Hameln pharma's sterile filling plant has won an international award for its layout and design. Dr Simone Dahlmanns, operations director, describes the thinking behind some of its winning features
Hameln pharma began planning its new sterile production facility in the spring of 2006. After a project term of 25 months, the contract manufacturer, located just south west of Hanover in Germany, was granted the manufacturing licence for its new plant to produce sterile pharmaceuticals predominantly for use in hospitals and intensive care units.
In March 2009, the company won the category Operational Excellence for the new sterile production plant in the "Facility of the Year" competition, held annually by the International Society for Pharmaceutical Engineering (ISPE).
The plant was planned and built on the philosophy of lean manufacturing, explains Dr Simone Dahlmanns, operations director and head of the project: "From the first draft of the building up to the initial operation our project team has designed the layout of the new sterile plant in such a way that the production process is supported in an optimal manner."
The main project partners in the project were: architect Koppenhoefer + Partner, with Daldrop + Dr. Ing. Huber responsible for the cleanroom technology, HVAC and pharma finishing; Neuberger Gebaëude-automation was responsible for the Q-BMS System and the general contractor was a joint venture between Daldrop + Dr. Ing. Huber and construction company Hans Lamers.
The arrangement of the work areas is logically based on the sequence of the individual production steps - from the receipt of raw materials, weighing and compounding to the filling process and ultimate shipment of filled vials and ampoules. "Material and personnel movements within the plant are thus organised as efficiently as possible", says Dr Dahlmanns.
This concept of planning and designing a layout to optimise functionality and efficiency is continued throughout the cleanroom and through the organisation of the production line. In the sterile production plant, differentiation is generally made between four cleanroom classes.
"The pass-through system that links all the different cleanroom classes is designed so that when passing from one zone to the next standardised processes are implemented," explains Dr Dahlmanns. "At the same time, the design of the cleanroom classes is functionally orientated to an optimised workflow. Thus the necessity of passing in and out through air lock doors is minimised. As a result, efficiency is increased and the contamination risk is reduced."
The principle of lean production has also been applied when arranging the filling lines. Setting up the machines in a U-shape reduces the space needed for the highest cleanroom class and increases the employees" productivity. Both bringing in the glass containers and removing the filled and sealed ampoules and vials can be carried out in a class D cleanroom by one and the same employee who consequently does not have to move between cleanrooms of different class. Another employee in the adjacent class B cleanroom is responsible for fully monitoring the filling process. Less action in the cleanroom means a reduced risk of contamination - while at the same time increasing productivity.
In the new sterile production plant the colours red, orange and yellow identify the two different cleanroom classes and the pass-throughs between them: the doors of the pass-through air locks used by employees are the colour of the cleanroom class they are entering on passing through the door.
"In general, the lighter the colour, the cleaner the area," says Dr Dahlmanns. "When entering the plant the colour accordingly is red; the four weighing rooms in the C area are again entered via an orange-coloured door. "Employees recognise at first glance in which area they are operating and what precautions they have to take before entering the next area. Product contamin-ation caused by the inappropriate behaviour of staff can thus be prevented from the outset."
Generous use of glazing throughout the plant helps employees achieve a flexible response to different situations. "Seventy per cent of all the inside walls are made of glass so they provide maximum transparency," says Dr Dahlmanns. "On the one hand that enables the employees to keep track of the production sequence, monitor it and make it suitably efficient and economical. On the other hand, employees can consult colleagues during the production process without having to leave their own work area."
transparency and security
In the production of aseptic medicinal products a Restricted Access Barrier System (RABS) presents the optimum synthesis of production flexibility and process safety. Hameln pharma introduced this technology consistently on all of the filling lines to guarantee optimal product safety.
Inside the fixed shield of RABS is a class 100 cleanroom, according to ISO 5. Doors with safety locks, a continous sterile air-flow from the inside to the outside, and handles operated by fixed installation gloves ensure an extremely clean environment. By the strict physical separation of product and producer the risk of contamination is reduced to a minimum.
In the spring of 2008, Annex 1 of the GMP guideline for aseptic production of liquid medicinal products was revised. One of the changes introduced was a considerable tightening of the regulatory standards for the environment of the crimping process. Hameln pharma took these new regulations into consideration when planning the sterile production plant.
"In our new facility, the complete, sensitive process from filling to crimping of the vials is carried out separately from the filling and sealing - as an aseptic process in the class A cleanroom. Operations in this area are performed exclusively using RABS technology, which offers reliable protection from possible contamination."
The new production building has been designed in such a way that it can be adapted flexibly to future demands and needs - taking both spatial and technological aspects into account. The roof space of the new building - only a third of which is currently in use - has been developed so that it can be fully extended.
In addition to extending the roof, the whole of the sterile production plant can be added to and extended. From the outset, the complete building has been planned and constructed in such a position and alignment that modular expansions can be made without problems. Thus enhancing capacities is just as easy as integrating new technologies or developing isolated production areas for highly potent or toxic products.
