Overall QRM process and implementation by Parag ghadigaonkar studied in M.Pharm(QA) Rajgad Dnyanpeeth College of Pharmacy,Bhor-412 206.

1. WELCOME

2. QUALITY RISK MANAGEMENT
PRESENTED BY:-
PARAG.P.GHADIGAONKAR
1ST YEAR M.PHARM IN PQA
Under Guidance Of:-PROF.V.V.KUNJIR.
Roll.No:-1.
Semester 1( SAVITRIBAI PHULE PUNE UNIVERSITY-2019 PATTERN)
Subject Name:- Quality Management System.
Date:-06-04-2021

3. CONTENTS
1) Introduction :-
-Scope.
-Definations.
-Principle.
2) General process of
QRM:-
-Initiating a QRM process.
-Risk assesment.
-Risk control.
-Risk communication.
-Risk review.
-Risk Management Tools.
3) Opportunities &
challenges for
implementation
of QRM
4) WHO
guidelines
on
QRM.
5) ICH to
revise
QRM
guidelines.
6)QRM to
address
product
impurities.

4. 1)Introduction:-
-It is a systematic process for the assessment, control, communication and review of risks to
the quality of the medicinal product.
-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.

5. -Scope Of QRM
-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, inspection and
submission processes throughout the lifecycle of drug substances.
-Principles Of QRM
- 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 commensurate with the level of
risk.

6. -Definations Involved in QRM Process:-
a) Decision Maker:-Person with the competence and authority to make appropriate and timely
quality risk management decisions is called decision maker.
b) Detectability:-The ability to discover or determine the existence, presence, or fact of a hazard.
c) Harm:-Damage to health, including the damage that can occur from loss of product quality or
availability.
d) Quality System:-The sum of all aspects of a system that implements quality policy and
ensures that quality objectives are met.
e) Risk Acceptance:-The decision to accept risk.
f) Risk Analysis:-The estimation of the risk associated with the identified hazards.

7. g) Risk Assessment:-A systematic process of organizing information to support a risk decision
to be made within a risk management process.
h) Risk Communication:-The sharing of information about risk and risk management between
the decision maker and stakeholders.
i) Risk Control:- The actions implementing the risk management decisions.
j) Risk Management:-The systematic application of quality management policies, procedures,
and practices to the tasks of assessing, controlling, communicating and reviewing risk.
k) Stakeholder:-Any individual, group or organization that can affect, be affected by, or
perceive itself to be affected by a risk.

8. 2)General Process Of QRM:-
-A model for quality risk management is outlined in the diagram.1.
-Various components are involved in QRM process are as follows:-
a)Initiating a QRM process.
b)Risk assesment.
c)Risk control.
d)Risk communication.
e)Risk Review.
f) Risk management tools.
Fig.no.1

9. a)Initiating a QRM process:-
-Quality risk management should include systematic processes designed to coordinate,
facilitate and improve science-based decision making with respect to risk.
-steps used to initiate a quality risk management process includes:-
I) Define the problem risk question, including pertinent assumptions identifying the potential
for risk;
II) Assemble background information or data on the potential hazard, harm or human health
impact relevant to the risk assessment;
III) Identify a leader and necessary resources;
IV) Specify a timeline, deliverables and appropriate level of decision making for the risk
management process.

10. b)Risk assesment:-
-It includes the 3 parts :-i)Risk identification.
ii)Risk analysis.
iii)Risk evaluation.
I)Risk identification:-
-Risk identification 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.
Fig.no.2

11. II)Risk analysis:-
-Risk analysis is the estimation of the risk.
III)Risk evaluation:-
-Risk evaluation compares the identified and analyzed risk against given risk criteria.
-It is the qualitative or quantitative process of linking the likelihood of occurrence and
severity of harms.

12. c) Risk control:-
-Risk control includes decision making to reduce or accept the risks.
-The amount of effort used for risk control should be proportional to the significance of the risk.
-It includes the 2 main components:-
I)Risk reduction.
II)Risk acceptance.

13. I)Risk reduction:-
- Risk reduction focuses on processes for mitigation or avoidance of quality risk
when
it exceeds a specified (acceptable) level.
- Risk reduction might include actions taken to mitigate the severity and probability of harm.
II)Risk acceptance:-
-Risk acceptance is a decision to accept risk.
-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.

14. d)Risk communication:-
- 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.
- Parties can communicate at any stage of the risk management process.
e)Risk review:-
- The output/results of the risk management process should be reviewed to take into
account new knowledge and experience.
- The frequency of any review should be based upon the level of risk.

15. f)Risk management tools / Methodologies of QRM:-
-It includes:-
I)HACCP.
II)Risk ranking & filtering.
I)HACCP:-
- HACCP consists of the following seven steps:
(1) conduct a hazard analysis and identify preventive measures for each step of
the process;
(2) determine the critical control points;
(3) establish critical limits;
(4) establish a system to monitor the critical control points;
(5) establish the corrective action to be taken when monitoring indicates that the
critical control points are not in a state of control;
(6) establish system to verify that the HACCP system is working effectively;
(7) establish a record-keeping system.

16. II)Risk ranking and filtering:-
-Risk ranking and filtering is a tool for comparing and ranking risks.
-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 fit the risk
ranking to the management.

17. 3) Opportunities and challenges in implementation of QRM:-
-The stakeholders included in QRM of a product/process constitute inter-multidisciplinary
team with sufficient expertise of relevant operation.
-The stakeholders can be divided into categories; Responsible, Accountable, Consulted
and Informed, shortly known as RACI.
-The team can define risk in question attributed to a target product.
-The risk question should also be agreed upon as to linking the risk evaluation and any
action with protection to patient.

18. 4)WHO guidelines on QRM:-
- Systematically analyze the products and processes to ensure the best scientific rationale is
in place to improve the probability of success.
- Identify important knowledge gaps associated with processes that need to be understand
to properly identify risks.
- Provide a communication process that will best interface with all relevant parties
involved in the QRM activities.
- Facilitate the transfer of process knowledge and product development history to
ease
product progression along the life-cycle and to supplement already available
knowledge about the product.

19. 5)ICH To Revise QRM Guidelines:-
- ICH Q9 states, “Although there are some examples of the use of QRM in the Pharma
industry today, they are limited and do not represent the full contributions that risk
management has to offer.”
- This statement still holds true today as citations for incomplete corrective action & preventive
action.
- Current thinking is that the EWG will focus on clarifying certain aspects of the document’s
concepts in an addendum to the document.
- Basically, the document itself will probably not be revised but instead will be enhanced by
creating a partnering document that will focus more on ‘how to do’ and less on ‘what to do’
with respect to QRM.

20. -Include a standardized CAPA.
-Remove the perception that QRM is not enforced and not part of the quality system.
-Include language that drives a holistic systems approach.
-Define roles, particularly decision-maker roles.
-Provide more guidance on risk acceptance.
-Guidelines:-

21. 6)QRM To Address Product Impurities:-
-N-nitrosodimethylamine (NDMA) impurities in drug substances such as ranitidine and
metformin have demonstrated the urgent need for manufacturers and regulators to control
impurities throughout the product life cycle to ensure patient safety.
-NDMA impurites may be classified as a:-
I) It is the carcinogenic substance for humans.
II)It is a known contaminant found in water and
foods.
III) It is also found in drugs as an impurity.
Fig.no.4

22. - QRM as a tool to assess the risk and control of impurities such as NDMA.
- This approach requires a thorough knowledge of the product, its manufacturing process, the
impurity of the product’s and the impurity’s chemical structures, situations ideal for the
formation of the impurity, and the controls are generally adopted.
- No matter how impurities are formed, the mechanism of their formation should be known and
controlled.

23. -References:-
1)ICH Of Technical Requirements For Registration Of Pharmaceuticals For Human Use,
`Quality Risk Management’,Step 4 version; page no:-1-7 & 12-13.
2)MJH Life sciences and pharmaceutical technology,``ICH To Revise QRM Guidelines”, by
Susan.J.Schniepp;Volume 44,Feb-2020;Page no:-57-58.
3) Revised Draft For Discussion,``WHO Guidelines On QRM”,Rev 1,2011:Page no:-7.
4)International Journal Of Research In Pharmacy and Science,``Opportunities and challenges in
Implementation Of ICH Q9 With emphasis to WHO approved pharmaceutical plant’’,by
Venkatesh.M.P.,Nagendra.S.R.,Pramod Kumar.T.M.;2017;Page.no:- 18-19.
5)Pharmaceutical Engineering,``Quality Risk Management”,by Muhammad Naeem,MS
Jan-Feb 2021;Page No:- 1-2.

24. THANK YOU