GMP LOGFILE: Lead Article

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.