Sean Moloughney, Associate Editor07.28.11
With federal Good Manufacturing Practice (GMP) requirements in full force for all dietary supplement firms, regardless of size, FDA has accelerated enforcement activities, conducting about 66 inspections through the first four months of 2011.
The agency began conducting inspections in the summer of 2008, during the first phase of GMP implementation for firms with 500 or more employees. For the 2008 fiscal year (FY), FDA carried out seven inspections, according to Bradford Williams, manager of the Division of Dietary Supplement Programs, Center for Food Safety and Applied Nutrition.
The GMP rule applied to companies with 21-499 employees beginning in June 2009, and to firms with 20 or fewer employees beginning in June of 2010. The agency completed 34 inspections in FY 2009 and 84 in FY 2010; and FDA has conducted 66 inspections this year, as of April 29th.
Mr. Williams offered some highlights from the agency’s findings during a presentation at the SupplySide East tradeshow in May. FDA’s inspectional priority includes firms that: blend and fabricate finished dietary supplement products, package and label finished dietary supplements from bulk products, apply the final product label to finished dietary supplement products or perform other operations.
During the course of their audits, FDA inspectors have found no or inadequate identity testing of dietary ingredients; failure to establish specifications for components, ingredients, steps and stages of manufacture; failure to conduct testing to ensure products meet specifications; inadequate Master Manufacturing Records, Batch Production Records and other recordkeeping requirements; failure to conduct material reviews; and inadequate corrective action plans.
For FY 2010, “violation rates” were nearly 25%, according to Mr. Williams. “Firms have had four years to get ready for this. If your policy is to wait for FDA to show up, it’s going to be a painful correction process,” he said. “We expected noncompliance to grow as the size of the firm decreased but we find that most types of firms don’t get it.”
If companies fail to comply with GMPs, FDA retains several enforcement options, including warning letters, regulatory meetings, product seizure, injunction and prosecution.
“Funding limitations and other forces are increasing on FDA to consider third party audits as a means of leveraging our resources,” Mr. Williams acknowledged. “We will explore this subject more once this program is ‘mature.’”
He noted the industry is “way ahead” of FDA in terms of third party audits, as many “seals of approval” currently promote a company’s GMP compliance, including established programs from NSF International, the Natural Products Association and USP.
The Essentials
In terms of process controls, a manufacturer must establish specifications for the components it uses to manufacture a dietary supplement regardless of whether it manufactures the component(s) itself, contracts with another firm to manufacture the component(s) or buys the component(s).
In addition to components, specifications must be set for any step in the manufacturing process where control is necessary to ensure the quality of the dietary supplement, as well as for labels, packaging materials and finished products.
Firms are also required to determine that specifications are met for their components. For a dietary ingredient, a firm must, at minimum, conduct an appropriate identity test on the ingredient. The firm may rely on a Certificate of Analysis (COA) for other specifications if the vendor has been qualified.
To qualify suppliers, companies should first establish the reliability of the supplier’s COA through tests or examinations. A legitimate COA must include a description of the test or examination of methods used, limits of the tests or examinations as well as actual results for the lot received (not just a specification sheet).
Companies should maintain documentation regarding how it qualified the supplier, along with records of any audits conducted. Mr. Williams also recommended periodically reconfirming the COA. Quality control personnel must review and approve the documentation establishing the basis for qualification and requalification.
Mr. Williams acknowledged that qualifying foreign suppliers could be difficult. However, FDA expects firms to meet the requirements of the regulation. For herbal ingredients, confirmation of the use of Good Agricultural Practices (GAP) is encouraged.
“We anticipate that industry will be creative in qualifying the global supply chain,” he said. Firms may use consultants to qualify suppliers, however, certain provisos should be considered. For example, a consultant report should be a complete, specific audit report, not an “opinion letter” or a generic evaluation of the overall manufacturing facility.
Additionally, companies should maintain protocol for handling complaints, investigating complaints and keeping records of complaints. Quality control personnel must review and approve decisions about whether or not to further investigate a product complaint and any follow-up action taken. “You must make and keep a written record of every consumer complaint that is related to good manufacturing practices,” according to Mr. Williams.
Firms must have all records required under Part 111 or copies of such records, readily available during the retention period for inspection and copying by FDA when requested.
The records retention period is one year past the shelf life date or two years beyond the date of distribution of the last batch of dietary supplements associated with those records.
In the end, “If it isn’t written down, it didn’t happen,” Mr. Williams said. In the event a firm receives a warning letter, a substantive and prompt response could also help avoid or lessen further FDA enforcement, he added.
The agency began conducting inspections in the summer of 2008, during the first phase of GMP implementation for firms with 500 or more employees. For the 2008 fiscal year (FY), FDA carried out seven inspections, according to Bradford Williams, manager of the Division of Dietary Supplement Programs, Center for Food Safety and Applied Nutrition.
The GMP rule applied to companies with 21-499 employees beginning in June 2009, and to firms with 20 or fewer employees beginning in June of 2010. The agency completed 34 inspections in FY 2009 and 84 in FY 2010; and FDA has conducted 66 inspections this year, as of April 29th.
Mr. Williams offered some highlights from the agency’s findings during a presentation at the SupplySide East tradeshow in May. FDA’s inspectional priority includes firms that: blend and fabricate finished dietary supplement products, package and label finished dietary supplements from bulk products, apply the final product label to finished dietary supplement products or perform other operations.
During the course of their audits, FDA inspectors have found no or inadequate identity testing of dietary ingredients; failure to establish specifications for components, ingredients, steps and stages of manufacture; failure to conduct testing to ensure products meet specifications; inadequate Master Manufacturing Records, Batch Production Records and other recordkeeping requirements; failure to conduct material reviews; and inadequate corrective action plans.
For FY 2010, “violation rates” were nearly 25%, according to Mr. Williams. “Firms have had four years to get ready for this. If your policy is to wait for FDA to show up, it’s going to be a painful correction process,” he said. “We expected noncompliance to grow as the size of the firm decreased but we find that most types of firms don’t get it.”
If companies fail to comply with GMPs, FDA retains several enforcement options, including warning letters, regulatory meetings, product seizure, injunction and prosecution.
“Funding limitations and other forces are increasing on FDA to consider third party audits as a means of leveraging our resources,” Mr. Williams acknowledged. “We will explore this subject more once this program is ‘mature.’”
He noted the industry is “way ahead” of FDA in terms of third party audits, as many “seals of approval” currently promote a company’s GMP compliance, including established programs from NSF International, the Natural Products Association and USP.
The Essentials
In terms of process controls, a manufacturer must establish specifications for the components it uses to manufacture a dietary supplement regardless of whether it manufactures the component(s) itself, contracts with another firm to manufacture the component(s) or buys the component(s).
In addition to components, specifications must be set for any step in the manufacturing process where control is necessary to ensure the quality of the dietary supplement, as well as for labels, packaging materials and finished products.
Firms are also required to determine that specifications are met for their components. For a dietary ingredient, a firm must, at minimum, conduct an appropriate identity test on the ingredient. The firm may rely on a Certificate of Analysis (COA) for other specifications if the vendor has been qualified.
To qualify suppliers, companies should first establish the reliability of the supplier’s COA through tests or examinations. A legitimate COA must include a description of the test or examination of methods used, limits of the tests or examinations as well as actual results for the lot received (not just a specification sheet).
Companies should maintain documentation regarding how it qualified the supplier, along with records of any audits conducted. Mr. Williams also recommended periodically reconfirming the COA. Quality control personnel must review and approve the documentation establishing the basis for qualification and requalification.
Mr. Williams acknowledged that qualifying foreign suppliers could be difficult. However, FDA expects firms to meet the requirements of the regulation. For herbal ingredients, confirmation of the use of Good Agricultural Practices (GAP) is encouraged.
“We anticipate that industry will be creative in qualifying the global supply chain,” he said. Firms may use consultants to qualify suppliers, however, certain provisos should be considered. For example, a consultant report should be a complete, specific audit report, not an “opinion letter” or a generic evaluation of the overall manufacturing facility.
Additionally, companies should maintain protocol for handling complaints, investigating complaints and keeping records of complaints. Quality control personnel must review and approve decisions about whether or not to further investigate a product complaint and any follow-up action taken. “You must make and keep a written record of every consumer complaint that is related to good manufacturing practices,” according to Mr. Williams.
Firms must have all records required under Part 111 or copies of such records, readily available during the retention period for inspection and copying by FDA when requested.
The records retention period is one year past the shelf life date or two years beyond the date of distribution of the last batch of dietary supplements associated with those records.
In the end, “If it isn’t written down, it didn’t happen,” Mr. Williams said. In the event a firm receives a warning letter, a substantive and prompt response could also help avoid or lessen further FDA enforcement, he added.
