Biological buffers (Hepes, Mops, Tris, etc) are commonly used in bio-manufacturing processes both upstream and downstream, as they offer better pH control in many instances, and can help protect valuable proteins. However, there are no compendial grade biological buffers - except for Tromethamine (Tris) - as monographs for these don't exist. Many of these products are also not available under cGMP - often as they have been produced for a very long time and originally introduced to the market as research grade materials. Frequently, they are made in manufactuirng plants that were not constructed to meet GMP guidelines - guidelines that did not exist at the time of their commissioning. It may be difficult to retroactively upgrade these facilities to full GMP and still produce a product that can be offered economically to the intended market.
What shall we do? In an instance such as this, under our Enhanced Quality Profile program, we look to upgrade the product as far as we can to full GMP for raw materials (not APIs) used in biopharm manufacturing. This makes sense for the intended application. Biological Buffers fall into our Elite tier. We want to upgrade the quality systems around that product as described in the Elite description (following link above) - and in particular be able to offer the level of change control and change notification described in the table. This is triggered by participation in our Change Control Notification Program.
What is tangibly different for a buffer under the Elite tier? Let's hit some of the highlights as described in Biological Buffers Quality System, and full details can be accessed via this link. The quality system has been modeled after those elements of Q7a that would be most germane to control of a raw material used in biomanufacturing. A major change is inclusion of these products in a Quality Management System with a Material Review Board and a Corrective and Preventative Action (CAPA) program. All product is released by Quality Assurance after review of complete batch records and there is an internal audit process.
What else? Training programs for all personnel were instituted and documented. Ditto, for institution of calibration and maintenance programs for critical equipment. We instituted a validated electronic document control system. Materials Management (supply chain) instituted ID testing on incoming raws, upgraded specifications, and established specification and supply agreements with key suppliers. Tighter process controls were adopted. Cleaning verification was performed and retroactive review of equipment was documented. All new equipment goes through an IQ/OQ process. Quality Agreements and Change Notification are available.
Better controls are in place and better communication to the customer is available. Thus, you can be assured that a product you've qualified is fit for purpose.