Insider Takes

• Its vital to determine which specific tests are appropriate for an application (fit for purpose).
• Any testing method must be scientifically valid and qualified by the lab performing them.
• Labs must be transparent in disclosure of the required work, as well open to a formal audit.

FDA is applying greater attention to and enforcement of dietary supplement regulations than ever before. This is not unexpected. The course of implementation of the regulations has come in waves of effort as inspections occurred after the finalization of GMPs (good manufacturing practices) for dietary supplements. The application of the term "transparency," when applied to the laboratory—whether as part of a contract manufacturer or vertically integrated manufacturer or even just a brand owner—involves two basic determinants. Looking at these from the standpoint of transparency is really a matter of knowing that the efforts are in line with the requirements of the regulations.

FDA is more commonly asking for this information during inspections with specific focus on testing and the qualification of said methods, as well as any reference materials. However, the root of it all is the establishment of specifications. The mandate for the establishment of specifications at each stage of manufacturing (component, in-process and finished product) is wher it all begins. Knowing what specifications to establish includes evaluation of the labeled claims for the product and the ability to test using a qualified scientifically valid method; this is wher the laboratory operations comes in.

Before a product can be tested in any lab, the lab has to know what it is looking for and how to test for it. Thus, the transparency between the lab and the client (especially if such work is contracted out) is essential to ensuring the absolute compliance of the brand owner. In return, two critical elements from different parts of the regulations require absolute transparency in the other direction. Specifically, these critical elements are: 1. the determination that a specific test is appropriate for the application (fit for purpose) and 2. whether the method itself is scientifically valid and qualified by said lab.

In instances wher the method employed is strictly in conformance with a compendial or other recognized method, generally no issues exist provided the method has been appropriately qualified in the given lab. Citation of the method as compendial (and most current), being applied without modification, merely requires demonstration that the lab is capable of performing this method, which should be available for review upon inspection/audit.

While a method itself may be compendial, the physical application of it still must be affirmed for the lab actually doing the work. This lab qualification is relatively straightforward to the experienced analyst and is a step that needs to be performed for absolute compliance. If the method is a modification of a compendial method or an in-house developed method, the transparency necessary includes documentation of how the method was developed for the application, along with all supporting data and recordkeeping. This is a separate qualification package and not the same as method validation. The data generated must ensure the accuracy and precision of the method, documented and demonstrative of this application.

This information must then be available not just for the company ordering the testing, but for the ultimate distributor of the product. The regulatory obligations do not stop at the contract manufacturers door. If an own-label distributor whose product for sale is obtained from a contract manufacturer, the brand owner will need to know whether the methods employed by the contracted laboratory are scientifically valid to the same expectation FDA has for the contract manufacturer who selected the contract laboratory.

When looking at the performance of the laboratory against the applicable regulations, one would expect to have a good bit of this transparency. In-house methods are not always provided publicly nor well qualified for the various products that roll into such laboratories, which can prove problematic during an investigation. Particularly, adjustments to the sample preparation are done on the fly in most instances, as the efficiency of these operations is critical to their fiscal success.

Any laboratory, whether contracted out or in-house, is required to evaluate the methods employed and produce results consistently. The two aspects—determination of the suitability for purpose and of the qualification of the methods employed—are the transparent items. Careful review of this documentation is required and should be a part of the evaluation of the performance of the laboratory. Knowing what is tested and how is critical and obvious, but there can be no forgetting the additional need to explain why the tests identified are appropriate.

Therefore, the consideration of transparency when it comes to laboratory operations really begins before the testing itself, with the establishment of appropriate specifications to ensure the identity, purity, strength and composition of the dietary supplement product. Establishing a specification that cannot be measured is just as inappropriate at establishing a specification that does not truly accomplish the affirmation of the product regarding the parameters outlined.

Additionally, recognition of the label claims made on the product must be performed in order to meet this obligation. The testing then may be determined as specifically as possible to meet the expectations of FDA. This means using methods that have been evaluated for application in the specific instance applied and documentation of the efforts made to determine such qualification.

The two main pieces of compliance involved are the establishment of meaningful specifications and the ability and documented appropriateness of the tests employed. It is incumbent upon anyone involved in the testing of said components, in-process materials and the finished products to adequately document why a method was chosen and then to document the demonstration of the applicability of the method in practice. Having one without the other is insufficient; if a brand owner is contracting to have the laboratory work done, the lab itself must be transparent in disclosure of the required work, as well open to a formal audit in order to be qualified, so brand owners can be in and maintain compliance.