6. sanitasi & higiene

TUJUAN

Mengkaji ulang tindakan-tindakan untuk menjamin good sanitation pada:

BangunanPeralatan Proses

Mengkaji ulang tindakan-tindakan untuk menjamin good personnel hygiene

Part One 4Semua aspek pembuatan:

Personalia

Bangunan

Peralatan

Bahan dan wadah produksi

Produk-produk untuk pembersihan dan desinfeksi

Semua sumber kontaminasi silang yang potensial

Part One 11Desain Bangunan

DesainDinding, lantai, plafon, jendela dan pintu, pembuangan, suplay udara, penyedotan debu

Pencegahan penumpukan debu dan kotoran untuk menghindari risiko kontaminasi yang tidak diharapkanProgram pembersihan, pembersihan yang tepat, catatan pembersihan

Pembersihan dan desinfeksi yang efektifPemilihan bahan dan bahan kimia, serta validasi

Tempat / saluran pembuangan

Perlindungan dari serangga, hewan kecil dan cuacaDari menerima bahan baku sampai pengiriman produk yang telah memenuhi syarat

Part Two 15.1 15.34Area-area yang terpisah

Sistem ventilasi dan airlocks

Pakaian

Sistem proses tertutup

Pembersihan dan dekontaminasi

Part Two 15.1 15.34Menghindari Kontaminasi Silang (2)

Area-area dan fasilitas yang terpisah (dedicated facility) untuk:

Material vaksin hidup & produk biologis lainnya

Produk penicillin

Proses campaign


Sistem ventilasi dan airlocks

Desain sistem ventilasi

Udara masuk harus difilter

Perbedaan tekanan dan ekstraksi udara

Airlocks

Pola aliran udara dan desain peralatan

Suplay udara bersih 100% atau resirkulasi

Part Two 15.1 15.34Menghindari Kontaminasi Silang (4) Pakaian

Proteksi terhadap operator dan produk

Produk potensi tinggi atau risiko khusus - perlu pakaian pelindung khusus

Personalia tidak boleh memasuki ke area yang memproduksi produk yang berbeda

Pakaian perlu dibersihkan


Sistem proses tertutup

Contoh:

Sistem pemurnian air

Tangki yang dilengkapi dengan filter udara Tanpa penutup yang dapat dibuka

Mengatasi kesulitan pembersihan khusus, Digunakan clean-in-place (CIP) dan steam-in-place (SIP)


Pembersihan dan dekontaminasi

Protap untuk menghilangkan debu dan kotoran

Menghilangkan semua residu kimia pembersihan atau residu desinfektan

Harus menghilangkan atau mengurangi mikro-organisme

Sanitasi untuk Operasional Produksi (1)Aliran kerjaDidesain untuk menghindari potensi kontaminasi Akses Ke area produksi dibatasi pada orang yang mendapat izin Operator langsung, petugas QC, petugas gudang, petugas pemeliharaan, dan petugas pembersihan

Area yang lebih kritis Semakin sedikit orang yang bekerja di sana

Operasi simultan:

Tidak diperbolehkan memproses produk-produk yang berbeda di area dengan sistem ventilasi bersama (umum)

Diperbolehkan melakukan pengemasan sekunder untuk produk-produk yang berbeda di ruang pengepakan tetapi dengan pemisahan fisik yang jelasSanitasi untuk Operasional Produksi (2)

Pengecekan kesiapan area produksi (area/line clearance)

Proses pengecekan

Semua bahan dan dokumentasi dari bets sebelumnya dibersihkan Seluruh peralatan dan ruang dibersihkan dan diberi label statusGunakan daftar periksa (check list)

Sanitasi untuk Operasional Produksi (3)

Pengecekan kesiapan area produksi (area clearance)

Pengecekan dilakukan oleh dua orang

Di antara bets dari produk yang sama, dibolehkan kedua pengecekan dilakukan oleh orang produksi

Untuk pergantian produk, pengecekan kedua oleh orang QC

Semua pengecekan harus sesuai dengan Protap dan hasilnya dicatat pada dokumentasi bets tersebutSanitasi untuk Operasional Produksi (4)

Pembersihan dan validasi pembersihan Derajat pembersihan tergantung pada apakah bets berikutnya merupakan produk yang sama atau berbeda

Periksa bahan pembersih: Apakah dapat dihilangkan sepenuhnya?

Jika perlu gunakan air panasSemua larutan pembersih dan desinfeksi harus dibuat dengan hati-hati dan diberi ED

Pembilasan akhir Dengan purified water (PW) atau deionized water (DIW) untuk produk non steril, atau water for injection (untuk produk steril)

Simpan semua catatan (dokumen)Sanitasi untuk Operasional Produksi (5)

Sistem pengolahan air

Air komponen utama untuk sebagian besar produk

Protap untuk pembersihan dan sanitasi sistem pemurnian air harus mencakup pula pipa distribusinya

Validasi dan penghilangan desinfektan sebelum penggunaan ulangSanitasi untuk Operasional Produksi (6)

Pemeliharaan dan perbaikanKegiatan yang tak terhindarkan di area produksi Tidak boleh menimbulkan risiko terhadap produk

Bila memungkinkan, Semua pemeliharaan direncanakan di luar jam kerja normal

Pekerjaan darurat di area kerja Harus diikuti dengan pembersihan dan desinfeksi menyeluruh sebelum memulai kembali proses produksi

Area/line clearance Dilakukan oleh petugas QCSanitasi untuk Operasional Produksi (7)

Part One 10.16 10.23Higiene Personalia (1)

Pemeriksaan kesehatan

Pada saat penerimaan , diulang secara teratur

Pelatihan

Pelatihan induksi untuk operator baru termasuk pelatihan higiene personal dasar

Protap Mencuci tangan sebelum memasuki area produksi

Penandaan di ruang ganti untuk mengingatkan pentingnya mencuci tangan

Part One 10.16 10.23Higiene Personalia (2)

SakitStaf yang sakit atau luka terbuka tidak boleh menangani bahan awal, produk antara, produk ruahan dan produk jadi

Kondisi yang berpotensi merugikanOperator dilatih untuk mengenali risiko Melaporkan kepada supervisornya jika sakit

Higiene Personalia (3)

Kontak antara produk and operator

Hindari kontak langsung

Jika penanganan langsung tak terhindarkan, gunakan sarung tangan

Lakukan desinfeksi sarung tangan (untuk produksi steril) dan pada tempat / saluran pembuanganPart One 10.20 10.23, 11.7 11.8


Pakaian dan fasilitas ganti

Ruang ganti pencucian tangan, handuk atau hot air hand dryers

Pakaian bekas kerja disimpan pada wadah terpisah dan tertutup saat menunggu pembersihan

Pencucian pakaian kerja di fasilitas cuci yang sesuai dan mengikuti protap

Perlu protap untuk sterilisasi dan penyimpanan pakaian untuk penggunaan di area sterilPart One 10.20 10.23, 11.7 11.8


Merokok, makan dan minum tidak dibolehkan di area produksi, laboratorium dan penyimpanan

Permen karet harus dilarang

Tidak boleh ada tanaman di dalam pabrik

Ruang istirahat harus terpisah dari area produksi.

Toilettidak berhubungan langsung dengan area produksi dan penyimpananPart One 10.20 10.23, 11.7 11.8

MASALAH DALAM SANITASI & HIGIENE I Mixed production produksi campuran

Penicillins golongan betalaktam

Product versus batch changeovers produk dan pergantian item produk

Water systems sistem pengolahan air

How long should a cleaned status last for? waktu status bersih

What should happen if a clearance check is required when no QC personnel are on duty? pengecekan jika petugas QC tidak hadir

MASALAH DALAM SANITASI & HIGIENE - II -

Personal hygiene higiene karyawanProcedures and records protap dan catatan/rekaman

Health checks pengecekan kesehatan Dealing with health problems masalah kesehatan

Personal responsibility tanggung jawab karyawan

Training records catatan/rekaman pelatihanFrequency of handwashing frekuensi cuci tangan

WASSALAMHAVE A NICE DAY & KEEP SMILING !

In this session, we are going to deal with an area of importance to the good functioning of a pharmaceutical factory, sanitation and hygiene.This will be a quarter-day session with the following approximate timings:Presentation45 minutesGroup session45 minutesGroup feedback 30 minutesTest paper 30 minutes(Timings are approximate and should be adjusted to suit the class and the course structure.)

There are three main objectives to this session:Firstly, we are going to look at the measures that need to be taken to ensure good sanitation during manufacturing. These relate primarily to the premises, the equipment and the process to prevent any type of contamination.Secondly, we are going to look at the measures that need to be taken to ensure that good levels of hygiene are achieved during manufacturing. These relate primarily to the personnel.Finally, we are going to relate everything back to the issues particularly relevant to your country. During the group session, you will be looking at the key factors that you need to be aware of during your inspections. We will be presenting you with some photographs to list all the sanitation and hygiene problems that you can.

The WHO GMP refers to sanitation and hygiene in part one, section 4. It makes the point that all aspects of manufacturing are affected by one or both of these factors. Consideration must be given to all personnel, both direct operators and other staff who enter the manufacturing area for whatever purpose. Then there are the premises in which manufacturing takes place. The level of attention to this aspect will vary with the operation that is carried out. All equipment and apparatus used in manufacturing must be controlled, together with production materials and the containers in which they are held. Production materials (if not handled properly) and the containers (if not properly cleaned) can contribute to dirt and contamination in the factory.Secondary materials, such as cleaning agents and disinfectants, must be controlled to ensure that they do the job for which they are designed but do not cause any contamination to the product. Cleaning tools, such as mops and brushes, must also be controlled.To summarize, the aim of sanitation and hygiene measures is to eliminate all potential sources of contamination and cross-contamination from all areas where the product is at risk.

Sanitation is covered as part of the general discussion of premises in part one, section 11 of the WHO GMP text.As discussed (or will be discussed) in the module on premises, the design of any area depends on the activities that are going to be performed there. However, in general terms, all areas should be designed in such a way that prevents the build-up of dirt and dust. This includes the absence of ledges and unnecessary surfaces, sealing of all joints in ceilings, coving at floor and ceiling and installation of a ventilation system that provides an appropriate flow of air.There are a number of aspects to be covered in looking at cleaning. An effective programme should be designed that covers both cleaning and disinfection. The frequency of each will vary with the function of each area and the particular activities undertaken there. There must be a written procedure (SOP) covering the programme, who is responsible for carrying it out, the materials to be used and methodology. The procedure should be appropriate to the area being cleaned. For example, the procedure for cleaning the warehouse would not be appropriate for cleaning a sterile area. There should also be a written record of cleaning that has been performed.While drains are inevitable in some manufacturing areas, they should be kept to a minimum and should certainly not be located in sterile areas. Their design must prevent the possibility of back-flow. Open channels should be easy to clean and disinfect.There should be maximum protection against the entry of insects or other animals. In loading bays in particular, there needs to be protection against the weather. In part two of the WHO GMP, section 15 covers the measures that need to be taken to avoid cross-contamination.These include:Segregated areasVentilation systems and airlocksClothingClosed processing systemsCleaning and decontamination

Certain products, such as live vaccines and other biological materials need to be produced in separated areas. In particular, penicillin should be produced in a separate facility. The trainer should also give emphasis to the WHO clause 15.12 (a) on campaign processing. The question of campaign batches and what cleaning may be appropriate is a matter of some controversy and many countries have different requirements.An important measure against cross-contamination is the design of the ventilation system. All incoming air should be filtered to an appropriate standard to achieve the grades of cleanliness specified for the room being supplied. The use of appropriate pressure differentials and air extraction, together with airlocks, is one of the main ways of achieving control over cross-contamination. (Airflow patterns and equipment design are other considerations.) Additionally, the recirculation of air must be examined carefully. If a ventilation system supplies 100% fresh air, then different rooms can be used for different products at the same time. However, if a system includes recirculation, then all rooms supplied by that system must be processing the same product, or the air must be filtered to an appropriate standard. If no filters are installed, then all ductwork will have to be cleaned during product changeover.Clothing relates to the protection of both the operator and the product. For highly potent products or those that create a particular risk of cross-contamination, special protective clothing needs to be worn. Decontamination processes for these clothes need to be in place. For all manufacturing areas where there is any risk of the product contaminating the clothing, the simple precaution of not moving between areas producing different products should be adopted.

Increasingly, facilities are being designed with closed processing systems. This trend is obviously one that should be encouraged, as it is a major element in the avoidance of cross-contamination. Cleaning should be a procedure for removing soil and dirt. It should not add or leave behind anything, including cleaning, chemical or disinfectant residues.It must remove or reduce micro-organisms.Cross reference to the module on validation can be mentioned if questions arise on how and what is cleaning validation.The work-flow has to be designed in such a way as to avoid any potential contamination. Access to production areas should be restricted to authorized personnel only. These will include direct operators, QC staff, warehouse staff, maintenance personnel and cleaners. The more critical the area, the fewer the people that should be in there during processing operations.

Processing of different products simultaneously within a single room or area supplied by the same ventilation system must not be carried out unless there is no risk of cross-contamination. Hence, it is permissible to dispense materials for different products within adjacent down-flow booths in a dispensary. This is because each booth creates its own protected environment. That is, it is not permissible to process different products in different parts of a tabletting facility, if the area is supplied by a single unfiltered recirculating air system It is also permissible to carry out secondary packaging activities for different products within a packing hall, provided there is adequate physical separation, such as a partition, since the product is sealed and there is no risk of airborne contamination. However, it is not permissible to process different products in different parts of a tabletting facility, if the area is supplied by a single recirculating air system, unless appropriate air filtration is used..

The first step in any batch processing operation is the area clearance check. This is the process of checking that all materials and documentation from the previous batch have been removed, and that all plant and equipment has been thoroughly cleaned. A useful group exercise is to use a flipchart to get the trainees to list all the requirements for a cleaning status label. Items can include: name of the equipemnt, cleaned or not clean, date cleaned, who cleaned, who passed, how long will the cleaned equipment remain clean before rrequiring recleaning, etc., The area clearance check should be carried out by two people (one performing the check and the other confirming the result). Between batches of the same product, it is acceptable for both checks to be carried out by production personnel. However, where there has been a product changeover as well, the second check should be carried out by QC staff. All checks should be carried out in accordance with a written SOP and the results recorded on the batch documentation and cleaning record. A checklist is very useful for this purpose.Discuss with the trainees the requirement for QC to do the second check for the area clearance check. We have already talked about cleaning of premises. Another important point is the cleaning of the equipment in which products are manufactured. The degree of cleaning will depend on whether consecutive batches are of the same product or of different products. It is important that any cleaning agent introduced is also fully removed so that it does not contaminate the product. Wherever possible, hot water alone should be used for cleaning. The final rinse should be with purified water or water for injection in the case of equipment used for processing sterile products. A validation programme should be based on the worst case situation, e.g. a relatively insoluble material that is active at low levels of concentration. Additionally, full records should be kept of cleaning and sanitation.The sanitation of water systems is particularly important, as water is such a major constituent of most products. Water heated >75oC and recirculated is a good sanitising agent. Water for Injection is usually stored at much higher temperatures. There should be a written standard procedure for cleaning and prevention of contamination, which should include not just the purification system but also the distribution pipework. The procedure should be validated, especially the removal of disinfectant before the system is put back into use. This is important because formaldehyde and peracetic acid are often used to disinfect water systems Repair and maintenance activities are inevitable in a manufacturing area. However, they should be carried out in a way that does not present any risk to the product. Therefore, whenever possible, all planned maintenance should be done outside of normal operating hours. Any emergency work in a working area should be followed by a thorough clean down and disinfection of the area before manufacturing recommences, AND area clearance by QCHaving dealt with sanitation, we now move on to the hygiene of the personnel involved in manufacturing. This is covered in the WHO GMP texts in part one, section 10. The recruitment process for direct operators in particular should include a medical examination. This should be repeated on a regular basis during the employment period. The definition of regular will obviously depend on the activities being undertaken and the products being processed. Induction training for new operators should include basic training in personal hygiene and should state the level of hygiene that is required for working in manufacturing areas. There should be written procedures covering the need to wash hands before entering a manufacturing area. In addition, signs should be posted in the changing rooms to reinforce this. Staff who have an illness or open lesions that are likely to present a risk to the product, should not be allowed to carry out operations that involve handling of starting materials, intermediates or finished products until the condition has cleared up. Since not all illnesses are going to be obvious, operators must be trained to recognize such risks themselves and be willing to report any illness to the area supervisor.Staff who have an illness or open lesions that are likely to present a risk to the product, should not be allowed to carry out operations that involve handling of starting materials, intermediates or finished products until the condition has cleared up. Since not all illnesses are going to be obvious, operators must be trained to recognize such risks themselves and be willing to report any illness to the area supervisor.Direct contact between the operator and the product should be avoided wherever possible. If direct handling is unavoidable, then gloves should be worn and, if appropriate, these should be disinfected after being put on.Clothing and changing facilities are covered in a number of the modules on this course. The type of clothing required and the changing procedure will obviously vary with the activities being carried out. They need also to apply to visitors. Used clothing must be stored in separate closed containers while awaiting cleaning. The laundering of clean area clothing must be carried out according to a written procedure and in an appropriate facility. If necessary, there should also be a procedure for sterilizing and storing clothing for use in the sterile area.

Smoking, eating and drinking should not be allowed in any manufacturing area, including laboratories and storage rooms. Chewing of gum should also be banned. There should be no plants kept inside any factory areas.Rest and refreshment areas should be separate from manufacturing areas. Toilets should not open directly into production or storage areas. However, there should be a reasonable access procedure. This should be taken into consideration when setting up changing procedures for entry to manufacturing areas.

If production demand is high, there may be resistance from the managers of the factory to spending time carrying out effective cleaning.Production of different products in the same area can cause serious cross-contamination.The issue of decontamination of a factory that has been used for the manufacture of penicillins needs to be addressed carefully.In an older building, the design may not be suitable for effective cleaning. For example, there may not be false ceilings, walls may be covered in tiles, etc.The design of the ventilation system needs to be reviewed, particularly with respect to standards of filters and recirculation. Cleaning of ductwork should also be discussed.Procedures for a changeover from one product to another should be more stringent than the procedure between batches.There should be written procedures for regular cleaning and prevention of contamination of the water system.The procedure for cleaning and prevention of contamination should include details of who is responsible, what they have to do and where it is recorded.

Personal hygiene is always a sensitive matter. However, the company must be able to ensure that operators not only understand hygiene requirements, but also fulfil them.Health checks should be carried out on all new operators and periodically on all staff during employment. This could be a problem if the managers are reluctant to carry the expense.There should be trained staff who can deal with issues relating to health problems. The operators must feel that they can report these problems in confidence without risking their jobs.As with any aspect of pharmaceutical manufacture, the final quality of the product depends, to a large extent, on the willingness of the operators to take personal responsibility for such issues as hygiene.Training should include references to procedures for cleaning and hygiene requirements, which should be included in written training records.

6. sanitasi & higiene

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