Engineering Considerations for the cGMP Manufacture of Hemp and Hemp Products

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.

With the passing of the 2018 U.S. Farm Bill, which allowed for the federal legalization of hemp production and interstate transport, consumer products containing hemp-derived compounds such as cannabidiol (CBD) have continued to expand in number and scope. CBD health, nutrition, and food products are readily accessible through a number of retail and online outlets and the variety and number of these products is continuing to increase (1,2). The use of hemp-derived compounds such as CBD will likely continue to expand into other markets. For instance, CBD usage is currently being evaluated for pharmaceutical applications (3–5), which will likely serve to increase the rigor at which producers of hemp and hemp-derived compounds manufacture their products. 

Manufacturers of hemp-derived products are evaluating quality certification programs such as current good manufacturing process (cGMP) manufacturing strategies to differentiate their products from competitors, enable the use of hemp raw materials in high quality or high margin products, and to access highly regulated industries like pharmaceutics. The use of cGMP manufacturing and subsequent certification programs such as the ISO 9000 and ISO 9001 series of standards allow raw materials and finished goods to be used in quality defined and controlled consumer and pharmaceutical products. 

As the boutique and industrial hemp production and extraction industries mature and expand into other applications, there has been a growing interest in cGMP certification for food grade processes. For example, cGMP principles have been applied to a number of hemp processes and products including:

  • CBD production
  • Finished consumer goods containing CBD
  • Terpene isolation and use

A quick side note on good agricultural practices (GAP) versus GMP: GAP are the precursor to GMP. This will ensure the safe, hygienic, and quality production of the agricultural product (that is, propagation and cultivation) prior to manufacturing (6).

Messaging from the U.S. Food and Drug Administration (FDA) describes cGMP practices as, “providing for systems that assure the proper design, monitoring, and control of manufacturing processes and facilities” (7,8). To summarize statements made in the Code of Federal Regulations (CFR) 21 Parts 110 and 117, the FDA describes the content of a cGMP system in food grade manufacturing to include the following principles:

  1. A review and qualifications of a cGMP system
  2. The definition and applicability of a hazard analysis and risk-based evaluation strategies of manufacturing and production processes
  3. Supply chain considerations from raw materials through finished goods and after-market monitoring
  4. The establishment of defined and followed practices that lead to the production of a consistent product
  5. Considerations in process and finished goods qualification and validation strategies, supported by rational characterization strategies

Generally, the information outlined in CFR 21 Part 117 may be concisely described as knowing what comprises your product, understanding your process and product, and knowing what process attributes define your product. Collectively, these concepts help owners and operators understand and control important aspects (often defined as key or critical process parameters) of product manufacturing and enable a quality evaluation and control strategy to minimize defects and variability in finished goods. The principles presented in the FDA and other expert documents on the topic of cGMP principles can best be described as general guidelines and typically include aspects of a cGMP system that are required for cGMP qualification, but do not explicitly lay out a cGMP plan for the hemp industry because every process is product-specific. 

The importance of defining roles, responsibilities, and lines of communications, as well as anticipated cGMP and certification milestones during initiation of facility development, cannot be overstated. A GMP consultant can be critical to success in obtaining cGMP certification for your facility. A list of activities critical to the successful build and launch of a cGMP manufacturing facility may look something like the following:

  • Define target product profile (TPP)
  • Identify manufacturing process flow, unit operation functionality, and product and human safety attributes
  • Conceptualize brick and mortar functionality, flow and governing cGMP requirements
  • Utilize risk-based tools including process hazards analyses (PHA), risk assessments (RA), design qualifications (DQ), and validation master planning (VMP) to pre-establish critical processes and facilities influencing design, construction, and qualification criteria
  • Integrate process, product, personnel, material, waste, and airflows predicated on identified risks corresponding to cGMP requirements and good industry practice
  • Initiate cGMP conforming design and installation for architectural, mechanical, electrical, and plumbing (MEP) systems directed at mitigation of product contamination and assurance of operational safety
  • Conduct qualification and validation demonstrating the concepts, criteria, and RA stated outcomes defined in master-planning
  • Build a structured quality management system (QMS) with the appropriate depth and scope required for anticipated certifications and TPP
  • Create protocols and standard operating procedures (SOPs) to support product manufacture and QMS needs using prequalified raw material vendors, build bill of materials (BOM)
  • Integrate analytical equipment required to support raw material testing, in process checks and finished product release testing
  • Establish an acceptable certificate of analysis that is supported by finished product critical quality attributes (CQAs) and anticipated market requirements
  • Staff with trained and qualified personnel, by function, capable of demonstrating operational proficiency within the prescribed regulated environment
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).