R. Zerafa, A. Serracino-Inglott, L. Wismayer, L. M. Azzopardi
The pharmaceutical industry in Malta has flourished in such a way to become an important contributor to the country’s economy. Malta’s legal and regulatory framework and later on its membership in the European Union (EU) have led to an increase in Malta’s pharmaceutical activities.
1
To determine the potential deliverables of a pharmaceutical mini-scale production facility in Malta; to plan and design such a facility as part of a pre-design study; and to draw up estimates of the capital investment involved in such a project.
The facility shown in Figure 1 is a standalone multi-purpose, non-sterile, OSD facility in which the active pharmaceutical ingredient (API) is to be processed under current
GMP. The building footprint is 2647m 2 . Another floor was considered so as to include offices and other supporting structures. The area covered by the first floor is 533.8m
2 .
For the purpose of the study it was assumed that the facility does not cater for the processing of highly potent and/or light-sensitive ingredients.
The facility can be divided into the classified zone consisting of the clean corridor and process rooms and the unclassified zone including the technical corridor, stores and auxiliary building. The air lock rooms act as buffer regions between the two zones.
The logical arrangement of the process rooms ensures unidirectional flow of material so as to avoid product mix-ups and cross-contamination. The main process to be carried out in the facility is outlined in Figure 2.
Phase 1—Market Analysis: Preliminary communications were carried out with the identified local generic oral solid dosage (OSD) facilities in order to benchmark the objectives of the project. Semi-structured interviews with the major pharmaceutical stakeholders (Malta Enterprise and Medicines Authority) were carried out and questionnaires were also conducted amongst the 5 local generic OSD pharmaceutical companies.
Phase 2—Planning: A literature review was carried out. The Good Manufacturing
Practice (GMP) guidelines related to the production of medicinal products for human and veterinary use 2 and studies carried out by Brocklebank et al.
3 and Vu et al.
4 related to OSD facility layout and design were consulted. A multi-disciplinary panel
of experts was assembled for the purpose of the study.
Phase 3—Design: Once the project scope and boundaries were determined, the layout
of the facility was designed using AutoCAD 2011 and was validated by the panel of experts assembly chosen for the project. Detailed consideration was given to: facility
To arrive at an estimate of the FCI, the cost of the delivered process equipment was layout, flow of personnel and material, process flow diagrams, main process used as the basis for the rest of the process-plant components. The delivered equipment and utilities. equipment cost amounted to approximately: €2,300,000. This value was assigned a
Phase 4—Capital Cost Estimate: The fixed capital investment (FCI) was estimated percentage of FCI equal to 30% and includes the price for the main process based on the method of percentage of purchased equipment cost.
5 Local equipment, documentation required, setting up of the equipment, packaging and governmental initiatives were also taken in consideration. transport. The cost associated with the rest of the process-plant components were based on expert advice. Taking into account all the process-plant components, the
FCI cost estimate amounted to approximately: €8,400,000 (±30%).
The potential deliverables identified during the market analysis are: research and development (R&D), manufacturing and quality control (QC), repackaging and
micronisation as well as training and education.
The plan developed in the study explores the different potential outcomes of a miniscale OSD facility and is based on standard, non-specific processes which must be tailor-made at a later stage of project design. The identified deliverables are: research and development of new formulations including the use of micronisation techniques, production of small batches for clinical trials including bioequivalence studies and development and validation of QC processes. From the feedback obtained from the local OSD facilities and the major pharmaceutical stakeholders in Malta, it can be concluded that the project is feasible for Malta.
Key: AL-Air lock, 1-Incoming goods store, 2- Finished goods store, 3-Changing rooms, 4-Clean room area
(enclosed in red line), 5-QC lab, 6-Technical corridor, 7-Workshop, 8-Electrical substation, 9-Utility building, 10-
Solvent room
ACKNOWLEDGEMENTS
The authors would like to thank Mr. J. Scerri, technical co-ordinator at Siegfried Generics (Malta), Mr. M. Galea, advisor to Executive Chairman at Malta Enterprise, Mr. M.
Cilia, Director Inspectorate & Enforcement at Medicines Authority, Mr. B. Croft, Chief Executive Officer, EU Pharma, Elder, Europe and Mr. G. Bellei, Area Manager, IMA
S.p.A—ACTIVE Division.
REFERENCES
1 McKenna A., et.al., The manufacture of generic pharmaceuticals in Malta: A first step, J. Gen. Med. 2, 63-70 (2004)
2 European Commission [online]. EudraLex Volume 4: Good Manufacturing Practice Guidelines. Brussels: European Commission [cited 2009 Jul 3]. Available from: URL: http://ec.europa.eu/health/documents/eudralex/vol-4/index_en.htm
3 Brocklebank M.P., et.al., A hub layout concept for oral solid dosage (OSD) facilities, Pharm. Eng. 26, 1-8 (2006)
4 Vu, J., et.al., Evolving concepts in OSF plant design: part 1, Pharm. Technol. Eur. 18, 23-28 (2006)
5 Peters, M.S., et.al., In: Glandt, E.D., et.al., (Eds.). Plant Design and Economics for Chemical Engineers, 5th edn. Singapore: McGraw-Hill, Inc; pp.226-278 (2004)