Kenapa hal ini Penting bagi industri Farmasi ?
- 5.3.1 Sistem produksi, penyimpanandan distribusi air untuk produksi hendaklah dirancang, dipasang, dilakukan commissioning, divalidasi dan dirawat untuk memastikan air yang dihasilkan dapat diandalkan sesuai kualitas yang diinginkan. SPA tidak boleh dioperasikan di luar kapasitas yang dirancang.
- 5.3.2 Air hendaklah diproduksi, disimpan dan didistribusikan dengan cara yang dapat mencegah pertumbuhan mikroba, kontaminasi kimia atau fisis (misal debu dan pengotor).
Aneks 1 CPOB 2012
Pemantauan Air
- 76. Air yang dipakai untuk membuat produk steril termasuk penyimpanan dan sistem distribusinya hendaklah selalu dikendalikan untuk menjamin bahwa spesifikasi yang sesuai dicapai tiap pengoperasian.
- 77. Air yang digunakan untuk formulasi hendaklah diperlakukan sebagai bahan awal.
- 78. Air untuk Injeksi (WFI) hendaklah diproduksi melalui cara penyulingan atau cara lain yang akan menghasilkan mutu yang sama.
- 80. Air untuk Injeksi (WFI) hendaklah disimpan dalam wadah yang bersih, steril, nonreaktif, nonabsorptif, nonaditif dan terlindung dari pencemaran.
- 81. Sumber air, peralatan pengolahan air, dan air hasil pengolahan hendaklah dipantau secara teratur terhadap pencemaran kimiawi, biologis dan, bila perlu, terhadap cemaran endotoksin untuk menjamin agar air memenuhi spesifikasi yang sesuai dengan peruntukannya. Hasil pemantauan dan tindakan penanggulangan yang dilakukan hendaklah didokumentasikan.
- 82. Alat perekam hendaklah digunakan untuk memantau suhu penyimpanan.
Quality of water should be specific for product quality Water contain :
- Organic and inorganic impurities
- Microbial contamination
- Endotoxin
- Particulate contamination
Danger of Low Quality of Water Low quality of water can lead to:
- product degradation
- product contamination
- loss of product and profit
Contaminants of water :
- Calcium and magnesium are probably the two most common mineral contaminants. They cause water hardness discussed in another slide. Heating or boiling water can precipitate these minerals leaving behind a scale deposit.
- Iron and manganese discolour water and can react with drug products, or act as catalysts in decomposition processes.
- Silicates may interfere with distillation equipment.
- Carbon dioxide picked up in the atmosphere can change the pH and hence the conductivity of water. Carbonates can cause precipitation of calcium, and carbonic acid can cause corrosion of water treatment systems.
- In areas of thermal activity, the water may be contaminated with sulphides, which even at low levels cause a rotten egg odour.
- Phosphates can also cause precipitation of metal ions and scaling, e.g. in boilers.
- Copper contamination can arise from corrosion of copper piping.
- Aluminium can pose a problem in the manufacture of dialysis products. It can be introduced from the flocculation treatment used to reduce sols and clays.
- Heavy metals, particularly arsenic, may be problematic in wells in certain areas. Lead contamination can arise from tanks which have had lead solder repairs. Lead pipes are not recommended. Cadmium can also be an issue depending on the where the aquifer percolates.
- Nitrates are an increasing problem for drinking water, but are easily removed by de-ionizers.
- (The trainer can also point out any local mineral-related contaminants that may be relevant in the region. For example, in some areas radioactive minerals may be a problem. )
Contaminants of water :
One of the major obstacles to successful treatment of water is the presence of micro-organisms. These are usually found in biofilms that develop on wet surfaces in almost any condition. The next slide explains how biofilm forms.
The major groups of contaminating micro-organisms are:
- Algae: These arrive from raw water but can also grow where water is uncovered and there is a light source. Sometimes algae grow when UV lights lose their lethal effect and are emitting only visible light.
- Protozoa: These include Cryptosporidium and Giardia. They can usually be easily filtered out since they are relatively large organisms.
- Bacteria. Of these, the normal aquatic microflora cause the most problems. Most of these belong to the Pseudomonas family or are Gram negative, non-fermenting bacteria. Some of them easily pass through 0.2 micrometer filters and are known to cause disease. Other Gram negative bacteria that are objectionable are Escherichia coli and coli forms. These are indicator organisms pointing to faecal contamination.
Biofilm formation:
- This illustration is shown handout
- Free swimming aquatic bacteria use polymucosaccharides, as a glue, to colonise surfaces. Biofilm is composed of cellular debris, organic material and very few apparent vegetative cells.
- Complex communities then evolve which, when mature, shed micro-colonies and bacteria into the downstream water. This gives rise to sporadic high counts.
- Even when disinfected, the biofilm can remain, to be recolonised quickly when the disinfecting agent is removed. Biofilms can form readily if water is stagnant, such as in dead legs or where there are rough surfaces, such as poorly finished welds.
Types Of Water
Drinking Water / Potable Water
yaitu air yang layak minum sesuai persyaratan yang berlaku (WHO 1998. Guidelines for drinking water quality, Addendum to Volume 2)
Purified Water
Air murni, digunakan sebagai pabrikasi produk farmasi non-steril
Water for Injection
Air kualitas tertinggi yang digunakan di industri farmasi, digunakan pada produk parenteral (produk yang diinjeksikan ke tubuh)
Water for Final Rinse
Air yang digunakan untuk pembilasan terakhir setelah pencucian peralatan. Kualitasnya harus sama dengan air yang dipakai dalam membuat produk
Definisi
Softened Water (SW)
Hard Water adalah air yang mengandung mineral tinggi khususnya Magnesium dan Kalsium. Mineral ini akan meninggalkan endapan kapur berwarna putih, juga akan mengurangi kemampuan reaksi sabun.
Soft Water adalah air yang sudah dihilangkan kandungan ion Ca2+ dan Mg2+. Air perlu dilunakkan untuk menghindari endapan zat kapur pada sistem perpipaan yang dapat mengurangi luas penampang pipa dan juga untuk mengoptimalkan fungsi cleaning agent.
Water softener adalah sejenis “filter” khusus yang mampu menghilangkan kalsium dan magnesium dalam air menggunakan plastik resin dan bisa melakukan pembersihan sendiri secara periodik dengan istilah “regenerasi”.
- Komponen utama water softener:
- Tangki resin, berisi resin jenis Sodium kompleks
- Tangki garam, untuk proses regenerasi
PW Generator
Merupakan alat yang mengolah feed water menjadi Purified Water dimana tahapan prosesnya sbb :
- Double open (DO) Filter
- Rondomat duo
- Testomat
- Single Open Filter
- Multistage Pump
- RO Membrane
- Electro De Ionizer (EDI)
WFI berasal dari purified water system, yang selanjutnya dilakukan destilasi (penyulingan) dengan terlebih dahulu melewati lampu UV untuk membunuh bakteri.
Proses destilasi di Ferron masih menggunakan 4 kolom destilasi
“Persyaratan mutu Air yang digunakan dalam industri Farmasi hendaklah ditetapkan berdasarkan karakteristik produk, proses produksi, dan cara pemberian obat”
Bisa Lihat Di Postingan Di bawah ini
Water System Design
Water can be used directly, or stored in a storage vessel for subsequent distribution to points of use
Design appropriately to prevent recontamination after treatment
Combination of on-line (TOC, Conductivity meter etc) and off-line monitoring (lab testing by proper sampling) to ensure compliance with water specification
How to minimized microbial contamination ?
- Much of the chemical and physical aspects of water system design are relatively straightforward. However, a significant part of good water system design is ensuring that microbial contamination is minimized. Microbial contamination can arise as a result of colonization of surfaces and stagnant areas by aquatic bacteria with the formation of biofilm. If the bacteria can be prevented from sticking to the surfaces, the battle is almost won. Smooth surfaces, moving water and no dead spots, all are good design elements.
- Ensure pipes are sloped so water does not pool and lines can be completely drained. Installation records should include a pipe slope check.
- Sanitary fittings and connections should have no crevices for bacteria to colonise (automatic orbital welding)
- Piping and fittings should be constructed of suitable materials such as stainless steel or special polypropylene tubing in order to prevent bacteria from sticking to the surfaces. If pipes need to be joined, then orbital welding is ideal. Check that there are documented records of the welding seam and electropolished surfaces. Stainless steel quality needs to be specified i.e. 316L. Other stainless steel qualities can corrode. Grade 316L stainless steel can be checked using a magnet, since it is non-magnetic.
- Circulating the water at high velocities prevents bacteria from adhering to surfaces and growing. The general guideline is that velocities should be above 2 lm/sec.
- Incorporate non-return valves (NRV) that prevent backflow which could cause contaminated water to mix with clean water. These are sometimes called backflow preventers or check valves.
