Water systems Flashcards
Draw a typical water system and talked through the specifications at each point.
How would you sanitise?
Are there any other ways?
Potable water (<500ppb), Chlorinate, Course filter (50, 25, 10 microns), Active carbon to remove chloride, softening to reduce RO scale up, RO to remove ions, micro, endo, deionisation, PW tank.
Heat sanitization >70.
Chemical sanitisation - rarely, ozone sanitisation required UV lamp to remove the excess ozone - nitrosamine risks
How would you approach the validation of this system?
Change control, URS, IQ (drawing walk down, weld logs, key components listed, correct valve types etc), OQ (including pump installed correct way, key components operating and should etc), PQ - period of intense sampling all points, reduced sampling for defined period, routine sampling, always include worst case which is sample point on return to tank as furthest away from generation system. Need to include seasonal variation of the system in summer and winter
What potential problems could you encounter with water systems?
Sampling errors, high conductivity, Micro oos and biofilm, rouging, break in continuous flow, needs to have zero dead legs and sanitary fittings
What quality of water is used for the various dosage forms? Any guidance for this?
Pharmacopeia. Purified water can be used in non sterile dosage forms, cleaning agents, solution prep, rinsing of equipment. WFI for manufacture of sterile products, final rinse of product contact equipment for sterile product and container closures
What is the limit for endotoxin in water for injection?
What action would you take when found?
It was found in the sample and not laboratory induced and the engineer says the system is fine and brand new. It is an ophthalmic product with a low level of endotoxin but just above specification.
<0.25EU.
Raise OOS, review other sample points and previous data, check operator training and sampling technique, correct sample container, correct flush, taken before chemical samples, etc
It is a failed specification so the batch is in the bin
Describe different types of water and their usage
Purified Water – Cleaning, manufacture of liquids / tablets etc
Water for Injection – Formulations for sterile products , can be used for cleaning sterile areas, product dilutions,
Describe a typical PFW and / or WFI system qualification process
Raise Change Control
Create a Validation Plan
Consider aspects such as ;- flow rate, deadlegs, temperature, direction of flow, water quality of feed water, sampling points, waste water management, Sanitisation Process,
IQ / OQ /PQ’s
Water testing
Equipment Qualification – RO Unit, UV Unit, EIU, etc
What are the key points in a purified water validation programme?
Validation Master Plan, Design Qualification, Installation Qualification, Operational Qualification, Performance Qualification
Alarms, Loop Construction, Slope, Weld Finish, Flow Rate, No dead legs
Chororination, Active carbon filters, TOC, Ozone
PQ – Over 1 year. Micro – Initially every point every day for first month then monthly. Chemical – Every point every month.
Micro < 100cfu/ml by filtration, Conductivity: 5.1mS, Endotoxin <0.25 IU/ml, TOC <0.5mg/l (500ppm) , Nitrates: 0.2ppm, Aluminium: 10ppb, Heavy Metals: 0.1ppm
I was shown a graph plotting CFUs from a single sampling point on a PW system and asked to discuss. The data points on the graph were generally at low levels (say approximately 20CFU) with intermittent random peaks at between 200 to 400 CFU
How would you investigate?
What would you consider in the investigation?
What are the micro limits for PW?
How could you sanitise the system?
It is single sampling point – what are the readings from other points?
Has there been investigations raised in to the higher peaks ?
What was the root cause of these failures? Where CAPA’s put in place?
Sampling Technique? Operator Training?
Microbe ID
Location of sampling point
Engineering Intervention
Trends
Seasonal
GENBA
Suitability of the system – dead legs, flow rate, sanitisation frequency,
Laboratory Investigation – control plates etc
100 cfu/ml
Heat – 80 degrees C
Chemical – passivation
Objective of water sampling
To demonstrate a state of control.
Selection of water sample sites
Assure quality of all grades at all stages
* Processing
* Storage
* Distribution
* Point of Use - Base Site Selection on:
○ Validation studies
○ Operational History
○ Worst Case locations
○ Problem spots
Good water sampling practice
- Pre-sanitize sample port
- Flush sample port
- Sampling procedure mirrors production use
- Collect sample in correct container (Sterile/pyrogen free)
- Label sample correctly (who, what, where, when)
- Transfer sample to lab as soon as possible
- Training of Sampler – explain the WHY behind the HOW
Water sample volume
- Identify the expected water quality – purer water will require a higher volume
- For WFI, a minimum volume of 100mL required.
For purified or potable water, volume can be less
- For WFI, a minimum volume of 100mL required.
Water sample frequency
Micro Sample Frequency
* Potable Monthly
* Purified for Product Weekly*
* for Washing Weekly*
* WFI for Product Daily
* for Washing Weekly*
* for Endotoxin Daily *
Rotation of user points sampled
Laboratory methods of isolation and identification - water testing
- General Practices for Low Quality Water (non-potable)
○ Inoculate small volume water sample onto a solid media
○ Alternative method is the dipslide but can be difficult to count colonies- General Practices for High Purity Water
○ Larger volumes
○ 0.22 or 0.45 micron rated filtration
○ Place filter directly onto a solid, reduced nutrient medium
○ Alternatively, bathe sample under surface with a liquid medium
○ Incubate at 20-30°C for 3-5 days
○ Count colonies
○ Identify any microorganism recoveries - Trend Analysis
○ All water types, sample points, organism types and the samplers should be trended
○ Trending analyses should be reported promptly and regularly reviewed
○ The trend analysis should look for cause and effect relationships and compare microbiological trends with Chemical results, Operating performance and any recent changes. - Action and Alert Limits
○ When Action levels are exceeded, action must be taken
○ Action levels are not reject limits!
○ When Alert limits are exceeded, it indicates that system performance is “drifting” from what is usually experienced
○ Alert levels are based upon actual operating performance and history
○ Multiple alert limit failures may be treated as an action failure
- General Practices for High Purity Water
