Risk Management for the Pharmaceutical Industry

1 Solutions88 March product and every process has an associated risk. Every en-terprise should have a methodology for identifying and evaluating therisks it faces and it should have a process for generating interventionplans to reduce the risks to an acceptable level. This process is gener-ally referred to as a Risk Management Plan (RMP).The FDA s Risk-Based Approach InitiativeIn early 2002, the FDA announced its Pharmaceutical CurrentGood Manufacturing Practices (cGMPs) for the 21st Century: A Risk-Based Approach. According to the FDA position paper, .. it is timeto step back and evaluate the currency of these [drug cGMP] pro-grams so that: The most up-to-date concepts of risk Management and qualitysystems approaches are incorporated while continuing to ensureproduct quality; The latest scientific advances in Pharmaceutical manufacturingand technology are encouraged; The submission review program and the inspection program oper-ate in a coordinated and synergistic manner; Regulation and manufacturing standards are applied consistently; Management of the program encourages innovation in the phar-maceutical manufacturing sector; and FDA resources are used most effectively and efficiently to addressthe most significant health risks .

2 The FDA defines a Risk Management Program (RMP) as, a strategicsafety program designed to decrease product risk by using one ormore interventions or tools. The FDA proposes that: ..the sponsor of every product submitted for approval considerhow to minimize risks from the product s use. Risk Management plan-ning generally encompasses all efforts by a sponsor to minimize therisk from its product s use and may include product labeling, risk as-sessment, pharmacovigilance, and special studies or interventions. The FDA expects the RMP to follow a basic process of: (1) learningabout and interpreting a product s benefits and risks , (2) designingand implementing interventions to minimize a product s risks , (3)evaluating interventions in light of new knowledge that is acquiredover time, and (4) revising interventions when appropriate. Risk Management Plans (RMP)A Risk Management Program starts with identifying the possiblerisks (and benefits) associated with a product or with the processused to develop, manufacture, and distribute the product.

3 The follow-ing questions should be asked at each stage of the product s life cycle: What are the safety risks ? Who is at the highest risk? What populations are at risk? Are the risks predictable? Are the risks preventable?The last question, are the risks preventable is very important be-cause it forms the basis of the intervention plan. In order to deter-mine if the risk is preventable, the root cause of each risk has to bedetermined. Once the root cause is established, the probability of oc-currence can be calculated and the risk Management Plans correlate the listing of risks with a listing ofRisk Reduction Goals. The Risk Reduction Goals are the endpoint ofthe intervention plans. For example, if the severity of the risk has beenevaluated as Severe with a frequency of one per ten thousand, theRisk Reduction Goal could be to reduce the severity to Moderate and reduce the frequency to one per five hundred thousand . The in-tervention plan details the steps that will be taken to reduce the riskto the acceptable levels and includes the metrics that will be used tomeasure the progress against the stated risk reduction goals.

4 Two critical elements of the intervention plan are the criteria thatwill be used to evaluate the progress toward achieving the stated riskreduction goal and the metrics use to measure the results. Accordingto the FDA, an overall approach to RMP evaluation ideally would:1. Select well-defined, validated metrics. 2. Use at least two different evaluation methods for key RMP goalsor objectives. Preferably, the different evaluation methods would beboth quantitative and representative to offset the biases that are in-trinsic to any single evaluation process. 3. Use qualitative data collected from a large and diverse group ofpatients when quantitative data are either not available or not appli-cable to the evaluation measurement. Qualitative data such as focusgroup testing may be useful in assessing the effectiveness of educa-tion and comprehension about safety and risk information. 4. Consider using evaluation methods to assess if each RMP tool isperforming as intended. The remaining element of a RMP is a process for continuous reviewand evaluation.

5 There should be a methodology established that as-sures the RMP is regularly reviewed and updated as necessary de-pending upon the status against the stated Risk Reduction Goals. Thefrequency of review should be based on the evaluation of the risk. TheRMP for moderate to severe risks should be reviewed and updatedmore frequently than less those that have a of a Risk Management PlanRisk and Issue Management StrategyThe Risk and Issue Management Strategy defines the approach, re-sponsibilities, and activities that should be done to effectively managethe risks and issues. The Risk and Issue Management Strategy con-tains a brief explanation on the manner in which risks and issues willbe handled by responsible individual(s) and how risks and issues willbe raised, analyzed, reviewed, communicated, and and Issue Management PlanThe Risk and Issue Management Plan documents the strategy formanaging the risks and issues and describes the corresponding ap-proach, responsibilities, activities, and approach to risk and issue Management specifies the mannerin which risks and issues will be handled.

6 The initial risk and issueidentification approach is defined, the notification process and theway to document the risks and issues are determined, and the escala-tion process is Risk and Issue Management Plan identifies the managers whohave primary responsibility for managing the risks and issues, and thedomains for which they carry this responsibility. It identifies the domainexperts who will lead the analysis for specific Management Risk and Issue Management Plan also provides tables to be usedwhen categorizing and evaluating the risks and Management for thePharmaceutical IndustryLearning about and interpreting a products benefits and risksRisk and Issue Management StrategyRisk Identification TechniqueRisk Evaluation TechniqueDesigning and Implementing InterventionsRisk Response PlanningRisk and Issue Management PlanEvaluating and Revising InterventionsRisk and Issue Management PlanFDA GuidelineRMP ElementsSolutionsRisk Identification TechniqueThe Risk Identification technique provides methods to identify risksthat could affect the safety, quality, reliability, or durability of a prod-uct, process or program and organizes the risks in order to evaluatethem and plan appropriate responses.

7 Sometimes this is referred toas a Hazards Analysis. A Hazard Analysis is often used in conjunc-tion with a Failure Modes and Effects Analysis. Risk Evaluation TechniqueThe Risk Evaluation technique evaluates the priority and severity ofan identified risk that threatens the safety, quality, reliability, or dura-bility of a product, process, or program. The Risk EvaluationTechnique allows the project team to assess the risk relatively quicklyand to organize the team for subsequent Criteria Determination TechniqueThe Impact Criteria Determination technique helps to identify theproject areas or product attributes that might be affected by a risk or aproblem, and establishes the criteria used to evaluate the impact ofproblems or the potential impact of project risk and problem will have an impact assigned to it inorder to determine its severity and priority. Risk Response Planning TechniqueThe Risk Response Planning technique allows the project team todetermine how it will react to specific risks or problems.

8 The range ofresponses can include accepting the risk as it is; changing the product,process or program; avoiding the risk altogether; or actively pursuingways to reduce the risk s threat to the product, process, or program. ChecklistsChecklists are used to assure that all of the necessary RiskManagement Procedures have been identified and on the circumstances of the project, checklist should bereviewed at key milestones throughout the PreparedAll products and all processes have an inherent element of risk. Theimportant questions include: What risks are involved? What impacts do the risks have? How do we manage the risks to keep them within acceptable levels?A Risk Management Plan helps to answer these Management Plans have been used as best business practicesfor many years, especially in business environments experiencing re-duced resources with increased liabilities. One such organization isthe FDA. The FDA recognizes that it needs to reorganize its proce-dures and processes to incorporate the use of Risk ManagementPrograms within the agency and wit hin the industries it regulates.

9 The key to being prepared it to understand the FDA s current think-ing on Risk Management Plans, as well as its recommended proce-dures for establishing, conducting, and communicating an effectiveRMP that will comply with the FDA guidelines. By Edward GriffithPrincipal Consultant, Fujitsu Consulting90 March 2004 LEVEL PLUS SENSORSKEEP YOUR PROCESS AND YOURBOTTOM LINE s a breakthrough, the best liquid level sensors don t have to cost the Sensors meet ASME BPE and 3 Asanitary standards and withstand CIP andSIP processes. For the best performingsensors at the lowest installed cost of ownership call or visit our website. Please visit us at theInterphex Show, booth # our new website and interactive InfoLINK 4C1395 or Call 800-369-8814