Regulatory Guidelines for Product Quality Are Necessary for the Success of the Medical Cannabis Industry

While medical cannabis products do not require federal regulatory approval by the US Food and Drug Administration (FDA) in states where it is legal, the emerging medical cannabis industry ought to adopt its regulatory guidelines and practices that assure the quality of all marketed US drugs and devices. This is because, at present, no universal regulatory guidelines or requirements exist to ensure medical cannabis quality and safety. Not surprisingly, the quality attributes of medical cannabis vary wildly from state to state and even between different locations within the same city, county or state. Clearly, this is not in the best interests of medical cannabis users.

FDA established mandatory federal quality guidelines to guarantee product safety, identity, strength and purity. According to FDA, product safety means that a product is free of unexpected side effects when it is used properly by a patient. Identity guarantees that a product is exactly what its label and related informational materials say it is. Strength means that a given product consistently delivers the correct dosage and potency over its shelf life from its manufacture to its expiration. Purity indicates that a product is free from physical, biological and chemical contamination.  Put simply, these guidelines guarantee consumers that products are safe, effective and meet defined quality attributes.

The agency has developed different sets of regulatory guidelines that ensure product quality during various phases of development, manufacturing and commercialization. The existing guidelines that are relevant to the medical cannabis industry include 1) Current Good Laboratory Practices (CGMP), Current Good Clinical Practices (CGCP) and Current Good Manufacturing Practices (CGMP).

CGLPs are the guidelines that regulatory laboratory activities during preclinical development of products. This includes data collection and documentation, creation of standard operating procedures (SOPs), safety and pharmacology testing in laboratory animals, and sample preparation, handling and storage. Traditionally, CGLP helps guide development and ensure the quality of individual molecules but can be applied to extracts, tinctures and other products derived from cannabis plants.

CGCP was developed to guide the planning, conduct and analysis of human clinical trials that are required before a prescription drug can garner FDA regulatory approval. While CGCP is not relevant for most medical cannabis growers and dispensaries, it is required for companies that are currently trying to develop cannabis-derived pharmaceuticals and related products.

The set of regulatory guidelines that is most appropriate for a majority of medical cannabis growers, formulators and dispensaries is CGMP.  CGMPs were developed to assure that:

  • Raw materials used in the manufacture of pharmaceutical and biotechnology products are of known and possibly standardized quality and are free from contamination
  • A manufacturing process is proven to produce a product that consistently meets its specifications and quality attributes
  • Adequate quality control and assurance testing measures have been employed to assure that a product meets its quality specifications at the time of release to market and at the end of its shelf life

There are 10 basic CGMP principles that help t o ensure product quality, safety and efficacy. They are:

  1. Proper design and construction of facilities
  2. Validation of facilities, equipment and manufacturing processes (materials testing, cleaning, software etc)
  3. Proper maintenance of equipment, facilities and utilities
  4. Creation of SOPs (and adherence to them)
  5. Documentation of all processes, data collection, record keeping etc
  6. Employee development, on-going training and certification
  7. Contamination protection and prevention
  8. Employee health and hygiene
  9. Product manufacturing records and reports (that enable product recalls)
  10. Audits and Inspections

Following these principles will help to create a process that produces a product that is reproducibly consistent, safe and effective.

Because FDA approval is not required for medical cannabis use in states where it is legal, there is no requirement that any CGLP, CGCP or CGMP must be implemented. That said, assuring product consistency, quality, safety and effectiveness will go a long way to help establish medical cannabis brand reputation and reliability.

References

  1. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=58  
  2. https://www.fda.gov/aboutfda/centersoffices/officeofmedicalproductsandtobacco/cder/ucm090259.htm
  3. https://www.gpo.gov/fdsys/granule/CFR-2011-title21-vol4/CFR-2011-title21-vol4-part210

Does a Regulatory Pathway for Cannabis-Derived Prescription Pharmaceuticals Exist in the US?

All new prescription drugs introduced to the US market must be evaluated by a “tried and true” regulatory approval process established by the Federal Food, Drug, and Cosmetic (FDC) Act of 1938 (1).  The United States Food and Drug Administration (FDA) is the federal agency that oversees new prescription drug approvals.  Of course, over the years, changes have been made to the approval process to accommodate the scientific, medical and technology advances that have been made in the biotechnology, pharmaceutical and medical devices industries.

While the approval process is somewhat arcane and difficult to navigate at times, the end result is always the same. That is, approved drugs are biochemically uniform, stable, safe and effective.  Further, new drugs must posses a practical and suitable delivery system and be manufactured according to current Good Manufacturing Practices (CGMP; 2)

And, probably surprising to some, the same pathway that is used to approve new pharmaceutical and biotechnology drugs can be used to garner regulatory approval for cannabis-based  prescription drugs.  At present there are several cannabis companies, most notably, GW Pharma, that are using the pathway to get approval for their products.  However, the progress of these approvals has been greatly slowed by the fact that cannabis is federally scheduled as a Schedule 1 drug and is illegal (3). Sadly, this adds another layer of complexity to the federally-mandated regulatory approval process.

To overcome this wrinkle, 27 states including the District of Columbia (DC) have made medical marijuana legal (4).  This means that medical marijuana products sold to the public in states where it is legal do not have to go through the rigorous regulatory approval process to assure drug uniformity, quality, efficacy and safety.  Put simply, there is no regulatory oversight and the quality, safety and effectiveness of medicinal cannabis products cannot be confirmed nor guaranteed.  Ironically, this is the environment that led to the approval of the 1938 Federal Food Drug and Cosmetic Act to ensure that prescription drugs are safe and effective.

The best solution to this conundrum is to reschedule cannabis so that it is no longer illegal at the federal level. This will require medical cannabis companies to follow the new prescription drug regulatory process (that ensures product quality, efficacy and safety) before their products can be sold to US consumers.  While this may increase the time  for medical cannabis products to hit the market, it will guarantee the safety and therapeutic benefits of cannabis products for patients who suffer from diseases that cannot be controlled by conventional prescription drugs.

References 

  1. https://www.fda.gov/AboutFDA/WhatWeDo/History/Milestones/ucm128305.htm Accessed August 24, 2017
  2. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=211 Accessed August 24, 2017
  3. https://www.fda.gov/downloads/aboutfda/centersoffices/officeofmedicalproductsandtobacco/cder/ucm498077.pdf  Accessed August 24, 2017
  4. https://en.wikipedia.org/wiki/Medical_cannabis_in_the_United_States  Accessed August 24, 2017

Commercializing Cannabis-Derived Pharmaceuticals: Manufacturing, Quality and Healthcare Challenges

While overcoming the legal and regulatory challenges for commercializing cannabis- derived pharmaceuticals is essential, there are a variety of technical, manufacturing and healthcare obstacles that must be addressed before this class of molecules can be successful.

First, substantial financial investment must be made in infrastructure and production facilities to breed and grow different cannabis strains to obtain appropriate chemical compositions and extracts to treat specific therapeutic indications (1). Industry experts contend that this investment must include research on strain construction, cannabinoid concentrations at different stages of plant growth/harvest times and yield improvements. Interestingly, crop failure (not having a redundancy of supply) is a serious issue that all commercial entities in the medical cannabis industry must address and contend with to meet commercial demand.

Second, plant growth (use of insecticides, herbicides etc), extraction processes, and product formulation of cannabis-derived pharmaceuticals must be conducted according to Current Good Manufacturing Practices (CGMP) and rigorous quality standards (1). After all, the primary reason for seeking regulatory approval for these drugs is to demonstrate to patients and healthcare providers that cannabis-derived pharmaceuticals have been thoroughly reviewed, are well characterized and determined to be safe and effective. Implementation of pharmaceutical CGMPs (2) will ensure cannabis-derived pharmaceutical product safety, efficacy and quality over time.

Third, the route of delivery and dosing regimens for cannabis-based pharmaceuticals for specific indications will be vitally important. While smoking/vaporizing cannabis is currently the most obvious method to deliver desired therapeutic effects, it may not be the most effective to maximize its therapeutic benefits for different indications and individual patients (3). Over the past few years, there has been a growing interest in exploring oral, oromucosal, topical and sustained release delivery of cannabis-derived pharmaceutical depending upon the therapeutic indication of interest.

Fourth, efforts must be initiated to get Cannabis-derived pharmaceuticals on the drug formularies of state government insurers and third party insurance companies. At present, medical marijuana costs are usually not reimbursable by conventional health insurance companies (4) and out-of-pocket expenditures can be costly especially for those individuals who suffer from long term, chronic clinical indications like cancer, multiple sclerosis and epilepsy. However, if Cannabis-derived pharmaceuticals are approved by the US Food and Drug Administration (and are rescheduled) it is likely that these drugs will be covered by government and third party healthcare payers (5).

Finally, safeguards must be put into place to ensure protection against misuse, fraud and abuse of Cannabis-derived pharmaceuticals by healthcare providers and patients. The development of novel metered dose devices to deliver these products will help to limit misuse and abuse.

References

  1.  https://daggacouple.co.za/wp-content/uploads/2014/07/Economies_Scale_Production_Cannabis_Oct-22-20131.pdf Accessed July 18, 2017
  2. https://www.fda.gov/food/guidanceregulation/cgmp/  Accessed July 18, 2017
  3. https://www.medicaljane.com/category/cannabis-classroom/consuming-cannabis/   Accessed July 18, 2017
  4. http://www.cheatsheet.com/money-career/why-your-health-insurance-wont-cover-medical-marijuana.html/?a=viewall  Accessed July 18, 2017
  5. http://www.medicalmarijuanainc.com/medical-marijuana-covered-health-insurance/ Accessed July 18, 2017