Understanding Some International Organizations – ICH, ICMRA and PIC/S

The ICH, ICMRA, and PIC/S are three important international organizations in the pharmaceutical regulatory space that folks should pay attention to and understand how they shape our profession’s future.

International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH)

The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) is a global initiative that brings together regulatory authorities and the pharmaceutical industry to discuss and establish common guidelines and standards for developing, registering, and post-approval pharmaceutical products.

History and Evolution

Establishment: ICH was established in 1990 by the regulatory authorities and pharmaceutical industry associations from Europe, Japan, and the United States. The goal was to harmonize the regulatory requirements for pharmaceutical product registration across these regions.
Reformation: In 2015, ICH was reformed and became a legal entity under Swiss law, transforming from the International Conference on Harmonisation to the International Council for Harmonisation. This change aimed to create a more robust and transparent governance structure and to expand its global reach.

Objectives and Goals

Harmonization: The primary goal of ICH is to achieve greater harmonization worldwide to ensure that safe, effective, and high-quality medicines are developed and registered in the most resource-efficient manner.
Efficiency: By harmonizing technical requirements, ICH aims to improve the efficiency of the drug development and registration process, reduce duplication of clinical trials, and minimize the use of animal testing without compromising safety and effectiveness.

Structure and Governance

ICH Assembly: This is the overarching governing body, which includes all members and observers. It adopts decisions on guidelines, membership, work plans, and budgets.
ICH Management Committee: This committee oversees the operational aspects, including administrative and financial matters and working group activities.
MedDRA Management Committee: This committee manages the Medical Dictionary for Regulatory Activities (MedDRA), standardizing medical terminology for adverse event reporting and clinical trial data.
ICH Secretariat: Handles the day-to-day management and coordination of ICH activities.

Guidelines and Categories

ICH guidelines are categorized into four main areas:

Quality: Covers topics such as stability testing, analytical validation, and good manufacturing practices (GMP).
Safety: Includes guidelines on genotoxicity, reproductive toxicity, and other safety evaluations.
Efficacy: Focuses on the design, conduct, safety, and reporting of clinical trials, including novel drug classes and pharmacogenetics.
Multidisciplinary: Encompasses cross-cutting topics like the Common Technical Document (CTD) and electronic standards for regulatory information transfer.

Global Impact and Implementation

Membership: ICH includes regulatory authorities and industry associations from around the world. It currently has 20 members and 36 observers.
Implementation: Regulatory members are committed to adopting and implementing ICH guidelines within their jurisdictions, ensuring consistent regulatory standards globally.

Key Activities

Guideline Development: ICH develops harmonized guidelines through a consensus-based process involving regulatory and industry experts.
Training and Support: Provide training materials and support to facilitate the consistent implementation of guidelines across different regions.

The ICH plays a crucial role in the global pharmaceutical regulatory landscape by promoting harmonized standards, improving the efficiency of drug development, and ensuring the safety and efficacy of medicines worldwide.

International Coalition of Medicines Regulatory Authorities (ICMRA)

The International Coalition of Medicines Regulatory Authorities (ICMRA) is a voluntary, executive-level, strategic coordinating, advocacy, and leadership entity. It brings together heads of national and regional medicines regulatory authorities worldwide to address global and emerging human medicine regulatory and safety challenges.

Objectives and Goals

Global Coordination: ICMRA provides a global architecture to support enhanced communication, information sharing, crisis response, and addressing regulatory science issues.
Strategic Direction: It offers direction for areas and activities common to many regulatory authorities’ missions and identifies areas for potential synergies.
Leveraging Resources: ICMRA leverages existing initiatives, enablers, and resources to maximize the global regulatory impact wherever possible.

Membership

Voluntary Participation: Membership is voluntary and open to all medicines regulatory authorities. It includes prominent entities such as the European Medicines Agency (EMA), the U.S. Food and Drug Administration (FDA), and many others worldwide.
Global Representation: The coalition includes regulatory authorities from various regions, with the World Health Organization (WHO) participating as an observer.

Key Activities and Projects

Antimicrobial Resistance (AMR): Developing a coordinated global approach to tackle AMR.
COVID-19 Response: During the COVID-19 pandemic, ICMRA has been pivotal in expediting and streamlining the development, authorization, and availability of COVID-19 treatments and vaccines worldwide.
Innovation and Pharmacovigilance: Ongoing investigations and case studies relating to emerging regulatory challenges and working on real-world evidence, adverse event reporting, and vaccine confidence.
Supply Chain Integrity: Ensuring the integrity of the global supply chain for medicines.

Strategic Importance

Enhanced Collaboration: ICMRA fosters international collaboration among medicine regulatory authorities to ensure the safety, quality, and efficacy of medicinal products globally.
Regulatory Agility: The coalition promotes regulatory agility and rapid response to global health emergencies, ensuring patients have timely access to safe and effective medical products.

The ICMRA plays a crucial role in the global regulatory landscape by enhancing communication and cooperation among medicines regulatory authorities, addressing shared challenges, and promoting the safety and efficacy of medicinal products worldwide.

Pharmaceutical Inspection Co-operation Scheme.

PIC/S stands for the Pharmaceutical Inspection Co-operation Scheme, a non-binding, informal co-operative arrangement between regulatory authorities in Good Manufacturing Practice (GMP) of medicinal products for human or veterinary use. Its main purpose is to lead the international development, implementation, and maintenance of harmonized GMP standards and quality systems of inspectorates in the pharmaceutical field.

History: PIC/S was established in 1995 as an extension to the Pharmaceutical Inspection Convention (PIC) of 1970. It was created to overcome legal limitations that prevented new countries from joining the original PIC due to incompatibilities with European law.

Membership: PIC/S is open to any regulatory authority with a comparable GMP inspection system. As of 2023, it comprises 56 participating authorities worldwide, including Europe, Africa, America, Asia, and Australasia.

Structure: PIC/S operates as an association under Swiss law, registered in Geneva, Switzerland. It has a committee, an executive bureau, and various working groups.

Relationship with Other Organizations: PIC/S works closely with other international bodies, including the European Medicines Agency (EMA), to promote GMP harmonization and share resources.

Objectives

Harmonizing inspection procedures worldwide
Providing training opportunities for inspectors
Developing common standards in GMP
Facilitating cooperation between competent authorities and international organizations

Activities

Developing and promoting harmonized GMP standards and guidance documents
Training competent authorities, particularly inspectors
Assessing and reassessing inspectorates
Facilitating networking among regulatory authorities

Benefits

Ensures high standards among members
Provides training and networking opportunities
May facilitate pharmaceutical exports indirectly
Increases confidence in medicines manufactured in member countries

PIC/S plays a crucial role in global pharmaceutical regulation by promoting harmonized standards, facilitating cooperation between regulatory authorities, and working towards ensuring the quality and safety of medicinal products worldwide.

The Three in Overview

Aspect	ICH	ICMRA	PIC/S
Full Name	International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use	International Coalition of Medicines Regulatory Authorities	Pharmaceutical Inspection Co-operation Scheme
Established	1990 (reformed in 2015)	2013	1995
Primary Focus	Harmonization of technical requirements for drug development and registration	Strategic coordination and leadership in global human medicine regulation	Harmonization of Good Manufacturing Practice (GMP) standards and inspections
Main Objectives	Develop harmonized guidelines for drug development, registration, and post-approval	Enhance communication, information sharing, and crisis response among regulators	Develop common GMP standards and train inspectors
Membership	20 members, 36 observers (regulatory authorities and industry associations)	Heads of medicines regulatory authorities worldwide	Guideline development, training, and implementation support
Scope	Global, with emphasis on technical aspects of drug development	Global, focusing on high-level strategic issues	Global, concentrating on GMP and quality systems
Key Activities	Guideline development, training, implementation support	Strategic direction, crisis response, addressing emerging challenges	Inspector training, assessment of inspectorates, developing GMP guidance
Legal Status	Legal entity under Swiss law	Voluntary coalition	Non-binding, informal co-operative arrangement
Industry Involvement	Direct involvement of pharmaceutical industry associations	Limited direct industry involvement	No direct industry involvement
Main Output	Harmonized guidelines (Quality, Safety, Efficacy, Multidisciplinary)	Strategic initiatives, position papers, statements	GMP guidelines, inspection reports, training programs

This table highlights the distinct roles and focuses of these three important international pharmaceutical regulatory organizations. While they all contribute to global harmonization and cooperation in pharmaceutical regulation, each has a unique emphasis:

ICH primarily develops technical guidelines for drug development and registration.
ICMRA focuses on high-level strategic coordination among regulatory authorities.
PIC/S concentrates on harmonizing GMP standards and inspection practices.

Their complementary roles contribute to a more cohesive global regulatory environment for pharmaceuticals.

How to Monitor

Organization	What to Monitor	How to Monitor	Frequency
ICMRA	– COVID-19 updates and guidance – Statements on regulatory issues – Reports on emerging topics (e.g., AI, RWE) – Strategic meetings and workshops	– Check ICMRA website regularly – Subscribe to ICMRA newsletter – Follow ICMRA on social media – Attend public workshops when possible	Monthly
ICH	– New and updated guidelines – Ongoing harmonization efforts – Implementation status of guidelines – Training materials and events	– Monitor ICH website for updates – Subscribe to ICH news alerts – Participate in public consultations – Attend ICH training programs	Bi-weekly
PIC/S	– GMP guide updates – New guidance documents – Training events and seminars – Inspection trends and focus areas	– Check PIC/S website regularly – Subscribe to PIC/S newsletter – Review annual reports – Participate in PIC/S seminars if eligible	Monthly

Key points for monitoring:

Set up automated alerts or RSS feeds where available
Create a calendar reminder for regular check-ins on each organization’s website
Collaborate with regulatory affairs colleagues to share insights and updates
Implement a system to disseminate relevant information within your organization
Consider joining industry associations that actively engage with these organizations

Key Links

Navigating the New Era of Quality Management

One of the topics I’m passionate about is exploring the changing landscape of quality management and the challenges we face. The solutions that worked in the past decade won’t be as effective in our current era, marked by post-globalization, capital rationalization, spatial dispersion, shrinking workforces, and an increasing reliance on automation. This transformation calls for a new perspective on quality management, as traditional instincts and strategies may no longer be sufficient. The nature of opportunity and risk has fundamentally changed, and in order to thrive, we need to adapt our approach.

The New Rules of Engagement

In this era of volatility, several key trends are reshaping the business environment:

Post-Globalization: The shift towards localized operations and supply chains.
Capital Rationalization: More stringent allocation of financial resources. This is a huge trend in biotech.
Spatial Dispersion: Decentralized workforces and operations.
Shrinking Workforces: Reduced human resources due to demographic changes.
Dependence on Automation: Increased reliance on technologies like AI, ML, and RPA.

We need to reevaluate how we approach quality management in light of these trends.

Prediction: Anticipating the Future

In a volatile environment, it is crucial to predict and anticipate disruptions. Quality management must shift from being reactive to proactive. This involves:

Advanced Analytics: Utilizing data analytics to anticipate quality issues before they emerge. This necessitates a strong data foundation and the capability to analyze both structured and unstructured data.
Scenario Planning: Developing multiple scenarios to anticipate potential disruptions and their impacts on quality aids in making well-informed strategic decisions and preparing for various contingencies.

Adaptability: Embracing Change

Adaptability is crucial in a constantly changing world. Quality management systems need to be flexible and responsive to new challenges.

Agile Methodologies: Implementing agile practices to allow for quick adjustments to processes and workflows, fostering a culture of experimentation, and learning from failures.
Virtualization of Work: Adapting quality processes to support remote and hybrid work environments involves re-evaluating governance models and ensuring that quality standards are maintained regardless of the location of work.

Resilience: Building Robust Systems

Resilience ensures that organizations can withstand and recover from disruptions. This capability is built on strong foundations:

Robust Systems: Developing systems that can operate effectively under stress. This includes ensuring that automated processes are reliable and that there are contingencies for system failures.
Organizational Culture: Fostering a culture that values resilience and continuous improvement ensures that employees are prepared to handle disruptions and contribute to the organization’s long-term success.

Implementing the New Quality Paradigm

To effectively implement these principles, organizations should consider the following steps:

Assess the Current State: Conduct a comprehensive assessment of existing quality processes, identifying areas for improvement and potential vulnerabilities.
Set Clear Objectives: Establish clear, measurable objectives that align with the principles of prediction, adaptability, and resilience.
Develop a Phased Approach: Implement changes gradually, with clear milestones and measurable outcomes to ensure smooth transitions.
Engage Stakeholders: Involve all relevant stakeholders in the transformation process to ensure alignment and buy-in.
Monitor Progress: Continuously monitor progress against predefined objectives and make adjustments as necessary to stay on track.
Invest in Training: Provide employees with the necessary training and development opportunities to adapt to new technologies and processes.

Conclusion

It is important to change our mindset and strategy. Embracing the principles of prediction, adaptability, and resilience can help organizations navigate the complexities of a volatile environment and position themselves for long-term success. Going forward, it is essential to stay vigilant, flexible, and proactive in our approach to quality management. We must ensure that we not only meet but exceed stakeholder expectations in this rapidly changing world.

Working on Silence

I’m working with my therapist to become more comfortable with silence, which has never been one of my strengths. I’m researching and writing to figure out how to address this. Here are some thoughts on how I plan to incorporate this at work.

Why Silence?

Enhanced focus and reflection: Silence allows team members valuable time to process information, reflect on ideas, and formulate thoughtful responses, leading to deeper understanding and more insightful contributions.
Improved inclusivity: Silent periods level the playing field for all participants, giving everyone an equal opportunity to contribute regardless of personality type or language proficiency. This can help draw out insights from quieter team members who might otherwise struggle to be heard.
Increased efficiency: Silent meetings or periods of silence within discussions can be more time-efficient by eliminating unnecessary chatter and keeping the focus on the agenda.
Higher quality discussions: When participants have time to reflect silently, they often formulate more articulate and considered responses, leading to higher-quality discussions when verbal communication resumes.
Better idea generation: Silence can be particularly effective for brainstorming and ideation. Research suggests that silent brainstorming can yield more and better ideas compared to traditional verbal methods.
Improved listening: Periods of silence encourage active listening, allowing team members to fully absorb what others are saying without immediately formulating a response.
Reduced dominance by vocal members: Incorporating periods of silence into discussions can prevent a few voices from dominating the conversation. This can lead to more balanced and diverse input from the entire team.
Enhanced creativity: Silence allows for diverse perspectives and unexpected ideas, fostering innovative solutions.
Better decision-making: By allowing time for reflection and careful consideration, silence can contribute to more informed and thoughtful decision-making processes.
Improved emotional intelligence: Strategic use of silence can help team members become more aware of nonverbal cues and develop a better understanding of group dynamics.

Okay, so based on this, here’s my plan to effectively incorporate silence into team discussions. I chose team discussions as it seems like a good place to start.

Explain the purpose and benefits of silent periods to the team
Use collaborative tools for quiet idea sharing and note-taking. This will require some alignment and effort to implement as I think my team needs work here to be truly comfortable. Been meaning to do this more.
Plan to take some time to reflect after important points or before making major decisions.
Encourage a culture that values thoughtful pauses and reflection.

Well this was a dizzy ride – thanks SCOTUS for everything (not)

The 2024 U.S. Supreme Court decisions have had significant impacts on the Food and Drug Administration (FDA) and other federal agencies. I don’t think we will truly understand the impact for years as matters move through the courts. This increased uncertainty has led to new questions arising as we assess risk.

Overturning the Chevron Doctrine

A significant decision was made to overturn the Chevron doctrine, a longstanding precedent that mandated courts to defer to federal agencies’ expertise when interpreting unclear statutes. This doctrine has played a crucial role in enabling agencies such as the FDA to establish and enforce regulations based on their specialized knowledge.

Reduced Authority: With the Chevron doctrine overturned, the FDA’s ability to interpret and enforce regulations without judicial interference is significantly curtailed. This change makes it easier for regulations to be challenged in court, potentially leading to increased litigation and uncertainty in regulatory enforcement.

Challenges to Regulatory Actions

The decisions made by the Supreme Court have made it harder for federal agencies to effectively carry out their regulatory functions. The court’s rulings have extended the time frames for challenging agency actions, leading to delays in implementing new regulations and enforcement actions. This could particularly affect the FDA’s ability to respond promptly to emerging public health issues.

Specific Cases Affecting the FDA

Several other cases have also directly impacted the scope of FDA regulations:

Environmental and Safety Regulations: Recent court decisions have impacted the FDA’s ability to enforce regulations concerning food safety and environmental protection. For example, the decision to block certain EPA regulations on cross-state pollution indirectly affects the FDA’s responsibility to ensure the safety of food and drugs that might be affected by environmental factors. It’s still uncertain how significant this impact will be, but I am more concerned about this issue than I am about the weakening of the Chevron defense.
The Supreme Court’s decision to protect access to the abortion medication mifepristone is an important exception. The court upheld the FDA’s regulatory decision, which ensures that the FDA can continue to regulate and approve medications important to public health. However, it’s worth noting that this ruling was specifically about the legal standing of the case, so it’s not an entirely straightforward situation.

Broader Implications

The recent decisions signal a change in the balance of power between the judiciary and federal agencies. The Supreme Court’s decision to limit the deference typically given to agencies such as the FDA has altered the federal regulatory landscape. This change could result in a more restricted and litigious regulatory environment.

Laboratory diagnostic testing regulations

The recent Supreme Court rulings, especially the overturning of the Chevron doctrine in Loper Bright Enterprises v. Raimondo, will first impact the FDA’s new laboratory diagnostic testing regulations.

Increased Legal Challenges: The removal of Chevron deference means that courts will no longer automatically defer to the FDA’s interpretation of ambiguous statutes. This change might result in more legal disputes regarding the FDA’s power to regulate laboratory-developed tests (LDTs) as medical devices. The American Clinical Laboratory Association (ACLA) has already filed a lawsuit against the FDA over the new LDT rule, and this Supreme Court decision could strengthen their case.
Uncertainty in Regulatory Framework: The FDA’s final rule, published on May 6, 2024, regulates Laboratory Developed Tests (LDTs) as medical devices, similar to in vitro diagnostics. However, due to a new Supreme Court ruling, the FDA’s authority to regulate LDTs may face greater scrutiny by the courts. This could lead to uncertainty in the regulatory framework for clinical laboratories.
Potential Delays in Implementation: The Supreme Court’s decision in Corner Post v. Board of Governors extends the timeframe for challenging agency rules. This could lead to delays in the implementation of the FDA’s LDT regulations because stakeholders may now have more time to challenge the rules in court.
Stricter Scrutiny of FDA Decisions: The new ruling emphasizes that courts should exercise independent judgment in deciding whether an agency has acted within its statutory authority. This could lead to stricter scrutiny of FDA decisions regarding LDT approvals and regulations.

Keep in mind that although these potential impacts are meaningful, the complete effects of the Supreme Court’s rulings on FDA regulations will likely become more apparent over time as cases are presented in court and as the agency adjusts its approach. The situation is still evolving, and those of us involved in FDA regulated industries should be prepared for significant changes ahead.

Choosing the Right Consultancy Firm

We’ve all been there. Crazy schedules, not enough resources, and timelines looming. We need to bring in the consultants. We bring in the consultants and then “meh,” widespread feeling we are better off doing it ourselves.

One of the significant problems is folks don’t look at consultant companies as part of a system, instead thinking bringing in an expert will just solve things. The other is picking the last company you used instead of properly vetting for the job.

Choosing the right fit is critical. I always look for an excellent systemic consultancy. Hard to find.

Aspect	Traditional Consultancy	Systemic Consultancy
Approach	Linear, top-down approach relying on “expert” advice	Process-oriented, viewing organizations as complex, interconnected systems
Problem-solving	Analyzes problems and proposes solutions based on expertise	Helps clients discover solutions by examining the entire system and its dynamics
Focus	Focuses on specific issues or departments in isolation	Looks at the whole organization and how different parts interact
Client Involvement	Positions consultants as outside experts delivering solutions	Involves clients deeply in the process, seeing them as co-owners of projects
Consideration of Social Factors	May overlook social and psychological aspects	Heavily considers social interactions, culture, and psychological factors
Implementation	Provides recommendations but may leave implementation to the client	Assists with implementation and provides ongoing support
Timeframe	Engagements can be lengthy, lasting months or years	Can be more time-efficient, sometimes requiring fewer sessions
Perspective	Relies more on logical-rational analysis	Expands the view to include aspects neglected by purely rational analysis
Adaptability	May be less flexible in adapting to changing circumstances	Designed to be more adaptable to complex, evolving situations
Outcome Focus	Aims for specific, predefined outcomes	Focuses on improving overall system functioning and adaptability
Industry Specialization	Often works across various industries without deep specialization	Often has deep excellence within a narrow corridor of competencies and roles
Real Solutions	May take time to understand the problem and suggest solutions	Can start work on day one, providing immediate, insightful solutions
Personal Skills	May require time to build rapport and understand the organizational culture	Often possesses the maturity to navigate difficult situations and build immediate rapport

To truly find a good fit, you must go through a robust selection process.

Define your needs and project scope clearly. Before evaluating a consultancy, clearly understand your project goals, timeline, budget, and desired outcomes. This will help you find consultants with the right expertise and capabilities.
Look for relevant experience and expertise. Seek out consultants with a proven track record in your industry and with similar types of projects. Ask for case studies and client references to verify their experience.
Assess their approach and methodology. Look for consultants who have a structured yet flexible approach that can be tailored to your specific needs. The above table can really help. Their methodology should align with your company’s culture and ways of working.
Evaluate their team and resources. Consider the qualifications of the specific team members working on your project. Also, assess whether the consulting firm has adequate resources and support to deliver successfully.
Check their communication style and cultural fit. The consultants should be able to communicate clearly and work well with your team. Their working style and values should align with your company culture.
Compare pricing and value. While cost is important, focus on the overall value the consultant can provide rather than just the lowest price. Consider their expertise, methodology, and potential ROI.
Assess their thought leadership and innovation. Look for consultants demonstrating forward-thinking approaches and staying on top of industry trends and best practices.
Consider the size and type of firm. Based on your project needs and budget, decide whether you need a large global firm, a boutique specialist, or an independent consultant.
Review their technology and tools. Evaluate whether the consultant has access to relevant technologies, data, and analytical tools that can benefit your project.
Trust your instincts. After evaluating all the factors, trust your judgment about which consultant you feel most confident partnering with for a successful outcome.

To select the right consultancy:

Create a shortlist of potential consultants based on the above criteria.
Request detailed proposals from your top choices.
Conduct in-person interviews and presentations.
Check references thoroughly.
Evaluate proposals against your key selection criteria.
Negotiate terms with your preferred consultant.
Ensure alignment on project scope, deliverables, timeline, and budget before finalizing.

A systematic approach to evaluating and selecting a consulting partner will help you find the right fit for your needs and set your project up for success.

Remember, criminal enterprises like McKinsey should be avoided.