By Abhay Ranjan & Shailesh Doshi
An increasing number of businesses are being challenged by their stakeholders regarding sustainability. In a world where businesses are facing intense challenges driven by growing complexities in their operations and compliances, demand is growing for total quality assurance solutions; solutions that extend beyond the quality and safety of products, to those that deliver sustainable solutions in the development of products and services for the present and future.
Sustainability is the core of any business. Optimized design and engineering ensures the inbuilt sustainability of the entire facility, systems and operating procedures. This becomes a qualitative competitive advantage for the industry. A scientific approach for proper and optimized design and engineering, in turn, results in overall improved performance of the business which ultimately create more avenues for sustainability and economies of scale.
It’s difficult to accept that biopharmaceutical or drugs manufacturing companies are facing issues related to sustainability.
Sustainability is a complex concept and is being used in various modes in different contexts. In this article, however, our focus is on the biopharmaceutical industry. Accordingly, in this context, sustainability means a balancing act and the ability to maintain a certain regulatory standard. Similar to Porter’s win-win hypothesis, a trade-off is not necessary. Therefore, the approach of in-built sustainability is essential when designing biopharmaceutical facilities.
From “Quality-by-test” to “Quality-by-design”
There is a shift in regulatory thinking from “Quality-by-test” to “Quality-by-design” with an emphasis on the level of risk to product quality and patient safety.
Design is a process that integrates human ingenuity with data and technology to revolutionize the development and application of manufacturing intelligence to all aspects of suitability in a business. Design should be a risk-based approach with rationales based on science and verifiable measurements.
Biopharmaceutical design should make use of resources more efficiently within the desired regulatory compliance. Industry has to tailor design to manage the entire supply chain, production sequences, disposal of waste, efficient utilization of energy and water and overall efficiency of business. Proper design results in energy-efficient buildings, infrastructure, optimized blueprints and efficient processes.
The maximum utilization of the facility and/or equipment machinery is critical in order to achieve better ROI. While conducting design, the designer should give due consideration to line balancing of production and ensuring the maximum occupancy of the equipment and machinery, irrespective of the in-built flexibility in the factory.
Costs increasing in biopharmaceutical industry
The biopharmaceutical industry has seen an increase in the cost levels of new facilities and in many instances the modification/correction costs in new facilities; this is partly due to uncertainty about the exact requirements or the URS. The designer should gain an appropriate understanding of the product and process requirements on which the conceptual layout is developed.
The facility layout must be an integrated design that satisfies process and equipment layout requirements, while catering for good levels of access for operability, maintenance, personnel, product, components, raw materials and waste. The design should provide a contained environment with an adequate level of hygiene and safety. The risk analysis with respect to the product, environment and humans must be established.
Optimized design should ensure the integration of EHS compliance and the efficient management of all operations. Design should ensure that all forms of compliance, albeit regulatory compliance, EHS, documentation, etc. are not necessarily a cost to the business.
Building design and building systems
Some studies have shown that about 40% of the world’s energy is consumed by buildings. If building design is within the correct framework as per the requirements of the process/product/ambient conditions etc., a large part of this energy consumption can be saved. This in turn will contribute positively to bottom line of factories.
In the biopharmaceutical industry, HVAC is a source of high energy consumption, which is directly linked with the design of the facility. Use of poor quality AHU results in leakage in technical areas which is never checked and accounted for. Inefficiency in the selection of AHU, on the other hand, results in excessive electricity consumption. Optimized and intelligent design and selection can help companies to maintain the controlled ambient conditions that are crucial for product quality and, at the same time, reduce the energy consumption of HVAC.
Another area of concern is the use of energy efficient devices such as motors or LED-based cleanroom lights etc. In a typical biopharmaceutical facility, for example, there are a large amount of motors. The proper selection of these motors can result in significant savings.
Maximizing use of natural resources – minimizing waste
Design should encourage the maximum use of natural resources such as light and air wherever possible, without impacting the product and regulatory guidelines. The biopharmaceutical industry is a heavy energy consumer and, therefore, it is crucial to have energy-efficiency inbuilt features in building design.
Several studies in the biopharmaceutical sector have quantified the generation of various types of waste. Waste is generally the result of poor design, engineering and inefficient processes. Inadequate design and inefficient processes often result in batch-to-batch product variations, in product failure/recalls/quality issues etc. Process optimization followed by customized design are essential to reduce such waste.
In biotech facilities, a new trend is the use of single-use technology. It has several advantages over traditional, fixed SS process equipment. The inherent advantages are the flexibility of the process, the reduction in turnaround time between batches and of expensive, classified cleanroom spaces, as well as the elimination of CIP/SIP. There are, naturally, cost impacts and the economics of single use is very different to that of SS equipment.
Quality and quantity are attributes required for drug manufacturing that can be achieved either by personnel attention or by systems. While designing a facility, engineering control should be given more attention so that reliance on personnel can be avoided. Accordingly, automation is picking up in the biopharmaceutical segment, which ensures the accuracy and consistency of product quality. This results in the reduction of product recalls and overall higher productivity.
The use of sensors and monitoring systems for various critical applications can be helpful for precise control and also to identify inefficiencies in facilities. An integrated process and automation system helps to ensure efficient and continuous manufacturing. Many biopharmaceutical companies are adopting advanced ERP systems that integrate all the business’ processes, monitor production processes in detail and generate data for management in real time. In order to receive regulatory approval for biopharmaceuticals production, effective tracking and control of all related processes from sourcing of raw materials to dispensing, manufacturing and shipment of finished products is mandatory.
Similarly, traceability systems for finished drugs are required to guard against counterfeiting and to support patient safety, which in turn necessitates drug serialization.
The VMP should be established during the very early stage (concept design stage) of a project and should be followed religiously throughout the project. The VMP must be a written document with a well-defined validation philosophy, methodology, as well as the responsibility and approval authority matrix within the organization.
Accordingly, the philosophy for all qualification and validation is designed inclusive of various protocols/SOP. Once the protocol is developed and established, it should be followed consistently. If there is a change in the protocol, the reason for the change should be documented.
Proper documentation is the key aspect of successful and sustainable manufacturing of biopharmaceutical products. During the design stage, an adequate and secured documentation storage and retrieval system needs to be established.
Keeping up to date with changing requirements
Another challenge for the biopharmaceutical industry is to keep track of new developments, regulatory expectations and to update skill sets accordingly in the organization. Hence, the continuous training of human assets is obligatory to achieve sustainable manufacturing in the biopharmaceutical industry.
The biopharmaceutical industry is a very cost sensitive and competitive industrial segment. Proper design aids in optimizing consumption of energy, water and reducing waste, while protecting people and achieving the desired drug quality and quantity. In-built sustainability in factories assists manufacturers to benchmark against their competition and to achieve sustainable long-term gains in the industry.
The design, construction, commissioning, qualification and validation of biopharmaceutical facilities raise significant challenges for manufacturers as well as for the designer. The GMP compliance is achievable through good science and sound justification of your approach.
The biopharmaceutical industry connects with countless lives around the world through research, development and production of lifesaving and life-enhancing drugs. Sustainability in the industry is reflected in a commitment to supply high-quality and safe drugs, while developing new therapies to address futuristic medical requirements. The biopharmaceutical industry should focus on operational excellence and sustainability, which can help it to differentiate and deliver value to society.
In its consistent efforts towards zero defect products with increased cost pressure, regulatory framework, and increased productivity goals, the bio pharmaceutical industry needs to adopt a proven scientific route to design and engineer facilities that herald an era of unprecedented sustainability.
URS - User requirement specification
EHS - Environment, Health and Safety
AHU - Air Handling Unit
CIP / SIP - Clean-in-place / Sterilisation-in-place
SOP - Standard operating procedure
VMP - Validation master Plan
About The Authors
B.E. (Production), MBA
Abhay Ranjan spearheads the operations of Elomatic, India. As an accomplished visionary and mission-oriented leader with strong strategic abilities, he has pioneered the growth-story of the company. He holds a bachelor’s degree in production engineering and a master’s degree in management from IIMC. He has been closely associated with the pharma and biotech industry for over 28 years. Under his leadership, Elomatic India has with distinction executed numerous projects of various complexities, spanning South East Asia, Middle East, Africa, CIS countries and other nearby countries including India. He is also a member of ISPE and PDA.
M. Pharm (Tech.), MBA
Mr. Shailesh Doshi has worked for the duration of his entire career in the pharmaceutical industry as a GMP and regulatory professional. He has hands-on experience in the manufacturing of a wide range of drugs under various regulatory inspection bodies. He has extensive know-how of processes, tech-transfer, operations, qualification and validation, quality, regulatory matters, as well as engineering and design.