简答
1. moAb
The process for creating a monoclonal antibody is that first we injected a specific
antigen protein into an animal, like horse, mice, etc. Then the animal’s body will
create the corresponding B-cells antibodies to kill the antigen. To incorporate
myeloma cells and B-cells in mice, and then filtered with the choice of a
particular medium. Third, the antibody will be screened. Only the fusion hybrid
cells can grow and then let the hybrid cells to proliferate in vitro culture
conditions, or injected into the abdominal cavity of mice to proliferate and are
collected. Finally, the antibody will be under some procedure to be purified.
Monoclonal antibody is produced by cloning a single B-cell; it is used because it is
highly uniform, highly produced, only for a specific antigen and high purity. It can
be used to treat many diseases and can be used to diagnose some disease.
2. What are the advantages of terminally sterilizing a drug instead of preparing it
aseptically?
Terminally sterilizing means that the drug can be manufactured in the aseptic
environment which is not very strict control the aseptic and the products
eventually are sterilized to meet the requirements of sterilization.
Preparing the drug aseptically means the process of production must with the sterile
operation to ensure that the final products’ sterilization.
It often used to produce the drug which is not a heat-resistant and cannot be
terminally sterilization, so we have to do emphasize the sterile operation in the
So theprocess
terminally
sterilizing
may costs less and more effective.
of drug.
production.
3 Cold chain
A cold chain is a temperature-controlled supply chain. An unbroken cold chain is an
uninterrupted series of storage and distribution activities which maintain a given
temperature range.
Unlike other goods or merchandise, cold chain goods are perishable and always en
route towards end use or destination, even when held temporarily in cold stores and
hence commonly referred to as cargo during its entire logistics cycle.
4. List 4 reasons why a pharmaceutical manufacturing process must be validated.
1. Good business sense
2. Good engineering sense
3. Ensure the safety of the patients and workers
4. Regulated by law
5. Good for control
6. Soft water
To remove calcium magnesium and other low solubility materials. To reduce
hardness.
7. D value
In microbiology, D-value refers to decimal reduction time and is the time required at a
certain temperature to kill 90% of the organisms being studied.
Thus after a colony is reduced by 1 D, only 10% of the original organisms remain, i.e.,
the population number has been reduced by one decimal place in the counting
scheme. Generally, each lot of a sterilization-resistant organism is given a unique Dvalue. When referring to D-values it is proper to give the temperature as a subscript
of the "D". For example, given a hypothetical organism which is reduced by 90%
after exposure to temperatures of 300° F for 20 minutes, the D-value would be
written as D300F = 20 minutes. D-value determination is often carried out to measure a
disinfectant's efficiency to reduce the number of microbes present in a given
environment.
8. 5 design of clean room
a. Temperature: 65-75 degrees Fahrenheit
b. Relative Humidity: 40-50 % RH
c. Microbiological: Coli forming units (CFU) per cubic meter
d. Particulates: (Viable and Non-viable) i.e. 100 particles per cubic meter
@ 0.5 microns
e. Differential Pressures: i.e. 0.05 inch water
i. Negative pressure controlled rooms
ii. Usually chemical cleaning to remove residual material from
processing
iii. Personnel wearing clothing only used in production
 Room Considerations
Personnel Airlocks
Gowning Rooms
Material Airlocks with washing/sterilization of material prior to movement
Wall, Floors and Ceiling should be non-shedding surfaces
Supplied with room HVAC design, construction and operations with the
appropriate conditioned air and air changes and air removal to minimize material
particles
9 rDNA produce drug process
The gene sequence must be located in the mammal cell
The gene must be transported into the bacterium
The gene must be activated in the bacterium
The gene must be activated in the bacterium
10.What are the advantages and disadvantages of a parenteral drug versus a topical
drug?
The parenteral drug can avoid the first pass effect. And it would take effect more
quickly than topical drug. Parenteral drug curative effect is reliable and can be
used to save the crisis of the patients.
However, the parenteral drug must be manufactured under strict control. The costs
are high.
It is not very convenient to take the drug and cause pain. And it also can cause safety
problems, if use the wrong dosage. It even can cause death if the patient was
The topical
cansrug.
also iodine
avoid the
allergicdrug
to the
. first pass effect. And it can control the release of
the drug. It was convenient to use. However, there are few drugs can quickly
the skin.
can be used to efficiently treat topical disease, like eyes disease.
passItthrough
Sometimes, it maybe will irritate the skin and cause skin irritation.
through the intact skin
Reverse osmosis (RO) is a water purification technology that uses a
semipermeable membrane. This membrane technology is not properly a
filtration method. In reverse osmosis, an applied pressure is used to
overcome osmotic pressure, a colligative property, that is driven by
chemical potential, a thermodynamic parameter.
Describe and Single-pass reverse osmosis its disadvantages compared to doublepass reverse osmosis.
Single-pass reverse osmosis is a method to purify the raw water by filtering once
through the reverse osmosis film. This process can eliminate the salts,
organic matters, macromolecule in the raw water.
Double-pass reverse osmosis is let the water produce by the single-pass reverse
osmosis pass through the film again. The ion-removal rate of double pass is
higher thanthasinglepass
1.
10 Steps to Conduct a PFMEA
Step 1Review the process—Use a process flowchart to identify each process component.
Step 2Brainstorm potential failure modes—Review existing documentation and data for clues.
Step 3List potential effects of failure—There may be more than one for each failure.
Step 4Assign Severity rankings—Based on the severity of the consequences of failure.
Step 5Assign Occurrence rankings—Based on how frequently the cause of the failure is likely to
occur.
Step 6Assign Detection rankings—Based on the chances the failure will be detected prior to the
customer finding it.
Step 7Calculate the RPN—Severity X Occurrence X Detection.
Step 8Develop the action plan—Define who will do what by when.
Step 9Take action—Implement the improvements identified by your PFMEA team.
Step 10Calculate the resulting RPN—Re-evaluate each of the potential failures once improvements
have been made and determine the impact of the improvements.
Over pressure in Clean room
Cleanrooms are classified into 2 categories of air pressurization, positive and negative air pressure cleanroom
HVAC ( Heating, Ventilating and Air Conditioning ) systems. Positive air pressure cleanrooms systems are
normally used for Electronics, Aerospace, Optics, Military and Defense applications, and Research, etc., where
the air escaping from doors, ceilings, or walls, due to the positive air pressure, is not hazardous and not creating
safety or health concerns. The amount of particulate cleanliness required determines the cleanroom design
concept, amount of air filtration, CFM (cubic feet per minute) and total HVAC. Our positive pressure cleanroom
designs are based on years on experience in air pressurization in a vast variety of applications.
Positive Air Pressure Cleanrooms normally operate in an air pressure range of 0.02 in. to 0.2 in water column
(H20). Positive air pressure means the cleanroom or rooms are "pumped up” with more filtered air then the
surrounding space outside the cleanroom(s). There are different cascading levels of positive air pressure from the
cleanest rooms at the highest pressure down to the gown room/or airlock room
5 design aspects of cleanroom
Filtration (Air filter)?
Airflow distribution and control
Room pressurization
HVAC DESIGN CONSIDERATION 1. Supplying airflow in sufficient volume and
cleanliness to support the cleanliness rating of the room. 2. Introducing air in a
manner to prevent stagnant areas where particles could accumulate. 3. Conditioning
air to meet clean room temperature, humidity and filtration requirements. 4. Ensuring
enough conditioned makeup air to maintain the specified positive pressurization. •Air
flow distribution and control •Filtration •Air re-circulation
Sensitive processes like scientific and pharmaceutical research, microprocessor
manufacturing, and culture development require sensitive environments. Critical
environments, also called clean rooms, can provide for those environments, but they
have to be designed very carefully to carry out such technical functions. Clean rooms
are complex and can be costly, so they have to be done right. Below are 10 aspects
of that design process that could be considered.
Clean room designs should take into
movement. That means critical processes
should be isolated from major pathways in
have single access and be out of the
contamination.

the account of staff and material
such as pharmaceutical production
the layout. These processes should
major pathways to prevent cross
Clean room classifications are important and will determine the overall design
and requirements of the clean room. The more sensitive the processes you need
to administrate, the more stringent standards required for clean room cleanliness.
Classes range from 1 to 100,000, with the lower numbers indicated higher
standards in particle removal. For example, a class 100 clean room requires
3,500 particles/cu ft or less at 0.1 microns and larger, 750 particles/cu ft or less at
0.2 microns and larger, 300 particles/cu ft or less at 0.3 microns and larger, 100
particles/cu ft or less at 0.5 microns and larger, and 24 particles/cu ft or less at
1.0 microns and larger. At higher classes, the requirements are lower, at lower
numbered classes, the requirements are higher. Knowing the sensitivity of your
project and how it corresponds to the clean room class requirements is important
in designing a critical environment.

Space supply airflow figures in terms of the clean room's class of cleanliness
and the amount of traffic and particles that will be coming in through the room. A
higher value indicates a higher trafficked area and should be considered when
designing a clean room.

What sort of space pressurization will your clean room use? Positive pressure
is useful for pushing air out of the room and keeping the contamination out. It
pays to think about pressure differentials between rooms as well, as a certain
differential will not only have consequences on cross contamination, but energy
used to maintain pressures and the difficulty of opening and closing doors.

Space exfiltration flow has to do with air moving from room to room when
doors are opened between rooms of various pressure differentials. Which
direction is this air moving? Which direction should it move? A good clean room
design should have carefully controlled air flow.

Space air balance has to do with the overall movement of air between rooms
that takes into account present air, air leaving, and air coming into the rooms.
This variable plays a role in the way clean rooms are designed as well.

HVAC systems can be used to manage temperature and humidity. Unless a
clean room process requires a higher temperature, a lower room temperature
should be planned on to account for present staff and their warm clothing (full
coveralls, hoods, goggles, masks, and gloves). Humidity on the other hand
should kept to a certain degree where particles aren't kept stuck to surfaces due
to higher electrostatic discharge, but not too high where microbes/bacteria can
thrive. HEPA filters with laminar air flows can take care of particles as well.

Mechanical system layout figures into the cleanroom design. This aspect can
be affected by such variables as space availability, available funds, project
requirements, classification level, energy, building codes, and local climate.

Heating and cooling calculations for the clean room take into account the
following considerations: required climate, air movement, humidifier manifold heat,

process load, and recirculation fan heat.
Finally, how much space will be needed for the mechanical systems that will
keep the clean room clean? What sort of classification of clean room will be built
and how clean must it be? The design may have to make room for machinery
depending to needs: filters, heating/cooling coils, fans, sound attenuators, return
fan, relief air section, outside air intake, humidifiers, discharge plenums, and
more. As you can see, clean rooms are quite complex and require much
deliberation in design.

Overpressure in cleanroom
Cleanrooms must be kept at a constantly higher pressure than their neighbouring
areas in order to prevent infiltration of contaminated air from outside. This is not just
required by the relevant standard ISO 14644-4. Every expert in this area knows hour
air quality can quickly deteriorate if the overpressure falls by just a few Pascal even
temporarily. In the area of semiconductors, dust particles and other pollutants
threaten to compromise highly clean finished products. In the pharmaceutical sector,
hazardous substances can penetrate highly critical medicines. Obviously, this must
be prevented safely.