An Ounce of Prevention Ensures Reliable Utility Systems in Drug Manufacturing
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.
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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.
Regulatory Oversight of Utility Systems
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:
- Your training records
- Customer complaints
- Preventative maintenance programs
They will closely analyze records of preventative maintenance programs in order to determine if companies are keeping their word and doing what they claim.
Categories of Utility Systems
When we refer to utility systems, they can really be classified into four key areas:
- Power equipment
- Production equipment
- Thermal energy management
- Treatment of by-products
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.
- Make sure dedicated teams are in place. While a full-time maintenance team should be responsible for overall utility system maintenance, specific roles are responsible for maintenance within each core category. And, ultimately, the Quality Assurance (QA) team should be responsible for auditing and inspections and ensuring all systems meet quality systems and maintenance is fully documented.
- Build in redundancies. A good CDMO should expect to invest in back-up systems for 80 percent of the utility systems it operates. Of course, having a back-up boiler wouldn’t make sense financially, but for the majority of mission-critical equipment, it makes sense to have a back-up.
- Don’t rely on FDA for inspections alone. CDMOs should be adhering to a regular schedule of inspections – on a weekly, monthly and annual basis depending on the systems. Although the Original Equipment Manufacturers (OEMs) are also responsible for ensuring the health of their equipment, QA teams should do their own inspections and then work closely with the OEMs to make sure equipment that needs servicing is done so proactively.
- Perform annual shutdowns. Here at PCI Synthesis we have an annual shutdown of our operations to make sure our boiler and other major equipment can be serviced and inspected. While production is put on hold during this time, it’s really the only way to bring down the boiler and ensure that chemical batches are not compromised in the process.
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.