Baratta, Francesca

English

Institutional Research Information System University of Turin

Paediatric galenics:  a challenge and an opportunity proposed by A.P.P.A.® Project for Developing Countries Francesca Baratta  Non-profit organization Aid Progress Pharmacist Agreement®, Turin, Italy  Department of Scienza e Tecnologia del Farmaco, University of Turin, Italy 8th A.It.U.N annual meeting  “Medicines for children's safe: challanges and opportunities” Pavia, 6-7th  March 2014 Alma-Ata Declaration - 1978 TODAY? “… the Primary Health Care… forms an integral part both of the country’s health system, of which it is the central function and main focus, and of the overall social and economic development of the community. It is the first level of contact… with the national health system, bringing health care as close as possible to where people live and work, and constitutes the first element of a continuing health care service…” As a result, medicines regulation was not carried out to the full extent required to ensure the quality, efficacy and safety of medicines in African countries. The findings confirm the results of a 2004 questionnaire survey conducted by WHO in 38 African member states, which found that 90% of countries did not provide or enforce adequate regulatory functions 2005 Problem to be addressed 2010 The World Health Report 2006 - working together for health Chapter 1: Health workers: a global profile ACCESS TO HEALTH SERVICES:  INEQUALITIES BETWEEN NORTH AND SOUTH OF THE WORLD «…water-borne diseases are not caused by lack of antibiotics but by dirty water, and by the political, social, and economic forces that fail to make clean water available to all; heart disease is caused not by a lack of coronary care units but by the lives people lead, which are shaped by the environments in which they live; obesity is not caused by moral failure on the part of individuals but by the excess availability of high-fat and high-sugar foods …» Borana Singing wells, Kenya PROBLEMS RELATED TO THE LIFE STILE “Closing the gap in a generation: Health equity through action on the social determinants of health” – WHO Commission on Social Determinants of Health - 2008 Essential medicines are those that satisfy the priority health care needs of the population. They are selected with due regard to public health relevance, evidence on efficacy and safety, and comparative cost-effectiveness. Essential medicines are intended to be available within the context of functioning health systems at all times in adequate amounts, in the appropriate dosage forms, with assured quality and adequate information, and at a price the individual and the community can afford. ESSENTIAL MEDICINES   More than fifty percent of the population in the Region have no regular access to essential medicines.   Medicine supply and regulatory systems are weak  Financial as well as human resources are inadequate to ensure delivery of pharmaceutical services and ensure access to essential medicines.   Circulation of poor quality medicines, high medicine prices, unethical promotion and irrational use of medicines poses additional challenges. BUT… “IMPERFECT” COUNTERFEITS «these products contain the right components, with an incorrect concentration and/or formulation resulting in defective quality specifications. In the vast majority of cases, they are devoid of any therapeutic efficacy» COUNTERFEIT MEDICINES “CRIMINAL” COUNTERFEITS «they are apparently similar to the original medicinal product, but do not contain any active ingredient and can even include harmful or toxic substances. They are usually sold at high prices and for the treatment of serious pathologies. Consequences for users of criminal counterfeits can be fatal» Di Giorgio D. Counterfeit drugs. The phenomenon and enforcement activities. Milano: Tecniche nuove; 2010. А counterfeit medicine is one which is deliberately and fraudulently mislabeled with respect to identity and/or source. Counterfeiting can apply to both branded and generic products and counterfeit products may include products with the correct ingredients or with the wrong ingredients, without active ingredients, with insufficient active ingredients or with fake packaging. WHO - General information on counterfeit medicines F.Baratta, A. Germano, P. Brusa  Diffusion of counterfeit drugs in developing Countries and stability of galenics stored for months under different conditions of temperature and relative humidity  Croat Med J. 2012; 53: 173-184 Analysis of 196 samples of medicinal products COUNTERFIET MEDICINES IN DC: ANALYSIS OF THE PHENOMENON F.Baratta, A. Germano, P. Brusa   Diffusion of counterfeit drugs in developing countries and stability of galenics stored for months under different conditions of temperature and relative humidity   Croat Med J. 2012; 53: 173-184 CAMEROUN 2012 CAMEROUN 2013 37% 47% PHARMACEUTICAL FORMS TESTS (Ph Eur)  Uniformity of content (2.9.6)  Uniformity of mass (2.9.5)  Disintegration (2.9.1)  Friability (2.9.7)  Hardness (2.9.8)  Sterility (2.6.1) 16% 32% 65% 3% CAMEROUN 2013  Population: 20 million  Pharmacies on the national territory: 331  Yaoundé+Douala: 81 pharmacies  HOW MANY ARE THE  STREET VENDORS? PRELIMINARY RESULTS:   1047 FAMILIES LIVING IN YAOUNDÉ: THE 99.6%, EVEN IF SCHOOLED, BUY MEDICINAL PRODUCTS BY STREET VENDORS   THE 34% OF SUBJECTS IS AWARE OF THE RISKS. THE 60% BUY THESE PRODUCTS DUE TO FINANCIAL DIFFICULTIES   74 STREET VENDORS HAVE BEEN INTERVIEWED: THE 80% IS MEDIUM-HIGH CULTURAL GRADE www.progettoappa.it                 appa.onlus@unito.it A.P.P.A.® PROJECT PLANNING, CARRYING OUT, STARTING LABS IN ORDER TO PREPARE GALENIC MEDICINAL PRODUCTS AND RELATIVE QUALITY CONTROL IN DEVELOPING COUNTRIES   FEDERAZIONE ORDINI FARMACISTI ITALIANI ORDINE DEI FARMACISTI PROVINCIA DI TORINO  With the patronage of: and Choice of the place where building the galenic lab, choice of medicines needed and of the correct pharmaceutical forms, related to the local pathologies. Stage in A.P.P.A.® lab of Turin, for a Pharmacy’s student of Pharmacy Faculty of Turin; the stage leads to learn all the necessary to be able to prepare the programmed medicinal products. A technician of the Country holding the lab comes to Italy to learn the procedures of galenic medicines in A.P.P.A.® lab of Turin, under a Pharmacy’s student supervision. During this period the material needed for galenic lab will be sent to local partners. Training period in the chosen Country, during which the local technician, who has been in Italy to learn galenic methods and procedures, will be coordinated in his work by the Pharmacy’s student sent to the A.P.P.A.® lab . Quality control of medicinal products routinely prepared in new galenic lab; moreover some sample of these are sent to University of Turin, Pharmacy Faculty, where they are tested to verify their quality. Periodical stages at new lab for Pharmacy’s students of Pharmacy Faculty of Turin are performed each year both to give a continuous supervision of medicinal products prepared in the lab and to create new formulations according to the requests of  medical doctors responsable of the medical centers. PHASES  OF  A.P.P.A.  PROJECT Preliminary pharmaco-economic study which implies a trip of the A.P.P.A.® staff on site to value the local situation and recipient areas. Some medicines should be purchased in local pharmacies and sent to the laboratory of the University of Turin to value if these medicinal products, present on the local market, respect the declared characteristics or are counterfeit. Phase «zero» WHY GALENICS IN DC? USING LOCAL PERSONAL TEACHING THEM A JOB: AUTONOMY  ALLOWING THE SALE OF CHEAP HIGH QUALITY MEDICINES    AVOIDING THE PURCHASE OF MEDICINES ILLEGALLY IMPORTED  CUSTOMIZING THE DOSAGES AND PHARMACEUTICAL FORMS ACCORDING TO THE ACTUAL NEEDS OF PATIENTS  HIGH PERCENTAGE OF COUNTERFEIT MEDICINES IN THE AREA  LOCAL POOR AVAILABILITY OF QUALITY MEDICINES    HIGH COST OF INDUSTRIAL MEDICINES  APPROVAL OF LOCAL AUTHORITIES  BASIC CONDITIONS FOR OPENING A LAB FOR THE PREPARATION OF GALENIC MEDICINAL PRODUCTS Garouà - Cameroun N’Djamena - Tchad ENDEMIC DESEASES IN THE AREA • MALARIA • SALMONELLA • VENEREAL DESEASES • HEPATITIS A,B,C,D,E, • HIV • TUBERCULOSIS • OTHERS CHOICE OF THERAPEUTIC CLASSES FOR THE GALENIC LAB •    ANTIMALARALS •    TOPICAL ANTIFUNGAL •    TOPCAL AND SYSTEMIC ANTIBIOTICIS  •    SYSTEMIC AND TOPICAL NSAD •    ANTIPYRETICS •    ANTIPARASITICS (antihelmintics, antiamebic, scabicidi) •    DISINFECTANTS FORMULATION PHARMACEUTICAL FORM ORAL SOLID OINTMENT FOR SKIN APPLICATION LIQUID • ORAL • FOR SKIN APPLICATION AIM The project was born from the need and the desire to teach a trade to people leaving in Developing Countries and to ensure the production of safe and effective medicines EASIER ACCESS TO MEDICINES DECREASE MORTALITY AFRICA: HIGH PRESENTS OF COUNTERFEIT MEDICINES NO THERAPEUTIC EFFECT CASES OF INTOXICATION SUPPOSITORY A.P.P.A.® LABS HANDBOOK SEMISOLID PREPARATIONS FOR CUTANEOUS APPLICATION LIQUID PREPARATIONS FOR CUTANEOUS APPLICATION SOLID PREPARATIONS LIQUID PREPARATIONS FOR ORAL USE Solutions Suspension Syrups Drops ORAL GEL POWDER FOR ORAL USE RECTAL PREPARATIONS STERILE PREPARATIONS Large volume parenteral solutions 101 FORMULATIONS HAITI: WHY? SAINT DAMIEN PAEDIATRIC HOSPITAL PORT-AU-PRINCE - HAITI MEDICINAL PRODUCTS LOT API PROVENANCE RESULTS 6C090 Acetazolamide 250 mg Haiti Unsatisfied:  Uniformity of content  (2.9.6), Friability (2.9.7) 0302609 Ampicillin 1g India Unsatisfied: Bacterial endotixins (2.6.14.) 071202 Chloramphenicol  1g USA Suitable 09K4840 A Phenobarbital 30 mg Haiti Unsatisfied: Friability (2.9.7), Hardness (2.9.8) 08E2978-A Phenobarbital syrup 18mg/5ml Haiti Suitable 08111487 Propanolol 40mg Brasil Unsatisfied:  Uniformity of content (2.9.6) L08111487 Spironolactone 25mg Domenican Republic Suitable PROBLEMS:  Method of preparation  Quality of industrial tablets  Stability of the preparations  Administration of capsules for the neonatal and paediatric treatment  PREPARATION OF CAPSULES FOR CHILDREN FROM INDUSTRIAL HIGH-DOSE TABLETS PAEDIATRICS: WHY? CAPSULES PRODUCED IN 2010 LOT API PROVENANCE RESULTS 200910-A Acetazolamide 25 mg St Damien Hospital Unsatisfied:  Uniformity of content (2.9.6) A-200S10-A Acetazolamide 25 mg St Damien Hospital Suitable 121110-B Exp Captopril 1,25 mg St Damien Hospital Unsatisfied:  Uniformity of mass (2.9.5) 230610-C Phenytoin 10 mg St Damien Hospital Suitable 230610-G Phenytoin 10 mg St Damien Hospital Suitable 0  STUDY AND FORMULATION OF ORAL LIQUID PAEDIATRIC FORMULATIONS: METHODOLOGICAL  APPROACH A.P.P.A.® GALENIC LAB IN HAITI:  SAINT DAMIEN PAEDIATRIC HOSPITAL In agreement whit local medical doctors the drugs for the paediatric therapy are chosen and then formulated: liquid oral formulations are preferred and appropriate excipients are selected.  For each formulation a specific card (written in local language) has been prepared. The card shows the procedure of preparation and the characteristics of each component present in the formulation.  Each preparation have been tested to check its quality and its stability under different environmental conditions in accordance with the EMA guidelines.  PREPARATIONS PEDIATRIQUES SIROPS ACIDE ASCORBIQUE 10 mg/ml CANREONATE  DE POTASSIUM 1 mg/ml FER SULFATE 5 mg/ml IBUPROFENE 20 mg/ml PROPANOLOL 0,5 mg/ml RANITIDINE 15 mg/ml SALBUTAMOL 0,4 mg/ml VITAMINE B6 1 mg/ ml SOLUTIONS CAPTOPRIL 1 mg/ml FUROSEMIDE 1 mg/ml GOUTTES NIFEDIPINE 1 mg/gtt RANITIDINE  4 mg/gtt SALBUTAMOL 0,2 mg/gtt VITAMINE B6 0,5 mg/gtt SUSPENSIONS VITAMINE B COMPLEX 5,8 mg/ml MAGNESIUM ET ALUMINIUM HYDROXYDE 200 mg/ml Saint Damien Hospital 0 STABILITY STUDY OF THE PREPARED  LIQUID PHARMACEUTICAL FORMS STORAGE  CONDITION T (°C) RH PERIOD COVERED BY DATA ANALYTICAL METHOD Standard 25±2 60±5% 12 months, analysis at time zero (T0) and every 30 days  (from TS-1 to TS-12) UV-VIS spectrophotometric assay Refrigerator 5±3 - 12 months, analysis at time zero (T0) and every 30 days  (from TR-1 to TR-12) Accelerated 40±2 60±5% 3 months, analysis at time zero (T0) and every 30 days  (from TA-1 through TA-3) EMA Guideline on stability testing: stability testing of existing active substances and related finished products, 2003, CPMP/QWP/122/02, rev 1 corr A.P.P.A.® GALENIC LAB IN HAITI Method: EVALUATION OF THE EXPIRATION DATE VALIDITY PERIOD:  3 MONTHS housing and environmental conditions are not suitable for a proper storage of the preparations BUT The stability has been demonstrated  for 12 MONTHS for  all formulations PREPARATIONS PEDIATRIQUES SIROPS ACIDE ASCORBIQUE 10 mg/ml CANREONATE  DE POTASSIUM 1 mg/ml FER SULFATE 5 mg/ml IBUPROFENE 20 mg/ml PROPANOLOL 0,5 mg/ml RANITIDINE 15 mg/ml SALBUTAMOL 0,4 mg/ml VITAMINE B6 1 mg/ ml SOLUTIONS CAPTOPRIL 1 mg/ml FUROSEMIDE 1 mg/ml GOUTTES NIFEDIPINE 1 mg/gtt RANITIDINE  4 mg/gtt SALBUTAMOL 0,2 mg/gtt VITAMINE B6 0,5 mg/gtt SUSPENSIONS VITAMINE B COMPLEX 5,8 mg/ml MAGNESIUM ET ALUMINIUM HYDROXYDE 200 mg/ml STABILITY STUDY: RESULTS PAEDIATRIC FORMULATIONS: NON ONLY IN HAITI EXTEMPORANEOUS SUSPENSION FOR ORAL USE SUPPOSITORY Galenics, in accord with the European Law (Ph Eur,), must guarantee “the quality as a fundamental support to the security and the efficacy” PHARMACEUTICAL FORMS TESTS (Ph Eur) Uniformity of content (2.9.6) Uniformity of mass (2.9.5) Disintegration (2.9.1) Friability (2.9.7) Hardness (2.9.8) Sterility (2.6.1) STABILITY TESTS (EMA) D.C. ITALY PHARMACEUTICAL FORMS TESTS  Ointments for skin application; Suppositories: •Verify of accuracy of followed procedures •Control of aspect •Control of the amount to sell •Control of the solidity of packing  Stiff capsules: •Verify the accuracy of followed procedures •Control of aspect and solidity of capsules •Control of the number of capsules prepared •Mass uniformity of capsules  Liquid medicinal products: •Verify the accuracy of followed procedures •Control of the amount of product to sell •Control of the solidity of packing RAW MATERIALS: Organoleptic control  Melting point  QUALITY CONTROL AND QUALITY ASSURANCE QUALITY CONTROL AND QUALITY ASSURANCE ANALYSIS METHOD REF. ACCEPTANCE CRITERIA General aspect Visual Posological unit integrity Uniformity of content Ph. Eur. 7 ed. Assay 2.9.6 Each individual content is between 85% and 115% of the average content (10 dosage units) Uniformity of mass Ph. Eur. 7 ed. Assay 2.9.5 Not more than two of the individual masses deviate from the average mass by more than ± 10% and none deviates by more than ±20% (20 dosage units) Disintegration Ph. Eur. 7 ed. Assay 2.9.1 At the end of the specified time all of the dosage units must have disintegrated completely Friability Ph. Eur. 7 ed. Assay 2.9.7 Maximum loss of mass not more than 1% Hardness Ph. Eur. 7 ed. Assay 2.9.8 Hardness between 3 and 12 N Sterility test  Ph. Eur. 7 ed. Assay 2.6.1 At intervals during the incubation period and at its conclusion, examine the media for macroscopic evidence of microbial growth: If no evidence of microbial growth is found, the product to be examined complies with the test for sterility Bacterial endotoxins  Ph. Eur. 7 ed. Assay 2.6.14 The test is considered valid when all replicates of tested solutions show no reaction and the result of control solution confirms the labelled lysate sensitivity. STANDARDIZATION OF RESULTS  LOW COSTS SIMPLE EXECUTION SPECTOPHOTOMETRY UV/VIS “…reuse, repair equipment and goods instead of throwing them in a landfill, exceeding the consumerist obsession of the obsolescence of objects and the tension to the new…”  A. Salza “Niente. Come si vive quando manca tutto. Antropologia della povertà estrema”, Sperling & Kupfer 2009 A.P.P.A.®  LABS IN THE WORLD ANGOLA – Cubal, Nossa Senhora de Paz hospital, Compañia de Santa Teresa de Jesus.  ANGOLA – Funda, A.M.E.N. ONG health care facility. CAMERUN – Douala, La Bethanie hospital. CAMERUN – Garoua, Notre Dame des Apôtres hospital, Djamboutou. CIAD – N’Djamena, Le Bon Samaritain hospital. HAITI – Tabarre Chateaublond, N.P.H. Saint Damien paediatric hospital. MADAGASCAR – Vohipeno, Henintsoa hospital. MADAGASCAR – Ihosy, Eglise Catholique Apostolique Romaine medical center. CAMEROUN Douala  Garoua ANGOLA  Funda  Cubal TCHAD N’Djamena MADAGASCAR Ihosy  Vohipeno HAITI Port au Prince 8 GALENICS LABS IN DEVELOPING COUNTRIES   ECONOMIC INVESTMENT IN RAW MATERIALS: ≈ 100.000 €   ADMINISTERED DOSES:  i.e. cps ≈ 7.500.000  A GOOD REASON TO GO ON   BUT WITH THE AIM OF  BECOME LESS AND LESS INDISPENSABLES A.P.P.A.® 2005-2013 

Paediatric galenics: a challenge and an opportunity proposed by A.P.P.A.® Project for Developing Countries

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Paediatric galenics: a challenge and an opportunity proposed by A.P.P.A.® Project for Developing Countries

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