Raw Material Qualification: How Regulations Affect Timing

As a contract manufacturer, one of the biggest challenges is meeting customer expectations for the timing of finished product delivery. There are many aspects of manufacturing FDA-regulated products that affect production schedules, and the timing can vary across regulatory classes. A generalization can be made that higher classes of products (over the counter [OTC] medicines, for example) may have longer lead times due to a higher level of required testing compared to a lower-class level, such as cosmetics. The various requirements of raw material qualification that affect lead time can include sourcing location, specification review, qualifying the vendor, identifying the raw material, validating the raw material identification, receiving and inspection.

In a facility that follows cGMPs (current good manufacturing practices), qualifying raw materials for use in products is one of the first hurdles, one that can flow smoothly or take days or weeks to accomplish. With increased FDA pressure to focus on raw materials, this is a critical aspect to manufacturing safe and effective products, and sets the stage for high quality in the manufacturing process.

For the manufacturer, if raw materials can be sourced from an existing (qualified) vendor, the sourcing process may proceed smoothly and timely. If the material is sourced from a new vendor, the vendor must first be qualified. The intention for qualifying a vendor is to provide confidence, via evidence, that the vendor manufacturers acceptable materials. The vendor for the raw materials must meet certain standards, and the contract manufacturer must ensure this. The qualification process may include: surveys, on-site audits and inspections, or proof of certifications such as organic, kosher, etc.

 Sourcing raw materials must meet customer requirements. The contract manufacturer must determine what specification the customer requires for each raw material. This can include the country of origin (is domestic sourcing required or are imports allowed?), the physical characteristics and the quality or grade, such as the requirements of meeting USP grade specifications.

Once the materials have been “spec’d," the vendors have been identified and qualified, and the raw materials have been ordered, the next critical steps are the delivery and inspection of the materials, followed by the identification of each.

Once the vendor is qualified and the materials ordered and received at the loading dock, the inspection and identification process begins. Inspection at delivery includes a review of packaging integrity to be sure no contamination has taken place during shipping. A statistical sampling of each material is made, with a higher sampling for critical materials, such as raw materials that are the “active" ingredients in the finished products. The certificate of analysis (CoA) is compared to the specifications for each material, and expiration dates are checked. If package integrity is compromised, if any specifications are not met or the visual appearance is suspect, the materials will be rejected.

For raw materials that pass inspection on delivery, the next requirement is identification. The identification process must ensure the materials received are correct and unadulterated. A contract manufacturer may use specific identification methods in-house or send materials out for other methods of identification at qualified laboratories.

This process can take up to 10 working days for completion depending on the identification testing requirements. Raw materials are also tested for microbial contamination.

An additional aspect of raw material sourcing required for some regulatory classes is CoA verification. This process is performed to confirm the physical and chemical characteristics of the materials, as well as to monitor the vendor’s conformance to the specifications. This process typically involves a significant amount of testing on the first three lots received, followed by annual checks on one or more lots. The process gives the contract manufacturer confidence that future lots will perform as expected and maintain the quality of the finished product. This check supports the aphorism “trust but verify" heard so often in quality control circles.

Sourcing, inspecting, identifying and documenting the use of raw materials are critical aspects to manufacturing and meeting FDA regulatory compliance issues, and all of these aspects affect the timing of product delivery.

Jennifer Cusick is director of sales operations at P.J. Noyes, a Nipro Diagnostics Company.