Current Good Manufacturing Practices (cGMPs) are intended to establish a comprehensive system of process controls—including documentation of each stage of the manufacturing process—that can minimize the likelihood of, or detect, problems and variances in manufacturing as they occur and before the product is finished.

The process controls that are a part of cGMPs are essential to ensuring the dietary supplement is manufactured, packaged, held and labeled in a consistent and reproducible manner. Thus, the regulations apply to manufacturers of dietary supplements and private label distributors (PLs) of dietary supplements. Indeed, PLs will need to monitor contract manufacturers and warehouses regularly to ensure these entities are complying with FDA’s cGMP requirements for dietary supplements.

Summary of Major Requirements
The requirements of the rule apply to companies based on the functions they perform. In this regard, a PL must know what and how manufacturing activities are performed so that it can make decisions related to whether the packaged and labeled product conforms to its established specifications and whether to approve and release the product for distribution.

The easiest way for a PL to satisfy that requirement will be to obtain certificates of analysis (CofAs) from the manufacturer.
However, a PL will not be able to rely on CofAs on their face. Rather, FDA is requiring that private label distributors first qualify the manufacturer by establishing the reliability of the certificate of analysis; maintain documentation of how the company qualified the supplier or manufacturer; and periodically re-confirm the supplier’s or manufacturer’s certificate of analysis.

This means a PL will need to establish an independent testing program for its dietary supplement products and not simply rely on the manufacturer’s testing to confirm the product meets label claim and is not otherwise adulterated. More specifically, a PL should have the following testing completed at least once per year on its dietary supplement products:

• Analytical testing of dietary ingredients to confirm identity and recommended use levels;
• Microbial testing;
• Heavy metal testing (e.g., lead, arsenic, mercury).

In addition to the new adverse event reporting requirements for dietary supplements, the cGMPs add additional requirements related to complaints. For example, the regulations require that holders of dietary supplements review and investigate all product complaints they receive to determine whether the complaint relates to a failure of the processes under the distributor’s control that could affect the identity, purity, strength or composition of the supplement. Thus, for example, holders/distributors of dietary supplements must investigate the conditions of temperature, humidity and light in which the supplement was held. If the distributor concludes the problem is unrelated to any process under control of the distributor, the distributor should contact the manufacturer. 

Contract Manufacturing Compliance
While the biggest issue facing PLs in regard to the cGMPs relates to product testing, PLs will need to verify that contract manufacturers, among other things, comply with the requirements to:

• Establish minimum requirements for personnel, including hygienic practices and qualifications.
• Establish minimum requirements for the physical plant and grounds, including (but not limited to) waste removal, grass cutting, maintenance of roads and parking lots, cleaning and sanitizing agents, pest control, water supply, plumbing, plant size, ventilation, temperature and humidity controls and lighting.
• Establish minimum requirements for equipment and utensils, including equipment calibration, utensil and equipment design and sanitation.
• Impose certain requirements on automatic, mechanical or electronic equipment used to manufacture a dietary supplement.
• Develop written procedures for most operations, including those related to equipment, physical plant sanitation, certain manufacturing operations, quality control, laboratory testing and product complaints.
• Establish written master manufacturing record for each unique formulation of manufactured dietary supplement, and for each batch size, to ensure the manufacturing process is performed consistently and to ensure uniformity in the finished batch from batch to batch.
• Establish written process controls in order to produce the product consistently and reliably each time. For example, there must be process controls in place to ensure that appropriate tests and examinations are conducted, a master manufacturing record is prepared, each batch production follows the master manufacturing record, and the finished tablet or capsule is placed in the intended package with the intended label.
• Establish written specifications for any point, step or stage in the product production that will ensure dietary supplements meet the identity, purity, strength and composition established in specifications and are properly packaged and labeled as specified in the master manufacturing record.   
• Establish adequate documentation as to the basis for why meeting the in-process specifications, in combination with meeting component specifications, will help ensure the specifications are met for the identity, purity, strength and composition of the dietary supplements and for limits on those types of contamination that may adulterate or may lead to adulteration of the finished batch of the dietary supplement.
• Establish quality control operations to ensure the quality of a dietary supplement.
• Implement the use of laboratory control processes related to establishing specifications and to the selection and use of testing and examination methods.
• Perform testing of a subset of finished batches of dietary supplements based on sound statistical sampling or, alternatively, testing all finished batches.
• Establish a batch production record every time a dietary supplement batch is made. The batch production record must accurately follow the appropriate master manufacturing record.
• Collect representative samples of each unique lot of components and in-process materials for each manufactured batch, a subset of finished batches of each dietary supplement before releasing for distribution, and of each lot of packaged and labeled dietary supplements.
• Establish a record retention policy associated with the manufacture of a dietary supplement to be kept for 1 year beyond the shelf life dating, or if shelf life dating is not used, for 2 years beyond the date of distribution of the last batch of dietary supplements associated with those records.
• Investigate any “product complaint” that involves a possible failure of a dietary supplement to meet any cGMP requirement, with oversight by quality control personnel.

Warehousing Compliance
In addition to ensuring that its contract manufacturer(s) are in compliance with the final rule, a PL will need to ensure the companies warehousing its dietary supplement products: 

• Establish minimum requirements for personnel, including hygienic practices and qualifications (Warehouse).
• Establish minimum requirements for the physical plant and grounds, including (but not limited to) waste removal, grass cutting, maintenance of roads and parking lots, cleaning and sanitizing agents, pest control, water supply, plumbing, warehouse size, ventilation, temperature and humidity controls and lighting (Warehouse).
• Impose certain requirements on automatic, mechanical or electronic equipment used to hold a dietary supplement (Warehouse).
• Implement quality control operations to ensure the quality of a dietary supplement. For example, the warehouse would need to establish a specification for the temperature and humidity level at which the product will be held (PL in conjunction with warehouse).
• Establish procedures to hold reserve samples of each lot of packaged and labeled dietary supplements that PL distributes in a manner that protects against contamination and deterioration (PL in conjunction with warehouse).
• Establish record retention policy to be kept for 1 year beyond the shelf life dating, or if shelf life dating is not used, for 2 years beyond the date of distribution of the last batch of dietary supplements associated with those records (PL in conjunction with warehouse).
• Establish procedures for the identification and quarantine of returned dietary supplements until quality control personnel conduct a material review and make a disposition decision, including the possible return of the product to stock if it is determined the product was held and shipped under conditions that would not cause the product to become adulterated (PL).
• Require quality control personnel to conduct a material review and make a disposition decision under certain circumstances. For example, it may be necessary to determine if a product held under excessive heat or humidity due to a power outage should be destroyed (PL).
• Require a qualified person to investigate any “product complaint” that involves a possible failure of a dietary supplement to meet any cGMP requirement, with oversight by quality control personnel (PL).

This column only gives general descriptions of the requirements. The regulations themselves are more detailed and FDA is ramping up its inspection of PLs. Thus, all PLs must take stock to ensure that not only their manufacturers are in compliance but that their own SOPs meet the requirements.    

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Todd Harrison is partner with Venable, which is located in Washington, D.C. He advises food and drug companies on a variety of FDA and FTC matters, with an emphasis on dietary supplement, functional food, biotech, legislative, adulteration, labeling and advertising issues. He can be reached at 575 7th St. NW, Washington, D.C. 20004, Tel: 202-344-4724; E-mail: [email protected].