Avoiding GMP “Showstoppers” Keeps Manufacturers Off FDA’s “Radar”

Compliance consultants warn that certain dietary supplement good manufacturing practices violations are inspection "showstoppers" and will draw agency enforcement.

Inspections have started since the first deadline under the supplement GMP final rule published in June 2007 - for firms with 500 or more full-time equivalents - passed last June.

Shelley Maifarth, a former FDA inspector who is now a regulatory compliance consultant, says some GMP issues will stand out more than others.

"If there are some big gaps - like you don't have any batch records, any manufacturing records, you're not making any kind of attempt at label control - we like to call those showstoppers, and FDA will probably take notice," Maifarth said.

Otherwise, when it comes to FDA's GMP rule, supplement firms can "stay below their radar," she added.

Maifarth and Martina LaGrange, both principals in Littleton, Colo.-based consulting firm FDA Compliance Group, outlined steps to prepare for FDA's inspections at the United Natural Product Alliance's GMP workshop in Salt Lake City Sept. 30.

They have nearly 50 years of FDA inspection experience between them: Maifarth held the titles of investigator, compliance officer and microbiologist during her 33-year tenure with FDA and LaGrange spent 14 years as a field investigator.

[Editor's note: This is second of a two-part report on GMP inspection preparation tips. The first part was published in ¹ (Also see "GMP Inspections Under Way in Southwest Region: “Be Ready,” Says FDA" - Pink Sheet, 27 Oct, 2008.), p. 4.]

Every supplement firm should have the most recent copy of its standard operating procedure for GMP inspections on-hand in the event agency inspectors arrive unannounced - as they often do - or the employees who normally conduct regulatory contacts happen to be off-site.

"This SOP gives some kind of guidance when FDA knocks on the door. ... This SOP should say what the receptionist should do, who should they call, there should be a kind of tree of people as to who they should call if someone's on vacation, out sick, etc.," Maifarth said.

Frequently updating the SOP and keeping a copy accessible at a facility are important because the document has instructions for every aspect of a GMP inspection tour, including the route of the tour as well as names of employees who will talk to the inspectors and managers' names and addresses - so FDA will know where to send warning letters.

"Never, Ever, Ever, Ever Lie"

During all points of an inspection, company representatives talking with FDA officials should be helpful, courteous and most importantly, honest, LaGrange and Maifarth say.

"Never, ever, ever, ever lie. ... Always be truthful even if it's bad news," LaGrange said.

She emphasized that if a firm is suspected of lying, FDA's Office of Criminal Investigation could become involved.

The basis for imposing GMPs on supplement firms is that their products are considered food under the Food, Drug and Cosmetic Act.

"If you have a supplement and you do not manufacture according to GMPs, you have an adulterated food," Maifarth observed.

FDA enforcement is limited to adulterated food products marketed in interstate commerce, but the agency will notify state agencies about GMP violations for products that are not shipped between states.

Discretion In Information Management

The consultants stressed that manufacturers should use discretion and proper management of information. "Do not provide information that goes beyond what was asked. But this can backfire ... you must appear to be cooperative," LaGrange said.

While firms should not attempt to conceal information or deceive FDA, they can plan GMP inspection routes that showcase their facilities' strong points while minimizing the weak areas.

LaGrange described an example of a firm in the process of building a new clean room when it is visited by FDA inspectors.

"That could be a weak area or it could be a strong area, but instead of maybe starting there - where it kind of has these plastic [sheeting] walls and there's a lot of dust around - maybe you want to go start at the incoming [materials] inspection area and walk them through in a flow that makes sense," she said.

To mitigate its appearance as a possible weak point, upon arriving at the construction area the guide could say, "This is our new sterilization facility. ... We've got some ventilation to make sure that this extra dust is controlled," LaGrange said.

"So, instead of throwing out, 'Here's this really neat area, but it's full of GMP problems,' we want to present this information to the FDA in a favorable manner."

Company representatives also should not give unsure answers to FDA questions, but defer to appropriate people, the subject matter experts who can accompany investigators through specific parts of a plant.

"Some people feel this tremendous pressure ... [but] it's perfectly acceptable to say you don't know," LaGrange said.

"Never guess at an answer either. If you tell FDA something and it turns out not to be true, the investigator will hang on to that first bit of information."

Put It In Writing

LaGrange also emphasized documentation as a significant change the GMPs require of manufacturers. "If it's not documented, it's not done. It doesn't matter if you've been doing it for five years, if you didn't document it in a training records, etc., it's not done."

Documenting the parties responsible for each component of manufacturing is a crucial preparation. All GMP training should be documented, with any shortcomings also recorded.

The next deadline in FDA's tiered system, for medium-sized companies, goes into effect in June 2009. Companies with fewer than 20 employees must be in compliance by June 2010 (² (Also see "Supplement GMPs Stress Responsibility, Put Firms In Driver’s Seat For Testing" - Pink Sheet, 25 Jun, 2007.), p. 3).

FDA intends to publish a small entity compliance guide in the coming year.

- Jessica Lake ([email protected])