Protection of patient by managing risk in the quality systems and manufacturing process is being given prime importance in the pharmaceutical industry. Every product and every process associated with risks. It is important that product quality should be maintained throughout the product lifecycle.

In earlier days risk in the product quality and process had been assessed in the following informal ways.

  • Trends review
  • Check lists
  • Flow charts
  • Observations compilation [From complaints, deviations etc.]
  • Changes review

Now the risk management approach initiated by regulatory agencies with recognized management tools along with support of statistical tools in combination, which make easy for application of quality risk management principles across the industry.

A Risk Management Program starts with identifying the possible risks associated with a product or with the process used to develop, manufacture, and distribute the product.An effective quality risk management ensures the high quality of drug product to the patient. Inaddition quality risk management improves decision making if a quality problem arises. It should include systemic processes designated to co-ordinate, facilitate and improve science-based decision-making with respect to risk.

The Fda’s Initiative On Risk Management Approach

The FDA defines a Risk Management as, “a strategic safety program designed to decrease product risk by using one or more interventions or tools.” The FDA proposes that: “…the sponsor of every product submitted for approval considers how to minimize risks from the product’s use. Risk management planning generally encompasses all efforts by a sponsor to minimize the risk from its product’s use and may include product labeling, risk assessment, pharmacovigilance, and special studies or interventions.”

The FDA expects the Risk management to follow a basic process of:

1. Learning about and interpreting a product’s benefits and risks,

2. Designing and implementing interventions to minimize a product’s risks,

3. Evaluating interventions in light of new knowledge that is acquired over time, and

4. Revising interventions when appropriate.

FDA Guideline Risk Management Elements
Learning about and interpreting a products benefits and risks Risk and Issue Management Strategy, Risk Identification Technique, Risk Evaluation Technique.
Designing and Implementing Interventions Risk Response Planning, Risk and Issue Management Plan
Evaluating and Revising Interventions Risk and Issue Management Plan

Risk Management Methods

To make risk-based decisions, a systematic approach is essential. The ICH Q9 guideline, Quality Risk Management, provides a structure to initiate and follow a risk management process. The following methods widely used in the industry for risk management.

  • Basic risk management facilitation methods (flowcharts, check sheets, etc.)
  • Failure Mode Effects Analysis (FMEA)
  • Failure Mode, Effects, and Criticality Analysis (FMECA)
  • Fault Tree Analysis (FTA)
  • Hazard Analysis and Critical Control Points (HACCP)
  • Hazard Operability Analysis (HAZOP)
  • Preliminary Hazard Analysis (PHA)
  • Risk ranking and filtering
  • Supporting statistical tools
No Method Area of Application
1 Basic risk management methods. Flow charts/Process mapping, Check lists, Cause & Effect diagrams Data organization to facilitate decision making in the areas of 1.Failure investigations 2.Root cause analysis
2 Failure Mode Effects Analysis (FMEA) Equipments and facilities which are involved in the manufacturing.
3 Failure Mode, Effects, and Criticality Analysis (FMECA) Risks associated with manufacturing process.
4 Fault Tree Analysis (FTA) Root cause analysis and failure investigations
5 Hazard Analysis and Critical Control Points (HACCP) Monitoring of critical points not only in the manufacturing process but also in other lifecycle phases.
6 Hazard Operability Analysis (HAZOP) Manufacturing processes, evaluating process safety hazards.
7 Preliminary Hazard Analysis (PHA) Analyzing existing systems or prioritizing hazards and commonly used early in the development.
8 Risk ranking and filtering Prioritize manufacturing sites for inspection/audit by Regulators or industry, to evaluate both quantitatively-assessed and qualitatively-assessed risks within the same organizational framework.
9 Supporting Statistical Tools Data assessment.

Four Major Components

The risk management program consists of four major components: risk assessment, risk control, risk review, and risk communication. All four components are essential. All the above methods should address the mentioned four basic components.

Team selection and method selection are also plays a vital role in the risk management process, so care should be taken while selection of risk management team and method.

FMEA is the preferable method for risk management in the pharmaceutical industry as FMEA analysis include higher reliability, better quality, increased safety and its contribution towards cost saving includes decreased development time and reduced waste and non value added operations.

Potential Areas For Risk Management Application

The following areas are identified as potential in the pharmaceutical industry for quality risk management application.

  1. Documentation [SOPs, Batch records etc.]
  2. Training [Schedules and effectiveness]
  3. Quality defects [Complaints, deviations, OOS etc.]
  4. Audits [Compliance]
  5. Periodic reviews [Revalidation assessment]
  6. Change controls [Impact assessment]
  7. Development reports [Process and controls verification]
  8. Facilities, Equipment and Utilities [Components, maintenance etc.]
  9. Material management [Receipt, storage and distribution]
  10. Packaging and labeling [Container closure system and labeling]

Conclusion

The use of a risk-based approach provides a consistent method for decision making which was easily associated with resource allocation and ensuring patient safety. Ultimately, applying risk management to pharmaceutical industry should reduce the number of threats or minimize their impact through the consistent use of the tools/methods and periodic review. The output of the risk management supports to the organization to meets the defined goals.

Reference

Guidance for industry “Q9 Quality risk management” by US department of Health and Human Services, Food and drug Administration, Center for drug and evaluation research June 2006.