Quality Risk Management (QRM) Report for Non Operational Area Shutdown

The scope of this Risk assessment report is to provide the procedure for Quality Risk Management study for the non operational area shutdown and we can save the utility bills of our organization and can implement the same at our respective sites without impacting the product quality.

The Approach adopted to carry out risk assessment is failure mode effect analysis (FMEA) and in this report we have to study various risk parts like Risk identification, Risk analysis, evaluation, Severity, occurrence, detection, critical control points, current control points and Risk priority number.

Risk Review :

As per the QRM execution for the process of non operational area shut down various risk were identified. All the identification parameter meets the current control points under acceptable mode. The risk level based on Risk Priority number (RPN) is found widely acceptable.

Conclusion :

Based on QRM execution and risk review it was concluded that the risk involve in shutdown of nonoperational area is widely acceptable.

Quality Risk Management ICH Q9

Introduction :

Risk managementprinciples are effectively utilized in many areas of business and government including finance, insurance, occupational safety, public health, pharmacovigilance, and by agencies regulating these industries.

Quality risk management is used in the pharmaceutical industries and it is becoming evident that quality risk management is a valuable component of an effective quality system.

Advantages of Quality risk Management:

An effective quality risk management approach can further ensure the high quality of the drug (medicinal) product to the patient by providing a proactive means to identify and control potential quality issues during development and manufacturing.

The use of quality risk management can improve the decision making if a quality problem arises.

Effective quality risk management can facilitate better and more informed decisions, can provide regulators with greater assurance of a company’s ability to deal with potential risks and can beneficially affect the extent and level of direct regulatory oversight.

Scope of Quality risk Management:

This guideline provides principles and examples of tools for quality risk management that can be applied to different aspects of pharmaceutical quality. These aspects include development, manufacturing, distribution, and the inspection and submission/review processes throughout the lifecycle of drug substances, drug (medicinal) products, biological and biotechnological products (including the use of raw materials, solvents, excipients, packaging and labeling materials in drug (medicinal) products, biological and biotechnological products).

Principle of Quality risk Management:

Two primary principles of quality risk management are:

The evaluation of the risk to quality should be based on scientific knowledge and ultimately link to the protection of the patient;

The level of effort, formality and documentation of the quality risk management process should be equal with the level of risk.

General Quality risk Management Process:

Quality risk management is a systematic process for the assessment, control, communication and review of risks to the quality of the drug (medicinal) product across the product lifecycle.

A model for quality risk management is outlined in the diagram (Figure 1). Other models could be used. The emphasis on each component of the framework might differ from case to case but a robust process will incorporate consideration of all the elements at a level of detail that is commensurate with the specific risk.

Figure 1

Responsibilities :

Quality risk management activities are usually, but not always, undertaken so When teams are formed, they should include experts from the appropriate areas (e.g., quality unit, business development, engineering, regulatory affairs, production operations, sales and marketing, legal, statistics and clinical) in addition to individuals who are knowledgeable about the quality risk management process.

Initiating a Quality Risk Management Process :

Quality risk management should include systematic processes designed to coordinate, facilitate and improve science-based decision making with respect to risk.

Possible steps used to initiate and plan a quality risk management 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 necessary resources;

 Specify a timeline, deliverables and appropriate level of decision making for the risk management process.

Risk Assessment:

Risk assessment consists of the identification of hazards and the analysis and evaluation of risks associated with exposure to those hazards (as defined below).

Quality risk assessments begin with a well-defined problem description or risk question.

When the risk in question is well defined, an appropriate risk management tool  and the types of information needed to address the risk question will be more readily identifiable. As an aid to clearly defining the risk(s) for risk assessment purposes, three fundamental questions are often helpful:

1. What might go wrong?

2. What is the likelihood (probability) it will go wrong?

3. What are the consequences (severity)?

Risk identification:

It is a systematic use of information to identify hazards referring to the risk question or problem description. Information can include historical data, theoretical analysis, informed opinions, and the concerns of stakeholders. Risk identification addresses the “What might go wrong?” question, including identifying the possible consequences. This provides the basis for further steps in the quality risk management process.

Risk Analysis:

It is the estimation of the risk associated with the identified hazards. It is the qualitative or quantitative process of linking the likelihood of occurrence and severity of harms. In some risk management tools, the ability to detect the harm (detectability) also factors in the estimation of risk.

In this stage, it shall be determined that what are the worst potential “effect” or consequence of the failure mode.

Risk Evaluation :

Based on risk identification and analysis data, risk evaluation shall be done using Risk Priority Number (RPN) that is multiplication of “severity rating”, “Probability of Occurrence Rating” and “Detection Rating”. These “severity rating”, “Occurrence Rating” and “Detection Rating” but it can be vary case to case.

Based on above rating Risk Priority Number (RPN) shall be calculated by multiplication of “Severity Rating (S)”, “Probability Of Occurrence Rating (P) and “Detection Rating (D), i.e. S X P X D. Level of risk i.e. unacceptable, high, moderate, low or acceptable based on Risk Priority Number (RPN).

RPNRisk level
Less than or equal to 80Low or Acceptable

Risk Control :

Risk control includes decision making to reduce and/or accept risks.

The purpose of risk control is to reduce the risk to an acceptable level and amount of effort used for risk control should be proportional to the significance of the risk.  Decision makers might use different processes, including benefit-cost analysis, for understanding the optimal level of risk control.

Risk control might focus on the following questions:

 Is the risk above an acceptable level?

 What can be done to reduce or eliminate risks?

 What is the appropriate balance among benefits, risks and resources?

 Are new risks introduced as a result of the identified risks being controlled?

Risk Reduction :

 It focuses on processes for mitigation or avoidance of quality risk when it exceeds a specified (acceptable) level (see Fig. 1). Risk reduction might include actions taken to mitigate the severity and probability of harm. Processes that improve the detectability of hazards and quality risks might also be used as part of a risk control strategy.

The implementation of risk reduction measures can introduce new risks into the system or increase the significance of other existing risks. Hence, it might be appropriate to revisit the risk assessment to identify and evaluate any possible change in risk after implementing a risk reduction process.

Risk acceptance:

It  is a decision to accept risk and risk acceptance can be a formal decision to accept the residual risk or it can be a passive decision in which residual risks are not specified.

 For some types of harms, even the best quality risk management practices might not entirely eliminate risk. In these circumstances, it might be agreed that an appropriate quality risk management strategy has been applied and that quality risk is reduced to a specified (acceptable) level. This (specified) acceptable level will depend on many parameters and should be decided on a case-by-case basis.

Risk Communication:

Risk communication is the sharing of information about risk and risk management between the decision makers and others. Parties can communicate at any stage of the risk management process (see Fig. 1: dashed arrows).

The output/result of the quality risk management process should be appropriately communicated and documented (see Fig. 1: solid arrows). Communications might include those among interested parties; e.g., regulators and industry, industry and the patient, within a company, industry or regulatory authority, etc. The included information might relate to the existence, nature, form, probability, severity, acceptability, control, treatment, detectability or other aspects of risks to quality.

Communication need not be carried out for each and every risk acceptance. Between the industry and regulatory authorities, communication concerning quality risk management decisions might be effected through existing channels as specified in regulations and guidance’s.

Risk Review:

Risk management should be an ongoing part of the quality management process.

The output/results of the risk management process should be reviewed to take into account new knowledge and experience. Once a quality risk management process has been initiated, that process should continue to be utilized for events that might impact the original quality risk management decision, whether these events are planned (e.g., results of product review, inspections, audits, change control) or unplanned (e.g., root cause from failure investigations, recall). The frequency of any review should be based upon the level of risk. Risk review might include reconsideration of risk acceptance decisions .

Risk Management Methodology :

Quality risk management supports a scientific and practical approach to decision-making. It provides documented, transparent and reproducible methods to accomplish steps of the quality risk management process based on current knowledge about assessing the probability, severity and sometimes detectability of the risk.

Traditionally, risks to quality have been assessed and managed in a variety of informal ways (empirical and/ or internal procedures) based on, for example, compilation of observations, trends and other information.

The pharmaceutical industry and regulators can assess and manage risk using recognized risk management tools and/ or internal procedures (e.g., standard operating procedures). Below is a non-exhaustive list of some of these tools….

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.

Definitions :


The ability to discover or determine the existence, presence, or fact of a hazard.


Damage to health, including the damage that can occur from loss of product quality or availability.


The potential source of harm (ISO/IEC Guide 51).

Product Lifecycle:

All phases in the life of the product from the initial development through marketing until the product’s discontinuation.


The degree to which a set of inherent properties of a product, system or process fulfills requirements (see ICH Q6A definition specifically for “quality” of drug substance and drug (medicinal) products.)

Quality Risk Management:

A systematic process for the assessment, control, communication and review of risks to the quality of the drug (medicinal) product across the product lifecycle.

Quality System:

The sum of all aspects of a system that implements quality policy and ensures that quality objectives are met.


The combination of the probability of occurrence of harm and the severity of that harm (ISO/IEC Guide 51).

Risk Acceptance:

The decision to accept risk (ISO Guide 73).

Risk Analysis:

The estimation of the risk associated with the identified hazards.

Risk Assessment:

A systematic process of organizing information to support a risk decision to be made within a risk management process. It consists of the identification of hazards and the analysis and evaluation of risks associated with exposure to those hazards.

Risk Communication:

The sharing of information about risk and risk management between the decision maker and other stakeholders.

Risk Control:

Actions implementing risk management decisions (ISO Guide 73).

Risk Evaluation:

The comparison of the estimated risk to given risk criteria using a quantitative or qualitative scale to determine the significance of the risk.

Risk Identification:

The systematic use of information to identify potential sources of harm (hazards) referring to the risk question or problem description.

Risk Management:

The systematic application of quality management policies, procedures, and practices to the tasks of assessing, controlling, communicating and reviewing risk.

Risk Reduction:

Actions taken to lessen the probability of occurrence of harm and the severity of that harm.

Risk Review:

Review or monitoring of output/results of the risk management process considering (if appropriate) new knowledge and experience about the risk.


A measure of the possible consequences of a hazard.

Reference : https://www.fda.gov/regulatory-information/search-fda-guidance-documents/q9-quality-risk-management

Handling of Market complaints


To lay down a procedure for receipt, investigation, review and response of market complaints


  • In charge / Designee – Quality Assurance shall be responsible
  • For handling market complaints
  • Maintaining relevant documents and market complaint register.
  • Keeping the procedure current and applicable
  • In charge– Quality Control and In charge – Production
  • Assist in investigation of the market complaint
  • In charge – Marketing.
  • Responsible to provide all relevant information on market complaint.
  • Head – QA –Ensure implementation /compliance of this procedure.
  • Qualified Person of respective contract Mfg- For contract Mfg Products-To provide all relevant information on market complaint.

3.         PROCEDURE

  • Any complaint received for the marketed product from the end user, customer, retailer, distributor or field staff or marketing manager regarding the purity, efficacy, labeling  defect, or any other such complaint shall be considered as a Market Complaint.
  • Any communication in written or verbal, received directly or through respective country    manager /representative shall be considered as a complaint.
  • Wherever possible efforts shall be taken to get the complaint sample. If complaint sample not available, investigation shall be carried out with the control sample based on the nature of complaint. After receiving of the sample the same shall be kept as per storage conditions mentioned on the sample till investigation of complaint.
  • Country Manager/representative shall send a copy of correspondence received from the complainant and a complaint sample (if available) to In charge – QA/designee.     
  • Control sample shall be taken from the control sample section by sending communication.
  • On receipt of complaint, In charge – QA/designee shall document the following details in  the Market complaint register.
  • Complaint number
  • Date of receipt
  • Product Name & Strength
  • Batch Number
  • Date of manufacture
  • Date of expiry
  • Name, address and telephone number of the complainant
  • Nature of the complaint.
  •  Replied on
  • Corrective and preventive action
  • Disposition date
  • After receiving the complaint sample,(If available) In charge – QA/designee shall document the details in complaint sample register.
  • Complaint receiving date.
  • Complaint number.
  • Complaint sample receiving date.
  • Product Name.
  • Batch Number.
  • Complaint received from.
  • Number of samples received.
  • Investigation for physical examination  / Analysis.
  • Investigation completed on.
  • The market complaint received shall be assigned with an alphanumeric numbering system market  wise:

C          –          Complaint

Z          –           U/E/O/B

U for USA Market. & E for Europe Market. & O for Other Market. & B for Brazil market.

XX       –           Market complaint number

YY       –           Year of the market complaint

  Example: First complaint received from US market in 2020 shall be numbered as follows:

  • If any complaint sample is received, the same shall be labeled with the complaint number.
  • Each complaint shall be entered into the “Market Complaint Information form”
  •  A personnel shall send a field alert report, where required, within two working days to    concern regulatory authority as per SOP
  • Note:  Complaint received, for the product not marketed, from any contract manufacturer or from our warehouse or distribution center   shall also be investigated and records to be   maintained. The numbering system for the complaints shall be five characters and mentioned below:

Where C – Complaint, XX   is the serial number  and YY is the year of the complaint.

  • Complaint shall be classified as follows to facilitate the investigation
  • Packaging complaints
  • Quality complaints
  • Medical complaints
  • Packaging and Quality complaints shall be jointly investigated by QA In – Charge, Manager – QC, Formulation Research Development In-Charge and Production In- Charge.
  • The following shall be considered while investigating the Packaging / Quality complaints:
    • Inspection of the defective product received.
    • Analysis of the defected product if required.
    • Review of the batch processing and packaging records.
    • Physical examination of the reference sample.
    • Analysis of the reference sample.
  • Before starting of investigation of market complaint, complaint information form to be filled as per available information, during investigation all supportive documents which were reviewed and  collection of documents (If required) and other information to be filled as per the market complaint checklist at the end of investigation the same should be retained along with investigation report.
  • Wherever required Medical complaints shall be investigated in co-ordination with medical doctor or equivalent or pharmacovigilance coordinator.
  • Investigation shall be extended to other batches, which were manufactured with same Raw Material and primary packaging material during same time period and likely to be affected.
  • A manager or designee in co-ordination with the concerned departmental head shall arrange for review of the batch documents for any abnormalities, deviations, and incidents. Where necessary the equipment /instrument usage logs, personnel training records, stability data, trends etc.shall be reviewed.
  • QA Incharge shall arrange for the examination of complaint sample, where available,  along with the reserve sample of the complaint batch as necessary.
  • Check if similar complaints have been received earlier, during the last one year. If the complaint is repeated, check and ensure whether the preventive actions proposed have been implemented and are effective.
  • Wherever applicable the Investigation shall be carried out as per SOP failure investigation and various investigation tools shall be used to find out the probable root cause and  reports shall be summarized. After completion of the investigation, incharge Quality Assurance shall discuss the findings with Head – Quality Assurance.

Refer Investigation tools used in pharmaceuticals https://pharmaceuticalupdates.com/2020/02/10/investigation-tools-used-in-pharmaceuticals/

  • The Quality Assurance incharge along with the concerned departments In-charge and Head- QA shall propose the necessary corrective and preventive actions to avoid the reoccurrence of the complaint.

In case of any intimation of market complaint received from contract giver a detail investigation shall be carried out and shall be forwarded to Qualified Person or equivalent designee of contract giver for necessary action.

  • If the investigation report concludes that the product will put the public at risk such    complaints shall be referred to recall committee for taking recall decision        .
  • The complaint investigation report shall be written and filed in Quality Assurance department.
  • Based on the complaint investigation report, Quality Assurance shall communicate the appropriate conclusions stating whether the complaint is substantiated or not to the concerned complainants or to the  appropriate agency.

The investigation report shall be sent to the complainant with in 30 days from the   date of the receipt of the complaint unless otherwise justified.

  • Incase where Head – Quality Assurance finds that investigation is not necessary such written records shall be maintained including the reason for not conducting the  investigation.
  • After completion of the corrective action and preventive actions, complaint shall be closed.
  • All the documents related to the Product complaints shall be retained for one year after   the     expiration date / one year after the date of receipt of the complaint whichever is longer.
  • Based on the nature of complaint, trend shall be prepared once in a year.
  • Quarterly summaries shall be prepared and forwarded to Director   Pharma and Head– Quality Assurance for information.
  • In case of any complaint which is already investigated and closed from the customer end, the same shall also be investigated at our site once again along with customer report.
  • Handling of Market Complaint Samples
  • The remaining complaint samples shall be maintained by incharge / designee QA at the storage conditions specified for the drug product for a period of one year after the expiry date of the drug product or one year after the date on which complaint was received which ever is longer.
  • On completion of the specified retention period the samples shall be destroyed and record of it shall be maintained.


4.1       QA       – Quality Assurance

4.2       QC       – Quality Control

5.         REFERENCES

5.1       Product Recall.

5.2       Failure Investigation.

5.3        Field Alert

5.4       Sampling, storage and Destruction of Reference/Control samples 

            of Raw materials and Drug Products

6.          ANNEXURES

6.1             Market Complaint Information Form.

6.2             Investigation form.

6.3            Requisition for  reference samples / Complaint samples

6.4       Market Complaint check list.