 Changes and challenges are on the horizon for innovative pharmaceutical companies. Do short-term savings mean long-term troubles?Settlement of patent litigation on pharmaceutical inventions, especially so-called “pay-for-delay” settlements, have attracted significant attention recently.Pay-for-delay, a controversial business practice, involves two drug companies—an innovative pharmaceutical company (a brand company in the “pay-for-delay” context) and a generic company. The brand company pays the generic company not to challenge the patent that covers the brand company’s drug, to stay out of the market, and to settle litigation brought under the Hatch-Waxman Act. Some interest groups claim that banning pay-for-delay will reduce prescription drug prices and speed the entry of generics onto the market. Others argue that not allowing these types of settlements could harm innovation and hinder the development of new drug products. The Supreme CourtChallengers to pay-for-delay settlements have sought recourse in the Supreme Court. Louisiana Wholesale Drug Co. Inc. v. Bayer AG, No. 10-762, is the latest in a string of lawsuits challenging “pay-for-delay” settlement, but the Supreme Court declined to hear the case March 7.The facts are simple. The antibiotic ciprofloxacin (Cipro) is one of Bayer’s best-selling drugs. Barr Laboratories submitted an Abbreviated New Drug Application (ANDA) to the U.S. Food and Drug Administration (FDA). To satisfy the ANDA requirements, Barr certified that the Cipro patent was invalid or would not be infringed by Barr’s making, using, or selling a generic version of Cipro. Bayer sued Barr. Two weeks before the trial in 1997, Bayer settled with Barr. In exchange for Barr’s promise to stay out of all but the last six months of the remaining patent term, Bayer agreed to pay $398 million. Louisiana Wholesale Drug Co., along with three other drug wholesalers, sued Bayer and Barr for violating the antitrust law. The district court found for Bayer on the ground that the antitrust law is not violated as long as the patent was not procured by fraud or the patent suit was not a sham. The appellate court twice affirmed the district court’s ruling, and Louisiana Wholesale Drug Co. petitioned the Supreme Court for a further review, which the court declined. Undeterred by the Supreme Court’s refusal, challengers to pay-for-delay agreements have sought recourse from Congress. On Jan. 25, Congress reintroduced a bill to “prohibit brand name drug companies from compensating generic drug companies to delay the entry of a generic drug into the market.” This bill, if passed, creates a rebuttable presumption that any pay-for-delay agreement is anticompetitive and, thus, unlawful if the generic company receives anything of value and agrees to limit or forego research, development, manufacturing, marketing, or sales of the generic drug for any period of time. In order to rebut this presumption, the parties to the agreement must demonstrate by clear and convincing evidence—a fairly high burden of proof—that the precompetitive benefits of the agreement outweigh the anticompetitive effects. In addition, this bill also gives the Federal Trade Commission (FTC) the authority to enforce this bill and to fine the “pay-for-delay” parties up to three times the value received by the brand company or the value given to the generic company reasonably attributable to the violation. If enacted, this legislation would significantly hinder companies’ ability to settle pharmaceutical patent litigation.  While the FTC treats any pay-for-delay agreements as anticompetitive, the Cipro court held that they do not violate the antitrust law as long as the anticompetitive effects are within the exclusionary power of the patent that covers the drug. Pay-for-delay settlements raise difficult questions that require balancing competing policy issues. On one hand, patents are critical for the pharmaceutical industry to invest in new drug discovery and development, and on the other, the cost of new drugs presents significant economic challenges to individuals, insurance companies, and the government. As a result, various industry organizations, political groups, and government groups take diametrically opposite positions. While the FTC treats any pay-for-delay agreements as anticompetitive, the Cipro court held that they do not violate the antitrust law as long as the anticompetitive effects are within the exclusionary power of the patent that covers the drug. Battle Lines DrawnHowever, the exclusionary power of pharmaceutical patents is particularly important to encourage innovative pharmaceutical companies to invest in drug discovery and development. The process of finding, developing, and obtaining marketing approval for a drug is lengthy, costly, and unpredictable. Recent studies show that it takes an average of 10 to 15 years and approximately $1.3 billion for a pharmaceutical company to develop a new drug, partially because of the low success rate in this industry. Only one out of 5,000 compounds tested is eventually approved by the FDA. In 2007, pharmaceutical companies invested about $60 billion in research and development. In addition, only about 20% to 30% of these approved drugs recoup their initial investment.Considering both of the laws that encourage innovation and competition, the Cipro court affirmed the lower court’s decision that the pay-for-delay practice should not be banned outright, stating: “Unless and until the patent is shown to have been procured by fraud, or a suit for its enforcement is shown to be objectively baseless, there is no injury to the market cognizable under existing antitrust law, as long as competition is restrained only within the scope of the patent.” In contrast, one primary reason asserted for banning pay-for-delay settlements is that they give pharmaceutical patents more exclusionary power than they should have. In order for a brand company to exclude a generic company from selling a generic version of the brand drug, the brand company must prove that the patent covering the drug is valid and will be infringed by the generic’s ANDA filing. While acknowledging that an agreement is within the exclusionary power of a patent if it is based on the patent being found valid and infringed, some have argued that a similar agreement is not justified if the validity or infringement of the patent is untested in litigation. Opponents of pay-for-delay argue that litigation is a more appropriate vehicle to resolve whether the patent is valid and infringed than a pay-for-delay agreement, where a generic company simply concedes the validity and infringement. Further, some argue that the generic company’s concession of the validity and infringement of the innovation patent is not justified by the “extremely poor” quality of patents in the U.S. A University of Houston Law School study showed that approximately 45% of all patents reviewed by courts in 2009 were found to have been undeserved. In addition, when challenged in the United States Patent and Trademark Office, 95% of patents have their claims canceled or changed. More importantly, studies show that 70% to 73% of fully litigated pharmaceutical patents were found either invalid or not infringed. Thus, allowing generic companies to simply concede the validity and infringement of pharmaceutical patents in “pay-for-delay” agreements would likely give these patents more exclusionary power than they truly deserve. Studies show that 70% to 73% of fully litigated pharmaceutical patents were found either invalid or not infringed. Allowing generic companies to concede the validity and infringement of pharmaceutical patents would likely give these patents more exclusionary power than they deserve. Opponents cite the ever-rising cost of prescription drugs as another important policy reason for banning the pay-for-delay practice. A generic drug costs substantially less than the corresponding brand drug, with discounts off the brand prices sometimes exceeding 90%.However, for a generic drug to enter into the market, the generic company must survive a near certain Hatch-Waxman litigation. Facing the high cost and the uncertainty of the outcome of the litigation, both the brand company and its generic counterpart have the incentive to settle out of court. As part of the settlement, the brand company usually pays the generic company and, in exchange, the generic company agrees not to enter into the market for a certain period of time. The proposed legislation argues that the Hatch-Waxman Act has been “subverted” by these settlement agreements, delaying the marketing of lower-cost generic drugs and benefiting both brand and generic manufacturers at the expense of consumers. The lost benefits for consumers are estimated to be between $3.5 billion and $14 billion annually. Banning the pay-for-delay practice has a broad appeal among many constituencies. Proponents include drug wholesalers, attorney generals of 34 states, law professors, and advocacy groups, including Consumer Federation of America, the Prescription Access Litigation Project, the National Legislative Association on Prescription Drug Prices, U.S. PIRG (the Federation of State Public Interest Research Groups), the American Association of Retired Persons, the American Antitrust Institute, National Association of Chain Drug Stores Inc., and the Public Patent Foundation. Banning the pay-for-delay practice may be shortsighted, however. While consumers would enjoy the added availability and low prices of generic drugs in the short term, they might have to suffer from lack of new drugs and therapies in the long run as the U.S. pharmaceutical industry loses its competitive edge. Dr. Ian Liu is an associate attorney with Finnegan, Henderson, Farabow, Garrett & Dunner, LLP. He has a diverse practice that includes patent litigation, alternative dispute resolution, patent preparation and prosecution, and patent counseling. He is active in the Hatch-Waxman Abbreviated New Drug Application litigations and international arbitrations. He has an extensive technical background and worked as a research scientist in process development for drug substances in clinical trials. Rebecca M. McNeill is counsel with Finnegan, Henderson, Farabow, Garrett & Dunner. Her practice focuses on client counseling and patent prosecution for biotechnology clients. She has worked with biotech start-ups, research foundations, and larger, established pharmaceutical companies, and has considerable experience managing patent portfolios. Editor’s Choice
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Thursday, July 14, 2011
INNOVATIVE PHARMA - Policy | The Pay-for-Delay Dilemma
Break the Stratum Corneum Barrier
By Maybelle Cowan-Lincoln
Enhance transdermal drug delivery through physical means
The market for products that use transdermal drug delivery (TDD) is exploding. In 2009, sales grew to $5.6 billion, and this growth is expected to continue for the foreseeable future.1-2This attractive technology already exists for a wide range of disease areas, including postmenopausal osteoporosis, angina, pain, Parkinson’s, and dementia. But products are in development for the treatment of a host of other disorders such as glaucoma, hypertension, attention deficit hyperactivity disorder, and central nervous system disorders, to name just a few.3
The growth of TDD systems is easy to understand given the advantages they offer over other delivery systems:
- Painless application;4
- Ease of use;
- Increased patient compliance;
- Avoidance of first-pass metabolism;
- Controlled release of drug; and
- Ability to maintain steadier plasma levels, often decreasing side effects by reducing peak plasma levels.
These challenges notwithstanding, TDD systems offer the opportunity for highly effective drug delivery. Transdermally delivered drugs cross the epidermis via one of three pathways: through the hair follicles and their sebaceous glands, through the sweat ducts, or across the stratum corneum.5 Once the barrier of the stratum corneum has been breached, the drug can enter the layer just below it—the dermis. This skin layer houses capillaries that transport approximately one-third of the blood supply throughout the body. When a drug reaches this system of capillaries, it can be absorbed into the bloodstream through passive diffusion.
The Problem with Peptides
Transdermal penetration is difficult for certain compounds, such as drugs with high molecular weight. Peptides, macromolecular drugs responsible for major biological reactions and processes, are too cumbersome for most existing TDD systems. More and more peptides are on the market to treat cardiovascular conditions, immunity, diabetes, and viral infections.6Delivering these cutting-edge drugs presents a significant challenge. The oral route is unacceptable. Peptides are degraded by the gastrointestinal enzymes and may display poor bioavailability because the intestinal mucosa is impermeable to their high molecular weight and hydrophilicity. The parenteral route is the current delivery system of choice, but there are drawbacks for this method: invasiveness, patient inconvenience, and systemic side effects. Given the challenges presented by the oral and parenteral routes, an effective TDD system for peptide drug delivery is certainly desirable.
Chemical penetration enhancers (CPEs) have been extensively researched as possible solutions to the peptide penetration challenge. These additives decrease the barrier function of the skin through stratum corneum lipid fluidization. Although some success has been demonstrated in the lab, the usefulness of CPEs is limited by the irritation they often cause; the more potent the CPE, the greater the irritation.7
continues below...
Case study
Intradermal Injection in the Developing World
eedle-free injection devices may well be the holy grail of TDD enhancement systems for vaccination delivery. The high presence of dendritic cells in the epidermis can help elicit a heightened immune response, significantly higher than that obtained after intramuscular injection.1-2This increased efficiency offers the potential to make vaccinations in developing countries substantially more affordable, more available, and safer. For some vaccines, intradermal (ID) delivery can fully immunize a person against a disease while using up to 80% less vaccine. The reduced dosage can cut costs and increase availability, allowing more children to be vaccinated.3
But accurate ID delivery is hard to guarantee. Needle-free technologies are a boon to the developing world, offering the advantages of targeted delivery while reducing the risks of needle reuse and needlestick injuries.
Several recent clinical trials have supported the benefits of needle-free injections. In a 2007 study in Oman approved by the World Health Organization (WHO), 373 infants received either a full dose intramuscular polio vaccine at 2, 4, and 6 months, or a fractional dose of the vaccine intradermally using the Biojector 2000 (Bioject Medical Technologies, Ore.) on the same schedule. Thirty days after completing the three-dose protocol, the rates of seroconversion were tested. The rates of seroconversion in the fractional, intradermally delivered group were similar to those in the full dose, intramuscularly delivered group.4
Fractional dose polio vaccines could transform health care in developing countries by controlling costs and stretching the vaccine supply. The savings are significant: The cost of the fractional dose polio vaccine would be about $3 per infant versus $9 per infant for the full dose.
Research continues to evaluate the safety and efficacy of similar needle-free vaccine delivery devices. A study completed in May 2010 in the Dominican Republic assessed the rates of seroconversion one month after trivalent inactivated influenza vaccination using the Biojector 2000. Results of the study, sponsored by the Centers for Disease Control and Prevention in collaboration with WHO, the Pan American Health Organization, and the Program for Appropriate Technology in Health, have not been published.5
Additional means to further enhance the efficacy of ID injections are being studied, including coating DNA nanoparticles in the vaccine to enhance the immune response. The success of these trials encourages further investigation into the benefits of this technology.
References
- Cui Z, Baizer L, Mumper RJ. Intradermal immunization with novel plasmid-DNA-coated nanoparticles via a needle-free injection device. J Biotechnol. 2003;102(2):105-115.
- Cui Z, Mumper RJ. Topical immunization using nanoengineered genetic vaccines. J Control Release. 2002;81(1-2):173-184.
- Medical Technology Business Europe. Bioject to provide needle-free injector for Global Polio Eradication Initiative study. MTB Europe website. February 22, 2011. Available at: http://www.mtbeurope.info/news/2011/1102056.htm. Accessed June 5, 2011.
- Mohammed AJ, AlAwaidy S, Bawikar S, et al. Fractional doses of inactivated poliovirus vaccine in Oman. N Engl J Med. 2010;362(25):2351-2359.
- U.S. National Institutes of Health. Needle-free jet injection of reduced-dose, intradermal, influenza vaccine in >=6 to <24-month-old children. ClinicalTrials.gov website. Available at: www.clinicaltrials.gov/ct2/show/NCT00386542. Accessed June 5, 2011.
Microneedles
Because CPEs are not the ideal solution, physical methods to increase transdermal delivery of peptides and higher molecular weight drugs are being developed. One option is the microneedle. These sharp projections pierce the skin, extending down for less than 1 mm, the level at which blood vessels and nerves typically reside. Because of the shallowness of their penetration, microneedles do not cause bleeding or pain.There are four models of microneedles:
- Piercing array of microneedles followed by the application of a drug patch to the site;
- Microneedles coated with the drug;
- Biodegradable polymeric needles that encapsulate a drug and release it in a controlled dose over time; and
- Hollow microneedles.
A primary concern with microneedles is the possibility that they may break off in the skin. The evidence suggests that this is unlikely. Since the introduction of the technology, minimal breakage has been recorded with correctly inserted silicon microneedles.
Metal microneedles
are even stronger. A safe alternative to both these materials is microneedles made from biodegradable polymers. Because microneedles provide enhanced delivery in a painless and convenient format, it is likely this system will appear in future TDD products.
An array of biodegradable polyethylene glycol-based microneedles with antimicrobial properties.
Encapsulation
Encapsulation is a process by which peptide drugs are entrapped in a particle-delivery system such as liposomes. These phospholipid-based vesicles deliver compounds to superficial skin layers. Extensive research has also demonstrated that they can achieve higher tissue concentrations of drugs like γ-interferon.Liposomes have their limitations, however. They are most effective for local skin delivery. Liposomes create a drug reservoir in the upper layer of the stratum corneum. If a compound needs to enter systemic circulation, ethosomes are more effective.8
Ethosomes are soft, phospholipid-based vesicles formulated with a high concentration of ethanol. The ethanol makes the ethosome a uniquely efficient transdermal drug transporter. Ethanol affects both the skin and the structure of the vesicle. In the skin, it increases permeability by disrupting the lipid bilayer of the stratum corneum. Concurrently, the ethanol concentration causes the lipid membrane to be more malleable than conventional vesicles but just as stable. This increased flexibility allows the ethosome to squeeze through smaller openings in the stratum corneum, namely the ones created when the skin came into contact with the ethanol in the ethosome. This efficient transport system has been demonstrated to be effective with macromolecules such as peptides, making ethosomes a promising candidate for future TDD products.
Electricity
Another exciting approach to TDD is the use of physical energy. Iontophoresis uses small voltage constant current to actively transport a charged medication within an electric field. This method works on several levels. Electrodes are placed on the skin in an area coated with a solute containing drug molecules with the same charge. The like charge repels the drug molecules into the skin. Simultaneously, the applied current promotes electroosmosis, the convective flow of water molecules. Also, the current itself may temporarily increase skin permeability.9
Coated microneedles are useful for bolus drug delivery. Hollow microneedles can deliver a larger dose of drug in a single application or can be used for prolonged infusion.
Another variable that influences transdermal delivery is the chemical properties of the drug itself. At present, the most successful transdermal delivery has occurred with lipophilic, positively charged drugs with low molecular weight. However, research has demonstrated that iontophoresis can effectively deliver a number of peptides, including luteinizing hormone-releasing hormone, cyclosporin, calcitonin, and insulin. To date, iontophoresis has not achieved the delivery of therapeutic levels of these compounds in humans.
In general, iontophoresis has been shown to be well tolerated by the skin. Adverse reactions were minor and included mild sensations from the current flow and erythema in the skin in contact with the electrodes, which was generally resolved within 24 hours.
Electroporation involves a different use of electricity. Unlike iontophoresis, electroporation uses short pulses of high voltage to increase skin permeability. These short bursts cause small, short-lived aqueous pores to appear in the stratum corneum lipid bilayers. During electrical pulses, the drug is driven into the skin. The increased permeability of the stratum corneum persists for several hours after treatment, allowing for continued transdermal delivery. This method has been shown to enhance peptide penetration substantially more than iontophoresis.10
To increase drug delivery during electroporation, a number of variables can be adjusted. Electrical charge, lipophilicity, and molecular weight affect transport. Increasing the charge of the permeant can enhance delivery. Also, the lower the molecular weight of the drug, the higher its transport. In addition, although it is less efficient, electroporation can be used for macromolecule delivery as well as for small and moderate molecular weight compounds, making it an attractive technology to pursue for future TDD systems.
Electroporation uses short pulses of high voltage to increase skin permeability. These short bursts cause small, short-lived aqueous pores to appear in the stratum corneum lipid bilayers. During electrical pulses, the drug is driven into the skin.
Additional Methods
A number of other TDD systems are being researched to facilitate medication delivery, particularly technologies that can be used with macromolecules.- Ultrasound is an effective physical TDD enhancement technique, proved efficient for the enhanced delivery of several peptides and proteins, including insulin, erythropoietin, and heparin. Interestingly, low frequency ultrasound (20 KHZ – 100 KHZ) has been shown to increase skin permeability more than high frequency ultrasound (1 MHZ – 16 MHZ). The mechanism by which this occurs is not fully understood, but it is hypothesized that the ultrasound waves disrupt lipids in the stratum corneum. This disruption allows the drug, housed in a coupling agent like gel, cream, or ointment, to pass through the skin.
- Several needle-free injection technologies use velocity to cross the stratum corneum. These jet-propelled devices can deliver a variety of medications, from human growth hormone to insulin in liquid and particle form, and achieve a bioavailability equivalent to conventional injections. But a particularly exciting use of needle-free injections is vaccine delivery. Compressed helium delivers vaccinations in the form of particles at velocities of up to 800 m/s. The benefit of this form of vaccine is that in the epidermis, particles can stimulate higher immune response than intradermal or intramuscular injection.
- Heat can enhance skin penetrability by increasing microcirculation and blood vessel permeability. One new TDD technology that employs heat is the controlled heat-aided drug delivery (CHADD) system. A small heating unit powered by oxidation upon exposure to air is placed over a medication patch to facilitate more effective delivery.
- Physically removing or disrupting the stratum corneum can increase transdermal penetration. Microscissuining abrades the skin by creating microchannels in the outer layer using microscopic metal granules. Laser ablation has been demonstrated to enhance the delivery of both lipophilic and hydrophilic compounds, but long-term safety and reversibility need to be assessed, particularly at the intensities necessary for higher molecular weight drugs.
References
- Salisonline. Advances in the transdermal drug delivery market: market size, leading players, therapeutic focus and innovative technologies. March 11, 2011. Available at: www.salisonline.org/market-research/ advances-in-the-transdermal-drug-delivery-market-market-size-leading-players-therapeutic-focus-and-innovative-technologies. Accessed June 6, 2011.
- Kumar R, Philip A. Modified transdermal technologies: breaking the barriers of drug permeation via the skin. Trop J Pharm Res. 2007;6(1):633-644.
- Mathias NR, Hussain MA. Non-invasive systemic drug delivery: developability considerations for alternate routes of administration. J Pharm Sci. 2010;99(1):1-20.
- Gill HS, Prausnitz MR. Coated microneedles for transdermal delivery. J Control Release. 2007;117(2):227-237.
- Benson HA, Namjoshi S. Proteins and peptides: strategies for delivery to and across the skin. J Pharm Sci. 2008;97(9):3591-3610.
- Mao S, Cun D, Kawashima Y. Novel non-injectible formulation approaches of peptides and proteins. In: Jorgensen L, Nielsen HM, eds. Delivery Technologies for Biopharmaceuticals: Peptides, Proteins, Nucleic Acids and Vaccines. West Sussex, U.K.: John Wiley & Sons, Ltd.; 2009:29-67.
- Karande P, Jain A, Ergun K, et al. Design principles of chemical penetration enhancers for transdermal drug delivery. Proc Natl Acad Sci U S A. 2005;102(13): 4688-4693.
- Anitha P, Ramkanth S, Sankari KU, et al. Ethosomes: a noninvasive vesicular carrier for transdermal drug delivery. Int J Rev Life Sci. 2011;1(1):17-24.
- Power I. Fentanyl HCl iontophoretic transdermal system (ITS): clinical application of iontophoric technology in the management of acute postoperative pain. Br J Anaesth. 2007;98(1):4-11.
- Denet AR, Vanbever R, Préat V. Skin electroporation for transdermal and topical delivery. Adv Drug Deliv Rev. 2004;56(5):659-674.
Tuesday, June 28, 2011
Some Traditional and Non-Traditional Cleanroom Uses and Related Contamination Control Practices
Products and processes in many high-tech industries may be severely compromised by airborne particles, dust, chemical vapors, electrostatic discharge, and other contaminants. Industries such as semiconductor manufacturing, pharmaceutical processing, and biotechnology research typically use cleanrooms to control these contaminants as well as temperature and humidity.
ISO 14644, the cleanroom standard series issued by the International Organization for Standardization (ISO), defines a cleanroom as “a room in which the concentration of airborne particles is controlled, and which is constructed and used in a manner to minimize the introduction, generation, and retention of particles inside the room and in which other relevant parameters, e.g. temperature, humidity, and pressure, are controlled as necessary.” This standard provides a method for classifying cleanrooms based on a specified number and size of particles per cubic meter of air. High efficiency particulate air (HEPA) and ultra low particulate air (ULPA) filtration is used to remove airborne contaminants.
Personnel and the activities they perform are a primary source of contamination. The human operator has been characterized as a broad-spectrum particle generator enclosed by inefficient mechanical filters that may also generate and release chemical and biological aerosols to the environment together with potentially destructive electric charges (ESD). To minimize such contamination, cleanroom personnel wear protective apparel such as face masks, gloves, boots, and coveralls, which they put on in a controlled gowning area.
Example Contaminants from Operator
Microelectronics (semiconductor/integrated circuits)
Microcircuits well below the sub-micron level are sensitive to a variety of contaminants, including particles and trace metal impurities (Na, K, Ca, Fe, Ni, Cr, Cu, and Zn). These contaminants cause detrimental device degradation, reliability problems, and manufacturing yield losses. For example a particle as small as 0.5 micrometers can severely impede the coating adhesion on a wafer or chip. To improve yields and lessen production defects, manufacturers put precision instrumentation such as etching and doping devices within a controlled environment such as a cleanroom. In addition to air filtration, the cleanroom must have vibration protection and temperature/humidity control to minimize static electricity.
Food
Food-borne illnesses and microbial contamination, especially pathogenic organisms, are a growing concern worldwide. The major focus of contamination control in the food industry is prevention of cross contamination between ready-to-eat products and raw materials. Food processors are concerned with the spread of bacteria, yeasts, and mold that grow in the moist conditions of processing areas and are carried by air currents throughout the food plant. Meat processing typically takes place in HEPA filtered cleanrooms or “positive pressure” rooms vs. the cold stagnant and contaminated air supplied by refrigeration systems. Cleanrooms allow the use of preservatives to be reduced or eliminated.
Hospitals/Healthcare
Unlike the tightly monitored pharmaceutical industry, in the United States, there is no federal agency responsible for monitoring hospital construction or operation. This function is usually handled at the state level. For example, in California hospital construction comes under the jurisdiction of the Office of Statewide Health Planning and Development (OSHPD). Licensing involves everything from contamination control to emergency procedures, to visitor management.
Tissue Engineering
A branch of biotechnology, this discipline involves growing living tissue, which is very susceptible to contamination. The use of single transit Class M5.5/10,000/ISO-7 cleanrooms with work done in Class M3.5/100/ISO-5 hoods; full multi-level gowning (protocols and apparel) are a must when there is a great concern about non-viable particulate contamination. Viable contamination is certainly also important—genetic engineering (“bacterial farming”).
Cosmetics
Per the U.S. Food, Drug, and Cosmetic Act of 1938 as amended (FD&C), cosmetics should not be “adulterated or misbranded” and remain in an uncontaminated condition when used by the consumer (unlike drugs, there is no pre-clearance requirement). Cosmetics are not manufactured in cleanrooms but are tested for microbials in a clean area under aseptic conditions. The industry is self-regulated i.e., testing of raw materials, microbiological controls, air handling, and the many things that go into GMP’s are established voluntarily through industry trade associations.
Automotive
The application of coatings and paint is subject to two types of contamination: process-related and environmental or human-sourced. Process-related contamination results from the paint, paint distribution system (robotics and spray equipment), airflow, and filtration. The need to control process-related contamination affects facility and booth design, airflow, filtration, humidification, robotics and spray equipment, paint delivery and atomization rates, paint filtration, water systems, and assembly processes. Environmental and human-sourced contaminants, such as personal hygiene products, machine lubricants, packaging materials, and fibers, can account for more than 25% of paint-related defects. Crater-causing contaminants limit paint from adhering to a surface. Particulate contamination under or on a painted surface can produce blemishes ranging from small visual detractors to corrosion-related defects.
The ISO 14644 Series, Cleanrooms and associated controlled environments, is used worldwide to establish the design and operation of cleanrooms. In addition, the Institute of Environmental Sciences and Technology (IEST,has published Standards, Recommended Practices, and Handbooks to assist users in designing, operating, and maintaining cleanrooms and other controlled environments at specification levels.
ISO 14644, the cleanroom standard series issued by the International Organization for Standardization (ISO), defines a cleanroom as “a room in which the concentration of airborne particles is controlled, and which is constructed and used in a manner to minimize the introduction, generation, and retention of particles inside the room and in which other relevant parameters, e.g. temperature, humidity, and pressure, are controlled as necessary.” This standard provides a method for classifying cleanrooms based on a specified number and size of particles per cubic meter of air. High efficiency particulate air (HEPA) and ultra low particulate air (ULPA) filtration is used to remove airborne contaminants.
Personnel and the activities they perform are a primary source of contamination. The human operator has been characterized as a broad-spectrum particle generator enclosed by inefficient mechanical filters that may also generate and release chemical and biological aerosols to the environment together with potentially destructive electric charges (ESD). To minimize such contamination, cleanroom personnel wear protective apparel such as face masks, gloves, boots, and coveralls, which they put on in a controlled gowning area.
Example Contaminants from Operator
- Particulate: Skin Flakes, Hair, Eyelashes, Cosmetics, and Tobacco Smoke.
- Chemical/Organic Matter: Na, Mg, Al, Si, P, S, Cl, K, Ca, Fe - Cosmetics (Bi, Ba, Ti) - Oils - Nasal Effluvia (rich in Na and K) - Oral Effluvia (rich in K and Cl).
- Biological: Bacteria, Viruses, and Pyrogens.
- ESD: 20 to 40,000 volts.
- Particulate: Silica Dust
- Fibers: Cellulose
- Chemicals: Varies
- Biological: Bacteria
Microelectronics (semiconductor/integrated circuits)
Microcircuits well below the sub-micron level are sensitive to a variety of contaminants, including particles and trace metal impurities (Na, K, Ca, Fe, Ni, Cr, Cu, and Zn). These contaminants cause detrimental device degradation, reliability problems, and manufacturing yield losses. For example a particle as small as 0.5 micrometers can severely impede the coating adhesion on a wafer or chip. To improve yields and lessen production defects, manufacturers put precision instrumentation such as etching and doping devices within a controlled environment such as a cleanroom. In addition to air filtration, the cleanroom must have vibration protection and temperature/humidity control to minimize static electricity.
Food
Food-borne illnesses and microbial contamination, especially pathogenic organisms, are a growing concern worldwide. The major focus of contamination control in the food industry is prevention of cross contamination between ready-to-eat products and raw materials. Food processors are concerned with the spread of bacteria, yeasts, and mold that grow in the moist conditions of processing areas and are carried by air currents throughout the food plant. Meat processing typically takes place in HEPA filtered cleanrooms or “positive pressure” rooms vs. the cold stagnant and contaminated air supplied by refrigeration systems. Cleanrooms allow the use of preservatives to be reduced or eliminated.
Hospitals/Healthcare
Unlike the tightly monitored pharmaceutical industry, in the United States, there is no federal agency responsible for monitoring hospital construction or operation. This function is usually handled at the state level. For example, in California hospital construction comes under the jurisdiction of the Office of Statewide Health Planning and Development (OSHPD). Licensing involves everything from contamination control to emergency procedures, to visitor management.
Tissue Engineering
A branch of biotechnology, this discipline involves growing living tissue, which is very susceptible to contamination. The use of single transit Class M5.5/10,000/ISO-7 cleanrooms with work done in Class M3.5/100/ISO-5 hoods; full multi-level gowning (protocols and apparel) are a must when there is a great concern about non-viable particulate contamination. Viable contamination is certainly also important—genetic engineering (“bacterial farming”).
Cosmetics
Per the U.S. Food, Drug, and Cosmetic Act of 1938 as amended (FD&C), cosmetics should not be “adulterated or misbranded” and remain in an uncontaminated condition when used by the consumer (unlike drugs, there is no pre-clearance requirement). Cosmetics are not manufactured in cleanrooms but are tested for microbials in a clean area under aseptic conditions. The industry is self-regulated i.e., testing of raw materials, microbiological controls, air handling, and the many things that go into GMP’s are established voluntarily through industry trade associations.
Automotive
The application of coatings and paint is subject to two types of contamination: process-related and environmental or human-sourced. Process-related contamination results from the paint, paint distribution system (robotics and spray equipment), airflow, and filtration. The need to control process-related contamination affects facility and booth design, airflow, filtration, humidification, robotics and spray equipment, paint delivery and atomization rates, paint filtration, water systems, and assembly processes. Environmental and human-sourced contaminants, such as personal hygiene products, machine lubricants, packaging materials, and fibers, can account for more than 25% of paint-related defects. Crater-causing contaminants limit paint from adhering to a surface. Particulate contamination under or on a painted surface can produce blemishes ranging from small visual detractors to corrosion-related defects.
The ISO 14644 Series, Cleanrooms and associated controlled environments, is used worldwide to establish the design and operation of cleanrooms. In addition, the Institute of Environmental Sciences and Technology (IEST,has published Standards, Recommended Practices, and Handbooks to assist users in designing, operating, and maintaining cleanrooms and other controlled environments at specification levels.
Modular Softwall Cleanrooms
Simple, Mobile, and Cost Effective
Softwall modular cleanrooms are designed for functionality and reduced cost while providing all the flexible benefits of modular construction. They are tent-like, lightweight, easy-to-assemble structures, which can be installed free standing or suspended from the ceiling of an existing building. Unlike their fixed-wall counterparts, softwall cleanrooms are generally smaller, portable, and can fit into tight spaces. The portable design enables the cleanroom units to be easily moved to another location or disassembled and stored. Because of their relative low cost, softwall cleanrooms are ideal for small or startup businesses, or manufacturers looking for a quick, easy way to expand their cleanroom operations.
The cleanrooms are available in a variety of sizes and classifications, with options to match a customer’s specific needs. From standard 4 feet by 4 feet units, to sizes as large as 24 feet by 36 feet. Larger, custom sizes can be designed and built to meet customer requirements. Because of their modular design, rooms can be expanded or reduced in size without taking the entire cleanroom down, making it easy to add or remove sections. Softwall rooms are also available in a variety of cleanroom classifications, but most commonly in Class 100,000 to Class 10 (ISO 8 to ISO 4) designs.
A wide variety of industries use softwall cleanrooms, from medical device manufacturers to makers of rolled films. This design is also popular in microelectronics and semiconductor manufacturing, as well as electronics repair industries where contaminants cannot be allowed into sensitive areas of electronic devices.
The basic building block of the softwall cleanroom’s modular design is a sectioned ceiling framework made up of tubular steel beams with T-bar cross members. This interlocking ceiling grid system enables easy assembly and cleanroom expansion. The ceiling is supported by tubular steel legs at each of the four corners and reinforced with heavy gauge, triangular steel gussets. Powered HEPA filter units, lighting systems, and ceiling panels are sealed to the grid using gaskets, providing a zero-leak cleanroom.
Interior height of the ceiling framework is commonly 8, 9, or 10 feet, although various heights are available depending on the customer application. Standard filter unit height is 14 inches, with a two-inch minimum space required between the filter unit and facility ceiling. The common structure height enables the modular softwall cleanroom to easily fit within an existing building.
Softwall cleanrooms, without a center support, have a maximum size of 12 feet by 12 feet with a leg on each corner. Larger rooms can be constructed, but additional support posts within the structure are required. For example, a room 16 feet by 20 feet would have one center post or a room 20 feet by 32 feet would have three center posts. Other options are available for clear spans without center legs. For example, ceiling-suspended softwall cleanrooms eliminate the need for all support legs and columns. This configuration allows the cleanroom to easily accommodate equipment layout and maximizes floor space utilization.
The walls of most standard softwall modular cleanrooms are made of 20 or 40 mil clear vinyl and are fire retardant with an anti-static additive. Cleanroom-grade softwalls with low outgassing and static-dissipative vinyl are an available option. Entering or exiting most softwall cleanrooms is by way of vinyl strip doorways. The strip door commonly consists of eight-inch-wide, 80 mil thick strips with a two-inch overlap on each side along the length. Entering a cleanroom requires only to push apart the strips, which automatically reseal as they come back together. The strip doors are pre-assembled and are easily mounted to the ceiling structure. Swinging doors in metal frames are an available option when acrylic or Lexan walls are used.
The controlled level of contamination will vary depending on quantity and configuration of filters. For example, the ceiling structure of a Class 10,000 (ISO 7) cleanroom will have a combination of powered HEPA filters, lights, and blank panels. In contrast, Class 10 (ISO 4) cleanrooms require 100% ceiling coverage with powered filters in all ceiling grid sections.
When ceiling space for lighting is limited due to filter requirements, flow-thru lights can be used. These are similar to standard cleanroom lights with the exception that a motorized ceiling HEPA filter unit is mounted directly on top of the light. This fixture is designed with open areas so filtered air is able to flow through the light fixture down into the cleanroom. Flow-thru lights are also valuable in situations where concentrated “clean areas” and lighting need to be achieved within a cleanroom. The filter unit and light fixture are pre-assembled together to form one complete flow-thru light unit.
Filtered air is exhausted from the cleanroom beneath the flexible vinyl walls. An adequate gap of about six-inches between walls and floor is necessary for air to flow through the room and escape. Air volume is typically about 200 feet per minute, and at that rate the flexible walls tend to bow outward a little because of positive air pressure created by the powered filters. A small amount of wall flex is nor mal, but if the wall-to-floor gap is too small, the air will push the panels outward to an unacceptable distance and inhibit good laminar airflow. If the gap is too large, the cleanroom will not keep enough positive pressure to push contaminants out.
Like their hardwall counterparts, softwall cleanrooms have a large number of options available depending on customer needs. Anterooms or gowning rooms can easily be added to the cleanroom. They, too, are portable and can be relocated along the outside perimeter of the cleanroom for adaptation or modifications to manufacturing processes.
If needed, softwall cleanrooms can be mobile. When equipped with optional braked casters, they can easily be moved to a different location within a facility or stored. Casters are used for smaller cleanrooms, and customers who wish to install casters on rooms larger than 12 feet by 12 feet should seek advice from their supplier.
Optional acrylic or Lexan panels provide a flexible, yet sturdy and attractive wall alternative. Product passthroughs can also be included in the design. Additional options include: special room heights, solid doors, yellow or opaque sidewalls for ultraviolet light filtration and security, stainless steel frames, building suspension brackets, and ionization equipment.
Modular softwall cleanrooms are pre-fabricated at the factory for quick installation. Customers can easily install standard rooms onsite within one-to-two days. All electrical connections are simplified using a continuous series of plug-together, pre-fabricated wiring system. Starting at the room’s electrical junction box, power cable segments are connected to each ceiling light and powered filter unit. This allows the user to connect any number of lights or filter units within their circuit.
Softwall cleanroom maintenance is simple, but requires regular cleaning to ensure optimum performance. Powered filter units use a prefilter and these must be visually checked on a regular basis. If the filters are dirty, they must be changed. The HEPA filters are somewhat maintenance free, but it is recommended they be re-certified by a third party every year. All interior surfaces and floors must be cleaned on a regular basis.
A modular softwall cleanroom is a low-cost investment, which provides a highly functional cleanroom solution for manufacturers. The flexible structure creates a controlled environment that is able to meet the needs and requirements of small- to large-sized companies. Softwall cleanrooms are designed with the customer in mind, covering a wide range of industries and diverse applications.
Softwall modular cleanrooms are designed for functionality and reduced cost while providing all the flexible benefits of modular construction. They are tent-like, lightweight, easy-to-assemble structures, which can be installed free standing or suspended from the ceiling of an existing building. Unlike their fixed-wall counterparts, softwall cleanrooms are generally smaller, portable, and can fit into tight spaces. The portable design enables the cleanroom units to be easily moved to another location or disassembled and stored. Because of their relative low cost, softwall cleanrooms are ideal for small or startup businesses, or manufacturers looking for a quick, easy way to expand their cleanroom operations.
The cleanrooms are available in a variety of sizes and classifications, with options to match a customer’s specific needs. From standard 4 feet by 4 feet units, to sizes as large as 24 feet by 36 feet. Larger, custom sizes can be designed and built to meet customer requirements. Because of their modular design, rooms can be expanded or reduced in size without taking the entire cleanroom down, making it easy to add or remove sections. Softwall rooms are also available in a variety of cleanroom classifications, but most commonly in Class 100,000 to Class 10 (ISO 8 to ISO 4) designs.
A wide variety of industries use softwall cleanrooms, from medical device manufacturers to makers of rolled films. This design is also popular in microelectronics and semiconductor manufacturing, as well as electronics repair industries where contaminants cannot be allowed into sensitive areas of electronic devices.
The basic building block of the softwall cleanroom’s modular design is a sectioned ceiling framework made up of tubular steel beams with T-bar cross members. This interlocking ceiling grid system enables easy assembly and cleanroom expansion. The ceiling is supported by tubular steel legs at each of the four corners and reinforced with heavy gauge, triangular steel gussets. Powered HEPA filter units, lighting systems, and ceiling panels are sealed to the grid using gaskets, providing a zero-leak cleanroom.
Interior height of the ceiling framework is commonly 8, 9, or 10 feet, although various heights are available depending on the customer application. Standard filter unit height is 14 inches, with a two-inch minimum space required between the filter unit and facility ceiling. The common structure height enables the modular softwall cleanroom to easily fit within an existing building.
Softwall cleanrooms, without a center support, have a maximum size of 12 feet by 12 feet with a leg on each corner. Larger rooms can be constructed, but additional support posts within the structure are required. For example, a room 16 feet by 20 feet would have one center post or a room 20 feet by 32 feet would have three center posts. Other options are available for clear spans without center legs. For example, ceiling-suspended softwall cleanrooms eliminate the need for all support legs and columns. This configuration allows the cleanroom to easily accommodate equipment layout and maximizes floor space utilization.
The walls of most standard softwall modular cleanrooms are made of 20 or 40 mil clear vinyl and are fire retardant with an anti-static additive. Cleanroom-grade softwalls with low outgassing and static-dissipative vinyl are an available option. Entering or exiting most softwall cleanrooms is by way of vinyl strip doorways. The strip door commonly consists of eight-inch-wide, 80 mil thick strips with a two-inch overlap on each side along the length. Entering a cleanroom requires only to push apart the strips, which automatically reseal as they come back together. The strip doors are pre-assembled and are easily mounted to the ceiling structure. Swinging doors in metal frames are an available option when acrylic or Lexan walls are used.
The controlled level of contamination will vary depending on quantity and configuration of filters. For example, the ceiling structure of a Class 10,000 (ISO 7) cleanroom will have a combination of powered HEPA filters, lights, and blank panels. In contrast, Class 10 (ISO 4) cleanrooms require 100% ceiling coverage with powered filters in all ceiling grid sections.
When ceiling space for lighting is limited due to filter requirements, flow-thru lights can be used. These are similar to standard cleanroom lights with the exception that a motorized ceiling HEPA filter unit is mounted directly on top of the light. This fixture is designed with open areas so filtered air is able to flow through the light fixture down into the cleanroom. Flow-thru lights are also valuable in situations where concentrated “clean areas” and lighting need to be achieved within a cleanroom. The filter unit and light fixture are pre-assembled together to form one complete flow-thru light unit.
Filtered air is exhausted from the cleanroom beneath the flexible vinyl walls. An adequate gap of about six-inches between walls and floor is necessary for air to flow through the room and escape. Air volume is typically about 200 feet per minute, and at that rate the flexible walls tend to bow outward a little because of positive air pressure created by the powered filters. A small amount of wall flex is nor mal, but if the wall-to-floor gap is too small, the air will push the panels outward to an unacceptable distance and inhibit good laminar airflow. If the gap is too large, the cleanroom will not keep enough positive pressure to push contaminants out.
Like their hardwall counterparts, softwall cleanrooms have a large number of options available depending on customer needs. Anterooms or gowning rooms can easily be added to the cleanroom. They, too, are portable and can be relocated along the outside perimeter of the cleanroom for adaptation or modifications to manufacturing processes.
If needed, softwall cleanrooms can be mobile. When equipped with optional braked casters, they can easily be moved to a different location within a facility or stored. Casters are used for smaller cleanrooms, and customers who wish to install casters on rooms larger than 12 feet by 12 feet should seek advice from their supplier.
Optional acrylic or Lexan panels provide a flexible, yet sturdy and attractive wall alternative. Product passthroughs can also be included in the design. Additional options include: special room heights, solid doors, yellow or opaque sidewalls for ultraviolet light filtration and security, stainless steel frames, building suspension brackets, and ionization equipment.
Modular softwall cleanrooms are pre-fabricated at the factory for quick installation. Customers can easily install standard rooms onsite within one-to-two days. All electrical connections are simplified using a continuous series of plug-together, pre-fabricated wiring system. Starting at the room’s electrical junction box, power cable segments are connected to each ceiling light and powered filter unit. This allows the user to connect any number of lights or filter units within their circuit.
Softwall cleanroom maintenance is simple, but requires regular cleaning to ensure optimum performance. Powered filter units use a prefilter and these must be visually checked on a regular basis. If the filters are dirty, they must be changed. The HEPA filters are somewhat maintenance free, but it is recommended they be re-certified by a third party every year. All interior surfaces and floors must be cleaned on a regular basis.
A modular softwall cleanroom is a low-cost investment, which provides a highly functional cleanroom solution for manufacturers. The flexible structure creates a controlled environment that is able to meet the needs and requirements of small- to large-sized companies. Softwall cleanrooms are designed with the customer in mind, covering a wide range of industries and diverse applications.
Floorplan: 5 simple steps for your next flooring project
New or refurbishment resinous floor and wall system projects can appear overly complex in the early planning stage. Yet, there are key criteria that all manufacturers and their contractors evaluate to arrive at a system recommendation. By understanding and rating the relative importance of these criteria, you can help your resinous system team help you. This article highlights simple steps you can take to optimize your resinous floor and wall system applications.
Step 1: Rank the floor system qualities by how important they are to the project team and assign a weight to them.
Assemble a site team of users of the space that is to be constructed or renovated. Also involve a cross section of facility and maintenance personnel. By allowing each group to voice their concerns and key issues you promote broad buy-in and help ensure you’ve covered all your bases.
Have the team document all important functional and aesthetic requirements you would like the resinous system to have. See Figure 1 for a list of key criteria.
Additional criteria might include:
Next, clearly establish how many square feet of resinous floor and wall finishes are going to be installed. For refurbishment projects, develop a realistic plan for how much space (how many square feet) you can allocate to the resinous contractor without interruption. Keep in mind access to critical corridors and spaces. This will help the contractor understand how many mobilizations will be required to complete your project.
Other relevant information you can supply includes: strong likes/dislikes with previous resinous systems at your site, how long you want the system to last, accessibility for the crew (how long does it take to get into the space and what is required), noise/vibration limitations, other work being performed concurrently both in the facility and as part of the construction process, and a venting plan.
Step 2: Establish a Budget
Take the results of Step 1 and schedule a meeting with your design team including the architect, resinous system supplier, and installer. At this point, the design team can provide samples and price ranges for options which meet your site team’s criteria. For example, an 1/8" thick double broadcast epoxy colored quartz system might be installed for $6.00 - $8.00 per square foot. An 1/8" thick methyl methacrylate flake floor might be installed for $15.00 - $18.00 per square foot.
The most basic impact on budget comes from how many square feet the contractor can address each day and the number of days required installing the system. For example, if the contractor is given a small space to work on with a system that requires a large number of steps, your installed cost per square foot will be high. Conversely, given the same set of circumstances, a large number of square feet with few installation steps will result in a low installed cost per square foot.
Step 3: Keep It Simple!
Your design team will most likely provide you with more than one resinous floor and wall system option that meets your site criteria. Don’t be afraid to ask the team why they are recommending a particular system or the downside to utilizing a less expensive option. Don’t be tempted to over-engineer your resinous flooring system. An excellent example of this relates to how you build thickness beneath the resinous flooring system. Added thickness could be necessitated by a need for slope-to-drain or to restore flatness after aggressive surface preparation. Rather than building thickness out of the resinous floor system resin, many manufacturers offer fast-setting, high strength cementitious mortar systems which can be half to a third of the cost of utilizing the flooring system resin. Just make sure these materials are produced and packaged by the flooring manufacturer and meet the strength requirements of the project.
Step 4: Look Ahead
Don’t make your resinous floor and wall system decision in a time vacuum. Think about long-term maintenance implications. In Figure 1, one of the selection criteria listed is ultraviolet (UV) resistance. The reason it is important is because many of the systems offered today discolor with exposure to light. UV resistance is a relevant consideration because if noncolorfast materials are selected, they will discolor as they age. A large percentage of resinous floor and wall systems are re-coated or completely redone because they have lost their aesthetics rather than lost their basic performance properties. If you think about what the system is going to look like five to seven years from now instead of what the shiny new sample looks like today, it may drive you and the site team toward color-stable technologies.
Another consideration for the future is how do you patch and repair the systems? There is no system that can’t be damaged over time. How disruptive and how involved are simple repairs and patches? What will they look like? Does the system have a strong odor? Can it be repaired while the facility is in operation or will it necessitate a shutdown of the entire cleanroom? Ask the design team these questions as well as cleaning recommendations and required equipment. Find out how long it takes for the materials to cure before normal operations can proceed.
Simply doing quarterly inspections and taking care of gouges, impact damage, etc. can save you a lot of money. This helps avoid always being in an emergency repair situation necessitated by having to patch damaged areas that started small but became large due to lack of attention. Ask the resinous system supplier and contractor if they will include an annual inspection in their quotation and who would be responsible for these inspections. See if there is a cost associated with these inspections. Also, set up a contact and speed of response procedure to report damage as it occurs.
Step 5: Check Out your Supplier/Contractor Team
Assuming a proper system is selected, the final step involves making sure you have the right supplier/contractor team lined up—before a contract is let. Most resinous floor and wall system architectural guide specifications call for certain submittal information. These items should be evaluated whether you are handling the resinous system contract directly or the project is being let as a subcontract by a general contractor or construction manager. Let’s take a close look at them one by one.
SUMMARY
Any successful project starts with a clear identification of needs. Establish key resinous system attributes and understand what is most important to your site team. Enlist a design team consisting of your architect, resinous flooring supplier, and contractor to establish your budget taking into account near-term and long term requirements. Finally, before you award your contract, perform a detailed check on your supplier/resinous system team to make sure they meet your needs. Following these simple steps will greatly enhance the probability of a successful resinous floor and wall system project.
Step 1: Rank the floor system qualities by how important they are to the project team and assign a weight to them.
Assemble a site team of users of the space that is to be constructed or renovated. Also involve a cross section of facility and maintenance personnel. By allowing each group to voice their concerns and key issues you promote broad buy-in and help ensure you’ve covered all your bases.
Have the team document all important functional and aesthetic requirements you would like the resinous system to have. See Figure 1 for a list of key criteria.
Additional criteria might include:
- Cleanability
- Slope to Drain
- Repairability/Maintenance
- Impact on Project Schedule
- LEED Impact
- Budget
- Detailing corners, coves, etc.
- Aesthetics of the System (gloss/low sheen; solid color; terrazzo; decorative flake; decorative quartz)
Next, clearly establish how many square feet of resinous floor and wall finishes are going to be installed. For refurbishment projects, develop a realistic plan for how much space (how many square feet) you can allocate to the resinous contractor without interruption. Keep in mind access to critical corridors and spaces. This will help the contractor understand how many mobilizations will be required to complete your project.
Other relevant information you can supply includes: strong likes/dislikes with previous resinous systems at your site, how long you want the system to last, accessibility for the crew (how long does it take to get into the space and what is required), noise/vibration limitations, other work being performed concurrently both in the facility and as part of the construction process, and a venting plan.
Step 2: Establish a Budget
Take the results of Step 1 and schedule a meeting with your design team including the architect, resinous system supplier, and installer. At this point, the design team can provide samples and price ranges for options which meet your site team’s criteria. For example, an 1/8" thick double broadcast epoxy colored quartz system might be installed for $6.00 - $8.00 per square foot. An 1/8" thick methyl methacrylate flake floor might be installed for $15.00 - $18.00 per square foot.
The most basic impact on budget comes from how many square feet the contractor can address each day and the number of days required installing the system. For example, if the contractor is given a small space to work on with a system that requires a large number of steps, your installed cost per square foot will be high. Conversely, given the same set of circumstances, a large number of square feet with few installation steps will result in a low installed cost per square foot.
Step 3: Keep It Simple!
Your design team will most likely provide you with more than one resinous floor and wall system option that meets your site criteria. Don’t be afraid to ask the team why they are recommending a particular system or the downside to utilizing a less expensive option. Don’t be tempted to over-engineer your resinous flooring system. An excellent example of this relates to how you build thickness beneath the resinous flooring system. Added thickness could be necessitated by a need for slope-to-drain or to restore flatness after aggressive surface preparation. Rather than building thickness out of the resinous floor system resin, many manufacturers offer fast-setting, high strength cementitious mortar systems which can be half to a third of the cost of utilizing the flooring system resin. Just make sure these materials are produced and packaged by the flooring manufacturer and meet the strength requirements of the project.
Step 4: Look Ahead
Don’t make your resinous floor and wall system decision in a time vacuum. Think about long-term maintenance implications. In Figure 1, one of the selection criteria listed is ultraviolet (UV) resistance. The reason it is important is because many of the systems offered today discolor with exposure to light. UV resistance is a relevant consideration because if noncolorfast materials are selected, they will discolor as they age. A large percentage of resinous floor and wall systems are re-coated or completely redone because they have lost their aesthetics rather than lost their basic performance properties. If you think about what the system is going to look like five to seven years from now instead of what the shiny new sample looks like today, it may drive you and the site team toward color-stable technologies.
Another consideration for the future is how do you patch and repair the systems? There is no system that can’t be damaged over time. How disruptive and how involved are simple repairs and patches? What will they look like? Does the system have a strong odor? Can it be repaired while the facility is in operation or will it necessitate a shutdown of the entire cleanroom? Ask the design team these questions as well as cleaning recommendations and required equipment. Find out how long it takes for the materials to cure before normal operations can proceed.
Simply doing quarterly inspections and taking care of gouges, impact damage, etc. can save you a lot of money. This helps avoid always being in an emergency repair situation necessitated by having to patch damaged areas that started small but became large due to lack of attention. Ask the resinous system supplier and contractor if they will include an annual inspection in their quotation and who would be responsible for these inspections. See if there is a cost associated with these inspections. Also, set up a contact and speed of response procedure to report damage as it occurs.
Step 5: Check Out your Supplier/Contractor Team
Assuming a proper system is selected, the final step involves making sure you have the right supplier/contractor team lined up—before a contract is let. Most resinous floor and wall system architectural guide specifications call for certain submittal information. These items should be evaluated whether you are handling the resinous system contract directly or the project is being let as a subcontract by a general contractor or construction manager. Let’s take a close look at them one by one.
- Industry Experience: Is the contractor and manufacturer familiar with typical cleanroom conditions? Ask for a list of previous projects.
- Project Experience: Has the manufacturer/contractor team dealt with projects of similar size and complexity to yours? Ask for references.
- Stability: How long has your contractor/supplier been in business? Ask for their annual volume and an annual report. If problems develop during an installation, they can be very expensive to fix, making financial strength and stability an extremely important piece to investigate.
- Workforce: Make sure the installer’s team has experience with cleanrooms. Ask for the names of key personnel that are going to be on your project and make sure they are company employees.
- Safety: Ask for documentation of the installer’s safety program, certificate of insurance, and incident rate.
SUMMARY
Any successful project starts with a clear identification of needs. Establish key resinous system attributes and understand what is most important to your site team. Enlist a design team consisting of your architect, resinous flooring supplier, and contractor to establish your budget taking into account near-term and long term requirements. Finally, before you award your contract, perform a detailed check on your supplier/resinous system team to make sure they meet your needs. Following these simple steps will greatly enhance the probability of a successful resinous floor and wall system project.
Point of View - The Importance of Ongoing Facility Monitoring
Facility Monitoring and the routine periodic documentation of this information are vital to maintaining the cleanroom facility at optimal operational efficiency.
Regardless of the manufacturer you select for your facility monitoring instrumentation, a decision has to be made early on as to how stringent the sensor tolerance must be for your specific application. IE: Can you accept a 3% tolerance of your Relative Humidity reading or do you need a 0.5% tolerance. This is where you do not want to buy price and want to know about on-site calibration or the turn around time for off-site calibration.
The first line of defense is the monitoring of the cleanroom’s pressurization, from the main cleanroom outward to lesser clean areas. Whether you have a remote monitoring system or gages on the wall, it is imperative that the Cleanroom Manager be aware of what the pressure readings are, on a daily basis.
If you are using gages that are measuring the pressure differential, have these gages mounted in a panel box on the wall just outside of the gown room where no one can avoid seeing them upon entering the room. This panel box will provide access for the calibration of these gages on an annual basis, as there is no such thing as a “For Reference Only” sticker in lieu of a calibration sticker when it comes to the first line of defense of monitoring.
It is also beneficial to monitor the ongoing pressure differential of the HEPA filters versus the initial pressure drop when the filter was new. Usually the monitoring of one HEPA filter is sufficient for this application in order to give a snap shot of all of the HEPA filters so that you will be aware of when to change them in accordance with current industry guidelines.
Regarding airborne particle counting: where will you place the sensors in a remote monitoring installation application that will provide you with real readings?
OR if a designated trained Technician will be doing manual readings with a particle counter make sure that the particle counter, hose, and probe are “zero counted” prior to taking any readings. Also note the elevation of the particle counter probe on the report sheet as well as the operational mode of the room when the counts were taken.
Don’t forget the Viable (Microbial) Monitoring Program, if applicable.
When doing any monitoring, it is the monitoring Technician’s responsibility to be observant of any items that may have a negative impact on the cleanroom’s environment, such as unsealed penetrations in the walls or ceiling, broken light lenses, unseated or broken ceiling tiles, etc. and report them to the Cleanroom Manager.
Regardless of the manufacturer you select for your facility monitoring instrumentation, a decision has to be made early on as to how stringent the sensor tolerance must be for your specific application. IE: Can you accept a 3% tolerance of your Relative Humidity reading or do you need a 0.5% tolerance. This is where you do not want to buy price and want to know about on-site calibration or the turn around time for off-site calibration.
The first line of defense is the monitoring of the cleanroom’s pressurization, from the main cleanroom outward to lesser clean areas. Whether you have a remote monitoring system or gages on the wall, it is imperative that the Cleanroom Manager be aware of what the pressure readings are, on a daily basis.
If you are using gages that are measuring the pressure differential, have these gages mounted in a panel box on the wall just outside of the gown room where no one can avoid seeing them upon entering the room. This panel box will provide access for the calibration of these gages on an annual basis, as there is no such thing as a “For Reference Only” sticker in lieu of a calibration sticker when it comes to the first line of defense of monitoring.
It is also beneficial to monitor the ongoing pressure differential of the HEPA filters versus the initial pressure drop when the filter was new. Usually the monitoring of one HEPA filter is sufficient for this application in order to give a snap shot of all of the HEPA filters so that you will be aware of when to change them in accordance with current industry guidelines.
Regarding airborne particle counting: where will you place the sensors in a remote monitoring installation application that will provide you with real readings?
OR if a designated trained Technician will be doing manual readings with a particle counter make sure that the particle counter, hose, and probe are “zero counted” prior to taking any readings. Also note the elevation of the particle counter probe on the report sheet as well as the operational mode of the room when the counts were taken.
Don’t forget the Viable (Microbial) Monitoring Program, if applicable.
When doing any monitoring, it is the monitoring Technician’s responsibility to be observant of any items that may have a negative impact on the cleanroom’s environment, such as unsealed penetrations in the walls or ceiling, broken light lenses, unseated or broken ceiling tiles, etc. and report them to the Cleanroom Manager.
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