The difference between sanitary and hygienic is like comparing milk chocolate to dark chocolate. Dark chocolate has a higher percentage of cocoa; hygienic systems are a higher grade of sanitary. Many professionals use the two terms interchangeably, but the difference is significant — ask any chocolate lover. Hygienic process systems must follow more strict fabrication, inspection and documentation requirements.
Surface finish and materials of construction traceability are the most important aspects of hygienic design. It is easy to mistake these as fabrication concerns, but hygienic process systems require carefully designed process equipment and meticulously designed quality assurance (QA) procedures. The standards these systems must follow are clear, but there is no exact recipe with step-by-step procedures for proper integration, sourcing and handling of equipment.
Preparing a perfect hygienic process system
All successful chefs expertly pursue an inspiring vision with a well-developed recipe that considers resources, quality and timing. Adapt the options below to your specific situation to create a hygienic process system that will pass validation and manufacture safe product for many years.
- (2+) Cups of coffee
- (1) Team of experienced sanitary process engineers
- (1+) Quality assurance expert(s) who understand hygienic requirements
- (All) Applicable standards, including:
- ASME BPE, FDA regulations, GMP practices
- (1+) CWI weld inspector
- (1+) Clean-in-place (CIP) system
- (All) Highly polished internal surfaces
- (Many) Material Tracking Reports (MTR) and Certificates of Conformance (COC)
- (Many) Well-documented procedures approved by internal and external QA experts
- (1+) 3D models
- (3 to 5 sets of) peer-reviewed and client-reviewed design plans
- (All) Traceability documentation
Step 1: Avoid Hell’s Kitchen with smart procedure design
Pour your coffee and get ready to plan. Every hygienic project begins with a careful review of applicable standards and the development of QA procedures during the design phase. From day one, your design team needs to address how to ensure quality on every aspect of your project.
Every person that encounters the materials, parts, design or fabrication of the system must be considered. What are the procedures at every point from piping and instrumentation diagram (PI&D) development (e.g., who verifies drawings against standards?) to receiving (e.g., what is the procedure for handling parts and materials when they arrive for fabrication?). Each procedure should consider who is responsible for keeping it sanitary. All steps must also be audited by a QA specialist.
This effort will culminate in a customized user requirement specification (URS). This document outlines all the requirements for procuring equipment and parts and is the Bible for designing and building a system that will pass qualifications. The URS defines a clear purpose for the equipment — critical specifications like capacity, output and speed, and quality standards. It also defines which materials of construction are allowed, surface finish standards, sanitary valve types and applicable documentation that needs to be provided by each vendor.
Step 2: Preparing the main course
Technical design can proceed once you have your URS document, procedures and QA program fully developed. It is important to separate essential technical specifications with ancillary features up-front. The strict quality standards for hygienic systems will create hard design choices and knowing what is optional versus essential will be important during design optimization.
Hygienic design is like normal process design but more detailed. It has to meet — and be documented to — ASME BPE standards. For example, not only does piping need to meet all the usual good manufacturing practices (GMP), but every length of pipe must be thoroughly checked for:
- Correct slope tolerances
- No dead legs
- Correct minimum distances
- Proper ability to drain
- Acceptable materials of construction (MOC)
- Approved methods of fabrication (e.g., fully
- welded. No tri-clamps can be used here!)
- Proper internal surface finish
- Typical QA design parameters
All QA measures that should be followed during fabrication need to be documented during design. At the end of the design phase, all documents should be validated with the URS.
Designing for cleanability is another major focus with any hygienic mixing system. When physical designs are being established, how the system will be cleaned must also be planned for and engineered. For example, pipe size matters during washout flushing. Achieving the correct Reynolds number, pressure and turbulence to remove all contaminates is harder the larger the pipe diameter gets. Designing pipes that don’t require massive pressure and temperature inputs to clean is important for both cost and system integrity.
Do maintenance personnel have easy access to test, clean and maintain all equipment? Hard-to-access equipment is likely to be ignored or miss servicing. How will instruments be calibrated and cleaned? What procedures should maintenance personnel follow to ensure a broken temperature sensor or a mis-calibrated flowmeter is detected and reported?
All equipment and instrumentation specified during design must fit the application and meet all sanitary requirements. Even the smallest valve matters to overall system sanitation. Inline components, equipment in contact with product, pressure and temperature sensors, etc., must meet stringent sanitary requirements. Diaphragm valves and a few specific types of pumps and agitators must be used in hygienic applications. Pipes must be fully welded, thereby minimizing the use of mechanical connections. The requirements leave limited choices during system design and purchasing to pass validation.
Step 3: Know the source of your ingredients
The fastest way to fail hygienic mixing system validation is to use inadequately sourced or documented materials. Materials of construction (MOC) matter more than anything else for passing validation and achieving hygiene, whether raw metal or highly machined preassembled parts.
Everything sourced for the system needs a material tracking report (MTR) with a certificate of conformance (COC). Chemical composition details must be included and verified upon receipt to ensure materials are qualified, tested and eligible for use in the system. Carefully log all documentation upon receipt for reference and validation throughout the project.
Vigilant handling is important from this step forward. Detailed procedures should be enforced, audited and documented. Everything from supplier shipment preparation through final system startup should be covered. Individuals responsible for each step need to log proper handling and sign off every time the procedure is used. Auditors need to verify MTRs and procedures are present and correct. Laying out these exact procedures during the design and planning stage ensures they match the intent of your URS and are not rushed at the end.
Step 4: Use clean, polished prep surfaces
Internal surface finish is important on any sanitary system, but on a hygienic project it is essential. What is your plan for achieving proper surface finish for all piping and equipment?
This may take more time and money than you expect. Even the tiniest micro-crack can harbor bacteria for products with the right molecular makeup. Make sure the system design and project timeline allow for proper polishing time and internal piping inspection, and that the system has proper slope and drainage ratios as outlined by American Society of Mechanical Engineers Bioprocessing Equipment (ASME BPE). Even the methodology used to polish internals should be well-documented and included in the procedure design.
Step 5: Always be checking the recipe
Plan for regular design reviews with all engineering and QA professionals during development, before final sign-off and at the conclusion of design. These reviews should always go over your design basis, technical design and planned procedure documents.
The design basis and technical design should be checked against the URS, materials of construction requirements and all relevant standards at each meeting. Systems evolve and mistakes develop if not carefully reviewed. Checklists, validation documents and individual completion sign-offs are optimal for making validation easier at project completion.
Reviews should ideally have all project stakeholders involved — the engineering team, quality assurance team, fabrication quality assurance team (if this is different) and project managers should be included at minimum. Best practice includes at least two peer review audits of the design with engineers outside the project.
At least three thorough audit reviews are best practice for documentation and are key to eliminating mistakes. Documentation should include equipment and material list with brands, serial numbers, types and properties. P&IDs should show slope ratios and QA forms must have details such as handler name, percentage of oxygen used during welding and internal finish verification.
Example from the test kitchen
More requirements and detailed procedures may make it seem like a hygienic process system could take years to design and build, but thorough documentation often expedites the process. A project that works toward validation from day one will be designed and implemented much faster than a project that uses validation as an end-procedure.
EPIC Process Systems recently designed a large hygienic process system for an injectable product. This system was part of a multibillion-dollar manufacturing expansion and is composed of eight hygienic mixing modules and two sanitary solvent recovery systems. The project was completed in 11 months, from design and installation through validation.
One major challenge with this project was fitting the system into a relatively tight footprint. Our focus was on maintaining accessibility and maintenance access. To solve this problem, detailed 3D models were designed and reviewed with the end client until the optimal arrangement was achieved. This procedure allowed for both GMP maintainability and fit within the allotted space. Since the engineering was completed well in advance of system fabrication, both time and re-work expenses were eliminated.
Detailed procedures that align with ASME BPE were used throughout the project. Beyond MTRs and COC records, welding procedure specifications (WPS), welder performance qualification (WPQ) records and other documentation were specified early on. These logs also tracked heat numbers at every phase and kept meticulous up-to-date weld maps, which helped validate proper fabrication methods throughout the project.
Every hygienic process system project is different. Your product’s chemical composition and manufacturing process affect the design standards the system must meet. However, the need for a thorough design process that starts with quality assurance and validation remains constant. Focusing on material sourcing and traceability is the most important part of any hygienic project.
A good hygienic design must balance meeting ASME BPE with other requirements. It must source the best parts and materials with a design for longevity and maintainability. Like dark chocolate, the level of higher sanitary design standard achieved by truly hygienic systems is not necessary for every situation. There are plenty of sanitary systems that don’t require hygienic design, however, many manufacturers opt for well-designed systems that protect customers in the long-run. Taking the time to design both the system and procedures correctly up-front is critical and necessary to long-term project success.
Jeff Koenigs, P.E., is a principal project manager at EPIC Process Systems. He has more than 25 years of experience in cGMPprocess system design, fabrication, and qualification.He specializes in managing Title 21 CFR Part 210 and 211 and Part 11 projects and managing URS/TS/FAT/IQ/QQ protocol development and execution. Visit EPIC’s hygienic process system design and fabrication webpage to learn more about their capabilities in this area: www.epicmodularprocess.com/sanitary-process-systems.