In pharmaceutical industry, QRM is a systematic process for the assessment, control and review of risks to the quality of the drug product.It is the overall and continuing process of appropriately managing risks to product quality throughout the product's life-cycle in order to optimize its risk-benefit balance. It is relevant to all pharma companies and should provide a rationale to understand risk and mitigate it through appropriate and robust controls.
The purpose of QRM is to protect patients in terms of quality, safety and efficacy of medicines through a risk-based approach to the life-cycle of a pharmaceutical product.
As per WHO technical report series, the two primary principles of QRM are that:
- The evaluation of the risk to quality should be based on scientific knowledge and ultimately linked to the protection of the patient.
- The level of effort, formality and documentation of the QRMprocess should be commensurate (in proportion) with the level of risk.
QRM process
Initiating a QRM process: QRM activities should be initiated using systematic processes designed to coordinate, facilitate and improve science-based decision-making with respect to risk. The possible steps to be taken in initiating and planning a QRM process might include the following:
- define the problem and/or risk question, including pertinent assumptions identifying the potential for risk;
- assemble background information and/or data on the potential hazard, harm or human health impact relevant to the risk assessment;
- identify a leader and the necessary resources;
- specify a timeline, the deliverables, and an appropriate level ofdecision-making for the risk management process.
Personnel involved in QRM: The personnel appointed should be able to –
- conduct a risk analysis;
- identify and analyse potential risks;
- evaluate risks and determine which ones should be controlled and which ones can be accepted;
- recommend and implement adequate risk control measures;
- devise procedures for risk review, monitoring and verification;
- consider the impact of risk findings on related or similar products and/or processes.
Knowledge of the product and process: QRM should be based on knowledge of the product or processes concerned, according to the stage of the product life-cycle.
Risk assessment: When risk assessment is conducted, safety and efficacy need to be considered in addition to the quality concerns.During the assessment all the risks that may reasonably be expected to occur when conducting the activity under evaluation should be listed. This isusually done when the risk assessment is made for the first time, i.e. initiated, when there is a change or a concern and may also be applied to existing processes. An analysis should be conducted to identify which risks it is essential to eliminate or to reduce to acceptable levels.Normally, potential risks in relation to the following should be considered:
- materials and ingredients;
- physical characteristics and composition of the product;
- processing procedures;
- microbial limits, where applicable;
- premises;
- equipment;
- packaging;
- sanitation and hygiene;
- personnel (human error);
- utilities;
- supply chain.
Risk control: Risk control is a decision-making activity designed to reduce and/or accept risks. It usually occurs after risk assessment, and at a fundamental level its purpose is to reduce the risk to an acceptable level.
Risk review: Appropriate systems should be in place to ensure that the output of the QRM process is periodically monitored and reviewed, as appropriate, to assess new information that may impact on the original QRM decision.
Verification of QRM process and methodologies: The established QRM process and methodologies need to be verified. Verification and auditing methods, procedures and tests, including random sampling and analysis, can be used to determine whether the QRM process is working appropriately.
Risk communication and documentation: Communication of the QRM process should include key stakeholders. Engaging the key stakeholders in both the data collection process for the risk assessment and the decision-making for risk control will ensure their commitment and support for the QRM.
Prior Knowledge
During development, the purpose of the QRM process may be to acquire sufficient product and process knowledge to assess risks associated with formulation development of the finished pharmaceutical product (FPP) according to the quality target product profile (QTPP). In recognizing risks and knowledge gaps, the QRM process plays a significant role in proactively enabling the prioritization and mitigation of risks. The objective is to develop the FPP through maximizing product and process knowledge and risk mitigation.In addition to supporting that development, the purpose of the QRM process is to determine and manage risks to bioavailability, safety, efficacy and product quality.