Microbiological Quality In Pharmaceuticals PDF

10 Microbiology ‫هذا العمل ال يغين عن حضور المحارضة‬ 49...

10 Microbiology ‫هذا العمل ال يغين عن حضور المحارضة‬ 49 ‫جـ‬### :‫السعر وجــــه‬ Microbiological Quality In ‫جـ‬### :‫السعر وجهني‬ Pharmaceuticals Microbiological Quality In Pharmaceutics Microbiological Quality Assurance (QA) Microbiological Quality control (QC)  Measures taken during manufacture which  Analytical procedures carried out on insure that the product will in fact comply with pharmaceutical products in order to test for specifications for microbiological quality conformity to specifications of microbiological ‫الخطوات اللي بيتبعها أثناء التحضير (يعني خالل انتاج ال‬ quality ‫ عبارة عن مراقبة العملية‬..... ‫تقليب‬، ‫) من وزن‬product ‫االختبارات اللي بعملها في المستحضر النهائي علشان اتاكد من‬ ‫كاملة وهل تمت وفقا البروتوكول وال أل‬ ‫جودته (يعني بعد ما خالص خلصت أنتاج ووصلت ان معايا‬ )‫برودكت اخد عينة منه وافحصها‬  Such quality control procedures are "destructive tests" and are hence applied to a "sample" of a batch, presumed to represent the entire batch. The batch here is presumed to be "microbiologically homogenous Standard operating procedures (SOPs):  "detailed, written instructions to achieve uniformity of the performance of a specific function"  The laboratory lives and dies by its standard operating procedures (SOPs) ‫تعريف مهم ف الصناعه الدوائية‬ standard product ‫ اللي المفروض امشي عليها في المصنع من حيث األدوات واألجهزة والخطوات علشان اطلع ال‬basic ‫الحاجات ال‬ quality ‫يكون بنفس ال‬ Total Quality Management (TQM):  integrated program for managing quality on a continuous basis with periodic up gradation and this requires all laboratory personnel to take ownership of the idea and its importance of adherence ‫البروتوكول اللي بيخلي كل الخطوات تمشي بالترتيب كل واحده مع اللي وراها كده ف ترابط او تسلسل واستمرارية‬ Accreditation :  is an approved procedure by which regulatory authorities or authorized body accord formal recognition to a laboratory to undertake specific task provided that the pre-defined standards are met by'. It involves re- assessment and surveillance at regular intervals so as to ensure that commitment to quality is a continuous process ‫او‬accreditation ‫ممكن نعتبره انه اعتماد بمعنى اني شوفت كل المواصفات بتاع البرودكت بتاعي والقيتها تمام ومظبوطه فيقدر ياخد‬ ‫اعتمده‬ Validation (not important) :  Validation is "Establishing documented evidence that provides a high degree of assurance that a specific process will consistently produce a product meeting its pre-determined specifications and quality attributes This is to maintain and assure a higher degree of quality of food and drug products.  Scope of validation :  Analytical Test Methods  Instrument  Process Utility Services  Raw Material Calibrations  Equipment  Facilities  Product Design  Cleaning  Operators ‫بتاعه وأنها مش مهمة ومشرحهاش‬scope ‫وال‬validation‫الدكتور قال مش بيحب جزء ال‬ 1  Microbiology Microbiological Quality In Pharmaceutical 01 Classes of pharmaceutical products : Sterile Non-sterile  parental and ophthalmic preparations  topical and oral preparations ‫ سواء‬sterile ‫ الزم تبقي‬parenteral ‫كل ال‬ ‫اي حاجه علي الجلد من بره او عن طرق الفم‬ intramuscler or intraveins  are tested qualitatively for absence of  are tested quantitatively for the presence of microorganisms. maximum number of microorganisms and living organism ‫ من اي‬free ‫هنا معناها ان المحلول‬ qualitatively for absence of certain pathogens. qualitative ‫ ده النها‬dead organism ‫ولكن ممكن تحتوي‬ ‫ فبيتعملها‬microorganism ‫ مسموح بيه من ال‬limit ‫هنا في‬ ‫بس‬ ‫ وكمان في انواع معينه الزم المستحضر يبقي‬quantitative test ‫خالي منها‬ Microbial Quality of Parental: Microbiological Quality of Ophthalmic:  Since such products are to be applied to  Ophthalmic preparations (eye drops, ointments and human tissues, they must be sterile otherwise lotions) are applied to diseased eye. they would contaminate such tissues and lotion ‫ و‬ointment ‫ و‬eye drops ‫دي بقا بتبقي للعين زي ال‬ cause infections. multidose ‫وعشان بتبقي‬steraile ‫وفيها مشكلتين الزم تبقي‬ intramuscler or ‫ هي الي بتبقي‬parentral ‫ال‬ ‫ بعد االستعمال االول فالزم نحط‬contamination ‫ممكن يحصل‬ skin ‫ او في‬intraveins ‫في التحضيرة‬preservatives  Such products require:  Since such preparations are a) Testing for sterility as a QC procedure. 1. liable to contamination during use, b) Research for reasons why a product may 2. they are required to contain a preservative prove non-sterile even though it has been especially effective against Pseudomonas sterilized. aeruginosa (opportunistic pathogen that may destroy the eye). Sterilization  refers to any process that eliminates, removes, kills, or deactivates all forms of life and other biological agents (such as fungi, bacteria, viruses, spore forms, prions, unicellular eukaryotic organisms such as Plasmodium, etc.) present in a specified region, such as a surface, a volume of fluid, medication, or in a compound such as biological culture media. ‫عادي جدا النها اتقتلت‬dead organism ‫ بس ممكن يبقي في‬living organism ‫ من اي‬free ‫التعريف ده مهم جدااااا معناها ان المحلول‬ steraile ‫ولكنها‬clean ‫وموجوده عشان كدة مقدرش اقول على التحضيرة انها‬ The official methods for sterilization are 1. Dry heat 2. Moist heat (autoclaving) 3. Ethylene oxide 4. Ionizing radiation 5. Filtration ‫ كل طريقه‬filtration ‫ و االخيره‬radiation ‫ الرابعه‬chemical ‫ اول اتنين الزم حراره والتالته دي‬sterilization ‫ طرق لل‬5 ‫وهنا‬ aplications ‫ و ال‬mechanism ‫ وكمان ال‬condition ‫ حاجات ال‬3 ‫الزم نعرف عنها‬ 2  Microbiology Microbiological Quality In Pharmaceutical 01 Steriliz Dry Heat ation : Conditions : ‫ دقيقه وفي من‬01 ‫درجه لمده‬051 ‫ في قال من‬medicaments ‫ في‬organism ‫عني عاوز اعرف هسخن لحد اي وكمان اموت كل ال‬ ‫ دقيقه االتنين صح بس كل واحده ليها ظروف معينه‬021 ‫ لمده‬071 for medicaments for glass  B.P recommends 150°C for 60 min  160°C for 60 min  U.S.P. recommends 160°C for 60 min  U.S.P. recommends 170°C for 120 min Mode of action for dry heat: death is due to slow protein denaturation through Oxidation of macromolecules. ‫مهمه جدا‬  This reaction requires high energy and longer time  Expressions of resistance : Decimal reduction time (D-value) Z-value  time at fixed temp or radiation dose required to  the increase in temp required to reduce the D- reduce the number of viable cells by 90% or value of an organism by 90% or one log cycle one log cycle, assuming linear curve  used as a measure for the degree of resistance of  It is a measure for the change in resistance upon an organism at particular temperature. changing the temperature.  Application: I. Suitable for thermo stable substances e.g. glass, metals, anhydrous oils, powders (talc, koalin), porcelain, silicon rubber, paraffin gauze, and cat gut. fixed oil ,‫ زي الزجاج البيركس‬thermostable ‫مواد‬ II. Not suitable for water containing substances, thermo labile substances, all fibers (dressing), plastics, and non-silicon rubber volatile oil‫ما ينفعش مع اي حاجه فيها ميه النها بتتبخروال‬ Advantages of dry heat: Disadvantages: 0(Less damaging to metals and glass. 1) Not suitable for water containing substances, 2) Articles remain dry. thermolabile substances 3) Used for substances damaged by moisture e.g. powders and oils. ‫ كذلك‬,‫مينفعش الى مواد بتجتوي على مايه عشان هتتبخر مباشرة‬ dry ‫ينفع لمواد زى البودر والزيت الن دول الزم لهم‬ ‫) زي‬thermolabile( ‫الى مادة متستحملش الحرارة عموما‬ ‫ الن ممكن البودر يتحول لعجين‬steam ‫ومينفعش معاهم‬heat ‫ والهرمونات‬C ‫فيتامين‬ ‫او الزيت يفسد‬ 3  Microbiology Microbiological Quality In Pharmaceutical 01 Methods of dry heat sterilization : 1) Hot air oven (sterilizer): 2) Infra red tunnel (IR (  Precautions :  I.R. radiation (wave length 700-950  Items should not be placed compact or over perforations to nm) lamps are used as source for allow circulation of air. heating.  Items, which resist heat transfer (talc powder), should be  I.R. lamps are concentrated at the entry placed in shallow layers. to shorten the heating up period and  Items which allow convection of heat (oils) could be cold sterile air is sprayed at the exit to sterilized in bulk. cool the sterilized articles.  the oven is allowed to cool to about 40°C before opening  It is a type of continuous sterilization, the door to avoid cold shock and cracking of glass. used mainly for sterilization and ‫فيه شوية احتياطات بنتبعها أوال مينفعش المواد تتحط فى الفرن فوق بعضها‬ depyrogenation of empty ampoules or ‫ ثانيا بعد ما يخلص‬.‫الزم تكون متوزعه صح عشان تسمح بمرور الجرارة‬ vials temp. ‫ ودا عشان ميدخلش هواء‬01 ‫تعقيم الزم نسيب الفرن يبرد لحد درجة حرارة‬ ‫فى الجهاز دا المواد بتمر على نفق جواه وبيكون فى‬ ‫بارد مباشرة للفرن والقزاز يفرقع‬ ‫ وبتكون هى مصدر الحرارة‬I.R. lamps‫اول السير‬..‫عشان التعقيم وفي نهاية المسار هواء معقم للتبريد‬ ampoules or ‫بيستخدم الجهاز خصيصا لتعقيم‬ vials Autoclaving ‫ ودا ال غالبا بيكون موجود في‬..‫ مايه متبخرة ( بخار ماء) درجة حرارته مرتفعه جدا وبتتم فى وجود ضغط معين‬Moist heat ‫عبارة عن‬ ‫المعامل وعيادات األسنان‬ 1. Condition of sterilization : 1. saturated steam temp 121oC for 15 minutes at 15 PSI pressure 2. or 115 C for 30 3. or 134 C for 3.5 min pre vacuum autoclave)‫ )مفرغ من الهواء‬for surgical dressing. ‫ ده عن‬..‫ ازاي‬020 ‫ هنوصلها ل‬011 ‫حد هيسال طيب الميه بتغلي عند‬ ‫فدرجه الحراره تعلى معايا عادي بمساعدة الضغط شبه‬.. pressure‫طريق اني اعمل‬ ‫حلل الضغط كدا‬  Mode of action: moist heat destroys microorganisms by the irreversible coagulation and denaturation of enzymes and structural proteins. ‫مهههم‬ 4  Microbiology Microbiological Quality In Pharmaceutical 01 Application: I. Suitable for the sterilization of the following: 1. Aqueous parenteral solutions and suspensions 2. Surgical dressings and fabrics )‫(الغيارات زى الشاش واالقمشة‬ 3. Metal instruments – immediate drying required protecting against corrosion. 4. Glass apparatus and containers – if unable to withstand dry heat, e.g. rubber parts. II. Unsuitable for anhydrous materials such as powders and oils. It cannot be used for thermolabile substances. ‫زى ما قولنا مش مناسب‬ ‫للبودر والزيوت الن لو دخلهم اى‬ ‫ كذلك الى ماده‬,‫ هيبوظو‬moist ‫مش يتستحمل الحرارة اصال‬ thermolabile ‫الصورة بيوضح دخول‬ ‫ وبيتم توزيعه‬..steam ‫ومسار‬ ‫بشكل متساوى على العينة‬ Advantages Disadvantages  High heat content plus rapid heat transfer  It does not destroy pyrogens pressure ‫بتنتقل بسرعة بسبب وجود‬heat‫ليه ال‬ M.O ‫مش‬pyrogen ‫ال‬  Destroys micro-organism more efficiently than dry heat (lethal action of water plus heat) and therefore a shorter exposure at a lower temperature possible dry heat‫بأكثر كفاءة عن ال‬M.O ‫الطريقة دى بتقتل ال‬  It rapidly penetrates porous materials and is therefore very suitable for sterilizing surgical dressings and materials 2. Types of autoclaves : 1) Pressure cooker types 2) Gravity displacement with automatic air and condensate discharge 3) Pre vacuum autoclave for surgical dressings 5  Microbiology Microbiological Quality In Pharmaceutical 01 ‫ملخص للفرق بين االستخدامات‬ Cold Sterilization Methods : 1. Radiation Sterilization 2. Gaseous sterilization 3. Filtration Sterilization cold‫وندخل على الطرق ال‬heating ‫كدة احنا خلصنا طرق ال‬ 1) Radiation Sterilization  lonizing radiation  Source of  Cobalt-60 (Co) used as source of gamma emission which has half life 3.25 radiation : years .It can be replaced by cesium ("Cs) of 30 years ‫سنة‬٥٢.٣ ‫بتاعه‬half life‫اللى ال‬٠٦ ‫هيكون من خالل أشعة جاما المنبعثة من الكوبلت‬radiation‫ال‬ ‫او السيزيوم‬  Condition: 1. Temperature 25°C 2. Time 3-5 hr 3. Dose of radiation: 0.5 mega rad (Mrad)  The device : ‫او‬Ce ‫نفترض عايزين نعقم سرنجات بالستيك بتخش على شاحنة وتبدأ تتفرغ وتعدى على غرفة فيها‬ 25 ‫تتفتح الغرفة دى وتعرضهم ألشعة جاما لمدة تالتة ساعات فى درجة حرارة الغرفة‬Co60 6  Microbiology Microbiological Quality In Pharmaceutical 01  Mechanism of  Gamma rays will react with microbes in two ways as follows: killing ; 1. Direct effect: Rays on microbes cause damage only 10% of total effect 2. Indirect effect: Rays will react with H,O in microbe forming super radical such as OH, O, H,O,, (H) and other which are extremely active  The radicals quickly combine with and destroy proteins and nucleic acids such as DNA, causing death ‫بس والتانية‬%٠١ ‫ودى بتقتل‬direct ‫طب ازاى أشعة جاما بتقتل الميكروب ؟ ليها طريقتين األولى‬ ‫فيفقد الماء إللى مخلياه عايش‬super radical ‫من خالل انها تحول الماء إللى جوا الميكروب‬indirect ‫بتاعها وبكدة يموت الميكروب‬DNA‫البروتين وال‬destroy‫دى تعمل‬radicals ‫وبسرعة ال‬  Application ; Suitable for: 1- Powder for internal and external use 2- Surgical equipment e.g. dressings and sutures 3- Heat sensitive pharmaceuticals as vitamins, hormones and antibiotics as well as certain plastics materials surgical ‫والهرمون وال‬vitamins ‫وال‬thermolabile‫وطريقة دى كويسة المواد ال‬ ‫إللى فيها يا فازلين‬dressings  Advantages : 1- Very high penetration power 2- Sterilization in final container 3- Large scale continuous process  Disadvantages: 1- Need expensive equipments 2- Danger on health 3- Many materials will be changed in their physical and chemical characters after radiation, so detailed studies must follow to ensure safety and stability of compounds sterilized by radiation ‫أعرف هل ممكن تأثرعلى‬radiation‫الزم اخذ احتياطاتى واعمل دراسات األول قبل مستخدم طريقة ال‬ ‫وال أل‬pharmacopia ‫بتاعة‬active material Questions: True Or False: 1- Dry heat is suitable for thermolabile substances.. F 2- Autoclaving is a saturated steam of a high temperature used with pressure... T 3- Moist heat (autoclaving) destroys microorganisms by oxidation... F 4- Powder and oils can be sterilized by dry heat.. T 7