Washers and Sterilizers: Design, Manufacturing & Qualification Documentation
Non-GMP or GMP Washers and Sterilizers: How to Choose article is featured in the November/December 2015 issue of Pharmaceutical Engineering®.
This three part series will present the standards and guidelines typically used by manufacturers to design and build GMP washers and sterilizers. It describes the characteristics that differentiate GMP from regular laboratory equipment. Part three covers the design, manufacturing and qualification documentation needed on GMP washers and sterilizers. The series also wraps up with helping you decide which option is best for your facility.
Washers and sterilizers used in research facilities are typically supplied with sufficient documentation to assist with uncrating, installation, operation, and maintenance of the equipment. General layout drawings with dimensions and information on utilities may be sent for approval prior to manufacture. Occasionally, some users may want to attend a factory approval test (FAT), which will generate the need for a dedicated FAT protocol. Good laboratory practices followed in some research facilities may dictate the need for protocols to execute installation and operation qualifications.
On the other hand, regulated industries such as drug manufacturers require a lot more documentation to support the validation process. In this area, various guidelines are available and several companies have developed their own checklists. The Parenteral Drug Association (PDA) provides some guidance in Appendix B of its Technical Report 48.9 But again, BPE offers a good summary of the typical requirements in section GR-5. Not all the requirements apply to washers or sterilizers. The following is a list of those that are commonly seen:
- Complete manufacturing and certification documentation for pressure vessels: ASME, pressure equipment directive (PED), etc.
- Material test reports and heat number/code traceable to test report
- Welding documentation for pressure vessels, tanks, and piping
- Welding procedure specifications (WPSs) and procedure qualification records (PQRs)
- Welder performance qualifications (WPQs) and welding operator performance qualifications (WOPQs)
- Examiner qualifications
- Weld maps and weld logs
- Weld examination and inspection logs, coupon logs
- Purge gas certifications
- Testing and examination documentation
- Passivation reports
- Electropolishing documentation
- Surface finish report
- Spray system testing (also referred to as “coverage test”)
- Pressure testing
- Slope check documentation
- Calibration verification documentation
- Heat numbers of components must be identified, documented, and fully traceable to the installed system
- Calibration reports
- Factory acceptance test protocol and report
- Certificates of compliance for instrumentation
- Control system documentation
- User requirement specifications (URS)
- Functional requirement specifications (FRS)
- Software history
- Hardware design specifications (HDS)
- Software specifications and test reports
- Loop diagrams
- Equipment arrangement diagrams (layout drawings)
- Traceability matrix
And the list goes on…
So why are pharmaceutical-grade washers and sterilizers so much more expensive than laboratory units? The higher cost can be partly attributed to a more expensive mechanical design. Hygienic-designed components such as valves, pumps, instrumentation, sensors, and so on can be several times more expensive than their standard counterparts. The additional time required for welding and polishing to obtain the acceptable surface finish, the additional process monitoring systems, and extensive documentation also contribute to the increased cost. Another factor is that laboratory washers and sterilizers are typically standard products that can be mass-produced. Pharmaceutical-grade equipment is generally customized and made to order. This also explains why the manufacturing process for pharmaceutical-grade units is longer than that of laboratory units.
Can an existing laboratory unit be upgraded to meet GMP requirements? It is definitely possible to upgrade some components (such as the control system, piping, and instrumentation) and add some process monitoring systems. However, that is not possible for all components. Replacing a washer chamber made of stainless steel 304 with one made of stainless steel 316, for example, may prove very difficult, if not impossible. Furthermore, obtaining necessary manufacturing documentation for critical components is likely to be a challenge.
Table 1 provides a condensed comparison between pharmaceutical-grade washers or sterilizers and standard laboratory units used in research facilities. It also includes a description of the typical applications for each type of equipment. Other good references include Section 3.4 and Appendix A of the PDA Technical Report (TR) 48.9 This includes design considerations of steam sterilizers.
Which One Should I Choose?
This is a common question that arises when washing and steam sterilization equipment is being selected for a facility. The most important first step is to develop a URS to define the intended use and then develop detailed design requirements according to the facility, local codes, or other requirements. Many times, units are over- or underspecified based on their intended use, and this can lead to increased costs or performance issues. A steam sterilizer used for waste disposal may not need all the features of a unit used for pharmaceutical-manufacturing area components. A laboratory washer may be able to provide the cleaning quality required without the expense of a pharmaceutical-grade unit. A pharmaceutical-grade unit can be as much as three to four times more expensive than the standard laboratory version and is more costly to validate and maintain, so having a well-defined unit is critical to the project and ongoing support cost.
In general, pharmaceutical-grade equipment is required in drug manufacturing facilities when used to clean or sterilize surfaces, parts, or components that are in contact with the drug product during its manufacturing process. For example, the following items are typically processed in pharmaceutical-grade equipment:
- Change parts from drug-manufacturing filling lines such as pumps, needles, and transfer hoses
- Components from manufacturing equipment such as blenders, mixers, blister machines, tablet presses/counters, and filter housings
- Various containers, drums, and trays that come in contact with the manufacturing ingredients or the final drug product itself
- Vials, ampoules
- Process media
Laboratory-grade washers and sterilizers are generally used for research applications and decontamination of waste. Here are a few examples:
- Glass- and plastic ware used in research or hospital laboratories
- Animal surgery and cage processing
- Laboratory media preparation
- Deactivation of biologically contaminated waste from laboratory research or biologic and vaccine drug manufacturing processes.
Finally, a previously owned unit or unit procured from another area may not have the required features or cycles to meet pharmaceutical-manufacturing process needs. In this case, the upgrades, documentation, and qualification may cost more than the unit itself. PDA TR 48 provides comprehensive system design guidance in section 4.0 for steam sterilizers,9 and this methodology can be used for other types of equipment.
Pharmaceutical-grade washers and sterilizers used in regulated pharmaceutical-manufacturing facilities are significantly different from those used in the research industry. The requirements for these applications directly affect the mechanical design of the equipment, the process monitoring systems that need to be provided, the control system and associated software, and, most importantly, the documentation required to ensure a smooth validation process. As a result, pharmaceutical-grade systems are more expensive and take more time to procure. In general, this grade of equipment is required only if the items to be processed are in contact with the drug product that is being manufactured. It is recommended to conduct a risk assessment to help determine if a pharmaceutical-grade washer or sterilizer is really required.
by Marcel Dion, Director of Marketing for Washing and Steam Sterilization Systems in the Life Sciences Division of STERIS Corporation and Matt Hofacre, responsible for global applications team with STERIS Life Sciences Capital Equipment Solutions
Missed part one and two? Catch up:
9. Parenteral Drug Association. “Technical Report 48: Moist Heat Sterilization Systems, Design, Commissioning, Qualification, and Maintenance.” 2010. https://store.pda.org/TableOfContents/TR4810_TOC.pdf.