Tag Archive for: GMP

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Pharmaceutical-grade use of generative AI: regulations, limits and concrete implementation approaches

Generative artificial intelligence (AI) and large language models (LLMs) have long since become part of everyday working life – including in the pharmaceutical industry. However, especially in regulated environments, the question is not whether, but how AI can be used safely, sensibly and in compliance with regulations. Between efficiency potentials, the EU AI Act, GMP requirements and the draft of Annex 22, uncertainty prevails for many companies.

In the Experts Talk “Pharmaceutical-grade use of generative AI”, we demonstrated in a practical way which regulatory framework conditions apply, where the real risks lie and which AI applications can already be used in a compliant and validatable manner today. This article summarizes the most important content of the webinar.

Experts Talk

Why generative AI is a critical topic in the pharmaceutical environment

The relevance of AI in the pharmaceutical environment is undisputed. Studies and market analyses show that there is great potential for AI-supported applications, particularly in quality control/manufacturing. At the same time, current figures highlight a serious risk: a large proportion of employees are already using AI tools today, often without approval, without training and without clear rules.

This phenomenon is known as Shadow AI. It occurs whenever employees use generic AI tools without the company being aware of it or controlling its use. The consequences range from data protection problems and compliance risks to breaches of the EU AI Act, in particular the obligation to be AI literate.

What regulations apply to the use of LLMs in the pharmaceutical industry?

A central topic is the classification of current and upcoming regulations. The decisive factor here is that not every AI system is subject to the same requirements. The context of use determines the regulatory depth.

The EU AI Act

The EU AI Act applies across all sectors and affects all AI applications in companies, from office chatbots to decision support in quality assurance. This is particularly relevant for pharmaceutical companies:

  • Mandatory AI literacy (employee training)
  • Classification of AI applications as high-risk
  • Mandatory human oversight for high-risk systems

Pharmaceuticals is clearly a high-risk industry, so automated decisions without human-in-the-loop are not permitted.

GMP frameworks

Irrespective of Annex 22, existing GMP regulations already apply, among others:

  • ICH Q9 – Quality risk management
  • Annex 15 – Qualification and validation
  • Annex 11 – Data management
  • GAMP 5 (version 2) with explicit AI reference

These already form the framework for a risk-based assessment and validation of AI systems.

Annex 22 (Draft)

The draft of Annex 22 specifies the expectations of AI in the GMP environment for the first time. Particularly relevant:

  • No generative AI for critical GMP applications
  • Static models only (no automatic retraining)
  • Deterministic results (same input → same output)
  • Requirements for explainability (XAI) – no black box systems

The focus is on applications with a direct impact on patient safety, product quality or data integrity.

What does this mean in concrete terms? AI use cases in the GMP environment

Despite clear restrictions, there is still a wide range of permissible, validatable and economically viable applications.

Compliant use cases:

The practical use cases include, among others:

  • Support with document design
  • Classification and extraction of information (e.g. deviations)
  • Research in existing documents and GAP identification
  • Hyper-individualized training for employees
  • Data aggregation and trend or cluster analyses
  • Identification of recurring deviations

These applications are supportive, not decisive – and can be operated in a validatable manner with clear governance.

Critical applications with high risk:

The following are not permitted or only permitted to a very limited extent

  • Automatic batch release
  • Real-time decisions without human control
  • Automatic CAPA generation
  • Fully automated incident descriptions

The risk of hallucinations, wrong decisions and regulatory violations is particularly high here.

Human-in-the-Loop, Intended Use & Performance Monitoring

Human-in-the-loop (HITL) means that AI systems support employees, but the decision always remains with the human. This principle is required and necessary both in the EU AI Act and in the draft of Annex 22.

At the same time, practical experience has shown that human-in-the-loop alone is not enough. The long-term use of AI can influence the decision-making behavior of employees. If AI suggestions are perceived as reliable over a longer period of time, there is a risk that decisions will increasingly be confirmed uncritically.

Additional measures are therefore required:

  • Clearly defined intended use: It must be clearly defined what the AI may and may not be used for. As generative AI can often do more than originally planned, any use outside the defined intended use must be consciously checked.
  • Monitoring the interaction between humans and AI: In addition to the technical function of AI, it is important to monitor how employees deal with AI suggestions and whether decisions continue to be made actively and critically.
  • Performance validation and version control: The performance of the AI must be checked over time – especially in the event of changes to processes, regulations or data. At the same time, it must be possible to trace which system or model version was in use at what time.
  • Structured data management: Training, test and productively used data must be clearly separated, documented and traceable in order to ensure the quality and validation of the AI application.

These points were identified in the webinar as key prerequisites for using generative AI in a GMP environment in a controlled, traceable and compliant manner.

Practical example: Generative AI with MyGPT from Leftshift One

In the second part of the Experts Talk, Robert Spari from Leftshift One used MyGPT to show how generative AI can be used in a controlled and compliant manner.

MyGPT is an AI platform that:

  • is operated in a protected private cloud environment
  • guarantees that no data is stored for retraining purposes
  • can be integrated into existing systems
  • enables the use of generative AI without data leakage(internal or sensitive data does not leave the controlled system and is not reused for other purposes)

Typical application examples:

  • Structuring unstructured audit notes into formal audit reports
  • Support with scientific texts according to defined formal criteria
  • Use of internal GMP documents using retrieval augmented generation (the AI specifically accesses approved internal documents for queries without training or permanently storing them)
  • Transparent source information for traceability (XAI approach)

Particularly important: The systems are configured in such a way that they do not hallucinate, but only access approved content, which is a decisive factor for GMP compliance. If you have any questions about the tool, please contact Robert Spari: robert.spari@leftshift.one

Conclusion: Generative AI can be used with clear guidelines

Generative AI is not a no-go for the pharmaceutical industry, but it is not a sure-fire success either. Companies have to today:

  • Actively address Shadow AI
  • Structured recording and evaluation of AI use cases
  • Ensure AI literacy
  • Implement governance, documentation and human-in-the-loop consistently

Those who act early can use AI as an efficiency and quality lever instead of experiencing it as a compliance risk.

Further questions? Meet us live at the lounges in Karlsruhe

If you would like to delve deeper into the topic of the pharmaceutical use of AI, we look forward to a personal exchange at the Cleanroom and Processes 2026 lounges in Karlsruhe. The trade fair brings together experts from the pharmaceutical, biotechnology, medical technology and related industries and offers space for professional exchange on cleanrooms, processes, technology and regulatory requirements.

Our AI presentation at the LOUNGES 2026

Expected on 24.03.2026 | 11:30 am – 12:00 pm | Room 11
Quality decisions with AI: Annex 22 and EU AI Act

In this presentation, we will show how AI and large language models can be used for quality decisions – without violating regulatory requirements. We will provide insights from real projects, give a practical overview of Annex 22 and the EU AI Act and talk openly about opportunities, limitations and typical hurdles to implementation.

Further lectures from us on 25.03.2026:

  • Annex 1: Big words, small media fill deeds – strategic use of media fill tests for the sustainable improvement of sterile processes
  • Water Wars: Challenges and opportunities of ultrapure water – biofilm risks, system design, standardization and sustainability in ultrapure water treatment


Visit us at stand K6.1 – we look forward to exciting discussions and professional exchange! Free tickets are available with the code EXPERTSLOUNGES26 (registration required). You can book a ticket via the following link: https://cleanroom-processes.de/lounges-karlsruhe-2026/besuchertickets-lounges-karlsruhe-2026/

How the Experts Institute can support you

The Experts Institute supports pharmaceutical companies in the classification of regulatory requirements, the practical implementation of AI governance as well as training courses and workshops on the EU AI Act, Annex 22 and AI in the GMP environment. Get ahead and in touch with us: info@expertsinstitut.de

In addition to this article, it is worth taking a look at our blog article on Annex 22 and the EU AI Act. There we show which AI applications are to be classified as low-risk, limited or highly critical from a regulatory perspective and what preparations companies should already be making today: https://experts-institut.de/ki-in-der-pharmaindustrie-annex-22-eu-ai-act/

You can also stay informed about other Experts Talks, blog posts and events on LinkedIn: https://de.linkedin.com/company/expertsinstitut

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AI in the pharmaceutical industry: Annex 22 & EU AI Act – current obligations and practical implementation

The use of artificial intelligence (AI) is rapidly gaining importance in the pharmaceutical industry – from increasing efficiency in everyday office work to complex applications in GMP-relevant processes. At the same time, regulatory requirements are increasing significantly. The EU AI Act and the planned Annex 22 to the EU GMP guidelines will provide a clear regulatory framework for the use of AI in regulated environments for the first time.

This article summarizes the key content of the Experts Talk “AI in the pharmaceutical industry – Annex 22 & EU AI Act as a framework for quality and efficiency”, which took place on 27 November 2025. The discussion focused on what these regulatory developments mean in concrete terms for pharmaceutical companies, what obligations already apply today and how the path from risk analysis to regulatory compliance can be successful.

EU AI Act

Why the EU AI Act and Annex 22 are relevant now

The EU AI Act is the first comprehensive European regulation for the use of AI. It takes a risk-based approach and differentiates between AI applications according to their potential impact on people, safety and fundamental rights. The AI Act is particularly relevant for pharmaceutical companies, as many AI applications can be classified as high-risk.

At the same time, the planned Annex 22 specifies the authorities’ expectations for the use of AI in the GMP environment. Even though Annex 22 had not yet been finally adopted at the time of the Experts Talk, it was clear from the exchange with the speakers that the regulatory direction is clear – and companies should prepare now.

Annex 22 & EU AI Act at a glance: Which regulations apply to which AI use cases – from office chatbots to AI in the GMP process?

A central topic of the Experts Talk was the clear demarcation of the various regulations and their areas of application. This is because not every AI application is subject to the same requirements. The decisive factors are the context of use, risk potential and impact on product quality, patient safety and human rights.

Two sets of rules – two perspectives

  • EU AI Act: The EU AI Act is a horizontal, cross-sector regulation that addresses the use of AI throughout the entire company. It applies not only to GMP processes, but also to AI applications in HR, IT, office areas and management. The aim is to protect fundamental rights, safety and health and to create trust in AI systems.
  • Annex 22 (Draft): Annex 22 is a vertical, GMP-specific supplement to the EU GMP guideline. It focuses exclusively on AI applications in the regulated manufacturing environment and particularly addresses systems with an impact on product quality, patient safety and data integrity. The annex is strongly oriented towards GAMP 5 principles and supplements existing regulations such as Annex 11 and Chapter 4.

Typical AI use cases and their regulatory classification

1. office and support applications (low to minimal risk)
Examples:

  • Office chatbots for text creation or translation
  • Spelling and formulation aids
  • AI-supported ticket or document sorting

These applications generally have no direct influence on GMP decisions or patient safety. Nevertheless, there are already requirements arising from the EU AI Act, particularly with regard to:

  • Transparency about the use of AI
  • Employee training (AI literacy)
  • Clear internal rules on the use and handling of data

2. decision-supporting AI systems (limited to high risk)
Examples:

  • AI-based decision support in QA or production
  • Forecast models for maintenance, deviations or capacity planning

Regulatory requirements are increasing significantly here. Relevant factors include

  • Structured risk assessment and classification
  • Documentation of models, data basis and decision logics
  • Clear governance structures and responsibilities
  • Concepts for human control (human-in-the-loop)

The more decisions are automated or prepared, the closer these systems come to the high-risk area of the EU AI Act.

3. AI in the GMP core process (high risk / Annex 22 relevant)
Examples:

  • AI-supported process monitoring
  • Automated quality assessments
  • AI systems with influence on approval decisions

These applications are clearly the focus of Annex 22, as the draft makes clear:

  • Critical AI systems must be deterministic, validatable and explainable (XAI)
  • Dynamic learning systems and generative AI are not currently intended for critical GMP applications
  • Human-in-the-loop is absolutely essential
  • Data quality, traceability and life cycle documentation are key success factors

The Experts Talk clearly showed that the EU AI Act and Annex 22 are not alternatives, but complement each other. Companies must consider both perspectives in order to use AI in a compliant and sustainable manner.

What pharmaceutical companies already have to consider today

A key conclusion of the Experts Talk: waiting is not an option. Even without the final adoption of Annex 22, there are already specific requirements from existing GMP regulations, the EU AI Act and general quality assurance principles.

It was particularly emphasized that companies must obtain a structured overview of all AI applications used or planned. Regardless of whether these are used in the GMP core process, in supporting areas or in everyday office work.

The key requirements include in particular

  • Transparency and traceability of AI systems
  • Risk assessment and classification of AI use cases
  • Documentation and governance over the entire life cycle
  • Training and qualification of employees

Shadow AI poses a particular risk here – i.e. the uncontrolled use of generic AI tools such as ChatGPT in day-to-day work. Without clear rules, approvals, training and documentation, this can quickly lead to deviations and compliance risks.

Implementing AI governance in practice: Tool to support regulatory requirements

It became clear that regulatory requirements such as the EU AI Act, Annex 22 (Draft) and ISO/IEC 42001 can only be implemented effectively if they are translated into clear, practicable structures.

This is where an AI governance solution from Goodly Technologies comes in, which is currently being developed specifically for regulated industries. The tool supports companies in managing AI systems in a structured and traceable manner throughout their entire life cycle: from planning and deployment to continuous monitoring.

Among other things, the focus is on:

  • Systematic recording and classification of AI applications
  • Documentation of responsibilities, risks and controls
  • Illustration of key requirements from Annex 22
  • Integration of SOPs, training and proof of audit and inspection capability

The aim is not to limit AI, but to make it usable in a controlled manner as a basis for innovation and regulatory security. If you have any questions about the tool, please contact Robert Hoffmeister: robert.hoffmeister@goodly-technologies.com

Conclusion: Set the course for compliant AI now

The Experts Talk on November 27, 2025 made it clear that the EU AI Act and the planned Annex 22 are not abstract future topics, but are already having a concrete impact on the day-to-day work of pharmaceutical companies.

Companies that already use AI or are planning to use it should act early:

  • Identify AI use cases
  • Assess risks
  • Clarify responsibilities
  • Define processes
  • Train employees

Structured preparation makes it possible to use regulatory requirements not as a brake, but as a foundation for the safe, efficient and sustainable use of AI.

How the Experts Institute can support you

The Experts Institute supports pharmaceutical companies in the classification of regulatory requirements, the practical implementation of AI governance as well as training courses and workshops on the EU AI Act, Annex 22 and AI in the GMP environment. Get ahead and in touch with us: info@expertsinstitut.de

The Experts Talk series will also be continued. The next Experts Talk will take place on January 22 at 10:30 a.m. on the topic of “Pharmaceutical-grade use of generative AI”. To register for the event:
https://academy.experts-institut.de/ExpertsTalkmitChristophKthRobertSpariPharmatauglicherEinsatzvongenerativerKI

You can find more articles in our newsroom:
https://experts-institut.de/newsroom/

And feel free to follow us on LinkedIn to make sure you don’t miss any more Experts Talks:
https://de.linkedin.com/company/expertsinstitut

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The most important GMP findings for 2025 and forecasts for 2026

The regulatory requirements in the GMP environment have changed noticeably in recent years. In 2025, it is clearer than ever that it is no longer enough to formally fulfill requirements. Authorities expect comprehensible decisions, stable processes and quality that is actually practiced in day-to-day work. For many companies, this means a fundamental organizational, technical and cultural rethink.

GMP is increasingly understood as an integrated system in which processes, people, data and technology are closely interlinked. Individual measures or isolated corrections are not enough to remain audit-proof in the long term.

GMP

From documentation to active GMP compliance

Inspections and audits are increasingly focusing on how quality systems actually function in day-to-day business. Deviation management, change control and CAPA processes are no longer viewed in isolation, but in the context of responsibilities, interfaces, escalation paths and decision-making logic.

2025 has shown that inspectors are increasingly questioning who makes decisions, on what professional basis they are made and how consistently they are implemented. Processes that appear conclusive on paper but are interpreted or applied differently in everyday life quickly come into focus.

A key learning: Consistency is a decisive GMP factor. Differences between shifts, locations or areas of responsibility are increasingly seen as a systemic risk. Especially if they are not recognized, evaluated or justified.

CAPA, change control and deviations considered in context

Current FDA warning letters make it clear that a purely formal processing of deviations and CAPA measures is no longer accepted. The FDA is particularly critical of so-called “testing to compliance”, in which tests are repeated without identifying the actual cause of a problem and eliminating it sustainably.

Instead, the FDA expects robust root cause analyses with a broader perspective: affected and adjacent batches, comparable products, shared facilities and historical trends must be systematically included. A comprehensible effectiveness test of the CAPA measures is also required.

Prompt and visible action is required when risks are high or unacceptable. Delays – even if they are corrected later – weaken confidence in the quality system from the FDA’s perspective. At the same time, there is a greater focus on the responsibility of the quality unit and management: effective CAPA requires active quality oversight, continuous trend analyses and clear decision-making processes.

Data integrity remains a critical checkpoint

Data integrity continues to be one of the most sensitive issues in the GMP environment – and 2025 has further intensified this development. Authorities are paying more attention to complete audit trails, consistent data flows, clear role and access concepts and the handling of exceptions and manual interventions.

It is striking that data integrity is increasingly understood not only as an IT issue, but as a cross-organizational task. Training, awareness and leadership play just as big a role as technical controls.

Technology, processes and quality units in interaction

Technical weaknesses – for example in system qualification, maintenance, cleaning or monitoring – continue to lead to frequent complaints. However, it is less and less the individual defect that is decisive, but rather the question of how systematically companies deal with such issues.

2025, it became clear that authorities are evaluating more closely whether processes are understood, monitored and continuously improved or whether they are merely reacting to deviations. A reactive approach is increasingly considered insufficient.

At the same time, the role of the quality unit is becoming more central. Quality units are no longer seen primarily as an approval office, but as an active control and monitoring unit. What is expected is technical depth, decision-making power and the ability to clearly address risks – also in relation to operational areas.

Lessons learned 2025: Recurring patterns from audits

Across many audits, a number of overarching findings can be identified for 2025:

  • Unclear responsibilities are a frequent starting point for GMP deviations
  • Decisions without documented professional justification are increasingly being questioned
  • Training alone is not enough, application and understanding count
  • Quality systems must function as a whole, not just in individual modules

Companies that recognize and address these patterns at an early stage are in a much better position than those that only react selectively.

Outlook: GMP will be even more digital, risk-based and networked in 2026

Looking ahead to 2026, it can be assumed that these developments will continue to intensify. GMP practice is clearly moving in this direction:

  • more integrated digital quality systems
  • Data-based trend analyses and key figures
  • Predictive quality assurance instead of pure error correction

Risk-based approaches are finally no longer a “nice to have”, but the regulatory standard. At the same time, the requirements for transparency, traceability and system understanding are increasing, especially for complex manufacturing processes, biologics and novel therapies.

Companies that take a holistic approach to their GMP organization today not only create audit security, but also long-term stability in an increasingly complex regulatory environment.

How the Experts Institute supports you

We support companies throughout the entire GMP life cycle: from GMP assessments and audit preparations to hands-on support in projects, interim management and practical training for specialists and managers. Our focus is always on practicable solutions, regulatory safety and quality that works in everyday life.

Our claim: GMP compliance that doesn’t just exist on paper, but withstands audits and strengthens processes in the long term. Contact us if you want to future-proof your GMP organization. Get ahead and in touch with us – info@expertsinstitut.de

Read our entire blog: https://experts-institut.de/newsroom/
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Continuous manufacturing: future trend in the pharmaceutical industry

The pharmaceutical industry is at a turning point. For decades, traditional batch processes characterized the production of pharmaceuticals. Although these have proven their worth, today they are often considered rigid, slow and resource-intensive. Continuous manufacturing opens up a new path: production no longer takes place in individual batches, but continuously and without interruption. This not only changes the speed of production, but also the quality, flexibility and sustainability of pharmaceutical processes.

Continuous Manufacturing

What does continuous manufacturing mean?

In contrast to the traditional batch process, continuous manufacturing enables end-to-end production in a closed system. While intermediate storage and waiting times used to be unavoidable, continuous manufacturing allows for constant production and monitoring. As a result, companies benefit from shorter production times, consistent product quality and more efficient use of resources. At the same time, the technology makes it possible to react more flexibly to fluctuations in demand and avoid supply bottlenecks. Continuous manufacturing is therefore much more than a technological innovation; it represents a fundamental paradigm shift in the pharmaceutical industry.

Digitalization as a driver for process stability

The benefits of continuous manufacturing can only be exploited through consistent digital transformation. Modern sensor technology, Process Analytical Technology (PAT) and Advanced Process Control (APC) make it possible to monitor production processes in real time. This ensures process stability and deviations can be detected and corrected immediately. At the same time, end-to-end data acquisition ensures that quality information is seamlessly documented and integrated into regulatory systems. The result is not only stable and safe production, but also greater transparency with regard to GMP compliance.

Focus on regulatory requirements

The authorities have also recognized the potential. The FDA is considered a pioneer and has already granted the first approvals for continuous manufacturing processes. In Europe, the EMA is also taking a closer look at the topic. For companies, this means that investing in continuous manufacturing at an early stage not only makes it easier to obtain approval later on, but also puts them in a strategic position with regard to future inspections. Pilot projects are a valuable way of gaining experience and taking regulatory expectations into account from the outset.

Impact on supply chains and sustainability

An often underestimated aspect of continuous manufacturing is its contribution to sustainability. Reduced energy and material consumption results in less waste. At the same time, continuous production enables production “on demand”, which reduces stock levels and makes medicines available more quickly. Continuous manufacturing therefore offers a decisive advantage, particularly in crisis situations or in the event of supply bottlenecks. For the global supply chains of pharmaceutical companies, this means greater flexibility, shorter response times and overall greater security of supply.

Challenges on the road to implementation

Of course, the switch to continuous manufacturing is associated with hurdles. High initial investments, complex interfaces between IT, automation and quality management as well as the lack of qualified specialists present companies with major challenges. However, this is precisely why it is advisable to proceed step by step: Pilot projects offer the opportunity to minimize risks and build up expertise before the technology is introduced on a large scale. Those who consciously plan this path can actively shape the learning curve and anchor the change in the long term.

Conclusion: Experts Institut as a partner for your transformation

Continuous Manufacturing is not a trend, but the future of pharmaceutical production. Companies that take this step at an early stage not only secure advantages in terms of efficiency and quality, but also with regard to regulatory acceptance and market position.

The Experts Institute supports you with practical advice, tailored training and support for your digitalization and modernization projects. From the feasibility analysis and the development of an implementation plan through to regulatory-compliant implementation, we accompany you on your path to continuous production.

Contact us for customized solutions, together we will make your production future-proof. Get ahead and in touch with us – info@expertsinstitut.de

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GMP standards for medicinal cannabis: guaranteeing quality in an emerging industry

The medical use of cannabis is gaining increasing recognition and legal approval worldwide, leading to growing demand and increased regulation. In this dynamic environment, Good Manufacturing Practice (GMP) standards are crucial for the production of safe, high-quality products. However, the implementation of GMP standards is a challenge for the medical cannabis industry, as many companies first need to establish the necessary structures and skills. Specialized consulting can make a significant contribution to the efficient implementation of GMP-compliant processes.

GMP standards and their importance in medical cannabis production

GMP standards, implemented by the Food and Drug Administration (FDA) and further developed by the World Health Organization (WHO) and adapted to the global market, are a global quality benchmark for the pharmaceutical industry. These standards require strict specifications for the documentation, control and monitoring of production processes in order to ensure product safety and efficacy [1]. In the medical cannabis industry, these standards are of fundamental importance, as there are no guidelines specifically developed for cannabis production, although cannabis products are also used as medicines and can affect vulnerable patient groups. Instead, reference is made to the general processing of herbal substances [2], which is particularly important in the drying and preparation of plants. GMP ensures that all products are manufactured in a hygienic environment under controlled conditions to avoid contamination and ensure the safety of the final products [3].

Challenges of GMP implementation in the cannabis industry

GMP implementation in cannabis production poses specific challenges. For example, ensuring consistent product quality requires precise control over the entire manufacturing process – from raw material extraction to bottling. Medical cannabis products must have consistent concentrations of active ingredients to ensure therapeutic effects, which requires precise process control and laboratory testing [4]. In many cases, however, companies lack comprehensive knowledge of GMP standards and their specific application to cannabis production.

GMP compliance is complex and requires not only the establishment of suitable processes, but also the training of personnel and the implementation of quality assurance systems. In addition, regulatory requirements vary from country to country and are constantly evolving. Strategic advice can help to overcome specific challenges and ensure ongoing compliance with GMP requirements.

Good manufacturing practice (GMP) in practice: important steps and measures

1. production environment and hygiene: GMP guidelines require a strictly controlled production environment to prevent contamination by microorganisms, heavy metals or pesticides. Cannabis products must not contain any undesirable residues that could impair efficacy or safety [5].

2. quality control and laboratory testing: Each production batch of medicinal cannabis must undergo rigorous testing to confirm the active ingredient content and rule out impurities. These laboratory tests ensure that the final product meets quality standards and that consumers are not exposed to any risks [3].

3. documentation and traceability: GMP compliance requires comprehensive documentation and complete traceability of products in order to be able to act quickly in the event of quality problems or recalls. Every production stage, every test and every release must be documented in detail in order to prove conformity [1].

4. staff training: GMP standards require continuous training and education of employees to ensure that all processes are carried out and documented correctly. For many companies in the cannabis industry, this poses an additional challenge, as specific GMP knowledge is often not sufficiently available in the team [4].

The added value of specialized consulting for GMP-compliant processes

Strict compliance with GMP standards is essential for companies in the medical cannabis industry in order to be successful on international markets and build trust with consumers. However, especially for companies that are new to the market, the implementation of these standards requires considerable organizational and financial effort.

Our consulting expertise supports you in all phases of GMP implementation – from the development of a customized quality management system to employee training and complete documentation. We also offer regular audits and support in preparing for inspections to ensure continuous GMP compliance.

Conclusion: GMP as a guarantee of safety and trust in the medical cannabis industry

The requirements for medical cannabis are constantly increasing, as patient safety is a top priority and regulatory requirements are growing. The implementation and maintenance of GMP standards are a basic requirement for any company that wants to establish itself in this market in the long term.

We are happy to support you in achieving GMP compliance cost-efficiently and sustainably, strengthening your market position and guaranteeing the safety of your products. Get ahead and in touch with us – info@expertsinstitut.de

Sources

1. Good Manufacturing Practices for Pharmaceutical Products: Main Principles. World Health Organization (WHO).

2. cannabis Q&A for the public

3. Quality Standards and Practices in the Medical Cannabis Industry. International Journal of Drug Policy.

4. WHO Guidelines on Good Agricultural and Collection Practices (GACP) for Medicinal Plants. WHO, 2003.

5. Good Distribution Practice for Medical Cannabis Products. European Commission, 2017.

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GxP audits: How important are they and how are they conducted?

In the highly regulated pharmaceutical industry, audits are more than just a control mechanism – they are an indispensable tool for ensuring the quality and compliance of processes. Audits play a key role in ensuring that companies adhere to the strict requirements of Good Manufacturing Practice (GMP) and other GxP standards. The aim is not only to identify errors, but also to continuously improve processes and eliminate weaknesses before they lead to errors or quality problems. The role of audits in quality management can therefore not be overestimated. They help to meet regulatory requirements and at the same time strengthen the trust of customers and authorities in the company.

Below you will find out what a GxP audit is, why it is so important for companies in regulated industries and how it can be carried out optimally.

What is a GxP audit?

An audit is a systematic, independent and documented review that serves to determine whether activities and results meet the planned requirements. So much for the theory.

In the GxP area, audits are particularly important in practice, as they ensure that all processes actually meet the strict requirements of GMP, GLP and GCP standards. These audits not only check compliance with regulations, but also whether processes are used for continuous improvement and risk reduction and actually make this contribution.

Why are audits in the GxP area so important?

Audits fulfill a central function in the so-called Pharmaceutical Quality System (PQS) and offer many advantages that are important for the entire industry:

  • Audits guarantee that companies comply with and implement the legal and regulatory requirements in such a way that the medicines produced are of truly impeccable quality and also safe.
  • Audits make it possible to identify potential errors in operations and production at an early stage so that measures can be taken to minimize risks. This prevents critical errors or weaknesses in the production process from leading to serious problems and questionable medicines from reaching the market and patients.
  • Audits offer the opportunity to evaluate existing processes and identify optimization potential. In this way, companies can increase their efficiency and improve quality at the same time.
  • Regular audits strengthen the trust of customers, partners and regulatory authorities. A well-documented and executed audit shows that the company is able to critically scrutinize itself in order to reliably deliver high-quality products to the market.

The audit process: step by step

An audit in the GxP area follows a structured procedure that enables the auditor to thoroughly examine the processes in the company. Typically, an audit consists of six main phases:

  1. Planning: Audit preparation is crucial for success. The parties involved must ensure that all relevant people and documents are available. Thorough planning ensures a smooth process.
  2. The initial meeting: In this step, the auditors and the representatives of the company to be audited meet at the start of the audit. The audit plan or the audit agenda is discussed again. Questions are also clarified here and expectations are defined if they have not already been clearly understood before the audit.
  3. Conducting the audit: The auditor checks the company’s premises, machines, documents and processes. Interviews with employees also take place during this phase in order to assess the practical implementation of the processes.
  4. The final meeting: At the end of the audit, the results are summarized. This is where we discuss what worked well and where there is room for improvement.
  5. The audit report: The auditor prepares a detailed report documenting the results of the audit. This report also contains recommendations to help the company eliminate weaknesses and further improve processes.
  6. Follow-up of the audit results: After the audit, follow-up is essential to ensure that the recommended measures have been implemented. This includes documenting the corrections and, if necessary, rechecks to ensure the sustainability of the improvements.

Preparing the audited company for a GxP audit: how to succeed

Thorough preparation is the key to a successful audit. Companies should ensure that their documents are complete and up-to-date and that their employees are aware of the requirements of the audit. Employee training plays a central role here, as a well-prepared team helps to ensure that the audit runs smoothly and possible deficiencies can be identified at an early stage.

Tips for audit preparation:

  • Review all important documents, including SOPs (standard operating procedures), batch documentation and qualification documents
  • If possible, carry out internal mock audits in advance to identify weaknesses in advance
  • Bring your team up to speed on regulatory requirements and audit expectations

Successful audit practice: the key to success

A successful audit requires careful preparation, a clear structure and detailed follow-up. Cooperation between the auditor and the audited company is of great importance in order to develop a common understanding of the requirements and expectations. This not only promotes compliance, but also the continuous improvement of processes. Companies that integrate regular audits into their business processes improve their quality assurance and reduce the risk of production errors or non-compliance with regulations.

Conclusion: Audits as the key to quality assurance

Audits are an indispensable part of quality management in the GxP sector. They not only help to ensure compliance with regulations, but also promote the quality and safety of products. Thorough preparation and the selection of experienced auditors are crucial to the success of an audit.

At Experts Institut, we not only offer training courses for auditors, but are also happy to support you in ensuring your compliance and continuously improving your processes. We can do “audits”. Contact us at info@expertsinstitut.de

Would you like to find out more?

Listen to our podcast episode “Audits in the pharmaceutical industry”, in which we examine the importance and challenges of audits in detail: https://podcasters.spotify.com/pod/show/experts-insights/episodes/Audits-in-der-Pharmaindustrie-e2of577

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GMP Guidance for Artificial Intelligence (AI), Machine Learning (ML) and Digital Transformation: How it Finally Begins to Enter the EU GMP Guide

The Now: Gaping Holes

When sifting through today’s status of the EU GMP Guide, it does not take an expert to see that there are gaping holes on topics of engineering, management of computerized systems, data integrity, digitalization and application of artificial intelligence.

Not that the guide has nothing to say to some of these areas. At least by means of implication the guide says lots of things between the lines. This very “in-between” is what gives pharmaceutical manufacturers quite a headache when facing governmental inspections.

The issue is that what it has to say does not cover what’s actually out there. And “by implication” is simply not a good advisor for the industry. It may be good enough for an inspector to set up interpretive requirements and for giving industry a hard time. But for a company it is simply not practicable when a text is elusive.

Although we have best practices like ISPE GAMP5 or other guidance somewhere out in the GxP universe, we would like to know from our most relevant guide-the EU GMP Guide-what is required. And this very guide has been doing a rather horrible job to provide the input industry needs (it seems not surprising that some EU countries struggle massively to keep life sciences and pharmaceuticals on their territory).

A New Hope

A new hope may be on the horizon as we have been expecting a revised version of Annex 11. There-so the concept paper tells us-we will receive a text that will address words such as artificial intelligence, clouds, and even digital transformation. One might wonder whether it is worth holding our breath for the release of the new Annex 11, as high hopes have been shown to greatly disappoint before. One might remember Annex 21 or interpretive documents from local supervizing authorities, that in the end have not been helpful for real life at all.

However, in this case it may be different. Can we guess some consequences from this next generation Annex 11?

GMP

GMP Data Integrity Finally Takes Center Stage

Although some would passionately disagree with me on this, the EU GMP guide has virtually lacked clarity on data integrity for decades. It was the US FDA who had to essentially teach us in Europe what Data Integrity is and why this is important. Without them we would still think that Good Documentation Practices and Validation of Spreadsheets is all it takes.

I love how every EU member state GMP inspector knows exactly what is necessary in terms of data integrity-only with next to no express textual basis for it in the EU GMP guide. I mean sure: evey company has by now heard of data integrity, letalone has received inspections that dealt with it. And yes, we were told after the fact that the GMP guide has “always meant” data integrity in various little phrases of the guide. But that seemed a bit of a crutch to assure the colleagues from US FDA that in Europe data integrity is something we “totally want and require!”

Point taken, it is true that in the Annex 11 we had such wording in some spots. And now the EU guide will finally take into consideration the fuller importance of data integrity-at least for computerized systems. One can tell that the EU grows more towards considering guidance from for example WHO or PIC/S.

The consequences will be that audit trails and audit trail review requirements will be clarified and likely deepend. More work. The bar for what is “basic” will be raised.

The same will happen for archiving, backups, and retrieval requirements for archived data. Companies will unlikely be able to keep playing the low-key game in the archiving area.

Management of Clouds will be a Topic

This will be upgraded, or actually decently considered in the new Annex 11. And here I must say that this is positive improvement. The GMP guide has been pretty much blind to this for quite some time now. It will be a reasonable change. It will be interesting to see how block-chain systems will be treated under the new Annex 11.

And I certainly will be interested to see how cloud hosts seriously validate and qualify their systems, software, and infrastructure. The hunsh is: this is going to cause trouble for some service providers. My recommendation to cloud providers who have pharma-clients: Get ready for it now, or You will be out of business before You know it.

If this enters Annex 11 it could mean:

– cloud services must qualify their infrastructure according to GMP.

– they must validate their software fully in line with GMP as well.

This essentially would require a quality-oriented quality management system (and no, ISO9001 would not suffice, not the slightest chance for anyone who wants to take this seriously).

GMP for Artificial Intelligence (AI) and Machine Learning (ML) will Hatch

We must be honest here: it might not be a whole lot of guidance what we will receive from the revised Annex 11:

The primary focus should be on the relevance, adequacy and integrity of the data used to test these models with, and on the results (metrics) from such testing, rather that on the process of selecting, training and optimizing the models.

https://www.ema.europa.eu/en/documents/regulatory-procedural-guideline/concept-paper-revision-annex-11-guidelines-good-manufacturing-practice-medicinal-products-computerised-systems_en.pdf

Though this quote from the concept paper is as elusive as sand running through one’s fingers, it does give us a tiny insight into what will be important to a regulator or a GMP-inspector: data (and their quality) used to feed AI models.

One of the biggest questions is: How in the world do we validate AI and ML? Will AI or ML need to be validated according to the typical V-model? In reality this seems almost impssible, since any software code change would required re-validation. And code changes might have to be expected, especially with machine learning. My assupmtion is that we will not receive much help here form the new Annex 11. Industry will be thrown back on non-governmental best practice guidance-as is often the case.

“No New Requirements”

It must be acknowledged that some of what we will find in the revised Annex 11 will likely be clarification and nailing down of requirements that were logical consequences from what is in the current version of the Annex. Yet, we will also find more work, new requirements.

For each company a careful gap assessment will be in order, and for those who have gotten away with mediocre management of electronic systems it will be time to act and invest in modernization.

Needless to say, that I am already looking forward to the next years at Experts Institut, when those projects will continue to fill our work schedules. It is a great challenge!

GMP Challenges for Small Pharmaceutical Businesses

I encourage representatives of small businesses – smaller pharmaceutical entities – to comment and to give feedback once the draft to the new Annex 11 is out. Often it is the larger pharmaceutical businesses that drive or influence what best practice is or what those texts may contain. A consequence can be that the requirements push smaller companies off the cliff of financial and infrastructural fesability. This does not need to be so. But small businesses must take a bit of a stand here. Take the chances You get, that is my recommendation. Digitalization and the use of AI and ML are unstoppable because neither society and nor the economy will not stop it. This is coming at the industry real fast. And it will likely make or break smaller business in the near future. So – get ahead with it!

Experts Institute can help!

Need help with GMP-Digitalization projects and AI-validation concepts? Contact us. Management consultancy GMP, GXP & Business Solutions | Experts Institut (experts-institut.com).

Read our full blog: https://experts-institut.de/newsroom/

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Crossing Cultures in Audits and Inspections

Today the world, with its regulated industry, is strongly globalized. The cultural diversity of a company’s staff can be huge, reflecting different cultures from around the world. This is one reason why many would assume that the entire world can be talked to, related to, and understood quite readily. It is part of everyday work for many after all-or so we think.

In the area of audits and inspections, crossing cultures happens all the time. Different cultures bring different perspectives, which can influence how audits are perceived and conducted. Where supply chains are globalized, trans-national and trans-continental audits and inspections are mandatory and pretty much normal in many company and regulatory settings. Understanding the nuances of each culture involved is essential for effective communication and successful outcomes.

True Multiculturalism and Cultural Limits

This poses a problem though: we learn to communicate, read, and perceive in our birth culture. And even if a society is highly diverse, we are still product of a cultural framework that is discrete-in other words, that has boundaries. It is simply impossible for one person to really become multicultural-ourlifespan is just not large enough. You may be the child of a double or third culture set of parents, but true multiculturalism in a single individual is virtually impossible.

So as we are controlled by our birth culture, we do not learn how to properly navigate in foreign cultural contexts (and globalization does not do away with this at all). We may think we know what is going on around us when we engage people from other host cultures, but we really do not. Even in a seasoned friendship with someone from another country, there will still be a vast degree of ignorance in understanding the other person. We believe we know and understand. But we miss most of it in reality. We continue to filter everything we experience, see, hear and judge through what we believe is normal, and our frame of reference is our birth culture. And we cannot stop doing it because we are not even aware of it.

The Impact of Culture on Audits and Inspections

And now it gets interesting: This problem includes audit and inspection situations!
Good auditing is more than knowing compliance requirements, audit methodology, and a work experience of 100+ or even 1000+ audits.

Culture is so powerful that it controls everything we think, say and do. And what we expect of others. In an audit situation (also in GMP inspections), this routinely produces misunderstandings. And many of them are never corrected, simply because neither the auditor nor the auditee is aware of them.

From document reviews, an auditor may conclude that a company is falsifying records, when the truth is though that what the auditor saw has nothing to do with cheating at all.

An auditor may think the auditee is trying to avoid saying the truth about a given audit question or subject, but there is no intent of this in the conversation at all. But the auditor is blind to this.

As a result of examples like these, auditors will put their impressions into the report, in a coded form of course, but it will color all parts of the report and the perception of GMP deficiencies-even the judgment on severeness.

If an auditor is not aware of what is missed and where the personal perception of things is going astray, then such an auditor must improve. The objectiveness of the report will suffer, and the picture that is brought home is greatly inaccurate. We do a disservice to the auditee and to our own sending unit. And frankly, to ourselves…

This plays out even more drastically in audits of suppliers or service providers where no GMP or GxP quality system is available. Such cultural ignorance can make or break the business relationship altogether.

How can you improve?

  • Stop thinking that cultural differences are easy to figure out. You cannot guess them. You need extra training for this.
  • Understand that cultural differences have little to do with differing food preferences or how a business card must be presented.
  • Respect that standards-even GMP-can be lived effectively in different ways.
  • Open to the truth that you do not know everything best.

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GMP reagent management: Many unspoken rules?

So inconspicuous and yet so important, especially from today’s perspective: Section 6.19 of Chapter 6 of the EU GMP guidelines once again significantly increased the effort required to carry out analytical tests:

6.19 Special attention should be given to the quality of laboratory reagents, solutions, glassware, reference standards and culture media. They should be prepared and controlled in accordance with written procedures. The level of controls should be commensurate to their use and to the available stability data.

Miniature manufacturing instructions

If strictly interpreted, this means that a miniature manufacturing instruction and therefore also a specification should be created for each affected article – and of course all of this should be integrated into the usual document control system. No, this has not yet been an explicit requirement to this extent, even if it was tacitly expected in some inspections.

But that’s not all: in order to determine whether and how often, for example, a reagent itself must be tested analytically, stability data must now be used(!) – in a strictly literal interpretation.

Pharmacopoeia descriptions

There are plenty of unanswered questions: Can pharmacopoeia descriptions (if available) replace written manufacturing instructions for reagents? Do expiry dates or re-test data from reagent suppliers also count as stability data in the broadest sense (and this is still not clear)? If I change the manufacturer of an initial reagent, do I have to document everything via a change control procedure, i.e. is this a ‘significant’ change?

No footnotes, no Q&A document from the EMA – until now. However, the consequence of non-compliance with section 6.19 is clear: in extreme cases, analysis results may be called into question and retesting of already marketed products may be necessary as a follow-up measure. Where results were included in the assessment of critical incidents (e.g. OOS events), a reassessment may also be appropriate.

Our recommendation: The legislator has obviously deliberately made long-standing unspoken requirements much clearer. If your lab has any gaps here, don’t put it off, but make an action plan now to fix it! Definitely better than only reacting when the child has fallen into the (GMP inspection) well…

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Sensible limit values for process capability

The calculation of the process capability in the form of the process capability index (Ppk or Cpk) sets the scatter of the individual results and the position of the mean value in relation to the specification limits. The higher the process capability index, the further away the individual results are from the specification limits.

Calculation of the process capability index:

The following parameters are included in the calculation of the process capability index:

  • Mean value (μ)
  • Standard deviation of the mean value (σ)
  • Upper and lower specification limit (OSG and USG)

The first step is to calculate the process capability indices “Cpo” and “Cpu” for the upper and lower specification limits:

Cpo = (OSG – μ)/(3σ) OSG = upper specification limit

Cpu = (μ – USG)/(3σ) USG = lower specification limit

Cpk = min(Cpo, Cpu)

In a second step, the lower value (Cpk = smallest process capability value) of the two values is selected:

The calculation of meaningful Cpk values is only possible from 25 – 30 individual values.

Sample calculation:

Investigated quality characteristic: content of a medicinal product

Specification limits: 95 – 105 mg

Average value: 98 mg

Standard deviation: 0.5 mg

Cpo = (105 mg – 98 mg)/(3×0.5 mg) = 4.7

Cpu = (98 mg – 95 mg)/( 3×0.5 mg) = 2.0

Cpk = min(Cpo, Cpu) = 2.0

But what do the Cpk values obtained mean?

Cpk = 1.00

If 1 million units are checked, 2699 faulty units would be found. The distance of the mean value to the next specification limit corresponds to 3 times the standard deviation (3σ) of the values.

Cpk = 1.33

If 1 million units are checked, 66 faulty units would be found. The distance of the mean value to the next specification limit corresponds to 4 times the standard deviation (4σ) of the values.

Cpk = 1.67

If 1 million units are checked, no faulty units would be found. The distance of the mean value to the next specification limit corresponds to 5 times the standard deviation (5σ) of the values.

Cpk = 2.00

If 1 million units are checked, no faulty units would be found. The distance of the mean value to the next specification limit corresponds to 6 times the standard deviation (6σ) of the values.

The limit values selected for the CpK value should be determined on a risk basis. This means that the more critical a quality characteristic is, the higher the acceptance criterion for the CpK value should be.

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