Home > Concept Design for Establishing an Eco-Friendly Pharmaceutical Production Facility in Malta

Concept Design for Establishing an Eco-Friendly

Pharmaceutical Production Facility in Malta
The authors discuss the concept design of a versatile, sustainable, small-scale facility
in Malta that conforms to the European Union’s current good manufacturing practices.
Apr 02, 2016
By Maria Mercieca [1], Frederick Schembri [2], Anthony Serracino Inglott [3], Lilian M.
Azzopardi [4]
Pharmaceutical Technology
Volume 40, Issue 4, pg 38-49

IMAGE COURTESY OF THE AUTHORS

For companies involved in logistical and distribution activities, Malta offers several
advantages, such as social and economic permanence, a robust legal framework,
governmental financial incentives for various industries, easy access to policy decision
makers, and a skillful, multilingual workforce with high productivity levels (1) (see
Sidebar on SWOT analysis [5]). Malta’s strategic geographical position, at the
crossroads of the Mediterranean between Europe and Africa, makes the island an
ideal gateway for value-added pharmaceutical services such as sorting, repackaging,
and distribution for the Euro-Mediterranean, Middle East, and North Africa (MENA)
regions. Medicinal products imported from Asian markets can have their marketing
authorization granted in Malta, as it is recognized in other regulated European
countries according to the mutual recognition procedure (2). Malta’s membership in
the European Union puts it at the same level as other EU member states according to
the Roche-Bolar provision and data exclusivity (3). The foundations for a sustainable
pharmaceutical industry have been established by the Malta Medicines Authority,
including an entrenched regulatory framework in line with the EU’s current good
manufacturing practices (cGMP).

In this paper, the authors took an innovative approach to the design of a versatile,
sustainable, small-scale facility in Malta that conforms to EU cGMP. The proposed
facility will employ cutting-edge technology in energy, which further enhances the
sustainability of the project while decreasing running costs.

Uses of a small-scale facility

Mini-scale pharmaceutical facilities are built to provide design data for larger
production facilities or to act as hubs for batch-release activities and provide services
that would otherwise be cost-ineffective for larger companies (4). Examples of
activities that could be undertaken by such facilities include research and
development, small-scale manufacturing and quality control studies, repackaging,
micronization, and batch releases to European and African markets (5).

Methods
This research group undertook this study to assess the costs incurred by a multi-story,
small-scale pharmaceutical facility. The first phase of the study involves designing a
sustainable facility that incorporates environmental and structural aspects. The
manufacturing unit is designed vertically to take advantage of height-to-volume ratio,
thus reducing the ground footprint. Site visits to local oral solid-dosage (OSD) form
facilities, together with extensive research in EudraLex Volume 4 guidelines on GMP
and peer-reviewed literature, were instrumental in accumulating sufficient information
to be able to design the facility, using AutoCAD 2014. Validation sessions with industry
experts were conducted to assess the practicality of the proposed facility plan. The
group of experts consisted of an architect, a qualified person with a pharmaceutical
set-up background, a pharmaceutical logistician with experience in various
pharmaceutical start-ups, a health and safety and security consultant, an engineer
with experience in the pharmaceutical industry, a regulatory officer, and a
pharmaceutical waste control specialist.

A fixed capital investment (FCI) plan has been drawn up, which forms part of the
second phase of this research. FCI was identified using the “detailed-item estimate”
method (6). A list of items required for the planned facility was established through site
visits and as part of the design criteria. This exercise was then carried out by
scrutinizing online product brochures and requesting quotations from corresponding
local suppliers. Careful planning was given to the construction, main process
equipment, and laboratory equipment, as well as utilities, such as heating ventilation
air conditioning (HVAC), and systems for water purification, steam, vacuum, dust
collection, and compressed air. The aforementioned considerations are the basic
requirements for a start-up and require the most extensive capital investment.
Quotations for building-integrated photovoltaic system, photovoltaic panels, and
intelligent lighting were also sought.
The third phase consisted of estimating the number of full-time personnel required to
run the facility. Average wage structure was gathered from a local pharmaceutical
company. The annual operational costs were estimated, taking into account bank loan
interests without security, depreciation expenses according to local legislation (7), and
land rent from Malta Enterprise (i.e., the national governmental agency responsible for
promoting and facilitating foreign investment and industrial development), electricity
expenditure in line with local unit costs, and other expenses gained according to local
expense rates.

Facility design

[6]
CLICK TO ENLARGE
Figure 1: Ground floor
plan.
The facility under consideration is a stand-alone, multi-story facility that could produce
several non-sterile OSD products, except drugs of abuse and cytotoxic drugs. Its
façade is planned to accommodate for the installation of integrated photovoltaic
technology. The facility is planned to be south-facing to optimize natural lighting for the
auxiliary area.

It is envisaged that the facility will make use of approximately 4700 m2 of land, with a
floor area of approximately 8000 m2 spanning four separate levels with interacting
industrial lifts. Waste and solvent rooms as well as an electricity substation were
planned separately from the facility to minimize safety risks. An underground parking
area can also be considered for the facility.

The ground floor (see Figure 1), with a height equivalent to two stories, will include
the warehouse that includes a dispensing area containing a down-flow booth using
extract technology. The notion behind having a dispensing area on the ground floor is
to reduce the waste flowing into the first and second level.
[7]
CLICK TO ENLARGE
Figure 2: First floor plan.
The first floor (see Figure 2) will be for the packaging of OSD, with locked storage for
the printed packaging material. It will have direct access to the lift from the dispensing
area. The plans accommodate for eight blister lines and/or bottling lines. It was taken
into consideration that both primary and secondary packaging processes will be
carried out in ISO Class 8 areas. This floor will also accommodate a microbiology and
chemistry laboratory. Through the latter, one can access the stability chambers.

The second floor (see Figure 3), with height equivalent to two stories, will host the
actual tableting process, including granulation, compression, and coating, which are
maintained at ISO Class 8 specifications. A technical corridor runs around the
perimeter of this level to enable technical support and maintenance of the equipment.
The rationale behind having these processes on the uppermost level is that they will
require extensive use of utilities and services. By putting them on the top level,
savings are achieved in duct work installation, and air system complexity is minimized
(8). Shafts for these processes can be constructed to provide to this level through the
ceiling and allow the other shafts to supply the ground and first floors. There is also a
research and development laboratory on this level, with an interacting samples room.
[8]
CLICK TO ENLARGE
Figure 3: Pressure
cascade system on
second floor.
A utility and services space is on the uppermost area of this unit, which will include
services for HVAC, vacuum, steam, water purification, dust collection, and
compressed air. This space will be roofed over to protect the equipment and pipes
from harsh weather.

Plans for the various floors take into consideration unidirectional flow of personnel,
material, and waste to prevent cross-contamination (9). Standard operating
procedures (SOPs) will form part of a quality system to regulate GMP activities within
the facility.
Pressure cascade system
The pressure cascade system is managed by the HVAC system, which provides air as
necessary to create pressure. Spaces that should remain cleaner than their adjacent
areas must have a higher positive pressure (8). Processing rooms have lower
pressure than the clean corridor, so that the higher pressure in the corridor helps in
leaving contaminants in their respective suites and prevents their transfer through the
corridor. The concept of the pressure cascade system for the second level of the
facility is depicted in Figure 3.

Bubble airlocks were designed to act as transitions between the unclassified and
classified zones. Bubble airlocks usually have higher pressures than the adjacent
areas, to keep any contaminants in their area (10). Prior to entering any lift in the
production area, airlocks (AL) were also designed so as to isolate any possible
contamination coming from the warehouse, which is essentially an unclassified area.

Figure 4: Pie chart depicting the breakdown of fixed capital investment.

Fixed capital investment

The capital expenditure, worked in a detailed-cost estimation, amounted to nearly
€13.4 million. Figure 4 shows a breakdown of the capital cost.

Consideration was given to items that enhance sustainability, such as a building

integrated photovoltaic system for the façade and photovoltaic cells on the roof, which
are feasible renewable energy sources for Malta’s subtropical-Mediterranean climate.
Sensors and LEDs for the auxiliary area, a reliable building management system, and
building insulation were also taken into account.

Operational costs
A GMP pharmaceutical facility should have an adequate number of well-trained and
qualified human resources (11). There will be 36 full-time employees engaged in the
facility; 15 of whom will be designated in production roles. The remaining staff will be
employed in non-production positions, including four personnel in quality and seven
working in laboratories. Their total salary cost (including national insurance according
to Maltese legislation) is just over €1 million.

Operational costs of this facility to hypothetically produce 100 million OSD over the
year 2015 were estimated to exceed €4 million. Included in this figure is the
depreciation cost. Depreciation is the measure of the decreasing cost of property over
time, which is seen as an expense (12). According to Maltese law, deductions for wear
and tear should be calculated in a straight-line method over a minimum number of
years (7).

Energy saving measures taken into account for this facility, are estimated to enhance
the bottom line by more than €70,000. Figure 5 shows a detailed breakdown of the
operational costs.

Figure 5: Pie chart illustrating breakdown of running costs.

Environmental benefits
In today’s world, priority is given to safeguarding the environment in response to global
warming. Large industries are wary of their carbon footprint, not only because of
concern for the environment, but also to uphold the reputation of the company among
the general public. “Green” issues to be tackled to boost a company’s environmental
credentials include waste management, recycling, energy reduction, and conservation
(13). Malta aims to encourage good practices, such as making optimal use of natural
resources in an environmentally friendly manner (i.e., least possible usage and
maximum re-usage) (14). The proposed facility will minimize carbon footprint by
embracing renewable (i.e., solar) energy, which will also help the enterprise financially
by reducing operational costs (15).

Efficient and sensible use of land and sea are crucial factors in the macroeconomic
and social development of Malta given the high population density, space
requirements for industry, and the land-intensive needs of waste disposal and shipping
(16). Bearing in mind that there are no imposed height restrictions in industrial parks, a
vertical facility will safeguard the relatively limited land space.

Conclusion
Local stakeholders believe that a small-scale OSD facility can meet the needs of a
potential niche sector for the pharmaceutical industry in Malta, apart from
biotechnology that will hopefully flourish on the island. It is imperative to note that
investing in efficient infrastructures will contribute to the local growth of the
pharmaceutical industry, thus having a positive effect on the biotechnology industry.

References
1. EY, “The Economy: Today & Tomorrow Malta’s Attractiveness Survey 2013 [9],”
EY.com (Malta, 2013).
2. Government of Malta, “Medicines (Marketing Authorization) Regulations [10],”
(Malta), Oct. 26, 2007.
3. Focus Reports, “Malta: A Healthy Location for the Pharmaceutical Industry,”
pharmaboardroom.com (London, January 2011),
http://pharmaboardroom.com/article/country-report-malta-a-healthy-location-for-the-
pharmaceutical-industry/ [11]
4. J.A. Toner and J.H. Worstell, “To Build or To Contract: The Economics of Pilot Plant
Decisions,” AIChE Annual Meeting Conference (Cincinnati, OH, 2005).
5. R. Zerafa and A. Serracino Inglott, “Proposal for Setting a mini-scale Solid Oral
Dosage Form Production Facility,” Dissertation (Malta, Feb. 28, 2012).
6. M.S. Peters, K.D. Timmerhaus and R.E. West, “Cost Estimation,” in Plant Design
and Economics for Chemical Engineers , pp. 150-215, (McGraw-Hill, Singapore, 5th
ed., 2004).
7. Income Tax Act, L.N. 298: Deduction (Wear and Tear of Plant and Machinery)
Rules, (Office of the Prime Minister, Malta), pp. B3188-B3190.
8. A. Bhatia, “HVAC Design for Pharmaceutical Facilities,” CED Engineering.
9. European Commission, EudraLex Volume 4, Chapter 3: Premises and Equipment
(Brussels, Aug. 13, 2014).
10. WHO, “Supplementary guidelines on good manufacturing practices for heating,
ventilation and air conditioning systems for non-sterile pharmaceutical dosage forms,”
WHO Technical Report Series (2011), pp. 215-260.
11. European Commission, EudraLex Volume 4, Chapter 2: Personnel (Brussels, Aug.
16, 2013).
12. M.S. Peters, K.D. Timmerhaus and R.E. West, “Depreciation,” in Plant Design and
Economics for Chemical Engineers, pp. 267-294 (McGraw-Hill, Singapore, 5th ed.,
2004).
13. D. Buker and J. Kaushik, Pharm. Eng. 31(3) 8-16 (2011).
14. Government of Malta, “Sustainable Development Act,” (Malta July 10, 2012).
15. M. Neelis, E. Worrell, and E. Masanet, “Energy Efficiency Improvement and Cost
Saving Opportunities for the Pharmaceutical Industry: An ENERGY STAR Guide for
Energy and Plant Managers” (Ernest Orlando Lawrence Berkeley National Laboratory,
June 2008).
16. National Commission for Sustainable Development, “A Sustainable development
strategy for the Maltese Islands 2007-2016” (Malta, Dec. 20, 2006).

Article Details

Pharmaceutical Technology
Vol. 40, No.4
Page: 38-49

Citation
When referring to this article, please cite it as M. Mercieca et al., “Concept Design for
Establishing an Eco-Friendly Pharmaceutical Production Facility in
Malta," Pharmaceutical Technology 40 (4) 2016.

© 2018 UBM. All rights reserved.

Source URL: http://www.pharmtech.com/concept-design-establishing-eco-friendly-pharmaceutical-production-facility-malta

Links:
[1] http://www.pharmtech.com/maria-mercieca
[2] http://www.pharmtech.com/frederick-schembri
[3] http://www.pharmtech.com/anthony-serracino-inglott
[4] http://www.pharmtech.com/lilian-m-azzopardi
[5] http://www.pharmtech.com/swot-analysis
[6] http://files.pharmtech.com/alfresco_images/pharma/2016/04/04/ebfda8ea-e2fe-40cb-96d5-3774ef353ed4/PT0416-Ground-Floor-Plan-.jpg
[7] http://files.pharmtech.com/alfresco_images/pharma/2016/04/04/ebfda8ea-e2fe-40cb-96d5-3774ef353ed4/PT0416-First-Floor-Plan.jpg
[8] http://files.pharmtech.com/alfresco_images/pharma/2016/04/04/ebfda8ea-e2fe-40cb-96d5-3774ef353ed4/PT0416-Second-Floor-Plan.jpg
[9] http://www.ey.com/Publication/vwLUAssets/EY%E2%80%99s_2013_Malta_Attractiveness_Survey_Event-
The_Economy_Today_and_Tomorrow/%24FILE/EY_Attractiveness_Invitation.pdf
[10] http://www.justiceservices.gov.mt/DownloadDocument.aspx?app=lom&itemid=11272&l=1
[11] http://pharmaboardroom.com/article/country-report-malta-a-healthy-location-for-the-pharmaceutical-industry/