Saturday, October 31, 2020

HEPA filters in pharmaceutical industries

HEPA Filter is an abbreviation of High-efficiency particulate air filter.HEPA filters are defined as the filter which removes 99.95% or 99.97% particulate of size less than equal to or greater than 0.3 microns.

Other Names

The HEPA filter is also called High-efficiency particulate absorbing filter or High-efficiency particulate arrestance filter.

History

History of HEPA filters is very old. It is in use since 1940 and was available for commercial use in 1950.

Material of Construction

The HEPA filter is made of a mat consisting of randomly arranged fibres of glass or semi-synthetic material.

Pharmaceutical Usage

HEPA filters are widely used in pharmaceutical industries to filter the air.

In pharmaceutical industries, HEPA filters are used in HVAC to supply clean air in clean rooms.HEPA filters may be installed in AHU but are more effective when used in terminal diffusers, supplying air directly into clean rooms. Air from the outside environment contain contaminants like pollens, fibres, dust, bacteria, viruses, and many other pollutants. So these should be filtered and removed from the air before supplying to the clean rooms.

Coarse filters

If the outside air is directly filtered through HEPA it will block the HEPA filter in a short period, so we will have to replace it after a short period. Protection to HEPA is provided by using other coarse filters of low efficiency.

For the protection of HEPA filter following filters are used which are installed in AHU and remove the majority of large size particulates.

  • Mesh filters

  • Bag Filters

Mesh filters are also called primary filters and bag filters are called secondary filters. Mesh filters protect bag filters and in return bag filters protect HEPA filters so the lifespan of HEPA  is increased.

Mechanism of HEPA Filter

The HEPA filter does not work like other common filters. Because the gap between fibres may be larger than 0.3 microns so it is a common question that than how it filters particles of size 0.3 microns or smaller. The answer is that the arrangement of fibres in HEPA filters  is unique and three different mechanisms are used to remove the contaminants and these are as follow,

  • Straining/Impaction/Sieving

  • Interception

  • Diffusion

Straining/Impaction/Sieving

This mechanism removes large particles of size 1 micron. As we know HEPA pore size is 0.3 micron so the large particles are stuck inside the glass fibres and it is called impaction or straining or sieving.

Interception

Particles of size 0.3 microns to 1 micron are removed from the air by interception mechanism. In interception, particles move along with airflow pattern but particulate speed is slow because of heavy size so they adhere to fibers and are removed from the air.

Diffusion

The particles less than 0.3 microns are removed by Diffusion method. Particles less than 0.3 microns are so little that they move in a zig-zag fashion in air streams so these are trapped in fibres due to arrangement of fibres.

So in summary HEPA filter removes particulates by a combination of any of three mechanisms, Impaction removes large particles, interception is for the filtration of medium particles and diffusion removes smaller particulates.

Classification of HEPA Filters

HEPA filters are classified according to two standard one is European Standards classification and other is US Standards.

European Standards 

According to European standards, the HEPA filter should be ≥99.95 % efficient.

US Standard.

According to US standards, the HEPA filter should be ≥99.97 % efficient.

European Classification 

According to European standards, HEPA filters are divided into 3 classes

  • EPA Filter(Efficient Particulate Air filter)

  • HEPA Filter(High-efficiency particulate Air Filter)

  • ULPA Filter(Ultra Low particulate Air Filter)

EPA

Filters with efficiency 85-99.95% are called EPA filters.

Subclasses

Class           Retention

E10                >85%

E11                >95%

E12                >99.5%

EPA filters usually filter following,

  • Embryo

  • Smoke of tobacco

  • The smoke of metal oxide

  • Black carbon

  • EPA is used as a pre-filter for H13 and H14 filters.


HEPA Filters


Class         Retention

H13            > 99.95%

H14            > 99.995%

HEPA filters filter,

  • Microparticles aerosol

  • Radioactive aerosol

  • H13 is usually used as a terminal filter for ISO class 5.

  • H14 is usually used as a terminal filter for ISO class 4.


ULPA Filter

  • For Microparticles aerosol.

  • ULPA filters are used usually for,

  • ISO class 1

  • ISO class 2 

  •  ISO class 3


            Class          Retention

U15              >99.9995%

U16             > 99.99995%

U17             > 99.999995%

Note

HEPA do not remove smell or order. for removing smell or odour Filters with activated carbon are used.

Test for HEPA filter

HEPA filters are installed in any area to purify the air to maintain the cleanroom classification, so HEPA filters should be routinely monitored for any type of leakage or filter damage. Because if any leakage is present in grass kit of HEPA filter or if HEPA filter is damaged then air quality will be poor and it will contaminate the cleanroom.

DOP Test (Dispersed oil particulate)

To check, the integrity of HEPA filter DOP test is used in which aerosol of poly alpha-olefin is used. In previous practices, DOP (Dioctyl phthalate) was used but it was found to be carcinogenic so its use is prohibited but the name DOP is still in use and it represents Dispersed oil particulate test. In DOP test aerosol of PAO is generated and it is scanned by prob of photometer first on upstream position and later on downstream position. The scanning is done by keeping a probe about 25mm away from the HEPA filter face. Scanning results should not exceed 0.01%. If the downstream position value is above 0.01% then filter needs inspection, means there may be any leakage in filter or gas kit so after rectification again scan with scanning prob and if the value is within range filter is pass and if again value exceeds, the filter should be replaced with a new filter. The leaked filter may be repaired but the repaired area should be only 0.5% of total filter surface.

According to PIC/S HEPA filter of class A and B should be tested for leakage after 6 months and class C and D after 1 year.

Cleaning of HEPA filter

It is a general question that can we wash the HEPA filter? The answer is that washing of HEPA filter is not recommended because washing with water damages the glass fibres arranged in HEPA filters.

Some people Clean the HEPA filter using Vaccume cleaner or compressed air but it is also not recommended because there are chances of damage to the glass fibres with vacuum cleaning or compressed air pressure. So the best practice is to replace the HEPA filter with a new filter.

When to Change the HEPA filter

No guidelines define the period after which HEPA should be replaced generally it is mentioned the word free from leakage. So HEPA life span depends upon its usage. Many HEPA filters can be functional for year's and some may be changed after months. Pressure drop is the main indication which gives an alert to replace the HEPA filter.

Also read

Clean room classification in pharmaceutical industries


Types of airlocks in pharmaceutical industries.


Pharmaceutical Questions and Answers.


Potency calculation of Active pharmaceutical Ingredient.


Easy Steps to calculate Double cone blender capacity.


Line Clearance in pharmaceuticals.


How to become a skilled pharmacist?


Recomended Sound level for working.


Friday, October 30, 2020

cleanroom classification in pharmaceutical industries


A clean room is a room in which particles and the viable count is kept within standard and defined ranges. As the name indicates, cleaning is the strict requirement for these rooms and it is necessary to maintain their defined cleaning level all the time. Cleans rooms play an important role in the manufacturing of pharmaceutical products.

In pharmaceutical industries, clean rooms are classified based on the size of particles and the number of particles per cubic meter of air.  For each clean room, there are specific limits for particle count,  microbial counts and air changes.

Classification of clean rooms

Clean rooms are classified according to following standards,

  • ISO 14644-1

  • Federal Standards (FS 209)

  • European standards

According to ISO 14644-1

ISO classify clean rooms into following

  • ISO 1

  • ISO 2

  • ISO 3

  • ISO 4

  • 1SO5

  • ISO 6

  • ISO 7

  • ISO 8

  • ISO 9


In ISO there are 9 classes of the clean rooms from ISO 1 to IOS 9.ISO 1 is cleanest from all classes of ISO and ISO 9 is least clean or dirtiest from all ISO classes but cleaning level of ISO 9 is superior to a regular room. In pharmaceutical Industries following ISO, classes are generally required,

  • ISO 5

  • 1SO6

  • ISO 7

  • ISO 8

According to FS 209

According to the federal standard, FS 209 Clean rooms are classified as,

  • Class100

  • Class1000

  • Class 10,000

  • Class100,000


According to the EU GMP

  • Grade A

  • Grade B

  • Grade C

  • Grade D


FS 209 is replaced by ISO 14644-1 but these terms are still in use. In ISO particle are taken as particles/m³ (cubic meter)and in FS 209 particles were taken as particles/ft³(cubic feet)

A  simple comparison of clean rooms classification for pharmaceutical industries is as follow,


 ISO             EU GMP               FS

 ISO 5          Grade A          Class 100

 ISO 6          Grade B          Class 1000                      

 ISO 7          Grade C         Class 10,000

 ISO 8          Grade D         Class 100,000


Particle Size Range

In pharmaceutical industries, two ranges of particle size are considered for classification of clean rooms one is ≥0.5 micron (equal to or greater than 0.5 microns) and other is ≥5.0 micron (equal to or greater than 5.0-micron particles).

ISO 5 /Grade A

ISO class 5 is cleanest in pharmaceutical industries and particle count limit for this class is 3520 particles/m³ for particle size  ≥0.5 micron, and particle count for particles ≥5.0 micron is 29 particles/m³.

Air changes per hour  are 240-480.

Microbial count in Grade A according to EU is <1 cfu/m³.

Class A is achieved under laminar airflow hood and critical operations take place in this class,

  • Filling

  • Sealing

  • Aseptic manufacturing(If sterile filtration is not done)

  • Handling of sterile starting materials.

  • Manufacturing and filling of sterile creams, ointments,

emulsions and suspension(when Product is exposed and is not subsequently filtered)

ISO 6  /Grade B

ISO class 6 is the second number for cleaning standard in pharmaceutical industries and particle count for particles ≥0.5micron  is 35200 particles/m³ and particle count for particles ≥5.0 micron is 293 particles/m³.

Air changes per hour  are 150-240.

Microbial count in Grade B according to EU is 10 cfu/m³.

  • Grade B is the background area of Grade A mean area in which laminar airflow hood is placed.

ISO 7 /Grade C

ISO class 7  is on the third number in pharmaceutical industries and particle count for particles ≥0.5 micron is 352000 particles/m³ and particle count for particles ≥5.0 micron is 2930 particles/m³.

Air changes per hour  are 60-90.

Microbial count in Grade C according to EU is 100 cfu/m³.

Grade C is for following operations,

  • Solution preparation( if sterile filtration is to be done later on)

  • Manufacturing and filling of creams, ointments,

emulsions and suspension before terminal steralization.

  • Liquid manufacturing area at rest is Grade C.

ISO 8/Grade D 

ISO class 8 is on forth number class in pharmaceutical industries and particle count for particles ≥0.5 micron is 3520,000 particles/m³ and particle count for particles ≥5.0 micron is 29300 particles/m³.

Air changes per hour  are 05-48.

Microbial count in Grade D according to EU is 200 cfu/m³.

  •  washing of components.

  •  Handling of components after washing

  • Tablet,Capsule section(OSD) is Grade D at rest.

  • Liquid manufacturing area in operation is Grade D.

All clean rooms are separated from each other through the Airlock system.

Also read:

Potency calculation of Active pharmaceutical Ingredient.

Easy Steps to calculate Double cone blender capacity.


Airlocks maintain the cleaning standard of clean rooms through proper air changes. Air changes are maintained by the HVAC system.

in clean rooms, the air is filtered through HEPA filters.HEPA filter stands for High-efficiency particulate air filter.HEPA filters remove particles of 0.3 microns and supply clean air in clean rooms.

At Rest

At rest mean all the equipment are installed in a clean room and HVAC system is operational but manufacturing activity is stopped. It means the area is cleaned and no operator is performing manufacturing activity.

At rest particle count in clean rooms is as follow,

Grade A

≥0.5 micron=3520 particles/Cubic meter

5.0 micron=29 particles/Cubic meter

Grade B

≥0.5 microns=35200 particles/Cubic meter

≥5.0 micron=293 particles/Cubic meter

Grade C

≥0.5 microns=352000 particles/Cubic meter

≥5.0 micron=2930 particles/Cubic meter

Grade D

≥0.5 micron=3520000 particles/Cubic meter

≥5.0 micron=29300 particles/Cubic meter

In Operation

In operation means all the equipment are installed in a cleanroom and HVAC system is operational and manufacturing activity is going on in the cleanroom. It means the area is cleaned and operators are performing manufacturing activity in a cleanroom.

In Operations particle count in clean rooms is as follow,

Grade A

≥0.5 micron=3520 particles/Cubic meter

≥5.0 micron=29 particles/Cubic meter

Grade B

≥0.5 microns=352000 particles/Cubic meter

≥5.0 micron=2930 particles/Cubic meter

Grade C

≥0.5 micron=3520,000 particles/Cubic meter

≥5.0microns=29300 particles/Cubic meter

Grade D

≥0.5 microns=Not Defined.

≥5.0 micron=Not Defined.

Note:

EU volume 4 Annex 1 and WHO Annex 6 describe

5.0 micron=20 particles/Cubic meter both for at rest and operation.


Important topics

Classification of HEPA filters


Types of airlocks in pharmaceuticals


HVAC or Heating Ventilation & Airconditioning System.


Loop Circulation system for purified water.


How to get protection from Coronavirus in pharma. 


Why we Use only 70% IPA


How to write a SOP.


Reconciliation in pharmaceutical industries.


How to become a skilled pharmacist?


Recomended Sound level for working.


Recomended lux level for Different areas in pharma.