Contamination - Innopharma Education PDF

Contamination Elaine Riordan 2024 © Innopharma  Course Content Contamination Personnel Mindset and Accountability Conditions that can effect Cleanrooms © Innopharma  Rules Please ask questions! Either unmute or use the chat box! This session will be way...

Contamination Elaine Riordan 2024 © Innopharma  Course Content Contamination Personnel Mindset and Accountability Conditions that can effect Cleanrooms © Innopharma  Rules Please ask questions! Either unmute or use the chat box! This session will be way more enjoyable if people ask questions! Don’t leave the session today with unanswered questions! Some activities I will ask for your input Some parts will be in Breakout Rooms Group setting for breakout rooms © Innopharma  Primary Concerns The main concern in a cleanroom is protecting the product being manufactured from microbial and other particulate contamination. We must limit exposure of our product to microbial contaminants. What is microbial contamination? ‘The non-intended or accidental introduction of infectious material like bacteria, yeast, mould, fungi, virus, prions, protozoa or their toxins and by-products’ © Innopharma  Contamination © Innopharma Contamination Contamination is defined as the undesired introduction of impurities of a chemical or microbiological nature, or of foreign matter, into or onto a raw material, intermediate, or API (Active Pharmaceutical Ingredient) during production, sampling, packaging or repackaging, storage or transport Chemical Microbial Particulate 6  What is contamination? Contamination is the undesired introduction of impurities (of a chemical or microbiological nature) or of foreign matter, into or onto a starting material or intermediate or API or product during: production sampling packaging or repackaging storage or transport. © Innopharma  Impact of contamination Patient safety – remember your customers are sick! Rework / Rejection (if contamination is identified in-house). If not....... Product recall Company Image Ultimately lives and jobs could be lost © Innopharma  What are Contaminants ? Contaminants are : 1. Products or substances other than the product manufactured a) Foreign products b) Particulate matter c) Micro-organisms d) Endotoxins (degraded micro-organisms) Cross-contamination is a particular case of contamination © Innopharma  What are contaminants? Contaminants are 1. Products or substances other than product manufactured 2. Foreign products 3. Particulate matter 4. Micro-organisms 5. Endotoxins (degraded micro-organisms) Also cross- contamination can be classified as contamination. © Innopharma  Measures that prevent/ control contamination of products and processes Use of properly designed, maintained and operated clean rooms. Controlled access of personnel and materials into clean rooms Limited to appropriately gowned & trained personnel Materials checked and sanitised prior to entry. Removal of chemical residues and/ or dirt by cleaning of clean rooms and equipment using cleaning agents such as detergents 11 © Innopharma Measures that prevent/ control contamination of products and processes cont’d Reduce the number of micro-organisms present by sanitisation of clean rooms as per relevant SOP. Kill or remove all micro-organisms by sterilisation of equipment, parts, components, product using validated methods. Use of aseptic technique - slow deliberate movements, do not disturb airflow, contact sterile product/ solutions only with sterile instruments, proper gown control. 12 © Innopharma Contamination Sources People The environment Can you identify Materials sources of contamination? Activities Equipment Cleaning Which would you say is the biggest source of contamination? 13 Contamination Sources People The environment Materials Activities Equipment Cleaning PEOPLE NATURALLY CARRY Particulates Bacteria/Virus Yeast/Mould Chemicals and process residuals Endotoxins and other pyrogens 14  Common sources of contamination People Facilities / Buildings Materials Equipment or tools Water / Fluids Environment Product being manufactured (cross contamination only) © Innopharma..... Main Source is.. People.........… (that includes you !) 16 © Innopharma  People Biggest source of contamination! Shedding Skin flakes, hair, saliva and oil. Shedding Clothing debris (lint, fibres etc.). © Innopharma  Personnel Biggest source of contamination micro-organisms. particles and fibres. © Innopharma People and Contamination How can people inadvertently Skin flakes, Hair Cosmetic contaminate the dandruff fragments particles cleanroom? Aerosol Tobacco spray Dust, soil smoke, ash particles Moisture Fibres from Mindset ! droplets clothing Key Facts Almost all microbe carrying particles found in a Industry Trends 1. cleanroom are human cells Contamination Sources Most microbes found in a cleanroom are bacteria. 2. People may disperse microbes from skin, mouth, nose, normal outdoor clothing, cleanroom clothing. 3. Dispersal rate into the air varies according to the individual and their activity. 4. Females generally disperse less than males. 5. People Ventilation/Air Room Structure Equipment People - 75% People shed Ventilation -15% approx 1 million Room Structure -5% particles in 24 hrs Equipment -5% 20  Personnel Mindset and Accountability © Innopharma What is wrong with this picture? Would you say he has the right mindset to work in a cleanroom area? Would you say he cares about the patient and product? 22 Have the right mindset… I’m sure it will be OK…. At least I’m pretty sure….. Well, I don’t think it’s an issue... It’s time to ELEVATE it!! It may be a potential risk. Personal Accountability What kind of person is required for working in a cleanroom? Conscientious Attention to detail Self-motivated Good level of personal hygiene Able to work as part of a team Ability to follow instructions exactly Awareness of mindset red flags Pressure from unrealistic production schedules. Lack of understanding and training. Operator fatigue and stress. Familiarity, boredom. De-motivation. Poor work planning.  People in Cleanrooms Walking: produce 1,000,000 particles >= 0.5 mm. several thousand microbe-carrying particles per minute. © Innopharma  Conditions that can effect Cleanrooms © Innopharma  Conditions that can effect cleanrooms: Skin conditions: skin cells, dermatitis, sunburn or bad dandruff. Respiratory conditions: coughing, sneezing Allergic conditions, which cause sneezing, itching, scratching, or a running nose Allergic to materials used in the cleanroom, (a) garments (polyester) (b) plastic or latex gloves, (c) chemicals: acids, solvents, cleaning agents and disinfectants, and (d) products manufactured in the room, e.g. antibiotics and hormones. © Innopharma  People – Non-viable contamination People are the biggest source of potential product and process contamination. People shed thousands of millions of dead skin cells every day i.e. particulates which are non-living contamination (called non-viable particulates). The more movement, the greater the shedding becomes. These skin cells carry micro-organisms i.e. living (viable) contamination. People also shed fibres from their clothing. 29 © Innopharma  People – viable contamination Micro-organisms live on and in people. People shed millions of bacteria all of the time from the skin, hair, saliva etc. Coughing, sneezing and itching spread large numbers of micro-organisms. Anyone suffering from cuts, grazes or illness must report this to their supervisor as this would be a serious source of potential product/ process contamination. 30 © Innopharma Sneezing produces 100’s of thousands of aerosol droplets that can then attach to dust particles. In the absence of any filtration system these particles which may contain bacterial spores, or viruses may be present in the air for weeks. Humans and bacteria Over 200 different species of bacteria are found associated with humans. Bacteria are found in the intestines, eyes, nose, mouth, hair and skin. Dry skin can have 1000’s of microbes / mm2 ! Staphylococcus epidermidis Scanning EM. CDC. Would you let these people into your processing area ? 33  Facilities / Buildings Poorly designed and poorly maintained buildings can result in contamination – flaking materials, paint in addition to dirt and dust. © Innopharma  Buildings/ Surfaces Contamination with flaking building materials/ paint, dust, dirt etc. As a result of: Poor housekeeping, e.g. Accumulation of dust Dirty containers Waste material e.g. packaging, tie wraps Drips from leaking flanges Poorly maintained building surfaces (e.g. flaking paint) Inadequately designed buildings Ineffective cleaning Dusty, dirty rooms provide ideal growth environment for micro-organisms. 35 © Innopharma  Materials Micro-organisms (viable contamination) may be present on or in the raw materials used for making products or the packaging materials. The materials may also be a source of dust or fibres (non-viable contamination). Raw materials used in the process can give rise to dusts which could contaminate the product or process with particles. Items like cardboard and paper produce huge quantities of fibres. Inadvertent use of wrong material would contaminate a product/ process 36 © Innopharma  Equipment or Tools Dirty equipment Friction and moving machine parts Belt drives Lubricants and emissions © Innopharma  Equipment Dirty equipment, moving machine parts and belt drives are a source of non-viable contamination (which typically means viable contamination also present). If equipment was not cleaned properly after use the next product to be manufactured could be contaminated with the previous product. This could have a detrimental effect on the health of the patient. Equipment can be contaminated with chemical residues such as cleaning agents © Innopharma  Water / Fluids Micro-organisms may be present in water. Remember water is anywhere that is wet including wet surfaces, wet floors, damp surfaces (eg of containers / equipment not properly dried. Ensuring surfaces are dry is essential. © Innopharma  Environment Particles (dust) can be invisible but present in air and could contaminate the product. They can be in air, on floors or other surfaces (walls, ceilings, equipment etc). © Innopharma  Product Product dust Silicon chips Quartz flakes Cleanroom debris Aluminium particles © Innopharma  Cross-Contamination Definition of Cross-Contamination: Contamination of a starting material, intermediate product, or finished product with another starting material or product during production. (WHO) © Innopharma  Cross-Contamination Where does Cross-Contamination originate? Poorly designed air handling systems and dust extraction systems. Poorly operated and maintained air handling systems and dust extraction system. Inadequate procedures for personnel and equipment. Insufficiently cleaned equipment. © Innopharma  Cross-Contamination © Innopharma  Cross-Contamination Cross-contamination can be minimized by: Personnel procedures Adequate premises Use of closed production systems Adequate, validated cleaning procedures Appropriate levels of protection of product Correct air pressure cascade © Innopharma