Drug and Process Development, Industrial Safety, and Lean Sigma Practice Flashcards

These practice questions cover drug development processes, analytical validation requirements, industrial safety standards (including hazardous zones and exposure limits), crystallisation principles, Lean Six Sigma methodologies, and the chemical engineering challenges of scale-up.

What is the production scale difference between a Discovery chemist and a Process development chemist?

Discovery chemists synthesize drug candidates on a mg-g scale, while process development chemists produce API target molecules on a 200\,g-200\,kg scale.

What does the 'Route selection' stage in crude API development involve?

It involves choosing a definitive route, cost estimation, health and environmental classification, and creating a project plan.

According to the lecture, what is the definition of analytical 'Accuracy'?

The closeness of the value obtained to the true value, which requires 7 measurements at each of 5 concentrations over the working range with $R^2=0.999$ and at least 1 order of magnitude $\pm 1\%$.

Compare the Signal to Noise ($S/N$) ratios required for the Limit of Detection (LOD) and the Limit of Quantitation (LOQ).

The LOD requires a signal to noise ratio of $S/N = 3$, whereas the LOQ requires a signal to noise ratio of $S/N = 10$.

What are the three components of a 'Drug Master File' (DMF) submission as listed in the transcript?

1. Process and process ranges, 2. Product and input specifications, 3. Impurities and stability, 4. Analytical methods, and 5. Recycle and reprocessing.

What are the three major regulators mentioned for Australia, the United States, and Europe?

Australia: Therapeutic Goods Administration (TGA); United States: Food and Drug Administration (FDA); Europe: European Medicines Agency (EMA).

Distinguish between 'Hazard' and 'Toxicity' as defined in industrial safety.

Hazard is the likelihood that a chemical will cause injury under circumstances of ordinary use, while toxicity is the ability of a chemical to cause injury once it reaches a susceptible site in or on the body or environment.

Define the safety standards TWA and STEL.

TWA (Time Weighted Average) is the airborne concentration over an 8-hour period; STEL (Short Term Exposure Limit) is the concentration over a 15-minute period.

What are the characteristics of Hazardous Zone 0, Zone 1, and Zone 2 for gases?

Zone 0: Explosive gas atmosphere present continuously or for long periods. Zone 1: Explosive gas atmosphere likely to occur in normal operation. Zone 2: Explosive gas atmosphere not likely to occur, or only for a short period.

What three elements must be present for a chemical explosion to occur?

Fuel (gas, vapour, mist, dust, etc.), Oxygen, and Ignition.

What is the 'Minimum Explosion Concentration' (MEC)?

The Lower Explosive Limit (LEL) for dust, typically ranging from $20\,g/m^3$ to $60\,g/m^3$.

Define 'Polymorphs' and explain their significance in drug processing.

Polymorphs are chemically identical but physically different versions of a crystalline phase with different molecular arrangements in the lattice; they affect solubility, bioavailability, and processing behaviors like filtration.

Why is 'Seeding' used in cooling crystallisation?

To control particle size distribution, control crystal form, and improve purity.

What represents 'Lean' and 'Six Sigma' in a business improvement context?

Lean focuses on the continuous elimination of waste (non-value added activities), while Six Sigma focuses on the pursuit of variation reduction to achieve better quality and less than 3.4 defects per million.

What are the five steps of the 5S tool?

1. Seiri (Sort), 2. Seiton (Storage/Straighten), 3. Seiso (Shine), 4. Seketsu (Standardise), and 5. Seketsu (Sustain).

List the 7 forms of waste identified by the acronym 'DOTWIMP'.

Defects, Overproduction, Transportation, Waiting, Inventory, Motion, and Over Processing.

What is the difference between Cp and Cpk in Process Capability Analysis?

Cp is Process Capability Potential which assumes a centered process; Cpk is Process Capability which takes into consideration a shift in the average.

State the 'Pareto Principle' as applied in Lean Sigma.

For many events, $80\%$ of the effects come from $20\%$ of the causes.

How is the rate of heat flow ($H$) mathematically represented in thermal conduction?

$H = k \times A \times \frac{\Delta T}{x}$, where $k$ is thermal conductivity, $A$ is the area of the conducting surface, $\Delta T$ is the temperature gradient, and $x$ is the thickness of the interface.

Why does the surface area to volume ratio change during scale-up?

When doubling the vessel diameter and fill height, the volume (and exothermic heat) increases 8 times, while the surface area only increases 4 times, effectively halving the surface area to volume ratio.

Distinguish between 'Off-line' and 'In-line' process monitoring.

Off-line monitoring involves collecting samples and taking them to a lab for detailed analysis (long turnaround), while in-line monitoring involves analysis occurring directly in the process stream for immediate results.

Define the 'Height Equivalent of a Theoretical Stage' in liquid-liquid extraction.

The vertical distance inside a column required to go from the starting concentration in the donor phase to an equilibrium concentration in both the donor and recipient phases.

What is the composition and boiling point of the water-ethanol azeotrope?

The azeotrope has a boiling point of $78.2\,^{\circ}C$ and is composed of $95.6\%$ ethanol and $4.4\%$ water.