Principles of Quality Risk Management found their application in our day to day life, apart from their application in the industry, production, regulations etc.

In pharmaceutical industries principles of QRM found their application for both manufacturers as well as reviewers/ regulators. For manufacturer’s, it should be well understood that regulatory requirements cannot be avoided by the implementation of QRM. The various ways, how QRM principles can be applied are as follows:

  1. Helps the manufacturer to design, develop, manufacture and distribute the product in an efficient way.
  2. Helps the manufacturer to comply with the regulatory requirements.
  3. Can be applied for planning self-inspection or internal audit.
  4. Promote the inclusion and implementation of newer technologies and other latest advancements.
  5. Helps reviewers or regulators for systematic and structured planning of product review.
  6. Helps auditors to perform risk-based inspections which shall include the extent and frequency of inspection. Manufacturers with history of poor GMP compliance can have inspections more frequently and shall cover all the critical aspects.
  7. Helps the reviewer to understand the residual risk in the system.
  8. Patient centric review of the product can be done.
  9. Helps to ensure the maintenance of quality, safety and efficacy of the product.
  10. Helps to ensure better communication among manufacturer, regulator and consumer i.e. patients.

A detailed overview of QRM Application is as follows:

  1. Product Development: QRM approach if implied thoroughly helps in the various stages of development of new product. Various types of risk assessment tools viz. flowcharts, decision trees, fault tree analysis (FTA), cause and effect diagrams etc. can be used at preformulating stages when product and process knowledge is scarce. Risk assessment shall cover all the risks associated with the formulation, stability, bioavailability and overall quality, safety and efficacy of the product under development.

QRM approach shall also be used in defining the Critical Quality Attributes (CQA’s)and Critical Process Parameters (CPP’s) of the process.

  1. To decide the extent and frequency of qualification and validation activities: During development of any process, one has to develop a certain extent of assurance. The same could be developed by rational design of experimentation and robust evaluation of data during the product and process development phase. During the process development one has to take number of validation batches. The design of these validation batches are based on risk assessments related to the product and process under development. The outcome of process validation reinforce the risk based decisions that should demonstrate control over all identified critical sources of variability.

The extent of qualification of equipment and calibration of instruments are also decided on the basis of impact assessment which is further derived from the QRM. Higher the risk, higher will be the level and extent of qualification and calibration required for any equipment / instrument.

  1. Plant Design: Whether the firm can construct a multi-product facility or a single product facility depends on the nature of drug to be manufactured. For example, in case the firm is intending to manufacture penicillin or sex hormones or oncology products etc., it is always advisable to have dedicated facilities as the risk severity is very high due to nature of product being handled as they are very sensitive and potent. Even regulatory guidelines suggest to have dedicated facility.

However, in case of multi-product facility level of contamination, cross-contamination, mix-up control required depends on various factors. A manufacturer may provide various controls and procedures to safeguard the products. Pressure differentials, dedicated equipment, dedicated areas, access control, containment studies, cleaning validation, residual limits etc are some of the few areas where a manufacturer can work before deciding about the multi-product facility.

  1. Training: QRM finds its application in identification of training and preparing Training needs matrix for each employee working in an organization. Even an employee who is entrusted with carrying out of QRM implementation shall be trained thoroughly on QRM principles and its applications.

An operator working in aseptic environment needs to be trained thoroughly w.r.t. to implementation of GMP principles in Aseptic processing than the operators working in the secondary packing area. As the risk involved is different w.r.t. difference in nature of operations. Hence, training needs shall also be different.

  1. Self Inspection or Internal Audit: A firm shall include the risk based self-inspection programme in their procedure in addition to the frequency-based inspections. An area with lower level of compliance may require frequent inspections to achieve better compliance level than the area meeting the compliance levels. Hence, QRM approach helps to give more emphasis on the weaker areas than the stronger areas.

 

The above-mentioned areas are only few of the vast number of applications that QRM have especially in a pharmaceutical industry. It can be applied on the simplest of the activities to the complex operations. Hence, QRM shall be made part of every aspect in a pharmaceutical company throughout the product life cycle.