A few hoods, a lab bench, and an office may be a bright beginning for a start-up biotechnology firm. But as biotech entrepreneurs begin their journey, very few are aware of future space challenges and the way decisions made during early product development can jeopardize the growth of the firm.
Product development in the biotechnology industry takes much longer than in most other industries, and the facility needs will change as the product evolves through the five phases from idea to market: basic research; process development; pilot production; manufacturing; and fill and finish
Here are some guidelines that will help make decisions about the laboratory space needed to take a product from research to market.
Basic Research
These facilities are designed to expand scientific knowledge of biology, chemistry, physical processes, disease mechanisms, and drug actions. They must comply with established local and national safety, environmental and personal protection standards; current Good Laboratory Practices (cGLP) may be enforced. These practices may include wet and dry laboratory benches, specialized facilities, biological safety cabinets, fume hoods, and specialized research equipment.
• Typical space requirements range from 20,000 to 40,000 square feet.
• About 30 percent to 40 percent of the space will be for labs; another 15 percent to 30 percent will house lab support and administration; the remaining space will support supplemental functions.
• Several pieces of highly sensitive equipment are used during the early stages of research, including electron microscopes, sensitive micro-balances, and nuclear magnetic resonance machines that have special environmental requirements and are sensitive to vibrations.
• The facility will need a full slate of utilities that support critical experiments, including water, sewer, gas, and electrical.
Process Development
These laboratories use larger equipment to increase production compounds or cell cultures and to develop and test the production process. These facilities comply with cGLP to prevent cross contamination or the mix up of material flows. Development facilities may be used to produce materials for initial pre-clinical studies in the early stages of testing a product.
• The typical process development facility will require 10,000 to 20,000 square feet.
• About 30 percent to 45 percent will go toward laboratory space; 25 percent will be needed to house lab support and administration, with the remaining space for supplemental functions.
• These facilities have the same equipment and utilities needs as basic research facilities.
Pilot Production
These facilities need to use the same processes, equipment and ancillary systems that will be employed by the full-scale operation. Products from pilot facilities are used in human clinical trials and must comply with current Good Manufacturing Practices (cGMP) and meet validation requirements.
• Typical space requirements range from 10,000 to 35,000 square feet.
• The variables of open versus closed processing must be evaluated: Closed processing places emphasis on protecting the product inside the process and is the preferred method for most biotechnology firms. Open processing places more emphasis on the facility and its people.
• Pilot production facilities are heavily regulated. A typical facility will be comprised of 30 percent regulated production plant and processing suites, and another 15 percent to 30 percent housing labs for purposes such as quality control. A regulated warehouse will occupy approximately 10 percent of the facility.
• A single-story building is preferred, with clear height production area requirements to approximately 20 feet.
• Production plant and processing suites require clean room space, gowning rooms, and air locks. Clean-in-place equipment, autoclaves, and other sterilizers are ancillary to this process.
• This facility may have highly sensitive equipment, but not as stringent as an R&D lab facility.
• Utilities needed will vary but will include water, sewer, gas, steam, and electrical. Sewer discharge will require a kill system and pH pretreatment.
Manufacturing
Theses are commercial production facilities in which biological or chemical compounds are produced in quantities sufficient to meet market demands in the final stages of clinical testing or for approved products. They have strict validation requirements and must earn FDA approval.
• Typical space requirements range from 50,000 to 150,000 square feet.
• Typically, 30 percent to 45 percent of the space will go toward regulated production plant and processing suites with another 10 percent to 15 percent housing quality control labs, gowning rooms, and air locks. A regulated warehouse will occupy approximately 10 percent of the facility.
• The facility must be suited for the specific process or a multi-process; it can be single or multi-story.
• Redundancy of the process, support equipment and utilities is critical
• Production plant and processing suites require Class 100,000; 10,000; and 100 clean room environment spaces.
• This facility may have highly sensitive equipment in specialized suites.
• Utilities needs are the same as in a pilot production facility.
This is the final stage for preparing the product and putting it into a container for delivery to the public. The container is capped or sealed, labeled, and inspected under the rules and regulations of cGMP, meeting validation requirements. Design of these facilities includes suites for both controlled and critical areas meeting specified HVAC classifications considered essential to attain regulatory acceptance.
• Typical space requirements range from 25,000 to 150,000 square feet.
• The typical space will be comprised of 35 percent to 50 percent regulated manufacturing plant; with 10 percent to 15 percent housing quality control labs, gowning rooms, and air locks. A regulated warehouse will occupy approximately 15 percent to 20 percent of the facility.
• The facility is typically attached to manufacturing, but may be a separate building. A single story is preferred.
• Manufacturing production suites require Class 1000 and 100 clean room environment spaces.
• Utilities needs will be significantly less than for other process steps, but will include water, sewer, gas, steam, and electrical.
Because of the unique nature of the biotech industry, only the basic research facilities and process development facilities are easily transferable from one company to another. Once a firm enters pilot production, the facility, the process setup, and the utilities are quite exclusive to that company’s specific biotech process.
When a company begins the search for a new research facility, it will find plenty of laboratories being marketed as “plug and play.” But many of these existing facilities do not meet the criteria and standards set under GLP by the Food and Drug Administration and may lead to experiment contamination. Renovating an existing process suite, meanwhile, often generates higher costs, requires a longer timeline, and creates more unexpected problems than simply building a new, customized suite.
Understanding the value of sharing knowledge and experience with growing companies, the Massachusetts Biotechnology Council spearheaded an effort by a group of its members and representatives of MassDevelopment and the Boston-area chapter of the International Society of Pharmaceutical Engineers to develop a reference guide to assist entrepreneurs and community leaders with the basics of biotechnology facility development. The publication is currently in final review and will be introduced in the coming months. It identifies important issues to keep in mind when reviewing potential properties:
• Avoid porous materials in lab areas, including wood cabinetry, because they harbor bacteria, chemicals and solutions that may harm your experiment.
• Understand the air supply/exhaust systems, how often they are maintained, and how often the filters are replaced. An owner with a scheduled maintenance plan and procedure in place will be important to the upkeep of your experiments.
• Find out whether your proposed space is zoned separately or has its own independent unit for HVAC and water, or if your space is sharing systems with the adjacent tenant. Shared systems can be a negative because of the risk of cross-contamination.
• Determine the source for lab water and gas supplies. Ask about capacity and whether supplies are shared with other tenants. Extreme requirements of another tenant could deplete supplies and leave you with less than you need for your work.
• Find out what organics and chemicals the last tenant used and how the facility was decommissioned when the last tenant left the premises.
• Look at the space with an eye towards the future. Is there laboratory expansion potential? Is the adjacent space viable?
The guide will offer a more in-depth view of the facility systems, utilities, and environmental and zoning issues that are key to biotechnology manufacturing development. But, it is only a guide — every product is unique and therefore can benefit from professional consulting services from the design, construction, and industrial engineering industries.
Gain a complete understanding of the 10- to 15-year multi-phased process your company will experience from initial research to shippable product before you commit to real estate. It’s a worthwhile exercise. You may be able to focus your spending on research and product development instead of sinking money into unnecessary facility options that a former tenant or owner felt were important.
