At a CDMO, there’s nothing more critical for our sponsors—and to our own reputation–than to have assurance that products are being manufactured to proper specifications. Moreover, those specifications have to mean something! After all, among our products are APIs that become drugs to be consumed by people and pets. Safety is also critical for the GMP functional foods we produce, and the polymers used in medical devices. We are extremely concerned with safety, and that’s why quality control (QC) is the second largest group in our organization after manufacturing
The U.S. FDA, the European Medicines Agency (EMA) and other regulatory bodies are also safety-focused. Consequently, their regulations change frequently as the science and methods evolve and lead to better understanding. But their goal and ours remains the same: to minimize the risks that might have an impact on the quality and reproducibility of pharmaceutical and other products that could impact health.
This article will provide an inside look at what a QC operation at its best looks like.
The large size of our QC group, and its specialized functions, reflects its importance. Our analytical services department is divided into three functional areas:
Our QC group operating hoursmatch those of plant operations, working 24 hours a day. The group designs and executes all the testing, from assuring the integrity of raw materials to conducting in-process and final product testing.
As a GMP facility we are subject to inspections by the FDA. Accordingly, the QC department follows very specific rules on manipulation of data and data integrity, and for good reason. You may recall that a few years ago dozens of patients died after taking Heparin. The main reason? Bad data. The deaths and adverse events resulted from Heparin adulteration. Investigations into this terrible occurrence revealed a number of systemic failures, including inadequate quality controls in plants operating outside the U.S. that supplied the raw materials.
Clearly, the drug product developer who purchased the raw materials did not test adequately enough to make sure that they met specifications before moving ahead. At our facilities raw materials are always checked against specifications by QC before being stocked for use in projects.
Meeting specifications at every step is vital. When samples arrive, in-process testing is conducted until the reaction has been completed and all critical points have been reached before moving to the next step: a reaction that doesn’t run to completion can result in the presence of impurities. In most instances we look for conversion of raw materials equal to or greater than 90 percent. If the specification calls for 90 percent, the batch fails at 89 percent, unless a risk assessment report by one of our engineers determines that due to the chemistry involved, the specification can safely be changed to 89 percent without drastically altering the impurity profile.
Method development is the responsibility of a team charged with developing all of the science and the analytical methods, including that determination of whether that reaction has run to completion. This group also designs studies to understand the molecule’s stability and the degradation it will undergo over time and under varying humidity and temperature conditions.
Every molecule we produce is subject to stability testing at 2-month, 6-month, and two- year intervals, and at intervals that are the same as, or simulate, the packaging proposed for storage and distribution.
Quality control also conducts final product testing and reports results on final certificates of analysis. All this testing data is sent to the Quality Assurance department, where it is reviewed to assure concurrence with Standard Operating Procedures (SOPs).
For a CDMO’s QC department that works 24 hours a day to run smoothly, it must have well-trained analysts. An analyst who’s training is lacking rigor makes mistakes, and they can be expensive mistakes. We’ve seen unnecessary delays in production or in the release of final products—and the problem was that the samples weren’t run correctly. There is nothing more frustrating than the plant sitting idle because an analyst gave an erroneous or negative reading. With solid training, mistakes can still happen occasionally, but they are rare.
Excellence in quality control requires that all specifications are thoroughly vetted, scientifically sound and meaningful. Do the specifications really reflect what’s going on with the project? It takes smart, experienced people to make that determination.
Equipment also plays a role. We are only as good as our equipment, and that equipment is only optimally deployed if it is properly calibrated and maintained. In our QC labs we have a strong preference for equipment manufactured by one vendor, just as Southwest Airlines does. For all their routes they use the same plane with the same parts, same training, and same maintenance schedule. That allows them to run the most efficient airline in the world. By using one vendor’s instruments, we can do preventive maintenance more easily and quickly than having to deal with multiple vendor service departments. It allows us to plan ahead. If one HPLC is temporarily idled for maintenance, there’s another HPLC next to it that we can use without project interruption.
Instruments are our lifeblood. We have found over the years that our instrument up time is significantly greater than that of most laboratories.