Articles in this series have previously covered several basic concepts related to botanical materials in order to help provide essential information about these ingredients for industry. This article frames the basics of good documentation content, which is at the heart of good manufacturing practices (GMPs). Knowing your raw materials is the key to intelligently implementing GMPs that pertain to botanical ingredients. Botanical raw materials are chemically complex and different from synthetic or natural ingredients composed of a single compound. Therefore, the evaluation of these materials requires a special approach in order to be properly understood, sourced and documented.

The first article in this series of botanical basics attended to nomenclature that can be used to differentiate the source plants, the crude herbs made from these source plants that enter commerce as agricultural commodities, the ingredients derived from the crude herbs and the finished products. In the second article, the basic types of extracts were described. This is a key piece of necessary knowledge when it comes to asking questions to suppliers regarding exactly what is offered for sale. The third article focused on the authentication of botanical ingredients. How do you demonstrate that the ingredient you have sourced is actually what you think it is? Confirming the identity of your dietary ingredient is a regulatory requirement, and it must be documented. The most recent article defined the action of chemical constituents in biological systems as potency and their quantitative amount was defined as strength. This is something that is not likely to make you popular when discussed at cocktail parties in mixed company. This is technical stuff not for the uninitiated.

This article focuses on documentation; specifically those documents that are most useful for characterizing botanical dietary ingredients in order to support quality, safety and regulatory compliance. Proper documentation can serve manufacturers in the evaluation of ingredients and in the investigation of quality issues or adverse events. In addition, the ability of an ingredient supplier to provide sufficient documentation that supports quality, safety and regulatory compliance for raw materials in a timely manner can increase the efficiency of the product development process. The quality of documentation can also be a deciding factor when choosing between two raw material suppliers.

The Paper Trail
The documentation trail usually starts with a specification sheet. A specification sheet is the document that communicates specifications for a raw material by defining the characteristics of the material along with an explicit set of requirements that must be satisfied for each production lot. It should include test parameters along with a numerical range of acceptable test results (when applicable), the test method used, recommended storage conditions and the shelf life of the ingredient. The test methods must include assays that will establish the identity, purity and strength of the raw material, as applicable. The name of the method should be specific (e.g., USP) so that it can be identified and reproduced, rather than simply listed as a technology (e.g., HPLC). Think of it as a recipe. You need all the steps, the ingredients and how to prepare a dish, not just a method of cooking (e.g., baking).

However, the proof of the recipe is not in the pudding in this case, but in the results of the test methods expressed in a certificate of analysis (CoA). A proper CoA is an authenticated document issued by an appropriate authority that certifies the compliance of a material to its specifications. It provides the test results confirming that a raw material meets specifications. The CoA should include the supplier name, raw material code, lot number, manufacturing date, expiration/retest date, specification and acceptance criteria, test methods, test results (numerical when appropriate) and a signature. As already mentioned, the identification test is an essential part of a specification sheet and CoA, and often deserves its own documentation.

An identification test confirms the ingredient you are buying is what you intend to buy. It is a critical document a manufacturer can use to prevent adulteration (intentional or unintentional) and to substantiate what ingredients are going into its products. The method used for the identification test must be consistent with what is designated in the specifications. Test results should include the lot number, reference standard, description of what is used as a reference standard and why it is an appropriate reference. The test method protocol, including sample preparation, experimental conditions and detection method should also be provided.

Botanical ingredients, particularly extracts, are often combined with other subcomponents, such as carriers and excipients. A composition statement document should be made available to provide information on all subcomponents present in the raw material or to confirm that 100% of the raw material is comprised of the botanical ingredient of interest. This information is necessary to evaluate the feasibility when formulating finished products and to generate an ingredient listing. It may also dictate the need for additional regulatory documentation. A composition statement should include all subcomponents (including excipients, preservatives, etc.), a specified source of the subcomponent if there is a regulatory concern and a quantitative amount or reasonable range of each subcomponent. These subcomponents should match those indicated on another important document, known as the manufacturing flow chart.

A manufacturing flowchart provides the basic steps as to how starting materials are transformed into finished raw materials. Knowing the general manufacturing process of a raw material is important because it can help predict the nature of the chemical composition of the end product. This is particularly true for botanically derived complex ingredients, because their composition is dependent on the process used to create them. Details of a manufacturing process may be proprietary, but a manufacturing flow chart should, at a minimum, provide information on the starting material(s), mixing, extraction, solvents, excipients, drying and the finished raw material in the order that these steps were performed. These flowcharts are not something that should be generated with one’s eyes closed. They should not be generic, but specific to the ingredient of interest, because a flowchart that does not provide detailed information regarding important processing steps (i.e., grinding-extraction-drying-powdering-packaging) provides little useful information.

Documenting Contaminants
Setting specifications for contaminants that are likely or certain to adulterate a material is also a regulatory requirement.
Contaminant specifications should be tailored to the particular ingredients at hand. With regard to extracts, documentation indicating residual solvents and solvent levels may be a good idea. Reporting of residual solvent levels (a solvent that remains in the raw material after processing has been completed) is required by regulation in certain countries and ensures that any solvent remaining is at a level safe for consumption. Residual solvents reported should be those that you would expect to find in the raw material based on the manufacturing process and must remain consistent throughout all documentation, including the CoA, specification sheet and manufacturing flowchart. When reported on a CoA, the residual solvent data should include the specification limit and the actual test result (“conforms” is not an appropriate test result).

In some markets, it is required by regulation to report pesticide residues for botanical or botanical-derived raw materials. Information on pesticide residue levels may also be requested due to safety concerns regarding the potential for the presence of certain levels of pesticides. Some countries have established limits while others default to standards set by the Codex Alimentarius Commission or the United States Pharmacopoeia (USP).

Another possible regulatory requirement, and increasingly a voluntary initiative, is documentation supporting the presence or absence of genetically modified organisms (GMOs). A GMO is an organism whose DNA has been altered to achieve a particular result (e.g., to obtain a crop of tomatoes with improved appearance or altering cereals to yield a higher production of grain). Many countries, especially in Europe, have different restrictions surrounding GMOs that dictate labeling requirements. Also, there are some countries that completely prohibit ingredients containing GMOs. Depending on the regulation, some countries allow testing to determine if an ingredient contains foreign genetic material while others require proof that an ingredient is identity preserved.

Identity preservation (IP) is a process or system of maintaining the segregation of an ingredient from those designated as GMO, and documenting the identity of this ingredient throughout the growth, storage, processing, shipping and sale of the plant material. Ingredients certified as IP have met specific requirements designed to preserve the genetic and/or physical identity of the product.

A statement confirming that an ingredient does not contain GMO material is appropriate when an ingredient is made from plant material known to have genetically modified sources (e.g., soy ingredients). It is also important to look at the composition statement for potential sources of GMO subcomponents. For example, an ingredient combined with 10% maltodextrin (which has high potential to be produced from a GMO crop such as corn), would trigger the need for GMO documentation in those countries that have regulation surrounding GMOs.

Collectively, the documents described in this article are very important for evaluating the quality of raw materials and may be required for product registration in certain countries. For manufacturers, obtaining complete raw material documentation can facilitate regulatory compliance and help to manage risk and liability. Good documentation practices (GDPs) often indicate a low risk supplier. For suppliers, providing good documentation for raw materials can help earn and retain customers. The net result is the establishment of a more strategic partnership between supplier and manufacturer. Details on guidelines for the format and content of these and other documents have been compiled by the Standardized Information on Dietary ingredients (SIDI) Working Group in its SIDI protocol and CoA Guideline, which can be accessed at www.sidiworkgroup.com.