Qualifying raw materials is probably one of the toughest tasks faced by contract manufacturing organizations. Intentional or not, 21 CFR 111 excluded raw material suppliers from cGMP (current good manufacturing practice) regulations. For now, the burden of sourcing raw materials and ensuring they meet identity, potency and purity continues to fall on the contract manufacturer, not the brand owner.
Over the past few years, we have all noticed the change in marketing strategy by various ingredient suppliers, who rather than shopping their products to the contract manufacturer, now market and dazzle brand owners with the wonders of their branded raw materials. This is done with the hope that the brand owner will specify its ingredients in its formulas, ensuring positive exposure for the supplier’s ingredient and efforts.
However, many times, ingredient suppliers sell more sizzle than steak, and key elements required to engineer or test the material itself are not as robust as required. In this case, the transparency among all parties is paramount. Otherwise, it becomes difficult for the contract manufacturing organization to use the ingredient in the brand owner’s product, causing a delay to market and additional unexpected costs to the project.
Practically, once the brand owner has selected the ingredient for their product, the contract manufacturer has two options for qualifying the material. The most complete pathway is when the contract manufacturing organization qualifies the ingredient supplier through a thorough audit of the supplier and complete testing of several lots of material according to their procedures. This will enable the contract manufacturer to accept incoming lots of the specific ingredient based on the supplier’s certificate of analysis (CoA) and basic analytical testing. However, this is an expensive and time-consuming process for the contract manufacturing organization.
The other option is to have a less robust audit program, but test incoming lots of the ingredient for identity, potency and contamination each time the material is received by the contract manufacturer. This method of compliance is preferred by most contract manufacturing organizations, especially if the material is from a credible supplier, as the costs are then budgeted on a per-order basis, rather than a huge investment at the beginning of the project. If it’s a single compound, botanical powder or extract, this is fairly straightforward to test, and within most contract manufacturer’s expertise.
As can be imagined, complications quickly arise when the ingredient supplier creates a proprietary blend of multiple ingredients. These blends are appealing to the brand owner to help differentiate the product in the marketplace. It also provides an excellent way to disguise the precise amounts of individual ingredients comprising the blend from the prying eyes of competitors, who may want to reverse engineer or duplicate the formula for their own brands.
While a blend can provide a great value proposition and potential health benefits, the transparency between the ingredient supplier, the brand owner, and the contract manufacturing organization as to the blend’s contents is critical to ensure regulatory compliance. Since the contract manufacturer must have confidence of the contents of the blend, the establishment of identify testing protocol is required. Cooperation between the contract manufacturing organization and supplier is needed to make this happen. If the ingredient supplier is not forthcoming with the composition and ratio of the blend, it becomes an expensive wild-goose chase for the contract manufacturer or specialized third-party labs to identify what is in the blend. At that point, it becomes necessary for the brand owner to help acquire this information, or to look to another material where the ingredient supplier is more cooperative and aware of its responsibilities.
For instance, a common issue with a blend would be where the product specification or CoA indicates a single source or marker compound, but without exact knowledge of the composition of the blend, it may be impossible to match a reference material or test to correctly identify the item. Also, when a blend is comprised of materials with similar or the same marker compounds, dissecting it to identify all of the constituents as required under cGMPs is almost impossible. For example, a “berry extract blend" of bilberry, blueberry, cranberry, raspberry and strawberry may not be able to be identity tested due to the lack of berry-specific compounds for each ingredient. Thus, cooperation with the ingredient supplier is key to have a harmonized, scientifically valid testing method between all parties, where otherwise the contract manufacturing organization has no choice but to reject the material, much to the disappointment of the brand owner.
These caveats do not mean contract manufacturers don’t like specialized ingredients or proprietary blends, or cannot handle their specific challenges. The use of branded ingredients helps increase partnerships through the supply chain, allows the exposure of the contract manufacturing organization to new science, and also may offer manufacturing efficiencies. The key is having an open dialogue between all parties and a partnership where everyone is working together. The ingredient supplier has to remember the brand owner and the contract manufacturer are on their side, and want to see their research pay off. However, ingredient suppliers need to recognize that until the GMPs are expanded to include them, there must be transparency and openness about their products so they safely may be put into the marketplace.
Michael Finamore is CEO of Gemini Pharmaceuticals Inc. (geminipharm.com), a contract manufacturer of both dietary supplements and over-the-counter (OTC) pharmaceuticals for more than 30 years. All Gemini production is carried out in a pharmaceutical cGMP (current good manufacturing practice) environment.