Reporting cGMP changes to the FDA

Reporting changes in your manufacturing process to the FDA can be jarring, and sometimes disastrous. Having to do these reports is something best avoided. But I’m not suggesting anything illegal.

Instead, I’ll present the (probably) ancient English phrase, “A stitch in time saves nine.” In other words, taking steps to make your pharmaceutical manufacturing process as hassel-free and controllable as possible prevents you from having to report changes once your product is in the marketplace.

I’ve watched the staff of regulatory affairs offices work unnecessary and long hours to report changes that would have been avoided if the drug product was developed properly. What steps can minimize these reporting needs? Because of the space consideration, I will mention couple of them:
Risk Assessment—All your quality assurance starts with assessment of risks. This is a science-based process, identifying material attributes and processes parameters that can affect your product’s quality. Risk assessment steps must start early in the pharmaceutical development process, and should be revisited as you learn more about your product’s attributes during development. Risk assessment tools identify and rank attributes that may impact quality, and this list will no doubt be refined and analyzed during development, to encompass better understanding and control of your manufacturing.

Quality by Design—This concept covers developing the manufacturing processes of your product (and the product itself) so they consistently attain quality attributes that you’ve already defined. You need to define product performance characteristics and critical quality attributes before you start manufacturing. This means understanding the characteristics of all your raw materials and the extent of variation of those materials, and the variations that could occur during the manufacturing process. Some of these quality attributes for oral solids include product purity level, dosage strength, drug release profile and stability. For drug substances, quality attributes would be particle size distribution and bulk density. This way, you can manage the product life cycle through effective monitoring of manufacturing (with far fewer surprises) and through continuous improvement.

Design Space—Part of quality by design, design space looks at the interactions of inputs, like raw material attributes and process parameters, that ensure final product quality. When establishing design space, you need to consider the effect of formulation component properties on manufacturing, scale-up issues, the effect of changing a manufacturing site on product quality, and interactions among these and any other variables. From design space, you can then devise a control strategy, to make sure your product is made consistently with a threshold of quality all the time. Your control strategy will address controlling raw materials and their impacts on manufacturing, controlling any operations that affect your final product quality (including drying effects on degradation, or the effect of particle size distribution on dissolution). You will establish design space, but it will have to be reviewed and approved by the FDA and other regulators.

These are all valuable individually, but together form a more seamless fabric which ideally should have any rifts that need stitching. But if they do, these concepts can help quickly identify a problem and may rectify it before your product reaches the market.

At Synergy Bioscience, you will have trusted advisors and partners who will help you with your medical product development from ideation to commercialization, by providing their unique perspectives and expertise in aspects such as Quality by Design, Design Space, Risk Assessment and others. Whether you are a virtual company or international pharmaceutical organization, we can help. Contact us to learn more about how your development and manufacturing activities could save nine stitches (or even more).