m-HACCP template Company/ Client Name: Product: Phase/ Dosage format: Start date: End date: Organization HACCP

Team and roles 1. 2. 3. 4. 5. Noted by: _______________________________________ CEO/ COO

Approved by: _______________________________________ VP-Manufacturing and Operations Cc: HACCP Team, VP-Mfg & Operations

Checklist for information prior to review and analysis 1. Pre-formulation and stability studies, materials characterization 2. Formulation, unit dose 3. List of suppliers and alternate suppliers used in manufacturing with complete CAs, route of synthesis, impurities, solvents, intermediates, starting materials 4. Manufacturing process 5. All equipment used, its design and operational specifications, calibration and maintenance history 6. Construction or review of PFD (process flow diagram) and P&ID if necessary (piping and instrumentation diagram), check if updated or an option for a walk-thru

Table1: The 12-step HACCP programme Features Descriptions 1) 2) 3) 4) 5) 6) Preliminary Tasks Define scope of system and risk question Assemble HACCP team consisting of R&D, manufacturing, QA and define scope Describe/ review product and process, equipment properties, characteristics etc. (in short, all information about productprocess-equipment-utility, PPEU) Identify intended use Challenge/ Review/ Refine PFD (process flow diagram) as well as P&ID Verify PFD and P&ID onsite but it must be updated frequently Risk Assessment, Monitoring, Control and Communication 1) Conduct Hazard Analysis 2) Determine CCPs 3) Establish critical limits for each CCP 4) Establish monitoring and control system for each CCP 5) Establish corrective actions for each CCP 6) Establish verification procedures to confirm if HACCP is working 7) Establish documentation and record keeping

Table2. Hazard identification, Critical Control Points, Limits and Actions Processing Step Dispensing Hazard identification (classification matrix: Equipment, Manpower, RM, Utility, Facility Microbiological, chemical and physical) F- Mechanical disturbances M-Dispensing the wrong ingredient (i.e. vitamin E-SD, vitamin E) M- Dispensing the wrong quantity (i.e. 0.1 grams vs. 0.01 grams of F&DC Red) M- Dispensing an expired lot Addition of pre-dispensed materials to inCritical control Points Critical Limits Corrective Action Cost Resp.

process containers F- Static charges M- Operator error R - Raw material debris from supplier Sifting of raw materials Damage or fracture on sieve during sifting. Cross contamination with products of previous batch during sifting. Exposure of materials to contamination during sifting Incorrect dry mixing time and speed of mixing blade Quantity of water in binder solution Mixing time Rotational speed of impeller Disheveled gown of operator, insufficient cleaning of equipment The loading of the processing bowl Incorrect outlet air temperature Improper air flow in the inlet-air plenum and velocity of airflow Incorrect choice of container and air distributor Blockage of filter bag Filter bag shaking Damage of inlet-air filter, damage of thermometer

Dry-Mixing Wet mixing Granulation Spray Granulation Drying

Compression Coating Packaging Summary

Three hazards ( note: RISK = HAZARD x DOSE/ EXPOSURE TIME ) Physical High and low Temperature operation, steam, glycols etc. High pressure compressed air, nitrogen, steam etc. Vacuum High pressure fluidizing air x-rays, radiation Electricals, Static charges Sources of ignition Rotating impellers, motors Removable parts (big and small) of equipment Small instruments, devices, fixtures near product, RM Elevated storage, platform Dust particles People Air, water Earthquakes Organic solvents (liquid-state) used in production (coacervation microencapsulation), maintenance, cleaning etc. All other solid-state raw materials, chemicals both and not GRAS used in production, maintenance, cleaning etc. Pesticides Personnel/ human wastes Microorganisms, viruses, parasites Insects , rodents Multi-cellular organisms Other unknown microbiological particles

Chemical

Microbiological

Hazard Identification and Critical Point Matrix Microbiological RM MOs - contamination Chemical Moisture microbial growth Physical Debris - contamination Particle size-dust explosion

Product Equipment Utility Facility Insects Insects, rodents High pressure compressed air, nitrogen, steam

References: 1. FAO (1998), Food Quality and safety system: A training manual on Food Hygiene and the Hazard Analysis Critical Control Points (HACCP) system, Food and Agriculture Organization of the United Nations, Rome. 2. The application of HACCP and risk management in the pharmaceutical process, Glory Bansal, Bharat Parashari, Dept. of pharmacyDEPT. OF PHARMACY, MANAV BHARTI UNIVERSITY, SOLAN (H.P.), INDIA. 1 Ph.d., Head, Dept. of Pharmacy, Manav Bharti University, SOLAN (H.P.), INDIA,2DEPT. OF PHARMACY, MANAV BHARTI UNIVERSITY, SOLAN (H.P.), INDIA