GxP-Blog

From the concept to implementation

In 2012, Chemgineering was commissioned by Riemser Pharma GmbH to prepare a concept study with the goal of generating and assessing scenarios for various company sites with regard to the implementation of new products and products to be transferred in compliance with Current Good Manufacturing Practices (cGMP).

The upgrade involved the manufacture of solid pharmaceuticals. The primary aspects to be investigated included:
· GMP requirements (EU and ANVISA)
· material and personnel flows
· upgrades of floors, walls and ceilings in compliance with GMP specifications
· identification of required upgrade measures for GMP-relevant areas (cleanroom, media, air-conditioning/ventilation with pressure cascades)
· investigation of necessary expansions for media supply (compare demand to generation)
· space requirements for changing rooms, break rooms, laboratories, etc.
· cost analysis

Based on the results of the concept study, Riemser decided to expand the production site in Schiffweiler. Within the framework of an implementation project, the production areas were to be modernized and enlarged, so that the increasing international GMP requirements could be fulfilled in the future as well. Likewise, an expansion in production via the addition of new produts was planned.

Riemser intended to commission a general contractor to implement the plans. Because there were no sufficiently detailed planning documents available after the concept study, a possible project management model was developed in collaboration with Chemgineering. This model specified that a further planning phase would first be initiated, during which the essential basics of the project would be established and defined. During this phase, the prerequisites were to be created that would offer optimal clarity to everyone involved with regard to the measures to be implemented. After this planning phase, the implementation of the project was to ensue in accordance with a general contractor agreement.

This model was subsequently implemented as planned. In early 2013, Chemgineering was awarded the contract for the basic engineering. The planning fundamentals were prepared during this phase. The measures to be implemented were planned in detail, specified and finalized. The basic engineering created a solid basis for project implementation. Based on this, Riemser made the final investment decision. In mid-2013, Chemgineering was appointed as the general contractor and entrusted with the implementation of the project.

The scope of the project was defined as follows:
· dismantling of existing production areas
· new construction of GMP-compliant facilities including the corresponding ventilation and air-conditioning technology (approx. 1000 m² with 30 rooms)
· implementation of new functional areas for new products
· procurement of new production equipment
· installation of ventilation and air-conditioning systems for existing laboratory and storage areas
· upgrade of media supply systems

With the investment decision and the commissioning of Chemgineering, a race against time began. The manufacture of stability batches under GMP conditions for a defined product was to begin in early 2014. To achieve this goal, it was necessary to divide the implementation into individual construction phases. Priority was given to the construction of the areas required for the manufacture of the specified product.

Another significant boundary condition for the project was the fact that the remodeling was to take place in the existing facility. This meant that a time period had to be found for production stoppage to facilitate the remodeling. As is usual in such cases, the operator wanted to keep this downtime as short as possible. In the end, a period of 2.5 months was specified, during which the main installations had to be carried out.

This resulted in a demanding list of tasks for Chemgineering:
· preparation of the order specifications for the executing trades (process technology, air-conditioning/ventilation, media supply, cleanroom enlargement, electrical and electronic installations)
· development of a phased plan for the remodeling
· procurement of all equipment and executing trades
· coordination of the installations and commissioning
· support of Riemser during qualification

In addition to the upgrade and expansion of the production areas, the production equipment to be procured was also important. The equipment to be procured was partially new and partially used. This specification was already implemented within the basic engineering project. The following main equipment was to be procured for the project:
· capsule deduster
· sieving machine
· blister packaging machine
· labeling machine
· winding machine for plastic films
· belt scale
· extraction devices
· highly purified water (HPW) system

It is worth noting that the procurement of the used equipment was successful as well and that it was easily integrated in the production process. The other equipment required for production was shifted from the existing facility and from other production sites of Riemser to the site in Schiffweiler.

Project management ensued in a close and very cooperative partnership with the Riemser project managers. The necessary coordination was accomplished in a timely manner, facilitating fast decision-making. This created a good basis for meeting the demanding schedule. In the end, the major project goals were achieved. The production of the stability batches began on schedule in early 2014 after only 2.5 months of remodeling. With regard to the planned inspection by the authorities, this was a decisive milestone for the project. The other production areas likewise began operation on schedule after a further month of remodeling.

However, a pharmaceutical project is successful only when the regulatory inspection is successfully passed. This was also achieved. Approximately three months after the start of production, the relevant state authority issued the manufacturing permit.