Outside Analytical Labs

Here are some tips on how to use contract laboratories inside the dietary supplement GMP framework.

By Paula Brown &
Steven Dentali, PhD

Contract laboratories provide an extensive range of services and can be a cost-effective way to test the quality of raw materials and finished products. Whether to assist in guiding purchasing decisions or to help develop claim and labeling information, your decision to identify and hire a laboratory partner should begin with the identification of your needs. From routine testing for compliance with cGMPs to clinical testing in support of a company-sponsored trial, it is imperative that you clearly state your requirements and compare these needs to a laboratory’s capability.

Many laboratories offer an impressive suite of testing services, but every laboratory has different areas of expertise and competency. So before deciding whether or not “one-stop-shopping” is best for you, evaluate each service independently. Focusing on the more mundane testing scenarios, it must be noted that with dietary supplement testing not much is really “routine” and the quality of contracted work can vary significantly. The complexity and variety of finished products, coupled with the freedom to change formulation at will, results in a constant challenge for analytical laboratories. As the majority of dietary supplement products are not generic, any analytical method used on a given product should be validated to ensure it is fit for that intended use.

Questions of Accreditation

When considering contract laboratories, make sure you seek out documentation in the form of certification or accreditation to ensure quality—unfortunately for the dietary supplement industry we are in a “buyer beware” en­vironment, as there are no accrediting bodies or specific regulations that govern the behavior of contract laboratories. Beware of laboratories that claim to be FDA certified. Contrary to popular advertisements, there is no such thing as an FDA approved or certified laboratory. Laboratories may be “inspected” by FDA, but the result of a passed inspection is not “certification”; it is merely a passed inspection. If you choose a laboratory that has been inspected, ask to see the FDA inspection report to determine whether the inspected facility operations are even relevant to the analyses you intend to contract. Laboratories might be certified or accredited by EPA under various state programs, however few, if any, of these programs are directly related to most dietary supplement analytical endpoints.

You may have heard the phrase “Good Laboratory Practices” (GLP) and wondered how this designation relates to your needs. Actually, the phrase is a term that applies to a limited scope of animal, drug and environmental testing. GLPs are designed for studies where a study director is involved (e.g., a clinical trial) and not for routine analysis. One type of certification that may be of interest when considering hiring a laboratory is that provided by the International Standards Organization (ISO). There are several levels of ISO certification that range from general quality management to specifics, so you really need to determine the level of certification for ISO compliant laboratories. The main standard used by testing and calibration laboratories, ISO 17025, only applies on a per-method basis, so be sure to ask which methods are included in the certification.

In Consideration of Dietary
Supplement cGMP

According to the 21 CFR Part 111, every step of the manufacturing, packaging, labeling and holding process for dietary supplements must be documented. This translates to having standard operating procedures (SOPs) for all protocols, including laboratory test methods. In choosing a laboratory, you must make sure its operations, with respect to testing your products, are in compliance with cGMP. While the GMP may seem rather vague and not particularly informative on this subject, keep in mind that FDA has provided considerable latitude to companies in establishing their specifications and testing protocols. Evidence must be provided that the laboratory examination and testing methodologies are “appropriate for their intended use” (21 CFR 111.320(a)) and that methods used to determine whether or not specifications are met are “appropriate and scientifically valid” (21 CFR 111.75 (h)(1)). Proof will require data collected by the laboratory specifically on your raw material or finished product. Remembering that the burden is on the manufacturer to document that these requirements are met, a close working relationship with the contracted laboratory is highly recommended.

Choosing a Laboratory for
Routine Testing

First and foremost, the question should be: Are the methods to be used by the contracted laboratory on your test articles compatible with your specifications? For example, if you are a vitamin manufacturer in search of microbiological testing, an experienced food laboratory may not be much use to you unless that laboratory can demonstrate experience with your matrix, or at least related matrices. If you’ve become comfortable with the concept of “off-the-shelf” testing on a one-off basis and shop for laboratories by price and/or turnaround time, you may be in for a surprise when FDA stops by and wants to see the documentation related to work conducted by the contracted laboratory. Keep in mind that FDA will expect SOPs for testing and for making the determination that the tests are both scientifically valid and appropriate to your test articles. Inspectors will also expect your sampling plan, calibration, data, justification for reference material selection, etc., to be readily available. Each time you begin a relationship with a new contract laboratory or change your formulation, expect to pay for this additional information. Ultimately, jumping from laboratory to laboratory is a false economy.

Quality Assurance & Quality Control

While the final regulations do not require each company to have a separate quality assurance unit, they do mandate individuals within a company be charged with this function. For that reason, any contracted analytical laboratory should have a quality control (QC) manual, if not a designated quality assurance (QA) unit. In considering hiring a laboratory, one should inquire about the existence of a QC manual and its implementation. Unless you are doing a site audit, laboratories are not likely to send their entire QC manual, however it is reasonable to request an outline of the manual or the table of contents.
If your company will only be submitting a few samples, do not expect a laboratory to fill out a huge questionnaire or submit to a site audit. However, the laboratory director or quality assurance officer (QAO) should be able to answer basic questions regarding QC procedures and analytical protocols. If a lab is completely unwilling to provide this information, then that should raise warning flags—and this is most certainly not the foundation on which to build this important relationship. Laboratories should be forthcoming with information, such as acceptance criteria for the method(s) of interest, and be able to explain how data are reviewed for quality control.

Before contracting a laboratory, ask it to provide raw data, such as chromatograms, data points and calculations from previous projects that employed the method of interest. Most labs can provide a redacted sample and explain the significance of the data. While it would not be appropriate for laboratories to demonstrate work done for another client, they should be able to show a calibration chromatogram and control sample analysis of a similar material. Keep in mind that if you expect or require a laboratory to engage in the educational aspects of analysis, it should be compensated. In contrast, laboratories should be willing to answer basic questions to ensure their clients understand the testing protocols.

Expect Disclosure, but Expect to Pay for It!

Finally, when contracting a laboratory you should expect to have all raw data collected on your test article made available, as such records are required within the GMP context. While some laboratories may resist, the method details and results validation data should be disclosed; of course while some manufacturers may resist, they should expect to pay for the contract laboratory to ensure the method is suitable for their product. After all, FDA has an abiding interest in all these points, and if the laboratory does not or cannot provide this information, you may have a problem.

This column was co-authored by Steven Dentali, PhD, who is the chief science officer at the American Herbal Products Association (AHPA), Silver Spring, MD. Recognized as a foremost expert in the natural products industry and a frequent lecturer, he is considered an authority on botanical quality issues. He is also an Editorial Advisory Board member for Nutraceuticals World. He can be reached at sdentali@ahpa.org.