Safeguarding public health Impact of ICH Q9 and the application of Risk Management An inspector s perspective on the impact on inspectional approaches and expectations Ian Thrussell Strategy and Development Team GMP Inspection Group I&S Division, MHRA, UK ian.thrussell@mhra.gsi.gov.uk
Content of the presentation Introductory background Words of caution Where are we coming from and where are we going? Issues from inspections Open forum for Q & As Slide 2
What do Regulators want from the so called 3 Qs Paradigm shift? Is the status quo any longer acceptable? How might the relationships between the pharmaceutical manufacturer and their suppliers support or inhibit whether and how these goals are met? What are the challenges? - How can we all work together to achieve these goals? Slide 3
Regulatory changes UK: Hampton Report Reducing administrative burdens: effective inspection and enforcement, March 2005 Executive summary: Risk assessment should be comprehensive, and should be the basis for all regulators enforcement programmes. Proper analysis of risk directs regulators efforts at areas where it is most needed, and should enable them to reduce the administrative burden of regulation, while maintaining or even improving regulatory outcomes. Slide 4
What is the big regulatory picture? EU regulators firmly believe that effective and robust processes should be - Designed from the outset to be optimally fit for purpose - Underpinned by the application of principles of Quality Risk Management - Operated under an effective quality system. EU Regulators are committed to safeguarding public health but are also committed to leaving sufficient flexibility to industry and to avoiding an increase in unnecessary requirements. EU Regulators are committed to fostering innovation! EU regulators firmly believe that they have been looking for RM in company inspections for many years! Slide 5
ICH Q9: Q9 which is unique as for industry and regulators : - Harmonised implementation within the EU (e.g. Q9 implementation group at the EMEA level for GMP related matters or working group of assessors) - Is optional but is not an open door to think that the EU legislation could also be optional - Already assessed by EU GMP inspectors with some good experiences and also lot of bad.. Slide 6
Inspecting industry risk cases involves a changing role of the GMP inspector: It is no longer just inspecting it is also: - to support companies to concentrate their ressources on real risks - to encourage companies to understand and use QRM - to encourage companies to make their risks transparent - to create an atmosphere of mutual confidence It is no longer just inspecting every 2 years inspectors will have to evaluate individually for each site the frequency and depth of inspections - not least based on company s overall QRM performance The inspector s job will become more scientific and related to real risks Slide 7 7
Sorts of industry risks Strategic risks: e.g. competitor advantage Operational risks: e.g. HSE (health, safety & environment) Financial risks: e.g. shareholder harm Compliance risks: e.g. patient harm Availability of goods / insufficient stock levels Slide 8
Reasons to apply QRM Support decisions to accept or not a risk Determine the minimum necessary effort to control a risk Determine cost-benefit of risk reduction measures Allocate ressources according to risk (staff, technical, financial) Prioritisation of risk reduction / control measures Show adequacy of risk reduction / control measures Review efficacy of risk reduction / control measures Survive an official GMP inspection [a misleading motivation ] Show compliance with Market Authorisation requirements (especially dossiers containing ICH Q8 QbD elements) Slide 9 9
Prospective uses lead question: what might go wrong? Examples Design of product development approaches Scope of qualifications, validations, tech transfers Evaluation of proposed changes - incl. intro of new products / processes / systems / people Focus of product quality reviews Scope of on-going stability programme Planning of self-inspections / third party audits Slide 10 10
Retrospective uses lead question: what has gone wrong? Examples reports of suspected quality defects OOS results at batch release testing undesigned deviations or OOL / OOT / OOE results, e.g. with respect to: - Manufacture - Environmental monitoring - Validation - Stability testing - Storage / transport Slide 11 11
Why do EU inspectors already look at an organisation s QMS and QRM programmes during inspections? Looking at how companies react when things go wrong and are under pressure is a major diagnostic indicator of the robustness of the scientific and organisational integrity of a company s operations - Do they investigate to improve knowledge or simply build arguments for release of product - Quality of investigations- appropriateness of depth of investigation - Reactive rather than proactive usage - Quality is everyone s responsibility Is this true when things go wrong? Slide 12
Importance of root cause investigations and risk management Slide 13
Management Responsibilities Senior management commitment Development and maintenance of the quality system Provide the leadership needed for the successful functioning of the quality system Adequate provision of resources Encourage internal communication on quality issues at all levels of the organization (QU, R&D, RA, manufacturing, etc.) Ensure assigned authorities and responsibilities support production, quality, and management activities Ensure that there is Informed decision-making processes with the participation of key components or the organization using product and process knowledge and risk management tools Slide 14
No use of QRM For release of a batch not meeting its specification [cf. EMA Reflection Paper on QP discretion] As a means not to comply with or to circumvent regulatory or GMP requirements As a means to hide risks As a means to hide insufficient risk control Slide 15 15
Debatable Examples Scope of testing of pesticides in herbal drugs to be used in homeopathic finished products TSE risk of animal origin starting materials to be used in vet products for non-food animals Control of transport conditions for finished products for which no particular conditions are specified Requirements for a clean area used only sporadically and only for incoming goods sampling of non-sterile APIs to be used in sterile finished products Slide 16 16
A few words about risk based C & Q Often the inspector is left wondering exactly why a company has done what it has done! Has the company really explained why it has qualified/validated what it has done? Does it know or is it simply the presenter? Is the company simply trying to waste the time of the inspector? Slide 17
Good risk assessment and summaries! Adds clarity! Aids communication! It tells a convincing story! Has the company a process map? - Can it demonstrate that it has covered what appear to be the key points? Is the output and outcome from the assessment actually implemented? Does the process actually perform better? What about the residual risks? Slide 18
What does MHRA Inspectors see as the greatest risks for processes seen in inspection? People: - Their lack of experience, knowledge & understanding Individually and at the corporate level Are companies learning organisations - Over confidence in process robustness - Human ingenuity to interfere in the best designed processes - Change control Process and Equipment: - Poor process design - Operational integrity of transfer technology processes Slide 19
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