LOGFILE Feature

7 min. reading time

"We have an active pharmaceutical ingredient (ICH Q7) in our GMP warehouse which may be stored up to max. 40°C according to the stability data available. This is the suspension of a UV filter. Now the existing monitoring system is to be replaced.

7 min. reading time | by Lea Joos and Doris Borchert

Mrs. Joos, you put in your new chapter "GDP inspections: Frequent deficiencies and how to avoid them" the 10 most common deficiencies in the qualification of logistics service providers. In your opinion, where are the biggest deficits?

National and international guidelines also require risk assessments when designing plants and when determining the scope of qualification/validation. This gives rise to special hygienic and cleanroom requirements for components. Different requirements also result from the intended type of usage.

At our GMP Conference, the “GMP-BERATER Tage“, in October 2019 we presented a GMP dialogue on "Microbiological Monitoring in non-sterile areas". Questions on the topic were asked by participants and answered by GMP inspector Franz Schönfeld, PhD and microbiologist Frank Mertens, PhD in a lively discussion.

10 min. reading time

As a LOGFILE subscriber you are already familiar with our "Question of the week". 

Pharmaceutical packaging materials have a variety of functions. The main purpose of primary packaging materials, for example, is to protect the medicinal product against the physical effects of light, air and moisture. Secondary packaging materials provide information on the amount, dosage type and application of the packaged medicinal product.

To assist pharmaceutical manufacturers and distributors to understand the areas where good manufacturing practice (GMP) inspectors have found compliance problems during GMP inspections in the UK and overseas, the UK Medicines and Healthcare Products Regulatory Agency (MHRA) GMP Inspectorate has issued data, during October 2019, relating to common deficiencies from previous GMP inspections conducted during 2018.

A GMP DIALOGUE of the GMP Conference, the GMP BERATER Tage, in October 2019 was entitled "Basic GMP questions and answers". Here, the questions could be asked to which the participants always wanted to have an answer. The two experts provided answers in the course of a lively discussion.

Numbers play a key role in the manufacture of medicinal products. From the receipt of the raw materials to the final release of the finished product, results (actual values) are repeatedly compared with specifications (target values) to decide whether the quality meets the requirements. This applies equally to measured values in the manufacturing process and to analytical results in the laboratory.

At our GMP conference, the GMP-BERATER Tage in October 2019 the GMP-DIALOGUE on the topic "Technology for the manufacture of medicinal products" took place. Questions on the topic were asked by participants and answered by GMP inspector Rainer Gnibl, PhD and technology-expert Ruven Brandes in a lively discussion.

Would you have known? Around 90% of all product recalls by pharmaceutical companies are due to errors in printed packaging materials. It is not the quality of the drug per se that calls patient safety into question, but incorrect or faulty information on the packaging.

Are you already training online or still offline? What do the employees, the management, the works council and other stakeholders want? How can this be controlled and GMP-compliant? How can blended learning be implemented?

A GMP dialogue of the GMP conference, the GMP BERATER Tage, in October 2019 was entitled "The QP should decide or lessons learned". The participants brought along concrete questions, the experts gave clear answers. A lively exchange developed, during which the participants also reported in detail on their experiences. We have summarised the most important results for you in this protocol.

Buildings for pharmaceutical production and the therein integrated infrastructure systems have in common that they have to be planned, realised and operated individually and according to the specific case. This individual character results in an increased risk of faults, which must be recognised and rectified in a timely manner so that they do not endanger the quality of the produced medicinal products.

In our company, every step of the production process is documented on the batch processing record, which is printed out on paper beforehand. Prior to this, all batches used were entered in the record by hand. This often resulted in an unclear spelling.

A GMP-DIALOGUE of the GMP Conference, the GMP-BERATER Tage, in October 2019 revolved around the topic "Disruptive technologies in the production of pharmaceuticals". The participants asked questions about the topic, which the two experts answered in an exciting discussion.

An excerpt from the GMP Compliance Adviser, Chapters 19.A Agency expectations of quality risk management and 19.B Application and benefits of QRM in the pharmaceutical industry

How often should I review my SOPs? And are electronic signatures acceptable on SOPs? Our authors provide answers to this questions – and beyond. 

Manufacturing is the origin of Good Manufacturing Practices - here is the core cell of GMP compliance. Many things must be observed and continuously implemented correctly. How do you deal with the challenges of everyday production? Who bears what responsibility? What can be delegated? How do you deal with deviations?

5 min. reading time | by Stephanie Blum

A management review is carried out on a regular basis to check the suitability and effectiveness of the pharmaceutical quality system (PQS). It is one of the most effective PQS tools available.

It's been 12 months since EU FMD came into force and after initial problems bedding in the new systems, false alerts remain a problem, preventing the realisation of the full benefits of the Directive. With many grace periods now coming to an end, where are manufacturers on the EU FMD journey and what are the real consequences of unresolved alerts moving forward? Grant Courtney of Be4ward examines the reasons behind these alerts occurring and looks at the action stakeholders must take now to keep the supply chain flowing.

5 min. reading time

5 min. reading time | by Richard Denk

When designing facilities there are numerous aspects to consider. These include not only the regulatory and normative requirements but also the functionality and cost effectiveness as well as the principles of hygienic design.

Any action related to medicinal products must be traceable, because the life and health of humans and animals are at stake.

Printouts must be labelled properly to ensure they can be clearly assigned. Attached printouts must be marked by an employee in such a way that their initials are half on the printout and half on the paper that the printout is attached to.

The differentiation between medical devices and medicinal products is a constant challenge for pharmaceutical manufacturers. Does my product meet the definition of a medical device according to the EU Medical Device Directive (MDD) or the definition of a medicinal product according to EU-Directive 2001/83 for medicinal products?

The integrity of the filter must be checked before and after use. This is a requirement of the EU GMP Guide1 and of the Ph. Eur. 2 The FDA3 also requires the integrity check, focussing on performance after the filter has been used.

Every pharmaceutical manufacturer must ensure that the responsible employees are informed about current changes and new requirements. This means that resources must be available. They should check the publications of the relevant authorities at close intervals and keep an eye on them. There are more than 50 public authority websites that need to be checked regularly.

In the case of the deviation inspected, it was found that the batch number, which had to be manually transferred to the product before production started, was not correctly transferred to the product. The cause was found to be a "human error" in the manual transfer of the batch number during the root cause analysis.

When selecting the number of sites to be sampled, the author recommends utilizing established guidelines. For example, ISO 14644-1:2015 contains a table used to establish the number of nonviable (total) particulate samples required based on the size of the room to be monitored.

For almost 30 years now, the PDA/FDA Joint Regulatory Conference has been taking place once a year. From 14 to 16 September 2020 it was a virtual-only event for the first time. The title of the conference was "The Future Is Now: Effective Quality Management and Robust Manufacturing".

8 min. reading time | by Christine Oechslein

In Part I, Paragraph 2.11 of the EU GMP Guidelines, it is required that "approved training programmes should be available" in GMP-liable establishments.

Issue identification is the most critical part of the process and relies on a team of people with high operational and GMP knowledge. All operational and quality areas should be represented and assessed.

8 min. reading time | by Hedley Rees

The Foundational Role of Pharma R&D in the Supply Chain

Not for the first time, pharma supply-chains have become the subject of global debate among key stakeholders, but for the wrong reasons.

Research, development and production of a medicinal product are usually in the hands of the marketing authorization holder (MAH). These processes are therefore subject to the direct supervision and control of the MAH.

There is no legal, ecological or pharmaceutical reason why a preparation should be heated from 12 °C (the outside temperature), for example, to a constant temperature of 20 °C (i.e. the mean of 15–25 °C) and stored at this temperature.

5 min. reading time | by Felix Tobias Kern and Liwa Schneider

The correct and consistent classification of deviations into the categories Minor, Major and Critical is a constant challenge for pharmaceutical manufacturers. A systematic specification is a prerequisite for the elimination of subjective components of the classifying QA function and the QPs.

Is there a normative source for the fact that the reviewer of a document cannot be the same person who prepared it?

During the cleaning validation, the PDE values of the active ingredients were determined in order to implement the EMA Guideline on setting health based exposure limits for use in risk identification in the manufacture of different medicinal products in shared facilities.

5 min. reading time | by Thomas Peither

In September 2020 the series of virtual autumn conferences of PDA and ISPE started. We were present and pick out some excellent sessions with this LOGFILE feature.

Modern packaging lines have a large number of online controls that continually monitor the process and certain parameters. Depending on the type of design, they can take various actions in case of non-compliant results.

The demands on manufacturers in the pharmaceutical industry are constantly increasing. Global competition and the international production and supply of raw materials and active ingredients increase the complexity of supply chains.

The literal meaning of containment is “holding together” or in its common sense “limiting expansion”. In the active ingredient, pharmaceutical and biopharmaceutical industries it is understood to mean the enclosure of a production process or a dangerous location.

There is a first time for everything - in this case for the digital format of the GMP Conference, which PTS Training Service organised for the 26th time on 1 December 2020.

10 min. reading time

Every week we publish GMP related questions which you might have asked yourself before. You get short and precise answers, links and working material to the corresponding chapters in the GMP Compliance Adviser.

ICH Q3D 'Guideline for Elemental Impurities' applies to finished drug products. It provides the basis for an adequate control of elemental impurities (generally referred as 'heavy metals' or 'metallic impurities'). The publication of this guideline has brought several consequences:

The 2020 EMA Guideline on the quality of water for pharmaceutical use deals with both purified water and water for injections (WFI). The document has been produced partly in relation to the change to the regulatory landscape in terms of producing WFI, where both distillation and reverse osmosis methods are permissible. 

Over the past several years, wall and ceiling systems have become the established state of the art in finishing technology. The numerous manufacturers of such systems also offer solutions that are suitable for fire zones and large, high rooms – such as warehouse storage rooms.

For all of us, the year 2020 turned out quite differently than we had ever imagined. People everywhere are struggling with new challenges. The GMP world was not spared, either. To name just a few: inspections were carried out remotely to a large extent and many regulations remained in draft form for the time being.

Rouging is a phenomenon that frequently occurs in water systems constructed from austenitic CrNi steel. The causes of rouging have been largely clarified. The mechanism of rouging formation and the parameters that have an influence have been described in the literature.

The deficiency

Time specifications for the start of production (preparation from 8:30) and for the end of production (15:30) were entered in the batch documentation.

This chapter deals with the practical aspects of implementing the European requirements for data integrity.

Today’s feature focuses on GMP risk analysis. It is an excerpt from the E-Learning GMP:READY – GMP for Engineers. GMP:READY provides knowledge for the planning, qualification and maintenance of the pharmaceutical equipment and facilities.

A correctly formulated packaging material specification provides a comprehensive description of the packaging material and serves as a guideline for the respective packaging materials supplier.

Were you able to follow the PDA Annual Meeting of the Parenteral Drug Association this year? Or were you like many others who spent the whole day with web meetings and have no time or mood for more online conferences?

A referral is a procedure used to resolve concerns over the safety, efficacy or quality of a medicinal product (or a class of medicines). In a referral, the EMA is requested to conduct a scientific assessment of the products in question on behalf of the European Union (EU).

Most companies have established different categories (qualification status) for the suppliers of starting materials and packaging materials they use.

Social distancing posed an interesting question for the Qualified Person (QP) in the early days of the COVID-19 pandemic:

The transfer of a product to a contract manufacturer can be divided into different phases.

The design qualification process may vary depending on the project and the client's requirements and may be carried out in two or three design phases.

When selecting balances, technical aspects such as resolution, precision and weighing range must be taken into account, as must special design features.

With this e-learning course you can get familiar with the topic of Good Distribution Practice (GDP)!

During a tour of the production area, it was discovered at several points that the rooms were not sufficiently maintained:

On the basis of the process-related requirements set out in the specifications, ISPE GAMP® 5 provides for a process risk analysis to identify risks relating to patient safety, product quality, data integrity and compliance requirements.

The inspection is carried out in the front office and prepared in the back office. The preparation room is used to train and instruct staff.

In addition to the preceding general statements on the PQS, Chapter 1 of the EU GMP Guidelines contains specific information on GMP for medicinal products and quality control.

The registration batches correspond as nearly as possible to the later commercial batches in the marketing phase with regard to the equipment, starting materials and manufacturing processes used.

The written contract on the outsourced activities can take the form of an internal service agreement or an external service agreement. In both cases, it is used to describe.

We operate a laminar flow above an injection moulding machine in a cleanroom, GMP Grade C (ISO 8 in operation, ISO 7/at rest). The laminar flow achieves ISO class 5 within the cleanroom area.

A GMP compliant and successful process validation is only possible when a 'robust' pharmaceutical development of the medicinal product has been performed, regardless of which development methods are applied.

Defect evaluation lists and defect pattern libraries are popular GMP documents that have been used for more than 45 years. They serve as a rationale for the quality assessment of individual batches and set quality standards for the manufacture and testing of pharmaceutical products.

The PDA/FDA Joint Regulatory Conference, which is now in its 30th year, took place as a virtual event from September 27 – September 29. The Conference focused on the role of effective quality systems in ensuring an ongoing state of control throughout the product lifecycle by vigilantly managing risks to manufacturing and quality.

The supplier of the packaging materials plays an important role when pharmaceutical packaging materials undergo testing. Because of the numerous materials involved, the complexity of the manufacturing process and the extremely specific test parameters, many of the packaging material tests are carried out at the supplier.

The PDA/FDA Joint Regulatory Conference, which is now in its 30th year, took place as a virtual event from September 27 – September 29. The Conference focused on the role of effective quality systems in ensuring an ongoing state of control throughout the product lifecycle by vigilantly managing risks to manufacturing and quality.

Figure 20.F-24 provides an overview of the GMP deficiencies that, in the author's experience, are frequently encountered during audits of active substance manufacturers.

The GMP-compliant and timely management of deviations is very often addressed in audits. One reason for this is that deviations reveal gaps in the defined quality systems or indicate that they have not been set up correctly.

Beginning from the definition of the User Requirements Specification (URS) the planning phase is subdivided into four stages:

In Europe, companies with a wholesale distribution authorisation, the management must appoint a responsible person who is responsible for the introduction and implementation of a quality management system and compliance with the GDP rules.

The types of Excel application acceptable for use in an organisation (in a department) should be clearly regulated. Suitable process models should be defined in the SOP for these types.

If a new service or material is required, the competent department first checks whether this service or material can be obtained from an already qualified supplier. If this is the case, the department initiates a follow-up qualification. Otherwise, the identification and pre-selection of potential new suppliers is carried out by the department itself.

For almost all purposes in the GMP sector, it is mandatory to use original data and documents or only true copies thereof. This requirement also forms part of the ALCOA principle. Since it is only possible in a few cases in operational practice to work with the sole original document, the question arises as to what requirements are to be placed on the requisite true copies (see definition in Figure 15.B-6). Figure 15.B-7 compares different types of copies with the concept of original data.

From a regulatory perspective, the year 2021 had plenty in store. Parallel to the omnipresent COVID-19 pandemic, the authorities around the world managed to finalize draft documents that became “sideshows” while the pandemic took centre stage. What topics kept the GMP professionals on their toes?

Receipt of medicinal products: When materials or products are delivered, their quality is assessed. Therefore, this work step should be carried out by experienced and particularly reliable employees.

"Contaminants in medicinal products – focus on nitrosamines" was the title of an online training course organised by the German FORUM Institute on 12 November 2021. Four renowned experts from the authorities, industry and consulting shed light on all aspects of nitrosamines that play a role in the life cycle of a medicinal product.

Deviation management plays an increasingly important role in the collection and review of KPIs (Key Performance Indicators) for pharmaceutical production and quality processes. Tracking the cause of deviations in particular provides information on how stable the respective processes are, where there are gaps and where countermeasures need to be taken with corrective and preventive actions (CAPAs).

Based on the risk assessment documented in the excipient dossier and the risk profile of the excipient, the risk team defines the necessary GMP requirements in the next step.

From the start of the project to the release of the technical design: Risk analysis is a constant companion.
Risk analyses can or must be carried out at different points in time within the process of procurement and qualification. Here is a brief outline of the phases of risk analyses in project implementation.

A CAPA system should be understood as an important element of the pharmaceutical quality system and implemented uniformly throughout the company or group. In principle, it can be implemented in two different ways: as an autonomous or as an integrated system.

The new Annex 21: Importation of medicinal products to the EU GMP Guide has been published on February 21, 2022 and will enter into force on August 21, 2022. The 6-page annex summarises the GMP requirements for Manufacturer/Importer Authorisation (MIA) holders to import medicinal products (human, investigational and veterinary) from outside the EU/EEA (we reported).

The question "How does process validation differentiate itself from other elements of quality management?" is not easy to answer, because there is still no uniform and generally applicable definition for validation. On the contrary, the term is becoming increasingly blurred with the related technical terms qualification and verification.

“While there are clearly defined GMP requirements for particulate and microbial air cleanliness for the sterile manufacturing area, there are no concrete requirements for air cleanliness for the non-sterile manufacturing area. In pharmaceutical practice, terms such as "cleanroom Grade E or F", "grey or black area" and, more recently, the terms "CNC" (classified not controlled) and "NC" (not classified) have become common for non-sterile manufacturing“, explains GMP Senior Expert Christine Oechslein.

The quality of a medicinal product cannot be left to chance, but must be the result of carefully planned actions. The sequence "planning, acting, evaluating, improving" is referred to as "management".

The first draft of version 9 of Annex 1 of the EU GMP Guide on 20 December 2017 attracted a lot of interest globally – firstly because it was the first publication on the topic in almost a decade, and secondly because PIC/S and WHO co-authored the document.

GMP or GDP – Which applies for importation? Although the import of medicinal products is an act related to distribution and logistics, this activity is considered GMP relevant in the EU and is therefore subject to GMP requirements.

A definition of the term “qualification master plan (QMP)“ is not to be found in the GMP guidelines, only the term “validation master plan (VMP)”, which serves as a parent document.

Standards such as those in the DIN EN ISO series are not laws, so they differ quite fundamentally from legally binding regulations. Good Manufacturing Practice (GMP), on the other hand, is laid down in laws, regulations and guidelines.

The life cycle of an equipment begins with initial qualification and ends with decommissioning. Once a qualification status has been achieved, it must be guaranteed over the entire life cycle until the equipment is decommissioned.

In this feature we take look at the ‘black sheep’ of pharmaceutical production. As cute and charming as they may be in the animal world, in the world of GMP they can be rather disturbing.

Pharmaceutical water systems are used for a number of different applications by pharmaceutical manufacturers. These include, for example, the cleaning of various pieces of equipment, the generation of pure steam and the use of water as an ingredient for solid, semi-solid and liquid medicinal products.

Assessment of GxP relevance

Every upcoming change must be checked for GxP-relevance by the responsible person for GDP.

You know the sustainability goals in your company, such as achieving CO₂ neutrality by 2030 or 2050. But what does that have to do with GMP?

A software quality plan – what is it and how do you create such a document?

The Swiss Biotech Day 2023 took place on 24 and 25 April in Basel. The conference is one of the industry's most important meeting places for developers and manufacturers of biopharmaceuticals and is growing in popularity every year.

Pharmacopoeial standards are obtained by the chemicals officer from the issuing body and do not require further characterisation before use.

“The new Annex 1 requires a comprehensive and overarching contamination control strategy (CCS). It records and links the different aspects and the associated accompanying measures, shows possible interactions and supports a corresponding analysis of any weaknesses or gaps in the system,“ explain Christoph Brewi and Florian Sieder in the GMP Compliance Adviser. 

Fundamentally, the use of computerised systems in GxP environments requires a consideration of regulatory requirements.

Adequate size and lighting of all areas where medicinal products, starting materials and packaging materials are stored is essential for the proper performance of operations.

One of the basic principles of a cleaning validation is the setting of limits for possible cross-contaminants in the subsequent product.

Gastrointestinal medicines, headache tablets and perhaps a gel to soothe insect bites? It's no big hassle to pack these and yet they give you a reassuring feeling of security.

According to the new Annex 1, a Contamination Control Strategy (CCS) must be implemented for the entire cleanroom and controlled environment system of the facility.

The monitoring of critical parameters is largely automated and is part of the plant control system. In the event of a critical system alarm (e.g. TOC outside of tolerance limits), the control system also performs the system shutdown or the transition to a safe operation mode.

To err is human - and is only too willingly used as the most probable cause for deviations of all kinds. It is also temptingly easy to look for the cause of error in individual (mis)behaviour. Everyone has a bad day, is distracted or unfocused, forgets or mixes things up and makes mistakes, even though they "actually" know how to do it correctly.

Subjectivity in QRM should be addressed in every organisation. I had the opportunity to attend a very stimulating presentation by Alex Viehmann, Division Director at OPQ, CDER, U.S. FDA, who shared insights into the new ICH Q9 Guideline on Quality Risk Management (QRM) at the PDA/FDA Joint Regulatory Conference 2023, 18-20 September in Washington.

‘Hygiene programmes adapted to the activities to be carried out shall be established and observed. These programmes shall, in particular, include procedures relating to health, hygiene practice and clothing of personnel.‘ This is explicitly stated in the EU GMP Directive 2017/1572.

The stability of a medicinal product or an active substance is defined as the maintenance of certain quality characteristics (specification) over a fixed period of time under defined conditions.

Every week we publish interesting questions and answers about GMP in our column GMP Question of the Week. Today we have compiled the most clicked questions of this year (as of November 2023). Browse the Top 15 and refresh your knowledge! Detailed information on each topic can be found in the GMP Compliance Adviser, the world's largest reference work on quality management in the pharmaceutical industry.

The life cycle approach to cleaning validation simply means that control of cleaning effectiveness must be maintained on an ongoing basis.

The pace of digitalisation is accelerating. And it is presenting us with new opportunities at ever shorter intervals. This means that all GMP professionals need to be informed and make risk-based decisions! This also applies to data storage in the cloud. What are the opportunities and risks? Which cloud and service models exist? 
In today’s feature, GMP expert Thomas Peither summarises the key points.

The monograph on Cannabis flower (3028) has been published in Ph. Eur. Supplement 11.5 in January 2024, with an implementation date of 1 July 2024. 
All member states of the European Pharmacopoeia are required to replace their national monographs with this new Ph. Eur. Monograph. 

Ensuring a clean production environment – sounds simple enough.However, in the pharmaceutical context, cleanliness and contamination are clearly defined, delineated and, of course, regulated, particularly in the manufacture of active ingredients and medicinal products.

Thomas Peither started his GMP journey nearly three decades ago. Throughout this period, he gained an in-depth understanding of the inner workings of GMP in the pharmaceutical sector. Now Thomas Peither – one of the founders of the GMP-Verlag – has stepped down from the board while still maintaining his role as a writer for the publishing house. Today's editorial offers his personal view on the development of GMP, highlighting important shifts and obstacles. He emphasizes the significance of employees in achieving GMP compliance and reflects on why his enthusiasm and confidence in GMP remains unwavering after 30 years.

Advanced therapy medicinal products (ATMPs) are an innovative class of medicinal products characterised by the use of advanced technologies.They target the underlying genetic, cellular, or tissue-based abnormalities of diseases and thus offer the potential for cure or at least a long-term therapeutic benefit.

To address the specific requirements for manufacturing ATMPs, separate GMP regulations were published as Part IV of the EU GMP Guidelines in late 2017.

The Contamination Control Strategy (CCS) is one of the few genuinely new requirements in the revised Annex 1. While Annex 1 provides quite comprehensive information on the content, the formal structure is not prescribed. In today’s feature you will read about an inspector’s point of view concerning the creation of this document, the responsibilities for review and approval, and the expectations for the first inspections to come.

Process validation is ubiquitous and always an important issue in GMP manufacturing and packing. In our today’s feature you can get a first insight into the basics of process validation and learn that only validated processes lead to consistently high quality products.

In 2015, with the revision of Chapters 3 and 5 and Annex 15 of the EU GMP Guide and with the publication of the EMA PDE Guideline a paradigm shift occurred in the setting of limits for the validation of cleaning processes. Instead of the previously used criteria, such as 10 ppm or 1/1000 of the therapeutic dose of the foregoing product, the only acceptable criterion is now a toxicological risk assessment based on PDE values.

Do you know the difference between “clean up period” and “recovery time”? Both terms are often used to describe the same procedure, but they are completely different from each other. 
Today's feature clearly explains the differences between test methods for determining the clean-up phase (Annex 1) and the recovery time (ISO 14644-3), using real-world examples.

What do you associate with the word “culture”? 
It’s likely to be literature, fine art, or music, but not necessarily GMP. Yet, the term culture has found its place in our professional world in recent years, especially when it comes to quality. Today's editorial by Doris Borchert, PhD, highlights the striking connections between quality culture and a symphony orchestra.

Carrying out quality testing internally may be a complex process, but it also has many advantages. A solid knowledge of product properties, stability and degradation products is built up over time in a laboratory and can be particularly valuable when carrying out quality risk analysis. However, some tests can be outsourced to external partners.

Empty shelves, incorrectly sorted goods and food that has passed its sell-by-date. A supermarket with such problems would have no chance of success. Materials management would have failed across the board. Fortunately, this scenario is rather unlikely. However, it illustrates the importance of efficient and reliable processes to ensure that the right material from the right source arrives at the right place in the right packaging and under the right storage conditions. The same holds true for pharmaceutical operations. Read more about the key requirements for material storage and internal logistics in this week’s brief extract.

The term "PUPSIT", which stands for the Pre-Use Post-Sterilization Integrity Test, has been included in the revised Annex 1. While the term is new, the requirement to check the integrity of a sterilizing filter after it has been sterilized and before it is used for sterile filtration is not new. This has been included in Annex 1 since 1998.

A pressure cascade is required between cleanrooms of different cleanliness levels to prevent cross contamination. Annex 1 of the EU GMP Guide requires a pressure difference of at least 10 Pascal between two different cleanliness classes. Today’s feature explains how these pressure differences can be achieved and maintained for two different types of pressure cascade systems. 

Reading SOPs is not Training! This powerful statement was echoed in several sessions with the PDA/FDA Joint Regulatory Conference 2024. It highlights a critical point: training is more than just reading procedures – it requires performance evaluation. Sabine Paris and Thomas Peither attended the event and have highlighted some of the other key takeaways in today’s feature.

The manufacture of sterile products involves a wide range of product types, primary packaging materials and technologies. The sterilisation process used must be appropriate and effective for the application. The specified sterilisation conditions must be consistently achieved in all parts of the load or over the entire surface of the system, equipment and components. In today's article, we look at the general requirements for sterilisation processes and the important definitions that go with them.

When establishing the basic design of equipment, containers, components and machines for pharmaceutical use, a wide variety of materials is required. These are typically subdivided into materials of construction and adjuvants or production aids.

Filters in safety cabinets: The filters are the most important part of a safety cabinet. To ensure comprehensive protection of the product and personnel, HEPA filters of at least class H13 must be used, usually H14 filters are used.

Looking at Annex 1, the use of barrier systems such as RABS or isolators is very common. Since Contamination Control Strategy (CCS) requirements are an important part of selecting the appropriate barrier technology, closed RABS or isolators should be preferred. As isolators have the additional feature of automatic surface decontamination with vaporized or finely nebulized H2O2 compared to a closed RABS and can be installed in a grade C/D cleanroom area, isolator technology is more commonly used. It also offers the highest level of safety and is more sustainable, as it requires fewer cleanroom zones and associated airlocks with the energy-intensive room air technology they require.

Pharmaceutical water is used in the manufacture of medicines, vaccines and other pharmaceutical products. High water quality is essential to ensure the safety and efficacy of the final products. In order to ensure that the quality is maintained at all times, there are many parameters that need to be monitored. In today's article, we look at the importance of physicochemical monitoring of pharmaceutical water.

Has it ever happened to you that ‘your’ medicine was not available in the pharmacy? It becomes problematic when the re-availability is not foreseeable, the medicine is urgently needed and no alternatives exist. The topic of ‘supply shortages’ is in the public eye and was also discussed at the 30th GMP Conference, which took place in Cologne, Germany, from 6 to 7 November 2024. Doris Borchert, PhD, attended the conference on behalf of GMP-Verlag. Today she reports on a panel discussion on the topic of supply shortages.

Analytical methods are used throughout the development, manufacture and release of pharmaceutical substances and dosage forms. The accuracy and reliability of analytical results are therefore essential. Successful method validation proves that the test procedure is suitable for the defined application. In today's feature, Joachim Ermer writes about the regulatory requirements for the validation of analytical methods. 

In the next LOGFILE you will learn more about important aspects of putting these requirements into practice.

Analytical methods are used throughout the development, manufacture and release of pharmaceutical substances and dosage forms. The accuracy and reliability of analytical results are therefore essential. Successful method validation proves that the test procedure is suitable for the defined application. In our last feature, we reported on the regulatory requirements for analytical method validation. Today, you can find out which aspects need to be considered when putting them into practice.

The call for Quality Oversight is getting louder – especially in FDA warning letters there is an increasing number of deficiencies observed in the context of quality oversight.

In today’s feature, Christian Gausepohl presents an approach for implementing Quality Oversight at shop floor level as a collaboration between Quality Assurance and Operations. What are the success factors for this model and how could the organisational structure look like?

Do you trust your pills? Are you sure that nothing went wrong during production? Actually, you should be able to say yes, because medicinal products must be manufactured in such a way that they do not pose any risk to the patient through lack of safety, purity, quality or efficacy.

However, every step in the manufacturing process of medicinal products involves potential risks. Effective management, control and thus minimization of potential patient risks is only possible with the help of effective risk management.

The authoritative guideline for quality risk management, ICH Q9, has been revised. In today's editorial, you will find a summary of the most important changes in ICH Q9(R1).

Pharmaceutical water has a unique position in pharmaceutical industry. As raw materials and excipients are only used after quality control and subsequent release, pharmaceutical water is used immediately after production. For this reason, pharmaceutical water is considered extremely critical. Three types of water are of particular interest: Drinking water as source water, purified water (PW) and water for injections (WFI). In today’s feature we report on drinking water as source water. In future LOGFILES, we will report on PW and WFI.

Do you know where your pills come from? They probably have a long journey behind them. Active ingredients from China meet excipients from India to be pressed into tablets in France, which are blister-packed in Italy and packaged in Spain before being imported to Germany – sounds unrealistic? No, because the manufacture and distribution of pharmaceuticals is a global business. Therefore it is important to speak the same language in terms of the underlying regulations. In todays feature you will read a short summary of the WHO GDSP guideline, which is not only the latest, but probably also the most globally oriented guideline on the topic of good storage and distribution.

Pharmaceutical water occupies a unique position within the pharmaceutical industry. Whereas raw materials and excipients are used only after quality control and approval, pharmaceutical water is used immediately after production. For this reason, it is considered extremely critical. Three types of water are of particular importance: potable source water, purified water (PW) and water for injection (WFI). In this issue we will focus on PW, while a future issue of LOGFILE will cover WFI.

Artificial intelligence is a highly relevant topic, and for good reason. It has the potential to provide innovative solutions to complex challenges. This is particularly true in the pharmaceutical industry, where implementing and using AI can result in significant benefits. Today's editorial explores the potential of AI applications in the GMP environment and the challenges that could come along with it.
The upcoming LOGFILE will tackle the current regulatory framework for AI, focusing on the EU AI Act, relevant ISO standards, and the EMA's reflection paper on the topic. Don’t miss out and benefit from the concise overview!

Artificial intelligence is developing faster than any previous technology, promising innovation and competitive advantage. Yet, integrating AI while maintaining safety, quality, and trust poses a challenging task for the pharmaceutical industry. It requires an appropriate regulatory framework as a fundamental condition. Today's editorial outlines which role the EU AI Act, the EMA's reflection paper, and various ISO standards play in shaping the regulatory landscape.

Pharmaceutical water plays a distinctive and vital role in the pharmaceutical industry. Unlike raw materials and excipients, which undergo quality control and approval before use, pharmaceutical water is used immediately after production. For this reason, it is considered extremely critical. Three types of water are particularly important: potable source water, purified water (PW) and water for injection (WFI). In this feature we focus on WFI. Two previous LOGFILES have already reported on drinking water as source water and on PW.

In today’s feature, our editor Sabine Paris reports from the PDA Good Aseptic Manufacturing Conference 2025 in Basel, where Swissmedic's Paula Walser provided valuable regulatory perspective alongside industry experts. The conference revealed that 25 % of companies remain non-compliant with Annex 1, facing challenges from cleanroom upgrades to contamination control strategies. However, speakers from Takeda, Novartis, and Charles River demonstrated how regulatory pressure is driving innovation – from questioning traditional monitoring methods to advancing digital transformation of sterility testing and rapid microbiological methods. The blend of regulatory insight and industry innovation showcased how Annex 1 compliance is reshaping aseptic manufacturing.

You might be thinking: “It's clear – GMP applies to manufacturing and GDP to distribution!” But is this distinction always so unambiguous? Unfortunately not, says Simone Ferrante, author of the knowledge portal GMP:KnowHow Pharma Logistics (GDP). From her many years of professional experience, she knows a number of topics where the legal situation is insufficiently harmonized and therefore unclear.
Find out more about the interfaces between GMP and GDP and test your knowledge in today's feature! 

The rapid development of information technology has made computer-based systems indispensable in the pharmaceutical and biotechnology industries. They are crucial for managing and processing sensitive data, controlling and monitoring production, and complying with regulations. With increasing digitalisation, there is a growing need to protect these systems from potential threats and ensure that they meet regulatory requirements. In today's feature, Dennis Sandkühler explains why the implementation and subsequent commissioning of computerised systems require careful planning and continuous monitoring, and which aspects you should consider.

How does the draft ICH Q1 guideline affect the stability study design and conduct of drug products and drug substances? Joachim Ermer, PhD, summarises the most important changes and comments on critical aspects. 

What are the important aspects of effective change management from an authorities' point of view?

Dr. Michael Hiob gives an overview on the relevant topics to observe when implementing changes in drug manufacturing. A detailed discussion of the change management procedure can be found in the chapter ‘Change Management’ of the GMP Compliance Adviser.

What are the key considerations for gas distribution systems for pharmaceutical gases?

How does subjectivity impact quality risk management? Martin Mayer discusses the dos and don'ts for an objective quality risk management.

Data integrity is a key element in the pharmaceutical quality assurance system which has gained importance in recent years, especially from the viewpoint of the authorities. In GxP-regulated companies, managers are responsible for identifying and minimising risks to data integrity (“data governance”).

The integrity of a primary packaging system (container closure system) is essential to prevent product loss by leakage or evaporation and at the same time protect the product from contamination. The task of a primary packaging system (container closure system) is essentially to prevent the product from being lost (e.g. leakage, evaporation, etc.) and to prevent the product from being contaminated from the outside.