Fundamentals of Pharmaceutical Manufacturing Technologies
Fundamentals of Pharmaceutical
Manufacturing Technologies
TU Dublin Course Code: VOMP3001
Written Questions – Assignment Booklet
Candidate Name: Philip Ryan Class:eclass 68 / VOMP Date: 20/09/22
3001
Written Questions VOMP3001 GetReskilled/TUD 2021 Page 1
Fundamentals of Pharmaceutical Manufacturing Technologies
WQ-1. Scenario: A doctor is about to inject an
aseptically manufactured injectable finished
pharmaceutical into the arm of a child.
Medicinal injection
a. How would you convince both the patient’s parents and the doctor that the
manufacturing process was robust and to proceed in confidence with
administration?
b.
Answer: I would explain to both the doctor and the parents of the child
that a pharmaceutical aseptically made injectable finished product is
prepared in accordance with stringent safety guidelines. This finished
product was prepared using a highly sophisticated and modern sterilization
process. The processing of the drug goes through many rigorous
manufacturing and quality validation processes. If necessary, I would also
explain the manufacturers obligations under the various regulatory boards,
for example the FDA’s role within the pharmaceutical industry.
c. What are the biggest risks to the child?
Answer: The biggest risks to the child may be an adverse reaction to the
drug. Another potential problem may be an infection at the site of
injection?
d. How are they controlled?
Answer: That the child is monitored for any adverse reactions and treated
accordingly. If any infection should occur this should be treated as
required. A small quantity of the drug might be given first and if there no
sign of a reaction the injection can be administered.
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Fundamentals of Pharmaceutical Manufacturing Technologies
WQ-2. Examine the graphical
representation on the next
page for “A Validation
Approach for a Complex
Project, Consisting of Many
Systems and Components”.
a. In terms of “Qualification Rationale”, describe the process of a system-
impact-assessment and component-level-impact assessment.
Answer: Direct Impact: The system is expected to have direct impact on
product quality. No Impact: The system would have no impact directly or
indirectly on product quality. Indirect Impact: The system would not have
direct or indirect on product quality but would support direct system
impact.
b. In your own words define the term installation qualification (IQ).
Answer: Installation Qualification (IQ) verifies that auxiliary systems and
any instrument or piece of equipment have been installed and configured
in accordance with manufacturer's instructions or checklist. The purpose of
the installation qualification (IQ) is to demonstrate that all necessary
components of the supporting installations and process equipment have
been installed correctly and in compliance with the applicable vendors'
specifications.
c. In your own words define the term operational qualification (OQ).
Answer: Operational Qualification, or OQ, is an important stage in the
development of machinery that pharmaceutical companies regularly use.
OQ can be summed up as a series of tests that guarantee machinery and
its individual parts will function dependably and consistently within the
boundaries that have been established. The item's individual functions are
inspected and confirmed to meet operational qualification in writing (OQ).
d. In your own words define the term performance qualification (IQ).
Answer: Gaining confirmation through appropriate testing that a finished
product or process made using a particular method exceeds all functional
and safety standards for release and that the processes are effective and
repeatable is known as performance qualification (PQ). Performance
Qualification (PQ) investigates and documents whether the devices and
systems satisfy the users' needs.
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BSc (Ord) Manufacture of Pharmaceutical Products
A Validation Approach for a Complex Project, Consisting of Many Systems and Components
High Level
Validation Master Plan Strategic Plan
System 1 Qualification System 2 Qualification System ‘X’ Qualification
Rationale Rationale Rationale
System System System
Qualification IQ Qualification IQ Qualification IQ
Protocol Protocol Protocol
System Level
OQ OQ Detail
OQ
PQ Rationale
PQ
PQ
Process Validation Documentation
E.g. SOPs, Training Records, Cleaning Validation, Analytical
Procedures, Validation Batches, etc.
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BSc (Ord) Manufacture of Pharmaceutical Products
WQ-3. Briefly describe the inter-relationships between the following
operational activities for a computerized system in a GxP
environment.
a. Handover
The procedure of handing over control of a system to another individual or
team.
b. Establishing and Managing Support Services
The process of establishing and maintaining system support services.
Should anything happen to the application or systems, who is going to
help with support?
c. Performance Monitoring
Monitoring a system's functioning and looking for potential problems
d. Incident Management
Is a mechanism used to respond to and resolve events when they
happen?
e. Corrective and Preventive Action
This procedure addresses systemic concerns by taking corrective and
preventative action.
f. Operational Change and Configuration Management
This is the process of managing changes to a systems configuration
g. Repair Activity
This is how a system is repaired.
h. Periodic Review
The process of periodically reviewing a system to ensure it is still
functioning properly.
i. Backup and Restore
The process of backing up and restoring a system.
j. Business Continuity Management
k. This is the process of ensuring that a system can continue to operate in
the event of an incident. This is when you must know the current
configuration.
l. Security Management
This is the process of managing the security for a system.
m. System Administration
This is the process of administering a system.
n. Archiving and Retrieval
This is the process of archiving and retrieving data for a system. This is
important to have in place in the case of a disaster you can rebuild the
system form back up & restore.
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BSc (Ord) Manufacture of Pharmaceutical Products
WQ-4. Examine the diagram on the
next page for a typical
vertical processing facility
designed for batch API
production.
Describe, with reference to the diagram, how synthetic API plants (Batch
Organic Chemical Synthesis) normally follow a sequence to produce a solid
product:
e. Reaction: (Continuously Stirred Tank Reactor (CSTR)
You would chemically combine A+B=C the product of interest + D the side
product.
f. Crystallization: This is where you go through a phase separation step
and convert C into crystals
g. Separation: When the solid crystals are in the slurry they would have to
be separated before moving to the next step.
h. Drying: The crystal would then be dried.
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BSc (Ord) Manufacture of Pharmaceutical Products
Typical vertical processing facility designed for batch production with barrier separation between processing steps
Process
Technical Liquid
Services Charging
Solids Solids Solids
Charging Charging Charging
1 2 3
Filter
Dryer
Process
Technical Reactor Reactor Reactor
Services 1 2 3
Elevator
Laminar Flow Booth
Process
Technical
Services
Solution Mother Tray
Liquor Dryer
Distillate
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BSc (Ord) Manufacture of Pharmaceutical Products
WQ-5. Study the following diagram that represents the basic unit
operations that most companies implement when manufacturing a
biopharmaceutical protein-based drug substance.
Briefly describe the following three stages of a typical process:
a. Stage I: Upstream Processing
b. Stage II: Fermentation
c. Stage III: Downstream Processing
Stage 1: Upstream processing: Tasks in the early stages of the fermentation
process in biotechnology is referred to as upstream processing. Media and inoculum
preparation would be added into a fermenter for fermentation to take place.
Stage 2: Fermentation: Typically, fermentation is carried out under strict controls
designed to promote the growth of the organism or the manufacture of a desired
microbial product. Fermentation media can be classified into defined, complex or
technical media.
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BSc (Ord) Manufacture of Pharmaceutical Products
Stage 3: Downstream Processing: All operations that take place after fermentation
are called downstream processing. Its main objective is to efficiently, repeatedly and
safely recover the target product to the necessary standards while maximizing
recovery yield and reducing costs. When the unprocessed bulk travels to the
downstream process buffer prep is added in to purify it in the purification area, it hen
goes on to bulk formulation where it is added to other buffers.
WQ-6. Describe the principals for a typical cleaning validation sequence as
listed below.
Cleaning validation is the procedure used to ensure that all chemical
and microbial remnants of active and inactive detergent components
have been removed from manufactured products. The main
objective of this validation is to improve the efficiency and uniformity
of cleaning in order to avoid cross-contamination by unwanted
chemicals and adulteration of the product.
a. Use the equipment for the process
Equipment should be cleaned of detergents and microbial remnants to
prevent infections, outbreaks and cross-contamination. In addition, the
efficiency of the cleaning process is influenced by the structure and design
of the equipment as well as the surface material. Therefore, it is important
to maintain a high level of cleanliness.
b. After processing hold the equipment and allow to dry
Machines should be dried after treatment to prevent microbial growth and
improve cleaning efficiency. This phase contributes to the preservation
and elimination of superfluous weight by preserving the biomechanical
properties of the materials.
c. Clean as per the procedure
To get rid of residues on the equipment, the cleaning method uses
brushing, scrubbing and steam pressurization.
d. Sample for product residue, cleaning-agent residues, and others
A crucial step in the cleaning validation process is sampling. Depending on
the productivity of the equipment, this should be done by rinsing/swabbing
or using other techniques. Sampling removes harmful cleaning chemical
residues and sticky objects.
e. Repeat twice more, giving three (3) consecutive runs
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BSc (Ord) Manufacture of Pharmaceutical Products
The first three runs of the validation process (batches) are used to show
the ability of a process to consistently produce high-level results.
Additionally, the amount of risk in the production process affects the
frequency of running batches or procedures. The quality sought is
considered accessory in the first batch, regulatory in the second batch,
and validating in the third batch. Therefore, at least three consecutive
passes are required for confirmation of manufacturing and cleaning
procedures.
f. Develop on post-cleaning monitoring strategies
The post-validation follow-up stage, which follows the first and second stages,
process design & process validation, is the third and most important. At this
level, strategies such as control, revalidation, data monitoring and evaluation,
and frequent management are all maintained. This stage is characterized by
monitoring and maintaining the toxic risk.
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BSc (Ord) Manufacture of Pharmaceutical Products
WQ-7. Describe the primary process
principals of a typical
pharmaceutical tableting
operation. List three (3) critical
parameters that must be
controlled.
A rotary tablet press is typically used in a pharmaceutical tablet manufacturing
operation as a continuous process to create tablets from a mixture of
powders. The tablet press is fed with the powder mixture, and the press ejects
the tablets into a collection bin. Typically, the tablet press runs at a steady
pace while the weight and hardness of the tablets are measured. Tablet
weight, hardness and speed are the three crucial factors that need to be
regulated in a tablet press operation.
The act of pressing a drug into a tablet or pill form is called tableting. The
three main operating principles of a typical pharmaceutical tablet
manufacturing operation are:
1. Blending: To produce a homogeneous blend, the
active components and excipients must be
properly combined.
2. Compression: By applying pressure to the
mixture, the tablet press forces the ingredients to
bind and create a tablet.
3. Ejection: The tablet is then ejected from the tablet
press.
To create a high-quality tablet, a lot of crucial variables need to be under control.
Particle Size: To guarantee correct mixing and compression, the particle size of the
materials must be under control.
Moisture Content: To avoid the tablet sticking to the die or punch during
compression, the moisture content of the ingredients must be kept under control.
Compression Force: The compression force must be managed to ensure that the
tablet is properly formed and has the desired strength.
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BSc (Ord) Manufacture of Pharmaceutical Products
WQ-8. Combining the principals of the FDA’s approach to
medical device classifications with the EU Medical
Device Directive 93/42/EEC, list three devices in the
following categories giving reasons for your answers:
Heart Stent
a. Class I
Class I: These medical devices have the lowest perceived risk.
E.g., Bandages, handheld surgical instruments, tongue depressors and
pregnancy tests fall under the category Class I as their failure poses no
risk to life.
b. Class II (or IIa / IIb)
Class II usually constitute low to medium risk. Hearing aids, thermometers
and blood pressure devices are Class II and pose no risk to life but must
comply with Class I standards.
c. Class III: These are devices that have the highest risk possible, and
permanent monitoring is required during their lifetime. Heart valves,
pacemakers are Class III, should one of these devices fail a patient may
die.
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BSc (Ord) Manufacture of Pharmaceutical Products
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