EVERYTHING YOU NEED TO GET YOU AND YOUR COMMERCIAL CANNABIS OPERATIONS FULLY UP TO SPEED ON EVERYTHING GMP. MOBIUSTRIMMER.COM

Transcription

1 EVERYTHING YOU NEED TO GET YOU AND YOUR COMMERCIAL CANNABIS OPERATIONS FULLY UP TO SPEED ON EVERYTHING GMP. MOBIUSTRIMMER.COM

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3 CONTENTS 1 2 WHAT IS GMP? WHAT DOES GMP HAVE TO DO WITH THE CANNABIS INDUSTRY? 5 WHAT ARE THE CONSEQUENCES OF NOT APPLYING GMP? 7 THE REQUIREMENTS BASIC REQUIREMENTS OF GMP 9 DIVING INTO DETAILS OF GMP 10 EQUIPMENT 11 PERSONNEL 14 SANITATION 18 CLEANING VALIDATION GUIDELINES GETTING READY HOW DO I GET MY OPERATIONS GMP-READY? 27 HOW DO I GET MY OPERATIONS GMP-CERTIFIED? 30 ADDITIONAL RESOURCES EDIBLE CANNABIS PRODUCTS AND HACCP 32 USING THE MOBIUS IN A GMP-CERTIFIED ENVIRONMENT 33 SAMPLE GMP AUDIT FORM EQUIPMENT SECTION 38 ENDNOTES 40

4 SECTION 1: WHAT IS GMP? GMP stands for Good Manufacturing Practices. In other words, it s a set of rules and procedures related to the handling, cleaning, quality assurance and packaging processes in manufacturing facilities and the products they make.

5 CHAPTER 1 WHAT DOES GMP HAVE TO DO WITH THE CANNABIS INDUSTRY? Regardless of the licensing authority, the category under which cannabis is produced (medical or recreational use) or the form of the end-product (flower, concentrate, edible), cannabis is considered a drug and is subject to the various regulations and guidelines governing drugs. Mutual Recognition Agreement (MRA) countries [i] define GMP as the part of quality assurance that ensures that drugs are consistently produced and controlled in such a way to meet the quality standards appropriate to their intended use, as required by the marketing authorization [ii],[iii]. MOBIUSTRIMMER.COM Many jurisdictions around the world, including Canada, USA, Australia, New Zealand, Japan and the European Union, require the application of Good Manufacturing Practices (GMP) in the manufacture of drugs intended for their marketplace. Essentially, GMP ensures that a food or drug product is safe for human consumption

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7 CHAPTER 2 WHAT ARE THE CONSEQUENCES OF NOT APPLYING GMP? Whether the cannabis is being grown and produced for local (in-state or in-country) consumption or for export abroad, virtually all cannabis legislation requires some level of production quality assurance. It s not always GMP, but GMP is the standard that pharmaceutical companies need to apply to the production of their medicines, and the production of medical-grade cannabis is no different. The application of GMP to the harvesting and production of cannabis means the end-user can be sure that what they buy is safe to consume and that it is consistent each time they buy it. While it s true that in many jurisdictions there are no GMP requirements for cannabis products, it s almost certain that in the future, cannabis regulations will require GMP certification for Licensed Producers (LPs) to receive and maintain their license. Even now, sales opportunities may be lost by not maintaining GMP certification. More and more consumers will expect to see the certification on the product they buy. For business to business cannabis sales, many LPs are already requiring GMP certification from any other LPs they buy product from. MOBIUSTRIMMER.COM - 7 -

8 SECTION 2: REQUIREMENTS There are many requirements that constitute GMP, but this guide will focus on those aspects of GMP that relate to the harvesting and trimming of cannabis. Citations will be sourced from Canada s GMP Guidelines iv which are harmonized with the requirements of other MRA countries.

9 CHAPTER 3 BASIC REQUIREMENTS OF GMP At a high level, the basic requirements of a GMP program for cannabis harvesting and trimming can be summarized as follows: Manufacturing processes are clearly defined and controlled to ensure consistency and compliance with approved specifications and procedures; Critical steps of manufacturing processes and significant changes to the process are validated, Instructions and procedures are written in clear and easy-to-understand language; All necessary key elements for GMP are provided, including the following: qualified and trained personnel, adequate premises and space, suitable equipment and services, correct materials, containers and labels, approved procedures and instructions, suitable storage and transport. Operators are trained to carry out and document procedures. MOBIUSTRIMMER.COM - 9 -

10 CHAPTER 4 Section 2: requirements DIVING INTO DETAILS OF GMP To really get to know GMP, we need to dive into the details. The following section provides an in-depth review of the GMP requirements related to equipment, personnel and sanitation. This is directly from the Health Canada guidelines, and can be a bit complicated and difficult to read. Not ready? No problem. Skip ahead to the GMP Quick Start section

11 EQUIPMENT The equipment with which a lot or batch of a drug is fabricated, packaged/labeled or tested shall be designed, constructed, maintained, operated, and arranged in a manner that permits the effective cleaning of its surfaces; prevents the contamination of the drug and the addition of extraneous material to the drug; and permits it to function in accordance with its intended use. RATIONALE: The purpose of these requirements is to prevent the contamination of drugs by other drugs, by dust, and by foreign materials such as rust, lubricant and particles coming from the equipment. Contamination problems may arise from poor maintenance, the misuse of equipment, exceeding the capacity of the equipment and the use of worn-out equipment. Equipment arranged in an orderly manner permits cleaning of adjacent areas and does not interfere with other processing operations. It also minimizes the circulation of personnel and optimizes the flow of materials. The fabrication of drugs of consistent quality requires that equipment perform in accordance with its intended use. MOBIUSTRIMMER.COM

12 INTERPRETATION OF THE EQUIPMENT REQUIREMENTS: Section 2: requirements For equipment used for significant processing or testing operations, usage logs are maintained. The design, construction and location of equipment permit cleaning, sanitizing, and inspection of the equipment. Equipment is maintained in a good state of repair. Where a potential for contamination during fabrication or packaging of a drug exists, surfaces are free from cracks, peeling paint and other defects. Gaskets are functional. The use of temporary devices (e.g., tape) is avoided. Equipment parts that come in contact with drugs are maintained in such a manner that drugs are fabricated or packaged within specifications. Equipment used for significant processing or testing operations is maintained in accordance with a written preventative maintenance program. Maintenance records are kept. Equipment does not add extraneous material to the drug. Surfaces that come in contact with raw materials, in-process intermediates or drugs are smooth and are made of material that is non-toxic, corrosion resistant, non-reactive to the drug being fabricated or packaged and capable of withstanding repeated cleaning or sanitizing. The design is such that the possibility of a lubricant or other maintenance material contaminating the drug is minimized. Equipment made of material that is prone to shed particles or to harbour microorganisms does not come in contact with or contaminate raw materials, in-process drugs or drugs. Chain drives and transmission gears are enclosed or properly covered. Tanks, hoppers and other similar fabricating equipment are equipped with covers

13 MOBIUSTRIMMER.COM PLAIN ENGLISH TRANSLATION: Look for quality equipment that is easy to clean and made of materials that will not deteriorate. Keep your equipment in good shape

14 PERSONNEL Section 2: requirements Every lot or batch of a drug shall be fabricated, packaged/labeled, tested and stored under the supervision of personnel who, having regard to the duties and responsibilities involved, have had such technical, academic, and other training as the Director considers satisfactory in the interests of the health of the consumer or purchaser. RATIONALE: Your senior management is responsible for providing adequate resources (materials, personnel, facilities and equipment). They must continually monitor and improve the effectiveness of your pharmaceutical quality system. Who you hire is one of the most important elements in any pharmaceutical operation. Without proper staff with a quality mindset and training, it is almost impossible to fabricate, package/label, test or store good quality drugs. It is essential that only qualified staff supervise the fabrication of drugs. These operations are highly technical in nature and require constant vigilance, attention to detail, and a high degree of employee competence. The reason products often fail to meet required standards is because of poorly trained staff or a lack of understanding of the importance of production control

15 INTERPRETATION OF THE EQUIPMENT REQUIREMENTS: The person in charge of your quality control department (if you are a fabricator, packager/ labeler, tester, importer or distributor) and the person in charge of your manufacturing department (if you are a fabricator or packager/ labeler): must hold a Canadian university degree or a degree recognized as equivalent by a Canadian university or Canadian accreditation body in a science related to the work being carried out must have practical experience in their area of responsibility directly controls and personally supervises on site each working shift during which activities under their control are being conducted (for importers and distributors, the person in charge can be off-site in Canada if they are fully accessible to the quality control department and have enough knowledge of on-site operations to fulfill the responsibilities of the position) may delegate duties and responsibility (for example, to cover all shifts) to a person who is qualified, while remaining accountable for those duties and responsibility (the person must have a diploma, certificate or other evidence of formal qualifications awarded after completion of a course of study at a university, college or technical institute in a science related to the work being carried out, combined with at least two years of relevant practical experience) The person in charge of the quality control department of a wholesaler: must be qualified by relevant academic training and experience may delegate duties and responsibility to someone who meets the requirements under interpretation 2.a Consultants and contractors must have the necessary qualifications, training and experience to advise on the subjects they are hired for. MOBIUSTRIMMER.COM

16 Section 2: requirements The person responsible for packaging operations (including control over printed packaging materials and withdrawal of bulk drugs): must be qualified by training and experience is directly responsible to the person in charge of the manufacturing department (or a person having the same qualifications) Personnel in charge of secondary labeling operations and the quality control department: must be qualified by relevant academic training and experience can delegate their duties and responsibilities to a person who meets the requirements under interpretation 4.a Ensure enough personnel are available on site with the required qualifications and practical experience relevant to their responsibilities. Do not place so many responsibilities on any one individual that quality is put at risk. Record specific duties for all responsible staff in a written work description. Ensure personnel have the authority to carry out their responsibilities. When key personnel are absent, appoint qualified replacements to carry out their duties and functions. Ensure all personnel conducting GMP activities are able to understand the written procedures for those activities. Your personnel must be aware of the principles of GMP that affect them. They must receive initial and continuing training relevant to their job responsibilities. Follow a written program and use qualified trainers to train personnel (including technical, maintenance and cleaning staff). Assess the effectiveness of continuing training periodically. Provide training before implementing new or revised standard operating procedures (SOPs). Maintain records of training. Give specific training to personnel working in areas where highly active, toxic, infectious or sensitizing materials are handled. Ensure access to relevant information (e.g. safety data sheets) Review the performance of all personnel periodically

17 PLAIN ENGLISH TRANSLATION: People are the most important part of any cannabis cultivation operation. Without appropriate personnel with the right attitude and the right training, it is almost impossible to fabricate, package/label, test, or store good quality products. The operations involved in the fabrication of cannabis products can be highly technical and require constant vigilance, attention to details and a high level of competence on the part of employees. Inadequate training of personnel or the lack of an appreciation for the importance of production control often accounts for the failure of a product to meet the required standards.

18 SANITATION Section 2: requirements Every person who fabricates or packages/labels a drug shall have a written sanitation program that shall be implemented under the supervision of qualified personnel. The sanitation program shall include: cleaning procedures for the premises where the drug is fabricated or packaged/labeled and for the equipment used in the fabrication or packaging/labeling of the drug; and instructions on the sanitary fabrication and packaging/labeling of drugs and the handling of materials used in the fabrication and packaging/labeling of drugs. RATIONALE: Sanitation in a pharmaceutical plant, as well as employee attitude, influences the quality of drug products. The quality requirement for drug products demand that such products be fabricated and packaged in areas that are free from environmental contamination and free from contamination by another drug. INTERPRETATION OF SANITATION REQUIREMENTS: Every person who fabricates or packages/ labels a drug shall have a written sanitation program available on the premises. Dusty operations are contained. The use of unit or portable dust collectors is avoided in fabrication areas especially in dispensing, unless the effectiveness of their exhaust filtration is demonstrated and the units are regularly maintained in accordance with written approved procedures

19 The sanitation program contains procedures that describe the following: cleaning requirements applicable to all production areas of the plant with emphasis on manufacturing areas that require special attention; requirements applicable to processing equipment; cleaning intervals; products for cleaning and disinfection, along with their dilution and the equipment to be used; the responsibilities of any outside contractor; disposal procedures for waste material and debris; The sanitation program is implemented and is effective in preventing unsanitary conditions. Cleaning procedures for manufacturing equipment are validated based on the Health Canada document entitled Cleaning Validation Guidelines (GUI-0028) Residues from the cleaning process itself (e.g., detergents, solvents, etc.) are also removed from equipment. Evidence is available demonstrating that routine cleaning and storage does not allow microbial proliferation; Where necessary, sanitizers and disinfectants are filtered to remove spores (e.g., isopropyl alcohol). MOBIUSTRIMMER.COM PLAIN ENGLISH TRANSLATION: Make the time to develop and document your cleaning protocol. Train your team on it and follow it!

20 CHAPTER 5 CLEANING VALIDATION GUIDELINES V Section 2: requirements Once you have the equipment, personnel and sanitation program in place, it is necessary to validate the cleaning procedures that are employed. Following are the GMP guidelines for cleaning validation: PRINCIPLES The objective of the cleaning validation is to verify the effectiveness of the cleaning procedure for removal of product residues, degradation products, preservatives, excipients, and/or cleaning agents as well as the control of potential microbial contaminants. In addition, one needs to ensure there is no risk associated with cross-contamination of active ingredients. Cleaning procedures must strictly follow carefully established and validated methods. Appropriate cleaning procedures must be developed for all product-contact equipment used in the production process. Consideration should also be given to non-contact parts into which product may migrate (e.g., seals, flanges, mixing shaft, fans of ovens, heating elements, etc.)

21 VALIDATION OF CLEANING PROCESSES: Equipment cleaning validation may be performed concurrently with actual production steps during process development and clinical manufacturing. Validation programs should be continued through full scale commercial production. Validation of cleaning processes should be based on a worst-case scenario including: challenge of the cleaning process to show that the challenge soil can be recovered in sufficient quantity or demonstrate log removal to ensure that the cleaning process is indeed removing the soil to the required level, and the use of reduced cleaning parameters such as overloading of contaminants, over drying of equipment surfaces, minimal concentration of cleaning agents, and/or minimum contact time of detergents. At least three (3) consecutive applications of the cleaning procedure should be performed and shown to be successful in order to prove that the method is validated. Equipment which is similar in design and function may be grouped and a worst case established for validation. It is usually not considered acceptable to test-until-clean. This concept involves cleaning, sampling, and testing with repetition of this sequence until an acceptable residue limit is attained. MOBIUSTRIMMER.COM

22 EQUIPMENT: DOCUMENTATION: Section 2: requirements All processing equipment should be specifically designed to facilitate cleanability and permit visual inspection and whenever possible, the equipment should be made of smooth surfaces of non-reactive materials. Critical areas (i.e., those hardest to clean) should be identified, particularly in large systems that employ semi-automatic or fully automatic cleanin-place (CIP) systems. Dedicated product-contact equipment should be used for products which are difficult to remove (e.g., tarry or gummy residues in the bulk manufacturing), for equipment which is difficult to clean (e.g., bags for fluid bed dryers), or for products with a high safety risk (e.g., biologicals or products of high potency which may be difficult to detect below an acceptable limit). In a bulk process, particularly for very potent chemicals such as some steroids, the issue of by-products needs to be considered if equipment is not dedicated. Detailed cleaning procedure(s) are to be documented in Standard Operating Procedures (SOPs). A Cleaning Validation Protocol is required to define how the cleaning process will be validated, including detailed cleaning procedures to be used for each product, each manufacturing system or each piece of equipment. When more complex cleaning procedures are required, it is important to document the critical cleaning steps. In this regard, specific documentation on the equipment itself which includes information about who cleaned it, when the cleaning was carried out, the product which was previously processed on the equipment being cleaned should be available. However, for relatively simple cleaning operations, the mere documentation that the overall cleaning process was performed might be sufficient

23 MICROBIOLOGICAL CONSIDERATIONS: PERSONNEL: Whether or not CIP systems are used for cleaning of processing equipment, microbiological aspects of equipment cleaning should be considered. This consists largely of preventive measures rather than removal of contamination once it has occurred. There should be some documented evidence that routine cleaning and storage of equipment do not allow microbial proliferation. For example, equipment should be dried before storage, and under no circumstances should stagnant water be allowed to remain in equipment subsequent to cleaning operations. Time-frames for the storage of unclean equipment, prior to commencement of cleaning, as well as time frames and conditions for the storage of cleaned equipment should be established. It is difficult to validate a manual cleaning procedure (i.e. an inherently variable/cleaning procedure). Therefore, operators carrying out manual cleaning procedures should be adequately trained, monitored, and periodically assessed. MOBIUSTRIMMER.COM

24 SAMPLING, RINSING, RINSE SAMPLES & DETERGENTS: Section 2: requirements There are two general types of sampling that are considered to be acceptable, direct surface sampling (swab method) and indirect sampling (use of rinse solutions). A combination of the two methods is generally the most desirable, particularly in circumstances where accessibility of equipment parts can mitigate against direct surface sampling. Rinse Samples: Rinse samples allow sampling of a large surface area and of inaccessible systems or ones that cannot be routinely disassembled. However, consideration should be given to the fact that the residue or contaminant may be insoluble or may be physically occluded in the equipment. A direct measurement of the residue or contaminant in the relevant solvent should be made when rinse samples are used to validate the cleaning process. It is important to use visual inspection in addition to analytical methodology to ensure the process is acceptable. When detergents are used in the cleaning process, their composition should be known to the user and their removal should be demonstrated. Direct Surface Sampling: Areas hardest to clean and which are reasonably accessible can be evaluated by direct sampling method, leading to establishing a level of contamination or residue per given surface area. Additionally, residues that are dried out or are insoluble can be sampled by physical removal. The suitability of the material to be used for sampling and of the sampling medium should be determined. The ability to recover a sample accurately may be affected by the choice of sampling material. It is important to assure that the sampling medium and solvent (used for extraction from the medium) are satisfactory and can be readily used

25 Detergents should be easily removable, being used to facilitate the cleaning during the cleaning process. Acceptable limits should be defined for detergent residues after cleaning. The possibility of detergent breakdown should also be considered when validating cleaning procedures. ESTABLISHMENT OF LIMITS Carry-over of product residues should meet defined criteria, which in this case could mean no quantity of residue to be visible on the equipment after cleaning procedures are performed. PLAIN ENGLISH TRANSLATION: This is where it all comes together. You ve done the prep work, made the right equipment selections, put in place SOPs and trained your team. But does it all work as intended? Are you achieving the level of cleanliness required for your operations? These guidelines help you determine if your cleaning protocols and execution are adequate or need adjustment. MOBIUSTRIMMER.COM

26 SECTION 3: GETTING READY

27 HOW DO I GET MY OPERATIONS GMP-READY? CHAPTER 6 The previous sections went into great detail on the various requirements under GMP and this can seem overwhelming at first. To help get you started, here are four things you can do right now to get your cannabis harvesting and trimming operations on the right track and GMP-ready. 1. DITCH THE JUNK + DEEP CLEAN! MOBIUSTRIMMER.COM This relates to the PREMISES portion of compliance. GMP requires that pharmaceutical and/or food production environments are designed and constructed in a manner that permits cleanliness and orderliness while preventing contamination, so clean out that junk that s been piling up in the corner of your cannabis drying room, check your building envelope for openings that could allow for pests to get in (and seal any that you find), and perform that floor to ceiling spring cleaning you ve been putting off for a few harvests. Once you have decluttered and performed a deep clean, you ll wonder why you didn t do it earlier and be motivated to keep it that way!

28 2. KEEP MAINTENANCE RECORDS! INSPECT, INSPECT, AND INSPECT AGAIN! Section 3: getting ready This relates to the EQUIPMENT portion of compliance. One of the goals of GMP is to prevent the contamination of drugs/food by dust, by other drugs/food, and by foreign materials such as rust, lubricant and particles coming from the equipment. There s no time like the present to give your cannabis harvesting and processing equipment a thorough visual inspection and review your maintenance records. Not keeping records? Start now! Set up a maintenance and inspection schedule and stick to it. Most of the time, a little TLC will bring your gear 3. KEEP YOUR TEAM TRAINED, AND GET NEW HIRES UP TO SPEED FAST! This relates to the PERSONNEL portion of compliance. People are the most important element in any pharmaceutical or food production operation without the proper personnel with the appropriate attitude and sufficient training, it is almost impossible to fabricate, package, label, test, or store good quality drugs and/or food. The operations involved in the fabrication of up to snuff, but if you find yourself going through bulk quantities of WD40 or duct tape to patch up your equipment, perhaps it s time to think about retiring your old stand-by and investing in a new piece of equipment. And remember, GMP is not just about getting your equipment ship shape for inspection day, but about keeping it that way over the long term. Regular maintenance and record keeping are essential. cannabis products are highly technical in nature and require constant vigilance, attention to details and a high degree of competence on the part of employees, therefore, your goal should be to adhere to the KISS Principle: Keep It Simple, Stupid. The KISS Principle states that most systems work best if they are kept simple rather than made complex. Keeping the KISS Principle in mind, perform a review of your SOPs (Standard Operating Proce

29 dures). Are they simple and straightforward? Is unnecessary complexity avoided? Are there steps that can be automated or eliminated altogether? Next, take a look at your onboarding practices for new employees or for people moving from one role to another within your organization. Are you setting them up for success or for failure? How long does it take to become fully competent in a given role and how much turnover are you experiencing for that position? Improving your hiring practices, training program and SOPs is a big investment, but it can result in a big payoff too in the form of reduced turnover, fewer workplace injuries, increased production quality and, ultimately, a positive bump to your bottom line. 4. CLEAN WELL, AND ON A SCHEDULE! This relates to the SANITATION portion of compliance. Sanitation in a food or pharmaceutical plant influences the quality of food and drug products, and helps ensure the products are safe for consumption. A written sanitation program provides some assurance that levels of cleanliness in the plant are maintained and that the relevant regulatory provisions are satisfied. If you don t already have a written sanitation program, it s never too late to start. Whether you re starting from scratch or reviewing an existing program, your written sanitation program should address each of the following three key points: Ensuring the cleanliness of the premises; Ensuring the cleanliness of any and all equipment used in your operations; and Ensuring employees are trained in and follow all required sanitation procedures. MOBIUSTRIMMER.COM Getting your cannabis cultivation facility GMP-certified (or at least aligned with GMP principles) can seem like a daunting task, but it doesn t have to be. The hardest part is getting started! Follow the above four actions and you ll be well on your way

30 CHAPTER 7 Section 3: getting ready HOW DO I GET MY OPERATIONS GMP-CERTIFIED? If you re located in Canada, you ll need to work with Health Canada s Health Products and Food Branch Inspectorate. To get a jump start on the certification process, check out Health Canada s GMP Audit Report Form. As cannabis is not yet federally legal in the United States, GMP certification through the US Food & Drug Administration is not available, but more information on their GMP requirements can be found here: FDA cgmp Regulations

31 SECTION 4: ADDITIONAL RESOURCES MOBIUSTRIMMER.COM

32 CHAPTER 8 Section 4: additional resources EDIBLE CANNABIS PRODUCTS AND HACCP Hazard Analysis Critical Control Points (HACCP) is an internationally recognized system used to enhance food safety throughout the food chain. A HACCP System consists of prerequisite programs and a HACCP Plan. Prerequisite programs are outside the HACCP Plan, but still within the HACCP System. They keep potential hazards from becoming serious enough to adversely impact the safety of foods produced. GMP is an example of a prerequisite program. The purpose of the HACCP Plan, or Food Safety Plan, is to prevent, eliminate or reduce potential food safety hazards to an acceptable level. When making any cannabis-containing edible product, many raw ingredients, including cannabis will be required. If the company producing the edible is following HACCP, they will implement a prerequisite program to ensure that incoming materials (i.e. the raw ingredients) are safe and of good quality vi. Procuring cannabis from a GMP-certified supplier would meet this prerequisite by verifying the quality of this particular input material, thereby providing justification for not adding the processing of cannabis to the HACCP Plan vii. CONCLUSION: Using cannabis from a GMP-certified supplier to produce an edible product does not negate the need for a HACCP Plan, but it does eliminate the need to consider the cannabis ingredient itself as a potential source of hazard that must be addressed in the HACCP Plan

33 USING THE MOBIUS IN A GMP-CERTIFIED ENVIRONMENT CHAPTER 9 In the past, one of the major obstacles for an LP that sought GMP certification was the cannabis trimming process, mostly because the hoses and dust collection components of the equipment were nearly impossible to clean and potentially carried contamination from one batch to the next. With the Mobius Trimmer M108, we set out to design a cannabis trimming system that could be operated, cleaned and put back into operation with minimal fuss. Here s how we did it: All plant-touching parts of the M108 are smooth and made of non-toxic, corrosion resistant, non-reactive materials, capable of withstanding repeated cleaning; All plant-touching parts of the M108 are accessible and/or removable for cleaning and can be effectively cleaned with non-toxic detergents or just water alone; The M108 does not have any hoses or hidden parts, which are exceptionally difficult to clean and have the potential to harbor microorganisms; The M108 is a semi-closed system that generates minimal airborne particulate because the system separating the trim from the flower is built into the machine; and SOPs for the M108 are simple and straightforward, ensuring consistency in operations and products. MOBIUSTRIMMER.COM The table below goes into detail on each of the trimming-related GMP requirements and the pertinent Mobius feature

34 EQUIPMENT REQUIREMENTS GMP REQUIREMENT The equipment does not add extraneous material to the end product. Plant touching parts are smooth and made of non-toxic, corrosion resistant, non-reactive materials, capable of withstanding repeated cleaning MOBIUS FEATURE All plant-touching parts of the Mobius are smooth and made of non-toxic, corrosion resistant, non-reactive materials, capable of withstanding repeated cleaning Section 4: additional resources Equipment made of material that is prone to shed particles does not come in contact with plant materials The possibility of lubricant or other equipment maintenance material contaminating the product is minimized Belts and gears are enclosed or properly covered All parts of the Mobius are entirely resistant to shedding (anodized metal, molded plastic, surgical-grade stainless steel, etc.) The Mobius is designed with all sealed bearings. Any other parts that could possibly require lubricating are closed off from those parts that touch the plant The cutter drive belt on the Mobius is fully encased and does not come into contact with any plant material

35 OPERATIONAL REQUIREMENTS GMP REQUIREMENT MOBIUS FEATURE Equipment is maintained in a good state of repair (i.e. free from cracks, peeling paint, temporary fixes like tape, etc.) Usage logs are maintained Personnel operating equipment must be adequately trained Personnel cleaning equipment must be adequately trained, monitored and periodically assessed The equipment sanitation program includes procedures for cleaning the equipment Cleaning procedures for equipment are documented Dusty operations are contained. The use of unit dust collectors is avoided, unless the effectiveness of the exhaust filtration is demonstrated and the unit is regularly maintained All parts of the Mobius have been designed to withstand regular, long-term operation and cleaning with minimal maintenance. None of the parts of the Mobius are painted, nor are they made of materials that will flake or crack. The Mobius is equipped with a digital log for each of the three motors in the machine. The logs can be accessed by the operator at any time by toggling through the control panel on the machine. The Mobius has been designed to be very simple to use and maintain. No tools are required to take pieces off or put them back on and no adjustments are required to dial-in the machine to perform properly. This simplicity makes it faster and easier to onboard personnel, mitigating the negative effects of turnover on production quality. All plant-touching parts of the Mobius are accessible for cleaning, All plant-touching parts of the Mobius are accessible and/or removable for cleaning and can be effectively cleaned with non-toxic detergents or just water alone. There are no hoses or occluded parts in which plant material or resin can build up. These features make it possible to establish clear and simple equipment cleaning procedures. Because all plant-touching parts of the Mobius are accessible, documentation of cleaning procedures can be simple and concise, making it more likely that operators will understand and consistently apply the procedures. The Mobius is a semi-closed system that generates minimal airborne material because the system separating the trim from the flower is built into the machine. There are no hoses or external vacuum/dust collecting components and the impeller housing is completely closed off, therefore it is not generating any airborne plant particulate. MOBIUSTRIMMER.COM

36 CLEANING REQUIREMENTS GMP REQUIREMENT MOBIUS FEATURE Section 4: additional resources Equipment parts that come in contact with the plant (flower or trim) are removable or are accessible to cleaning All processing equipment should be specifically designed to facilitate cleanability and permit visual inspection. Whenever possible, the equipment should be made of smooth surfaces of non-reactive materials. Critical areas that are hardest to clean should be identified Detergents used for cleaning the equipment should be easily removed Carry-over of product residues should meet defined criteria, which in this case could mean no quantity of residue to be visible on the equipment after cleaning procedures are performed Cleaning procedures for equipment are validated Microbiological contamination should be prevented rather than removed after the fact. Equipment must be dried before storage and stagnant water must not be allowed to remain in equipment subsequent to cleaning. Equipment made of material that is prone to harbour microorganisms does not come in contact with plant materials All plant-touching parts of the Mobius are removable and/or accessible to cleaning. All plant-touching parts of the Mobius are accessible and/or removable for cleaning and can be effectively cleaned with non-toxic detergents or just water alone. There are no hoses or occluded parts in which plant material or resin can build up. All parts of the Mobius are smooth surfaces made of non-reactive materials. All plant-touching parts of the Mobius are fully accessible for cleaning, visual inspection and surface sampling The smooth, non-absorbing, non-reactive surfaces of the Mobius make it easy to remove detergent applied to clean the equipment. Because all plant-touching parts of the Mobius are accessible for visual inspection, operators can ensure no residue remains on the equipment after cleaning procedures are performed. Because all plant-touching parts of the Mobius are accessible, validating cleaning procedures through visual inspection, direct surface sampling and rinse sampling is very straightforward. None of the plant-touching materials of the Mobius are conducive to microbiological growth. All plant-touching parts of the Mobius are accessible to clean and visually inspect, which also means that operators can ensure equipment is fully dried after cleaning so that microbial growth on wet equipment parts does not occur. The Mobius does not have any hoses, which are exceptionally difficult to clean and have the potential to harbour microorganisms

37 NOTES ON EQUIPMENT AND OPERATIONAL PERSONNEL The more complex a piece of equipment is to operate or to clean, the more complex and lengthy SOPs and instructions will be and the more difficult it will be to adequately train personnel. The ability of an organization to adequately train its personnel is increased by having simple SOPs and decreased by having high turnover. Ideally, an organization will aim to have simple operational procedures in place that are executed by thoroughly trained and experienced personnel. While an organization can take steps to increase employee retention, the results of those efforts may not always be as successful as hoped and even under the best circumstances, some level of employee turnover is inevitable. With this in mind, it behooves LPs to keep their SOPs for trimming and cleaning as simple as possible so that they can onboard new employees quickly and effectively. MOBIUSTRIMMER.COM

38 CHAPTER 10 SAMPLE GMP AUDIT FORM EQUIPMENT SECTION Section 4: additional resources The following table has been excerpted from Health Canada s GMP Audit Report Form (FRM-0211 viii ). Section C of the form pertains to equipment and has been completed assuming that the Mobius M108 is being used for trimming operations. EQUIPMENT [C ] The equipment with which a lot or batch of a drug is fabricated, packaged/labeled or tested shall be designed, constructed, maintained, operated and arranged in a manner that: permits the effective cleaning of its surfaces; prevents the contamination of the drug and the addition of extraneous material to the drug; and permits it to function in accordance with its intended use. IF YES, DESCRIBE. All plant-touching parts of the M108 are smooth and made of non-toxic, corrosion-resistant, non-reactive materials, capable of withstanding repeated cleaning All plant-touching parts of the M108 are accessible and/or removable for cleaning and can be effectively cleaned with non-toxic detergents or just water alone. The Mobius does not have any inaccessible parts or hoses, which are exceptionally difficult to clean and have the potential to harbor microorganisms Yes Yes Yes X X X No No No

39 The Mobius is a semi-closed system that generates minimal airborne material because the system separating the trim from the flower is built into the machine. There are no hoses or external vacuum/dust collecting components and the impeller housing is completely closed off, therefore it is not generating any airborne plant particulate. SOPs for the M108 are simple and straightforward, ensuring consistency in operations and products. IF NO, PROVIDE A RATIONALE (e.g. Not applicable because ) DEVIATIONS Identify and describe any noted GMP deviation(s) and the rationale for the deviation, where applicable. NO. OBSERVATIONS RISK CLASSIFICATION MOBIUSTRIMMER.COM CORRECTIVE ACTIONS Detail the corrective action(s) taken and/or to be taken. ATTACHMENTS Attach supporting documentation such as SOPs, action plans with timelines for each corrective action identified above. List of attachments:

40 CHAPTER 11 ENDNOTES i. mutual-recognition-agreements/updates.html ii. iii. iv. Good manufacturing practices guide for drug products (GUI-0001): drugs-health-products/compliance-enforcement/good-manufacturing-practices/guidance-documents/gmp-guidelines-0001/document.html v. Cleaning Validation Guidelines (GUIDE-0028): compliance-enforcement/good-manufacturing-practices/validation/cleaning-validation-guidelines-guide-0028.html vi. sept6_2017.pdf vii. pdf?mod=ajperes viii. Good Manufacturing Practices Audit Report Form (FRM-0211), Health Products and Food Branch Inspectorate, Health Canada:

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