Tuesday, May 3, 2016

Poly Alpha Olefin (PAO) Used in HVAC Validation?

Know more about the Polyalphaolefin (PAO) used in HEPA filter integrity test during HVAC system qualification including their molecular structure. 

Poly Alpha Olefin (PAO) is used for HVAC qualification in pharmaceuticals. PAO is used as a replacement of the DOP (Dioctyl Phthalate) that was used for this purpose from a long time.

Dioctyl 
Phthalate is found as a carcinogen (cause cancer) for human. Scientists were trying to find a material to replace the DOP from a long time. Finally in 2001 Japan Air Cleaning Association (JACA) published a guideline to replace the DOP with PAO. It gives the equal performance to the DOP and doesn’t have any harmful effect on health. FDA also clearly says that alternative aerosols are also acceptable but they should not promote the microbial growth in area. Therefore, it is recommended to replace the DioctylPhthalate with Poly Alpha Olefin (CAS #68649-12-7). The size of PAO generated aerosol ranges from 0.1 to 1.0 μm. The PAO aerosols are generated by aerosol generator and passed through the HEPA filter then the integrity is checked using a photometer. 99.97% particles having size larger than 0.3 μm should not be passed through HEPA filters.

Molecular Structure of Alpha OlefinPoly alpha olefin is a polymer of alpha olefin. Alpha olefin is a class of olefins those have double bond between first and second carbons of the polymer chains. PAO is a mixture of the dimers, trimers and tetramers of the 1-octene, 1-decene and 1-dodecene. Poly alpha olefins have good lubrication properties and greater viscosity than mineral oils. Poly alpha olefins are also used as synthetic lubricants and as a coolant in radiators.

Shelf life of the poly alpha olefin is 10 years in sealed container but for opened container it is one year. It should be protected from UV lightand direct sunlight.

Wednesday, March 16, 2016

Vial washing machine Qualification

Different tests done during the validation of vial washing machine

Sterile pharmaceutical preparations as injections are filled in glass vials. These vials should be cleaned properly before filling. Automatic vial washing machines are used to clean but the process of cleaning of the vials should be validated. The efficiency of these machines is verified by following tests.

1. Chloride Content Test:

A 30% solution of sodium chloride is prepared in water. 10 containers or vials are spiked with 0.1 ml of this sodium chloride solution. Containers are swirled to coat the inner surface and evaporate the solution to dryness at room temperature. Spiked test containers are marked in series with permanent marker on the outer surface.


2. Particulate Matter Test:
10 gm of charcoal is dissolved to make 1% charcoal slurry. Approximately 0.1 ml of charcoal slurry is used to spike each of 10 containers by swirling the container to coat the inner surface and evaporate the solution to dryness at room temperature. Spiked test containers with charcoal are marked in series with permanent marker on the outer surface.


3. Bacterial Endotoxin Test:
Add 100 endotoxin units into 10 vials and allow them to dry at 45 - 50°C. Mark these spiked vials with permanent marker on outer surface.
Separate 10 containers are used for each of above tests.

Procedure: About 3000 vials of selected size are loaded on the feed belt and vial washing machine is operated as per the standard operating procedure. Place the spiked vials marked with permanent marker in between the other vials while machine is running. These vials should be placed at the initial, middle and end of the washing session. Collect the marked vials after washing and store properly to avoid the other contamination from environment. These spiked vials are analysed separately. It should be done three times for each vial size.


Acceptance Criteria: 
1. Sodium chloride content should be absent in any of the spiked vial.
2. Vials should be free from foreign particle & fibers on visual inspection. 10µ particles should not be more than 25 and 25µ particles should not be more than 3.
3. Vials should comply endotoxin limit i.e 0.25 EU/vial.