements, or to maintain or clean the physical plant and devices.
Facility: A place, amenity, utility, or piece of equipment provided for a particular purpose.
Federal Food, Drug, and Cosmetic Act: Federal Food, Drug and Cosmetic Act (FFDCA or FD&C Act) [United States Code (U.S.C.) Title 21, Chapter 9] is the official compilation and codification of the federal statutes of the U.S. that gives authority to the Food and Drug Administration (FDA) oversee the safety of food, drugs, medical devices and cosmetics in the U.S.
Ingredient: Any substance that is used in the manufacture of a dietary supplement and that is intended to be present in the finished batch of the dietary supplement.
In-process control (or process control): Checks performed during production in order to monitor and, if appropriate, to adjust the process and/or to ensure the dietary supplement conforms to its specification.
In-process material: Any material that is fabricated, compounded, blended, ground, extracted, sifted, sterilized, derived by chemical reaction, or processed in any other way for use in the manufacture of a dietary supplement.
In-process tests: Tests which may be performed during the manufacture of the dietary supplement, rather than as part of the formal battery of tests which are conducted prior to release.
Instrument (or instrumentation): A sophisticated measuring device or tool used for analytical or scientific work.
Installation qualification (IQ): IQ is the documented collection of activities necessary to establish that an equipment or instrument is delivered as designed and specified, is properly installed in the selected environment, and that the environment is suitable for the instrument.
Label: A display of written, printed, or graphic matter upon the immediate container of a dietary supplement.
Labeling: All labels and other written, printed, or graphic matter upon any dietary supplement or any of its containers, or wrappers, or accompanying such dietary supplement at any time while the dietary supplement is held for sale after shipment or delivery for shipment in interstate commerce. The term “accompanying” is interpreted liberally to mean more than physical association with the dietary supplement. It extends to posters, tags, pamphlets, circulars, booklets, brochures, fillers, etc.
Lot: A batch, or a specific identified portion of a batch, that is intended to be uniform and that is intended to meet specifications for identity, purity, strength, and composition.
Manufacture: All operations of receipt of components, production, packaging, labeling, quality control testing, release, storage and distribution of dietary supplements and related controls.
Material: A general term used to denote components, in-process materials, dietary supplements, and packaging and labeling material.
May: Used to indicate a permission.
Microorganisms: Yeast, molds, bacteria, viruses and other microscopic organisms having public health or sanitary concern. This includes undesirable species that may have public health significance; that may cause a component or dietary supplement to decompose; that indicate that a component or dietary supplement is contaminated with filth; or that otherwise may cause a component a dietary supplement to be adulterated.
Must: Used to state a requirement.
Nonconformity: An event that occurs when a specified requirement is not met or results from an undesirable situation or defect. This covers departure from a procedure, standard or requirement, or the absence of dependability. This typically arises from the inability to meet documented procedures, expectations or specifications.
Operational qualification (OQ): OQ is the documented collection of activities necessary to demonstrate that an equipment or instrument will function according to its operational specification testing in the selected environment. OQ demonstrates fitness for the selected use and demonstrates user requirement specifications.
Packaging material: Container and/or closure for components, in-process material and dietary supplements.
Performance qualification (PQ): PQ is the documented collection of activities necessary to demonstrate that an equipment or instrument consistently performs according to the specifications defined by the user, and is appropriate for the intended use. PQ verifies the fitness for purpose of the equipment or instrument under actual conditions of use.
Pest: Any objectionable insect or other animal including, but not limited to, birds, rodents, flies, mites, and larvae.
Physical plant: All or any part of a building or facility used for or in connection with manufacturing, packaging, labeling, or holding of a dietary supplement.
Preventive Action: An action taken to eliminate the cause of potential nonconformities or other undesirable situations in order to prevent occurrence, and continuously improve an existing system or process.
Preventive Controls Qualified Individual (PCQI): A qualified individual who has successfully completed training in the development and application of risk-based preventive controls at least equivalent to that received under a standardized curriculum recognized as adequate by FDA or is otherwise qualified through job experience to develop and apply a food safety system .
Procedure: A documented description of the operations to be performed, the precautions to be taken, and measures to be applied directly or indirectly related to the manufacture of a dietary supplement.
Process evaluation: A set of tests performed on a process intended to evaluate its capacity to consistently produce the results that it is intended for.
Product complaint: Any communication that contains any allegation, written, electronic, or oral, expressing concern, for any reason, with the quality of a dietary supplement, that could be related to current manufacturing practice.
Purity:The identity and amount of a substance that is the intended substance, typically expressed in units of percentage, and determined using tests for assay or content.
Qualification: Action of proving and documenting that equipment or ancillary systems are properly, work correctly, and actually lead to the expected results. Qualification is part of validation, but the individual qualification steps alone do not constitute process validation.
Quality: Means that the components, in-process materials, packaging materials, labeling and dietary supplements meet established specifications for identity, purity, strength and composition, and limits on contaminants, and that the dietary supplement has been manufactured, packaged, labeled, and held under conditions to prevent adulteration.
Quality assurance: The sum total of the organized arrangements made with the goal of ensuring that all dietary supplements are of the quality required for their intended use and that quality systems are maintained.
Quality assurance personnel (or unit): Any person, persons or group, within or outside of the firm who is designated by the firm to be responsible for the duties relating to quality assurance.
Quality control: A planned and systematic operation or procedure necessary to ensure the quality of the dietary supplement, by checking or testing that specifications are met.
Quality control personnel (or unit): Any person, persons or group, within or outside of the firm, who is designated by the firm to be responsible for the duties relating to quality control operations.
Quality unit (or personnel): An organizational unit independent of production, which fulfills both quality assurance and quality control responsibilities, which can be in the form of separate quality assurance and quality control units or a single individual or group, depending upon the size and structure of the organization.
Quarantine: The status of materials isolated physically or by other effective means pending a decision on their subsequent disposition decision.
Records: Records are documents stating results achieved or providing evidence of activities performed, e.g., training records, executed batch production records, executed batch packaging records, validation reports, laboratory test results forms, laboratory notebooks, equipment logbooks, memos, and emails.
Reduced testing (or sampling): A reduced level of testing (or sampling) for a particular specified parameter(s) based upon one or more of the following: statistical analysis of an adequate quantity of historical test data; statistical confidence in the capability of the manufacturing process as determined by suitable verification; or ongoing monitoring of the process using recognized statistical process control (SPC) techniques.
Reference standard, primary: A substance that has been shown by an extensive set of analytical tests to be authentic material that should be of high purity. This standard is obtained from an officially recognized source, i.e., USP RS.
Reference standard, secondary: A substance of established quality and purity, as shown by comparison to a primary reference standard, used as a reference standard for routine laboratory analysis.
Remedial (short term) Action: Action taken to provide temporary control over a situation or condition until permanent corrective actions are implemented (e.g., issuance of a temporary procedure, segregation of material).
Representative sample: A sample that consists of an adequate number of units that are drawn based on rational criteria, such as random sampling, and that is intended to ensure that the sample accurately portrays the material being sampled.
Reprocessing: Introducing clean and uncontaminated components or dietary supplements, back into the manufacturing process and repeating a step or other appropriate physical manipulation step (e.g., milling, packaging) that are part of the established manufacturing process. Continuation of a manufacturing process step after an in-process control test has shown that the step is incomplete is considered to be part of the normal manufacturing process and not reprocessing.
Reworking: Subjecting in-process material or dietary supplements that do not conform to standards or specifications and that have been removed from processing for reasons other than unsanitary conditions, to one or more processing steps that are different from the established manufacturing process to obtain acceptable quality in-process material or dietary supplement.
Reserve sample: A representative sample of an article that is held for a designated period of time.
Root cause: Any cause that is acted upon by a solution such that the problem does not recur.
Sanitize: To adequately treat cleaned equipment, containers, utensils, or other cleaned contact surface by a process that is effective in destroying vegetative cells of microorganisms of public health significance, and in substantially reducing numbers of other microorganisms, but without adversely affecting the product or its safety for the consumer.
Serious adverse event: An event that results in death, a life-threatening experience, inpatient hospitalization, a persistent or significant disability or incapacity, or a congenital anomaly or birth defect; or requires based on a reasonable medical judgement, a medical or surgical intervention to prevent an outcome previously described.
Serious adverse event report: A report that must be submitted to the FDA using the MedWatch form when a manufacturer, packer, or distributor of a dietary supplement receives any report of a serious adverse event associated with the use of the dietary supplement in the United States. (See section 761(a)(3) and (b)(1) of the FD&C Act (21 U.S.C. 379aa-1(a)(3), (b)(1)).
Shall: Used to indicate a requirement.
Shelf-life (use by or expiry) date: The date before which the dietary supplement is ensured to meet applicable specifications of identity, strength, quality, and purity, when stored under labeled conditions.
Should: Used to indicate a recommendation.
Signature (signed): The record of the individual who performed a particular action or review. This record can be initials, full handwritten signature, or authenticated and secure electronic signature.
Specification: A list of tests, references to test procedures, and appropriate acceptance criteria for the tests described. It establishes the set of criteria to which a material should conform to be considered acceptable for its intended use. “Conformance to specifications” means that the component, in-process material and/or dietary supplement, when tested according to the listed test procedures, will meet the listed acceptance criteria. Specifications are critical quality standards that are proposed, justified and approved by the manufacturer. Material specifications include test specifications for identity, purity, strength, limits on contaminants and/or performance that define a standard of quality for the material.
Strength: The concentration or amount of a dietary ingredient per unit serving of a dietary supplement. Strength only applies to a dietary supplement.
Utensil: A simple tool or device serving a useful purpose.
Utility system (utility): A useful system and source of material such as water, steam, gases, compressed air, and heating, ventilation and air conditioning.
Validation: A documented program that provides a high degree of assurance that a specific process, method, or system will consistently produce a result meeting pre-determined acceptance criteria.
Validation Protocol: A written plan stating how validation will be conducted and defining acceptance criteria. For example, the protocol for a manufacturing process identifies manufacturing equipment, critical process parameters/operating ranges, product characteristics, sampling, test data to be collected, number of validation runs and acceptable test results.
Water activity (aw): A measure of the free moisture in a component or dietary supplement and is the quotient of the water vapor pressure of the substance divided by the vapor pressure of pure water at the same temperature.
Yield, actual: The quantity of material or percentage of theoretical yield that is actually produced at any appropriate step of production, or packaging and labeling of a particular dietary supplement.
Yield, expected: The quantity of material or the percentage of theoretical yield anticipated at any appropriate phase of production, or packaging and labeling, based on previous laboratory, pilot scale, or manufacturing data.
Yield, theoretical: The quantity of material that would be produced at any appropriate step of manufacture or packaging and labeling of a particular dietary supplement, based on the quantity of components, packaging labeling to be used, in the absence of any loss or error in actual production.