Risk analysis for the presence of pesticides in dry cannabis floss cultivated under indoor conditions

Prospective risk analysis methods have significant potential for risk reduction and should be an integral part of any patient safety improvement strategy (Stojkovic et al., 2021). Risk management principles are effectively utilized in many areas. In the pharmaceutical industry risk is defined as the combination of the probability of occurrence and the severity of the damage it can cost. To meet regulatory and quality control standards, cannabis products should be tested for all pesticides, especially high-risk pesticides to health (Atapattu and Johnson, 2020; Jepson et al., 2020). Determination of pesticides in cannabis facilities is increasingly important as medicinal uses of cannabis products expand rapidly (Craven et al., 2021). Therefore, risk analysis as a systematic process for detection of probability occurrence of harm can improve the decision making if a quality problem arises (ICH, Q9, 2015).


Introduction
Prospective risk analysis methods have significant potential for risk reduction and should be an integral part of any patient safety improvement strategy (Stojkovic et al., 2021). Risk management principles are effectively utilized in many areas. In the pharmaceutical industry risk is defined as the combination of the probability of occurrence and the severity of the damage it can cost. To meet regulatory and quality control standards, cannabis products should be tested for all pesticides, especially high-risk pesticides to health (Atapattu and Johnson, 2020;Jepson et al., 2020). Determination of pesticides in cannabis facilities is increasingly important as medicinal uses of cannabis products expand rapidly (Craven et al., 2021). Therefore, risk analysis as a systematic process for detection of probability occurrence of harm can improve the decision making if a quality problem arises (ICH, Q9, 2015).

Materials and methods
To achieve our goal, we used the ICH Q9 guideline on quality risk management as a basis for analysis the possible sources of pesticide residues in the Cannabis dry flowers that may occur in dry cannabis floss cultivated under indoor conditions. Our goal was to recognize, analyze and classify the process steps during cultivation in which pesticides can occur. Thus, Failure Modes and Effects Analysis (FMEA) was conducted in all steps during cultivation process of cannabis floss form the beginning to the final packaging.

Results and discussion
Quality risk assessments begin with a well-defined problem description or risk question. The criteria for risk assessment can be grouped in four categories:  severity of consequences (great impact, medium, low impact)  possibility of occurrence (often, occasionally, almost never)  detection possibility (high, medium, low)  risk classification on human health (high, medium, low)

Cultivation process
Cultivation part is consisting of severe phases: seeds to be plated, vegetation phase, flowering phase, harvesting, and drying. In these phases a possible source of pesticides can arise from water and feeding material.
Checking the starting material that is used for cultivation is one step to prevent contamination of cannabis plants with pesticides. There is no risk of contamination with pesticides during harvesting and drying if the process is going under indoor controlled conditions.

Environmental impact
Pesticides can come from outside in the growing rooms if non-adequate air filtering system is installed, or if inappropriate filters are used, or if changing of the filters is untimely. Not treated air can contaminate the plants with pesticides, so implementation of proper Pharmaceutical Analysis/Quality Assurance/Regulatory Affairs Maced. pharm. bull., 68 (Suppl 1) 157 -158 (2022) HVAC system is another step to prevent contamination of indoor cultivated cannabis plants with pesticides.

Personal related and quality control related risks
Personnel can have impact for contamination with pesticides if they do not follow the process as it is described in Standard Operating procedures (SOPs) for using only approved materials or if they are not proper trained or if they are unaware of proper behavior during the process. Thus, well trained employers in accordance with GMP requirements are another step to prevent contamination of indoor cultivated cannabis plants with pesticides. All processes and materials used in the production/ growing part should be accurately described and specified in the SOPs as well as in the Batch protocols for each phase of the process.
In quality control laboratory the risk of not detecting pesticides is only if not adequate, not validated methods are used for quality testing. Training of the people who do analysis is also very important. Detection of the pesticides in reference standard material that is used is is a confirmation that the method is adequate for pesticide testing.

Conclusion
Risk identification is a systematic use of information to identify hazards. Risk analysis is the estimation of the risk associated with the identified hazards, while risk evaluation compares the identified and analyzed riskagainst given risk criteria. FMEA analysis is recommended to be made for possible deviations that may arise because of the risk have been identified, the severity of the consequences, the frequency of occurrence, and the possibility of detecting the risk before the damage occurs.
According to the conducted FMEA analysis it can be concluded that the risk of contamination the dry cannabis floss as a starting material used for extraction with pesticide residues is not possible in indoor cultivation if pesticides are not used in any phase of the process of cultivation, if starting material used for growing is purchased from approved suppliers and in the same time is regularly controlled, if employers are adequate trained and follow the process as it is described in SOPs.
FMEA relies on product and process understanding. Once failure modes are established, risk reduction can be used to eliminate, contain, reduce or control the potential failures.