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CREATING SOPS AND DEVELOPING ADVANCED PROCESSES FOR PRODUCT CONSISTENCY CANNABIS 2017 CULTIVATION CONFERENCE PRESENTED BY RINO FERRARESE
CREATING SOPS AND
DEVELOPING ADVANCED PROCESSES FOR
PRODUCT CONSISTENCY
CANNABIS 2017 CULTIVATION CONFERENCE
PRESENTED BY RINO FERRARESE
RINO FERRARESE
• COO of Connecticut Pharmaceutical Solutions, a grower/processor in Connecticut.
• QA/QC Background
• Experience working in FDA regulated industries producing human products for;
• Prescription (Rx), Over-The-Counter (OTC), Cosmetics and Homeopathic industries.
• Additional certifications: Six Sigma Black Belt and ISO lead auditor (9001 and 13485).
• Elite Cannabis Enterprises
About the company:
• Grower/Processor• Operate under cGMPs in compliance with 21CFR111 (Dietary Supplement
Regulations)• Local State Drug Control Regulations for MMJ
Phase 1 facility: 15,000 ft2 total, 6,000 ft2 of canopy Phase 2 facility: 107,000 ft2 total, 32,000 ft2 of canopy
Committed to contribute 25% after tax revenue to researching medicinal benefits of marijuana.Currently partnered with major Medical School located in New Haven, CT.
Before we get into SOPs or Process Improvements, let’s look at FDA regulated Industry, Adult Use and Medical Marijuana industries within the past few months.
SERIOUS ADVERSE EVENTS WITHIN LAST 6 MONTHS IN USAPATIENTS AND CONSUMERS
• February 2017 – Cancer patient with chemotherapy-induced weakened immune system died from smoking cannabis that was infected with a rare fungus.
• December 2016 – Emerald Cup; About 25 percent of 263 samples in the concentrates categories disqualified because they tested positive for pesticides; 40 out of 735 flower samples entered into the contest also tested positive for banned pesticides.
SERIOUS ADVERSE EVENTS WITHIN LAST 6 MONTHS IN USAPATIENTS AND CONSUMERS
• November 2016 – Oregon issued 2nd health alert “for marijuana contaminated with pesticide ingredients”. Ended up on store shelves even after failing lab testing!
• Oct. 2016 - Oregon issued 1st health alert “for marijuana contaminated with pesticides or pesticide ingredients”. About 130 people bought dried flower contaminated with Spinosad (insecticidal with a neural Mode of Action)
• October 2016 – Steep Hill Labs reports 84.3% of samples submitted to their Berkley lab test positive for pesticide residue.
AN EMPLOYEE WITHIN A FACILITY SUES FOR$9 MILLION IN BURN DAMAGES
• A recent law suit alleges that a COMPANY’s facility did not have
adequate safety measures in place for handling butane extraction…
• “Employee/victim alleges that Employer 1 was improperly handling
butane…which is combustible…claims Employer 2 triggered the the
explosion when he lit his dabbing rig.
In 2012, a fungal meningitis outbreak killed 64 people and sickened nearly 700 more in 20 states across the country.
• Linked to contaminated steroid injections (used to treat pain) produced at the Framingham-based NECC. (Compounding pharmacies produce custom-mixed medications.)
• The center was accused of using expired ingredients and failing to follow safety standards, which resulted in the tainted drugs and patients’ deaths.
More than a dozen employees were charged in connection with the outbreak, in what authorities called the biggest criminal case ever brought in the U.S. over contaminated medicine.
• Criminal charges include fraud, criminal contempt, misleading regulators, falsifying records, preparing drugs in unsanitary conditions, and shipping mislabeled drugs and prescriptions with fake patient names.
64 Dead, 700 sick in 20 states nets $200 Million Lawsuit
HISTORY IS REPEATING ITSELF (FOR THE GOOD)
• In the USA we have an expectation that consumer packaged goods (non-durable goods like soft drinks, toiletries, over-the-counter drugs, processed foods, and many other consumables) are regulated, safe, effective, and that a product’s label accurately reflects the necessary characteristics about that product.
• This is optimistic and we are fortunate. Our confidence comes at the expense of a large regulatory agency tasked with making sure that these products meet requirements for Safety, Identity, Strength, Quality and Purity.
• It wasn’t always like this here in the USA…
• The Jungle, 1906 novel that exposes contaminated meat.
• Turn of the 20th century about immigrant life inadvertently exposes horrendous food conditions in factories.
• Major problem in the U.S. – No recourse for consumers
• 1906 Pure Food and Drug Act• Consumer protection agency
Brief History
POISONOUS ELIXIR – 1937 SULFALINIMIDE TRAGEDY
Raspberry Flavored Cough Medicine • Diethylene glycol – colorless, odorless, sweet taste• Poisonous - Antifreeze• How? No mandated toxicity or safety testing• Of 240 gallons manufactured and
distributed, 234 gallons and 1 pint was retrieved• 100 fatalities in 15 states
1938 Food, Drug, and Cosmetic Act
• Required drug testing for SAFETY• Provided for inspection
• Established the FDA• Still a major drug law in the USA
FDA SAVES CHILDREN FROM POTENTIAL DISASTER
• Thalidomide drug used to treat morning sickness in Europe, Canada and other countries causing birth defects.
• FDA medical officer blocked it because insufficient safety data – more anecdotal than clinical, but not before the company distributed 1,200 samples to expectant mothers which resulted in 17 birth defects.
• Fast federal action in 1962 called Kefauver-Harris Drug Amendment to FD&C Act
• Emphasis on EFFECTIVENESS and SAFETY!
• GMP origins (1962)
CHILDREN EXPOSED TO THALIDOMIDE IN UTERO
GMPS PUBLISHED(CURRENT GOOD MANUFACTURING PRACTICES)
FIRST FOR MEDICINES:
• EU (1975)
• US GMP Revision (1978)
• Japanese & WHO GMP (1980)
THEN FOR OTHER PRODUCTS
• Food
• Medical devices
• Blood & Blood Products
• Active Pharmaceutical Ingredients (API’s)
• Cosmetic Ingredients
• Dietary Supplements
• Excipients
GMP BASICS
• The basis of all GMP’s involves the generation of procedures that detail what you do, how you do it, the desired results and actions taken for those results that do no meet final specifications.
• The GMPs do not specify the “how to” steps, but rather are purposely left general in nature to allow each company to develop their own procedures and then follow them as written.
PERSONNEL
• Education, training and experience for their position
• Dressed appropriately
• Clean, not sick
• Trained annually, proficiency testing
• Consumption of food, drink or tobacco is restricted to designated areas
BUILDING AND FACILITIES
• Designed and Constructed Properly
• Maintained
• Clean and Sanitized
• Validation provides a high degree of assurance that systems are appropriate for their intended purpose
• Building Management Systems for;• Light• Temperature• CO2• Humidity• Security
EQUIPMENT • Design appropriate
• Maintained – Total Preventive Maintenance
• Clean and sanitized
• Validated for its intended use
CLEANING/SANITIZING
• Processing / Manufacturing Areas
• Utensils, Implements, and Instruments
• Process Equipment
• Packaging Lines
• Cleaning validation – rinse water samples, surface monitoring, environmental monitoring
PROCEDURES
• Written Instructions• Raw Materials – Specifications, Receipt/Test/Release• Batch Records – Cultivation, Dry/Cure,
Extraction, Post-extraction, Formulation• Packaging Components• Packaging and Labeling Batch Records• Quality Assurance/Quality Control
BATCH RECORDS(PRODUCT RECIPE)
What should they include?
• Amount of Product being Manufactured
• Raw Materials (Active and Excipient) to be Used
• Procedures, i.e. step-by-step directions
• Testing required by QA
• Assignment of Lot #’s to Finished Product
We must establish
Traceability and Control
PACKAGING
• Control Procedures
• Label Control - reconciliation
• On-Line Inspection
• Inventory Control
• Yield Reporting
• Activities Required After Packaging
• Line clearance, cleanup
• Never pack 2 different products at same time without adequate controls in place
QUALITYCONTROLRESPONSIBILITIES
• In-house testing of Raw Materials, Components, Intermediates and Finished Product
• Method Development
• Product Development
• Directs Equipment Calibrations
• Conducts Product Stability Studies
• Product Validation Studies (IQ, OQ, PQ)
QUALITYASSURANCERESPONSIBILITIES
• Ensures Compliance with Regulatory and Customer Requirements
• Oversee Quality Management System
• Maintains SOPs
• Conduct Audits
• Issues Batch Records
• Product Release
• Supplier/Vendor Maintenance
• Product Complaints, Corrective/Preventive Actions, Recalls, Out of Spec Investigation, Change Controls
WRITTENPROCEDURESFORWAREHOUSING(STORAGE)
• Quarantine/Reject/Release of Final and Intermediate Product
• Storage of Products Under Appropriate Conditions of Temperature, Humidity and Security
• Distribution of Oldest Approved Products First
First In First Out
LOT CODING -TRACEABILITY
• Date of Manufacturing
• Ability to;
• Track – where each product unit was sold
• Trace – identify each product that was formulated with an ingredient
• Testing and Approval – Certificates of Analysis
• Quantity Produced/Shipped
• Who is the purchaser?
STABILITYTESTING
All Products should undergo a systematic testing program
• Indicates product shelf life
• Takes into consideration;
• Chemical Stability
• Microbiological Stability
• Physical Stability
• Packaging Compatibility
PRODUCTCOMPLAINTSAND RECALLS
• Every complaint should be documented and investigated
• Retain products tested
• Returned product tested – immediately
• Returned products should be stored in a quarantine area
• In case of consumer safety issue, notify relevant authorities
• Complaints trended periodically
RETURNEDPRODUCTS
• Identified
• Inventoried (separately)
• Tested
• If OK, can be reprocessed for distribution under guidance of relevant authority
• Rejected product is destroyed. Supporting paperwork as objective evidence.
AUDITS
• Internal audits challenge the quality system
• Monitor progress of compliance with cGMPs and relevant regulations
• Audits are documented• Cite observation requiring mitigation
through Corrective Actions as needed.
• Audits discussed with Senior Management
• Follow-up audits verify effectiveness of Corrective Actions
• Audits occur yearly
Date Brand NameProduct Description Reason/ Problem Company
03/20/2017 Barnsdale Farms®, HoundsTooth® and Mac's Choice®
Dog treat- Pig Ears
Samonella EuroCan Manufacturing
03/20/2017 Ronzoni Thin Spaghetti Undeclared egg Riviana Foods Inc
03/18/2017 Nutiva Protein shake Undeclared peanuts Nutiva
03/17/2017 BLUE Wilderness, Rocky Mountain Recipe
Dog food Contains beef thyroid hormone
Blue Buffalo Company
03/17/2017 Wellness Beef Topper for Dogs
Contains beef thyroid hormone
WellPet LLC
03/17/2017 Nabelsi Thyme Lead Aroma Imports Inc.
03/16/2017 (no brand name) Edamame Edamame (Soybeans)
Listeria monocytogenes Advanced Fresh Concepts Franchise Corp.
03/14/2017 Dolcetta Chocolate Candy Undeclared soy and milk Dolcetta Artisan Sweets
03/13/2017 Vulto Creamery Cheese Listeria monocytogenes Whole Foods Market
03/11/2017 Vulto Creamery Cheeses Listeria monocytogenes Vulto Creamery
Recalls, Market Withdrawals, & Safety Alerts
https://www.fda.gov/Safety/Recalls/default.htm
ASQ - A quality management system (QMS) is a formalized system that documents processes, procedures, and responsibilities for achieving quality policies and objectives. A QMS helps coordinate and direct an organization’s activities to meet customer and regulatory requirements and improve its effectiveness and efficiency on a continuous basis.
SOP = Standard Operating Procedures
• Regulations - Tell us what has to be done.• SOPs - How to do it.
• Collect all relevant information about new batch of clones/cuttings
• Establishes traceability and accountability
• Chain of custody
• Creates a record
• Record gets filed in QA department for X years
A CURRENT STATE PROGRAM REQUIRES THESE THINGSGrowers/processors generally.Plans of operation.Grower/processor facilities.Start-up inventory.Visitor access to grower/processor facilities.Security and surveillance.Requirements for growing and processing medical marijuana.Forms of medical marijuana.Inventory.Storage requirements.Equipment, operation and maintenance.Sanitation and safety in a facility.Packaging and labeling of medical marijuana.Transportation of medical marijuana.Evidence of theft, diversion or discrepancy during transport.Electronic tracking system.Disposal of medical marijuana.Complaints about or recall of medical marijuana.Pesticides.
State Regulations are the first stop but typically don’t include enough info about Quality Management Systems or SOPs or continuous improvement.
We can look to the following as additional resources
• FDA Dietary Supplement Regulations (21 CFR Part 111)
• USDA Good Agricultural Practice/Good Handling Practices
• ISO Standards
• American Herbal Products Association (AHPA) Recommendation for Regulators, Cannabis Operations
• American Herbal Pharmacopoeia Cannabis Inflorescence
• No specific requirement for SOPs or Process Controls
Regulations
Subpart
A General Provisions (including coverage and definitions)B PersonnelC Physical Facility and GroundsD Equipment and UtensilsE Requirements to Establish a Production and Process Control SystemF Requirements for Quality ControlG Requirements for Components, Packaging, Labels and for Product Received for Packaging or LabelingH Requirements for the Master Manufacturing RecordI Requirements for the Batch Production RecordJ Requirements for Laboratory OperationsK Requirements for Manufacturing OperationsL Requirements for Packaging and Labeling OperationsM Holding and DistributingN Returned ProductsO Product ComplaintsP Records and Recordkeeping
Good Agricultural Practices/Good Handling Practices
ISO 9001:20080 Introduction1 Scope2 Normative Reference3 Terms and Definitions4 Quality Management Systems5 Management Responsibility6 Resource Management7 Product Realization8 Measurement, Analysis, and
Improvement
ISO 9001:20150 Introduction1 Scope2 Normative Reference3 Terms and Definitions4 Quality Management Systems5 Management Responsibility6 Resource Management7 Product Realization8 Measurement, Analysis, and
Improvement9 Performance Evaluation
10 Improvement
CANNABISMONOGRAPH
Cultivation• Clone/Seedling records• Daily production batch records• Weekly Grow Room Inventory• Integrated Pest Management• Integrated Crop Management
Harvest/Cure/Trimming• Harvest Record• Trimmer Logbook• Cure Room Transfer Log
Extraction/Purification• Extractor Logbook(s)• Extraction Dataset• Inventory log (per extractor run)• Purification Batch Records
Analytical Laboratory• Testing protocols• Analyst proficiency• Equipment calibration• Equipment validations
External Laboratory Testing• Chain of Custody Form• Certificate of Analysis• Preliminary Data Reports• ISO13485 Compliance
Marketing• Label Design• Product Photographs• Product Inserts
Product Registration• Registration Spreadsheet• Brand Registration to State• Labels, Photos, Inserts
Packaging and Labeling• Scale calibration• Packaging Batch Record• Label Reconciliation• Finished Goods Log (Vault)
Product Sales• Order Form• Product Invoice• Transport Manifest• Return Log
EXAMPLE QUALITY MANAGEMENT SYSTEM FOR CANNABIS MFG
Thank you!
