Aseptic Preparation and Safe Handling Flashcards
What are some examples of sterile pharmaceutical products?
- Chemotherapy drugs and antibody preparations
- Total parenteral nutrition (TPN)
- Intravenous additives
- Eye products e.g. intravitreal use (injection to the eye)
- Drugs used in clinical trials
- Some ‘medicated’ dressings
> Where an IV route is preferable
What are the potential contaminants of a sterile pharmaceutical product, and how could these occur?
- Microorganisms (fungi and bacteria)
- Particulate matter (skin, hair, fibres, condensate)
- Pyrogens (endotoxin produced from G-ve bacteria)
> From ingress during preparation or administration.
What are the purposes of patient safety alerts?
Give examples.
To seek to understand and address errors w/injectable medicines.
- Breckenridge report (1976); CIVA services
- Farwell report (1995); Aseptic preparation
- NPSA Alert (2007); safer use of injectables
- NHS Alert (2016); restrict use of open systems
How did the Breckenridge Report (1976) arise, and what did it recommend?
- Accidental infusion of potassium that was incorrectly mixed on the ward; KCL denser than H2O, precipitated at bottom = ‘bolus dose’ of strong conc KCL administered leading to cardiac arrest.
- Lead to development of CIVAS; Hospital Centralised IV Additive Services = additions to infusions to be made by the manufacturer or by the hospital pharmacy department.
What did the Farewell report (1995) and the 2007 NPSA Alert recommended?
- Farwell; set out requirements for aseptic dispensing in NHS patients.
- NPSA; promoted safer use of injectable medicines, requiring all healthcare organisations to perform new risk assessments. Came about after 800 errors w/injectables; 25 fatalities.
What legislation governs the preparation and supply of medicines?
What do these specify?
- Medicines Act 1968 and various statutory amendments, now part of the Human Medicines Regulations 2012.
- Marketing Authorisation (MA) required with any medicinal product sold or marketed; liability of product defects lies with manufacturer.
What guidance is availible for the preparation and supply of medicines?
- Orange Guide (MHRA); Good Manufacturing Practice (GMP)
- Yellow Guide; Quality Assurance of Aseptic Preparation Services.
What does The Yellow Guide entail, and what regulation does it include?
- Provides guidance on GMP for aseptic dispensing e.g. procedures, competencies, responsibilities, control of materials, provision/maintenance/monitoring of facilities and equipment
- EL(97)52 Regulation/Farwell report; guidance on aseptic dispensing contained within The Yellow Guide.
What does the Crown (Parliamentary) Section 10 Exemption entail?
Where does liability lie?
- Allows medicines to be prepared ‘manufactured’ under the supervision of a Pharmacist, against a written Rx, for subsequent administration to a named patient.
- Includes manipulation of raw materials incl. licensed medicines e.g. addition to a syringe/infusion bag.
> Liability for defects lies with the Pharmacist, company or NHS Hospitals Trust.
How do rules for manufacturing medicines vary in the Orange Guide to Section 10 Exemption preparation by a pharmacist, and why is this so?
- Rules and regulations much more stringent for large-scale batch manufacturing than Section 10 dispensing for an individual patient (whether a small batch or single)
- Potential to harm many more people w/mass manufacturing opposed to tailored preparation
- Medicines made in manufacturing have to be put to market; sold and distributed.
Why is there a need for a Special Manufacturer’s Licence (Specials), and what rules are they governed by?
- Used where there is no suitable commercially availible product, often in small hospital production units
- Does not require a full MA; meets ‘special’ need.
- Rules similar to medicines prepared under a Manufacturer’s Product License (MA) (not as lax as Section 10 Dispensing)
List and compare aspects of manufacturing (via specials manufacturing licence) and dispensing (under section 10 exemption).
Manufacturing:
- Preparation by suitably trained person (not necessarily qualified pharmacy technicians)
- Extended expiry (stability); longer shelf lives and less waste (provided stability data supporting)
- Batch prepared for stock
- Final product check and batch release done by separate people (pharmacy technician former, registered and degree-qualified person latter e.g. pharmacist, scientist, Qualified Person)
- Inspected by MHRA on risk-based approach (more frequently if more risks identified)
Dispensing:
- Prepared or directly supervised by a pharmacist (pharmacy technicians prepare product ‘under supervision’)
- Max 7 day expiry (stability allowing)
- Prepared against Rx (though small batches up to 10 items can be infrequently prepared in anticipation of a prescription; subject to limited shelf life and full dispensing requirements e.g. labels)
- Final check and release together by suitably qualified pharmacist
- Regional audit under EL(97)52 QA on 1-3 year cycle
What is the PQS?
Pharmaceutical Quality System; overall system of quality management, providing assurance of product quality as a result of the systems and processes in place.
What is the Beaney (2016) definition for Quality management/assurance?
“The sum total of organised arrangements with objective of ensuring that medicinal products are of the quality required for their intended use.”
What does quality assurance cover?
All aspects of manufacturing process:
- Product design
- Clean room environment
- SOPs
- Training
- Documentation
- Internal audit
- Final release of product
- Product recall and complaints
What documentation might be involved in PQS?
- Policy and procedures
- Worksheets
- Labels
- Computer systems
What roles and responsibilities for staff may be defined in PQS?
- Standards of hygiene
- Changing into clean room protective clothing
- Training
- Assessment
What are the differences in roles and responsibilities of the Chief, Accountable, Authorised and Suitably Qualified Pharmacists in a PQS? (Section 10 Exemption)
- Chief; overall boss man.
- Accountable; also an Authorised Pharmacist, responsible for all aspects of aseptic preparation unit.
- Authorised; supervises the aseptic process and release of products inc. Rx verification for each product, ensures clinical check has been carried out by a Suitably Qualified Pharmacist.
- SQ Pharmacist; Clinical checks, but not specifically authorised to supervise or oversee routine aseptic preparation activities (Authorised Pharmacist).
What is the role of the Chief Pharmacist in a PQS?
Overall responsibility and accountability for the PQS and safe supply of medicines.
What is the role of the Accountable Pharmacist in a PQS?
The named Pharmacist responsible for all aspects of the aseptic preparation unit e.g. approval of work systems.
What is the role of the Authorised Pharmacist in a PQS?
- Specifically designated to routinely supervise the aseptic process and release of products for use.
- Including prescription verification at an individual product level.
What is the role of a Suitably Qualified Pharmacist in a PQS?
Any registered pharmacist e.g. a clinical pharmacist, performs clinical checks.
How is the Sterile environment designed?
- Legislation and guidance govern design around workflow, health & safety, cleaning and ongoing maintenance.
What system maintains a sterile environment, to what controls?
- Maintained by air flow and pressure from highest to lowest
- Creates a positive pressure drop (10 - 15 Pa) carrying contaminants from sterile (cleanest) to non-sterile (dirtiest) environment.
- Achieved by careful design, use of air handling unit, laminar air flow and extraction between rooms.
How many air changes per hour are desirable in a sterile environment?
A minimum of 20-30 complete air changes per hour.
What are the typical configuration of clean zones? (EU GMP Grading)
- Grade A - Sterile; Laminar air flow (LAF) cabinets and isolators i.e. point of fill.
- Grade B - the aseptic preparation room (where LAFCs are housed)
- Grade C - Change areas or inner support room (where materials are assembled)
- Grade D - Outer support rooms
Which zone is aseptic manipulation carried out in?
In critical zone EU GMP Grade A (EC 2015).
Where are Grade A isolators installed?
Can be installed in Grades B-D rooms.
What is meant by the Validation Master Plan?
- Includes all documentation and testing of Design Qualification (DQ), Installation Qualification (IQ), Operational Qualification (OQ) and Performance Qualification (PQ).
- Rigorous procedures and processes to ensure aseptic sterility are maintained before, during and after use.
- There is an essential requirement for commissioning facility and ongoing audit and inspection.
What equipment is required for sterile pharmaceutical production?
- Laminar airflow cabinets (open)
- Isolator devices (closed)
- Clothing and PPE
What variants of LAFC and isolator devices are there for aseptic manipulation?
- Horizontal or vertical LAFCs
- Class II safety cabinets
- Cytotoxic cabinets
- Negative and positive pressure isolators
How are different clean zones connected?
- Interlocking hatches and doors
- Allow time for decontamination and audible alarms if breach of environment or malfunction (e.g. needle through isolator sleeve, failure in Air Handling Unit, AHU).
Where are washing facilities and changing facilities located in an aseptic manufacturing unit?
- Washing facilities; on way into facility only (never in clean zones)
- Changing facilities; at entrance and between rooms when required e.g. Grade C inner support room to Grade B clean room with LAFC.
What is deemed a hazardous material in relation to manipulation by the operator?
- Cytotoxic chemotherapy
- Monoclonal antibodies
- Penicillin antibodies
Are hazardous materials prepared in the same space as non-hazardous preparations?
No; they must be prepared in separate work zones/rooms/equipment.
How and where is cytotoxic chemotherapy prepared?
Why is this the case?
It must only be prepared in a safety cabinet (like in chemistry/ceutics lab) or negative pressure isolator, to maximise operator protection.
Do procedures for hazardous materials also apply for the preparation of licensed and unlicensed products?
Yes; in that preparation of licensed and unlicensed products must be clearly separated.
What clothing/PPE is required for a Grade D outer support room?
- Non-shedding protective coat
- Overshoes
- Covered hair/facial hair
What clothing/PPE is required for a Grade B aseptic preparation room?
- Single piece clean room garment
- Boots
- Non shedding headgear
- Facemask
- Non-powder sterile gloves
- Armlets
What is the role of PPE?
Minimises risk of exposure via inhalation/absorption of hazardous substances
What are the PPE requirements when handling cytotoxic chemotherapy?
- Full-length suit w/sleeve protection
- Gauntlets (outer hench gloves)
- Double gloving w/inner thin layer latex gloves and nitrile cytotoxic-grade outer gloves
- Balances operator protection with ability to manipulate product safely (using syringes and needles etc.)
What are the PPE/clothing requirements when preparing products outside of a closed containment system?
- Full length suits
- Gloves
- Eye protection
In what activities is eye/respiratory protection required on top of gloves and gowns?
- Raw materials, Setting up, Preparation = G&G OG
- Administration (eye)
- Waste disposal (eye & respiration)
- Spillage (eye & respiration)
Define: cleaning.
The removal of dirt.
schedule & approach accordingly
Define: decontamination.
Removal of a chemical (or microbiological) contaminant e.g. in cytotoxic
Define: disinfection.
Process of reducing number of viable micro-organisms.
What is an effective cleaning schedule?
- Ceilings and walls monthly
- Floors and benches daily
- Critical zones before/after each session
What is the best cleaning approach?
- To clean from least to most contaminated; from Grade A to D.
- Wipe down walls to push down particles
- Wipe cabinets from back to front in overlapping strokes using clean wipe for each surface (walls, bench etc.)
- Clean slowly (to avoid generating particles)
- Methodically (to cover all areas)
What is the minimum contact time required for disinfectants to work?
At least 2 minutes
What cloths are used to wipe down surfaces, and what process follows?
- Lint-free, non-shedding sterile cloths
- Disinfect w/freshly diluted products afterwards
What is the standard disinfectant product used for critical zones?
70% w/v IMS (industrial methylated spirits)
What are the ideal attributes for a disinfection/sanitisation agent?
- Bactericidal (must) Ideally: - Fungicidal - Virucidal - Sporicidal
How do alcohols compare with aldehydes/hydrogen peroxide for disinfection agent activity?
- Alcohols have good BFV (bacterio-fungal-virucidal) activity, but lack sporicidal
- Aldehyde and hydrogen peroxide are sporicidal, but hazardous.
What are the different ways to monitor cleaning/sanitation?
- Environmental
- Microbiological
- Physical
What does environmental monitoring entail, and why is it required?
- Alarm panels (e.g. temperatures/pressures of AHU) and gauges
- To ensure facility and equipment are performing correctly, within controlled limits, and SOPs being followed.
- Involves physical, microbiological and chemical testing.
What does microbiological monitoring entail?
- Settle plates
- Contact plates
- Swabs
- Finger dabs
- Active air samples (onto agar strips)
- Plates exposed during working sessions then incubated.
What are some examples of physical monitoring of sanitation?
- Airflow; anemometer
- HEPA filter integrity; dispersed oil particulate (DOP)
- Particle counter (at rest and during activity)
- Differential pressures; isolator/glove ‘leak tests’ for pressure decay
What does chemical monitoring of sanitation entail?
- Residue swabs
- Surface wipes
How often are quality assurance reports reviewed for cleaning/sanitation?
Monthly.
Define: ANTT.
- Aseptic non-touch technique; to avoid any contact with any surface which will be in contact with the sterile fluid path.
- Preparation and administration of injectables
Where is ANTT used?
- Near-patient (wards, patient home)
- Aseptic environments (aseptic units, operating theatres etc.)
What is a ‘closed procedure’ w/reference to ANTT?
‘Transfer of sterile ingredients or solutions to a pre-sterilised sealed container, directly or using a sterile transfer device, without exposing the solution to the external environment’
- Must be within an EU GMP Grade A (EC 2015) environment.
- Used in pharmacy aseptic areas
Is a single withdrawal from a sterile ampoule, using a sterile syringe and needle a closed procedure?
Yes
What needs to be considered w/regards to ANTT approach to safe aseptic technique in near patient areas?
(6 step approach)
- Risk assess
- Manage environment
- Decontaminate and protect (product + patient)
- Use aseptic fields
- NTT
- Prevent cross-infection
What are some examples of critical surfaces?
- Walls
- Bench
- Syringe hub
- Syringe needle
Why is needle safety important?
- Reduce risk of needlestick/sharp injury
- Risk of exposure to blood borne infections e.g. HIV, Hep C
- Risk of contamination w/concentrated cytotoxics and other drugs
What regulations govern needle safety and what do they specify?
- Health and Safety (Sharps Instruments in Healthcare) Regulations 2013 (May 2013)
- Requires all employers to risk assess use of sharps, introduce controls to avoid unnecessary use, to utilise needle-safe or needle-free equipment, ensure sharps bins are availible in all relevant areas, and that all sharps-related incidents continue to be acted on and reported.
What is meant by needle-safe equipment?
- Blunt needles
- Protection mechanisms
- Re-sheathing of needles using single-handed re-sheathing devices e.g. needle block; re-sheathing usually not advised as increases risk of needlestick injury (dispose of after use immediately) but required for containment/asepsis to avoid cross-contamination e.g. infusion bags in the confined space
What is meant by needle-free devices?
- Devices designed to reduce risk of needle-stick injury
- Incorporate closed systems to reduce exposure to hazardous drugs
- E.g. Tevadaptor, Braun OnGuard and Phaseal.
What are the COSHH regulations (2002)?
- Control of Substances Hazardous to Health Regulations (2002)
- Chemicals, biological agents etc.
- NOT radioactive substances.
Where do carcinogens appear in COSHH, and what are the guidelines?
- Appendix 1 approved code of practice
- Require risk assessment and safety data sheets to cover products, covering control measures (e.g. PPE and health surveillance)
What is a safety data sheet?
Required for carcinogens as per COSHH:
- Raw materials
- Control measures
What organisation cover/manage COSHH?
The UK Health and Safety Executive (part of NHS Public Health)
What are the 5 steps to risk assessment with COSHH?
- Identify hazard
- Who is at risk of being harmed and how (attention to high risk employees e.g. pregnant women)
- Adequacy of existing control measures (frequency of use, previous incident records)
- Documented risk assessment
- Review date
What regulations other than COSHH govern the safe handling of chemicals/biologicals etc?
- Health and Safety at Work Act 1974
- Management of Health and Safety Work Regulations 1999
What is safe storage of cytotoxics?
- Secure storage at bench height (heavy objects near the floor)
- Clearly labelled areas
Which organisation provides guidelines on the safe transport of cytotoxic drugs from manufacturer to pharmacy?
What do these entail?
- The International Society of Oncology Pharmacy Practitioners (ISOPP)
- Using manufacturer’s that meet recognised standards e.g. oncotainers (plastic sheath around glass vials to prevent smashing)
- Transport documentation
- Damage check
- Certification containers are not contaminated
How must chemotherapy be supplied from the manufacturer?
Containers must be:
- Secure
- Sealed
- Clearly labelled
- Spill-proof
Cytotoxic bag (clear) with product double wrapped, transported in person or within secure transport box.
What is the procedure for dealing with cytotoxic spillages?
- Act immediately
- Cordon off area
- Collect spill kit
- PPE (double glove, disposable gown, goggles, mask, overshoes)
- Lay down ‘chemosorb’ pads over liquid spillage
- Use absorbent towel to clean from uncontaminated outer to centre of spillage
- Wash down contaminated area with copious water
- Dry w/absorbent towels
- Double bag all waste in cytotoxic waste bag
- Complete incident form
- Replace spillage kit
What is a spill kit?
- Protects personnel and contains the spillage
Should include: - PPE
- Hazard signs
- Absorbent materials (e.g. chemosorb pads/granules)
- Scoop/scraper
- Container for safe disposal and subsequent high temperature waste incineration
Where are spill kits located?
Every area with chemotherapy is stored, manipulated, administered or disposed.
What regulations cover the spillage of chemotherapy?
- European Waste framework Directive 2008/98/EC
- UK Health Technical Memorandum
- Hazardous Waste Regulations
- UK Health and Safety Legislation
What is defined as product waste, and how is it disposed?
- Empty vials
- Consumables
- Contaminated administration equipment
> Disposed of in designated sharps bins w/purple lids
Sealed, double bagged and disposed of by high temperature incineration
How is cytotoxic/cytostatic medicinal waste classified?
- H6 = toxic
- H7 = carcinogenic
- H10 = toxic for reproduction
- H11 = mutagenic
What is the significance of a purple-lidded sharps bin?
- For cytotoxics
- Sent with authorised consignment note for high temperature incineration in a licensed facility
What are the dangers of patient waste, and how should it be discarded?
- Potentially hazardous metabolites excreted in urine and faeces
- Contaminated linen and clothing may be treated as infected clinical waste
- Heavily contaminated to be disposed by incineration
What factors influence the duration that a patient excretes hazardous waste?
Give examples.
- Drug
- Dose
- Route
- Patient factors (e.g. hepatic-renal function)
> Cisplatin excreted largely unchanged in urine for 7 days
Methotrexate in urine for 3 days, 7 days in faeces
Define: aseptic processing.
The 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.
What is included in the process design of aseptic processing?
- Entry/exit from sterile facility
- Choice of clothing/PPE
- Choice of equipment/materials
- Adoption of principles of good aseptic practice (e.g. sanitisation of all starting materials, correct choice and use of equipment)
- Product segregation
- In-progress checks
Where can hazards arise during aseptic manipulation, and how can they be minimised?
- In constitution due to use of wrong equipment/technique; positive pressure in a vial results in liquid aerosols/vapours escaping, contaminating equipment and transferred by operators
- Validated operator checks to check for contamination and decontamination of surfaces (e.g. w/fluorescein)
What size needles are most preferable during aseptic processing?
- Wide range of sterile needles availible
- 16-20 gauge (13 largest bore to 27 finest)
- Use smallest bore to reduce risk of coring rubber septum on vials/ports
What syringes are availible for aseptic processing/manipulation?
- Luer-slip (septic manipulation)
- Luer-loc (as final container)
> 1-50 mL size
What is the purpose of using aseptic transfer devices?
- Maintain closed procedure
- Minimise manipulations and connections
- Phaseal; equalises pressures in vials without need for push/pull technique.
What are the three stages of aseptic processing?
- Pre-production; worksheet selection, preparation, labels, assembly of tray, record batch numbers, sanitise, transfer to aseptic room
- Preparation; aseptic manipulation of raw materials into final container, in-process checks, reconciliation, decontamination
- Post-production; labeling, reconciliation of materials/consumables used, check final product, pack for supply, final release.
What are the steps involved in product check and release?
- Verification
- Inspection
- Reconciliation (HELP)
- Final product checks
- Product approval (Release)
What does the Verification process involve?
Checking something is correct:
- Clinical; against Rx by suitably qualified pharmacist (ensure product appropriate for patient)
- Aseptic services; to check clinical check has been undertaken, the prescibed components are compatible, formulation stable and product presentation appropriate for intended use (route), by an authorised pharmacist
What does the Inspection process involve?
Occurs at various stages:
- Initial visual examination of starting materials (correct, signs of degradation/colour change/particles/leaks/label defects)
- Consumables; visually checked before sanitisation and transfer to aseptic room.
- Documentation; inspected to ensure it is correct
- In-process checks; products well-mixed, volumes accurately measured, no physical signs of discolouration or precipitation on assembly
What does the process of Reconciliation involve?
Accounting for materials, consumables, labels:
- No. of drug containers (vials/ampoules) compared w/quantity expected on worksheet
- Labels checked against worksheet before affixing to pre-filled syringe/infusion bag etc.
How does the acronym (HELP) aid the process of reconciliation?
H - how many? (check worksheet)
E - expiry date
L - label (details of patient & product)
P - product (drug, strength, final volume, diluent)
What does the final product check entail? Who does it?
- Reconciliation of product and labels
- Visual inspection, sign off worksheets
> Only carried out by fully trained competent staff e.g. senior PTs routinely involved
What is involved with product approval/release?
Who does it?
- A formal, recorded decision of release after all checks have been completed and documented.
> Suitably qualified person, under Section 10 dispensing under supervision of a pharmacist
What is a Laminar Air Flow Cabinet (LAFC), and what does it protect?
- Continuous, unidirectional flow of sterile air
- Protects the product, but not the worker
What are the dos and don’ts of using a LAFC?
Do:
- Work behind the red line
- Use the needle safe tool
Don’t:
- Obstruct air flow
- Pass hands over product
- Lean into the LAFC
- Talk
What does HEPA stand for, and how small a particle can they remove?
- High Efficiency Particulate Air Filter
- Removes at least 99.997% of airborne particles down to 0.3 micrometres in diameter
How must the product record sheet be completed with regards to weights/volumes/trailing zeroes/corrections/units?
- Weights = three d.p., with 0.001 tolerance
- Volumes = 1 d.p.
- Zeroes = 0.5g instead of 0.500g
- Corrections; initialled
- Units; include
