Design of the times

Commissioning the design for commercial buildings is a fairly straight forward process, but when it comes to facilities for pharmaceutical development laboratories and clinical trials facilities, the experience is more complex, highly regulated and, if badly handled, highly costly. Peter Rimmington explains how to avoid the pitfalls.

Designing pharmaceutical buildings is an exacting process and with well defined procedures that anticipate how the facility will be used for its working life. This demands the development of a clear strategy for design and its implementation.

Over the last 30 years the regulatory criteria used as the basis for the design has not changed significantly but the proving or validation of compliance has become much more challenging.  However, in recent years, many previously unlicensed development laboratories and small scale manufacturing facilities used for clinical trials materials have now been brought within the regulatory framework. 

Partly because of this, and financial pressures, pharmaceutical clients are increasingly looking for architects and engineers to build a faster and more responsive procedure and to reduce the construction time of a building, so they have longer to develop, test and produce drugs before patents run out.  

However, no matter how much they develop and quicken that process, testing and re-testing to ensure buildings are able to meet the standards of manufacture set out by regulatory bodies will always remain key to success – and that inevitably takes time.

No matter how large or small, pharmaceutical buildings must be designed in full recognition of the guidelines, which govern manufacture of the drugs.  The guidelines are embodied in codes of current Good Manufacturing Practice (cGMP) published in Europe by the EU and regulated by the Medicines and Healthcare products Regulatory Agency (MHRA).  Where drugs are to be sold in the USA, then the Code of Federal Regulations and the FDA are the relevant authorities.  The objective of all this regulation is the protection of consumers from contamination and mistakes in the manufacturing process.

Ensuring it conforms to the highest standards of cleanliness is a major factor in how the building is designed. Minimising the risk of contamination from microorganisms is key, so the room finishes must comprise smooth, robust, easy-to-clean surfaces.

This involves designing walls, ceiling and floors with coved corners and flush doors, windows and light fittings to make surfaces easy to clean. Where the product is protected then these standards can be reduced but in any area including storage, good housekeeping is important.

Meeting the regulations involves many specialists, including architects, engineers, quality and process advisors and not forgetting the end user. They need to work closely as a team, each contributing their expertise in the understanding and interpretation of guidelines, and the constraints which they place on building layouts as they develop.

This knowledge is also vital in reviewing the economics of incorporating future flexibility in production and often the need for expansion. 

Change is a constant in the industry and managing and minimising the impact on production is key. Current trends are moving away from ‘bespoke’ buildings to flexible ‘shells’ requiring less time to design and build, but also giving the client greater opportunity to change their mind.

As well as working for large multi-nationals, Dewjoc is increasingly working for small firms in the emerging field of biotechnology, for example companies involved in Newcastle’s Science City project. Such clients often, understandably, struggle to move forward from the initial development of a product through scale-up to the manufacturing stage, due to a lack of experience when it comes to interpreting the complex regulations governing manufacture. 

One critical element clients, both large and small, find hard to define at the early design stage is the quantities of drugs they want to manufacture. This is because the market forecasting of a new product is difficult to predict and so the design strategies of flexibility and expansion become important. 

This uncertainty does not necessarily stop the client or the design team from progressing but it does have an impact on the approach to the final facility. Identifying at crucial stages what is or is not important requires the experience found in a good team.

The result is that although two companies may have, say, a similar tablet to manufacture, the design and construction of the facility may be achieved in very different ways. Ultimately this depends on the client’s business case, which will inevitably dictate expenditure and determine the timescale.

Standards must also be defined. Manufacturing steriles, topicals and tablets all require different equipment to produce them which in turn means differing regulatory requirements, all of which influence the building design. Cutting corners at the design stage could well lead to hold-ups and spiralling construction costs later down the line and potentially a refusal by the regulatory authority to allow manufacture.

To minimise time and cost wasted during the design phase a detailed brief setting out the scope of the project is essential.  This will include an outline of the processes to be carried out, range and volumes of drugs to be produced, a preliminary schedule of manufacturing equipment and an assessment of potential contamination risks.  It will also define requirements for validation.  Referred to as the User Requirements Specification (URS) it is also the first piece in the validation jigsaw.

Design work commences with a detailed review of the URS. Optimum room sizes to suit manufacturing equipment are discussed and agreed.  Air conditioning requirements to satisfy cleanliness conditions and other engineering services are also developed.  From this process detailed building layouts can be prepared.

Everyone involved in the design also has a duty to ensure a safe working environment for the staff at the facility. If, for example, a product is toxic then the equipment used for manufacturing it, as well as the protective equipment worn by employees, must be identified and incorporated as part of the design development. Once all considerations have been assessed, the initial design is agreed with the client.
 
These first steps  are recorded in the a Design Qualification document (known as the DQ stage), which will also consider people and material flows, fire and access strategies and outline specifications for the construction and engineering systems all designed to ‘respond’ to the client’s URS.

Finally at this stage cost, programme and quality standards are also defined. The document can then be made available to the appropriate regulator for his observations (but never approval).

The DQ is the next key part of the validation trail – it establishes what, why and how the building will be designed and starts the process of creating a facility that once validated, can maintain the defined standard for the rest of its working life.

This trail is documented in the Validation Master Plan (VMP) which identifies the key components that need to be validated and the extent of the testing procedures needed to satisfy the regulatory authority.

Once the DQ document has been approved by the client the design team will develop these preliminary proposals into construction drawings and specifications for tendering and procurement of the building, and the processing equipment incorporating the requirements of the VMP to ensure compliance by the various suppliers. 

At the construction stage the facility is built and the process services incorporated. However to satisfy the VMP, checks must be made to ensure the correct materials and specifications have been used for both building and services.

All this testing and checking is compiled into a document known as the Installation Qualification (or IQ). At the end of this stage, the building has been verified as constructed in accordance with the URS.

The project then progresses to the Operation Qualification (or OQ stage) where airflows, filtration, pressures, temperature and humidity levels are checked and documented with the manufacturing equipment installed. This equipment will also receive checks for compliance with the design requirements.  The facility is then ready to test the client’s manufacturing processes and the procedures they employ to carry them out.

The final stage is the Process Qualification (or PQ), when the installed manufacturing equipment is tested with multiple batches to ensure it can produce products of consistent quality to the accepted regulatory standard.

The final Validation Master Plan document, including all maintenance manuals incorporates all the data accumulated documenting the design and build as back-up information. This plan also provides all the information needed to run and maintain a facility. It remains a ‘live’ document recording any changes that are made.

Although the immediate project task is to satisfy the brief on the table, the client should always consider the future of their building. The pharmaceutical and biotechnology industry is fast moving, with new methods of processing evolving and developing often as a response to known risks.

If the facility is designed in an adaptable way it is more likely to meet regulatory demands in the future and can be more economically recycled improving its asset value. The usual life of a manufacturing area is approximately10 years before major refurbishment is needed.

No matter how small your business, ensuring you have the right facility, designed and built to the appropriate quality standards to manufacture your product requires experienced professionals. To achieve best value, make sure you choose the right team to help you deliver this. 

By Peter Rimmington. Peter is a director at Dewjoc Architects, one of only a few specialist practices in the world uniting expertise from the disciplines of architecture, engineering and pharmaceutical process design.