Quality Risk Management PDF

 Unit III: Quality Risk Management ANABELLE B. ALEJO Associate Professor I [email protected] COLLEGE OF HEALTH SCIENCES Department of Pharmacy  Objectives: By the end of the unit, the students must have: 1. understood the prin...

 Unit III: Quality Risk Management ANABELLE B. ALEJO Associate Professor I [email protected] COLLEGE OF HEALTH SCIENCES Department of Pharmacy  Objectives: By the end of the unit, the students must have: 1. understood the principles of quality risk management and contamination (IO1, IO3, IO4, IO8, PO2, CO3). 2. identified the possible risk in the preparation of different dosage forms (IO1, IO3, IO4, IO8, PO2, CO3). 3. created a quality risk management plan in the preparation of creams following the principle of Failure Mode and Effects of Analysis (FMEA) tool (IO1, IO3, IO4, IO8, PO2, CO2). COLLEGE OF HEALTH SCIENCES Department of Pharmacy Risk - It is described as the combination of the probability of an adverse occurrence and its severity. Detectability is also considered for the risk characterization. - Considers various stakeholders: 1. Patients 2. Medical practitioners 3. Government regulators 4. Industry QUALITY RISK MANANGEMENT A systematic process for the assessment, control, communication and review of risks to the quality of the drug product across the product life cycle. Principles of Quality Risk Management 1. The evaluation to the risk to quality should be based on scientific knowledge and ultimately link to the protection of the patient. 2. The level of effort, formality and documentation of the quality risk management should be commensurate with the level of risk. The Regulatory Basis for Process Validation 1. ICH Q8 – Pharmaceutical Development 2. ICH Q9 – Quality Risk Management 3. ICH Q10 – Pharmaceutical Quality System QRM – What is it? Structured approach to understanding and managing risk in the Pharmaceutical Industry Started from ICHQ9 “Quality Risk Management” working group Becoming more of a regulatory expectation FDA guideline in June 2006 EU added in January 2006 Japan adopted in September 2006 QRM – Why do it? Regulatory and Compliance Becoming more and more a regulatory expectation Patients and Customers Greater assurance of patient safety - elements of risk more visible - risk reduction actions can be better identified and linked to each risk Business Case: Makes decisions more robust Priorities/focus resources Eliminate un-required activities and thus reduce workload Support lean/agile endeavors/projects Support our continuous improvement Quality Risk Management (ICH Q9) - a systematic process for the assessment, control, communication and review of risks to the quality of the drug product across the product lifecycle - Use of policies / procedures designed to minimize the occurrence of patient harm due to an incorrect test result - Example: 1. Run QC material to ensure the instrument is performing properly. 2. Monitoring refrigerator temperature where reagents are stored. Two Primary Principles of QRM 1. Evaluation of the risk to quality should be based on scientific knowledge and ultimately link to the protection of the patient. 2. The level of effort, formality and documentation of the risk management process should be commensurate with the level of risk. Overview Process Quality Risk Management Process 1. Risk Assessment a. Risk Identification - Methodological use of information to identify sources of failure, related to the risk or problem in question, and forms the basis for subsequent steps. b. Risk Analysis - To rate the risk by linking probability and severity. c. Risk Evaluation - Comparison against criteria is performed and the level of evidence obtained is analyzed. Quality Risk Management Process 2. Risk Control Risk Control Four Essential Questions Is the risk level acceptable? What can be done to reduce or eliminate the risk? What is the balance between benefits, risks and resources? Are there new risks introduced as result of the risk being controlled? Quality Risk Management Process 3. Risk Review - The risk management process should be revised whenever a change occur, planned or unplanned, namely changes originated by change controls or failure investigations. Frequency of risk reviews is dependent on the level of risk and may result in the reassessment of previous decisions. Determine Risk Factors Severity What are the factors which must be considered that will have an impact on the patient/compliance/company (consequences) Probability/Occurrence What is the likelihood that the impact on the patient/compliance/company will occur? Detection Can you detect the risk? Choose a Tool Define Risk Reduction Measures Two basic risk control strategies: 1. Prevent - Stop the hazard occurring at all Define Risk Reduction Measures Two basic risk control strategies: 2. Protect - Decrease the severity/impact Ex: If severity is unknown, get a medical opinion Installing an eye-wash station - Decrease the probability Ex: Slow down the machine rate Perform maintenance less frequently - Increase the detection Ex: Perform 100% visual inspection Implement additional routine checking Define Risk Reduction Measures Once measures have been implemented, reapply tool to show - How each individual potential risk was reduced - What the overall level of risk is Shows that we have: - Followed the QRM process - Understood and accepted the residual risk - Effectively completed the analysis Conclusion Bad decisions cannot be “made right” by applying QRM QRM works best with multi-disciplinary perspectives. Even if the tool is simple (informal), you must document how you reached your decision. There are no strict rules for applying tools and adapting tools. Each situation is different, but all situations should relate back to consumer and compliance risk. CONTAMINATION/CROSS CONTAMINATION Definition of Terms Contamination - The undesired introduction of impurities of a chemical or microbiological nature, or of foreign matter, into or onto a raw material, intermediate, or active pharmaceutical ingredient during production, sampling, packaging or repacking. Storage or transport. Cross Contamination - Contamination of a starting material, intermediate product or finished product with another starting material or product during production. Mix-up - Mix of different items but not necessarily contaminated. Contaminant - Any particulate, molecular, non-particulate and biological entity that can adversely affect the product process. Origin of Cross Contamination 1. Poorly designed air handling systems and dust extraction systems. 2. Poorly operated and maintained air handling systems and dust extraction systems. 3. Inadequate procedures for personnel and equipment. 4. Insufficiently cleaned equipment. Cross Contamination can be Minimized by: 1. Personnel procedures (skilled manpower, technical awareness). 2. Adequate premises (proper lay-out, area classification). 3. Use of closed production systems (man & material Movement). 4. Adequate, validated cleaning procedures. 5. Appropriate levels of protection of product. 6. Correct air pressure cascade (HVAC design and Air Distribution). How are Contaminants Removed? 1. By efficient filtration of supply air. 2. By dilution of contaminants or flushing contaminants by supplying adequate air quantities to the room Clean Room? - An environment where the particulate contamination and bacterial contamination are limited to prescribed levels. Facility Parameters that Need to be Controlled: 1. Temperature 2. Humidity 3. Air cleanliness 4. Room pressure 5. Air movement 6. Lighting Parameters Influencing the Level Protection 1. Number of particles in the air 2. Number of micro-organisms in the air or on surfaces 3. Number of air changes for each room 4. Air velocity 5. Air flow pattern 6. Filters (type, position) 7. Air pressure differentials between rooms 8. Temperature, humidity Prevention: Proper Hygiene 1. Proper dress - Clean uniform, no tears, closed toe shoes, no heels, clean footwear, hair restraints, no jewelry, no visible body piercing, no nail polish, false fingernails, no false eyelashes 2. General Habits - No eating, no drinking, no smoking, no spitting, no chewing gum - Inform the supervisor if exhibit any of the following symptoms: jaundice, diarrhea, vomiting, fever, sore throat with fever, boils or cuts, discharges from ears, nose or eyes, excessive coughing or sneezing 3. Washing habits Before: starting to work After: handling raw ingredients, smoking eating or drinking using handkerchief or tissue, touching any dirty object or surface, touching any part of the body, cleaning or taking out of garbage, using the washroom. MICROBIAL CONTAMINATION Source: Air carrying dust. Outer skin of the personnel. Persons walking will liberate 5000 bacteria/min. A single sneeze will produce upto 1 million bacteria. Manufacturing process itself can generate contaminants. CLEANING PROCEDURES 1. General Housekeeping Cleaning and housekeeping of all areas within a facility should be performed routinely. This includes floors, ceilings, walls, work surfaces. Empty bins regularly Clean any spills immediately Remove all unnecessary equipment and store appropriately. 2. Cleaning Validation Documented evidence that provides high degree of assurance that approved cleaning procedure will provide equipment that is suitable for processing of pharmaceutical products. Cleaning validation is the heart of pharmaceutical industry. If the proper cleaning is not done, contamination may occur in the product and whole process of formulation hampered by this. CLEANING PROCEDURES 3. Facility and Equipment a. Facility Be suitable size, construction and location to facilitate suitable cleaning, maintenance and appropriate operation. Have adequate space for placement of equipment as well as production and packaging materials. Consider the sequence of operation during the design phase, paying particular attention to the location of equipment and removal of unnecessary traffic. Have adequate internal temperature, ventilation and lighting. Have smooth surfaces (no cracks, crevices or shedding), which are easily cleaned. Have adequate segregation materials products and components to further reduce the risk of cross contamination. CLEANING PROCEDURES 1. Facility and Equipment b. Equipment All equipment should have smooth inert surfaces which are not additive or adsorptive, and installed in an area that is easily cleaned. If the equipment is difficult to clean, then consider using it for a dedicated purpose. CLEANING PROCEDURES 4. Manufacturing process Dedicate a facility to the manufacture of a single formulation of product. Manufacture products in a campaign, with the appropriately qualified cleaning processes and checks performed in-between batches to minimize the amount of product changeovers. Utilize a closed manufacturing system. Perform an area line clearance according to approved procedures following each cleaning process and between each batch. Zone the facility. Use cleaning status labelling on all equipment and materials used with manufacturing facility. CLEANING PROCEDURES 5. Mitigation CONTAMINATION MITIGATION STRATEGIES People Clean room garments Ventilation Using HEPA Filters Equipment Good housekeeping Room Structure Good design Get in Touch With Us Send us a message or visit us City of Batac, Ilocos Norte, Philippines (63) 77-600-0459 [email protected] Follow us for updates facebook.com/MMSUofficial www.mmsu.edu.ph