Quality Risk Management (ICH Q9): WHO Model for Sustainable Quality Medicines Longe Sunday Anthony Head- Quality Assurance May & Baker Nigeria Plc. Pharmacentre, Ota, Nigeria eaglesconsult@gmail.com; Slonge@may- Baker.com.
Preamble The Pharmaceutical Industry is constantly being challenged to comply with rigorous regulatory requirements. Therefore the need to ensure that a company s processes are being operated at a level of control using risk management approach Compliance is evolving from a reactive approach - Inspection, checks and comprehensive testing to a Proactive approach scientific and risk management approach. However, compliance is not a one-time event and organizations are redesigning their compliance programs to make them repeatable processes that could be sustained.
Challenges Rising Standards of Quality Rising Regulatory requirements and reporting mandates- ADR s, ADE s etc. Competitive sector within a harsh business environment- Conversion Cost vs Quality Compliance is not just a regulatory requirement, but a Quality Culture that guarantees good quality product.
Who Governs
Regulators Speak through GLP Good Laboratory Practices 21 CFR Part 58 40 CFR Part 160 ( EPA ) GALP Good Automated Laboratory Practices EPA Directive 2185 ( 1995 Ed. ) ICH Guidelines Quality, Efficacy, Safety, CTD / e CTD Regulations cgmp Current Good Manufacturing Practices 21 CFR Part 211 ( Pharma ) 21 CFR Part 820 ( Med devices) 21 CFR Part 110 ( Food ) 21 CFR 600 680 Biologics Q1A(R2) Q1B Q1C Q1D Q1E Q7 Q8(R1) Q9 Stability Testing GAMP Good Automated Manufacturing Practices GAMP 5(ISPE) Guide GCP Good Clinical Practices 21 CFR 312 Sub part Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients Pharmaceutical Development Quality Risk Management Q10 Pharmaceutical Quality System M4(R3)* Organization of the Common Technical Document for the Registration of Pharmaceuticals for Human Use
Concept of Quality Risk Management -The assessment of individual risks related to specific products and starting materials and the recognition of hazards at specific stages of production or distribution. - Quality risk management (QRM) is a process that is relevant to all countries and should provide a rationale to understand risk and mitigate it through appropriate and robust controls. - QRM is the overall and continuing process of appropriately managing risks to product quality throughout the product's life-cycle in order to optimize its benefit risk balance.
ICH Q9 Quality Risk Management
MACHINES (Equipment) METHODS (Processes) MILIEU (Environment)
Road to Compliance
MATERIAL CONTROL Importance of Vendor Development & Qualification Using a pharmaceutical ingredient without a knowledge of the specific manufacturing site, Regulatory status, and how it got to you is like traveling without a definite destination.
Are ultimately responsible for the use of appropriate ingredients and assuring ingredient quality at every stage of the supply chain and Storage before final conversion. Pharmaceutical Ingredient Supply Chain A Shared Responsibility! API Manufacturers & Vendors Are responsible for assuring that ingredients they supply comply with GMP, are not misbranded or contaminated, are packaged/stored appropriately, and adhere to signed Quality Agreement. FPP (MAH) & Regulators
Process Control CCP Dispensing Equipment e.g. RLAF, Balance, scoops MAN Environment e.g. HVAC, Drains, lightings Cross contamination, inaccurate quantities,failure incidence; Reprocessing/rework, Overdosing or underdosing, Poor product quality Temp/RH/DP out of control; contamination Material Mixups; inaccurate weighing etc.
Equipment Controls Equipment must be located, designed, constructed, adapted and maintained to suit the operations to be carried out. The layout and design of equipment must aim to minimize the risk of errors. Permit effective cleaning and maintenance in order to avoid cross-contamination, build-up of dust or dirt, and, in general, any adverse effect on the quality of products.
URS (To specify the end use requirement) Design (By manufacturer to meet expectations) Manufacturing of Equipment (Easy to handle, Easy to clean. Good surface Finishing) Retirement/ decommissioning Usage Evaluation BM Breakdown Maintenance (Trending) PM (Preventive Maintenance to maintain equipment as per functionality) PQ Placebo run (Matrix approach to qualify for intended use) FAT (To ensure for functioning as per expectation at manufacturing site) SAT (Receive at site In proper condition) IQ/OQ Qualify equipment as per SOP
Calibration What? A set of operations that establish, under specified conditions, the relationship between the values of quantities indicated by a measuring instrument or measuring system, or values represented by a material measure or a reference material, and the corresponding values realized by its standards. Why? When process measuring instruments age and experience physical stress or temperature variations, critical performance gradually declines. This is called drift. The slow variation with time of metro logical characteristics of the measuring instruments. As a result of this, the measurement results become unreliable and ultimately the production quality can suffer. Drift cannot be eliminated, but it can be discovered through calibration.
Qualification & Validation Risk-based approach. Conduct appropriate levels of product impact and critical risk assessment of systems and system functionality early in the planning stage and then throughout the validation life cycle as required. Qualification URS, DQ, FAT, SAT, IQ,OQ, PQ Process Validation & Cleaning Validation Process & equipment Design Vs Equipment performance are critical to process validation and cleaning validation success.
Calibration Benefits Calibrated equipment provides confidence that products/services meet their specifications. Calibration: -Increases production yields, Optimizes resources, - Assures consistency and ensures measurements are compatible with those made elsewhere. Ensures measurements are appropriate based on National and International standards and traceable. Avoid wastages due to uncertainties.
New FDA guidance on Process Validation January 2011 Concept Stages Outcome Process Validation: General Principles and Practices WEF: Jan'11 Stage 1- Process design: (The commercial manufacturing process is defined during this stage based on knowledge gained through development and scale-up activities). Stage 2 Process Qualification: (During this stage, the process design is evaluated to determine if the process is capable of reproducible commercial manufacturing). Stage 3 Continued Process Verification: (Ongoing assurance is gained during routine production that the process remains in a state of control). PQR for each year Robust manufacturing process. Compliance to the regulatory requirement.
Laboratory Controls Qualified personnel Effective sample management Approved specifications and methods Appropriate Qualified instruments Effective calibration program Effective preventive maintenance program Adequate SOP for OOS and OOT Trending of laboratory failures and CAPA management. Glassware Controls
Pharmaceutical Quality System Quality by Statistical Process Control Review of historical output of process to identify the limits of a stable process and source of error. Quality by Inspection Inspect Approve / Reject
Pharmaceutical Quality System Product Quality Reviews/ Management reviews Change Control Planned Deviation Internal Quality Audit Training Incidence Investigation CAPA Market Complaint
CAPA Sources Supplier Audits Nonconforma nces Deviations Out of Specification Regulatory Audits Complaints Internal Inspections Out of Specification Adverse Drug Reactions Adverse Events Incoming Inspections And others
Road to Compliance
When it comes to ensuring drug product quality and ultimately Consumer/Patient Safety... We need to think and act globally!