CAPITULO V Incorporación al régimen de pago único de las
Gráfica 15.- Evolución de la superficie cultivada de limón y lima, entre Argentina,
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This document resides on the ISPE HVAC COP website.
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11.2.1 Introduction 7273
7274
Many engineering students are exposed to the basic laws of fluids and 7275
thermodynamics in college. Then sometime after graduation and taking a 7276
job in the pharma industry, the laws of physics are repealed and often 7277
contradicted by ‖GMP drivers‖ and business practices. The engineer 7278
often does not ask if physical requirements dictated by management or 7279
the Quality Group make sense from an engineering standpoint. The 7280
successful pharmaceutical HVAC engineer applies the laws of physics to 7281
satisfy GMP as well as business drivers and does not turn his back on 7282
those basic laws.
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These laws go back hundreds of years, based on Newton‘s theories. The 7285
experienced HVAC designer will remember these laws; neophytes should 7286
rocket science in college, so I should know.
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Note that this article is written in English (i.e. AMERICAN) units. I 7293
leave it to the calculator experts to convert to metric.
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11.2.2 Room Differential Pressure 7296
expands (becomes less dense) about 1 percent.
7300 7301
The ideal gas law states that the pressure P and the volume V of a gas 7302
are proportional to its temperature. If you heat a gas (in HVAC, the 7303
gas is air) it wants to expand to a larger volume, but if it‘s 7304
constrained in a fixed volume container, its pressure will increase and 7305
it becomes more dense.
7306
particular situation, the equation boils down to 7312
7313
PV is proportional to T 7314
7315
Bernoulli‘s Equation for fluid dynamics also plays a role in HVAC.
7316
7317
P/ + V2/2 +gh = constant 7318
7319
Where g is earth‘s gravitational constant, h is elevation, and (rho) 7320
elevation are essentially constant. Thus Bernoulli‘s Equation applied 7324
airflow path, such as in a duct.
7331
From this we can deduce that pressure is proportional to the SQUARE of 7341
the airflow velocity. In other words, if we want to double the velocity 7342
of airflow between two points along a fixed path, we must quadruple the 7343
pressure difference between them. In HVAC, V2 is often zero (it‘s the 7344
air inside a space at essentially no velocity) and we want to 7345
accelerate it into an opening to move it to another location, or under 7346
This can be used in calculating the velocity of air flowing through the 7352
March/April 2001 Pharmaceutical Engineering.
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VP ~ P2 – P1 7358
7359
Where VP is the velocity pressure of the airflow WITHIN the door crack 7360
(i.e. where the air is moving faster, creating a pressure drop).
7361
little.
rooms. Since rooms are rarely as tight or well constructed as we would 7377
like, this method gives us a little extra calculated airflow quantity 7378
to play with during commissioning. In this case, we can replace VP 7379
with DP (the differential pressure between the two spaces, inches w.g.) 7380
inches w.g. or 12.5 Pa. The above equation implies that the air flowing 7385
through the cracks between two rooms at 0.05‖ DP has a velocity of 890 7386
would still measure a DP of 0.05‖. However, where the area of the crack 7390
is large, as for an open door, and the differential pressure required 7391
is significant (as for a classified room needing 0.05‖ or more) 7392
outrageous quantities of airflow will be needed. Using the equation 7393
7394
Q = V x A 7395
7396
where Q is cubic volume per time, usually cubic feet/minute (CFM), V is 7397
velocity in feet/minute, and A is area in square feet, an open 20 7398
square foot door with air flowing through it at 890 ft/min (to maintain 7399
certain leakage rate without knowing about the type of door to be used 7406
- is it a tight sterile room door with seals (leaking as little as 50 7407
A useful equation for fan power is:
7414
is fan pressure and Q is fan airflow in cubic volume per time (such as 7419
CFM). From the pressure equations above, if airflow in an existing duct 7420
system must be doubled, we must QUADRUPLE the fan‘s delivery pressure 7421
as well as double its airflow, thus needing EIGHT times the horsepower.
7422
It is better to slightly oversize an HVAC system‘s fan and ductwork and 7423
not need all the horsepower installed than to run out of horsepower 7424
when the system can‘t supply enough air to meet required room 7425
particulate levels. When this happens, additional filtered airflow must 7426
be provided from the HVAC system at considerable cost and construction 7427
time, or by adding local filtered air supply units serving only the 7428
areas needing more air.
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11.2.3 Room Air Balance:
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The most basic AIR BALANCE equation is:
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Air Volume in = Air volume out, or Q in = Q out or 7435
7436
SUPPLY + INFILTRATION = RETURN + EXHAUST + EXFILTRATION 7437
measure (it‘s the air flowing under the door and out the cracks in the 7441
wall), but it can be calculated. It‘s surprising how many HVAC 7442
designers forget to do an air balance check on EACH fixed volume.
7443
Beside rooms, air handlers are also fixed volumes.
7444
leave the room nor enter it, and does not affect the room's air balance 7448
relative to the building. However, the FFU unit DOES add its air 7449
changes as well as filtered air supply volume to the room HVAC supply, 7450
and it will contribute to faster room recovery time and help reduce 7451
room airborne particle levels. (See the next section) 7452
7453
11.2.4 Airborne Particle Levels 7454
feet/minute including contributions from in-room fan-HEPA units (FFU).
7465
will eventually approach the particle counts in the supply air.
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Note that the equation above ignores air changes and room volume. The 7472
value of C avg will be the same regardless of room volume as long as 7473
the airflow (Q) and particle generation (PGR) are constant. Therefore, 7474
the particle counts in a big room running a certain process will be the 7475
same as the particle counts in a small room running that identical 7476
process, as long as the Q and particle counts of the supply airflow are 7477
However, room volume does come into play when we measure a room‘s AIR 7482
CHANGES. Here is the formula for air changes:
7483 7484
AC/hr = 60 x Q/Volume 7485
7486
Where AC/hr is room air changes per hour, Q is CFM supply in cubic feet 7487
per minute*, and Volume is the volume of the room in cubic feet. From 7488
the two equations above it appears that AC/hr is merely an indicator of 7489
high enough to assure enough turbulence in the room to achieve thorough 7493
dilution, such that particles counts are relatively the same throughout 7494
the room (except under local unidirectional hoods). Usually, this 7495
requires more than 10 and usually more than 20 air changes per hour. It 7496
also implies that the term ―air changes per hour‖ does not apply to 7497
unidirectional flow hoods, which are unidirectional flow zones, not 7498
turbulent. However, a hood or FFU operating in the room does contribute 7499
15 to 20 minutes, although quicker recovery would not be criticized.
7508
Where Cop is in-operation particle count, N is number of air changes, t 7515
is time, and Cs is supply air particle counts (usually close to zero) 7516
changes per hour. So, for cleaner classified rooms (EU grades B and C), 7521
a minimum starting point would be an HVAC supply CFM that creates 20 7522
AC/hr, although more Q may be necessary if internal PGR is high (common 7523
to a small room with high equipment or people activity).
7524
configuration of air supply and return openings. A single supply outlet 7528
near a single return inlet would lead to cleaner air in the path 7529
between the two, with poor mixing (and higher particle counts) in other 7530
parts of the room. Such a room would show a slower recovery (with the 7531
same number of air changes) than a room with multiple well-distributed 7532
air supply outlets and low level returns.
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11.2.6 Cascaded Hepa Filters 7535
7536
A HEPA filter passes a certain percentage of upstream particles of the 7537
most penetrating particle size (MPPS), in the traditional case, 7538
particles at 0.3 microns. In reality, the MPPS of a modern HEPA is more 7539
like 0.15 to 0.25 micron. In another filter (ULPA for example) the MPPS 7540
is in the range of 0.10 to 0.15 microns. For a given particle size, the 7541
overall leakage of a series of HEPA filters in a supply air path is the 7542
product of the leakages for each of the filters. If L is the leakage as 7543
HEPA, and L2 is the leakage of the second HEPA. For a pair of standard 7550
99.97% HEPA filters (assuming 0.03% leakage at MPPS), 7551
the primary HEPA is at the air handler and the second HEPA filter is at 7560
the room (a terminal HEPA). The terminal filter sees very little 7561
challenge, and therefore its pressure drop increases so slowly that its 7562
Sterile Baseline Guide.
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Note also that (according to EN1822) HEPA filters may be rated at MOST 7571
would perform even better but would cost more at higher cost.
7578
99.97%. A HEPA filter rated at 99.97% at 0.3 microns may actually be as 7583
low as 99.9% at 0.1 to 0.2 micron MPPS. If viruses are a concern, the 7584
HEPA may be scanned to 99.99% or better using a smaller aerosol (such 7585
as thermally generated PAO), or ULPA filters may be advisable.
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11.2.7 Summary 7588
7589
These equations are meant to be a starting point for the HVAC designer 7590
and commissioning person. They do not address all the nuances that 7591
affect the HVAC in a pharmaceutical facility. But HVAC personnel who 7592
ignore the basics of physics are doomed to long drawn-out start-ups and 7593
less than desirable system performance. Those who over-design because 7594
they don‘t understand the facility are wasting the Owner‘s money.
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Readers desiring more information, perhaps to the point of nausea, are 7597
welcome to attend the three-day ISPE Pharmaceutical HVAC course where 7598
these principles, and the overzealous aspirations of erstwhile 7599
designers, are explored.
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12 REFERENCES
7601 7602
Airlocks for Biopharmaceutical Plants, del Valle, Pharmaceutical 7603
Engineering , Volume 21, Number 2, March/April 2001 7604
7605
ISPE Baseline® Guide for Sterile Manufacturing, Volume 3 first edition, 7606
January 1999 7607
7608
ISPE Baseline® Guide for Biopharmaceuticals, Volume 6 first edition, 7609
2003 7610
7611