Rocky Road to ICH Q12 Implementation

Prior to the adoption of Q12 in Singapore at the end of 2019 there was a lot of rumbling from regulatory agencies on how Q12 would be more aspirational in many ways. In the last few weeks we’ve started to see just what that will mean.

FDA to release a guidance

The FDA’s Mahesh Ramanadham, from the Office of Pharmaceutical Quality in the FDA’s Center for Drug Evaluation and Research, provided an update on the agency’s implementation of ICH Q12 in the US on 25 February at the annual IFPAC meeting in North Bethesda, Md. He started that the FDA will soon be issuing guidance implementing the International Council on Harmonization’s Q12 guideline in the US that will, among other things, translate ICH post-approval change classification categories to FDA supplement categories, and address how to file established conditions (ECs).

This Q12 guidance will replace the agency’s 2015 draft guidance for industry on established conditions and reportable chemistry, manufacturing and controls changes to approved drug and biological products. It is expected to be issued in May 2020. The guidance will also discuss the relationship between FDA comparability protocols and the post-approval change management protocol (PACMP) established by the ICH Q12 guideline.

EU says not so fast in their adoption

However, additional scientific risk-based approaches to defining Established Conditions and
associated reporting categories, as described in Chapter 3.2.3, and the Product Lifecycle
Management (PLCM) Document, as described in Chapter 5, are not considered compatible with the
existing EU legal framework on variations.

It is important to note that the legal framework always takes precedence over technical and
scientific guidelines. More specifically this means that the definition of Established Conditions and
their reporting categories must follow the requirements laid down in the current EU Variations
Regulation and associated EU Variations Guidelines. With respect to the Product Lifecycle
Management (PLCM) document, in case such a document is submitted, it cannot be currently
recognised in the EU due to the fact that it is not referred to in the EU legal framework.

EMA/CHMP/ICH/78332/2020

In an explanatory note accompanying the adoption of ICH Q12 and related annexes, the European Commission and the European Medicines Agency point out that there are “some conceptual differences” between the ICH guideline and the EU legal framework on managing post-approval changes, ie, the variations regulation (Regulation (EC) No 1234/2008).

The EU authorities offer no clarity on when and how ICH Q12 would be fully implemented in the EU. The note merely states that the new “tools and concepts in the ICH Q12 guideline that are not foreseen in the EU legal framework will be considered when this framework will be reviewed.” The EU regulators said they would continue to work on the implementation of the ICH Q12 within the existing EU legal framework. The explanatory note also points out that despite some conceptual differences between ICH Q12 and the EU framework, there is also considerable common ground. In fact, some tools and concepts in ICH Q12 tools can already be applied by industry by following the current EU variations framework.

Next Steps

Companies should be ensuring that their knowledge management and risk management processes and understanding continue to grow. ICH Q12 will be a rocky road and I’m not sure we’ll see some of the potential streamlining of regulatory processes for a long time.

ICH Q12 pathway for established conditions

Understanding the Levers of Change

As part of my presentation “Sustaining Change – Executing a Sustainability Plan” at the ASQ Lean and Six Sigma Conference tomorrow I’ll be talking about levers of change.

Understanding the change landscape

Change Management practitioners usually talk about seven levers:

  1. Infrastructure – Investing in the tools, processes, and other resources that employees need to be successful with the change initiative.
  2. Walk the Talk – active leadership is about ownership; it includes making the business case clear, modeling behaviors, clearing obstacles and making course corrections.
  3. Reward and Recognition – acknowledgement and compensation for employees who work to move the initiative forward
  4. Mass Exposure – getting out information about the change through broadcast messages and other communication pathways
  5. Personal Contacts – creating opportunities for advocates to share their experience of the change with peers who feel disengaged
  6. Outside advocates – bringing in resources (internal or external) to gain expertise for the change initiative
  7. Shift Resisters – moving people to areas less affected by the initiative.
7 levers of change

Conference Speaking -2020 Lean and Six Sigma

In February I will be presenting at the 2020 ASQ Lean and Six Sigma Conference in Phoenix on Sustaining Change – Executing a Sustainability Plan.

Here’s the presentation summary:

For Lean and Six Sigma projects a central question should always be “how do we sustain this change?” Sustainability is a major part of all the major change models but is often the easiest to neglect. This session will engage the participant in building a Sustainability Plan, a key tool to ensure the change is anchored and embedded in the organization. Through three case study examples of changes at the three major change levels -transactional, organizational and transformational – the participant will gain the knowledge to create and execute an effective change plan.

During this session examples will be given for each component of a sustainability plan:

  • Communication: Mechanisms for persuasive communication and ongoing socialization of the change, rites of parting (saying goodbye to the old ways of doing things), and rites of enhancement (acknowledgment of quick wins and continued adoption)
  • Metrics Tracking: How to identify and execute consistent and effective ongoing measurement and results reporting to track progress and ensure sustained results • Performance Management: Process for observing and objectively measuring desired behaviors and attitudes, including performance appraisal process, promoting, demoting and transferring, and training and development
  • Rewards and Recognition: Program of intrinsic and extrinsic incentives to reinforce desired behaviors and attitudes
  • Sustaining Ownership: Consistent process for ensuring sustained ownership of the change through the ongoing transfer of experience and knowledge
  • Continuous Improvement: Mechanisms for responding to changing requirements and implementing improvements based on feedback, observations, and metrics

The following questions will be explored, and tools for finding answers will be provided:

  • How should organizational achievements reinforcing the change be commemorated
  • What behaviors should be observed and measured on a regular basis?
  • What results should be observed and measured on a regular basis?
  • What metrics should be used for measuring behaviors and results?
  • What mechanisms should be used for reporting results? • What criteria should be used to allocate rewards and promotion?
  • What mechanisms should be used for training, coaching, and role modeling?
  • What processes and procedures should be put in place to ensure sustained ownership of the change?
  • What continuous improvement mechanisms will address low adoption rates and ensure the change becomes part of the organization’s normal functioning?

At the end of the session the user will have a template for creating a sustainability plan and will have been provided tools to successfully execute the sustainability phase of a change.

Learning Objectives 1. Assess the role of sustainability in the major change management methodologies and apply to lean and six sigma projects. 2. Facilitate the sustainability phase of change management. 3. Compose a sustainability plan.

MHRA on Passing the Baton from GPvP to GMP

I love the MHRA Inspectorate blog. They don’t write often, but when they do, good stuff. Here are some of my thoughts on the post on moving patient safety data from determination as part of the pharmacovigilance efforts to labeling to distribution.

Starting in the Good Pharmacovigilance Practice (GPvP) realm, triggers for updates may be identified by pharmacovigilance staff and the corresponding variations submitted by regulatory affairs staff, who will also receive notification of variation approval. At this stage Good Manufacturing Practice (GMP) processes come into play with arrangements for printing the updated leaflets and incorporating these into the supply chain.

MHRA Inspectporate Blog “Passing the baton from GPvP to GMP: Three top tips for protecting patients and staying compliant ” 17 Dec 2019

Unless otherwise stated, updates to patient information leaflets should be introduced within 3 to 6 months of approval” – this is the critical point stressed in this post. The recommendations given in the blog post are solid.

Blog RecommendationThoughts
Check that the end to end process facilitates the timely implementation of updates and that there is seamless transition from written procedures covering GPvP, regulatory affairs and GMP processes. Labeling is often a separate change control process. Integration and simplification in change management is critical and companies should look seriously at balkanization of systems.
Define what is meant by ‘implementation’ of an updated leaflet and make sure this is in advance of regulatory deadlines to prevent the need for batches being re-worked should there be any unexpected delays Effective dates on changes need to take into account deadlines.

Appropriate linkages to ERP and supply chain systems.
Ensure the QP has access to up to date information on the correct leaflet version that should be used at batch certification. Communication, and the use of integrated change management

I also read this morning Teresa Gorecki’s post “Dedicated, Integrated Quality Assurance Systems Critical to Successful Clinical Trials.” All of her points are highly relevant here.