Full HTML 07 V1 I4


Dr. D. Y. Patil College of Pharmacy, Akurdi, Pune-411044, Maharashtra, India.


ICH Q9 Quality risk management guidelines from the ICH provide an excellent high level framework for the use of risk management in pharmaceutical product development and manufacturing. This guidance was developed within the Expert Working Group (Quality) of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) Quality Risk Management is a systematic process for the assessment, control, communication and review of risks to the quality of the medicinal product across the product lifecycle.”

(ICH Q9). 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 these are well-recognized risk-management tools.

Keywords: QMR, risk assessment, methods of QRM, Potential applications.


ICH Q9 – Quality Risk Management provides an excellent high-level framework for the use of risk management in pharmaceutical product development and manufacturing quality decision-making applications. It is a landmark document in acknowledging risk management as a standard and acceptable quality system practice to facilitate good decision-making with regard to risk identification, resource prioritization, and risk mitigation / elimination, as appropriate. Risk management has been part of the pharmaceutical industry for many years. The publication of ICH Q9 ―Quality Risk Management‖ in 2005 is having significant impact on pharmaceutical industry.

The FDA and other regulatory bodies, is embracing the Q9 concepts. ICH ―Q9 QRM is developed by the Expert Working Group (Quality) of the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use which describes a model for a pharmaceutical quality system by providing principles and examples of tools for quality risk management and approach to identifying, scientifically evaluating and controlling potential risks to quality. In general Q9 provides high level guidance regarding identification, estimation, evaluation, controlling, monitoring and documentation of risk management process. The Q9 defines risk as the combination of the probability of occurrence of harm and the severity of that harm.

It is commonly understood that risk is defined as the combination of the probability of Occurrence of harm and the severity of that harm. However, achieving a shared understanding of the application of risk management among diverse stakeholders is difficult because each Stakeholder might perceive different potential harms, place a different probability on each harm occurring and attribute different severities to each harm. In relation to pharmaceuticals, although there are a variety of stakeholders, including patients and medical practitioners as well as government and industry, the protection of the patient by managing the risk to quality should be considered of prime importance 1.


Quality risk management that can be applied to different aspects of pharmaceutical quality. These aspects include development, manufacturing, distribution, inspection, and submission/review processes throughout the lifecycle of drug substances, drug products, biological and biotechnological products (including the use of raw materials, solvents, excipients, packaging and labelling materials in drug products, biological and biotechnological products).


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; and
  • The level of effort, formality, and documentation of the quality risk management process Should be commensurate with the level of risk.

Figure: 1 Integration of Quality risk management

1.3 INTEGRATION OF QUALITY RISK MANAGEMENT 3, 4: QRM is a process that supports science-based & practical decisions when integrated into quality systems such as: (as depicted in Figure)

  • Development
  • Validation
  • Quality defects investigations
  • Auditing & Inspection
  • Change Management
  • Documentation and Training
  1. QRM PROCESS OVERVIEW 5, 6, 7, 8, 9

The QRM program consists of four major components:

  • Risk Assessment
  • Risk Control
  • Risk Communication
  • Risk Review

All the QRM methods (as described in Table: 1) should address the mentioned four basic components.

Table 1:  The QRM Methods

Quality Risk assessment Quality Risk control Quality Risk communication Quality Risk review
Quality Risk Identification Quality Risk reduction Documentation and communication of result to stakeholders Review events
Quality Risk Analysis Quality Risk acceptance
Quality Risk Evalution



Quality Risk assessment is 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.” (ICH Q9)

Figure: 2 Overview of a typical quality risk management process

2.1.1 Quality Risk Identification: Risk identification shall consist of the use of information to identify hazards or potential risks. Information used to identify risk includes historical data, theoretical analysis, and informed opinions. The risk to be considered includes patient safety, product non-conformance, and fitness for use, specification and adulteration.

2.1.2 Quality Risk Analysis: During quality risk analysis a detailed understanding of the probability that the identified risk will occur shall be estimated. It can also include detect ability. The key activities to be performed during risk analysis include to understand the impact of risk, to rank the significance of risk (by scoring 1 to 5, where 1 = low & 5 = high), to calculate the risk score (Risk Score = Severity x Probability), colour code the risk based on score (define Red, Blue and Green bands e.g. acceptable risk = Green, unacceptable risk = Blue, Intolerable = Red).

2.1.3 Quality Risk Evaluation: Quality risk evaluation includes comparison of identified and analysed risk against pre-defined acceptance criteria and consideration of probability, severity and detects ability. The complete risk assessment shall result in an overall risk value expressed as either,

  • A qualitative description of a range of risk using descriptions such as high, medium or low.
  • A quantitative description of risk expressed numerically on probability scale of 0 to 100 percent.

2.1.4 Different Steps Involved In the Risk Assessment 13, 14

  1. Collect & organize the information.
  2. Formulate the Risk Question
  3. Choose Tool different tools include-
  • Basic risk management facilitation methods (flowcharts, check sheets etc).
  • Failure Mode Effects Analysis
  • Failure Mode Effects and Criticality Analysis.
  • Fault Tree Analysis.
  • Hazard Analysis and Critical Control Points.
  • Hazard & Operability Analysis.
  • Preliminary Hazard Analysis.
  • Risk Ranking & Filtering.
  • Supporting statistical tools.
  1. Identify Risks Factors and Related Hazards
  2. Define the Risk Components &Scales
  3. Evaluate the risk for each hazard.
  4. Determine acceptability of risks
  5. Determine Action Threshold
  6. Apply the tool

2.2Risk control 5, 16, 17 : Risk control includes decision making to reduce and/or accept risks. The intention of risk control is to reduce the risk to an acceptable level. The amount of effort used for risk control should be proportional to the significance of the risk.

2.2.1 Risk reduction: Risk reduction focuses on processes for mitigation or avoidance of quality risk when it exceeds a specified level. Risk reduction might include actions taken to mitigate the severity and probability of harm. 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.

2.2.2 Risk acceptance: Risk acceptance is a decision to accept risk. 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.

2.3 Risk Communication: 18 Risk Communication is the sharing of information about risk and risk management between the decision makers and others. The output/result of the quality risk management process should be appropriately communicated and documented. The included information might relate to the existence, nature, form, probability, severity, acceptability, control, treatment, detestability or other aspects of risks to quality.

2.4 Risk Review: 19 Risk Review is 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. Risk review might include reconsideration of risk acceptance decisions


A key early step in the execution of a risk analysis is to determine the appropriate risk-assessment methods or tools. There is no single best choice for any given assessment process, and the selection of the appropriate risk methodology should be based on the depth of analysis required, complexity of the subject risk of concern, and the familiarity with the assessment tool.

3.1 Diagram analysis, Flowcharts, Check sheets, Process mapping, and Cause/effect diagrams:

Simple techniques that are commonly used to gather and organize data, structure RM processes and facilitate decision making. Potential applications are Compilation of observations, trends or other empirical information to support a variety of less complex deviations, complaints, defaults or other circumstances.

Eg. Cause and effect diagram of tablet hardness 23

Figure: 3 Cause and effect diagram of tablet hardness

3.2 Failure Mode Effects Analysis:

FMEA provides for an evaluation of potential failure modes for processes and

Their likely effects on outcomes and/or product performance. Once failure modes are established, risk reduction can be used to eliminate, contain, reduce, or control the potential failures. FMEA relies on product and process understanding. FMEA methodically breaks down the analysis of complex processes into manageable steps. It is a powerful tool for summarizing the important modes of failure, factors causing these failures, and the likely effects of these failures.

Figure: 4 Failure Mode Effects Analysis 

3.3 Fault Tree Analysis:

The FTA tool is an approach that assumes failure of the functionality of a product or process. This tool evaluates system (or subsystem) failures one at a time but can combine multiple causes of failure by identifying causal chains. The results are represented pictorially in the form of a tree of fault modes. At each level in the tree, combinations of fault modes are described with logical operators (AND, OR, etc.). FTA relies on the experts’ process understanding to identify causal factors.Eg. Investigation of laboratory failure

Table: 2 Failure Mode Effects And Criticality Analysis: Calibration Of Equipment/Instrument)

Potential failure mode  Potential effect  Contributory factors


Current control measures 
Deficient calibration practises /

Use of uncelebrated Instrument/ equipment for processing / testing

  • May lead to improper functioning of equipment / instrument or affecting the performance of equipment / instrument which directly affects the product quality/ patient safety.


  • SOP not available to define the requirements of calibration and its traceability standards.



  • SOP should be place for the calibration activities.
  • For calibration of equipment /instrument Individual SOPs should available.
  • Calibrations of equipment/ instrument should carried out in-house or by external approved agency.

Ø Trained personnel for calibration activity.

  • Improper planning of calibration activities. / Non availability of calibration schedule.


  • Calibration schedule is available to maintain the yearly calibration activities.
  • Calibration schedule report should prepared by department head, approved by Unit QA and noted by Unit head.
  • Calibration schedule should reviewed every six months.
  • Lack of technical expertise.


  • SOP should place for training program.
  • All employees should trained regularly.
  • Calibration frequency not defined




  • Calibration frequency of each instrument/ equipment and its sub components are specified in individual instrument/ equipment operating SOP


  • Inappropriate environment conditions


  • Daily monitoring of temperature & RH of area as per SOP.
  • Modification in existing equipment


  • Change control procedure should place.
  • If modification changes are done in existing system recalibration / requalification of instrument / equipment.

Figure: 5 Investigation of laboratory failure

3.4 Hazard Analysis and Critical Control Points: 24

HACCP is a systematic, proactive, and preventive tool for assuring product quality, reliability, and safety. It is a structured approach that applies technical and scientific principles to analyze, evaluate, prevent, and control the risk or adverse consequence(s) of hazard(s) due to the design, development, production, and use of products.  

(Table: 3 Failure Mode Effects And Criticality Analysis: Blister Packing)


failure mode


Potential effect





Current control measures



Fault in product feeding station.





  • May delay packing activity.
  • Empty/ missing blister will be packed.
  • Broken tablets may be packed.
  • May cause market complaint.


  • Inadequate tablets in hopper / bowl / feeding channel / flooding box.


  • Operating SOPs should available
  • Product level sensor should provide in feeding channel / feeding station/ flooding box to maintain adequate quantity of tablets.
  • Trained personnel.



Wrong IPC loading on hopper.

  • Cross contamination.
  • May cause market complaint & product recall
  • Improper labelling to IPC


  • SOP MT 110 ‘Transfer of materials from one stage to another’ should available.
  • Before sequential loading of IPC to hopper label details should checked

Improper blister formation.

  • May lead to leak test failure.
  • May lead to Knurling.
  • May result into missing / broken tablet.
  • May lead to market complaint.
  • Incorrect setting of preheating plate temperature / blister forming roller.
  • Qualified blister pack machine
  • Blister forming roller /Pre-heater plate/film heater temperature set properly as per the specified limit given in BPR
  • Machine set up should checked before start of packing
  • Quality of PVC rolls.


  • Approved vendors.

Improper  sealing

  • Failure in leak test which may affect quality of product.
  • May result in market complaint.


  • Incorrect temperature setting of sealing roller/plate.


  • Qualified blister pack machine
  • Sealing temperature is set as per specified limits given in BPR during machine setting and same should recorded in BPR.

Empty/ partially filled  blister

  • It may cause market complaint.
  • Product recall


  • Incorrect setting of NFD camera.


  • Qualified equipment.
  • Operating SOP’s should available for setting of NFD camera.
  • Camera system should validate for detection for empty & partially filled blister.




Less quantity of blister in final pack.

  • Market complaint.


  • Incorrect setting of carbonator.


  • SOP’s should available for operation of carbonator machine.
  • Blister stack level sensor should available for controlling & rejecting of less or more blisters as, when the blisters are more than the set level machine stops & if less than the set level respective carton is rejected.



Wrong carton or Mix up of carton.

  • Product mix-up & it may cause market complaint.
  • May cause product recall.
  • Mix- up of carton from supplier end.
  • Improper setting of pharma code reader.



  • Approved vendor.
  • Artwork should approved by packaging development.
  • SOP should available for setting & operation of pharma code reader.

3.5 Hazard & Operability Analysis:

HAZOP is based on a theory that assumes that risk events are caused by deviations from the design or operating intentions. It is a systematic brainstorming technique for identifying hazards using so-called guide words. Guide words (e.g., No, More, Other Than, Part of) are applied to relevant parameters (e.g., contamination, temperature) to help identify potential deviations from normal use or design intentions. HAZOP often uses a team of people with expertise covering the design of the process or product and its application.

3.6 Preliminary Hazard Analysis:

PHA is a tool of analysis based on applying prior experience or knowledge of a hazard or failure to identify future hazards, hazardous situations and events that might cause harm, as well as to estimate their probability of occurrence for a given activity, facility, product, or system. The tool consists of: (1) the identification of the possibilities that the risk event happens, (2) the qualitative evaluation of the extent of possible injury or damage to health that could result, (3) a relative ranking of the hazard using a combination of severity and likelihood of occurrence, and (4) the identification of possible remedial measures.

Figure: 6 Hazard Analysis and Critical Control Points

Figure: 7 Hazard & Operability Analysis

Figure: 8 Preliminary Hazard Analysis


Figure :9 Risk ranking and filtering

3.7 Risk ranking and filtering 25:

Risk ranking and filtering is a tool for comparing and ranking risks. Risk ranking of complex systems typically involves evaluation of multiple diverse quantitative and qualitative factors for each risk. The tool involves breaking down a basic risk question into as many components as needed to capture factors involved in the risk. These factors are combined into a single relative risk score that can then be used for ranking risks. “Filters,” in the form of weighting factors or cut-offs for risk scores, can be used to scale or fit the risk ranking to management or policy objectives.

3.8 Supporting statistical tools :

Statistical tools can support and facilitate quality risk management. They can enable effective

Data assessment, aid in determining the significance of the data set(s), and facilitate more reliable decision making. A listing of some of the principal statistical tools commonly used in the pharmaceutical industry is provided:

  • Control charts, for example:
  • Acceptance control charts
  • Control charts with arithmetic average and warning limits
  • Cumulative sum charts
  • Weighted moving average
  • Design of experiments
  • Histograms
  • Pareto charts
  • Process capability analysis

Figure: 10 Analysis of variables that may impact the coating process  


4.1 QRM as a part of development of a new drug product 26, 27:

To establish appropriate specifications, identify critical process parameters, and establish

Manufacturing controls (e.g., using information from pharmaceutical development studies

Regarding the clinical significance of quality attributes and the ability to control them during


To decrease variability of quality attributes:

  • reduce product and material defects
  • reduce manufacturing defects

The product lifecycle included the following technical activities for new and existing products:

  • Pharmaceutical Development
  • Formulation development
  • Manufacturing process Development& scale‐up

Knowledge management:

Product and process knowledge should be managed from development through the commercial life of a product Knowledge management is a systemic approach to acquiring, analyzing, storing, and disseminating information related to products, mfg. processes, and components.

Figure: 11 Comparison of different spray nozzles and spray patterns

Knowledge Acquisition includes:

  • Defining the Product Profile
  • Public domain literature, patent review
  • API attributes and limitations
  • Definition of the DP manufacturing process
  • Ranging the manufacturing process

Knowledge Analysis includes:

  • Determining elements of intrinsic criticality, e.g. API attributes, process parameters,

Environmental conditions.

  • Risk analysis of the critical elements, e.g. FMEA, HACCP
  • Defining a Control Strategy, e.g. integration of the process controls into facility QMS

Eg. Knowledge management and QRM- A Case Study Saxagliptin

Dipeptidyl peptidase IV inhibitor (DPP4) for Type II diabetes

  • pKa = 7.2
  • BCS Class III

Controlling Intramolecular Cyclization:


Cyclization Occurs in solid and solution state, Cyclization Accelerates with commonly used excipients, Cyclization Accelerates when processed under wet & dry granulation, Acidic environment stabilizes saxagliptin. Process Knowledge Acquired in Development and Transferred Forward to Production:

  • Key Quality Attributes identified after risk assessment content uniformity potency
  • Design space established using fundamental process understanding, modelling and Design of Experiments (DOE)
  • A predictive model for CU and potency created for the Coating Step

Production Process was assessed for Criticality, Risk and Control. Applicable for either drug substance or drug product. When considering CPPs, determine what is critical and then how to control it.

4.2 Quality Risk Management for  Equipment:

To determine appropriate product contact materials for equipment and containers (e.g., selection of stainless steel grade, gaskets, lubricants).

To determine appropriate utilities (e.g., steam; gases; power source; compressed air, heating,

Ventilation, and air conditioning (HVAC); water).

To determine appropriate preventive maintenance for associated equipment (e.g., inventory of necessary spare parts).

Qualification of equipment to determine the scope and extent of qualification of equipment and/or laboratory instruments (including proper calibration methods)

Eg. Failure Mode Effects and Criticality Analysis: Calibration of Equipment/Instrument

4.3 Quality Risk Management as Part of Materials Management:

Assessment and evaluation of suppliers and contract manufacturers

To provide a comprehensive evaluation of suppliers and contract manufacturers (e.g., auditing, supplier quality agreements)

Starting material

To assess differences and possible quality risks associated with variability in starting materials (e.g., age, route of synthesis).

Use of materials

To determine whether it is appropriate to use material under quarantine(e.g. for further internal processing).

To determine appropriateness of reprocessing, reworking, use of returned goods.

Storage, logistics and distribution conditions

To assess the adequacy of arrangements to ensure maintenance of appropriate storage and

Transport conditions (e.g., temperature, humidity, container design).

To determine the effect on product quality of discrepancies in storage or transport conditions

(e.g., cold chain management) in conjunction with other ICH guidance.

To maintain infrastructure (e.g., capacity to ensure proper shipping conditions, interim storage, handling of hazardous materials and controlled substances, customs clearance).

To provide information for ensuring the availability of pharmaceuticals (e.g., ranking risks to the supply chain).

4.4 Quality Risk Management as Part of Packaging and Labelling Design of packages

To design the secondary package for the protection of primary packaged product (e.g., to ensure product authenticity, label legibility).

Selection of container closure system

To determine the critical parameters of the container closure system.

Label controls

To design label control procedures based on the potential for mix-ups involving different product labels, including different versions of the same label. For Eg. Failure Mode Effects and Criticality Analysis: Blister Packing

4.5 QRM application in product manufacturing operations 28

Effective QRM can facilitate the “How to do it?” and, therefore, ensure that the products will meet acceptable standards for safety, quality, and compliance. Among others, QRM methodology can support the following actions to assess and control quality risks:


  • manufacturing process risks
  • validation
  • In-process sampling and testing controls
  • Production planning
  • Deviation and investigation management
  • change management;

Laboratory control and stability studies:

  • Out-of-specification results
  • retest period and expiry date
  • Method transfers;

Packaging and labelling:

  • Design of packages
  • Selection of container-closure system
  • label controls;

Storage, transport and distribution:

  • g. cold chain.  

4.6 Quality Risk Management as Part of Laboratory Control and Stability Studies

  • Out of specification results
  • To identify potential root causes and corrective actions during the investigation of out of specification results.
  • Retest period / expiration date

To evaluate adequacy of storage and testing of intermediates, excipients and starting materials.


4.7 Quality Risk Management as Part of Integrated Quality Management

Effective QRM can facilitate the decision on “What to do?” and, therefore, support better and more informed decisions. QRM should be integrated into existing quality system elements and related business processes and documented appropriately. Accordingly, the use of QRM can be beneficial across a broad spectrum of operations, e.g.:

Integrated quality management:

  • Documentation
  • Training and education
  • Quality defects
  • Auditing and inspection
  • Change management and change control (includes equipment, facilities, utilities, control and IT systems)
  • Continual improvement and corrective and preventive actions
  • (CAPA)

Facilities, equipment and utilities:

  • Design
  • Qualification
  • Maintenance and decommissioning of facility or equipment
  • Hygiene aspects
  • cleaning of equipment and environmental control
  • Calibration and preventive maintenance
  • Computer systems and computer-controlled equipment

Supplier, materials and contract service management:

  • Assessment and evaluation of suppliers and contract manufacturers
  • starting material
  • Use of materials
  • Storage
  • Logistics and distribution conditions

Technology transfer:

  • From development to manufacturing
  • During commercial manufacturing between sites
  • From commercial manufacturing to product discontinuation.

4.8 Quality Risk Management as Part of clinical therapy 29,30,31,32:

Quality risk management aspect can be applicable to clinical therapy to identify and eliminate whatever risk comes during clinical therapy. Medication Therapy Management (MTM) can be used.

Defined as a distinct service or group of services that optimize therapeutic outcomes for individual patients.

  • The 3 GOALS of MTM include:
    • Improved medication understanding
    • Adherence to medication therapy
    • Detection of medication-related problems, including adverse drug reactions
  • The 5 Core elements of MTM
    • Provide a comprehensive or targeted medication therapy review
    • Complete and update the patient’s personal medication record (PMR)
    • Develop a medication-related patient-directed action plan (MAP)
    • Intervene and/or refer when appropriate
    • Document all services and interventions, communicate results encounter, and provide appropriate follow up.

Eg. Prevention of Risk due to particulate contamination in Infusion Therapy

Causes of particulate contaminations of IV fluids

  • Glass
  • Plastic
  • Rubber
  • Undissolved particles/drugs

Prominent risks

  • impairment of microcirculation
  • blockages of blood vessels
  • damage to various organs
  • phlebitis

Preventive actions:

  • Open ampoule or vial according to standards of care.
  • Use filter straw for withdrawal of the infusion.
  • In-line filter and infusion set filter prevent the infusion of particles into the patient.
  • avoid glass ampoules
  • use filter straws or filter needles
  • incorporate appropriate filters into IV administrations

Ecoflac® plus: The state of the art IV solution container that offers safe and convenient application of all IV procedures from drug admixture to drug delivery. The superior properties of the resalable port membrane prevent coring of elastomeric particles when punctured with a needle or an infusion set.

Intrafix® SafeSet: IV set for safe and convenient infusions. A 15 μm particle filter prevents the infusion of particles. Using 15 μm particle filters in IV sets is recommended

in the international standards for infusion sets for single use in ISO 8536-4 (gravity) and in ISO 8536-8 (infusion equipment for use with pressure infusion apparatus).

Intrapur® and Sterifix® Infusion Filters

A whole range of filters for safe infusion therapy. Membranes of 0.2 μm and 1.2 μm separate particles and lipid macro micelles larger than the pore size of the filter.


Vented dispensing pins for safe and convenient fluid transfer with syringes. Particles such as undissolved lyophilisates in the fluid are retained due to the inbuilt 5 μm filter.

Sterifi x® filter straws

Filter straws for particle free withdrawal and filtration of fluids from ampoules. A 5 μm filter prevents the administration of glass particles, which can occur when ampoules are opened. The filter is already integrated in the hub of the straw.

Mini-Plasco® connect / Mini-Plasco®

The plastic ampoule offers small volumes of IV solution for drug preparations.

Low intrinsic particle load as Mini-Plasco   plastic material does not produce such particles.

Can  easily be opened without particle creation.

Figure: 19 Fault Tree Analysis of incorrect insulin drug administration

4.9 Quality Risk Management during drug administration:

Quality Risk Management also applicable during drug administration to identify and eliminate risk during drug administration. It is helpful to assure proper amount of drug is administered by proper way without any complaints. For e.g. Fault Tree Analysis of incorrect insulin drug administration


Quality Risk Management is a systematic process for evaluation, control, communication and review of risks to the quality of the drug product across the product lifecycle. 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 might affect the extent and level of direct regulatory oversight. 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 towards protection of public health.


  • Lotlikar MV, A Review : Quality Risk Management (QRM), journal of drug delivery & therapeutics; 2013; 3(2), 149-154
  • Maithani A, Kumar G, Quality Risk Management (Q9): An Overview Int J of Pharm and Med Research Int. J. Pharm. Med. Res; 2014; (2):68-71
  • International Conference on Harmonization Guidance for industry: Q9 quality risk management. ICH; 2006.
  • US Food and Drug Administration. Guidance for Industry: Q9 Quality Risk Management. Accessed March 13, 2007. http://www.fda.gov/cder/guidance/7153fn1.pdf.
  • International Conference on Harmonization of Technical requirements for registration of pharmaceuticals for human use (ICH). Q9 quality risk management. Geneva: ICH; 2005.
  • FDA Global Harmonization Task Force, “Implementation of Risk Management Principles and Activities within a Quality Management System”: Rockville, MD, 2000.
  • FDA, Guidance for Industry: Quality Systems Approach to Pharmaceutical CGMP Regulations: Rockville, MD, 2006.
  • Hazard and risk analysis in pharmaceutical products. who: 2003: technical report series, no. 908. annex 7
  • Guidance for Industry Q9 Quality Risk Management ,U.S. Department of Health and Human Services Food and Drug Administration Centre for Drug Evaluation and Research (CDER) Centre for Biologics Evaluation and Research (CBER) June 2006 .
  • Pharmaceutical CGMPS for the 21st century – A risk-based approach. FDA: 2004.
  • Pharmaceutical quality system. ICH Harmonized Tripartite GuidelineQ10: ICH: 2008.
  • Development and Manufacture of Drug Substances (Chemic al Entities and Biotechnological/Biological Entities). Draft Consensus Guideline Q11: ICH: 2011.
  • Risk assessment and quality control by Max Williams, MPA, November
  • Quality Risk Management- the pharmaceutical experience ann’omahony 11 November
  • Risk Management: Guidelines and Best Practices Missouri Information Technology Advisory Board project Management Committee Risk Management Sub committee , November
  • Risk Management – Vocabulary – Guidelines for Use in Standards, International organization for standardization, Jan 1, 2002
  • Reddy V, Gupta N, Raghunandan S, Kashyap U, A Review : Quality Risk Management in Pharmaceutical Industry ,Int J of Pharm Tech Research CODEN (USA) , 2014 ; 6(3): 908-914
  • ICH Harmonised Tripartite Guideline, Quality Risk Management Q9, Current Step 4 version dated 9 November 2005
  • WHO Technical Report Series No. 981,
  • Analysis techniques for system reliability. Procedure for failure mode and effects analysis (FMEA). Norme international / CEI/ IEC, 1985.
  • Pharmaceutical development, ICH Harmonized Tripartite Guideline Q8 (R2): ICH: 2009.
  • Merck & Co., Pfizer, AstraZeneca, Center for Drug Evaluation – FDA, Wyeth, Bristol Myers Squibb, Johnson & Johnson Quality Risk Management Principles and Industry Case Studies Final Draft – Rev. December 28, 2008.
  • Quality Risk Management ICH Q9 Annex I: Methods & Tools, July 2006
  • Application of Hazard Analysis and Critical Control Point (HACCP) methodology to pharmaceuticals, World Health Organization WHO Technical Report Series, No. 908, 2003 Annex 7
  • Akilesh K, Dr. Reddy D, Siababa SV  and Dr. Rajkamal B, Review: Role of ICH Guidelines in Pharmaceutical Quality Risk Management, European J of pharm and med  res,2016; 3(7):161-169.
  • Stephen Liebowitz , A Case Study in Quality Risk Management : Saxagliptin (Onglyza), Pharmaceutical Quality system (ICH Q10) conference ,October 4­6,2011.
  • Hanna-Leena Saari, Risk Management in Drug Development Projects, Laboratory of Industrial Management Report 2004/1
  • Chavda V, Maru S, & Patel B , How Quality Risk Management is Useful for Pharmaceuticals Global, Research J of sci & nature; 2015;1(1):10-13
  • Preston ST, Hegadoren K. Glass contamination in parenterally administered medication. J Adv Nurs ;2004; 48(3): 266-70
  • Puntis JW, Wilkins KM, Ball PA, Rushton DI and Booth IW. Hazards of parenteral treatment: do particles count? Arch Dis Child ;1992; 67(12): 1475-7
  • Walpot H, Franke RP, Burchard WG, Agternkamp C, Muller FG, Mittermayer C, Kalff G. The fi lter eff ectiveness of common 15- micron filters (DIN 58362). II: Scanning electron microscopy and roentgen analysis, Infusions  therapie; 1989; 16(3): 133-9
  • Heiss-Harris GM, Verklan MT. Maximizing patient safety: filter needle use with glass ampoules, J Perinat Neonatal Nurs; 2005; 19(1): 74-81