Design of the times

Designing pharmaceutical buildings is an exacting process and with well-defined procedures that anticipate how the facility will be used for its working life.

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

This, combined with financial pressures, means that pharmaceutical clients are increasingly looking for architects and engineers to make the design and build a faster and more responsive procedure.

Dewjoc has more than 24 years of experience designing such buildings and its design process is continuously evolving to meet industry needs. But testing and re-testing to ensure buildings meet the regulatory standards inevitably takes time.

Pharmaceutical buildings must be designed in accordance with current Good Manufacturing Practice (cGMP) guidelines, published in Europe by the EU and regulated in the UK by the MHRA. Where drugs are to be sold in the US, then the Code of Federal Regulations and the FDA are the relevant authorities.

Ensuring that a building conforms to the highest standards of cleanliness is a major factor in its design. To minimise the risk of contamination from micro-organisms the room finishes must have smooth, robust, easy-to-clean surfaces. Walls, ceiling and floors are designed with coved corners and flush doors, windows and light fittings to avoid dust traps.

Meeting the regulations involves many specialists, including architects, engineers, quality and process advisors and the end user, working together. Dewjoc’s pool of experts become this team and leave the client, once he has agreed the brief, to carry on his daily business.

The practice has extensive knowledge of laboratory design and the various manufacturing processes, enabling it to develop building layouts quickly to assess the efficiency of product and personnel movement, and their impact on lifecycle costs.

This knowledge is also vital in reviewing the economics of incorporating future flexibility in production and the need for expansion. Current trends are moving away from bespoke buildings to flexible shells, which require less time to design and build and give the client greater opportunity to change their mind.

Dewjoc is increasingly working for small biotech firms. Such clients often struggle to move forward from the initial development through scale-up to the manufacturing stage, due to a lack of experience in 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, so the design strategies of flexibility and expansion become important. The result is that although two companies may have a similar dosage form to manufacture, the design and construction of the facility may be achieved in very different ways, depending on expenditure and timescale.

Manufacturing steriles, topicals and tablets all require different equipment, which means differing regulatory requirements that in turn 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 and air conditioning requirements to satisfy cleanliness conditions and other engineering services are also developed. From this process detailed building layouts can be prepared.

If a toxic product is involved then the manufacturing equipment 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 Design Qualification document (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.

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.

The DQ establishes the what, why and how of the building design 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.

During the construction stage to satisfy the VMP, checks must be made to ensure the correct materials and specifications have been used for both building and services. This testing and checking is compiled into a document known as the Installation Qualification (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 (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 procedures.

The final stage is the Process Qualification (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.

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.