5 OUTLINE Introduction Compounded Pharmaceuticals U.S. Pharmacopeia FDA and Contemporary CompoundingCurrent USP Compounding ActivitiesNew Drug Delivery SystemsSummary
6 INTRODUCTION History of Pharmacy Compounding in the United States Reasons for the Growth of CompoundingSpecial Patient PopulationsExamples of Pharmaceutical Compounding
7 History of Pharmacy Compounding in the U.S. In the past, Compounding Was Pharmacy1900s gave way to commercially prepared pharmaceuticalsMany strengths/dosage forms availableEconomics changed all thatLimited strengths/dosage forms“One Size Fits All” approach
8 Reasons for the Growth of Pharmacy Compounding Limited dosage formsLimited strengthsHome health careHospiceNonavailable drug products/combinationsDiscontinued DrugsDrug ShortagesOrphan drugsVeterinary compoundingNew therapeutic approachesSpecial Patient Populations
50 Pharmacopeia Pharmakon drug poiein to make Used together in Pharmacopeia means any recipe or formula or other standards required to make or prepare a drug.1580 Bergamo, Italy…..first used in connection with a local book of drug standards.
51 Pharmacopeias Local, City and National Pharmacopeias in Europe The London, Edinburgh and Dublin Pharmacopeias were official until 1864Replaced by the British PharmacopoeiaHow about in the U.S.?
52 Pharmacopoeias of the U.S. 1778 Lititz PharmacopeiaFirst Pharmacopeia in the U.S.Published in Lititz, Pennsylvania for use by the Military Hospital of the U.S. Army1808 Massachusetts Medical Societypublished a 272 page pharmacopeia with information on 536 drugs and preparations
53 Pharmacopoeias of the U.S. Jan Dr. Lyman SpaldingSubmitted a planMedical Society of the County of New YorkCreation of a national pharmacopeia----Divided U.S. into 4 geographical districtsMedical schools and societies were to develop apharmacopeia and appoint delegates to a general convention to be held in Washington, DC
54 Pharmacopoeias of the U.S. Jan First U.S. Pharmacopeial ConventionOnly 2 districts submitted plansThese were reviewed, consolidated and adopted.Dec 1820 First U.S. Pharmacopeia was published272 pages containing 217 drugs/preparations
55 USP I Preface:(in part) It is the object of the Pharmacopeia to select from among substances which possess medicinal power, those, the utility of which is most fully established and best understood; and to form from them preparations and compositions, in which their powers may be exerted to the greatest advantage……..
57 U.S. PHARMACOPEIA AND FDAMA 1985 USP ConventionResolution 4Compounding Information in the USPResolution 5Standards for Repackaged and Compounded Parenterals1990 USP ConventionEstablished the Expert Advisory Panel on Pharmacy Compounding
58 Resolution #4Be it resolved that the COR examine the desirability and feasibility of developing, with a view to inclusion in the USP, the following types of information:1. The short-term stability of drugs when dissolved in common diluents and stored in common standardized containers and/or delivery systems at room, refrigerator and freezer temperatures;
59 Resolution #4 (cont’d)2. pKa and minimum solubility of drugs in common diluents; and3. pH, osmolality and osmolarity of reconstituted injectables and liquid dosage forms.
60 Resolution #5Be it resolved that the COR be charged with the responsibility for providing standards and test methods; specifications for packaging, labeling, and storage; guidelines for appropriate documentation; and, where necessary, procedures for compounding parenteral preparations.
61 PSD SubcommitteeExpert Advisory Panel on Pharmacy Compounding was formed to advise the PSD SubcommitteeAlso, the Review Panel on Pharmacy Compounding Practices was formed to assist the Expert Advisory Panel by providing immediate expert review on materials produced by the Panel
62 Expert Advisory Panel Oct 1993 First meeting Organized into 2 groups General Chapter Groupto prepare a general informational chapter on compoundingMonograph Groupdevelop monographs for specific preparationsthose widely compounded but not available commercially
63 U.S. PHARMACOPEIA AND FDAMA Expert Advisory Panel ActivitiesI. General Chapter Group<795> Pharmacy CompoundingII. Monograph Groupdevelop monographs for specific preparations
65 FDA ACTIVITIESMid 1990s FDA began investigating a number of pharmacies that were compounding large quantities of selected drug products.Manufacturing under the guise of compounding“New Drugs”
66 Food and Drug Administration Activities FDA considered compounded preparations as “New Drugs” and subject to the New Drug ProvisionsINDNDASafetyEfficacyEnforcement Activities
67 FDAMA 97 Passage Pharmacy professional organizations U.S. Congress Compounding provisions
68 FOOD AND DRUG ADMINISTRATION MODERNIZATION ACT New Drug Requirementsshall not apply to a drug product if the drug product is compounded for an individual patient based on the unsolicited receipt of a valid prescription order…..if the compounding is by:a licensed pharmacista licensed physician
69 FOOD AND DRUG ADMINISTRATION MODERNIZATION ACT Anticipatory CompoundingPhysician-Patient-Pharmacist “Triad”
70 FOOD AND DRUG ADMINISTRATION MODERNIZATION ACT Compounding must be done using the following sources of ingredients:USP/NF monographsCommercial productsBulk Drug Substances List (being developed)
71 FOOD AND DRUG ADMINISTRATION MODERNIZATION ACT Compounding cannot be done from:Drugs on the “Negative List”drugs that have been withdrawn due to safety or efficacy reasonsList was developed
72 FOOD AND DRUG ADMINISTRATION MODERNIZATION ACT Cannot compound regularly or in inordinate amounts any drug products that are essentially copies of commercially available products
73 FOOD AND DRUG ADMINISTRATION MODERNIZATION ACT Cannot compound a drug product that “presents demonstrable difficulties for compounding that reasonably demonstrate an adverse effect on the safety and effectiveness of that drug product”. (list)
74 FOOD AND DRUG ADMINISTRATION MODERNIZATION ACT Memorandum of UnderstandingDistribution of inordinate amounts interstateHandling of complaints
75 FOOD AND DRUG ADMINISTRATION MODERNIZATION ACT AdvertisingThe pharmacy, pharmacist or physician cannot advertise or promote the compounding of any particular drug, class of drug, or type of drug.
76 FDA Modernization Act of 1997 FDA Advisory Committee on CompoundingFunction: to advise the FDA in the areas of bulk drug substances, safety and efficacy and difficult-to-compound products.FDA Pharmacy Compounding Steering Committee (Internal to FDA)
77 FDA Modernization Act of 1997 Three Lists Products not to be compounded because they were withdrawn from the market based on safety and efficacy concernsBulk drug substances of proven quality accepted for use in pharmacy compoundingDifficult-to-compound products
78 IMPLEMENTATION OF FDAMA Ongoing since 1997FDA Steering Committee (Internal)FDA Compounding Advisory Committee (External)Work with USP
79 USP I Preface:(in part) It is the object of the Pharmacopeia to select from among substances which possess medicinal power, those, the utility of which is most fully established and best understood; and to form from them preparations and compositions, in which their powers may be exerted to the greatest advantage……..
80 FDAMA IMPLEMENTATION AND THE USP <1161>Pharmacy Compounding Practices became <795 Pharmacy CompoundingMonographs of accepted bulk drug substances are being developed<1206> Sterile Preparations-Pharmacy Practices has been recommended as guidelines for sterile preparations compounding…being renumbered as <797>New chapters being written
82 USPNew structure from Committee of Revision to Expert CommitteesCompounding Pharmacy Expert CommitteeGeneral Chapters, incl <795>Nonsterile preparation monographsParenteral Products--Compounding and Preparation Expert CommitteeGeneral Chapters, incl <1206>Sterile preparation monographs
83 USP Convention 2000 Resolution Continue to develop and institute, in collaboration with other organizations as appropriate, specific initiatives focused on the development of appropriate compounding guidelines and monographs for non-commercially available, but commonly prescribed, medicines and dosage forms for use in special populations, notably neonatal, pediatric, geriatric, and terminally ill patients.
84 U.S. PHARMACOPEIA AND FDAMA Activities to date:15 official compounding monographs8 more stability studies underway6 formulas being processed through PF2 official chapters and 2 additional chapters in process:Pharmacy CalculationsGood Compounding Practices
85 CURRENT ACTIVITIES OF PHARMACY COMPOUNDING EXPERT COMMITTEE Survey of compounding pharmacists in hospitals, community pharmacies and long-term care facilities (August 2000)List of over 150 preparations, mostly pediatric, that need to be considered.2000 Resolution:
86 U.S. PHARMACOPEIA2001Recent survey listed over 1000 other preparations need monographsWell over 5,000 different formulations routinely compounded
88 FDAMA and the 9th District Early 2001the Ninth Circuit ruled that the FDAMA section dealing with compounding was invalid in the 9th Circuit District (NV, CA, WA, OR, MT, ID, AZ, AK, HI) but still in effect in the rest of the US.
89 FDAMA and the 9th District April 29, 2002U.S. Supreme Court ruled the advertising restrictions unconstitutional and the section not severable.Entire 503a now is thrown out and nonenforceable
90 SUMMARYPharmacy compounding is now legally recognized by the FDA, the Supreme Court, Congress, etc. as a necessary component of quality health careEmphasis on quality of compounding is increasing with documentation of quality being recommended and requiredClinical pharmacy becomes more of a reality with compounding pharmacy
100 NANOTECHNOLOGYThe art and science of building molecular structures so they are sufficiently large and complex to function as machines or devicesAtomically precise, functional machine systems developed on the scale of the nanometerBuilds objects atom by atom, molecule by molecule
101 POTENTIAL PRODUCTS Activated Pharmaceuticals (Magic Bullets) Cell-herding machines to stimulate rapid wound healingNanosurgeons to repair damaged cellular partsNanocruisers to attack viruses and bacteria
102 FORECASTS: 2-5 YEARSInexpensive handheld biosensors built on the basis of nanoscale ion channel switchesSimple detection of diseases, within minutes, from a small sample of saliva or blood
103 FORECASTSDNA vaccines will begin to be available in the next 5-10 yearsSuperior and safer than traditional vaccinesAbility to directly mimic body components and can “rebuild” worn, defective, damaged, diseased cells/tissues/organsBlood products, artificial skin products, bioartificial organs, blood vessels
104 FORECASTSIF a breakthrough to a universal assembler occurs during the next years, an entirely new field of “nanomedicine” and “nanopharmacy” will emerge by 2020.
105 NANOMEDICINEMonitoring, repair, construction and control of human biological systems at the molecular level, using engineered nanodevices and nanostructures.
106 NANOPHARMACYPreparation and delivery of ultra-small pharmaceuticals, therapeutic substances and delivery systems.
107 NANOPHARMACY AND NANOPHARMACEUTICALS Motors consisting of, for example, ATPase molecules with a metallic substrate and a chemical “propeller” on the other. As the ATP breaks down, the biomotor moves.This motor may be able to compound tiny quantities of drugs and pump them directly to the target tissues.
108 NANOPHARMACY AND NANOPHARMACEUTICALS The uses of biomolecular motors could be used for sensing or placing in living cells as a pharmacy to deliver medicine when required.
109 NANOPHARMACY AND NANOPHARMACEUTICALS New formulations and routes for drug deliveryPharmaceuticals based on an individuals genome
110 CONCLUSIONS We must live in today and prepare for tomorrow Compounding pharmacists roles in “individualizing drug therapy” is preparing the foundation for the “NANOPHARMACY” of tomorrow.