PHA111 Specials PDF

MPharm Programme Principles Of Extemporaneous Preparations and ‘Specials’ Cheng Shu CHAW 1 What is extemporaneous dispensing? Definition: Impromptu, performed with little or no preparation Also known as Compounding Preparation of a single medicinal product tailor made to the patient’s requireme...

MPharm Programme Principles Of Extemporaneous Preparations and ‘Specials’ Cheng Shu CHAW 1 What is extemporaneous dispensing? Definition: Impromptu, performed with little or no preparation Also known as Compounding Preparation of a single medicinal product tailor made to the patient’s requirements Unlicensed medicines Commonly known as “Specials” 2 What are ‘Specials’?  Different viewpoints on definition  A mixed bag of products and included cannabis based products  Anything which does not have a UK Marketing Authorisation (MA)  Imported items licensed in another country  Extemporaneous preparations  Batch produced, e.g. many sterile products such as ampoules or eye drops 3 Approaches In Different Countries USA- Hub pharmacy model. One Compounding pharmacy serving a community. Certain European countries e.g. Belgium-all compounding performed in Pharmacies UK-Use of Specials Manufacturers 4 Regulation 167 of the Human Medicines Regulations 2012 • Exemption from requirement of marketing authorisation • Need to fulfil the stated conditions 5 Guidance Note 14-MHRA  Guidance note on procurement of Specials  Must keep record of procurement in Pharmacy and report any Adverse Drug Reactions.  Specials manufacturer can only supply to Pharmacy, Doctor, Dentist or Wholesale Dealer (WL)  Maximum 30 day shelf life if no formal stability data of your own  Can download document from MHRA website  Prescriber awareness of unlicensed status & liability 6 Principle for the procurement and supply of specials 1. Establish a clinical need 5. Monitor and review 2. Understand the patient experience 3. Identify a preparation and supplier 4. Ensure effective governance 7 Principle for the procurement and supply of specials 8 Requirements: Facilities 1. Facilities  Space  Work bench with cleanable surfaces  Somewhere to store clean equipment  Raw materials’ storage  Equipment storage and cleaning  Control of cross contamination 9 Requirements: equipment 2. Equipment  Government stamped measures  Balances  Unguators or Topitec  Mortar and Pestle (avoid wood)  Stirring rod  Spatulas  Tiles  Method of heating e.g. water bath, microwave 10 Traditional Pharmaceutical Balances  Class A and B  Almost obsolete  Place weight on one side and ingredient on other on paper  Calibration unlikely 11 Electronic Balances  Check daily or before use with standard weights which are UKAS calibrated  Machines themselves should have maintenance and calibration schedule  Sitting is important: bubble should be centralised to level balance 12 Unguator  Closed system  Good operator protection  Nozzle attaches to pot to dispense ointment  Hygienic  Set mixing speeds/times 13 Requirements: documentations 3. Documentations  Reference materials, e.g. Martindale, BP, BPC etc.  Standard Operating Procedures  Worksheet including check signatures and manufacturing method  Labelling systems: Computerised PMR systems have difficulties with extemporaneous prescriptions  Certificates of analysis for raw materials 14 Example of worksheet 15 Cross Contamination  At worst a complete mix up, e.g. a product labelled as another product  Microbial: Bacteria or fungi. Does the product have a preservative system?  Physical: Particle, e.g. dust, plastic  Chemical: Residues or particles of another drug 16 Risk Analysis: A Twofold Exercise Risk To Patient • Error (both calculation and dispensing) • Cross Contamination • Nil or little formal stability data • No clinical trials • Excipient suitability, e.g. sugar or lanolin free Risk to Dispenser • Control of Substances Hazardous to Health or COSHH assessment • PPE available: safety glasses, gloves, masks & sleeve protectors • Risk to other employees e.g. fumes which can be harmful or unpleasant e.g. Cade Oil ”empyreumatic” odour 17 The Peppermint Water Case Death of a 3 week old baby due to the incorrect dilution of Chloroform Water Concentrate 18 A Basic Approach To Risk Analysis  Picture the worst case scenario  What would be the consequences to the patient?  How likely (frequency) is this type of error to occur?  Would the checking pharmacist or the patient be able to detect the error? 19 Common Problems with Specials Prescriptions  If short dated, will patient use up quantity prescribed within that time?  Cost if using specials company, very important if private prescription  Lack of details on prescriptions especially creams and ointments where no base is indicated  Computer generated prescriptions where unlicensed preparations are not in the standard menus  Finding a formula  Regional Differences with non-compendial formula, e.g. Knox Mouthwash means different things in different parts of UK 20 Common “Specials” Script Enquiries  Ingredients of creams or ointments expressed as % but don’t add up to 100%!  Readily available licensed medicine written generically, e.g. Duofilm Paint written as: Salicylic Acid 16.7%, Lactic Acid 16.7% in Flexible Collodion.  A licensed medicine should be dispensed wherever possible. 21 Sources of Formulae  Compendia e.g. BP, Martindale and etc.  Hospital-often continuation of treatment in primary care  GP’s own e.g. Dr Ives wart paint  Published literatures or journal articles available on internet 22 Availability of Raw Materials  Need to obtain a Pharmaceutical Grade, BP , PhEur or USP  Laboratory Grades (AnalaR or GPR) may be all that’s available  May be using a licensed medicine, e.g. crushing tablets, diluting a steroid cream such as Betnovate  Difficult to obtain small quantities of pure drug powders  Need to consider TSE-Transmissible Spongiform Encephalopathy e.g. Lanolin  Good practice to obtain a Certificate of Analysis  May need to use another unlicensed medicine ,e.g. imported tablets. Need to be assured of Quality 23 Formulation-Microbial Considerations  Is there any preservative system in the formula? This must be considered when allocating shelf life  Is the product prone to microbial growth, e.g. cream compared to ointment?  Traditional-Single strength Chloroform Water  NIPA’s such as Methyhydroxybenzoate and propyhydroxybenzoate  Widely used in Pharmaceuticals and Cosmetics  Cold water soluble salts available but raise pH of product which is often undesirable  Ester is soluble at 80oC-little effect on pH-more useful 24 Formulation General  Physical problems –cracking, caking, precipitation etc.  Chemical degradation-usually pH dependent  BP limits for actives are usually 95-105%. Published data may accept wider limits such as 90%.  Microbial-preservative system, closed pack shelf life may be longer than opened pack e.g. use 14 days after opening 25 Commonly Requested Non sterile Dosage Forms  For Application to the skin  E.g. Creams, Ointments, Pastes, Lotions, External Solutions  For Oral Ingestion-Liquids  E.g. Suspensions, Solutions, Mucilage  Traditional terms: Elixir, Mixture, Linctus  Now all referred to as Oral Solution/Suspension unless using a compendial title 26 Less Common Dosage Forms (Non Sterile)  Reefers (cigarettes injected with drug)  Capsules and Powders  Bars of Soap  Lozenges/Pastilles  Lollipops  Suppositories/Pessaries- need displacement value of ingredients 27 Prescriptions For External Use  Prescription says “Coal Tar Ointment”  Coal Tar Ointment BPC 1934 or other formula?  Coal Tar Solution BP (20%): Brown solution  Strong Coal Tar Solution BP (40%)  Coal Tar BP: Thick black semi-solid  Remember COSHH!!  MSDS= Material Safety Data Sheet  Ointment bases: WSP, YSP, Emulsifying Ointment 28 Prescriptions for External use Cont’d  Cream bases: Aqueous Cream, Hydrous Ointment (oily cream), Unguentum M (amphiphilic)  Common ingredients: Salicylic Acid Powder  Dithranol, Sulphur, Steroid Creams/Ointment  Can use crushed tablets or use injection, e.g. Genticin Injection 40mg/1ml to make Gentamicin Cream 29 Oral Liquids  Is drug soluble in vehicle at dose required?  If not could a suspension be prepared?  Crush tablets or use Powder  Use the highest strength tablets to reduce overall excipients  Check tablet characteristics: Controlled Release, Sugar Coated, Film Coated, Enteric Coated  Good Practice: Always use same brand and strength. Care with generics.  Good Practice: Standardise to dose/5ml or dose/1ml  May dilute injection fluid from ampoules 30 Making a Suspension From Tablets Crushing, grinding Wetting and pasting These steps are vital to give homogeneous product 31 Importance Of Calculation Skills  A full understanding of what’s required can prevent dispensing errors  Ensure correct clinical interpretation of prescription  Overdose or Sub-therapeutic dose 32 Importance Of Calculation Skills Cont’d  Simple %’s to 100%  Parts: 1:4, Five Parts Total. This is 20%.  ¼ is 25%  Relationship between mg/5ml and %  Use of International Units  Dealing with odd doses when making crushed tablet suspensions  Dilutions (Peppermint Water Case) 33 Beware of Complacency  We all know 1+1=2  Check this every day as a pharmacist  Errors are usually silly mistakes  Consequences can be tragic  Establish rules and routines  Standard Operating Procedures and Worksheets 34 Summary-Dealing with Prescription  Often lacking in details  Don’t take at face value  Usual clinical assessment  Has patient had medicine before, possibly from hospital?  Save details, e.g. worksheet or GN14 record  Consider shelf life, closed and open, pack size and storage conditions  Use your scientific knowledge 35 Summary-Managing Your patient  Collection and delivery arrangement  Good Practice-Establish a routine  Consider bank holidays  Logistics-especially fridge lines  Compliance, e.g. Administering 1ml may be easier than administering 5ml  Accurate dosing-Counselling, Oral Syringes  Pack down options- e.g. 1 bottle for home and 1 bottle for respite care 36 MPharm Programme Making Specials on an Industrial Scale 37 Licences and Regulations  Medicines Act 1968  Human Medicines regulation 2012  MHRA: Specials Manufacturing Licence  MHRA :Wholesale Dealers Licence  Retention of licence depends on successful MHRA inspections  Misuse of Drugs Act 1971  Licences issued by Home Office  Registered Pharmacy Premises  (Clinical Trial Directives) 38 Compliance With Other Regulations  Employment Law  Weights and Measures  Health and Safety  Waste Disposal and Environmental issues 39 The Guides • Orange Guide: Rules and Guidance for Pharmaceutical Manufacturers and Distributors • This document introduces the concepts of a Quality Assurance System and Good Manufacturing Practices • Green Guide: Rules and Guidance for Pharmaceutical Distributors 40 Specials Patients  Paediatric  Geriatric  Terminally ill  Drug Misusers  Special Needs  Tube fed  Allergies 41 Specials Manufacturing License Two Key Personnel  Head of Production  Head of Quality Control  These have both different and common responsibilities  Should be two individuals with relevant experiences & qualifications to the same level 42 Extemporaneous Dispensing in Industry  Cleanrooms  MHRA Licences  Operate a Quality Management System  Full GMP Compliance  SOP’s/QC worksheets/Environmental monitoring/ Training records  Validation System  Full audit trail  Perform risk assessments and in house risk mitigation techniques to prevent errors  Develop best practice 43 Scaling Up  Change from crushing tablets to using powder (API)  Need to QC test  Need TSE compliance certificate  Shelf life extension/Stability Testing (ICH)  Full set of Processing Equipment: Mixing, filling, packaging, Labelling, Bar Codes for shipping, shrink wrap/pallets  Bulk storage-Quarantine and Released 44 Scale Up Continued  Dispensing of Raw Materials  Chemical and microbial cleaning validation  Process validation  Cleaning large equipment-shower heads, floor drains, high pressure hoses  Drying and storage of cleaned equipment 45 Scale Up Cont’d  Methods of Heating-melting waxes, water  Source of Purified Water EP-daily monitoring of still  Use of Solvents e.g. Ethanol-spark proofing of equipment  Room changeover and work scheduling  Different staff for different parts of process 46 Reference • MHRA guidance note 14 • Royal Pharmaceutical Society. Professional guidance for the Procurement and Supply of Specials. 2015. 47