Ref: Proposed Rule; Reopening of the Administrative Record for Topical Antimicrobial Drug Products for Over-the-Counter Human Use; Health-Care Antiseptic Drug Products. (68 Federal Register 32003), May 29, 2003. [Docket No. 75N-183H]
Liberty Place, Suite 700
325 Seventh Street, NW
Washington, DC 20004-2802
(202) 638-1100 Phone
Wednesday, August 27th 2003
Mark B. McClellan, M.D., Ph.D.
Food and Drug Administration (HFA-305)
Dockets Management Branch
Docket No. 75N-183H
5630 Fishers Lane, Room 1061
Rockville, Maryland 20852
Dear Dr. McClellan:
On behalf of our nearly 5,000 member hospitals, health systems and other providers of care, the American Hospital Association (AHA) appreciates the opportunity to comment on the Food and Drug Administration's (FDA) reopening of the administrative record regarding the tentative final monograph (TFM) for over-the-counter health care antiseptic drug products.
The AHA has been impressed with the efficacy and health benefits of alcohol-based hand rubs, which have proven to reduce health care-associated infections (HAIs). Given the importance of reducing HAIs, we are concerned that the FDA's proposed rule would undermine this critical goal by taking hand rubs off the market and requiring manufacturers to reformulate these products in a way that is at best, unnecessary, and at worst, detrimental to their proven efficacy.
The 2002 publication of the Centers for Disease Control and Prevention (CDC) Guidelines for Hand Hygiene increased general recognition of how alcohol-based hand rubs can improve hand hygiene practices and reduce the incidence of infection.1 The AHA strongly supports the use of these products in all appropriate locations in order to enhance hand hygiene compliance and achieve related reductions in HAIs. We believe that the FDA's proposed rule could unintentionally reduce the widespread usage and effectiveness of alcohol-based hand rubs.
Our comments address the performance criteria proposed for health care antiseptic drug products, and more specifically, products that fall under the Antiseptic Handwash/Health-Care Personnel Handwash category (§333.410(a)). Our comments do not refer to the performance criteria for the Surgical Hand Scrub or Patient Preoperative Skin Preparation categories.
The safety and effectiveness of currently marketed over-the-counter alcohol-based hand antiseptics are supported by a well-established body of scientific evidence. These studies in health care and community settings have demonstrated the effectiveness of these products to reduce disease and the transmission of pathogens.2-11 Furthermore, alcohol-based hand rubs have been shown to provide superior efficiency in accomplishing hand hygiene as compared to use of antimicrobial soap and water.12 In fact the CDC Guidelines for Hand Hygiene notes that alcohol-based products are more effective for standard handwashing or hand antisepsis by caregivers than soap or antimicrobial soaps.
However, the proposed language of the 1994 TFM creates an inherent conflict for alcohol-based hand rubs. These hand rubs are designed for repeated, routine and rapid hand disinfection and are not intended to have any residual antimicrobial effect. The FDA apparently recognizes the effectiveness of these products because the 1994 TFM classified the rubs' main active ingredient, ethanol 60-95%, as a Category I (i.e. highly effective) active ingredient. But, at the same time, the Health Care Personnel Handwash Test methodology and performance criteria in the TFM require all antiseptic products -- including alcohol-based hand rubs -- to exhibit a cumulative ("persistent" or "residual") antimicrobial effect. The inherent conflict: The 1994 TFM comments acknowledge the lack of such residual effect for ethanol 60-95%, yet classified it a Category I active ingredient.
This inconsistency will cause most existing alcohol-based hand sanitizers in use in health care facilities to fail the 1994 TFM efficacy standards. Despite the acknowledged lack of residual effect of waterless, alcohol-based hand antiseptics, regrowth of skin microflora occurs slowly after application of alcohol-based hand rub. In fact, because of the superior antimicrobial activity of many waterless, alcohol-based hand antiseptics, in vivo studies have shown alcohol to be comparable, if not better, than topical over-the-counter antimicrobials even though the latter have residual activity. 10-11; 13-14
In order to pass the 1994 TFM performance criteria for a Health Care Personnel Handwash, alcohol-based hand rubs would have to be reformulated to include an antimicrobial ingredient that provides residual activity. The risk/benefit of this additional antimicrobial chemical is not sufficiently demonstrated or studied to be a mandated requirement for alcohol-based hand antiseptic products. Alcohol alone has been demonstrated to be effective for hand hygiene for health care personnel.
Alcohol-based antiseptic handwash products are intended for frequent, repeated use by health care workers to rapidly reduce the level of transient skin microorganisms. As such, the most important performance factors are speed of action and spectrum of activity. A persistent or cumulative effect is not a necessary requirement. In fact, reformulation of waterless, alcohol-based hand antiseptics to include an additional ingredient for persistence might pose several unintended adverse effects:
The residual biocides could result in higher incidence of dermatitis in caregivers who use these products.
Unknown long-term effects upon natural skin flora.
Increased theoretical risk of developing biocide-resistant organisms.
A false sense of security for users based upon the belief that a "long lasting" formula provides a type of ongoing barrier protection.
In spite of the well-documented benefits of alcohol-based hand sanitizers, finalizing the 1994 TFM in its current form will effectively remove a majority of the currently-available products from the market. This runs counter to public health concerns and will impose unnecessary restrictions on health care organizations. Furthermore, this scenario will almost certainly result in reformulated products with less proven risk/benefit considerations. Reducing health care-associated infections through increasing the use of alcohol-based hand sanitizers is too important of an issue to undermine through unnecessary reformulations of the product. Each year, an estimated 2 million health care-associated infections occur in the United States.15 Scientific research has shown that many of these infections are transmitted to the patient from caregivers' hands and that use of these alcohol-based hand sanitizers is an effective way to address these concerns.
For these reasons, it is imperative that the Final Monograph for Health Care Antiseptics correct the inherent conflicts in the 1994 TFM. We recommend that the persistence/cumulative requirement for waterless, alcohol-based hand antiseptics be eliminated or that an exception for this class/formulation of antimicrobials be created. The test performance criteria should be limited to the first wash, thereby correlating with actual conditions of use and the established history of current product effectiveness.
We appreciate the opportunity to submit these comments and strongly urge reconsideration of the proposed language. If you have any questions or concerns about these comments, please feel free to contact Roslyne Schulman, senior associate director for policy development, at (202) 626-2273.
Executive Vice President
1. Boyce JM and Pittet D. Guideline for Hand Hygiene in Health-Care Settings: Recommendations of the Healthcare Infection Control Practices Advisory Committee and the HICPAC/SHEA/APIC/IDSA Hand Hygiene Task Force. Infection Control and Hospital Epidemiology. 2002; 23(Suppl):S3-S40.
2. Bischoff WE, Reynolds TM, Sessler CN, Edmond MB, Wenzel RP. Handwashing compliance by health care workers: The impact of introducing an accessible, alcohol-based hand antiseptic. Arch Intern Med. 2000; 160:1017-21.
3. Fendler EJ, Ali Y, Hammond BS, Lyons MK, Kelley MB, Vowell NA.. The impact of alcohol hand sanitizer use on infection rates in an extended care facility. American Journal of Infection Control. 2002; 30:226-233.
4. Harbarth S, Pittet D, Grady L, Zawacki A, Potter-Bynoe G, Samore MH, Goldmann DA. Interventional study to evaluate the impact of an alcohol-based hand gel in improving hand hygiene compliance. Pediatr Infect Dis J. 2002; 21:489-95.
5. Hilburn J, Fendler E, Groziak P, Hammond P. The use of alcohol hand sanitizer as an effective infection control strategy in an acute care facility. American Journal of Infection Control 2002;30 (4): Poster 129.
6. Hugonnet S, Perneger TV, Pittet D. Alcohol-based handrub improves compliance with hand hygiene in intensive care units. Arch Intern Med. 2002;162:1037-43.
7. Pittet D, Hugonnet S, Harbarth S, Mourouga P, Sauvan V, Touveneau S, Perneger TV. Effectiveness of a hospital-wide programme to improve compliance with hand hygiene. Infection Control Programme. Lancet. 2000; 356:1307-12.
8. Pittet D. Compliance with hand disinfection and its impact on hospital-acquired infections. J Hosp Infect. 2001;48 Suppl A:S40-6.
9. Ehrenkranz NJ, et al. Failure of bland soap handwash to prevent hand transfer of patient bacteria to urethral catheters. Infect Control Hosp Epidemiol. 1991 Nov;12(11):654-62.
10. Girou E, et al. Efficacy of handrubbing with alcohol based solution versus standard handwashing with antiseptic soap: randomised clinical trial. BMJ. 2002; Aug 17;325(7360):362 11. Parienti JJ, et al. Hand-rubbing with an aqueous alcoholic solution vs traditional surgical hand-scrubbing and 30-day surgical site infection rates: a randomized equivalence study. JAMA. 2002 Aug 14;288(6):722-7. Erratum in: JAMA 2002 Dec 4;288(21):2689.
12. Voss A, et al. No time for handwashing!? Handwashing versus alcoholic rub: can we afford 100% compliance? Infect Control Hosp Epidemiol. 1997 Mar;18(3):205-8.
13. Larson EL, et al. Assessment of two hand hygiene regimens for intensive care unit personnel. Crit Care Med. 2001 May;29(5):944-51.
14. Zaragoza M, et al. Handwashing with soap or alcoholic solutions? A randomized clinical trial of its effectiveness. Am J Infect Control. 1999 Jun;27(3):258-61.
15. Weinstein RA. Nosocomial Infection Update Emerging Infectious Diseases. 1998; 4(3): 418-20; and Morbidity Mortality Weekly Report. Monitoring Hospital-Acquired Infections to Promote Patient Safety -- United States, 1990-1999. March 3, 2000; 49(08):148-53.