Sampling and Quality control Flashcards
what are the steps taken to ensure compliance
- HACCP and GMP
- ICH adherence and standardised manufacture, incorporating process testing
- quality control, calibration and sound measurements in respect of error and variation
- sampling- from capture to strategy and planning
- process analytics, recovery of sample and cleaning validation
who is the founder of good manufacture
GMP or cGMP
what is HACCP
hazard analysis of critical control points
- basis for safety
what does HAZOP stand for
Hazard and operability study
what do the ICH guidelines aim to address
aim to address concerns of producing the medicine
where are production concerns covered in ICH guidelines
ICH Q7 and Q11
where are HACCP and HAZOP addressed in ICH guidelines
ICH Q9
what does Q1 cover in ICH guidelines
product stability
what does Q2 cover in ICH guidelines
analytical methodologies
what does Q3 cover in ICH guidelines
contaminants
what does Q4 cover in ICH guidelines
Pharmacopoeias, compendia
what does Q5 cover in ICH guidelines
biological and biotech products
what does Q6 cover in ICH guidelines
specifications
what does Q7 cover in ICH guidelines
good manufacturing practice
what does Q9 cover in ICH guidelines
risk management (HACCP)
what does Q10 cover in ICH guidelines
quality systems
what does Q11 cover in ICH guidelines
manufacturing of drug substances
What does HACCP consist of
- points of weakness
- points of loss of control
- points of external influence
flagged up notifiers at these points - involves testing point analysis as part of a regime of quality control
outline the 7 point system of HACCP
- conduct a hazard analysis
- establish critical control points based on decision tree
- temperature, time, pH, particle size - establish critical limits/thresholds so that each CCP has 1 or more limits
- establish procedure to monitor CCPs
- establish corrective action in event of exceeded limits
- record keeping, full documentation
- verification of findings in terms of effective working of HACCP policy
give examples of limits used in HACCP
content of drug, impurities, toxins, microbes
what are the advantages of the documentation process
- regulatory compliance
- validation and assurance
- legal protection
what are the disadvantages of the documentation process
bureaucracy
what are the advantages of using a formal guide
- reduction of systematic error
- fulfilment of a licence requirement
name the key activities used in quality control
- physical sampling
- statistical testing
- routine in and on process tests
how is physical sampling used in quality control
- confidence and reproducible sample recovery
- lab tests using valid analytical methods (VAM)
- system suitability
Give examples of routine in and on process tests
- magic eye- metal, colour, obscuration, smart materials
- rapid tests- impedance/DEFT, limit tests (chemical analysis), product history markers
- manual sorting
what process aids can be used
- magic eye technologies for on-line/in-line/at-line testing
- light beam magnetic field- transmission reflection, interruption, barcode reading
Why is calibration performed
- standard purity
- consistency
- reliability and trueness of results
- compatibility with other data
- removes systematic error
- maximises capabilities of equipment and technologies
what is standard deviation
the root of variance and lies at the heart of measured quantity variation
what is experimental variance
the sum of individual contributions
what is meant by propagation of errors
errors can be additive or multiplicative
- additive- routine variability
- multiplicative- multifactor driven increasing change
what are sampling regimens
- physical capture of a representative sample
- physical sampling is associated with quality control
- strategy for sampling is associated with manufacturing
describe how a sample pot is used
- plastic containers are taken into production area for sampling purposes
- glass is generally not allowed due to risk of contamination of product by shards - the compounds that can leach out of non inert plastic sample containers are:
- bisphenol A, which is used in tough polycarbonate products (antioxidant)
- plastic softeners called phthalates
- vinyl chloride monomer from PVC
describe what lot sampling in manufacture involves
- inert container, blank/control
- avoidances: sifting, carry over, deabsorption, atmospheric addition, volatilisation
what are the procedural modes in lot manufacture
- continuous mode sampling
- portion
- continuous flow (liquid/gas) trapping - batch mode sampling
- Auger, quartering, coning, rifling, sampling thief
- random
what is a major contributor to experimental error
sampling
what are the 4 most important features limiting analysis
- cost
- time
- staff skill base
- equipment
what are the uses of analysis in cleaning validation
- surface techniques
- contact, settle
- swab or rinse
- air impingers
what is used for measurement of analysis in cleaning validation
use a modified product assay
- chromatographic- HPLC, LC/MS
- total organic carbon
- UV VIS
-pH
- colony counts, microbial load (DEFT)
