Aseptic Operation - PDF

Aseptic operation and environment Dr Atheer Awad [email protected] Office F157 Hillside House Aseptic operation and environment Learning outcomes 2 Describe the theory of aseptic products Understand the implications of...

Aseptic operation and environment Dr Atheer Awad [email protected] Office F157 Hillside House Aseptic operation and environment Learning outcomes 2 Describe the theory of aseptic products Understand the implications of non- sterility in aseptic manufacturing Describe the key components of aseptic processing Aseptic operation and environment 3 Cleanliness ❑ Health and Safety ❑ Storage ❑ Application Aseptic operation and environment 4 How clean is clean? ▪ Clean ▪ Fairly clean ▪ Really clean ▪ Very clean ▪ Sterile Aseptic operation and environment 5 Sterility “Sterility” is the complete destruction or elimination of all viable microorganisms But does “sterilisation” completely destroy all infectious matter? Aseptic operation and environment 6 Sterility Problems with the definition: Not all microorganisms can be isolated and/or detected Different microorganisms inactivation rate Sterility of the product cannot be guaranteed mathematically or practically Aseptic operation and environment 7 Sterility assurance level (SAL) The probability that a single unit that has been subjected to sterilisation nevertheless remains nonsterile. ❑ SAL of 10-6 means that for every 1,000,000 items sterilised there may be one that contains bacteria ❑ SAL is a statistical probability that is used because it is impossible to prove that all bacteria have been killed during the sterilisation process Aseptic operation and environment Pharmaceutical product requirements 8 ❑A 10-6 SAL or greater [1 in 1 000 000] is used for: Products in contact with breached skin or compromised tissue Invasive products that enter normally sterile tissue Products with claims of sterile fluid pathways Surgically implanted devices ❑A 10-3 SAL or greater assurance of sterility is used for: Products not intended to come into contact with breached skin or compromised tissue Topical products that contact intact skin or mucous membranes Aseptic operation and environment 9 Non sterile pharmaceutical products Permitted to contain some viable microorganisms PhEur specifies the maximum concentrations acceptable Total aerobic Total yeast and Specified microorganisms Route of microbial count (cfu mould count (cfu (must be absent in 1 g or administration g−1 or cfu mL−1) g−1 or cfu mL−1) 1 mL) Nonaqueous oral 103 102 Escherichia coli products Aqueous oral products 102 101 Escherichia coli Rectal products 103 102 Products for use in the Staphylococcus aureus mouth, nose, and ears 102 101 Pseudomonas aeruginosa and on the skin Staphylococcus aureus Vaginal products 102 101 Pseudomonas aeruginosa Candida albicans Aseptic operation and environment 10 Sterile pharmaceutical products Complete sterility required All parenteral products – IV infusions, parenteral nutrition (PN) fluids, small-volume injections and small-volume oily injections; Noninjectable sterile fluids – noninjectable water, urological irrigation solutions, peritoneal dialysis and haemodialysis solutions, nebuliser solutions; Ophthalmic preparations – eye drops, lotions and ointments and some contact lens solutions; Dressings; Implants; Absorbable haemostats; Surgical ligatures and sutures (absorbable and nonabsorbable); Instruments and equipment – syringes, metal instruments, respirator parts, medical devices, endoscopes Aseptic operation and environment 11 Sterile pharmaceutical products “Parenteral” comes from two Greek words, “par”(avoid) “enteral” (alimentary canal) meaning “beside the intestine”. Need to circumvent the body’s protective barriers, the skin and mucous membranes, therefore, must be “essentially free” of biological contamination. Should be free from physical, chemical, and biological contaminants. This is why they have to be manufactured under the current good manufacturing practices (cGMP). Aseptic operation and environment 12 Aseptic STERILE ≠ ASEPTIC describes the process for complete absence of viable handling sterilised materials in a microorganisms controlled environment designed to maintain contamination at levels known to present minimal risk Aseptic operation and environment 13 Aseptic Preparation ❑ “Aseptic (sterile) preparation: drawing up medicines into syringes or making infusion bags (such as intravenous antibiotics). Ensures patient and staff safety. ❑ Cytotoxic drugs: are also made up within the aseptic preparation areas and are used in the treatment of cancer (e.g. Chemotherapy). They are supplied in a ready-to-use form to the ward which means that ward staff are not exposed to the toxic nature of the medicine. Ensures patient/staff safety. ❑ The ‘tailor made’ preparation of non-sterile products (e.g. creams, ointments) also takes place within the department. Aseptic operation and environment 14 Implications ❑ What are the implications to a sterile product becoming infected (or contaminated) with: ▪ VIABLE: bacteria, viruses, etc ▪ NON VIABLE Particles, chemicals Aseptic operation and environment 15 Implications - Life Threatening 1971-2: Devonport incident Death of five patients traced to dextrose ‘sterilised’ using a faulty autoclave. 1994“Manchester Incident” Death of 2 children following administration of contaminated TPN 1996: Romaira Death of 35 newborn infants, sepsis attributed to locally produced IV solutions 2005: USA Contaminated heparin IV flush infected several patients in different states Aseptic operation and environment 16 Implications - Product Recall Aseptic operation and environment 17 Implications - Product Spoilage 1. Breakdown of the ACTIVE PHARMACEUTICAL INGREDIENT (API) - Drug itself BIOTRANSFORMED 2. Breakdown of the FORMULATION 3. Reduced ACCEPTABILITY (to patient) 4. Degradation of the PRESERVATIVE Aseptic operation and environment 18 Implications ❑ What are the implications to a sterile product becoming infected (or contaminated) with: ▪ VIABLE: ▪ PRODUCT RECALL bacteria, viruses, etc ▪ PRODUCT SPOILAGE ▪ DEATH ▪ NON VIABLE Particles Aseptic operation and environment 19 What can go wrong? ❑ Background ▪ Pharmacy aseptic units prepare and supply injectable to minimise risks ▪ The UK National Aseptic Error Reporting Scheme (NAERS) has been collecting data on pharmacy compounding errors, including near-misses, since 2003 Aseptic operation and environment 20 What can go wrong? ❑ Results ▪ 4691 / 958 532 errors over 3 years (