01 Sep 2015

 

The Contract Manufacturer’s Role in Safety

The contract manufacturer plays a key role in providing a quality product produced according to cGMPs, one that will stand up to all regulatory scrutiny and consumer safety parameters.

As a raw material contract manufacturer/supplier producing premixes and drum to hopper formulations there are three pathways that a customer can pursue: 1) a total turnkey product; 2) a product where the ingredients/raw materials are customer provided; or 3) a combination of the above.

A company, specifically one just entering the marketplace, needs to seek out a CM that can perform to its expectations and minimize product liability. A CM with a historically good track record and either a full laboratory or the capability to ensure analysis by a reliable and certified third party is key.

In a total turnkey process, the customer and the contract manufacturer need to definitively and clearly outline their respective responsibilities and deliverables, preferably in writing or in a performance agreement.

Once these parameters have been established, the customer should provide the formula and the CM’s R and D/QC, purchasing, and operations departments should begin their initial review and discuss any discrepancies they may see. The most common discussion topics are sourcing of raw materials to meet specifications, QC testing parameters and establishing internal specifications and controls for the product, and overage evaluation as it relates to shelf life stability “reality.” Having a purchasing department with long-term and established relationships with reliable raw material vendors significantly reduces exposure from a liability standpoint and minimizes potential for contamination risk.

Many companies want to break into the market quickly. However, strategizing includes navigating through the stability challenges early on, which will yield success for the product on the shelf.

We have also found that some ingredients do not pair well, and when working with active ingredients there could be a “chemistry response” that may reduce the activity level in finished products over time or result in the creation of an unwanted active component. An experienced CM could be very helpful here in educating the customer.

In a total turnkey process, materials are placed in quarantine until evaluation of each raw material that will be used in the blend is complete—the onus is on the CM to ensure product is safe for use. This includes active ingredient analysis according to existing or customer provided methods, microbial activity, heavy metals, pesticides, gluten activity, moisture, ash, known raw material specific contaminants (i.e., melamine), and visual inspection for extraneous matter prior to production. We can also evaluate to see if there are effects of uncontrolled storage conditions that may also play a role in the quality of the raw material.

Included in the process would be supplying a full dossier of statements for addition to the customer’s regulatory file—fully investigating the non-GMO status of an ingredient as well as being able to verify the existence of any allergen components.

We then continue to test certain parameters in process, specifically particle size analysis, bulk density, and solubility (if applicable).

All of the above yields to the ease of performing the final analysis on the finished blended product.  If all of the steps have been followed, there should be no surprises!

However, in the case where we are not producing the finished product (tablets, capsules, etc.) there is still one more step that needs to be evaluated by the customer and that is with the finished product CM involved in the tablet/capsule manufacture and bottling of the product. They typically rely on our C of A, however, upon receipt there are basic tests the tableting/bottling CM should perform and upon completion of the finished product should be evaluated and compared to label claim.  Throughout their manufacturing process they must give the customer assurances that every effort has been made to produce the material according to specifications.

In the second case, where a customer provides the raw materials, we will outline certain expectations of meeting specifications upon delivery. We will typically evaluate for microbial contamination and upon customer request will perform additional testing to ensure safety and accuracy. After manufacture, we will provide a C of A containing the agreed-upon category analyses, most often this will be the microbial evaluation.

In all instances, maintaining samples throughout each step of the initial evaluation and production processes until final issuance of certificate of analysis will provide useful information for traceability in the event of a contamination issue. They may also be useful in providing protection to the originating CM in the event of a contamination occurrence at another finished product manufacturing facility.

All of the above efforts seek to minimize any issues of discovering contaminants in the raw material. In the end product in either CM position, this should yield a positive outcome.

If by chance contaminants are discovered at a late stage, investigations would begin with the starting raw materials, any events resulting in the potential for cross contamination, exposure to certain unforeseen environmental components, equipment failure, batch record analysis, and human contact.

With the implementation of cGMP monitoring throughout the entire manufacturing process, every effort is made to eliminate the possibility of contamination. The more stringent quality and regulatory measures you and your CM have in place, the less likely is the occurrence a contaminated product will land on the shelf.

Re-printed with permission from Natural Products INSIDER

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