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GMPs: Lack of records starting to sound like broken record

By Hank Schultz, 17-Sep-2012

Related topics: Regulation, GMPs, QA & QC

Lack of good record keeping forms the lion’s share of mentions on the warning letters companies receive from FDA after a GMP inspection, a consultant said in an industry meeting recently.

Marion Boardley, a Moab, Utah-based consultant who specializes in helping dietary supplement companies meet GMP requirements, spoke Sept. 13 at the Rocky Mountain Dietary Supplement Forum in Boulder, Colo. Boardley had made a detailed analysis of the deficiencies mentioned in warning letters and and found that problems with record keeping were tops on the list of things that FDA inspectors find during GMP inspections. Her results gave a picture of the prevalence and persistence of the problem.

It’s an old saw, repeated by Dr. Dan Fabricant of FDA and others in connection with GMP compliance, that “if you didn’t write it down, it didn’t happen.” Nevertheless, it seems as if some companies in the dietary supplement realm are taking a while to take this lesson to heart.

“A lot of companies that get warning letters did a very poor job of responding to 483s,” Boardley said.

Boardley did a search of warning letters connected with GMP compliance and came up with more than 60 as of August 2012. Boardley said she used warning letters, as opposed to 483s, because they are public information, they highlight the most important portions of the issues mentioned in a previous 483 that the firms in question failed to adequately address and they represent the opinion of more than one FDA official.

In addition, Boardley said, “Warning letters actually cite the regulation in question as opposed to 483s.”

Documentation failures abound

Boardley divvied up the mentions the violations of the subparts of Part 111 and assigned them to a spreadsheet.  She could then manipulate the data to yield some trend results.

She found that 60% of the items cited in the warning letters pertained to documentation failures, parceled out as follows:  25% – process and control, 20% – batch production records and 15% – master manufacturing records.

Breaking down the production and process control slice of the pie, Boardley found that the biggest chunk – 42% – pertained to problems with specifications.  Smaller portions of this pie piece include identity testing failures (17%) and finished product testing deficiencies (also 17%).

“The biggest part of all is specifications. Setting specifications is the single most important thing you can do to make sure you are GMP complaint,” Boardley said.

In the warning letters companies were cited for failure to “establish product specifications for the identity, purity, strength, and composition of the finished batch of dietary supplement.”  Other failures included not setting specs for each component of a finished product.

Record-keeping failures in batch production records included lack of statements of actual yield versus theoretical yield, the identity of the equipment used to make the batch and the lack of maintenance and cleaning records for that equipment and processing lines.

MMRs needed for every formulation

Among the master manufacturing record problems that Boardley quantified, lack of an MMR for each unique formulation was mentioned most often, having been mentioned in 22 of the letters.  Eight letters cited lack of a statement of expected yield, and another eight mentioned lack of procedures of sampling.

“People are not being very careful about their sampling procedures and they are not documenting it properly,” she said.

Boardley cautioned against taking away from her pie charts the thinking that the most prevalent failures are necessarily the most important things that companies need to pay attention to and to fix to avoid a costly GMP inspection failure.  All the shortcomings that an inspector might find, including the rarer citations of problems with labels, procedures on returns of products or deficiencies in personnel qualifications are important, she said.

“You have to weigh up your own company.  Every company is going to have a different set of issues,” she said.