OR WAIT null SECS
By developing proper SOPs for laboratory qualification, industry can hopefully work to eliminate the problem of "dry labbing" altogether.
As a much-discussed June 30 Chicago Tribune article reported, FDA has uncovered GMP violations in nearly half of the dietary supplement manufacturers inspected to date. Since the final GMP rule for dietary supplements took effect in 2007, the number of annual GMP inspections FDA conducted jumped from just 7 in 2008 to 175 in 2011. Moreover, FDA has made it very clear that GMP inspections should be a major priority for dietary supplement manufacturers.
To ensure GMP compliance, companies should qualify each aspect of the manufacturing process, including personnel, physical plant and grounds, equipment and utensils, process control systems, packaging and labeling, Master Manufacturing Records, batch records, holding and distributing, product complaints, recordkeeping, and more.
Part of adhering to GMPs also includes ensuring that any third-party contractor a dietary supplement manufacturer hires does its job properly. Third parties include contract manufacturers, certainly, and they also include any third-party testing laboratories that a manufacturer hires. (It may also include a testing laboratory that a company’s contract manufacturer hires to assist with the company’s project.)
What happens when a testing laboratory doesn’t do its job properly? In March, the television show Dateline NBC investigated the so-called process of “dry labbing.” A “dry lab” is the industry term for a testing laboratory hired to analyze products that, instead of performing actual testing, provides fabricated testing results. (Editor’s note: Read more about this Dateline NBC story at NutritionalOutlook.com/news/dateline_dry_labbing.)
Although the Dateline NBC investigation unveiled alleged dry labbing at one lab in particular, some industry experts believe there are more labs practicing dry labbing-although perhaps not as obviously as the lab that Dateline NBC reported on.
Clearly, these false laboratory practices risk putting a dietary supplement manufacturer in serious violation of GMP compliance. Athough a third-party testing lab may help a manufacturer produce its final product, it is important to remember that FDA ultimately holds the manufacturer-the company that markets and sells the finished product-responsible for GMP compliance, from start to finish. Therefore, it is ultimately the manufacturer’s responsibility to ensure that the laboratories that it or its contract manufacturer uses-whether third party or in house-are properly qualified and testing product properly.
How should a manufacturer go about qualifying a lab? This article focuses on the importance of meeting requirements for laboratory operations as specified in 21 CFR 111, and how to go about ensuring GMP compliance.
GMP regulation 21 CFR 111.75 essentially states that, in order to determine whether product specifications are met for raw materials, at least one test must be performed to verify the identity of a raw material. This test may be conducted by a third-party lab. (A certificate of analysis from the ingredient supplier may also be relied on, as long as: 1) the ingredient supplier has been qualified by way of the manufacturer confirming the results of the ingredient supplier’s testing, 2) the certificate of analysis describes the analytical methods used and the actual results of the test, 3) the certificate of analysis is periodically reconfirmed, and 4) the company’s quality-control personnel approve the basis for the supplier’s ongoing qualification.)
Proper laboratory qualification is an important part of the GMP process. A manufacturer should confirm that a laboratory has the capability and the components to produce accurate and reliable test results. Although the testing methods that FDA describes in the GMP regulation are vague to a certain extent, the burden still remains on the manufacturer to ensure that the methods used are scientifically valid.
When pre-qualifying a laboratory, a manufacturer is responsible for first ensuring that a laboratory can adequately determine whether the dietary ingredients/raw materials used meet specifications. After that, the manufacturer must ensure that the laboratory can adequately determine whether the finished dietary supplement product meets specifications. In other words, the manufacturer needs to be certain to show that it did its due diligence, with respect to any lab it used, to be certain that the laboratory was capable of properly testing raw materials and finished products. All of this will ensure that the finished product accurately contains what is supposed to be in it.
In order to accomplish the above, manufacturers should develop standard operating procedures (SOPs) for laboratory qualification as well as laboratory re-qualification. Such procedures should be made an integral part of any GMP compliance program.
Part of laboratory qualification should include a site visit to the lab. In fact, a manufacturer’s SOPs should specify precisely what the steps are for a site visit, including the steps of the audit and what would be needed to draw a conclusion that the lab meets the company’s standards for laboratory qualification. If a manufacturer doesn’t have the expertise to perform such an audit, or it doesn’t know what specifications to set, it could hire a third-party company with expertise in laboratory sciences, GMP compliance, and analytical chemistry to help.
Another thing to keep in mind is that most likely, a manufacturer won’t find one single laboratory that can provide all of the laboratory services it needs. Different laboratories have different areas of expertise. For example, not all labs may have the capability to analyze complex polysaccharides accurately; therefore, in such a case, a company should find a lab that specializes in that area. A manufacturer should be certain to identify what each lab’s specialty is.
It is also wise to invest in some simple tests to covertly test a lab’s performance. This is a crucial investment, as it will uncover whether a laboratory practices dry labbing. Also, some labs may practice dry labbing only some of the time; therefore, a manufacturer should develop an ongoing lab re-qualification policy.
For instance, a manufacturer could take the following steps: First, purchase and send the laboratory a reference standard. (A reference standard is a highly characterized material, which has undergone several analytical tests to be certain of its identity and purity and which contains no noticed contaminants.) Ask the lab to identify the purity of the reference standard material, without giving the lab any specification sheet, to see if it can accurately confirm the material’s concentration.
Another simple method to flush out potential dry labbing practices is to ask the laboratory to test for the presence of a different compound, one that the manufacturer knows should not be present. If the laboratory reports not finding that compound, that’s a good sign. In fact, manufacturers should periodically send the lab “dummy” samples in this manner, keeping in mind that a dry lab is more likely to report a result that is close to any specification the manufacturer sent, even if the specification is fake.
Or, instead of having a lab test individual ingredients, another way for a manufacturer to test a lab is to have the lab test a finished product for which the manufacturer knows the amount of the ingredients present-and compare the data with the lab’s analysis.
Whether there are many or few labs practicing dry labbing, the simple fact is that dry labbing is illegal. For the dietary supplements industry, dry labbing remains a problem as long as any laboratories do it. In the way that one bad apple spoils the bunch, any laboratory practicing dry labbing can mar the impression that the dietary supplement industry can self-regulate.
Thus, it is the responsibility of manufacturers to ensure GMP compliance-and to make sure the laboratories they work with do the same. By working together and developing laboratory qualification SOPs, the industry can hopefully work to eliminate the problem of dry labbing altogether.