ratna sosialin - farmasiindustri.com€¦ · obligation of senior management to execute the...
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Jakarta, 10 - 11 Oktober 2018
RATNA SOSIALIN
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Bukti terdokumentasi berisi
penyajian derajat pemastian mutu
(yang tinggi) bahwa suatu
proses spesifik terencana
menghasilkan produk yang
memenuhi spesifikasi dan
karakteristik yang dikehendaki secara
konsisten
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VMP – Therminologies
Annex 15 EU GMPAll validation activities should be planned. The key elements of a validation program should be clearly defined and documented clearly in a VMP or equivalent documents.
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Validaton Policy
Organization and responsibilities’Company specific definitions
Description of the validation project
List of individual projects (qualifications and validations)
Key acceptance criterion or procedure for determining acceptance
criterion
Documentation formats for protocols and reports
List of relevant SOP`s
Schedule (and estimated resources)
Management System of Change Control
Continued Process Verification (APR/PQR outputs)
VMP should be confirmed and approved by the management.
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Obligation of Senior Management to execute the validaton
faultlessly and to provide the required resources.
Company specific definition and terms
Company specific implementation of legal requirements
Definition of a structured approach to qualification and
validation projects
Information about the general organization of validation
activities, responsibilities,delegated tasks, interfaces,
controlling bodies.
Overview of the individual projects, including time and cost
planning
Function of VMP
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Define the qualification/validation system and include or
reference information on at least the following:
• Qualification and Validation policy;
• Organisational structure including roles and responsibilities for
qualification and validation activities;
• Summary of the facilities, equipment, systems, processes on site and
the qualification and validation status;
• Change control and deviation management for qualification and
validation;
• Guidance on developing acceptance criteria;
• References to existing documents; and
• Qualification and validation strategy, including requalification, where
applicable.
For large and complex projects, planning takes on
added importance and separate validation plans may
enhance clarity.
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Merupakan bagian esensial dari
Sistem Manajemen Mutu Industri Farmasi (IF).
Memuat kebijakan dan filosofi IF melaksanakan
validasi dan tujuan aktifitas validasi.
Mencakup macam kegiatan kualifikasi dan validasi.
Paparan organisasi dan tanggung jawab.
Penjadwalan (tahunan) aktifitas kualifikasi dan validasi.
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◦ Kualifikasi Peralatan Produksi, Instrumen pengujian dan fasilitas serta sarana penunjang
----------------> DQ - IQ - OQ - PQ
◦ Validasi Prosedur Analisis dan Transfer Metoda Analisis
◦ Validasi Sistem Komputerisasi
◦ Validasi Prosedur Pembersihan
◦Validasi Proses◦ Validasi Transportasi
◦ Validasi lain (misal: Media Fill Validation)
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Dokumen Validasi Proses :
Rencana Induk Validasi Proses
Protokol Validasi Proses
Laporan Validasi Proses
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Dokumen yang memuat :
Filosofi IF secara menyeluruh dalam menangani
Validasi Proses
Pendekatan yang dipakai sebagai acuan
Ruang lingkup : area yang dicakup aktifitas validasi
Organisasi dan tanggung jawab - interdisiplin berbagai
departemen : minimal (lit-bang), produksi, QC, QA, teknik/
engineering, pengadaan
Jadwal berkala dan skala prioritas
Kaji ulang dan pembaharuan berkala (tahunan)
Kebutuhan revalidasi dan pengelolaan perubahan
(Change Control)
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Tim Pengkajian – Manajemen :Manajer departemen : litbang, produksi, QC,
QA, logistik, teknik , Site & QA Heads
Tim Pelaksana :Pengawas, pelaksana
dari setiap departemen:
operator, teknisi, analis, personil QA
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RIV (Rencana Induk Validasi) yang disetujui
Validasi Proses terencana dalam Protokol
Peralatan terkualifikasi dan terkalibrasi
Prosedur pembersihan alat tersedia (tervalidasi)
Spesifikasi produk tersedia
Metoda analisis tervalidasi (dan validasi transfer metoda)
Pelatihan personil yang terlibat - terdokumentasi
Tersedianya prosedur penanganan perubahan ------------>
Change Control Management
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Dokumen kunci yang digunakan
untuk merinci bagaimana validasi
proses akan dilaksanakan.
Berisi paparan pokok tentang alur
proses, parameter kritis,
pengambilan dan analisa sampel
serta acceptance criteria suatu
proses menuju pada kesimpulan
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Isi yang tercantum dalam protokol sesuai
dengan dokumen registrasi dalam hal:
• Formulasi (Q/Q Formula)
• Proses
• Spesifikasi Obat Jadi
• Metoda analisis
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1. Pendahuluan
2. Tujuan
3. Lembar Persetujuan
4. Daftar Isi
5. Ruang lingkup : spesifik untuk produk, ukuran bets,
proses serta tipe validasi
6. Tim Validasi : produksi, pengambilan sampel, analisa
sampel, dokumentasi
7. Komposisi, Formula, Besar Bets dan Spesifikasi
8. Informasi bahan awal (karakteristik kritis) : misal ukuran
partikel, densitas, serta referensi metoda pemeriksaan
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9. Peralatan dan Ruangan serta Protap peralatan yang digunakan:
10. Alur proses produksi (* Contoh)
10. Parameter kritis (contoh):
Tahap Proses Alat/ mesinSetting Kecepatan
(rpm) - misal
Setting Waktu
(menit) – misalParameter Kritis
Pencampuran
APITumbler Mixer
20 15
Kadar
dan homogenitas
API
Nomor Protap Judul Protap Tanggal Berlaku
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11. Pola pengambilan sampel (contoh):
12. Analisa data dan kriteria keberterimaan (acceptance criterion)
13. Peruntukan bets (sesuai ruang lingkup, misal: untuk komersial, menunggu data uji stabilitas 6 bulan)
14. Kebutuhan Uji Stabilitas protokol (sesuai protap)
DIAGRAM Alur proses produksi
Contoh
Tahap
Proses
Jumlah
Sampel per
titik
Posisi pengambilan
sampel
Pengujian
sampel Catatan
Pencampura
n API 20 gram Lihat gambar
Kadar API
(HPLC)
10 titik
pengambilan
sampel
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Bahan baku Active (API)
Bahan baku sebagai pewarna
Bahan - bahan baku untuk lubrikasi
Campuran semua bahan menjadi
masa granul siap cetak.
API
API
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• Identitas / logo Industri Farmasi
• Judul Dokumen
• Nomor dokumen mengikuti sistem IF yang ditetapkan
• Tanggal berlakunya dokumen
• Riwayat perubahan dokumen dan alasannya.
• Penyusun, Dikaji, Disetujui dan Diketahui oleh:
Nama Fungsi Tanda Tangan Tanggal
Ali Imron QA Supervisor dd/mm/YYYY
Nomor Versi Alasan perubahan Tanggal Efektif
01 Dokumen baru dd/mm/YYYY
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• Mengikuti tahap PROTOKOL yang
disetujui / berlaku.
• Setiap penyimpangan serta
pengamatan selama pelaksanaan
didokumentasikan serta
dievaluasi dampaknya yang
tercermin dalam Laporan Validasi Proses
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Mendokumentasikan aktifitas, temuan, analisa data dan evaluasi penyimpangan terhadap protokol maupunseluruh kriteria penerimaan (acceptance criterion) serta menyajikan kesimpulan.
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1. Lembar persetujuan
2. Daftar Isi
3. Nomor, jumlah dan ukuran bets
4. Daftar bahan awal dan nomor bets yang dipakai dalam setiap bets – Referensi dokumen bets
5. Paparan penyimpangan serta evaluasi dampaknya
6. Analisa data/ perhitungan terhadap parameter dan kriteria pnerimaan (acceptance criterion)
7. Diskusi output pelaksanaan validasi
8. Kesimpulan dan Rekomendasi (revalidasi, uji stabilitas)
9. Disposisi dan peruntukan bets validasi(QA)
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Tujuan : memelihara status validasi (termuat dalam RIV)
1. Revalidasi berkala:
berdasarkan trend terhadap data bets - bets
dalam PMP (Pengujian Mutu Produk) / PQR / APR
2. Revalidasi karena usulan perubahan
(Change Control) :
- perubahan sumber zat aktif (API) atau bahan awal
- perubahan parameter proses
- perubahan peralatan atau fasilitas penunjang
- perubahan ukuran bets
- perubahan lain
Dasar evaluasi : Analisa Risiko (Risk Analysis)
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Jika hasil pelaksanaan proses validasi gagal dalam
memenuhi kriteria penerimaan yang dapat
menyimpulkan suatu proses dalam status valid,
maka kesimpulan dalam laporan adalah tahap
optimisasi dengan konsekuensi penentuan
perubahan (change control) sebagai dasar
pembuatan protokol baru (follow - up protocol) untuk
melaksanakan proses validasi berikutnya yang lebih
konsisten .
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Protokol
Paparan rinci dan runut dalam dokumen yang disetujui untuk melaksanakan Validasi Proses
Catatan
• Semua catatan
bukti
pelaksanaan
validasi proses
• Data yang
dikumpulkan
untuk menyusun
laporan dan
pengambilan
keputusan (QA)
Laporan
Dokumen disusun berdasarkan seluruh catatan dan data melalui aktifitas yang dilakukan mengikuti protokol beserta diskusi menghasilkan kesimpulan dan rekomendasi.
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• Outputs of APR/ PQR are used to update VMP to
demand process improvement, e.g poor process
robustness statistically with Cpk < 1. 33
• Continous Process Verification must be executed
only by defining approved plan/ protocol
updated VMP.
• Risk Assesment is used as the basic to develop
CPV/OPV which should be covered in
updated VMP
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1
2Ditulis/ dilengkapi mengikuti
tahap proses pada waktunya.
3
Penulisan Catatan (raw data entry):
Jelas, terbaca
(tinta warna selain hitam, bukan pensil)
Bisa dipertanggungjawabkan
melalui ketertelusuran
(tandatangan / paraf dan tanggal)
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The Importance of Data Integrity
Patient`s Safety:Without DI: the safety, quality and efficacy of drugs can not be assured.
Business : Significant damage to company Reputation. Risk to face `ON HOLD` Registration Submission. Potentally Product Recall.
Regulatory Compliance:Ensure compliance with Regulations, Specifications and Standards.
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Training Requirement on Data Integrity
Investigate deviations, document investigation
and conclusion: do not think an isolated issue
perform CAPA and Report
escalation to management
Do not discharge ORIGINAL DATA or Quality Records: Data must be recorded in such a way that source can be traced
by identified responsible person. Documents must be retirievable
Complete and accurate records of manufacturing, testing
and all supporting activities: Validation, calibration, maintenance,
Traceability : who, when what, which activity
Testing including raw data and calculation
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ALCOA Principles - Documents
Attributable data can be assigned to the individual performing the task
Legible data can be read by eye/electronically, & retained
permanent format.
Contemporaneous data is created at the time the activity is performed
Original data is in same format as was initially generated, or as ‘verified copy’
which retains content and meaning.
Accurate data is true/reflective of the activity or measurement performed
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Protokol Records (training, raw data, dll) Laporan
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Tetapkan protokol dengan jelas, sistematis
termasuk tugas dan tanggung jawab setiap
bagian terkait .
Analisa bahan awal, kondisi proses terhadap
parameter kritis dan acceptance criterion untuk
menetapkan kondisi yang memberikan
probabilitas keberhasilan .
Libatkan personil yang terlatih dan upayakan
kerjasama yang baik .
Tetapkan jadwal dan ikuti jadwal dengan baik
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