How to use this Presentation: Purpose of this presentation: This presentation gives Guidance to users on each Step of the GMP Risk Management tool It attempts to answer some common questions which may arise when using the tool.. so, this is mainly a Q&A Document How to make the most out of these slides: When performing a GMP Risk Management exercise with this tool, each participant of the team should have a paper copy of these slides for reference When at a particular Step of the tool, the corresponding slides for that Step can be checked and consulted for Guidance Guidance for Step 1 –Preliminary Info What is Step 1 about? Page 1 of Step 1 is where we define the purpose of the RM exercise, and here also we state what is being studied (e.g. a Manufacturing Process). Page 2 is where we scope out the RM exercise, and it is where we state the reason for the exercise. Selecting from the available three Options in Step 1 Options 1 and 3 are similar in that they both relate to Change Controls, but Option 3 goes beyond looking merely at the Q & V requirements associated with a proposed Change, as it assesses the change control from a broader viewpoint…it asks “If we implement the proposed change, what risks does it present?”Option 1 & 2 cannot both be selected at one time. Guidance for Step 1 –Preliminary Info What could a Specific Issue or Problem look like in Step 1? This could be something such as glass in vials, a series of batch rejects due to high impurity levels, a product recall issue, etc. What is meant by “Item Under Study”in Step 1? This is just the term used in the tool to refer to the subject of the Risk management exercise. Guidance for Step 1 –Preliminary Info What kind of info do we record under “Reason & Relevant Background Info”? Under “Reason & Relevant Background Info”give as much useful info as possible on why we are doing this exercise. It can be useful here to think in terms of a Risk Question, or in terms of a Problem Description when completing this section. Also, here is where we should clearly state or reveal any pertinent assumptions which may be relevant to the RM exercise. For example, a pertinent assumption might be that all equipment used in a process has been qualified. This becomes very useful later on, when we get to Step 8, which is about Qualification & Validation. Also for example, we could record the following here “It is assumed that all personnel have been successfully trained on the SOPs in question”. Guidance for Step 1 –Preliminary Info What kind of info do we record under “Reason & Relevant Background Info”? Note: Revealing and documenting any assumptions which are relevant helps us to have confidence in the output of the RM exercise, and also, it helps to identify the limitations of the RM exercise. Guidance for Step 2 –The RM Team Who should be on the RM Team? It is important to include experts from the appropriate areas which are of relevance to the item under study in the Risk Management exercise. (Ref: ICH Q9) Also, there should be at least one person who is knowledgeable of the Risk management process, its principles and techniques. (Ref: ICH Q9) This person need not be the team leader. Why should the RM Team be multi-disciplinary? Multi-disciplinary teams can offer diverse viewpoints and are beneficial for this reason, especially if the RM exercise will use brainstorming to identify potential negative events. There is no ideal size for the team, but probably at least 4 people are required Guidance for Step 3 –P, S & D Levels The Laminated Card –Some General Considerations The card shows the various levels for Probability, Severity, and Detection which the tool uses. These levels should not be changed. The card gives default definitions for each of these levels. These are simple and basic definitions, and there are purposely non-quantitative. They are qualitative definitions. For example, a Medium probability defined as one where “the negative event may occur”. However, these qualitative definitions can be changed, especially where there are data available which support the use of quantitative definitions. See next slide, and also, follow the instructions in Step 3 of the Tool Worksheet if you want to change the default qualitative definitions given on the laminated card. The laminated card also shows the Risk Table, and the associated risk acceptability criteria. Guidance for Step 3 –P, S & D Levels Modifying the S, P & S Definitions on the Laminated Card As noted on the previous slide, the definitions for P, S & D are qualitative, but they may be modified to suit the case at hand, allowing for quantitative definitions to be drawn up. e.g. The definition for a high probability could be modified to mean that the negative event occurs in more than 50% of the time, or in more than 90% of the time, or most of the time, or every day, etc. However, it is difficult to put numbers on P, S & D levels, and what works for one negative event may not for another, even within the same risk management exercise. Note also that when modifying the Severity level definitions, it is important to consider who the stakeholders for the item under study are. (See next slide.) Guidance for Step 3 –Stakeholders What is a Stakeholder? This is “any individual, group or organisation that can affect, be affected by, or perceive itself to be affected by a risk.”(Ref: ICH Q9) In the GMP area, the main stakeholders will usually be: Patients, users of medicines, and animals (for Vet. meds) Healthcare Professionals of various types Wider Society (this is more relevant for some medicines, such as vaccines, than for others, such as analgesics.) The Company itself –this is because the company can be affected by GMP risks which are not adequately addressed. Wider Industry GMP Regulators Guidance for Step 3 –Stakeholders What is a Stakeholder cont’d? There may be other stakeholders too, e.g. supplier and customer companies, and these may need to be considered if new Severity Levels are being defined. The tool assumes that the above make up the main stakeholders of any GMP item under study: Guidance for Step 4 –Potential Negative Events What is a Negative Event? A Negative event is defined broadly as “something that can go wrong”. “What can go wrong”is a phrase borrowed from ICH Q9, and it has been found to be useful and easier to understand than the other terms such as “Failure Modes”. Why do we select just three potential Negative Events? This is a formal RM tool. It is designed to apply RM to only the most critical and/or complex issues or problems. It is not intended to be used to address more minor issues which can be addressed by other, less formal, means. ICH Q9 (10/2004) states: “The degree of rigor and formality…can be commensurate with the complexity with the complexity an/or criticality of the issue to be addressed”. “It is not always appropriate nor necessary to use a formal RM process.”“The level of effort, formality & documentation of the quality RM process should be commensurate with the level of risk ….. “Guidance for Step 4 –Potential Negative Events Some General Considerations when Identifying Potential Negative Events Risk Management is not an exact science, and identifying potential negative events is a subjective task to a degree, especially when expert judgement and informed opinions are used. There will be uncertainty associated with whether some suggested potential negative events could actually occur, and this is okay, because the tool addresses this uncertainty in Step 5. Also, the item under study will have different stakeholder group. Each group can have different concerns, and different stakeholders might perceive different consequences for the same negative event. These factors can influence what we decide are the potential negative events. Guidance for Step 4 –Potential Negative Events Some General Considerations cont’d So, while identifying potential negative events is a subjective task to a degree, protection of the patient should be considered of prime importance, this principle, (protection of the patient), is a useful guide when we are working to