Fette Compacting


Trends in the manufacturing and processing of high-potency active pharmaceutical ingredients

Containment technologies have progressed in leaps and bounds over the last few decades. At the same time, operator protection requirements have risen due to new, highly potent and highly hazardous active ingredients. Richard Denk analyzed what that means for future technological developments as part of an expert group set up by the International Society for Pharmaceutical Engineering (ISPE). A look at the future of containment.

I have been passionate about containment for almost 20 years. I first came across the subject at an ISPE conference in the USA in 1996. Some time later, I became an active member of the US ISPE Containment Group, which I subsequently co-chaired for several years. During this time, a number of fundamental ISPE guidelines were initiated, such as the Standardized Measurement Of Equipment Particulate Containment (SMEPAC) covering maximum levels for containment systems. In 2008, the time was right to set up a regional ISPE containment group for Germany, Austria and Switzerland. I have been chairing this expert group ever since – something I love doing.

Three major containment trends

Containment technologies have developed more and more over the last 20 years. New technologies for safe and efficient pharmaceutical production have constantly emerged. But will that continue to happen over the next few years? How will the world of pharmaceuticals change in the foreseeable future and what does that mean for containment moving forwards? We have discussed these issues at length within the German/Austrian/Swiss ISPE group and talked to numerous industry representatives. This formed the basis for the Pharma 2025 initiative, within which we are also considering the question of containment. In short, as have identified three main focal points:

1. Process-integrated containment will replace adapted containment. The production process will merge with containment. This will enable optimum containment production with the smallest possible footprint. As a consequence, there will be fewer contaminated surfaces, resulting in considerable advantages for cleaning and refitting. Should it become possible to create a small, self-enclosed clean room inside the containment area, the GMP environment for this process could also be simplified. There have already been several initial developments along these lines – for example in the packaging of tablets and capsules.

2. Single-use systems will be another focal point over the next ten years. Disposable technologies have a major advantage in that the manufacturing process can be adapted quickly and easily to containment requirements. These systems offer the greatest advantages for relatively small production quantities and the field of research and development. Single-use technologies are also worth considering if the product being manufactured changes frequently or highly flexible process management is needed. Examples of such systems include disposable liners and single-use isolators for the transportation and pharmaceutical processing of highly potent substances. The biotech industry is also increasingly replacing stainless steel systems with single-use technologies.

3. Continuous manufacturing will play an important role for the production of high-potency or highly hazardous active pharmaceutical ingredients. Continuous manufacturing has a number of advantages over batch production: the process equipment is more compact, meaning it has a smaller surface to be cleaned. The processes are also linked with one another or several process stages are completed by a single machine. This makes for fewer containment interfaces.

We will continue to examine these trends in depth within the ISPE Containment Expert Group over the coming years.

Food for thought: containment pyramid and handbook

When I developed the containment pyramid about 15 years ago (see diagram), it had five levels with corresponding limits. Now, some of the substances in use are so highly potent or highly hazardous that we have added a sixth tier. This category is for products with a maximum particulate contamination level of less than 200 nanograms per cubic meter. Even more efficient containment systems will be needed in the future to comply with such low limits.

We compiled our latest containment findings in the ISPE group and used them to develop a containment handbook specifically for pharmaceutical production. The book will be available from ISPE from late September 2015. It is designed to serve as a guideline and reference work for users in the pharmaceutical industry on all containment issues – from the basics to system life cycles.

Personally, I have no doubt that there are many more changes to come in the field of containment over the next ten years. It will be interesting to see how things develop.

Richard Denk
Chair of the ISPE Containment Expert Group (Germany, Austria, Switzerland),
Containment Sales Manager at SKAN AG
Author at Maas & Peither GMP-Verlag