GxP-Blog

Who is Constructing my GMP-Compliant Manufacturing Plant?

When a pharmaceutical development (Investigational Medicinal Products, IMPs) is transferred from laboratory trials to production, the medicine or the active substance for clinical trials must already be manufactured in compliance with GMP-guidelines. To do this, it first requires a GMP-compliant plant to manufacture it for clinical trials. If this is not available, it must be built. Only the question is by whom. And how does the developer recognize a suitable plant engineer?

 A new product always starts in development and is not yet commercially available for the time being. In order to be able to enter commercial production and thus be put on the free market, first it is required to carry out clinical trials. This requires test material which has already been manufactured in accordance with pharmaceutical law, i.e. it must be GMP-compliant. However, the developers of medicinal products rarely have a second job dealing with the construction of plants – which is why an external service provider must be hired, who builds the factory according to the desired manufacturing conditions. At such an early stage of the planned production, however, little data is available on the investigational medicinal product (IMP). How it will behave in the production itself can only be guessed.

Developers often do not know what subtleties are important for the later plant. In the case of temperature-sensitive substances, it may also be unclear in advance in what kind of environment in the factory the product can persist and for how long. It is difficult to deduce what the plant should look like to enable effective production. However, if the product is toxic, for example, it is clear from the outset that an enclosure is essential to ensure the safety of employees.

The people responsible for the product to be manufactured are mostly not experts in GMP compliance. So "triangular relationships" are common in which the developer joins forces with external consultants and seeks their advice. These will then find the right plant builder. But they also design the plant so that the construction company only has to implement the plans. Conceptual planning is based on experience and empirical values and the industry expertise of the consultants who look at the entire process: how much space is needed, how must the surrounding periphery be built, where are locks, walls and enclosures needed, where are the important piping systems for water, etc.?

The experts define a clear concept together with the developers. In this, two goals are equally important to determine:

• Which regulations are applicable and what does that mean concretely for the project?

• Which criteria apply specifically for plant design and plant construction?

In this way, important foundations are laid for the project and the following questions are answered:

• What are the critical process steps?

• Where is additional technical know-how required?

• What measures should be taken?

Just as important as the selection of the suitable plant manufacturer is the inspection of all suppliers, as all components of the manufacturing plant must comply with the guidelines. Here it is important to understand where the components come from - not that one gets in the end a nice shell where the interior is not easy to clean or that has other shortcomings, which later adversely affect the product.

In the end, everything is a matter of cost. The investors want clear numbers. All in all, however, it cannot be said what a commercial plant costs under pharmaceutical law. That depends on many factors. Starting with the fact that not much time and effort should be spent on the evaluation of potential plant engineers, but experts are here to advise. It is not absolutely necessary in the pharmaceutical industry to choose a plant manufacturer with GMP experience. In theory, any construction company can supply a GMP-compliant production factory. But in the worst case, if it has to be readjusted at many critical points, it can get expensive. It is therefore advisable to choose partners who are experienced in the industry from the outset and who will examine the eligible plant constructors, identify any gaps that may be present, list the existing issues and suggest countermeasures to make everything fit according to pharmaceutical legislation. In addition, subject matter experts can estimate how large the planned plant must be. The more detail is given, the more accurate will the cost estimate be.

In order to find a suitable plant construction company, the experts use certain catalogs of measures according to which the components and thus also the suppliers can be evaluated. Based on this, one can measure what is still missing or where additional work is required. The assessment of whether the plant builder meets the requirements for GMP-compliant pharmaceutical manufacturing is done unbureaucratically. Such documents in accordance with national and international regulations can be flexibly adapted to the manufacturing company.