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0 1 from Peter Samuel, 12131 Main Street, PO Box 99 Libertytown MD 21762, Te1301/898-5882 DC:202/4E8-8451 Fenr 301/898A465 September 23, 1992 FDA, EPA mug company with bad test, then demand it fix the test by Peter Samuel It was a cmalli news item in thc May 15 issue of the trade journal Hospital Purchasing News: "3M exits glutaraldehyde business after 15 ycars." Opting "not to get bogged down in the federal government's regulatory prOcess;' tha 3M company was pulling Glutan:x off the market atter fifteen years. A company spokesman said that Glutarex was a very small part of the company's business and it was not worth going through the hassles of gaining Food and Drug Administration (FDA) approval. Glutarex was the 3M brand name for a disinfecting and sterilizing solution basc:d on the chemical glutaraldehyde. It had been one of about eight competing products - mostly based on glutaraldehyde too -- used in hospital operating rooms, dental clinics and doctors surgeries for disinfecting sensitive • instruments and keeping tables and other surfaces dear of germs. For years the EPA has regulated sudi germicides but lately the PDA has claimed jurisdiction too - by defining the disinfectant solutions as "medical devices" (How expansionist regulators will stretch the language!) And the Federal Trade Commission has gott into the act by questioning the advertising claims made in connection with marketing the products. The three federal agencies have been wreaking havoc for established mannfactttrers of the germicides. A couple they are forcing close to bankruptcy for no good reason, and as thv 3M withdrawal shows, they are adding a massive risk premium to the calculations of anyone doing business in territory where the FDA, EPA, FTC gangs rnam. The agenriPs that are supposedly dedicated to serving public health are in this case endangering it by spreading disinformation about the products, disrupting the supply chain for disinfectants for medical and dental instruments, and heavily assaulting the economic viability of the manufacturing companies. Their tnp managements have been forced to hire large crvws of lawyers in place of salesmen and manufacturing personnel. The most powerful and most easily used medical disinfectant, Sporicidin was forced off the market completely on December 13 last year by a p -4 A ~ 0 ~ O .P W

. 2 combined team of the Lnvirotunent Protection Agency, the Food and Drug Adnunistration and the Fpdrral Trade Commission. The Sporicidin products -- a cold sterilizing solution, disinfectant sprays, disinfectant tnwalettes and a general disinfectant solution -- had been used by hospitals, clinics, physicians and denflsts unchanged since their introductiuu 14 years ago and gained nearly a quarter of the 860m to 570m annual market for medical instrument disinfectantc. Until 1977 the dominant disinfectant was Cidex, a Johnson and Johnson product that is ntainly glutaraldehyde. In a replay of a venerable capitalist theme a little guy came along with an improvement. A Washington area dentist turncd inventor/entrepreneur Dr Robert Schattnpr took on J&J. He't1 already made several million dollars with his invention of the wQllknown throat spray Chioraseptic (Proatur and Gamble bought out Schatttter's rights and now markots it). Schattner then experimented with a mir of the throat spray's main constituent, phenol together with the gluaraldehyde used in the Johnson and Johnsnn product to try and produce a better operat9ng room disinfectant. The two germicides combined into a • product he called Sporidtlin. This mixture turned nut to have a synorgistic disinfectant effect which was considerably more powerful than the straight glutaral.dchyde based products. Fur many purposes it could be diluted with water. It had less of a clouding effect on optical instruments and was easier to use. Diluted with water, Sporic.idin was able to kill germs, viruses and epnres more quickly and at room temperatures. It grew in market share partly because of the inf.uuvenience of storing the bulkier non-dilutable simple glutaraldahyde based disinfectants and the nuisance of having to heat them to got their advertised genn killing capabilities, as compared to Sporicidin's effeetiveness at (iA degrees. For example to be sure of killing the tuberculosis bacteria an nperating room instrument must be immersed in undiluted Cidex for 45 minutes at 77 degrees (requiring a bit of heat in aircondltioned hospital conditions), whereas the same disinfection will be achieved in 1/16th solution of Sporicidin in 10 minutes at room temperature of 68 degrers, uCcurding to EPA registered tests. Plain glutaraldehyde composed disinfoctants have several other No disadvantages; V i 0 ~ 4~- 0 ~ ~

i 3 - their vapors sting the eyes, irritate the nose, cause snme skin allergy problems and are noxious enough to be regulated by the OccupaUonal Health and Safety Administration. If the disinfectant is plentifully used in operating rooms and doctors' offices its gaseous concentration can easily exceed the 0.2 partc per million OSHA safety level - the chemical can cloud the glass of instnuments such as endoscopes and mirrors rendering them ineffective for some time after disinfection -- it is harsh on the hands of medical personnel leaving a yellow stain on the skin - it needs to be heated slightly beyond room temperature fnr greatest effectiveness The danger then for operating room patients is that the unpleasantness and inconvenience of the glutaraldphyde-heavy disinfectants will cause staff not to use them extensively enough to thorouglrly decvntaminate instrumenis end surfaces. tirhattner's contribution to the cnvironment of the operating room • and doctors surgery was to provide them with a morP user-triendly, hence more usable, disfnfactant. As documented in a number of product reviews in professional hospital journals, he was able to take a powerful but rather unpleasant disinfectant (glutaraldahdye) and exploit its previously unknown synergistic effect with a less powerful but more-pleasant-handling disinfectant mouthwash (phenol), and make sanifting work a little easier in hospital operating rooms and doctors offices. The innovation produced some contrnvarsy in the mid-1980s with claims and counter-daims. Some of these appear to have been simply honest differences of professional opinion, but many were mntivated by competitive considerations. The regulators chose to disregard the fact that hospital teehnieianc, doctors and dentists are qualified by years of scientific education and daily work experience to make informed judgments about the products they buy. What is most extraordinary about the recent draconian intervention against the disinfectants is that these products are bouRht and used almost exclusively by lrained wcll-infotmed professionals who have a menu of choices and appear to be satisfied with the products. Normally, regulaLors intervene where customers are unhappy with a product, or arr tncapable of ~ making informed decisions. Yet the users of Sporicidin or othor similar `t . ~ A 0 .P a+

• 4 disinfectants have not been lodging complaints with the agencies. I 'he Centers for Disease Control says it dnes not have a record of any case of a diRPase acquired as a result of failure of Sporicidin or other similar disinfectants. The Sporicidin product has hven repeatedly tested by independent testing laboratories. As late as December 12, 1991 - ironically the day before the raid -- a rwtariced letter to Sporicidin's Robert Schattner from Tohn H.Lee, the product manager of the Antimicrobial Programs Branch of the Office of Pesticides and Toxic Substaaces of the EPA said that Sporicidin coitd sterilizing solution was "properly registered and certified" and that it was approved for sale for the disinfecting and sterilizing uses Indicated on its lahal (See facsimile). But the trade press had carried a story at the begituting of December 1991 that the feds had decided to act against Sporicidin. The company made a set of tPlephone calls but could find out nothing. On the morning of December 13, a massive interagency assault on the company began. Three agencies itSued long press releases and gave press briefings. Teams of agents representing the Food and Drug Administration (FDA) and the Environmental Protection Agancy (EPA) accompanied by armed U.S. Marshals arrived unannounced at the Rockville Maryland offices of Sporidtlin Inc and simultaneously at its rontract manufacturing facility in Jonesboro Tennessee with a slew of orders and charges against the company's producta. Stocks were seized. Stop sale, stop use and removal (movement) orders wore issued. A formal complaint was filed alleging the products were "adulterated and misbranded." The government agents demanded the company recall all its rrodncts, and began searching and copying ita files and records in a hcavyhanded display of power. One pretext for all this was the claim that Sporicidin did not have an FDA marketing permit (called a 510k). This was a Kafkaesque complaint since the FDA had not issued any rules or even given any unofficial guidance as to how companies could obtain such clearances. No dearances had been given, so the same coniplaint could have been made -- and muld be made today - about any of Sporiddin's competitors. The company has EPA permits dating back to 1976 which were renewed periodically, the last being issued the day before the regulators hit the company December 13. The FDA treated the EPA permits as irrelevant. 0

• • 0 The more serious sounding pretext for the assault on Sporicidin was the claim that its products were ineffective. David Kessler the FDA administrator was quoted in a pzebs release as saying: 'These products do not wurk. Doctors, dentists and othpr health professionals should stop using them." Adding some newsworthy drama, the FDA also charged that Sporicidin products could cause "serious, adverse health consequences or death." (In an interesting qualification the Centers for Dibease Control was quoted as saying that it had no record of any actual case of nosocomial or hospital/dnctnrs' office infection attributed to the failure of Sporiddiut products in their 14 year histury) The EPA and FI'(.' joined the FDA in publicly accusing the company of false and misleading advertising. The three government agencies claimed that joint FDA laboratory tests had shown the Sporicidin products failed to storilize as claimed on the labels. That would on the face of it seem to be an excellent case for the government action and there was considerable positive npws coverage of the government action including the obligatury one line denial by the company. The regulators were pictured as brave and forceful public sorvants cracking down on pharmaceutical charlatans. Trouble is; it was the iegulators who were the charlatans! It has transpired in the seven months since the FDA and the EPA staged their media circus on December 13 last year that what Is ineffectual and a menace to public health is not the Sporicidin disinfectant product but the government testing procodure for disinfectants. Moreover it Is now clear that the EPA at least knew its tests were highly quostionable, but participated in tha raid on Sporicidin and all the phony publicity all the same. Pive months after the raid and denunciation of St+oridicin's products the FDA flipped On May 25, the agency quietly signed an agreement wilh Sporicidin allowing several of the psuducts that administrator Kessler last December said were "inrfforrive" and "adulterated" back on the market without any change whatever in their formulation! FDA spokesman Sharon Snider told inquirers that the agency had settled the case with Sporicidin. It could go back on the market, she said. The FDA thereby tacitly ackitowledged the bogus nature of its sweeping charges against tiporicidin that it had so righteonsly and forcefully made late last year. In an apparent facesaving move the agency insisted that the cuutpany add some inconsequential detail to the Instructions in the form of an extra instruction insert in the packaging boxes s

• 6 of its products. And in an extraordinary acsatilt on the first amendment of the constitution it insisted that the company deatroy reprinls of scientific Journal articles that touch on its products. FDA officers have demanded to supervise the dumping of boxes full of articles on glutaraldehyde based disinfectants publishcd in THE JOURNAL OF OPERATING ROOM Rl•'SHANC'H, THE JOURNAL OF CLINICAI. MICROBIOLOGY, OPTOMETRY AND VISION SCIENCE and such like. Shades of Nazi book-burning! The EPA is in an extraordinary situation. For years it has issued approvals of Sporicidin and other competitive disinfectants, knowing that the limitations o( the AOAC test will produce regular 'failures' of good product. It knows the tests of disinfectants are fattlty. Yet it joined in the multi-agency mugging of Sporiudin. Its fellow muggers at the FDA now appear to want to make amend< with the victim, yet the EPA Is stalling over lifting its bana against Sporicidin. Although the EPA has repeatedly endorsed the validity of the product over the years and in December it allowed the FDA to take the laad role against Sporicidin, it now says it has now said It is not bound by any • FDA settlement with the company. Just over a year before it participated in the raid on the Ruckville company the EPA formally acknowledged serious deficiencies in the test used against Sporicidin. It laid out ten deficiencies in the test in a request for applicants for a contract to research a replacement testing system for disinfectant5. This is published in the Federal Register dated December 6, 1990. There the EPA said that the existing test methods (the so-called AOAC sporicidal test) "lack reliahility and reproducibility" and cited ten problems in the test. There wae variability in results because of vnryirtg hardness of water and neutralizers used, lack of standardi~.ation of the soil extract medium used, unreliability in the growth medium for the Closlridlunt spore, lack of uniformity in carrier (container) conditions, lack of standardization of the spore load in the carriers, and a ten fold variation allowed in the test pathogens' resistance to hydruchlurIc add. The EPA subsequently awarded a $700,000 researr•h contract to a Canadian university to develop an improved test, becausc of shortcomings in the AOAC test. Yet !t was this test which the HhA acknowledged as lacking reliability that had been the basis for assaults against disinfectant manufaciurers. Sporicidin is not the only manufacturer being harassed. A competitor p Metrex Corporation of Colorado which markets MetriCide -- a similar -4 O A w

• 7 glutaraldehyde-based disinfectant - was also the cuhject of attack by the regulatnrs with the L•PA itself the chief hitmen. The EPA was hwnlliated when It was taken to court by Metrex Corporation, mamttacturer of MetriCide. The company established to the catisfaction of a federal court judge that iwt only was the EPA test ittelf deficient if carefully and prnPerly carried out, but that the EPA testing was in fact ahamefully badly conducted. A bad test was badly dune! Judge Lewis T. Babcock of the U.S. INstrict Court in Colorado concluded June 18 in the case of Metrex Corp vs. William K Reilly (EPA adtuini5trator) that the g,overnment had failed to follow proper laboratory procedures in testing MetriC'ide. It failed to properly establish the ineffectiveness of the products it had said were ineffeWve, the judge said. The case rrvPaled sloppy testing procedures by the EPA. In some cases samples were overdiluted as compared to the label instructfons. An Inappropriate neutralizing snlutinn was used that did not properly neutralize the disinfectant. The tests showed that a more highly diluted sauiple of the . disinfectant was more effective than the lass watered sample -- the reverse of what should be expected. Yat the EPA testers failed to retest where sudt anomalous results were found. And they failed to use control samples, which prntPssional testers said were essential. The EPA's documentation of its tests was sloppy and inadequate, ittdepettdent scientists all said. The EPA failed to adhere to the estahlished code of Good Laboratory Practices which it requires of independent laboratories. (The L•PA's own laburatury staff followed poor recording and other lab procedurPs, thp exact kind of negligent lab behavior for which it levies fines against oubide laboratories of hundreetls of thousands of dollars.) The EPA was apparently so frightened of revealing its shoddy laboratory practiceb that it declined to put any of the actual testing staff on the witnms stand in Denver. As a result Metrex Corp persuaded thc judge that the EPA had done the company a grave injustice In declaring Its product ineffective. Judge Babcock said in his judg,ment that the EPA'b test results of the sterilant "simply cannot be said to ho valid" and that the EPA's press releases and telephone hot line announcements about the test failures of Metrex pruducts were "as a matter of fact and of law false." He issupd an injunction N M ordering the EPA to cease its statements that the Mctrex disinfectants were V A i ~ ~ ~ A ~

0 8 ineffective or had failed tests. And he said that the EPA "either knew or should have known that the restdts in this case were not sufficionfly reliable to bc called valid." Metrex Corp brought as witnesses miaobiologists who said they had frequently performed the EPA test (called the AOAC sporiddal test) and that It was unreliable and inconsistent even when ronducted with maximum care. They noted it is not a quantitative test since it starts without any count uf the spures tu be killed by the sterilant There may be as many as 700,000 spores or as few as 200 to be killed. Moreover the tests call for carrier vessels with quite variable numbers of fissuwes aud 'utterstices In which the spores can 'hide' from the rhamicat, a condition that is designed out of modern medical instruments and modern operating rooms aud detttist/doctors offices where there are stainless steel and varinuc glazed surfaces. As a result there is great variability in the results of the EPA test and all sterilants fail the test regularly. Mary Bruch, a microbiologist at MicmHin 1'est Jnc, a Chantilly Virginia based private laboratory said that even the best practitioners of the EPA . sporiciddl test get false results almost as often as they get correct results. !;hp said her laboratory uses the test only because the EPA requires it, adding "Jt's a game." Another microbiologist Norman Miner, former manager of biological sciences at a Johnson and Johnson, said that he teated the leading glutaraldehyde based prndurts, including Cidex - the dominant product used in hospitals and that in hundreds of tests, all lhe producls failetl the AOAC test 20 to 25 percent of the time. He said the hPA's testing of the Metrex sterilants was particularly badly done and that the documented result "doesn't nteke sense." "Hither there has been a mislabelling, or a mistranscription of results from some raw data...it duesn't make sense...as a scientist I wouldn't draw a conclusirtn based on something that doesn't make sansQ " On the basis of such botched testing the EPA aiutututced to the public that the Metrex sterilantc wern inpffvNive, and started the process of sending its brown shirts in to close down the company. Only the Colorado court has stopped It. The tests used to discredit Sporicidin were apparently just as bad. They were conducted strangely nut by the EPA but in a food testing laboratory run N . My tho FDA in Minneapolis. Like many such products, Sporicidin has a v ~ ~ A ~ 0 tn 0

0 • 0 liuuted shelf life, after its two components are mixed. It says on the hattle that after mixing or 'activation' it may only be used for 30 days. Beyond that it tends to lose its orip,inal wlur and goes yellowy-amber. The Fl )A test data sheets describe the tested product as "amber" in color indicating the lab may have tested aged and bruken-duwn Sporicidin. Moreover the laboratory analysis showed it was tested at 1.92% glutaraldehyde whereas it is registered for use at a minimum 2.0% concentration of glutaraldehyde. The lab may just have overdiluted the sterilant. Even yu Spuricidin's cold sterilizing solution passed 239 out of 241) tests. Joseph ICon2elman clinical director of oral health research at the large Walter Reed Army medical center testified in the Sporicidin case wrote that his review of the tests on Sporicldin persuaded him the tests were improperly conducted, and said he regarded the PDA report as mis]eaQing. Said the Walter Reed mare "fhe (H•!]A) shidy purports to show that the cold sterilizing solution failed some tests at full strength. In actuality 239 out of 240 tubes passed the test. The (FDA) analysts failed to inquire whether the Ione failure might have been contaminated by other sources, a common scientific oonfirmatury technique which should have been followed." A newsletter of the Chemical Specialties Manufacturers Association dated July 19 quotes James Danielson, a micrubiulogist at the FDA lab which tested Sporicidin, as saying that "over half° the many disinfectant products they tested failcd the AOAC tcst, yet Kessler of the FDA, Reilly of RPA and the FfC chose to single out the one company for an espPrially savage attack, Virginia Chamberlain the person in charge of disinfection and sterilization at the PDA's office of compliance and surveillance Is quoted in the CSMA newsletter as acknowledging that the AOAC sporicidal test is "outdated" and as saying that the FDA is working to improve its test methods. Tim Ulatowski, associate director of the FDA's Center for Devices and Radiological Health is quoted in the same industry newaletter as bayinK: "AOAC methods are troublesome." Apparently ron<wrn ahout the inadequacy of the tests at the working lovcl of the FDA never filtered up to elevated level of the agency's multi-media wonderboy, David Kessler. Or else he doesn't care't At the press conference December 13 when the government muggers were beating up on Spuricidin, they told journalists that Sporicldln's Lustomers could safely switch to the Johnson and Johnson product Cidex. Yet 9

0 10 Cidex fails the AOAC test just as oftcn as Sporicidin and MetriCide, acmrding to the Jolumun and Johnson tester, Norman Allen Miner. He told the rourt in Colorado that he had run the AOAC sterilant test "hundreds, approaching a thousand times." About half dte tests were of Cidex, his product; the other half were C'idex's rompetitors, such as MetriCide and Sporicidin. Cidex failed just as often as the others, he said - 20 to ?a^'16 of the titne. The court testimony was as fnuows: Q. Did you ever see failing results out of either of these producta...? A. Yes. Q. Once in a while? With some regularity? About how frequently? A. (With) sunte regularity. Maybe once in four or five runs. t1. How does the performance of MetriCide...compare to that of Cidex. A. It is absolutely statistically equivalenL All the cnld sterilizing solutions are based on glutaraldehyde, so it was only to be expected they would perform similarly, the former Johnson and Johnson tester said, because their principal active disinfectant component was _ the same. All the companios buy their glutaraldehyde from the same manufacturer. What of the dramatic charge by the feds December 13 that Sporicidin was "adulterateJ." It turns out this allegation arose from the regulators innoconce of basic chemistry, and their failure to consult anyone with a working knowledge of chemistry. Kessler's super-yleutlts had noticed a discrepancy between the list of ronstihtents on the label and the manufacturing formula. The product label names sodium phenate aa a constituent whereas the factory invoices show that sodium hydroxide and phenol are used, but no sodium phenate. It was on the basis of this supposed discrepancy that the FDA publicly charged the company with adulteration of its product and misbranding. What they did not know was that sodium phenate is obtained by mining wdiwn hydroxide and phenol. As soon as the iwn liquids aro mixed they become sodium phenate. The charge that the company had misbranded its product was therefore baseless and the charge that it was adulterated was absurd. In the consent agreement between Sporicidin and the IDA the company agreed to what the FDA chose to call a"reconditioning' of its product. Now in regular English usage reconditioning mcans that the product N is reworked to somehow change its composition and characteristics. But the y ~ A A O th lV

0 11 Fi)A hae acknowledged in the May 15 consent agreement that Sporicidin as manufactured for years is quite OK, and the fine print of the consent agreement provides that axisting stocks will be allowed onto the market again chemically unchanged. Production will resume using exactly the same constituents. The disinfectants will hv exactly the same as before. So what is this "reconditioning" that the FDA is requiring? The word "recurtditioning" is being used by the FDA solely to dascrihe the insertion of an extra instruction sheet in the packaging. This misleading language is part of the PDA's cover up uf itb backdown. It is an attempt to mislead people tntn thinking that the agency forced the company to change its product, when in fact the agency has backed down and acceptetl the prutiuct unchanged. The other face-savar for the FDA is contained in a legal maneuver by which the agency has permitted Sporicidin products back un the market not by approving them but by a "finding of substantial equivalence" to products marketed by the company prior to enactment of the law under which it claiuis jurisdiction. In fact the products are identical. They haven't changed _ and such a 'grandfathering' is simply a way for the FDA to avoid saying ' explidtly that it has approvetl thent. A lPttor from the FDA to Sporicidin dated September 15 spells this out: "This letter will immediately allow yuu to begin (It began in 1975. The FDA writer means: 'resume' P.S.) markating your devices (disinfectant solutions - P.S.) in accordance with the terms of the consent decree. An FDA fuiding of substantial equivalence of your devices (disinfectants N.S.) to a pre- Amendment device (disinfectant P.S.) results in a classification (approval P.S.) of your devices (disinfectants P.S.) and pennits your devices (disinfectants P.S.) to proceed to the market, but it does not mean the FDA has~ approved your devices (disinfectauts) "~ -ir a ~q Q~d.t w b m/lie (~) Such Orwellian verbal contortions anstic sleights-of-han ld cannot cover up the simple fact that the e,autct saine ytvducts which FDA said had to be immediately banned as a monace to health last December 13 are okay as of September 15 this year to go back oz~market unchanged. At time of writing the EPA Is still holding out on Sportcidin with some bi2arre maneuvers of its own. Its many pre-Decembcr 13, 1991 approvals of Sporicidin products have remained in effect throughout the assault on tha company even though the EPA joined the FDA in issuing an N • emergency Stop Sale, Use and Removal Order Deceutlrer 13, 1991 because of a 4~h ~ A .fa ® Cn ta

12 . the supposed inuniuent risks that had been demonstrated in thv NI7A test. The F.PA is now offering to lift this freeze on Sporicidin's cold sterilizing solution but only on condition that SpuriLidirt do its own laboratory testing on the product to demnnstratp its efficacy. But it was the supposed inefficacy of the product as suggested by FDA tests that led to the Deceutber 13 1991 bans. So we have reached the situation where the FDA has allowed products back on the market which David Kessler said last year "don't work." The old AOAC test is disnmdited and there is no generally accepted test to demonstrate spnre killing power. But Sproricidin is being asked by the EPA to devise a new test which will be aLceptable to it. But wait! T'hn N.1JA already has research contracts out with the Canadians for an improved test, and estimates it will be another two to three years before that new test protocol for spore killing is completed. EPA wants a small private company to finance n competitive researdi project fur a uew spuricidal test protocol while fts products remain banned on the basis of the discredited test. "Only in Attterica!" say its international competitors. Sporiddin estimates itc losses to the end of July at the hands of Washington's blundering hiimen at nture than $10 million -- $5 million in lost sales, $2m in custnmer reimbursements, over $1m in legal fees and $2m in lost inventory. 30 people in the manufacturing plant lust their jobs and a dozen administrative and sales people have gone. In their place a team of lawyersl What's behind this destructive madness on the part of regulators? Several agencies fighting for regulatory turf; an effort to 'get' a little upstart company that has upset the established players; a drive by regulators to get scalps on the wall to justify their budget claims in Congress; the huge ego of the likes of PDA administrator D. Kesslet) just normal Washington blundering. Perhaps iYs a hit of all of these. ends Peter Samuel runs Greentrack International, a Washingtnn UC' area news service that Lovers environmental issues from a skeptical perspective. Pnds all 3Mout3/9/23/92 N O V ~ A P O N A