A quality control unit shall be established that has the responsibility and authority to approve or reject all raw materials, product containers, closures, in-process materials, packaging material, labeling, and finished dietary supplements, and the authority to review production records to ensure that no errors have occurred or, if errors have occurred, that they have been fully investigated. The quality control unit should be responsible for approving or rejecting products manufactured, processed, packed, or held under contract by another company.

Adequate laboratory facilities for the testing and approval (or rejection) of raw materials, product containers, closures, packaging materials, in-process materials, dietary ingredients, and dietary supplements should be available to the quality control unit.

The quality control unit should have the responsibility for approving or rejecting all procedures or specifications that impact on the identity, strength, quality, and purity of the dietary supplement. All responsibilities and procedures applicable to the quality control unit shall be in writing.

The designated person within the Quality Control Unit who conducts a material review and makes the disposition decision must, at the time of performance, document that material review and disposition decision.

Each person engaged in the manufacture of dietary ingredients and dietary supplements should have the proper education, training, and experience (or any combination thereof) needed to perform the assigned functions. Training should be in the particular operation(s) that the employee performs as they relate to the employee's functions.

Appropriate documentation of training shall be retained by the company.

Each person responsible for supervising the manufacture of a dietary ingredient, a dietary supplement, or both should have the proper education, training, and experience (or any combination thereof) to perform assigned functions in such a manner as to provide assurance that the product has the safety, identity, strength, quality, and purity that it is represented to possess.

An adequate number of qualified personnel to perform and supervise the manufacture of each dietary ingredient, dietary supplement, or both product should be provided.

The company management shall take all reasonable measures and precautions to ensure the following:

The grounds about a dietary ingredient manufacturing plant and a dietary supplement manufacturing plant under the control of the operator shall be kept in a condition that will protect against the adulteration of dietary ingredients and dietary supplements. The methods for adequate maintenance of grounds include, but are not limited to, the following:

Any building or buildings used in the manufacture of a dietary ingredient, a dietary supplement, or both should be of suitable size and shall be constructed in such a manner that floors, walls, and ceilings may be adequately cleaned and kept clean and in good repair; that drips or condensates from fixtures, ducts, and pipes do not adulterate raw materials or in-process or finished dietary ingredients and dietary supplements, or contaminate product containers, utensils, or packaging materials; and that aisles or working spaces are provided between equipment and walls and are adequately unobstructed and of adequate width to permit employees to perform their duties and to protect against adulterating in-process or finished product, or contaminating processing equipment with clothing or personal contact. Adequate screening or other protection against pests and insects should be installed, where necessary. The building should have adequate space for the orderly placement of equipment and materials to prevent mixups between different raw materials, product containers, closures, labeling, in-process materials, or finished products, and to prevent contamination. The flow of raw materials, product containers, closures, labeling, in-process materials, and products through the building or buildings should be designed to prevent contamination.

Operations should be performed within specifically defined areas of adequate size to prevent contamination or mixups or adulteration of in-process or finished dietary ingredients and dietary supplements, or contamination of processing equipment, utensils, or packaging materials with microorganisms, chemicals, filth, or other extraneous materials. The potential for mixups and product adulteration may be reduced by adequate product safety controls and operating practices or effective design, including the separation of operations in which contamination is likely to occur, by one or more of the following means: location, time, partition, airflow, enclosed systems, or other effective means. There should be separate or defined areas as follows:

Any building used in the manufacture of a dietary ingredient or a dietary supplement shall permit the taking of proper precautions to protect dietary ingredients or dietary supplements in outdoor bulk fermentation vessels by any effective means, including the following:

Adequate lighting shall be provided in all areas and should not expose bulk or finished product to adulteration or contamination. Adequate lighting should be provided in hand-washing areas, dressing and locker rooms, and toilet rooms, and in all areas where product is examined, processed, or stored and where equipment or utensils are cleaned; and such lighting should provide safety-type light bulbs, fixtures, skylights, or other glass suspended over exposed product in any step of preparation or otherwise protect against product adulteration in case of glass breakage.

Adequate ventilation shall be provided, as well as equipment for adequate control over microorganisms, dust, humidity, and temperature when used in the manufacture of a dietary ingredient and a dietary supplement to minimize odors and vapors (including steam and noxious fumes) in areas where they may adulterate dietary ingredients and dietary supplements; and to locate and operate fans and other air-blowing equipment in a manner that minimizes the potential for adulterating raw materials, in-process or finished dietary ingredients and dietary supplements, or contaminating processing equipment, utensils, or packaging materials.

The plumbing in the physical plant must be of an adequate size and design and be adequately installed and maintained to:

Potable water at a suitable temperature, and under pressure as needed, should be supplied in a plumbing system free of defects that could contribute contamination to any dietary ingredients and dietary supplements. Potable water should meet the standards prescribed in the Environmental Protection Agency's Primary Drinking Water Regulations (40 CFR Part 141) or any state or local drinking water requirements that are more stringent. Water not meeting such standards should not be permitted in the potable water system for Purified Water. If potable water is to be used as a raw material, it should be further purified to satisfy compendial requirements.

Drains should be of adequate size and, where connected directly to a sewer, should have an air break or other mechanical device to prevent back-siphonage.

Sewage, trash, and other refuse in and from the building and immediate premises shall be disposed of in a safe and sanitary manner.

Adequate washing facilities shall be provided, including hot and cold water, soap or detergent, air driers or single-service towels, and clean toilet facilities easily accessible to working areas.

Any building used in the manufacture of a dietary ingredient, a dietary supplement, or both should be maintained in a clean and sanitary condition and shall be kept in repair sufficient to prevent raw materials and in-process or finished dietary ingredients and dietary supplements from becoming adulterated. It shall be free of infestation by rodents, birds, insects, and other vermin. Trash and organic waste matter shall be held and disposed of in a timely and sanitary manner.

Cleaning compounds and sanitizing agents used in cleaning and sanitizing procedures shall be free from undesirable microorganisms and shall be safe and adequate under the conditions of use. Compliance with this requirement may be verified by any effective means, including purchase of these substances under a supplier's guarantee or certification, or examination of these substances for contamination. Only the following toxic materials may be used or stored in a plant where product is processed or exposed:

Written procedures assigning responsibility for sanitation and describing in sufficient detail the cleaning schedules, methods, equipment, and materials to be used in cleaning the building and facilities shall be required.

Toxic cleaning compounds, sanitizing agents, and pesticide chemicals shall be identified, used, held, and stored in a manner that protects against adulteration of raw materials or of in-process or finished product, or contamination of processing equipment or packaging materials. All relevant regulations promulgated by other federal, state, and local government agencies for the application, use or holding of these products should be followed.

No pests shall be allowed in any area of a dietary ingredient manufacturing plant and a dietary supplement manufacturing plant. Effective measures shall be taken to exclude pests from the processing areas and to protect against the adulteration by pests of product on the premises. The use of insecticides or rodenticides is permitted only under precautions and restrictions that will protect against the adulteration of raw materials, in-process or finished product, or contamination of processing equipment, utensils, or packaging materials.

Written procedures are also required for use of suitable rodenticides, insecticides, fungicides, fumigating agents, and cleaning and sanitizing agents. These procedures should be designed to prevent the contamination of equipment, raw materials, product containers, closures, packaging, labeling materials, or products. Rodenticides, insecticides, and fungicides should be registered and used in accordance with the Federal Insecticide, Fungicide, and Rodenticide Act.

Sanitation procedures shall apply to work performed by contractors or temporary employees as well as work performed by full-time employees during the ordinary course of operations.

All equipment and utensils shall be:

Equipment and utensils must have seams that are smoothly bonded or maintained to minimize the accumulation of dirt, filth, organic material, particles of raw materials, in-process materials, dietary ingredients, or dietary supplements, or any other extraneous materials or contaminants, in order to minimize the opportunity for growth of microorganisms.

Each freezer, refrigerator, and cold storage compartment used to hold raw materials, in-process materials, dietary ingredients, or dietary supplements

The design, construction, and use of equipment and utensils shall preclude the adulteration of raw materials, packaging materials, in-process materials, or finished product with any substances required for operation, such as:

Instruments or controls used in the manufacturing, packaging, labeling, or holding of a dietary ingredient, a dietary supplement, or both; and instruments or controls that are used to measure, regulate, or record temperatures, hydrogen-ion concentration (pH), water activity, or other conditions, and to control or prevent the growth of microorganisms or other contamination must be:

For any automated, mechanical, or electronic equipment that is used to manufacture, package, label, or hold a dietary ingredient, a dietary supplement, or both:

Compressed air or other gases introduced mechanically into or onto raw materials, in-process materials, dietary ingredients, dietary supplements, or contact surfaces, or that are used to clean any contact surface, must be treated in such a way that the raw material, in-process material, dietary ingredient, dietary supplement, or contact surface is not contaminated.

Equipment and utensils shall be cleaned, maintained, and sanitized at adequate intervals, between the manufacture of different batches of the same product and between the manufacture of different products, to prevent malfunctions or contamination that would alter the safety, identity, strength, quality, or purity of the product beyond the established requirements.

In wet processing during manufacturing, all contact surfaces must be cleaned and sanitized, as necessary, to protect against the introduction of microorganisms into components, dietary ingredients, or dietary supplements. When cleaning and sanitizing is necessary, all contact surfaces must be cleaned and sanitized before use and after any interruption during which the contact surface may have become contaminated.

In a continuous production operation or in back-to-back consecutive operations, which involve different batches of the same dietary ingredient or dietary supplement, the contact surfaces must be adequately cleaned and sanitized.

The surfaces that do not come into direct contact with raw materials, in-process materials, dietary ingredients, or dietary supplements must be cleaned as frequently as necessary to protect against contaminating raw materials, in-process materials, dietary ingredients, or dietary supplements.

Single-service articles (such as utensils intended for one-time use, paper cups, and paper towels) must be:

Cleaning compounds and sanitizing agents must be adequate for their intended use and safe under their conditions of use.

The portable equipment and utensils that have contact surfaces must be cleaned, sanitized, and then stored in a location and manner that protects them from contamination.

Written procedures for cleaning and maintaining equipment, including utensils, used in the manufacture of a product should be established and followed. These procedures should include, but are not necessarily limited to, the following:

A written record of calibration, inspection, maintenance of equipment, and major equipment cleaning and use shall be maintained in individual equipment logs that show the date, product, and lot number of each batch processed. The persons performing the cleaning shall record in the log that the work was performed. Entries in the log should be in chronological order.

Written procedures shall be established and followed describing the receipt, identification, examination, handling, and sampling of raw materials. Upon receipt and before acceptance, each container or grouping of containers of raw materials, product containers, and closures should be examined visually for appropriate labeling as to contents, container damage, or broken seals, and for contamination. They are then stored under quarantine until they have been tested or examined, as appropriate, and released.

Raw materials shall be held in bulk, or in containers designed and constructed so as to protect against adulteration, and shall be held at such temperature and relative humidity and in such a manner as to prevent a dietary ingredient or dietary supplement from becoming adulterated. Frozen raw materials and other ingredients shall be kept frozen. If thawing is required prior to use, it shall be done in a manner that prevents the raw materials and other ingredients from becoming adulterated within the meaning of the Act.

Each lot of raw materials, product containers, and closures should be sampled, tested, or examined, as appropriate, and released for use by the quality control unit. Based upon adequate process verification, in-process controls and statistical confidence, a skip-lot testing plan is an alternative to fully testing every batch provided that at least one identity test is conducted. An appropriate amount of each lot of raw materials should be reserved for 3 years beyond the shelf life appearing on the label of finished dietary supplements in which the raw materials were used. If adverse event reports are received (see the subsection Adverse Event Reports), the reserved raw materials should be kept for 6 years (serious events) or 3 years (nonserious events) from the date the first report is received.

Representative samples should be collected for testing or examination. Sampling of botanicals should be in compliance with the provisions set in Articles of Botanical Origin 561. The number of containers sampled, and the amount of material taken from each container, should be based upon appropriate criteria such as statistical criteria for raw material variability, confidence levels, and degree of precision desired, the past quality history of the supplier, and the quantity needed for analysis and reserve where required. The following procedures should be used to collect the samples:

Use the following procedure to examine and test the samples:

Raw materials, product containers, and closures approved for use should be rotated so that the oldest approved stock is used first. Deviation from the requirement is permitted if such deviation is temporary and adequate.

Raw materials, product containers, and closures should be retested or reexamined, as appropriate, for identity, strength, quality, and purity and approved or rejected by the quality control unit after a specified time in storage or as necessary, e.g., after exposure to air, heat, or other conditions that might adversely affect the raw material, product container, or closure or after storage of active and inactive ingredients and in-process materials for long periods of time.

Rejected raw materials, product containers, and closures should be identified and controlled under a quarantine system that prevents their use in manufacturing or processing operations for which they are unsuitable.

Written procedures should be provided for production and process controls designed to ensure that the dietary ingredients and dietary supplements have the identity, strength, quality, and purity they are represented to possess. These procedures should be drafted, reviewed, and approved by the appropriate organizational units and reviewed and approved by the quality control unit. These production and process control procedures should be followed in the execution of the various production and process control functions and should be documented at the time of performance. Any deviation from the written procedures should be recorded and justified.

Written production and control procedures should include the following, which are designed to ensure that the dietary supplements have the identity, strength, quality, and purity they are represented to possess:

Material scheduled for rework shall be identified as such.

All compounding and storage containers, processing lines, and major equipment used during the production of a batch of a product should be properly identified to indicate their contents and, when necessary, the phase of processing of the batch.

To ensure batch uniformity and integrity of dietary supplements, written procedures should be established and followed that describe the in-process controls and tests or examinations to be conducted on appropriate samples of in-process materials. Based upon process verification, in-process controls, and statistical confidence, a skip-lot testing plan is an alternative to testing every batch of finished products provided that at least one representative measure is performed. Control procedures should be established to monitor the output of those manufacturing processes that may be responsible for causing variability in the characteristics of in-process material and the finished product. Such control procedures may include, but are not limited to, the following, where appropriate:

In-process specifications for such characteristics should be consistent with finished product specifications. Examination and testing of samples should ensure that the in-process material and dietary supplement conform to the established specifications.

In-process materials should be tested for identity, strength, quality, and purity as adequate, and approved or rejected by the quality control unit during the production process, e.g., at commencement or completion of significant phases or after storage for long periods.

Rejected or adulterated in-process materials should be identified and controlled under a quarantine system designed to prevent their use in manufacturing or processing operations for which they are unsuitable and to prevent the adulteration of other products.

Written procedures should be provided describing in sufficient detail the receipt, identification, storage, handling, sampling, examination, testing of labeling and packaging materials, or products received for packaging or labeling. Each immediate container or grouping of immediate containers in a shipment of product received for packaging or labeling, or of packaging and labeling materials, must be visually examined for appropriate content label, container damage, or broken seals to determine whether the container condition may have resulted in contamination or deterioration of the received product. The supplier's invoice, guarantee, or certification in a shipment of the received product must be visually examined to ensure that the received product is consistent with the purchase order. Labeling and packaging materials or products received for packaging or labeling should be quarantined until:

Those that do not meet such specifications should be identified and rejected to prevent their use in operations for which they are unsuitable.

A record should be kept of each shipment received of each different labeling and packaging material, or each different received product for packaging or labeling, indicating receipt, date of examination or testing, and whether accepted or rejected.

Each unique lot within each unique shipment of received product for packaging or labeling, or of packaging and labeling materials, must be identified in a manner that allows the recipient to trace the lot to the supplier, the date received, the name of the received product, the status of the received product (e.g., quarantined, approved, or rejected), and to the product that was packaged or labeled and distributed.

This unique identifier must be used whenever the disposition of each unique lot within each unique shipment of the received product for packaging or labeling, or of packaging and labeling materials, is recorded.

Labels and other labeling materials for each different product, strength, product type, or quantity of contents should be stored separately under conditions that will protect against contamination and deterioration and avoid mixups. Only authorized personnel should have access to the storage area.

Packaging and labels must be held under appropriate conditions so that the packaging and labels are not adversely affected (e.g. contamination, deterioration).

Gang printing of labeling to be used for different products or different strengths of the same product (or labeling of the same size and identical or similar format or color schemes) should be minimized. If gang printing is employed, packaging and labeling operations should provide for special control procedures, taking into consideration sheet layout, stacking, cutting, and handling during and after printing.

Printing devices on, or associated with, manufacturing lines used to imprint labeling upon the product unit label or case should be monitored to ensure that all imprinting conforms to the print specified in the batch production record.

Obsolete and outdated labels, labeling, other packaging materials, and products received for packaging or labeling should be destroyed and documented.

Strict control should be exercised over labeling issued for use in product labeling operations. The control procedures employed should be in writing with sufficient detail.

Labeling materials issued for a batch should be carefully examined for identity and conformity to the labeling specified in the master and batch production records.

Procedures should be used to reconcile the quantities of labeling issued, used, and returned, and should require evaluation of discrepancies found. If discrepancies are found between the quantity of product finished and the quantity of labeling issued and are outside preset limits based on historical operating data, such discrepancies should be investigated.

Returned labeling should be maintained and sorted in a manner to prevent mixups and provide proper identification.

All excess labeling bearing lot or control numbers should be destroyed and documented.

Written procedures designed to ensure that correct labels, labeling, and packaging materials are used for dietary supplements should incorporate the following features:

Packaged and labeled products should be examined during finishing operations to ensure that containers and packages in the lot have the correct label. A representative sample of units should be collected at the completion of finishing operations and visually examined for correct labeling. Results of these examinations should be recorded in the batch production or control records.

The manufacturer, packer, or distributor of dietary supplements is required to comply with the current labeling requirements in the law that also include a domestic address or phone number through which an adverse event report for a dietary supplement may be received.

Dietary supplements should bear a date indicative of their shelf life, determined by appropriate testing, to ensure that they meet applicable standards of identity, strength, quality, and purity at or before the labeled shelf-life date.

Shelf life should be related to any storage conditions stated on the labeling.

Storage and transportation of finished product shall be under conditions that will protect product against physical, chemical, and microbial adulteration as well as against deterioration of the product and the container.

Written procedures describing the warehousing of dietary supplements should be established and followed and should include the following:

Written procedures describing the distribution of dietary supplements shall be established and followed and should include the following:

There should be appropriate laboratory determination of satisfactory conformance to specifications for the finished product, including the identity and strength prior to release. Based upon adequate process verification, in-process controls, or statistical confidence, a skip-lot or composite testing plan is an alternative to testing every batch.

There should be appropriate laboratory testing, as necessary, of each batch of dietary supplement required to be free of objectionable microorganisms. The accuracy, linearity, sensitivity, specificity, and precision of test methods employed by the firm, when they differ from compendial methods, should be established and documented.

Written procedures should describe any sampling and testing plans, which should include the method of sampling and the number of units per batch to be tested.

Products failing to meet established standards or specifications and any other relevant quality control criteria should be rejected. Rejected or adulterated dietary ingredients and dietary supplements shall be identified, stored, and disposed of in a manner that protects against the adulteration of the other products. Reprocessing may be performed. Prior to acceptance and use, reprocessed material must meet established standards, specifications, and any other relevant criteria. Written procedures shall be established and followed prescribing the method for reprocessing batches or operations start-up materials that do not conform to finished goods standards or specifications. Finished goods manufactured using such materials shall meet all established purity, composition, and quality standards.

There should be a written protocol designed to assess the stability characteristics of dietary supplements. The results of such testing should be used in determining appropriate storage conditions and shelf life. This protocol should include the following:

An adequate number of batches of each dietary supplement should be tested to determine an adequate shelf life, and a record of these data should be maintained. Accelerated studies combined with basic stability information on the raw materials, dietary supplements, and container-closure systems may be used to support tentative shelf life if full shelf-life studies are not available. Simplified stability testing procedures may be used where data from similar product formulations are available to support a shelf-life estimation of a new product. Where data from accelerated studies are used to project a tentative shelf life date that is beyond a date supported by actual shelf-life studies, stability studies should be conducted, including dietary supplement testing at appropriate intervals, until the tentative shelf life is verified or the adequate shelf life is determined.

An appropriately identified reserve sample that is representative of each lot or batch of dietary supplement should be retained and stored under conditions consistent with product labeling until at least 3 years after the shelf life of the product. The reserve sample should be stored in the same immediate container-closure system in which the finished product is marketed or in one that has essentially the same characteristics. The reserve sample consists of at least twice the quantity necessary to perform all the required tests. If an adverse event report is received, the reserve samples of dietary supplements and dietary ingredients from the same lot or batch must be analyzed by an appropriate procedure to confirm their identity and determine any adulteration or contamination. The recovered samples associated with adverse event reports from consumers, distributors, or both should also be analyzed, following the same method used for the reserved samples, if available. The results should be reported with other required information to the federal authority, using the required form. The reserve samples from a particular lot or batch associated with an adverse event report should be held for 6 years (serious events) or 3 years (nonserious events) from the date when the first adverse event report is received by the manufacturer, packer, or distributor.

To ensure uniformity from batch to batch, master production and control records for each product should be prepared, dated, and signed by one person and independently checked, dated, and signed by a second person from the quality control unit.

Master production and control records should include the following:

Batch production and control records should be prepared for each batch of product produced and should include complete information relating to the production and control of each batch. These records should be reviewed and signed by a second person from the quality control unit. These records should include accurate reproduction of the appropriate master production or control record and documentation that each significant step in the manufacture, processing, packing, or holding of the batch was accomplished, including the following:

The following records must be made and retained:

Laboratory records should include complete data derived from all tests necessary to ensure compliance with established specifications and standards, including examinations and assays, as follows:

Complete records should be maintained of any modification of an established method employed in testing. Such records should include the reason for the modification and data to verify that the modification produced results that are at least as accurate and reliable for the material being tested as the established method.

Complete records should be maintained of any testing and standardization of laboratory reference standards, reagents, and standard solutions, the periodic calibration of laboratory instruments, and all stability testing performed. Any deviation should be reviewed and signed by the management of the quality control unit.

The following records must be made and retained:

Distribution records should contain the name and strength of the product, name and address of the consignee, date and quantity shipped, and lot or control number of the finished product.

The manufacturer, packer, or distributor of dietary supplements must keep all required records, as shown in this chapter, for 3 years beyond the shelf life of dietary supplements associated with those records. If adverse event reports are received, those records must be kept for additional 6 years from the date when the first report is received. All records must be accessible by the regulatory authority when requested.

Records must be kept as original records, as true copies (such as photocopies, microfilm, microfiche, or other accurate reproductions of the original records), or as electronic records.

All electronic records must comply with part 11 of Code of Federal Regulations Title 21 (21 CFR part 11).

If reduction techniques are used, such as microfilming, suitable reader and photocopying equipment must be readily available to auditors and inspectors.

Written procedures describing the handling of all written and oral complaints regarding a dietary supplement shall be established and followed. These procedures should include provisions for review by the quality control unit of any complaint involving the possible failure of a product to meet any of its specifications and a determination as to the need for an investigation.

Each complaint should be recorded in a file designed especially for dietary supplement complaints. Written records should be maintained until at least 3 years after the shelf life of the product, or 3 years after the date when the complaint was received, whichever is longer.

The written record should include the following information, where known: the name and strength of the product, lot number, name of complainant, nature of complaint, and reply to complainant.

If an investigation is necessary, the written record should include the findings of the investigation and follow-up.

The review and investigation of the product complaint by a qualified person, the review by quality control unit about whether to investigate a product complaint, and the findings and follow-up action of any investigation performed must extend to all relevant batches and records.

Adverse event reports include reports on any health-related adverse event associated with the use of a dietary supplement that is adverse. It includes both nonserious and serious adverse event reports.

The manufacturer, packer, or distributor of a dietary supplement (called the responsible person) whose name appears on the label shall be responsible for keeping reports of all nonserious adverse events along with any related records (e.g., records of communications with the person who reported the nonserious event). All such records of nonserious adverse events should be kept for 6 years.

The responsible person whose name appears on the label shall also be responsible for reporting any serious adverse event reported to it, and associated with a dietary supplement that is marketed and used in the same country, to the regulatory authority as soon as appropriate, but no later than 15 business days after receipt of the report, using the appropriate form as defined by the regulation (http://www.fda.gov/Food/DietarySupplements/Alerts/ucm111110.htm). A serious adverse event is an event that results in any of following:

A retailer whose name appears on the label as a distributor may, by agreement, authorize the manufacturer or packer to submit the required reports to the regulatory authority, as long as the retailer directs all received adverse event reports to the manufacturer or packer. Each serious adverse event report should include a copy of the product’s label, the information described in the preceding section Complaint Files, and if possible, the contact information of the complainant; daily intake; alcohol consumption and amount; use of prescription medicine and OTC medicine, including a daily dose; and other medical information. The information associated with personal identification and medical records should be obtained only for the reports and kept safe from disclosure. Any new medical information that is related to an already submitted serious adverse event report that is received within 1 year of the initial report shall be submitted to the regulatory authority as soon as appropriate, but no later than 15 business days after receipt of the information. The records related to each report of a serious adverse event received by the manufacturer, packer, or retailer should be maintained for 6 years. The authorized person who is designated by the regulatory authority should be permitted access to those records.

Returned products should be identified as such and held. If the conditions under which returned dietary ingredients and dietary supplements have been held, stored, or shipped before or during their return, or if the condition of the product, its container, carton, or labeling, as a result of storage or shipping, casts doubt on the safety, identity, strength, quality, or purity of the product, the returned product should be destroyed unless examination, testing, or other investigations prove the product meets appropriate standards of safety, identity, strength, quality, or purity. The returned products associated with adverse events must be destroyed after a sufficient sample of products is stored for the purpose of further investigation only. The products related to the adverse event that have been returned should be kept for 6 years (serious events) or 3 years (nonserious events) from the date when the first report is received. A product may be reprocessed provided that the subsequent product meets adequate standards, specifications, and characteristics. Records of returned products should be maintained and should include the name and label potency of the product, lot number (or control number or batch number), reason for the return, quantity returned, date of disposition, and ultimate disposition of the returned product. If the reason for a product being returned implicates associated batches, an appropriate investigation is necessary.

Products that have been involved in adverse events or subjected to improper storage conditions, including extremes in temperature or humidity, smoke, fumes, pressure, age, or radiation due to natural disasters, fires, accidents, or equipment failures should not be salvaged and returned to the marketplace. Whenever there is a question whether products have been subjected to such conditions, salvaging operations may be conducted only if there is (a) evidence from laboratory tests and assays that the products meet all applicable standards of identity, strength, quality, and purity, and (b) evidence that the products and their associated packaging were not subjected to improper storage conditions as a result of the disaster or accident. Organoleptic examinations should be accepted only as supplemental evidence that the dietary supplement meets appropriate standards of identity, strength, quality, and purity. Records including name, lot number, and disposition should be maintained for salvaged products. If the products are involved in adverse events, the instructions described in the preceding section Records and Reports should be followed.

Some dietary ingredients and dietary supplements, even when produced under current good manufacturing practice, contain natural or unavoidable defects that at low levels are not hazardous to health. The Food and Drug Administration establishes maximum levels for these defects in dietary ingredients and dietary supplements produced under current good manufacturing practice and uses these levels in deciding whether to recommend regulatory action.

Defect action levels are established for dietary ingredients and dietary supplements whenever it is necessary and feasible to do so. These levels are subject to change upon the development of new technology or the availability of new information.

Compliance with defect action levels does not excuse violation of the requirement in section 402(a)(4) of the Act that dietary ingredients and dietary supplements shall not be prepared, packed, or held under unsanitary conditions or the requirements in this part that manufacturers, distributors, and holders of both dietary ingredients and dietary supplements shall observe current good manufacturing practice. Evidence indicating that such a violation exists causes a dietary ingredient and a dietary supplement to be adulterated within the meaning of the Act, even though the amounts of natural or unavoidable defects are lower than the currently established defect action levels. The manufacturer, distributor, and holder of a dietary ingredient or a dietary supplement shall at all times utilize quality control operations that reduce natural or unavoidable defects to the lowest level currently feasible.

The mixing of a dietary ingredient or dietary supplement containing defects above the current defect action level with another lot of dietary ingredient or dietary supplement is not permitted and renders the final product adulterated within the meaning of the Act, regardless of the defect level of the final product.

A compilation of the current defect action levels for natural or unavoidable defects in dietary ingredients and dietary supplements that present no health hazard may be obtained upon request from the Industry Activities Staff (HFS-565), Center for Food Safety and Applied Nutrition, U.S. Food and Drug Administration, 5100 Paint Branch Parkway, College Park, MD 20740-3835.