Aseptic Production 3 Flashcards
Sterility test
- Only test available
- Inadequate, as only assures that the part of the batch sampled is sterile
- Relies on assurance that the batch was produced under homogenous conditions
Sterility test - GMP states:
“The sterility test applied to the finished product should only be regarded as the last in a series of control measures by which sterility is assured. The test should be validated for the product(s) concerned.”
Sterility test samples
• Samples should be representative of the whole batch
• Should include samples from parts of the batch particularly at risk
– Filled containers at beginning and end of batch run
– Heat sterilised in final containers – take from coolest part of the load
BP Sterility Test
Adopted by the European Pharmacopoeia
• Complex and requires dedicated facilities
– Grade A laminar airflow cabinet in Grade B
environment
– Expensive machinery (if producing small batches - cost not worth it)
– Robotics (automated)
BP Sterility Test - Two methods:
- Membrane filtration
- Direct innoculation
- Membrane filtration is preferred method where possible
- A very complicated procedure
Membrane filtration
• Filter product (mostly aqueous products) through 50mm disc • All equipment sterilised before use • Aseptic conditions throughout • Transfer membrane to culture media – Aerobic bacteria – Anaerobic bacteria – Fungi
Membrane filtration
• Incubate
– Aerobic and anaerobic bacteria for at least 7 days at 30‐35oC
– Fungi for at least 7 days at 20‐25oC
Direct innoculation
- Preparation transferred directly into culture media (liquid agar used)
- Must be at least 10x dilute for liquid preparations (to ensure any bacteria or micro-organisms are caught)
- Incubate at same temperatures as membrane filtration for at least 14 days
Sterility testing in routine hospital manufacture
NOT DONE!!
• Manufacture to order, so no batches
– Therefore cannot sample
• Sterility test takes up to 14 days
– Products have to be given directly to patient
– Most products have short expiry dates
• Therefore must assure sterility in manufacture
Assuring sterility (Quality Assurance)
• Adherence to GMP – Aseptic process – Quality control of materials – Validate all processes – Air quality must be checked regularly – Routine environmental monitoring – Cleaning process – Training to a certain standard
Asepsis definition
“The absence of harmful bacteria, viruses or other microorganisms”.
Similar to sterile
Aseptic definition
“Free from contamination caused by harmful bacteria, viruses or other microorganisms”
Describes techniques used
Medicines Act 1968
Stipulates that a manufacturer’s license is required to “manufacture or assemble a medicinal product”
Manufacture
- Includes any process carried out in the course of making a product
- Does not include dissolving or dispensing the product in, or diluting or mixing it with, some other substances used as a vehicle for administration
• Why is this second point important?
-it gets us out of the need of a manufacturing license
Assembly definition
- Assemble is defined as: “Enclosing of the product in a container which is labelled before the product is sold or supplied or, where the product is already enclosed in a container in which it is to be sold or supplied, labelling the container before the product is sold or supplied in it.”
- Aseptic dispensing is technically assembly under the Medicines Act 1968
