STATE OF FLORIDA

DIVISION OF ADMINISTRATIVE HEARINGS

LEMMON COMPANY, )

)

Petitioner, )

)

vs. ) CASE NO. 89-2644RX

)

DEPARTMENT OF PROFESSIONAL ) REGULATION, BOARD OF PHARMACY ) and BOARD OF MEDICINE, )

)

Respondent. )

)

FINAL ORDER

Pursuant to notice, formal hearing in the above-styled case was held on June 19-20, 1989, in Tallahassee, Florida, before William F. Quattlebaum, Hearing Officer, Division of Administrative Hearings.

APPEARANCES

For Petitioner: Charles A. Stampelos, Esquire

600 First Florida Bank Building Tallahassee, Florida 32301

For Respondent: John Rimes, Esquire

Department of Legal Affairs The Capitol, Suite 1601

Tallahassee, Florida 32399-1050 STATEMENT OF THE ISSUES

The issue presented for consideration is whether Rule 215-5.001(13), Florida Administrative Code, which adds carbamazepine to the negative drug formulary, is an invalid exercise of delegated legislative authority.

PRELIMINARY STATEMENT

At the hearing, the Petitioner presented the testimony of Jerry F. Wells, Dennis Szymanski, Elizabeth Lane, and Melvin Van Woert, the deposition testimony of Ronald B. Stewart and Carlo P. Michelotti, and offered into evidence exhibits numbered 1-7, 9-10, 13, 16, 18-19, 21 and 24, which were admitted. The Respondent presented the testimony of Ronald B. Stewart and Martin R. Natter, and had three exhibits admitted into evidence. Joint exhibits numbered 1 through 16 were admitted. The transcript was filed on June 30, 1989.

By agreement of the parties, proposed orders were due twenty days following filing of the transcript. Both parties filed proposed orders on July 17, 1989. The proposed findings of fact are ruled upon either directly or indirectly in the Order and in the Appendix which is attached and hereby made a part of this Order.

FINDINGS OF FACT

1. Section 465.025(2), Florida Statutes, states that, when filling prescriptions for medication, Florida pharmacists must substitute less expensive generically equivalent drugs for the physician-prescribed medication, unless the physician or patient requests otherwise. A "generically equivalent drug product" is defined at section 465.025(1)(b), Florida Statutes, to mean the same active ingredient, finished dosage form, and strength. For a physician to indicate that the prescription should be filled as written, the statute provides at section 465.025(2), Florida Statutes, that the doctor must write the words "medically necessary" on the prescription, or in the case of an oral prescription, so indicate to the dispensing pharmacist.

   
   

2. Section 465.025(6), Florida Statutes, provides for the establishment of a "negative drug formulary." The formulary is a list of drug products which are determined by the Boards of Pharmacy and Medicine "to demonstrate clinically significant biological or therapeutic inequivalence and which, if substituted, would pose a threat to the health and safety of patients receiving prescription medication." Substitution by a pharmacist of a generic drug for a physician- prescribed brand name drug is prohibited in cases where the drug is included in the negative formulary. The Boards have established the formulary by Rule 215-

   5.001 Florida Administrative Code. Neither the statute nor rule provide a definition of "clinically significant biological or therapeutic inequivalence."

   
   

3. In the case of carbamazepine, it is clear that clinically significant biological or therapeutic inequivalence between brand Tegretol and the generic formulations would pose a serious threat to the health and safety of patients taking the medication. The rate at which active ingredients are dissolved and absorbed into the blood stream, and the time period during which such ingredients remain at therapeutic levels are critical in terms of properly titrating patient dosage levels. In the case of carbamazepine, the task is further complicated by the fact that carbamazepine affects its own elimination from the human body.

   
   

4. On May 1, 1987, the Board of Pharmacy received a request from Ciba- Geigy, a pharmaceutical company, to add carbamazepine to the "negative drug formulary." Carbamazepine is the generic name for an anticonvulsant drug used in the treatment of epilepsy and other disorders. The effect of placing carbamazepine on the negative drug formulary would be to prohibit the substitution of generic carbamazepine for physician-prescribed "Tegretol," a Ciba-Geigy product.

   
   

5. Carbamazepine was first marketed under thee brand name Tegretol, the

   so-called "innovator" form of the medication. Following the expiration of Ciba- Geigy's proprietary rights to the chemical formulation marketed as Tegretol, generic carbamazepine manufacturers began to produce the drug.

   
   

6. Tegretol is still manufactured and marketed by Ciba-Geigy. In addition to Ciba-Geigy, there are six manufacturers of generic carbamazepine. Lemmon Company manufactures and markets "Epitol," one of the generic carbamazepine products. Tegretol and Epitol are conceded by the Respondent to be virtually identical.

7. Lemmon Company manufactures and markets innovator and generic drugs distributed in Florida through sales to small independent pharmacies, wholesalers and chain pharmacies. Annual Epitol sales in Florida are estimated to be approximately $560,000.

   
   

8. Ciba-Geigy, as justification for the request to add carbamazepine to tide negative formulary, asserts that the biological and therapeutic inequivalence between brand Tegretol and generic carbamazepine causes seizures or other side effects in patients who are switched from Tegretol to generic carbamazepine. However, the evidence does not establish clinically significant differences between Tegretol and generic carbamazepine which would support a finding of biological or therapeutic inequivalence. The evidence does not support a finding that alleged seizures or other side effects, where they have occurred, have resulted from the change in medication.

   
   

9. The prohibition against the substitution, by a dispensing pharmacist, of a generic drug for a brand name drug is clearly beneficial to the branded drug's maker and detrimental to the manufacturers of the generic products. Because Tegretol, as the innovator, was the sole available formulation of carbamazepine for an extended period of time, prescribing physicians are more likely to be aware of, and to prescribe, the brand name Tegretol. Prohibition of generic substitutions undoubtedly impacts the sales of such generic drugs; thus Lemmon Company is substantially affected by the action of the Respondent in placing carbamazepine on the negative drug formulary.

   
   

10. Following receipt of the Ciba-Geigy request, the Director of the Board of Pharmacy referred the issue to the Negative Formulary Study Committee for review. The study committee includes consultants to the board from the University of Florida Colleges of Pharmacy and Medicine. The review process apparently provides for initial consideration by the study committee which makes recommendations to the Negative Formulary Committee which, in turn, makes recommendations to the Boards of Pharmacy and Medicine.

    
    

11. On July 1, 1987, the study committee considered the Ciba-Geigy request, including information submitted by Ciba-Geigy apparently consisting of limited anecdotal data, and thereafter elected not to recommend carbamazepine for inclusion on the negative drug formulary. The rationale for the determination was that the anecdotal information provided by Ciba-Geigy was not persuasive, and that there was no well-controlled clinical evidence demonstrating therapeutic differences between carbamazepine brands.

    
    

12. On September 22 and November 25, 1987, the study committee met and again considered the Ciba-Geigy request. Additional anecdotal information had been received, primarily letters from physicians supporting inclusion of carbamazepine on the negative drug formulary. Further, Ciba-Geigy had submitted information related to six European studies purporting to establish the inequivalence of various carbamazepine formulations. The study committee found the information to contain "considerable inconsistency" and again elected not to recommend placement of carbamazepine on the negative drug formulary. The study committee suggested deferral of further consideration pending completion of a controlled study (the "Penry" study, which remains in progress) which may provide additional information related to alleged inequivalence of Tegretol and generic carbamazepine.

13. On May 31, 1988, the study committee met and again declined to recommend that carbamazepine be included on the negative drug formulary. The study committee considered information, apparently erroneous, related to the Veteran's Administration Hospital System, but nonetheless chose to await the results of the Penry study.

    
    

14. On November 1, 1988, four members of the Negative Formulary Committee, met by telephone conference call. The Negative Formulary Committee includes members of the Boards of Pharmacy and Medicine. At that time, the committee decided to recommend, to both boards, that carbamazepine be included in the negative formulary.

    
    

15. There is limited evidence indicating the basis upon which this committee took the action. The committee may have considered the anecdotal information contained in letters submitted by physicians supporting the placement of carbamazepine on the formulary. It may have also considered a prior recall of a substantial number of generic carbamazepine dosages which apparently failed to meet FDA standards for tablet dissolution. The committee may have reviewed copies of adverse drug reports (ADRs) provided by Ciba-Geigy purporting to show adverse patient reactions to generic carbamazepine. At least one member of the committee may have considered telephone conversations with randomly selected physicians in his vicinity.

    
    

16. Notice of the intent to add carbamazepine to the negative drug formulary was published in the December 16, 1988 edition of Florida Administrative Weekly. The Board of Pharmacy met on January 10, 1989. The Board of Medicine met on February 5, 1989. Both boards considered essentially the same materials and evidence related to the issue of placing carbamazepine on the negative drug formulary. Both boards elected to place carbamazepine on the negative drug formulary. Materials considered by the boards included physician letters, ADRs, and scientific articles relating to carbamazepine equivalency studies. The boards were aware of the recall of a significant quantity of generic carbamazepine tablets. There was discussion related to FDA standards and testing methods, and concern expressed related to interchangeability between carbamazepine products. There was discussion of Florida's Medicaid program, apparently, at least in part, based upon erroneous information, and on the carbamazepine-related issues being considered in at least one other state.

    
    

17. Standards and specifications relating to the quality and purity of drugs available in the U.S. are established by the United States Pharmacopeia (USP), an independent entity, which has established such standards for carbamazepine. There is no evidence which would suggest that USP standards for carbamazepine are inadequate or erroneous. Such standards are found to be reasonable.

    
    

18. The U.S. Food and Drug Administration (FDA) has responsibility for evaluation and control of prescription and generic drug products marketed in this country. The FDA utilizes the specifications and standards developed by the USP. As part of this responsibility, the FDA monitors the therapeutic equivalency of innovator and generic drugs marketed in the U.S., and makes specific findings as to such equivalence. Such findings are identified in the publication, Approved Drug Products with Therapeutic Equivalence Evaluations, commonly referred to as the "Orange Book."

    
    

19. Drug products considered to be therapeutic equivalents by the FDA are pharmaceutical equivalents that can be expected to have the same therapeutic effect when administered to patients under the conditions specified in the

    labeling. As stated in the Orange Book, the FDA evaluates as therapeutically equivalent those products that meet the following general criteria:

    
    

    1. they are pharmaceutical equivalents in that they

       1. contain identical amounts of the same active drug ingredient in the same dosage form, and

       2. meet compendial or other applicable standards of strength, quality, purity, and identity;

    2. they are bioequivalent in that

       1. they do not present a known or potential bioequivalence problem, and they meet an acceptable in vitro standard, or

       2. if they do present such a known or potential problem, they are shown to meet an appropriate bioequivalence standard matching both rate and extent;

    3. they are adequately labeled; and

    4. they are manufactured in compliance with Current Good Manufacturing Practice regulations.

       
       

20. According to the FDA Orange Book, drug products are considered pharmaceutical equivalents if they contain the same active ingredients and are identical in strength or concentration, dosage form, and route of administration, and meet the same or comparable standards, as to strength, quality, purity, and identity. They may differ in characteristics such as color, flavor, shape, scoring configuration, packaging, preservatives; expiration time, and, within certain limits, labeling.

    
    

21. Bioequivalent drug products are those which display comparable bioavailability when studied under similar experimental conditions. Bioavailability describes the rate and extent to which the active drug ingredient or therapeutic ingredient is absorbed from a drug product. Drugs are considered to be bioequivalent when the rate and extent of absorption of the test drug do not show a significant difference from the rate and extent of absorption of the reference drug, when such drugs are administered at the same therapeutic ingredient dose under similar experimental conditions. (There are further, unrelated standards by which bioavailabilty may be determined which are not relevant to this proceeding.) The FDA does not compare generic drugs for equivalency between generics, the assumption being that if the generics are biologically and therapeutically equivalent to the innovator reference, they will be equivalent among themselves. The greater weight of the evidence indicates that the assumption is reasonable.

    
    

22. The FDA utilizes a series of two letter codes to identify therapeutic equivalency evaluation findings. The first letter of the code identifies whether a drug is considered to be therapeutically equivalent; the second letter identifies the basis for the equivalence evaluation. The drug products are listed in the Orange Book according to active ingredient, dosage form and strength.

    
    

23. The FDA Orange Book identifies the 200 mg. oral tablet generic carbamazepine formulations and the 200 mg. oral tablet Tegretol brand carbamazepine, as being "AB" rated. As stated in the Orange Book, the AB evaluation generally denotes products that contain an active ingredient in a dosage form for which the submission of bioavailability or clinical data is required for approval or to permit therapeutic equivalence evaluations, and for which the applicant has provided adequate studies to establish the

    bioavailability and bioequivalence of its product. Otherwise stated, the generic carbamazepine products and Tegretol meet FDA therapeutic equivalence standards.

    
    

24. The FDA finding of bioequivalence is based upon controlled tests performed on healthy live subjects. Such tests measure the maximum drug concentration in the blood stream (the "C-max") and the time required for the drug to reach such concentration levels (the "T-max"). Such statistical information is plotted, with the resulting graphic display (the "AUC," or "area under the curve") visually indicating the therapeutic effect the drug may be expected to provide. The generic drug test results are compared to the innovator brand test results. The suggestion that FDA tests should be performed on unhealthy persons so as to monitor effects in such situations was not supported by the greater weight of the evidence. The purpose of the tests is apparently to evaluate the expected therapeutic effect as measured by the C-max, T-max, and AUC, without complications induced by illness. In light of the purpose of the testing program, such evaluation procedures are reasonable.

    
    

25. The FDA guidelines provide that a generic drug is considered bioequivalent when, at least 90% of the time the tests are performed (the "90% confidence interval"), the statistical indicators are within a 20% range of the innovator drug reference point. The permissible variance appears to reflect the use of live subjects for testing purposes and the fact that, even in tightly controlled situations, test results may be affected by factors related to individual body chemistry or metabolism. Even the same formulation may produce differing statistical data depending on extrinsic variables. The greater weight of the evidence establishes that the FDA guidelines utilized in determining therapeutic equivalence are reasonable.

    
    

26. Although the FDA is reviewing the means by which determinations of equivalency for generic drugs are made, the evidence does not support a finding that the current FDA conclusions are erroneous or otherwise invalid. The evidence does not support a finding that the manner is which the FDA establishes therapeutic equivalence is unreasonable or inappropriate. The testing program utilized by the FDA in ascertaining equivalence is reasonable.

    
    

27. Section 465.025(6)(a), Florida Statutes, provides that the party requesting the boards to include a drug on the negative formulary has the burden of proof to show why such inclusion should be made. In attempting to establish the alleged biological or therapeutic inequivalence between Tegretol and generic carbamazepine, Ciba-Geigy likely encouraged physicians to contact the boards through letter, and may otherwise have mobilized and demonstrated support for their position that carbamazepine should be placed on the negative formulary. A number of physicians sent letters to the Respondent addressing the issue of placing carbamazepine in the negative drug formulary. The letters provide anecdotal allegations of instances where therapeutic failures, generally seizures or side effects, are attributed to use of generic medication instead of Tegretol. The letters provide little evidence upon which a scientific determination can be based. There is no reason to presume that the anecdotal information contained within the letters is false. Although such anecdotal information gives cause for concern, concerned physicians can assure that brand Tegretol is used in filling prescriptions simply by writing "medically necessary" on the prescription, or by orally communicating such instructions in oral prescriptions. The letters are not sufficient to establish clinically significant biological or therapeutic inequivalence between Tegretol or generic carbamazepine.

28. The Adverse Drug Reports (ADRs) do not establish that the alleged adverse reactions were related to the use of carbamazepine or substitution of the generic drug for Tegretol. Such reports are filed on a voluntary basis when a patient on medication experiences an unusual occurrence or incident which may by some means be related to use of the medication. ADRs are completed and submitted to the FDA by physicians or pharmacists who choose to do so. The FDA investigates the reports and monitors for trends which could indicate problems in manufacturing or equivalence. In fact, a reported adverse reaction may have no relationship to medication. The evidence did not establish that the FDA has identified biological or therapeutic equivalence concerns related to carbamazepine ADRs. Although the ADRs supplied by Ciba-Geigy to the boards imply that the alleged reactions resulted from substitutions of generic carbamazepine for Tegretol, no information is provided which specifically establishes a connection between the alleged reaction and the use of, or substitution of, generic carbamazepine.

    
    

29. The bioequivalence of carbamazepine formulations is the subject of current scientific research, as reflected by a number of scholarly articles published in reputable medical journals, which suggest that various formulations may or may not be therapeutically equivalent. One of the studies compared liquid carbamazepine suspension to tablet form and concluded that the formulations were not equivalent due to absorption rates. However, the evidence indicates that the liquid suspension and the tablet formulation would not be classified as generically equivalent drugs in that they are not the same finished dosage form. Other studies have compared United States formulations of carbamazepine to other formulations which are not available within the United States or to formulations for which insufficient identification prevents determining availability. The evidence suggests that such foreign formulations are not commercially available within the U.S. Substitution by a Florida pharmacist of such a foreign formulation for a physician-prescribed carbamazepine product would be improper. The articles do not establish clinically significant biological or therapeutic inequivalence between generically equivalent carbamazepine products which may be used by a Florida pharmacist in dispensing medication.

    
    

30. A recall of the generic carbamazepine tablets due to manufacturing difficulties does not establish biological or therapeutic inequivalence. It is possible for any pharmaceutical company to encounter problems related to manufacturing or storage which require the recalling of previously shipped dosages, as was apparently the case with the recall considered by the boards. Such recalls do not establish that the formulation of a drug is, in a clinically significant manner, biologically or therapeutically inequivalent.

    
    

31. There is no clinically significant evidence which would establish that all generically equivalent carbamazepine products, containing the same active ingredient, finished dosage form, and strength are biologically or therapeutically inequivalent. The action of the Boards of Pharmacy and Medicine in placing carbamazepine on the negative drug formulary was arbitrary or capricious.

    
    

32. The economic impact statement prepared as part of the Board of Pharmacy's rule adoption process clearly fails to address, or even mention, the economic impact to manufacturers and consumers of carbamazepine products. The summary of the estimated economic impact published in the December 16, 1988 edition of Florida Administrative Weekly minimally identifies the impact on consumers and manufacturers, however, the economic impact statement, contrary to statutory requirement, fails to properly include the estimated cost or economic

    benefit to all persons directly affected by rule adoption. The evidence indicates no more than cursory review of the economic impact of the rule adoption on manufacturers and consumers of the drug.

    
    

33. The rule as adopted erroneously listed the referenced drug as carbomazepine, rather than the correctly spelled carbamazepine. There is no evidence that there was any confusion or harm resulting from the erroneous spelling, which apparently was the result of scrivener's error.

    
    

    CONCLUSIONS OF LAW

    
    

34. The Division of Administrative Hearings has jurisdiction over the parties to and subject matter of this proceeding. Section 120.56, Florida Statutes. The Petitioner is substantially affected by the action taken by the Respondent relevant to Rule 215-5.001(13), Florida Administrative Code, and therefore has standing to challenge the rule.

    
    

35. According to the stipulation filed by the parties prior to the hearing, the issue presented for consideration is whether Rule 215-5.001(13), Florida Administrative Code, which includes "carbomazepine" in the negative drug formulary, is an invalid exercise of delegated legislative authority. In relevant part, section 120.52(8), Florida Statutes, provides that a proposed or existing rule is an invalid exercise of delegated legislative authority if:

    
    

    (a) The agency has materially failed to follow the applicable rulemaking procedures set forth in s. 120.54;

    * * *

    (e) The rule is arbitrary or capricious.

    
    

36. The burden of proof falls to the Petitioner to establish that the rule is an invalid exercise of delegated legislative authority. Here the Petitioner asserts that the rule is arbitrary or capricious, and further, that the agency's economic impact statement fails to meet the requirements of the applicable rulemaking procedures. In this case, the burden has been met.

    
    

37. Section 465.025(2), Florida Statutes, provides that "[a] pharmacist who receives a prescription for a brand name drug shall, unless requested otherwise by the purchaser, substitute a less expensive, generically equivalent drug product . . . unless the prescriber writes the words "MEDICALLY NECESSARY," in his own handwriting, on the face of a written prescription or unless, in the case of an oral prescription, the prescriber expressly indicates to the pharmacist that the brand name drug prescribed is medically necessary."

    
    

38. Section 465.025(6), Florida Statutes, provides in part that the Boards of Pharmacy and Medicine "shall establish by rule a formulary of generic drug type and brand name drug products which are determined by the boards to demonstrate clinically significant biological or therapeutic inequivalence and which, if substituted, would pose a threat to the health and safety of patients receiving prescription medicine . . . . No pharmacist shall substitute a generically equivalent drug product for a prescribed brand name drug product if the brand name drug product or the generic drug type drug product is included in said formulary."

39. Rule 215-5.001, Florida Administrative Code, provides for establishment of the "negative drug formulary" and, in relevant part, states as follows:

    
    

    "The negative drug formulary is composed of medicinal drugs which have been specifically determined by the Board of Pharmacy and the Board of Medical Examiners to demonstrate clinically significant biological or therapeutic inequivalence and which, if substituted, could produce adverse clinical effects, or could otherwise pose a threat to the health and

    safety of patients receiving such prescription medications.

    Substitution by a dispensing pharmacist on a prescription written for any brand name equivalent of a generic named drug product listed on the negative formulary or for a drug within the class of certain dosage forms as listed, is strictly prohibited.

    * * *

    
    

40. The following are included on the negative drug formulary:

    
    

    * * *

    (13) Carbomazepine".

    
    

41. The statute does not define "clinically significant biological or therapeutic inequivalence," or suggest what evidence is necessary to make such a determination. Although a witness for Respondent asserted that he believes the anecdotal information from physicians to be clinically significant, the greater weight of the evidence does not support his view. Without further definition and in light of the role of the FDA in evaluating the equivalency of generic drugs, it is reasonable to utilize FDA definitions. The evidence does not establish that carbamazepine products, classified as therapeutically equivalent by the FDA, demonstrate "clinically significant biological or therapeutically inequivalence" as required by Florida law.

    
    

42. The Respondent asserts that had the Florida Legislature intended for the Boards of Pharmacy and Medicine to simply defer to the determinations of the FDA in establishing inequivalency of generic drugs, there would need be no provision for the boards to establish a negative formulary, in that drugs found to be inequivalent by the FDA would not be substituted as generic by Pharmacists. Respondent asserts that the Legislature intended for a "higher standard" of review in providing that, where generic drugs demonstrate clinically significant biological or therapeutic inequivalence, substitution of such drugs would be prohibited. Even if it were assumed that such a "higher standard" were intended, the facts of this case do not establish that the drugs, in fact, demonstrate such inequivalence. To determine that carbamazepine products, meeting FDA equivalency standards, are, insofar as Florida's negative formulary is concerned, inequivalent, would require that the evidence be sufficient to invalidate the FDA evaluation process or results. In this case, the greater weight of the evidence indicates that the FDA evaluations are reasonable. The evidence fails to establish clinically significant biological or therapeutic inequivalence of the relevant drug products.

43. The action is placing carbamazepine on the negative drug formulary is not factually supported. Facts in the record do not demonstrate clinically significant biological or therapeutic inequivalence between carbamazepine products and do not support, the actions of the boards. Therefore, the action of the boards in placing carbamazepine on the negative drug formulary were arbitrary or capricious. A capricious action is one taken without thought or reason or which is taken irrationally. An arbitrary decision is one that is not supported by facts or logic or that is despotic. Agrico Chemical Company v. Department of Environmental Regulation, 365 So.2d 759 (Fla. 1st DCA 1979)

    
    

44. As to the economic impact statement, the agency failed to materially comply with the applicable rulemaking procedure. Section 120.54(2)(b), Florida Statutes, requires that, in promulgating an administrative rule, an agency must prepare a "detailed economic impact statement." Here, the economic impact statement does not even mention the estimated impact of the rule on the manufacturers or consumers of carbamazepine products. While the summary of the rule's impact, as published in the Florida Administrative Weekly, does briefly state in general terms the impact on consumers and manufacturers, such does not meet the requirement of section 120.54(2)(b), Florida Statutes. A flawed economic impact statement is generally not fatal to a rule promulgation where the evidence establishes that there will be no impact or that the agency fully considered the impact. However, to find that the economic impact statement provided in this case meets the statutory requirement would be tantamount to disregarding the requirement altogether.

FINAL ORDER

Based upon the foregoing findings of fact and conclusions of law, it is determined that Rule 215-5.001(13), Florida Administrative Code, is an invalid exercise of delegated legislative authority.

DONE and ENTERED this 25th day of July, 1989, in Tallahassee, Florida.

WILLIAM F. QUATTLEBAUM

Hearing Officer

Division of Administrative Hearings The DeSoto Building

1230 Apalachee Parkway

Tallahassee, Florida 32399-1550

(904) 488-9675

Filed with the Clerk of the Division of Administrative Hearings this 25th day of July, 1989.

APPENDIX

CASE NO. 89-2644RX

The following constitute rulings on proposed findings of facts submitted by the parties. Proposed findings are accepted as modified in the Order except as follows:

Petitioner

1. Rejected, the three-way crossover bioavailability comparison between Epitol and Tegretol is immaterial. The Respondent concedes that Epitol and Tegretol are virtually identical.

2. Rejected in part as to reference to Ciba-Geigy California activities, irrelevant. The implication that Ciba-Geigy was somehow inappropriate in mobilizing physicians to express support for the Ciba-Geigy position Is rejected.

27-38. Rejected, irrelevant.

42. Rejected, unnecessary.

44. Rejected, see #7.

46. Rejected, unnecessary. 48-49. Rejected, unnecessary

54. Rejected as to restatement of the meaning of "AB" rating, which is defined in the Orange Book. Otherwise rejected, cumulative.

58-59. Rejected, see #7. Respondent

1. Rejected as to reference to study comparing liquid suspension carbamazepine to tablet formulation, irrelevant.

2. Rejected as to reference to DHRS "study", irrelevant. The "study" used physician-identified seizure disorders and does not establish that any seizures occurred, as stated by the cited witness.

14. Rejected as to indication of concern related to economic impact of rule, not supported by greater weight of evidence.

COPIES FURNISHED:

Charles A. Stampelos, Esq.

600 First Florida Bank Building Tallahassee, Florida 32301

Dorothy Faircloth, Executive Director Board of Medicine,

Department of Professional Regulation 1940 North Monroe Street, Suite 60

Tallahassee, FL 32399-0792

John Rimes, Esq.

Department of Legal Affairs The Capitol, Suite 1601

Tallahassee, Florida 32399-1050

Lawrence A. Gonzalez, Secretary Dept. of Professional Regulation 1940 North Monroe Street Tallahassee, FL 32399-0792

Liz Cloud, Chief

Bureau of Administrative Code The Capitol - 1802 Tallahassee, FL 32399-0250

Kenneth E. Easley, Esquire

Dept. of Professional Regulation 1940 North Monroe Street Tallahassee, FL 32399-0792

Carroll Webb, Executive Director Administrative Procedure Committee

120 Holland Building Tallahassee, FL 32399-1300

NOTICE OF RIGHT TO JUDICIAL REVIEW

A PARTY WHO IS ADVERSELY AFFECTED BY THIS FINAL ORDER IS

ENTITLED TO JUDICIAL REVIEW PURSUANT TO SECTION 120. 68, FLORIDA STATUTES. REVIEW PROCEEDINGS ARE GOVERNED BY THE FLORIDA RULES OF APPELLATE PROCEDURE. SUCH PROCEEDINGS ARE COMMENCED BY FILING ONE COPY OF A NOTICE OF APPEAL WITH THE AGENCY CLERK OF THE DIVISION OF ADMINISTRATIVE HEARINGS AND A SECOND COPY, ACCOMPANIED BY FILING FEES PRESCRIBED BY LAW, WITH THE DISTRICT COURT OF APPEAL, FIRST DISTRICT, OR WITH THE DISTRICT COURT OF APPEAL IN THE APPELLATE DISTRICT WHERE THE PARTY RESIDES. THE NOTICE OF APPEAL MUST BE FILED WITHIN 30 DAYS OF RENDITION OF THE ORDER TO BE REVIEWED.

Docket for Case No: 89-002644RX

Orders for Case No: 89-002644RX