Cancer mid-module rogo

• • Sterile pharmaceutical products include
  • Chemotherapy drugs and antibody preparations 
  • Total parenteral nutrition
  • Intravenous additives
  • Eye products
  • Drugs used in clinical trials 
  • Some medicated dressings
• • Potential contaminants
  • Microorganisms (fungi and bacteria)
  • Particulate matter (skin, hair, fibres, condensate)
  • Pyrogens (endotoxin produced from gram (-) bacteria)
• • Breckenridge report (1976) and CIVA services
  • All additions to infusions should be made by the manufacturer or hospital pharmacy department
  • This followed KCl being added and settling at the bottom of infusion on wards - resulting in a fatal bolus dose
• • Farwell report (1995) and Aseptic preparation
  • Requirements for aseptic dispensing in NHS bodies
  • Following the death of two babies from contaminated TPN
• • NPSA Alert (2007) and promoting safer use of injectable medicines
  • All organisations to have risk assessments, up-to-date SOPs, training, and an annual audit of injectable medicines use
  • Following 800 reports of errors
• • NHS Alert (2016) and restrict the use of open systems
  • Not to use open unlabeled systems for injectable medicines
  • E.g. when radiology staff draw up contrast media from unlabelled bowels which can be confused with antiseptic products for skin decontamination
• • Medicines Act 1968
  • Any product with an MA - liability with the product lies with the manufacturer 
  • Section 10 exemption - allows medicines to be prepared under the supervision of a pharmacist
• • Good manufacturing practice (GMP)
  • Orange guide
  • Rules are more stringent as there are more risks with batch manufacture
  • Also needed for a special manufacturer license
• • EL(97)52 regulation and QA of aseptic preparation services
  • Yellow guide
  • Quality assurance and external audit of all aseptic dispensing activities
• Factors of manufacturing

  • specials manufacturer license
  • preparation by a suitably trained person
  • extended expiry due to stability
  • batch prepared for stock

  • final check and release must be done by separate people
  • release by any registered person
  • external MHRA inspection
• Factors of dispensing

  • section 10 exemption
  • prepared or directly supervised by a pharmacist
  • max 7-day expiry
  • prepared against prescription
  • final check and release together
  • any suitably qualified pharmacist
  • standards comply with local and regional QA
  • Regional audit under EL(97)52
• • Quality management (assurance)
  • Sum total of organised arrangements made with the objective of ensuring that medicinal products are of the quality required for their intended use
  • Includes design, validation, documentation control, training and SOPs, error reporting deviation management, quality review, internal audit, product recall, and complaints
• • Documentation
  • Policy and procedures
  • Worksheets
  • Labels
  • Computer systems
• • Roles and responsibilities (section 10 exemption)
  • Chief pharmacist (PQS and safe supply)
  • Accountable pharmacist (named responsible person)
  • Authorised pharmacist (routine supervisor)
  • Suitably qualified pharmacist (any registered pharmacist but not authorised to supervise)
• • Design of workflow (sterile objects → non-sterile areas) and airflow (pressure from highest to lowest - negative pressure to carry contaminants away from sterile areas)
  • Grade A - Laminar airflow (LAF) cabinets and isolators i.e. the point of fill. All aseptic manipulations carried out in critical zone 
  • Grade B - the aseptic preparation room.
  • Grade C - Change areas or inner support room.
  • Grade D - Outer support rooms. (Grade A isolators be installed in Grade C or D rooms)
• • Validation
  • Validation Master Plan
  • Design qualification - DQ
  • Installation qualification - IQ
  • Operational qualification - OQ
  • Performance qualification - PQ
• • Equipment 
  • Laminar airflow cabinets (open)
  • Isolator devices (closed)
  • Clothing and PPE
• Summary of PPE

  • raw materials = gloves and gown/apron
  • setting up = gloves and gown/apron
  • preparation = gloves and gown/apron
  • administration = gloves and gown/apron and eye protection
  • waste disposal = gloves and gown/apron and eye protection and respiratory protection
  • spillage = gloves and gown/apron and eye protection and respiratory protection
• • Cleaning 
  • Removal of dirt
  • Scheduled (e.g. critical zones before and after each session, floors daily, etc)
  • Approach - least to most contaminated (e.g. Grades A-D and cabinets back to front)
• • Decontamination
  • Removal of chemical/microbiological contaminants
• • Disinfection/sanitisation 
  • Process of reducing the number of viable micro-organisms 
  • Cleaning agents/activities 
  • Ensure sufficient contact time of over 2 mins
  • Ideally bactericidal, fungicidal, virucidal, and sporicidal
• • Environmental monitoring
  • Facility and equipment performing correctly 
  • SOPs being followed
• • Microbiological monitoring
  • Settle plates
  • Contact plates
  • Swabs
  • Finger dabs
• • Physical checks 
  • Airflow checks using an anemometer 
  • HEPA filter integrity checks 
  • Particle counting
• • Chemical monitoring
  • Residue swabs
  • Surface wipes
• • Principles of ANTT
  • Aseptic non-touch technique 
  • Used near patient areas
  • Closed procedure = transfer of sterile ingredients to a pre-sterilised sealed container either directly or using a sterile transfer device like a syringe and needle
  • Critical surfaces (e.g. needles) should not be handled
  • Needle safety - re-sheathing of needles using a single-handed re-sheathing device (NeedleSafe)
• • COSHH covers chemicals, biological agents, and carcinogenic substances
  • Carcinogenics require a risk assessment and safety data sheets
• • 5-steps of risk assessment 
  • Identify hazard
  • Who is at risk and how
  • Adequacy of existing measures
  • Documented risk assessment 
  • Review data
• • Safe storage and supply 
  • Secure storage at bench height with heavy objects near the floor
  • Clearly labelled items and areas
  • Cytotoxic drugs supplied in securely sealed and spill-proof containers
• • Spillage 
  • Act immediately and cordon off the area
  • Collect spill kit and PPE
  • Lay “chemosorb” pads and use an absorbent towel to clean from uncontaminated to the centre of the spillage 
  • Wash down the area with plenty of water and dry
  • Complete the incident form and replace the spill kit
• • Waste disposal
  • Covered by European Waste Framework directive, UK Health Technical Memorandum, and Hazardous Waste Regulations
• • Product waste
  • Designated sharp bins with purple lids - cytotoxic and cytostatic medicine waste
  • Double-bagged and disposed of by high-temperature incineration
• • Patient waste 
  • Potentially hazardous metabolites are excreted in urine and faeces
  • Cisplatin unchanged in urine for 7 days and methotrexate for 3 days and 7 days in faeces
  • Contaminated linen and clothing treated as infected clinical waste but heavily contaminated may need to be incinerated
• • Aseptic processing 
  • Manipulation of sterile starting materials and components in such a way that they remain sterile and uncontaminated whilst being prepared for presentation in a form suitable for administration to patients
• • Equipment 
  • wide range of sterile luer-slip (septic manipulation) and luer loc (as final container) 
  • Syringes 1-50mml size
  • Sterile needles 16-20 gauge (higher number = finer needle)
  • Phaseal device to equalise pressure in vials
• • Pre-production 
  • Worksheet selection
  • Preparation labels
  • Assembly of tray
  • Record batch numbers
  • Sanitise
  • Transfer to aseptic room
• • Preparation
  • Aseptic manipulation of raw materials into the final container
  • In-process checks
  • Reconciliation
  • Decontamination
• • Post-production
  • Labelling
  • Reconciliation of materials/consumables used
  • Check final product
  • Pack for supply
  • Final release
• • Verification of product
  • Clinical - suitably qualified pharmacist
  • Aseptic services - authorised pharmacist
• • Inspection of product
  • Starting materials, consumables, and documentation
  • In-process checks (mixing, volumes, assembly)