5 min. reading time | by Martin Mayer

The introduction of the ICH guideline Q9 ‘Quality Risk Management’ in 2005 was crucial for the introduction of QRM approaches in the pharmaceutical regulatory framework. However, over the years, regulators and industry have realised that the QRM principles were not being applied and used as intended. Therefore, the Q9 guideline was revised and published in version (R1) in 2023. The basic principles and concepts of the original 2005 version have been retained but supplemented to achieve the intended clarifications.

6 min. reading time | by Christian Gausepohl, PhD

Quality oversight at the operational level offers many advantages. The company’s quality culture can be positively influenced through close integration.

But what is the best way to implement Quality Oversight directly at the shop floor level?

7 min. reading time | by Joachim Ermer

Important aspects in the implementation of regulatory requirements

The ICH guideline contains general requirements and some recommendations for basic statistical performance parameters and experimental approaches. However, this should not be understood or misused as a checklist. The responsibility of the user to adapt to the task is explicitly pointed out: "It is the responsibility of the applicant to choose the validation procedure and protocol most suitable for their product". Validation that is not tailored to the specific test procedure and its intended use is, at the very least, a waste of time and resources, as the suitability cannot be reliably assessed.

7 min. reading time | by Joachim Ermer

Proof of the suitability of analytical test methods is a general GMP requirement. While the EU GMP Guideline Part I generally requires "validated test methods", Part II refers to the ICH guidelines with regard to the content of method validation. 21 CFR Part 211 also requires in §194(a)(2) that the suitability of the test methods must be verified.

5 min. reading time | by Doris Borchert, PhD

Supply shortages for pharmaceuticals are a serious problem for the public security of drug product supply. At the 30^th GMP Conference, Dr. Josef Landwehr (PTS), Thomas Brückner (Bundesverband der Pharmazeutischen Industrie e.V.) and Andrea Schmitz (Pharma Deutschland e.V.) discussed the background, possible solutions and foreseeable developments in this area.

We have summarised the most important questions and answers for you.

5 min. reading time | by Ruven Brandes and Fritz Röder

How can the quality of pharmaceutical water be monitored?

The quality of pharmaceutical water is defined by a large number of specified parameters. Monitoring is required to ensure that this quality is maintained dur­ing operation of the water system. This includes regular physical measurements as well as chemical and microbiological tests. The European Pharmacopoeia spe­cifically mentions microbiological monitoring and the testing of TOC and con­ductivity.

5 min. reading time | by Richard Denk

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.

5 min. reading time | by Andreas Nuhn

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.

7 min. reading time | by Ruven Brandes

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.

7 min. reading time | by Florian Sieder, PhD

General Requirements

The current Annex 1 of the EU GMP Guide provides guidelines and minimum requirements for the manufacture of sterile products. Some of the requirements contained therein are also relevant for the manufacture of non-sterile products, where the control and reduction of contamination is important.

7 min. reading time | by Sabine Paris, PhD, and Thomas Peither

The 33rd Annual PDA/FDA Joint Regulatory Conference was held in Washington from September 9-11, bringing together over 900 participants. It was a great opportunity for knowledge sharing, connecting theory with real-world practice, and plenty of networking.

We attended the event as representatives of GMP-Verlag and have highlighted some of the key takeaways in this article. The full report will soon be available on our online GMP knowledge portal, the GMP Compliance Adviser.

3 min. reading time | by Raimund Brett

Between rooms of different cleanliness grades, it is required to establish a pressure cascade 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. These pressures can be achieved if the structure (walls, ceiling, windows and doors) is tight. The pressure level is usually controlled in such a way that the supply air is kept constant, and the exhaust air is controlled via volume flow controllers to maintain the corresponding pressure difference. The pressure differences in a manufacturing area for sterile pharmaceuticals must be continuously measured and recorded. If a pressure drop occurs, an alarm must be triggered. This also applies to the airlocks.

5 min. reading time | by Xenia Dimont

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.

5 min. reading time | by Thomas Peither

In-house logistics encompasses all the processes required to manage and transport materials within a company. This is particularly important in the pharmaceutical industry, where not only efficiency but also compliance with safety and quality standards are crucial. Efficient logistics can help streamline production, cut costs, and ensure legal compliance. The provision of safe and effective medicines relies on pharmaceutical companies prioritising material management and flow. It ensures the availability, quality, and compliance of materials.

5 min. reading time | by Christine Oechslein, PhD

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.

5 min. reading time | by Doris Borchert, PhD

When was the last time you went to a concert? What images have stuck? The conductor guiding his orchestra through the repertoire with grand gestures and high commitment? The first violin, connecting conductor and orchestra? Or the musicians working as a coordinated team, bringing the music to life? Either way, hopefully it was an amazing experience.

7 min. reading time | by Sabine Paris, PhD

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.

5 min. reading time | by Harald Flechl

Both of the terms "clean up period" (Annex 1) and "recovery time" (ISO 14644-3, informative part B.4) are often used to describe the same procedure but they are completely different from each other. These test methods have no validity with respect to the airborne microbes, which depend greatly upon the number of persons in the room as well as their clothing and activity.

5 min. reading time | by Christine Oechslein, PhD

For most manufacturing and packaging processes it is technically not feasible or much too expensive to check every single unit of resulting product (100% control). Instead, random samples are relied on which are taken on an ongoing basis at specific times during the process (in-process controls), or random samples are taken for quality control of the final product prior to market release.

However, it would hardly be possible to find the famous needle in the haystack using these random samples. For this reason, validated manufacturing and packaging processes are required by law in addition to the final product checks and IPCs. The company must prove that the processes are all so reliable that, under everyday routine manufacturing conditions, they result in medicinal products of a high and reproducible quality.

7 min. reading time | by Xenia Dimont, PhD

The concept of contamination control is not entirely new in the context of the EU GMP Guideline - the basic principles are already contained in Chapter 5 of the Guideline regarding cross-contamination and in Annex 2 regarding specific risks for biological products.

7 min. reading time | by Birte Scharf, PhD

Regulatory framework for ATMPs in the European Union

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

7 min. reading time | by Birte Scharf, PhD

What are advanced therapy medicinal products (ATMPs)?

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.

10 min. reading time | by Thomas Peither

When I worked on the first GMP projects as a consultant in 1994, the internet was still in its infancy. Getting an official copy of 21 CFR 210/211 was more than a hassle. You had to send a written request to the USA and after weeks, a barely legible copy would arrive by post.

6 min. reading time |  by Thomas Peither

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.

5 min. reading time | by Sabine Paris

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.

7 min. reading time | by Thomas Peither

What is cloud computing?

Cloud computing is not a new technology, but a new way of providing resources for data processing.

5 min. reading time | by Thomas Peither

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

5 min. reading time | by GMP-Verlag Peither AG

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.

7 min. reading time | by Thomas Peither

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.

‘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.

7 min. reading time | by Thomas Peither

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.

13 min. reading time | by Christian Gausepohl, PhD

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.

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.

4 min. reading time | by Harald Flechl

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.

3 min. reading time | GMP-Verlag

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.

10 min. reading time | by Cornelia Wawretschek and Jens Hrach, PhD

Cleaning Validation

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

8 min. reading time | by Thomas Peither

General 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.

5 min. reading time | by Dennis Sandkühler, PhD

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

8 min. reading time | by Thomas Peither

Standards and Data Types

The following standards can be used as a basis for cleanroom monitoring plans:

5 min. reading time | by Christoph Brewi and Florian Sieder, PhD

What is meant by CCS?

The current Annex 1 (version of 22/08/2022) of the EU GMP Guide marks a paradigm shift in the rules and regulations of Good Manufacturing Practice (GMP).

5 min. reading time | by Stephanie Blum

Reference standards

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

5 min. reading time | by Sabine Paris

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.

10 min. reading time | by Petra Berlemann

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

7 min. reading time | by Thomas Peither

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?

9 min. reading time | by Harald Flechl

7 min. reading time | by Simone Ferrante

Assessment of GxP relevance

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

4 min. reading time | by Fritz Röder

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.

7 min reading time | by Stephanie Blum, PhD

In the course of an audit, the auditors collect the information necessary to achieve the audit objectives on a sample basis, e.g. by inspecting premises, observing operations, interviewing personnel and examining documents and records. Interviews may be conducted at any time during the audit, including during the walkthrough and review of documentation.

8 min. reading time | by Thomas Peither

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.

9 min. reading time | by Petra Berlemann and Thomas Peither

User Requirements, User Requirements Specification (URS), Specification Sheet

What is it? How do you create such documents? Is it all the same? Or is it something completely different?

9 min. reading time | GMP-Verlag

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.

13 Min. reading time | by Doris Borchert, PhD, and Christian Gausepohl, PhD

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.

7 min. reading time | by Thomas Peither

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

11 min. reading time | by Thomas Peither

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.

11 min. reading time | by Cornelia Wawretschek, Jens Hrach, PhD

Cleaning Validation

6 min. reading time | by Simone Ferrante

GMP or GDP – Which applies for importation?

Although the import of medicinal products is an act related to dis-tribution and logistics, this activity is considered GMP relevant in the EU and is therefore subject to GMP requirements.

8 min. reading time | by Richard Denk

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.

6 min. reading time | by Christine Oechslein, PhD

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".

9 min. reading time | by Frank Studt and Thomas Peither

9 Min. Lesezeit | Auszug aus dem Interview mit Frank Studt, Managing Director gempex GmbH, und Thomas Peither beim GMP:talk auf den LOUNGES 2022

7 min. reading time | by Christine Oechslein, PhD

8 min. reading time | by Thomas Peither

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.

10 min. reading time | by Sabine Paris, PhD

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).

7 min. reading time | by Alexandra Fürst

8 min. reading time | by Thomas Peither

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.

5 min. reading time |

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.

7 min. reading time | by Stephanie Blum, PhD

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.

7 min. reading time | by Felix Kern, PhD and Liwa Schneider

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).

7 min. reading time | by Torsten Knöpke

8 min. reading time | by Sabine Paris, PhD

"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:

8 min. reading time | by Simone Ferrante

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.

7 min. reading time | by Doris Borchert, PhD

The 27th PTS GMP Conference took place face-to-face and in parallel digitally from 30.11. to 01.12.2021 in Mainz, Germany. The hybrid event was broadcast live from the Atrium Hotel in Mainz, where most of the speakers were present in person.

The presentation by Rico Schulze, Saxon State Ministry for Social Affairs and Social Cohesion, on the revision status and publication of Annex 1 to the EU GMP Guideline was particularly eagerly awaited.

13 min. reading time | shortened version

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?

8 min. reading time | GMP-Verlag

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. This is ensured by regular calibration, maintenance, effective change management and periodic review.

6 min. reading time | by Christine Oechslein, PhD, and Cornelia Wawretschek

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.

7 min. reading time | by Stephanie Blum, PhD

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.

8 min. reading time | by Thomas Trantow, PhD

Definition of the types of Excel applications

8 min. reading time | by Simone Ferrante

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.

6 min. reading time | by Harald Flechl

Good Engineering Practice (GEP) for procurement

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

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

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.

7 min. reading time | by Norbert Waldöfner, PhD

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.

6 min. reading time | by Sabine Paris, PhD

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.

7 min. reading time | by André Deister, Sabine Mendel

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.

7 min. reading time | by Sabine Paris, PhD

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.

7 min. reading time | by Felix Tobias Kern, PhD, and Fritz Röder

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.

11 min. reading time | by Cornelia Wawretschek and Jens Hrach, PhD

7 min. reading time | by GMP-Verlag

A GMP compliant and successful process validation is only possible when a 'robust' ¹ pharmaceutical development of the medicinal product has been performed, regardless of which development methods are applied.

12 min. reading time | by Harald Flechl

Question:

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.

8 min. reading time | by Markus Roemer, Siegfried Schmitt, PhD

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.

7 min. reading time | by Heike Meichsner, Olaf Mundszinger, PhD, Susanne Schweizer

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.

12 min. reading time | by Thomas Peither

8 min. reading time | by Richard Denk

Isolator applications and design

Isolators are used in the handling of toxic and highly potent substances and in the production of sterile products.

9 min. reading time | by Stephanie Blum

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.

9 min. reading time | by Thomas Peither

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.

11 min. reading time | by Thomas Peither

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.

9 min. reading time | by Dennis Sandkühler

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.

9 min. reading time | by Lea Joos

The deficiency

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

7 min. reading time | by Stephanie Blum

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

10 min. reading time | by Christian Gausepohl

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

7 min. reading time | by Harald Flechl

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.

10 min. reading time | by Chistian Gausepohl

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

15 min. reading time | by Ulrich Kissel and David Cockburn

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

7 min. reading time | by Christian Gausepohl

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

8 min. reading time | by Thomas Peither

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?

4 min. reading time | by Michael Hiob and Sabine Paris,PhD

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).

The time has come, the curtain goes up! Now your brand-new online journal is launched.
Let the newly designed GMP:Blog support you in the work with GMP.

5 min. reading time | by Roland Kleissendorf

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.

8 min. reading time | by Sabine Paris

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 took place in establishing limit values for the validation of cleaning processes.

18 min. reading time

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.

5 min. reading time | by Markus Veit

Introduction

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

12 min. reading time | by Dr. Sabine Paris

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.

12 min. reading time | by Herbert Bendlin

What is rouging?

11 min. reading time | by Sabine Paris

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.

8 min. reading time | by Harald Flechl

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.

12 min. reading time | by Tim Sandle

Controlling water quality in pharmaceutical facilities requires an assessment of chemical and microbial risks. Of foremost concern is water-for-injections (WFI). This grade of water can be prepared using either reverse osmosis or by distillation.

10 min. reading time | by Doris Borchert and Christian Gausepohl

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.

10 min. reading time | by Paulino Alonso

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:

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.

12 min. reading time | by Doris Borchert

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 | by Richard Denk

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.

9 min. reading time | by Felix Michler

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.

6 min. reading time | by Vera Werner

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.

6 min. reading time | by Rainer Gnibl

Excerpt from the GMP Compliance Adviser Chapter 14.J and the GMP Series e-book EU-Compliant Batch Release of Medicinal Products

5 min. reading time | by Lea Joos

The deficiency

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.

3 min. reading time

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

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.

6 min. reading time | by Christoph Frick

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.

13 min. reading time | by Axel Radke

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.

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.

5 min. reading time | by Mark Tucker

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 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.

7 min. reading time | ​by Sabine Paris

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".

5 min. reading time | by Crystal Booth

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.

5 min. reading time | by Harald Flechl / Doris Borchert (editorial editing)

In cleanrooms, it is necessary to create a clear demarcation to adjacent, less clean areas. Since the beginning of clean room technology, airlocks have established themselves as an effective means of separating rooms.

5 min. reading time | by Lea Joos

The deficiency

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.

8 min. reading time | by Thomas Peither

5 min. reading time | by Rainer Gnibl

Some essential differences between EU GMP Guide Part I (GMP for medicinal products) and Part II (GMP for APIs) are:

7 min. reading time | by Ruven Brandes

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.

5 min. reading time | by Felix Tobias Kern

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?

7 min. reading time

5 min. reading time | by Christine Oechslein

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

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.

5 min. reading time

9 min. reading time | by Grant Courtney

8 min. reading time

1 Introduction: environmental risk evaluation

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.

8 min. reading time | by Dr. Sabine Paris

Experts:            GMP inspector Lea Joos, Christian Gausepohl, PhD, QP and Head of Quality Unit

7 min. reading time | by Brian Matye, Jeanne Moldenhauer, Susan Schniepp

Question: How often should I review my SOPs?

9 min. reading time | by Petra Rempe and Martin Mayer

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

8 min. reading time | by Nadja Schaubhut

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.

5 min. reading time | by Doris Borchert

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.

7 min. reading time | by Harald Flechl

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.

7 min. reading time | by Sabine Rabus

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.

7 min. reading time | by Sabine Paris

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?

5 min. reading time | by Doris Borchert

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.

7 min. reading time | by Doris Borchert

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.

11 minutes reading time | by Hansjörg Gutmann, Markus Kopf, Markus Salemink, Dr. Christian Sander

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.

15 min. reading time | by Sabine Rabus

EMA: Update of Q&A on EU/US MRA, December 2019

7 min. reading time | by Dr. Sabine Paris

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.

15 min. reading time | by Tim Sandle

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 [1].

5 min. reading time | by André Deister, Sabine Mendel

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.

10 min. reading time

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

7 min. reading time | ​by Doris Borchert

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.

5 min. reading time | ​by André Deister, Sabine Mendel

Selection and procurement

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?

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.