Engineering Considerations for the cGMP Manufacture of Hemp and Hemp Products: Page 3 of 3

March 11, 2020
Volume: 
3
Issue: 
2
Abstract / Synopsis: 

As the global hemp industry continues to mature, the rules and regulations that encompass the space are constantly evolving. Hemp businesses preparing for success and scaling for future growth have a variety of best practices to consider, but one set of regulations becoming increasingly important in the early stages is current good manufacturing practices (cGMPs or GMPs). GMPs are the rules and regulations that ensure the quality, safety, and efficacy of food or pharmaceutical products by addressing all aspects of the production process. GMP certification is becoming paramount for hemp extraction facilities looking to remain competitive and align with international industry standards. This column discusses some of the most important considerations involved in the GMP certification process.

Other Specific Requirements

There may be other requirements specific to your process or facility. As an example, many facilities will opt to keep conduit and piping behind walls to make it easier to clean the wall surfaces in the facility. However, some clients need access to piping for experimental changes. In this case, you may direct your designer to design the piping and conduit so that it is exposed within the room, yet held off the wall so that you can easily clean behind and around the piping and conduit to maintain your cGMP facility requirements.

A Word About HVAC

Your HVAC designer will be critical to the success of your cGMP facility. It is important to consider and keep in mind what your HVAC system can and cannot do (9).   

What HVAC Can’t Do

HVAC cannot clean the surfaces of a contaminated room or equipment. The SOPs defined by the owner should specifically cover cleaning protocols. HVAC cannot compensate for workers who do not follow procedures. Ensuring that staff is trained and following SOPs is critical to the success of your cGMP facility and is the owner’s responsibility. HVAC cannot be left unmaintained. If not maintained, the HVAC systems may not adequately meet your cGMP requirements.

What HVAC Can Do

HVAC can control airborne contaminants through proper air filtration. There are numerous levels of air filtration, generally stated on the minimum efficiency reporting value (MERV) measurement scale. In commercial applications, filtration will generally range from a typical MERV 8—such as what would normally be utilized in a basic residence—through MERV 20, which will meet the requirements of a cleanroom. High efficiency particulate air (HEPA) filters, which will remove 99.97% of particles whose diameter is greater than .3 μm, fall into the range of MERV 17 through MERV 20. HEPA filters are generally utilized in cleanrooms, among other applications. The air filtration level needs to be considered when selecting the HVAC systems, as the higher the MERV rating, the more air restriction there will be, so the fans need to be sized to overcome this static pressure, both with an unloaded and loaded filter. Prefilters are generally utilized prior to the HEPA filters to capture the larger particles, so as to not unnecessarily load the HEPA filter. This allows the owner to change the prefilter often (which are generally a lower cost item than the HEPA filters), and the HEPA filter less often. Pressure gauges and simple alarms can be helpful in alerting the facility’s maintenance crew that the filters need to be changed. Changing the filters at regular intervals is critical in meeting cGMP because an overly loaded filter will affect particulate capture rates and air change rates within the room, potentially causing the facility to fall out of spec. 

HVAC can maintain room pressure differential requirements (delta P or ΔP). Proper air cascades are critical in ensuring that air flows from clean to dirty spaces, and not the other way around. Areas that must remain cleaner than surrounding areas must be kept under positive pressurization with respect to the surrounding area. This can be done in various ways. Oftentimes an airlock, sometimes referred to as a vestibule, is utilized in the entrance to the cleanroom. This is a separate room with one door opening into the main corridor and another into the cleanroom. The doors are controlled so that they cannot be opened at the same time (either by interlocks or simply by SOP). Fan filter units can be a low cost way to ensure that the pressure cascades between the main corridor, airlock, and clean room are appropriately maintained, and with the proper filtration to protect the cleanroom.

HVAC can maintain room temperature and humidity. Temperature and humidity are controlled via air handlers with cooling coils and reheat coils. There are other methods to control temperature and humidity, and your mechanical engineer can determine the best type of equipment for your application. Note that while your engineer can design and select the proper equipment to meet your temperature and humidity needs, it is the owner’s responsibility to determine the target temperature and humidity levels, as well as the acceptable range. This will vary depending on what the process needs are. Facility owners will often set a very tight temperature and humidity range. Be cautious: more stringent than required temperature and humidity requirements can result in your engineer selecting an expensive HVAC system to meet the requirements, oversizing your HVAC system, and resulting in higher than necessary utility costs to run the equipment. Be sure to select a reasonable temperature and humidity range for what your process requires.

Closing Remarks

For any project—but especially a cGMP facility­—it is incredibly important that the owner engage their internal team that will run the facility, a GMP consultant, architect, and engineering team early and often. Proper coordination is key to success. All team members must know their roles and responsibilities within the facility design process, and ultimately it is the owner’s responsibility to be sure that everything is covered in order to obtain and maintain the desired cGMP certifications.

References: 
  1. A. Gasparro, The Wall Street Journal, January 9, 2020,  https://www.wsj.com/articles/cloudy-regulation-slows-cbds-seep-into-food-and-drinks-11578574807.
  2. M. Gauthier, HealthMJ, January 2020, https://www.healthmj.com/cbd/hemp-cbd-bubble-prices-market-growth/.
  3. https://international-cdp.com/.
  4. V. Rees, European Pharmaceutical Review, August 2019, https://www.europeanpharmaceuticalreview.com/article/96609/cannabinoids-in-pharma-series-cannabinoids-on-the-market-today.
  5. https://www.gwpharm.com/healthcare-professionals/research/cannabinoid-compounds.
  6. https://www.rhizosciences.com/gxp-good-cannabis-practices/gap-good-agricultural-practice/.
  7. U.S. Food and Drug Administration, Current Good Manufacturing Practices (CGMPs) for Food and Dietary Supplements, https://www.fda.gov/food/current-good-manufacturing-practices-cgmps-food-and-dietary-supplements.
  8. Electronic Code of Federal Regulations, https://www.ecfr.gov/cgi-bin/text-idx?SID=3f7125891958b3eb9380856f26065b5c&mc=true&node=pt21.2.117&rgn=div5.
  9. A. Bhatia, HVAC Design for Pharmaceutical Facilities (Continuing Education and Development, Inc., Stony Point, New York) https://www.cedengineering.com/userfiles/HVAC%20Design%20for%20Pharmaceutical%20Facilities.pdf.
  10. https://www.mecart-cleanrooms.com/learning-center/cleanroom-classifications-iso-8-iso-7-iso-6-iso-5/.

About the Columnists

Laura J. Breit, PE, is the founder and owner of Oregon-based firms Root Engineers and Cole-Breit Engineering. She is a professional mechanical engineer specializing in the design of HVAC, plumbing, and process systems for the cannabis industry. Since legalization in her home state of Oregon in 2014, Laura has led her team of mechanical and electrical engineers and designers on more than 100 cannabis-related projects across the country.

 

 

Jeffrey F. Breit, PhD, has more than 15 years of experience leading program development efforts for pharmaceutical and health and nutrition products. He has played a leading role in the development of both organic and cGMP compliant manufacturing facilities and processes.

 

 

 

How to Cite this Article

L.J. Breit and J.F. Breit, Cannabis Science and Technology 3(2), 16–20 (2020).