Liquids Flashcards
What types of raw material make up a liquid oral product?
API, solvent, humectant (used to reduce the loss of moisture), Enhancer, Flavour, Colour, Preservative
What is the difference between a suspension and a liquid?
Suspensions are defined as mixtures of fluid and solid particles where a emulsion is a type of suspension, where two immiscible liquids are mixed together.
Can you talk me through a typical specification for a non-sterile liquid including microbiological tests?
Appearance colour and particle free, Assay, uniformity of content, uniformity of dose, viscosity, Preservative testing, related substances, micro and absence of
Water is a major component of non-sterile liquid. Can you tell me what specification of water you would expect to be using, where the specification is located and the detail of the specification?
Purified water. Specification located in the pharmacopeias - TOC <500ppb, Conductivity 5.1ms at 25oC, Nitrates <0.2, Micro <100cfu/mL
Describe what you expect to see in a liquids manuf. Facility?
Closed systems
Vessels with high speed stirrer & heating with vacuum or by transfer pump
All material transfer are done by vacuum or by transfer pumps.
The gaskets used are of silicon (food grade).
All contact parts are of 304 or 316 stainless steel and are crevice free.
The entire plant is equipped with CIP & SIP connections
Sanitary valves and fittings
Closed circuit manufacturing facility feeding of liquid to loading the Volumetric Liquid Filling Machine.
Where would you find guidance of manufacture of liquids and what are the important factors?
Annex 9 – manufacture of liquids , creams and ointments.
Temperature, Mixing Speeds, Holding Times, Microbial Quality of Water, Closed / Open Systems (= filtered air)
What is important on a liquids filling line?
Bottle inverter / Blower, Fill Weight, Cap Torque / Crimp,
Why is the source of raw materials important?
Suppliers play a crucial role in the product life cycle. They source raw materials to expedite production and find better quality raw material in a saturated market. Without access to reliable, high-quality raw materials, businesses may struggle to meet demand and maintain quality. A secure and cost-effective supply chain for raw materials is essential. Selection of the right raw materials can also increase production efficiency. Using raw materials that are easy to process and have good stability can speed up the production process and reduce the risk of production failure.
What is a PET test and how do you complete it?
Preservative Efficacy testing - Testing requirements are detailed in BP, Ph.Eur, USP and ISO11930. Product is inoculated with specific organisms to simulate possible contamination (challenge organisms) and incubated at 20-25 °C for a period of 28 days. Samples are taken at various intervals and tested to determine the number of surviving viable organisms.
The number or organisms and testing intervals will depend on the type and route of administration of the product (parenteral, eye, intrauterine, intramammary; ear, nasal; cutaneous, inhalation; oral, oromucosal, rectal). Preservation is considered adequate if there is no increase, or a reduction of the number of viable organisms over the storage time
What facility grade would you expect it to be?
Manufacture and Fill in Grade C – if open systems or potentially grade D if closed systems
For non-sterile manufacturing formal area classifications are not required hence the design and monitoring requirements will reflect the risk profile pf products manufactured (e.g. tablets < liquids/creams ≤ inhaled products) and process and patient – RISK ASSESSMENT
Limits based on RA and historical data (so that deviations from the norm can be readily detectable).
How would you design an environmental monitoring programme for this product?
Environmental monitoring would be based on a risk assessment outlined as part of your contamination control strategy.
What is the product ? – sterile
What media would you use for the EM of a liquid manufacture?
TSA - Trypticase soy agar or SDA Sabouraud Dextrose Agar Casein soy bean (TAMC) or Sabouraud Dextrose (Yeasts)
What is the EM specification for graded cleanrooms?
AS (air)settle (90mm)contact (55mm)
Grade A: no growth no growth no growth
Grade B: 10 CFU/m3 5 CFU/4 hrs 5 CFU/plate
Grade C: 100 CFU/m3 50 CFU/4 hrs 25 CFU/plate
Grade D: 200 CFU/m3 100 CFU/4 hrs 50 CFU/plate
Where would you place settle plates in that room?
- Tends to be areas as close to exposed product as possible
- Areas of significant Activity
- CP tend to be taken from contact parts and areas that are regular touch points
You are a QP for a liquid manufacturer, you have a new product coming on line and it is a
paediatric leukaemia treatment
What are your concerns as a QP and how would you bring this product on line?
Concerns:-
Is this product covered under the current terms of the MIA
Is this product highly potent, toxic or allergenic?
Will this product be made with dedicated equipment
Implications to the site contamination control strategy
How would you bring online
Change Control would be required to perform an impact assessment
Is it sterile or non-sterile?
Medical device impact ?
Water Plant / WFI ?
Micro ?
