GMP Production Facilities Equipment Change Control – Part 1 of 2

Figuring Out What Kind of Utility/IT the Equipment Needs

This is the first and most vital stage of ECC. In order to make an informed decision about purchasing the necessary equipment, you must first define its specific purposes. The phrase “before you purchase” is stressed here since the cost of the equipment and the time it takes to commission it can both treble if utility improvements and other associated equipment purchases are required to assure the appropriate operation of the equipment you plan to acquire.

You can get this information from the manufacturer or the owner’s handbook. The manufacturer is usually able to supply specification files outlining the equipment’s needs in terms of power, ventilation, heat removal, water purity, gas purity, steam purity, drainage, and explosion proofing. Equipment used in Good Manufacturing Practice (GMP) production will have certain construction materials that must be included on the specification sheet. When the machinery is working at full capacity, it is essential to figure out the utility demands. If you need assistance compiling a comprehensive list, the engineers and mechanics at your organization can be of tremendous assistance.

Connections to GMP servers and networks are essential but often neglected. These days, it’s expected for instruments to have outputs compatible with GMP servers. This is just one piece of the puzzle that helps keep digital files trustworthy. The purchase of old or refurbished equipment that was initially intended to function alone, without the need for a network, might provide a number of challenges. Even if the equipment is unable to establish connections to trusted networks, data integrity compliance remains intact. It raises compliance concerns that necessitate action on the part of your company.

Conducting a Pre-Installation Assessment, Utility Evaluation & Addressing Problems

Electric Utility

The installation location of your new equipment is necessary so that facilities management can check the availability of an electrical utility that can support it.  Equipment purchasers frequently lack complete information on the final installation location. “The equipment will be placed in one of the cleanrooms,” is a usual response. I see an issue there. It’s likely that the kind of power outlets and quantity of connections in each cleanroom is different.

When installing equipment with high power consumption, your circuit panel needs to be checked to make sure it is receiving adequate power from the correct source and is properly balanced. In a shared-neutral system, the entire amperage demands of the electrical gear are split across the number of active electrical circuits. The individual buying the equipment is clearly not the best person to make this call. An integral part of effective change management is the following: It is essential to bring in subject matter specialists (such as an electrician or capable facilities technician) to perform technical assessments of key factors.

Emergency Generators Capacity

Typically, emergency generators are placed during a building’s construction phase, and their sizing is determined solely by the appliances that were present or anticipated to be present at that time. Evaluate the emergency generator’s capacity in relation to the present load if connecting the new piece of equipment to an electric power circuit is crucial and the power requirements are high.

It’s not a good idea to depend simply on the architect’s as-built drawings, as it’s common for new pieces of machinery and electrical outlets to be installed without the as-builts being updated to reflect the changes. Electrical experts can place a meter at the building’s power supply and plot power consumption over the course of a month or two. The capacity of the emergency generator may then be checked against the power requirements of the new equipment.

I ran into this issue in a GMP manufacturing plant, where the CDMO had installed five big stability chambers in the quality control laboratory for use in GMP stability studies for a sponsor. All that was needed to be done to plug in the five stability chambers was to plug in the cords, as the lab had an abundant 220-volt power supply and each outlet was marked as e-power, indicating that it was linked to emergency power. A 10-hour power outage occurred in the middle of the night, few months after the stability chambers were installed, and affected the whole city block where the CDMO was located. Workers in quality assurance noticed that all five of the new chambers had stopped functioning the next morning.

An inspection revealed that the electrical panel supplying the outlets with 220 volts had been moved to a non-e-powered circuit during the renovation of the neighboring laboratory. The CDMO had to notify all impacted sponsors because stability samples kept in these chambers had been compromised. An essential takeaway from this is to not put any stock in what is written on the plugs of electrical outlets. Be sure to have an electrician inspect the wiring before you plug in any equipment. 

Removing Solvent Exhaust

Cleanrooms used in the pharmaceutical and biopharmaceutical industries must be completely free of any potentially harmful vapors. The dangers connected to exhausting solvents include fire or explosion and the ensuing contamination of production, storage, and cleanroom areas by smoke or other compounds produced by the fire. Solvents must be vented out of the building using ducting that is fireproof and does not corrode.

Ducting made of stainless steel covered with fluoropolymer can be more efficient and safer than using copper or plastic pipes. The use of fluoropolymer-coated stainless-steel duct, rather than a pipe, is advantageous in a number of settings, including cleanroom exhaust, fume hoods, snorkels, walk-in reactor enclosures, and biological safety cabinets (BSCs) used to store compounds with corrosive gases. For information on the materials that must be used to build ducting in your location, see NFPA Standard 318, as well as any other applicable NFPA standards.

Temperature Control & Heat Removal

Heat from production equipment can affect temperature management in GMP production suites, a factor that is often overlooked. If the space is not set up with insulated ducting to dissipate heat, ovens used for drying products and pan coaters used for tablet coating might raise the ambient temperature. Consider this, since the manufacturing equipment’s heat might make it challenging for the HVAC to keep to its temperature targets and stay within its certified operating parameters.

Using chilled water or dedicated chillers operating with specific refrigerants is necessary for the operation of certain industrial equipment, such as big production spray dryers. Cleanrooms sometimes require the installation of process pipes encased in non-shedding insulation to transport chilled water to the point of usage. In order to install process piping, cleanrooms must be cleared so that pipes may be drilled into the walls and refrigerant leaks can be checked.

Recently, a similar issue occurred between a sponsor and its CDMO. The sponsor had its preferred CDMO produce its solid oral medication product exclusively. A very big spray dryer of pharmaceutical quality was ordered by the CDMO, and the sponsor was notified of this. This spray dryer would be used for the Phase 3 product. Once the equipment arrived, the engineering team determined the spray dryer needed a powerful chiller that wasn’t made by the spray dryer’s manufacturer. There was a nine-month wait time for delivery because a custom chiller had to be made to order.

Additionally, a cement pad had to be poured outside the cleanroom for the chiller’s placement, 10-inch holes were bored into the cleanroom walls for pipe penetrations to and from the chiller, and a component of the HVAC validation was rendered null and void as a result of the installation. The huge spray dryer’s installation, together with the chiller and process piping, took twice as long as expected and pushed back the sponsor’s Phase 3 supply production schedule. The moral of the tale is that it is in everyone’s best interest to do as much research as possible before making any major purchases of equipment to ensure that all parties involved are satisfied and that corporate goals are met on time. 

Water Grades & Usage

Water for injection (WFI), pure steam, water for hemodialysis, and purified water are the four most common grades of water used in the pharmaceutical industry, and all four grades of water are frequently generated and utilized on-site at production facilities. Water pressure, flow rate, and temperature specifications for new machinery must be verified in advance (as applicable). Some machines, like an autoclave, need both RO/DI water (indirectly) and clean steam (directly), as RO/DI water is often used as the feed water for clean steam generators. Summarize the consumption rates of all equipment utilizing clean steam and those using just RO/DI before deciding whether to construct a new autoclave or upgrade an existing one to a bigger capacity.

Generation & Distribution of Gases

Production equipment, spray drying applications, container head space, fermentation, extraction, and purification all make use of high-purity gases in the pharmaceutical industry. Common examples include nitrogen, oxygen, argon, carbon dioxide, clean compressed air, and others. Several different types of utilities may be used to produce gases within the manufacturing plant and pipe them to various cleanrooms. 

Some establishments, alternatively, employ large, fixed tanks with capacities of 6,000 liters or more, outfitted with telemetry equipment that notifies service providers when the gas supply is running low. An evaluation of the utility’s capability to satisfy the needs of all connected equipment is necessary whenever new equipment needing one or more clean gases is introduced.

It’s crucial to evaluate not just the gas-producing equipment and storage tank capacity, but also the piping’s length and inside diameter. For instance, if the distribution piping’s internal diameter is really small, no clean compressed air system capacity can meet the needs of a newly installed piece of machinery. The system’s capacity to keep up with demand may be determined by calculating the flow rate, pressure, and volume requirements of each piece of installed equipment.

Drain Systems

The quality of a drain depends on its location and design. Some are made to divert liquids to regular garbage collection, while others need further processing before they can be dumped in the city’s garbage. The position of the new apparatus presents similar challenges. Is there already a functioning drain system with floor connections in the area close to where we plan to put the machinery? Be ready to invest huge money and plan for extensive downtime to trench new drains if the room does not have drains or has an improper sort of drain. Be aware that new drainage may necessitate securing city permission, depending on your location.

Protection Against Explosion & Fire

Cleanrooms and other machinery used in the pharmaceutical industry are classified according to the degree of explosion danger they pose. In North America, the “class, division” approach is used as the foundation for the categorization of hazardous areas in electrical codes and regulations. There are three types of places, and two types of divisions. The danger of fire or explosion is classified into a number of different categories, depending on the type of hazard and the explosive properties of the item in question.

Keeping cleanrooms safe from explosions requires isolating the room’s electrical outlets, lights, and heat/spark sources to prevent them from coming into contact with dust, moisture/vapors, or other pollutants. As a bonus, this separation can prevent hazardous circumstances like outgassing, heat, arcing, air pressure leaks, and electromagnetic interference from jeopardizing the process’s safety and reliability. It is wise to consult with a certified industrial electrician or specialist to evaluate the present controls and determine which ones need to be strengthened in cleanrooms that provide an explosive risk due to the materials that will be processed.

This is extremely critical for industrial procedures that involve the movement of combustible chemicals and solvents from one machine to another without the use of physical containment or isolators (i.e., reliance on just the cleanroom infrastructure). To further ensure the safety of the process, the facilities, and the employees, some production equipment, such as specialist computers, must be certified to fulfill the standards of the particular class and division.

Servers and Networks Integration

Data integrity and the principles of ALCOA (attributable, legible, contemporaneous, original, accurate) can only be guaranteed if the organization defines and enforces Critical to Quality Attributes (CQAs) for equipment owners and IT that require data to be automatically sent from equipment to servers, backed up on a schedule, and periodically tested for retrieval of data and metadata. This prerequisite is frequently disregarded in the process of setting up new equipment.

When connecting to GMP networks, a formal change control process must include an ALCOA evaluation for any new or relocated equipment. This is crucial when new network data cabling must be built to handle the expensive new gadgets. The network design must be able to track out which pieces of machinery are linked to which IDs of data ports in cleanrooms, and then forward the machinery’s data to safe and legally compliant servers.

The FDA has issued warning letters about computer networks due to insufficient validation documentation, including the lack of up-to-date design documentation and wiring/network diagrams that properly identify each computer and device in the network. Given the dynamic nature of networks, revision control is essential for keeping top-to-bottom diagrams up-to-date with actual network configurations (i.e., formal change control). GxP computer systems and network validation, according to the World Health Organization’s (WHO) guidelines, should account for the system’s physical and logical architecture and map out the pertinent workflows and data flows.

Takeaways & Conclusion

The majority consider equipment change control to be little more than a formality to satisfy quality assurance. Contrary to this, the reality is far different. Serious threats to GMP operations arise from a lack of preparation, an inadequate understanding of the utility demands of all linked equipment, and a lack of adequate utility capacity.

Collaboration between engineering, manufacturing, mechanical/facilities and external contractors can help you anticipate and overcome obstacles during the installation of new equipment. The influence of new equipment on utility validations, new equipment validation, assessment of turnover packages and validation reports, and the change control effectiveness check will all be covered in the next installment of this series.