By George Miller

Despite the highly publicized antics, a poorly attended biolab protest may have done more to illustrate the growing acceptance of Biosafety Level 3 and 4 facilities-even in urban areas-than to rile up residents. It also provided a reminder to lab managers of the importance of maintaining relationships with the communities in which they reside.

The lackluster effort, intended to protest a BSL-4 laboratory now in the final stages of construction at Boston University, coincided with the huge Biotechnology Industry Organization (BIO) trade show in Boston in early May.

At a time of growing competitiveness among state and local governments to attract biotech business, and among academic and medical institutions to win government research contracts, the likelihood of a BSL-3 or -4 lab popping up in a city setting or suburban neighborhood is on the rise. And in these days of color-coded terrorism threat levels, more residents are beginning to understand the need for infectious disease research, which is required whether disease is spread by terrorists or Mother Nature.

Boston University’s $178 million National Emerging Infectious Diseases Laboratories BSL-4 facility is one of several being built with funding from the National Institute of Allergy and Infectious Diseases (NIAID), part of the U.S. National Institutes of Health (NIH), in an effort to bolster United States biodefenses. BU Medical Center will receive $128 million in federal funds for the project, which is expected to be complete next year.

Document standardizes operating procedures

Legislation approved in 2003 calls for the NIH to establish national and regional biocontainment labs as well as regional centers of excellence for biodefense and emerging infectious disease research. A national-level guidance document, Biosafety in Microbiological and Biomedical Laboratories (BMBL) 5th Edition, provides operations and protocol details and is available at the U.S. Centers for Disease Control and Prevention web site (www.cdc.gov).

“All of our grantees are required to follow this guidance, as well as state and local requirements,” says Rona Hirschberg, senior program officer at the Office of Biodefense Research Affairs, NIAID.

National and regional biocontainment laboratories (top) support the research activities of NIAID’s regional centers of excellence (bottom) for biodefense and emerging infectious disease research. The biosafety labs also will be available to assist national, state, and local public health efforts in the event of a bioterrorism or infectious disease emergency, according to NIAID. Source: NIAID.Click here to enlarge image

Given a standard for operating BSL-3 and -4 facilities, the community relations job becomes one of transparency-letting the public know what you’re doing and that systems are in place for residents to be informed of mishaps and for authorities to respond.

Strained relations

Since NIAID awarded BU a grant to build its lab in 2003, the university’s relationship has been rocky with its neighbors in Roxbury, a low-income, densely populated part of Boston’s South End. In response to community actions, BU and NIH are currently conducting a second environmental impact assessment and alternative site evaluations for the BSL‑4 portion of the lab, even as construction continues on the building’s façade and interior. Residents’ opposition to the lab may have been fueled by a contamination incident in 2004, when three university researchers working in a BSL-2 lab were infected after exposure to tularemia. BU acknowledged that the researchers had violated safety procedures.

Historically, biosafety labs have an excellent safety record. Hirschberg of NIAID cites the safety studies of Karl M. Johnson, MD, adjunct professor of medicine and biology, at the University of New Mexico-Albuquerque, on the long-term safety records of BSL-3 and -4 facilities. As part of an environmental impact statement prepared prior to construction of a lab at Rocky Mountain Laboratories, Johnson, the retired founding chief of the CDC’s Special Pathogens Branch, reported in 2003 that no clinical infections occurred over 31 years at the three BSL-4 institutions studied. The study period reflected nearly half a million hours of lab and field exposure time, the majority spent in positive-pressure suits. No major defects or incidents in operation of the physical facilities were reported. No escape of any agent with clinical consequences for neighboring communities occurred.

In a separate study of BSL-3 labs, Johnson likewise found that no agent had escaped to cause infection in adjacent civilian communities.

Community needs view into lab ops

Those running such labs agree that a clear view into lab operations is key to community acceptance. “The number one [job] is transparency and keeping the community fully informed,” says Hirschberg.

At the Howard T. Ricketts Regional Biosafety Lab in Chicago, research operations manager Debra Anderson has adapted a community relations template established more than half a century ago for nuclear energy research. The lab’s work is temporarily being conducted at the University of Chicago. When a new facility is completed in 2008 some 25 miles southwest at Argonne National Labs-where Enrico Fermi led the first controlled nuclear chain reaction in 1942-biosafety lab operations will shift there, to be co-located with NIH’s Great Lakes Regional Center of Excellence for Biodefense and Emerging Infectious Diseases.

“We’ve designed a community relations plan that models Argonne’s historical methods: very transparent, very active,” says Anderson, who is also associate director of the Great Lakes Regional Center of Excellence. “If you’re not transparent, it’s easy for assumptions to be made [by the public],” she adds.

Outreach addresses common fears

Ricketts Lab outreach has done a lot to calm community fears, Anderson notes. Organizers of the $31 million BSL-3 lab created a committee to advise the University of Chicago on outreach strategy and topics of interest to the community. “The committee has been very valuable and was recently formalized,” she says. “What we hear routinely is, ‘How will we know if there’s a problem? Will physicians know?’ You get to see [residents’] understanding of containment safety levels. We’ve provided education and it’s been well received.”

Direct contact with residents is also working at Tufts Cummings School of Veterinary Medicine. The school is building a $26 million BSL-3 regional biocontainment lab in Grafton, MA, a town of 15,000 residents located 40 miles west of Boston. Completion is estimated for August 2009.

A community advisory group provides a means for quarterly public discussion between Tufts and Grafton residents. It is the Cummings School’s “key connection to its neighbors,” said interim dean Sawkat Anwer, providing dialogue between the campus and the community.

Tufts established several community boards in its outreach efforts, according to Anwer, and has participated in town-sponsored boards and committees. The school also works with the Grafton liaison group on local government issues and an institutional biosafety committee to meet regulatory requirements.

Accepting USP <797>as a robust quality and patient safety regulation is the first step to enforcing it

By Eric S. Kastango, MBA, RPh, FASHP

What do all these situations have in common?

• A 25 bed critical-access hospital in rural Minnesota
• A physician’s office where intramuscular antibiotics are given to children with pneumonia
• An allergist who manages the care of 200 patients with allergies
• A floor nurse who compounds medications to be given to patients in critical care
• A homecare company with 72 pharmacies in 44 states delivering home infusion therapy to more than 10,000 patients daily
• A national outsourcing company that is both licensed as a pharmacy and registered with the FDA as a manufacturer

Unlike pharmaceutical manufacturing, where companies are more similar than dissimilar (though some would strongly disagree), the standards of sterile compounding must be applied to all of the situations listed above and others that were not described.

In the introduction of USP Chapter <797>, it is stated that the standards are intended to apply to all persons who prepare compounded sterile preparations (CSPs) and all places where CSPs are prepared, e.g., hospitals and other health care institutions, patient treatment clinics, retail pharmacies, physicians’ practice facilities, and any place where CSPs are prepared, stored, and transported. Persons who perform sterile compounding include pharmacists, nurses, pharmacy technicians, and physicians, and all are required to comply with this chapter.

USP Chapter <797> first appeared in the pharmacy lexicon on January 1, 2004, spawned by patient incidents starting in the 1970s. It was the genesis of years of voluntary practice standards attempting to prevent future errors. The process started with the National Coordinating Committee on Large Volume Parenterals (NCCLVP), which led to the American Society of Health-System Pharmacists Guidelines on Quality Assurance for Pharmacy Prepared Products in 1993, USP Chapter <1206>: Sterile Drugs for Home Use in 1995, and to the present day chapter, which is considered enforceable by the FDA.

Now that we are into this enforceable chapter for more than three years, how did the USP Council of Experts, Sterile Compounding Committee do? Well, if you ask the hundreds of stakeholders who submitted thousands of comments including several prominent organizations like the Centers for Disease Control (CDC), the American Society of Microbiology (ASM), Association for Professionals in Infection Control and Epidemiology, Inc. (APIC), and the FDA, there was opportunity for improvement. Since the USP process is a dynamic one and relies on stakeholder feedback, a revised chapter is scheduled for release in 2007.

The revised chapter was written to consider all of the perspectives of the various groups, some of which are at odds with the standards of practice expected of pharmaceutical manufacturers and by the FDA.

Some of the principles, concepts, and requirements within the revised USP Chapter <797> have been challenged by the question “Where is the science behind the requirements?” Many pharmacists and other stakeholders believe that the requirements are too stringent and have questioned their need especially in the areas of facilities, environmental monitoring, personnel garbing, and cleaning and disinfection. These sections involve spending money in areas that have historically been misunderstood, overlooked, ignored, or routinely de-funded. In the pharmaceutical industry, many of the thought leaders and even the editor of this publication have stated that they believe the chapter is not stringent enough. Aseptic processing in the practice of pharmacy is, most of the time, not the same as manufacturing. However, there are parallels with many of the same practices, processes, and procedures. There are several factors that make this chapter as a “one-size-fits-all” regulation tenuous. They include:

• Many pharmacists by choice or by necessity have to handle and compound patient-specific sterile preparations using bulk non-sterile active pharmaceutical ingredients in order to meet the patient’s therapeutic needs because no commercial drugs are available. When does the pharmacy cross the line and become a manufacturer?
• Patients won’t be able to access care because the cost of compliance will discourage practitioners in rural areas who only compound a few CSPs per week. At what point does a practitioner have to comply with the regulations?
• Some state boards of pharmacy permit pharmacists to compound non-patient-specific sterile preparations for office use (bulk vials), making some pharmacies appear more like manufacturers. This flies in the face of federal regulations. Do these pharmacies have to comply with different standards?
• The ongoing tug of war between the FDA, compounders, and state boards of pharmacy in identifying the point at which a compounding pharmacy becomes a manufacturer spurred the FDA to post on May 31, 2007 a document titled “The Special Risks of Pharmacy Compounding” (http://www.fda.gov/consumer/updates/compounding053107.html) on its Consumer Health Information Page.

Some would argue that these situations don’t make the matter of compliance very easy or clear. However, with all of that being said, is there an easy answer to the “one-size-fits-all” regulation? I think so. As the new revisions get assimilated into practice, and everyone starts believing that the moving target known as USP Chapter <797> isn’t moving any more, the excuses as to why people can’t comply will go away. It is a robust document with the express purpose of building quality into compounded sterile preparations and ensuring patient safety. This chapter will continue to spark the scientific research that will, in turn, generate the scientific evidence needed in the area of sterile compounding.

The bottom line is that USP Chapter <797> is a regulation that is not going away and compliance is required. Unlike registered manufacturers who have the FDA to enforce the cGMPs, not all state boards of pharmacy are on board with this regulation yet. It is my hope that the state boards will rise to the challenge and take responsibility for this chapter and start enforcing it in order to ensure patient safety and keep the FDA out of the practice of pharmacy.

Eric S. Kastango is president, CEO, and owner of Clinical IQ LLC, a provider of customized process and educational strategies for the pharmaceutical, medical device, and health care industries. He also serves on the CleanRooms Editorial Advisory Board.

Consumer Inquiries:
888-INFO-FDA

May 25, 2007 — /FDA News/ — The U.S. Food and Drug Administration is alerting health care professionals and their patients who wear soft contact lenses about a voluntary recall of Complete MoisturePlus Multi Purpose Solution manufactured by Advanced Medical Optics of Santa Ana, CA.

The company is taking this action as a precaution because of reports of a rare, but serious, eye infection, Acanthamoeba keratitis, caused by a parasite. The link between the solution and the infection was identified as a result of an investigation by the Centers for Disease Control and Prevention (CDC).

Consumers who wear soft contact lenses should stop using the solution, discard all partially used or unopened bottles, and replace their lenses and storage container.

“We believe the company acted responsibly in taking this voluntary action and support their decision to be proactive in the interest of public health,” said Daniel Schultz, M.D., director of FDA’s Center for Devices and Radiological Health. “FDA and CDC are working closely with the company to collect additional information and we will continue to alert consumers and advise them as more information becomes available.”

Acanthamoeba keratitis may lead to vision loss with some patients requiring a corneal transplant. The infection primarily affects otherwise healthy people who wear contact lenses.

Consumers should ask their doctor about choosing an appropriate alternative cleaning/disinfecting product and seek immediate treatment if they have symptoms of eye infection as early diagnosis is important for effective treatment. The symptoms of Acanthamoeba keratitis can be very similar to those of other more common eye infections and may include eye pain or redness, blurred vision, light sensitivity, sensation of something in the eye, or excessive tearing but Acanthamoeba is more difficult to treat.

It is estimated that Acanthamoeba keratitis infections occur in approximately 2 out of every 1 million contact lens users in the United States each year. However, in a multi-state investigation to evaluate a recent increase in Acanthamoeba keratitis cases, CDC determined that the risk of developing AK was at least seven times greater for those consumers who used Complete MoisturePlus solution versus those who did not. Additional information regarding the CDC results is available at the CDC web site (http://www.cdc.gov/mmwr/preview/mmwrhtml/mm56d526a1.htm).

“The ongoing CDC investigation is a collaborative effort,” said Michael Beach, M.D., a Division of Parasitic Diseases team leader with CDC. “We are working with FDA, state, territory, university, and clinical partners in an effort to further understand whether usage or contamination of this solution led to these Acanthamoeba infections.”

All contact lens users should closely adhere to the following measures to help prevent eye infections:
-Remove contact lenses before any activity involving contact with water, including showering, using a hot tub, or swimming.
-Wash hands with soap and water and dry them before handling contact lenses.
-Clean contact lenses according to manufacturer guidelines and instructions from an eye care professional.
-Use fresh cleaning or disinfecting solution each time lenses are cleaned and stored. Never reuse or top off old solution.
-Never use saline solution and rewetting drops to disinfect lenses. Neither solution is an effective or approved disinfectant.
-Schedule regular eye exams with your eye care professional.
-Wear and replace contact lenses according to the schedule prescribed by your eye care professional.
-Store lenses in a proper storage case.
-Storage cases should be irrigated with sterile contact lens solution (never use tap water) and left open to dry after each use.
-Replace storage cases at least once every three months.

FDA and CDC want to gather information related to Acanthamoeba keratitis in contact lens users. Report adverse events related to these products to MedWatch, the FDA’s voluntary reporting program: www.fda.gov/medwatch/report.htm; Phone: 800-332-1088; Fax: 800-332-0178; Mail: MedWatch, Food and Drug Administration, 5600 Fishers Lane, Rockville, MD, 20852-9787.

Consumers who believe they are in possession of the recalled product may call the company at 1-888-899-9183. Additional information about Acanthamoeba infection is available from the CDC web site at http://www.cdc.gov/ncidod/dpd/parasites/acanthamoeba/index.htm.

May 24, 2007 — /PRNewswire/ — IRVINE, CA — Inscent, Inc. has received a Small Business Innovative Research grant from the U.S. National Science Foundation to develop a novel biosensor that will protect public health and national security by ensuring food and water supplies are free of bacterial contaminants that cause disease in humans. The new biosensor is a high-sensitivity, rapid response system designed to detect the presence of bacterial metabolic by-products in samples up to 20 times faster than existing technologies. The biosensor is based on Inscent’s Attenu high-throughput assay system and is the first in a series of novel devices under development that are intended to detect disease agents, pollutants, toxins, or other harmful substances such as explosives. This novel platform technology will positively impact several industries, including environmental monitoring and medical diagnostics.

Inscent, Inc. (www.inscent.com) has developed a number of novel platform technologies to exploit the wide variety, selectivity, and high sensitivity of insect chemosensory systems. The company’s platform technologies are crucial for the development of highly sensitive biosensors, and its designs utilize a versatile in-house collection of insect chemosensory proteins. This proprietary collection of chemosensory proteins is also being used to develop a series of non-toxic, highly efficient insect pest control products. Inscent’s platform technologies utilize the latest developments in molecular genetics, genomics, and bioinformatics to design advanced, environmentally responsible insect pest control solutions and effective, sensitive biosensors.

The National Science Foundation (NSF; www.nsf.gov) is an independent federal agency that supports fundamental research and education across all fields of science and engineering, with an annual budget of $5.58 billion. NSF also encourages scientific innovation and discovery in the commercial sector, primarily through the Small Business Innovative Research (SBIR) program. Inscent’s proposal for the development of a novel biosensor to ensure food and water supply safety has led the federal agency to fund continued development work that will be carried out at Inscent’s laboratory in Irvine, CA. Inscent, Inc. continues this project while maintaining its wide development base that includes products for public health, security, public safety, agricultural, and domestic applications.

Source: Inscent, Inc.

Contact:
Daniel F. Woods, chief scientific officer of Inscent, Inc.
Tel: 949-955-3129
Fax: 208-693-4743