At any manufacturing organization, but even more so at Contract Development & Manufacturing Organizations (CDMOs) that produces drug substances, it’s essential that the operation of critical utilities is monitored regularly to ensure reliability of the process equipment, and ultimately the safety and efficacy of drugs that are developed.
This is addressed through preventive maintenance, a system of procedures and series of tests performed on production equipment to ensure it runs reliably during the manufacturing process.
It makes good business sense to ensure that all critical systems are ago, after all, CDMOs can only make New Chemical Entities (NCEs) and Active Pharmaceutical Ingredients (APIs) if the equipment is running. Malfunctioning machines not only cause companies to lose valuable revenue and time, but it also costs tens of thousands of dollars when they break — and could result in batches of product that could be compromised or produced out of specification.
The process of properly maintaining vital utility systems is also a key facet of business operations, since it is an area that the FDA inspects. Companies involved in manufacturing are noticing that during inspections the FDA no longer just looks at the equipment used in production lines, but now also inspects the manufacturing environment where they are used, especially in terms of critical utilities like water systems or air systems, etc.
When the FDA comes in for an inspection, it generally wants to see three things:
They will closely analyze records of preventative maintenance programs in order to determine if companies are keeping their word and doing what they claim.
When we refer to utility systems, they can really be classified into four key areas:
Electric Power is used to run all of the facilities and process equipment, which is managed by a series of Motor Control Centers (MCC) and distribution systems. The compressed air utility is generated by a group of air compressors which provides power to pneumatic equipment, tools, instrumentation and provides breathing air as Personal Protective Equipment.
The Purified Water System and the Nitrogen Distribution system are parts of the second group of utilities which are an integral part of the manufacturing operations. The Purified Water System purifies the potable water by means of cation exchange resin, softeners, reverse osmosis filters, carbon beds, inline filters and an ultraviolet treatment device. Quality of the purified water is monitored to ensure that it is within appropriate levels. The Nitrogen Distribution is the system that consists of a Bulk Nitrogen Tank, a distribution loop and pressure regulators. The Nitrogen system is used for inerting process equipment during manufacturing.
The third group of thermal energy utilities consists of steam, ambient water and chilled water. These are used to provide heating or cooling to process equipment. These utilities are tied to the process equipment and managed according to manufacturing procedures.
Within these key utility systems operations, there can be lots of complexity and moving parts, so what is the best way for CDMOs to ensure that systems are maintained efficiently?
Below are four key guidelines.
Preventative maintenance of utility systems is intended to help CDMOs manage risk, reduce corrective repairs, prolong the life of equipment and help to meet FDA guidelines, but most importantly, a focused commitment to going above and beyond to ensure that all systems are in tip-top shape is what separates the really good CDMOs from the average ones.