Therapeutic Dose: Protecting Pharma's Supply Chain
Until we can examine every supplier of excipient and API, we’ll need to do our own detective work, but that will help us with Quality by Design.
By Emil W. Ciurczak, Contributing Editor
Recently, various LinkedIn groups have been hosting some interesting discussions on the pharmaceutical supply chain. Pharma shares many characteristics with the food industry. I recently read  that one frozen pizza can contain as many as 50 ingredients from 10 or more countries. A law had been proposed in Congress that would have required companies to be able to trace the suppliers of any ingredient, at any point in its life cycle. That law was shot down. Right now, food companies only have to track who sold them something and whom they sold sold their product to.
Why does this concern us in the pharmaceutical industry? Many of the excipients we use are supplied by the same people who supply food companies. Remember, pharma buys only a small portion of the lactose, sucrose, cocoa butter, and other “fillers” that are sold. The typical pharma company has dozens of suppliers around the world for each material it uses to manufacture its products. Aside from any potential health problems they may pose (remember heparin?), the consistency of the raw materials is problematic, at best.
Sadly, most drug manufacturers today don’t know what a “good” raw material really is. One discussion chain suggested that we include ingredient vendors in formulation planning sessions (on a forum started by my friend Hedley Rees, author of a critical new book ). Vendors may not know pharmaceutical production, per se, but they know the grades of materials they can provide. If proposed formulations were discussed with vendors (under a confidentiality agreement, of course), these vendors might be able to make positive suggestions as to the correct grades and specs for the materials used. While suppliers will seldom change material properties to meet our specs (remember: we are small customers, by comparison with food people), they can suggest the best grade for the process we describe to them.
That is fine for correct physical parameters, but what about purity and consistency? While we now have vendor validation programs where we audit a supplier for cGMP violations, it is not inclusive of all suppliers. Even the FDA cannot inspect all the venues with which it is tasked. An example of futility might be China, where the FDA needs an “invitation” from the government to inspect a facility. I’m sure no one in the government would alert the manager of the facility of the upcoming “surprise” visit, would they? There are a number of steps we can take on the “home front” to help ourselves.
While I was researching suppliers for my NIR raw materials work (we didn’t have vendor validation in 1983), I traced every material back to its point of origin. I accounted for every place where material could be repackaged or relabeled as well as the origin of every material. One purpose was to determine whether any other material was produced at the point of origin. One example was talc; it was quarried in Alabama, crushed, packaged, and ETO-sterilized at the point of quarry. Since there was no chance of product mix-up, we did not need to do containerwise qualification, just a quick ID. Another example was aspirin. Several suppliers also made other materials and, consequently, we checked every container. One produced aspirin in an isolated building, packaged and shipped from there. This product only needed cursory examination upon receipt.
Until we can examine every supplier of every material, both excipients and APIs, we need to do our own detective work. The good news is that the data needed to produce meaningful tests (not LOD, sieve size and other USP tests) will apply to QbD processes. If we determine which are critical parameters, find accurate purity tests, and find the will to implement them, it almost doesn’t matter that the sources may be questionable. Forget about $50 Rolexes. As it turns out, Caveat emptor applies to all points of the supply chain.
1. “Your Food has been Touched by Multitudes,” Bloomberg Businessweek, August 29- September 4, 2011, pp. 29ff
2. Rees, H. “Supply Chain Management in the Drug Industry: Delivering Patient Value for Pharmaceuticals and Biologics”, Chapter 5, J. Wiley & Sons, Hoboken, NJ, February 11, 2011.