Maged Sharaf, PhD, American Herbal Products Association (AHPA)01.05.15
Dietary supplement contract manufacturers and their “own-label distributor” customers must navigate a host of issues in order to establish effective business partnerships that ensure quality and compliance with federal laws and regulations, including current good manufacturing practice (cGMP) requirements.
The American Herbal Products Association (AHPA) convened industry veterans from contract manufacturers, “own-label distributors” (OLDs), legal and regulatory experts, and an official from the U.S. Food and Drug Administration (FDA) in November to present a webinar that explored the issues faced by contract manufacturers and companies that use their services. The webinar also provided draft documents that informed attendees on the FDA position regarding cGMP regulatory requirements for contract manufacturers and their customers.
Compliance Considerations
FDA’s cGMP requirements are rigorous with respect to the documentation of manufacturing operations and the evaluation, analysis and release of finished products. The cost of manufacturing and burdens of documentation and quality control are especially heavy for small and mid-size companies that cannot spread these costs to large volume production. Accordingly, many small and mid-size companies turn to contract manufacturers to produce and label their products.
When one company contracts with another for the manufacture and/or packaging of its product, the parties must ensure there are no misunderstandings about what measures each party will take to ensure the quality and regulatory compliance of the product. There are many steps involved, including, but not limited to:
There are also more global quality assurance/regulatory compliance measures that may be considered. Although most are not required by regulation, these may include:
Defined Responsibilities
In addition to these steps, there are a number of other issues to be addressed, such as change control, documentation, confidentiality, intellectual property, and of course, pricing. Since there will be at least two companies (the OLD and the contract manufacturer), and sometimes three or more companies (the OLD, a contract manufacturer, a contract packager and/or various subcontractors), involved in the process, it is essential to clearly define which party will be responsible for which elements of the process, and what constraints or requirements do or will apply to each party. The resulting decisions should be documented either in contracts, purchase orders, “terms and conditions” documents, quality agreements or elsewhere.
It should be noted that many of these steps are interrelated and require close collaboration between the parties. Furthermore, certain of these steps are required by regulation to be performed by or for the manufacturing company or the packaging company and therefore cannot be wholly assigned to the OLD to perform, although the OLD may choose to duplicate or augment the work performed by the manufacturer or packager. Conversely, as a practical matter certain functions required by regulation, such as creation of batch production records, can only be performed by the manufacturer or the packager.
One issue the AHPA webinar addressed is the position that FDA has expressed through warning letters issued to customers of contract manufacturers over the last three years. FDA assigns overarching and ultimate responsibility to OLDs that contract with other firms to manufacture, package or label dietary supplements to know what and how manufacturing activities are performed, ensure that all phases of production are in compliance with cGMPs and that the products conform to established specifications.
When the first such warning letter was issued in 2011, AHPA President Michael McGuffin noted this is contrary to certain statements included in the preamble to the final cGMP rule, which states, “The firm that conducts the manufacturing operations … would be responsible for complying with all relevant cGMP requirements in this final rule related to its operations;” “Under this final rule, you must comply with the cGMP requirements that apply to your operations related to the manufacture, packaging, labeling, and holding of dietary supplements;” and “A distributor who purchases a packaged and labeled dietary supplement and who then holds the product in a warehouse for distribution to another physical location is subject to the requirements related to its operations.”
A recording of the webinar, the presenters’ slides and the guidance documents are available for purchase on the AHPA website: www.ahpa.org.
Maged Sharaf, PhD
American Herbal Products Association (AHPA)
Maged Sharaf, PhD, is the chief science officer of the American Herbal Products Association (AHPA), the national trade association with a focus primarily on herbs and herbal products. AHPA’s membership represents U.S. and international growers, processors, manufacturers, marketers and institutes specializing in botanicals and herbal products. Before AHPA, Dr. Sharaf was the director, Foods, Dietary Supplements and Herbal Medicines at the United States Pharmacopeial Convention (USP). Before USP he was pharmacy associate professor and has preceding experience conducting bioanalytical assay development and validation, and human bioequivalence studies in support of the pharmaceutical industry; and quality control and manufacturing of pharmaceutical dosage forms. He can be reached at 301-588-1171; E-mail: msharaf@ahpa.org; Website: www.ahpa.org.
The American Herbal Products Association (AHPA) convened industry veterans from contract manufacturers, “own-label distributors” (OLDs), legal and regulatory experts, and an official from the U.S. Food and Drug Administration (FDA) in November to present a webinar that explored the issues faced by contract manufacturers and companies that use their services. The webinar also provided draft documents that informed attendees on the FDA position regarding cGMP regulatory requirements for contract manufacturers and their customers.
Compliance Considerations
FDA’s cGMP requirements are rigorous with respect to the documentation of manufacturing operations and the evaluation, analysis and release of finished products. The cost of manufacturing and burdens of documentation and quality control are especially heavy for small and mid-size companies that cannot spread these costs to large volume production. Accordingly, many small and mid-size companies turn to contract manufacturers to produce and label their products.
When one company contracts with another for the manufacture and/or packaging of its product, the parties must ensure there are no misunderstandings about what measures each party will take to ensure the quality and regulatory compliance of the product. There are many steps involved, including, but not limited to:
- Establishing label claims (including the supplement facts, structure/function or other nutritional support claims, health claims, and any other statements that make representations about the product, its ingredients, or its benefits);
- Establishing whether the product will be packaged with a statement of shelf life, and if so the length or term;
- Establishing bulk product specifications consistent with the intended label claims and shelf life;
- Establishing retail packaging specifications;
- Establishing product formula consistent with the bulk product specifications, shelf life, supplement facts and other intended label claims;
- Establishing ingredient specifications consistent with the product formula and specifications, and approval of ingredient vendors;
- Establishing packaging component specifications consistent with the retail packaging specifications, and approval of packaging component vendors;
- Acquiring ingredients;
- Acquiring packaging components;
- Sampling, testing and approval of each ingredient lot for production;
- Sampling, testing and approval of each packaging component lot for retail packaging;
- Manufacturing the bulk product, including in-process sampling and testing;
- Retail packaging of the product;
- Sampling, testing and approval of the finished bulk and/or retail packaged product.
There are also more global quality assurance/regulatory compliance measures that may be considered. Although most are not required by regulation, these may include:
- Vendor qualifications of component suppliers by the OLD and/or the contractor;
- Auditing of contractor or subcontractor facilities by the OLD and/or the contractor;
- Third-party cGMP auditing or certification of contractor or subcontractor facilities for the OLD and/or the contractor;
- Review of the contractor’s documentation by the OLD;
- Independent verification of the contract manufacturer’s finished product testing by the OLD.
Defined Responsibilities
In addition to these steps, there are a number of other issues to be addressed, such as change control, documentation, confidentiality, intellectual property, and of course, pricing. Since there will be at least two companies (the OLD and the contract manufacturer), and sometimes three or more companies (the OLD, a contract manufacturer, a contract packager and/or various subcontractors), involved in the process, it is essential to clearly define which party will be responsible for which elements of the process, and what constraints or requirements do or will apply to each party. The resulting decisions should be documented either in contracts, purchase orders, “terms and conditions” documents, quality agreements or elsewhere.
It should be noted that many of these steps are interrelated and require close collaboration between the parties. Furthermore, certain of these steps are required by regulation to be performed by or for the manufacturing company or the packaging company and therefore cannot be wholly assigned to the OLD to perform, although the OLD may choose to duplicate or augment the work performed by the manufacturer or packager. Conversely, as a practical matter certain functions required by regulation, such as creation of batch production records, can only be performed by the manufacturer or the packager.
One issue the AHPA webinar addressed is the position that FDA has expressed through warning letters issued to customers of contract manufacturers over the last three years. FDA assigns overarching and ultimate responsibility to OLDs that contract with other firms to manufacture, package or label dietary supplements to know what and how manufacturing activities are performed, ensure that all phases of production are in compliance with cGMPs and that the products conform to established specifications.
When the first such warning letter was issued in 2011, AHPA President Michael McGuffin noted this is contrary to certain statements included in the preamble to the final cGMP rule, which states, “The firm that conducts the manufacturing operations … would be responsible for complying with all relevant cGMP requirements in this final rule related to its operations;” “Under this final rule, you must comply with the cGMP requirements that apply to your operations related to the manufacture, packaging, labeling, and holding of dietary supplements;” and “A distributor who purchases a packaged and labeled dietary supplement and who then holds the product in a warehouse for distribution to another physical location is subject to the requirements related to its operations.”
A recording of the webinar, the presenters’ slides and the guidance documents are available for purchase on the AHPA website: www.ahpa.org.
Maged Sharaf, PhD
American Herbal Products Association (AHPA)
Maged Sharaf, PhD, is the chief science officer of the American Herbal Products Association (AHPA), the national trade association with a focus primarily on herbs and herbal products. AHPA’s membership represents U.S. and international growers, processors, manufacturers, marketers and institutes specializing in botanicals and herbal products. Before AHPA, Dr. Sharaf was the director, Foods, Dietary Supplements and Herbal Medicines at the United States Pharmacopeial Convention (USP). Before USP he was pharmacy associate professor and has preceding experience conducting bioanalytical assay development and validation, and human bioequivalence studies in support of the pharmaceutical industry; and quality control and manufacturing of pharmaceutical dosage forms. He can be reached at 301-588-1171; E-mail: msharaf@ahpa.org; Website: www.ahpa.org.