BPOM RI Implementasi CPOB dalam Pemastian Mutu Produk

(1)

IMPLEMENTASI CPOB

DALAM PEMASTIAN MUTU

PRODUK

Disampaikan pada Workshop Peningkatan Daya Saing Industri Farmasi

5 Oktober 2015, Malang – Jawa Timur

(2)

TOPIK BAHASAN

CPOB DALAM PEMASTIAN MUTU PRODUK

TOPIK

BAHASAN

PENUTUP

TEMUAN INSPEKSI

TREND PENGAWASAN OBAT BEREDAR PROFIL INDUSTRI DI JAWA TIMUR

(3)

TOPIK BAHASAN

CPOB DALAM PEMASTIAN MUTU PRODUK

TOPIK

BAHASAN

PENUTUP

TEMUAN INSPEKSI

TREN PENGAWASAN OBAT BEREDAR PROFIL INDUSTRI DI JAWA TIMUR

(4)

PERATURAN PERUNDANG-UNDANGAN TERKAIT CPOB

1. Undang - Undang

2. Peraturan Pemerintah

 Undang-Undang No. 8 Tahun 1989

tentang Perlindungan Konsumen

 Undang-Undang No. 36 Tahun 2009 tentang Kesehatan

 Undang-Undang No. 35 Tahun 2009 tentang

Narkotika

 Undang-Undang No. 5 Tahun 1997 tentang Psikotropika

Peraturan Pemerintah No. 72 Tahun 1998 tentang Pengamanan Sediaan Farmasi dan Alat Kesehatan

 Peraturan Pemerintah No.51Tahun 2009 tentang Pekerjaan Kefarmasian

(5)

3.Peraturan Menteri Kesehatan

 Peraturan Menteri Kesehatan No. 1010

tahun 2008 tentang Registrasi Obat

 Peraturan Menteri Kesehatan no16 Tahun 2013 tentang perubahan atas Peraturan Menteri Kesehatan No.1799 Tahun 2010 tentang Industri Farmasi

 Keputusan Menteri Kesehatan No.

43/MENKES/SK/II/1998 tentang Pedoman Cara Pembuatan Obat Yang Baik

4. Keputusan

Menteri Kesehatan

(6)

PERATURAN PERUNDANG-UNDANGAN TERKAIT

CPOB

6. SKB Menpan dan Menkes No. 264 A/Menkes/SKB/VII/2003

tentang Tugas, Fungsi dan Kewenangan di Bidang Pengawasan Obat dan Makanan

5. Peraturan Kepala

Badan POM RI Peraturan Kepala Badan POM No HK.

03.1.33.12.12.8195 tahun 2012 tentang Penerapan Pedoman CPOB tahun 2012

 Keputusan Kepala Badan POM No.

HK.04.1.33.12.11.09937 Tahun 2011 tentang Tata Cara Sertifikasi CPOB

(7)

TANTANGAN PENGAWASAN

OBAT DAN MAKANAN 2015-2019

• Jumlah dan variasi Obat dan Makanan yang beredar meningkat seiring dengan perkembangan Iptek

• Perubahan Gaya Hidup Masyarakat

• Teknologi, Deteksi dan Manajemen Risiko Semakin Canggih vs Kesiapan Infrastruktur dan SDM Bidang Pengawasan Obat dan Makanan

• Meningkatnya produk impor

• Tuntutan pengamanan pasar dalam negeri semakin gencar

• Daya Saing Produk Obat dan Makanan Indonesia, terutama yang diproduksi UMKM belum optimal

Globalisasi, MEA, persaingan

dagang

• Ekspektasi masyarakat terhadap perlindungan kesehatan meningkat

• Emerging dan Reemerging Diseases meningkatserta Perubahan Masalah Kesehatan

• Pengembangan JKN

perlindungan kesehatan masyarakat PENINGKATAN KINERJA PREMARKET PENINGKATAN KINERJA POST MARKET FOKUS PENGAWASAN OBAT DAN MAKANAN

(8)

IMPORT EXPORT

BB LOKAL

EXIM INDUSTRI PRODUK DISTRIB RITEL MASYATAKAT

INSPEKSI

STANDARDISASI & CPOB

EVALUASI REGISTRASI

MONTR. S, E, Q/ PENANDAAN SURV. IKLAN INVESTIGASI INSPEKSI SAMPLING UJI LAB

PRE-MARKET POST - MARKET

PENGHENTIAN SEMENTARA PENCABUTAN IZIN EDAR PENARIKAN PRODUK

R E G U L A S I

SISTEM PENGAWASAN OBAT & MAKANAN

_{SISTEM PENGAWASAN OBAT}

DI INDONESIA

PENCABUTAN IIF

PERINGATAN PUBLIK

(9)

 Berperan aktif dalam forum Product Working Group di ASEAN

 Melakukan penyesuaian regulasi, peningkatan kapasitas SDM dan kelembagaan

 peningkatan daya saing produk obat dan makanan melalui:

 Peningkatan kemandirian industri dalam penerapan cara produksi yang baik

 Asistensi regulatori dalam pengembangan produk

 Pemberantasan produk palsu/ilegal

 Peningkatan kemitraan dengan seluruh stakeholders

 Meningkatkan kesadaran masyarakat dalam memilih obat dan makanan yang memenuhi syarat

Strategi Badan POM Menghadapi

MEA 2015

(10)

TOPIK BAHASAN

CPOB DALAM PEMASTIAN MUTU PRODUK

TOPIK

BAHASAN

PENUTUP

TEMUAN INSPEKSI

TREND PENGAWASAN OBAT BEREDAR

PROFIL INDUSTRI DI JAWA TIMUR

(11)

DATA INDUSTRI FARMASI DI JAWA TIMUR

• 41 Industri Farmasi yang

tersebar di 9 Kabupaten/Kota

• 2 IF mengembalikan Sertifikat CPOB

Tahun 2014

• 41 Industri Farmasi yang

tersebar di 9 Kabupaten/Kota

• Penambahan 2 IF Baru

• 10 industri memiliki fasilitas produksi steril

(12)

JUMLAH INDUSTRI FARMASI

DI PROVINSI JAWA TIMUR

Kota SBY, 8

Kab. Gresik, 4 Kab.Jombang,

Kota. Kediri, 1 Kota. Malang, 1

Kab. Malang, 2 Kab. Mojokerto,

Kab. Pasuruan, 11

Kab.Sidoarjo;

11 Jumlah Industri Farmasi 40

(13)

TOPIK BAHASAN

CPOB DALAM PEMASTIAN MUTU PRODUK

TOPIK

BAHASAN

PENUTUP

TEMUAN INSPEKSI

TREND PENGAWASAN OBAT BEREDAR

PROFIL INDUSTRI DI JAWA TIMUR DASAR HUKUM TERKAIT CPOB

(14)

TREND HASIL SAMPLING NASIONAL (1)

0 10 20 30 40 50 60

Antibiotika Analgesik AIS Antihistamin Vitamin

Trend Kelas Terapi Obat TMS (5 besar)

2011 2012 2013 2014

5 besar obat TMS berdasarkan kelas terapi: 1. Antibiotik 2. Analgesik 3. AIS 4. Antihistamin 5. Vitamin 0 20 40 60 80

Uji Disolusi Kadar pH Pemerian Keseragaman Sediaan

Trend Parameter Uji Obat TMS

2011 2012 2013 2014

3 besar obat TMS berdasarkan parameter uji: 1. Uji Disolusi 2. Kadar

3. Keseragaman Sediaan

(15)

0 10 20 30 40

2011 2012 2013 2014

25 ₂₃

Trend Jumlah Industri Farmasi yang memiliki Riwayat Obat TMS ≥ 2 kali Tahun 2011 - 2014

Jumlah IF

Dari tren tersebut, diketahui bahwa ditemukan sedikitnya 2 obat TMS dari > 20 Industri Farmasi yang sama setiap tahunnya (2011 – September 2014)

Jawa Barat Jawa Tengah Jawa Timur Banten

3 ₂ 3 ₂

Sebaran 10 Besar Industri Farmasi yang diperintahkan untuk Recall Obat TMS Berdasarkan Provinsi Tahun 2011

- 2014

Jumlah IF

IF yg masuk dalam 10 besar terdapat di 4 Provinsi dan terbanyak di Jawa Barat dan Jawa Timur

(16)

PENARIKAN PRODUK

OBAT DARI IF JAWA

TIMUR

2013 -2015

TAHUN 2013



21 penarikan obat



10 industri farmasi



Penyebab :

1. TMS Kadar

2. TMS Disolusi

3. TMS pH

TAHUN 2014



23 penarikan obat



7 industri farmasi



Penyebab :

1. TMS Disolusi

2. TMS Kadar

3. TMS Pemerian

TAHUN 2015



27 penarikan obat



8 industri farmasi



Penyebab :

1. TMS Disolusi

2. TMS Kadar

(17)

TOPIK BAHASAN

CPOB DALAM PEMASTIAN MUTU PRODUK

TOPIK

BAHASAN

PENUTUP

TEMUAN INSPEKSI

TREND PENGAWASAN OBAT BEREDAR PROFIL INDUSTRI DI JAWA TIMUR

(18)

CPOB DALAM PEMASTIAN

MUTU PRODUK

Why GMP?

 Provides a high level assurance that medicines are

manufactured in a way that ensures their safety, efficacy and quality

 Medicines are manufactured to comply with their marketing authorization



Quality is built in



Testing is part of GMP, but alone does

not provide a good level of quality

(19)

Tujuan Utama GMP

Mengurangi risiko



yang tidak dapat dikontrol dengan

pengujian produk

atau



yang mempunyai ambang deteksi yang

rendah

Kontaminasi dan

kontaminasi silang

(20)

PRINSIP CPOB

• Produksi dgn “taking care”

• Tdk

tergantung hanya hasil pengujian saja

• Tdk memenuhi std

• Kontaminasi

• Keslhan penandan

• Bioavailability

• Keamanan dan efektivitas

• Standar senantiasa

berkembang dari waktu ke waktu

• Pedoman rinci utk jaminan mutu

• Merupakan standar minimal untuk

jaminan mutu

• Bukan mutlak

“best practices”

• Pelaksanaannya bukan presentase ( tdk menjadi

“predominant”)

(21)

GMP: „soft” and „hard” law

„

Semua bagian sistem Pemastian Mutu hendaklah

didukung

….

(Bab I,Prinsip Manajemen Mutu CPOB 2012)



Ketersediaan personel yang kompeten...



Bangunan dan sarana serta peralatan yang cukup dan

memadai...

Impossible to specify the values in a law!

(22)

Quality Management Cascade

Quality relationships

Quality Management (overall policy)

Quality Assurance (concept ensuring that the policy

is achieved)

GMP (how to do it)

(23)

PIC/S The 10 Golden Rules of GMP (1)

Golden Rule # 1

Get the facility design right from the start

Ex. Facility layout

Aim to :



Remove unnecessary traffic in the production area which

could result in a hazardous environment



Segregate materials, products, and their components to

minimize confusion and potential for mix-up and errors

(24)

PIC/S The 10 Golden Rules of GMP (2)

Golden Rule # 2

Validate processes



All validation activities should be well planned and clearly

defined

VMP



Consider all the critical parameters that may affected and

impact product quality



Define the testing and documentation required



If a change to the validated state is required then it must

be subject to change control evaluate the impact of

the change and define the extent of re-validation

(25)

PIC/S The 10 Golden Rules of GMP (3)

Golden Rule # 3

Write good procedures and follow them

 Procedures should be clear, concise and logical

 Frequently, the steps in the procedures may not appear to be the most efficient way of working taking shortcut may save time or make it easier, but :

never deviate from a written procedure without the approval of a supervisor or the Quality Department, Because :

 Many shortcuts may create pitfalls that can be costly in the end

 Each step in a procedures has been included for a purpose

(26)

PIC/S The 10 Golden Rules of GMP (4)

Golden Rule # 4

Identify who does what

There should be no gaps or overlaps in responsibilities

Golden Rule # 5

Keep good records

It is essential part of GMP to keep accurate records, and

during an audit, it helps convey that you are following

procedures. It also demonstrates that processes are known

and under control

‘If it’s not written down then it didn’t happen!”

(27)

PIC/S The 10 Golden Rules of GMP (5)

Golden Rule # 8

Maintain facilities and equipment

 Prevent equipment breakdown

 Reduce the risk of product contamination

 Maintains the “validated state” of the facility or equipment

Golden Rule # 9

Build quality into the whole product lifecycle

 Controlling components

 Controlling the manufacturing processes  Packaging and labeling controls

 Holding and distribution controls 27

(28)

PIC/S The 10 Golden Rules of GMP (5)

Golden Rule # 6

Train and develop staff



It’s essential to have the right people to do the right job



Do your employees have the skills and knowledge to

complete their job?



Have you equipped them with the right tools?

Golden Rule # 7

Practice good hygiene

The fight against contamination is a constant battle and is

one that requires attention of every single employee, every

day

(29)

PIC/S The 10 Golden Rules of GMP (5)

Golden Rule # 10

Perform regular audit



Self Inspection



CAPA System

(30)

TOPIK BAHASAN

CPOB DALAM PEMASTIAN MUTU PRODUK

TOPIK

BAHASAN

PENUTUP

TEMUAN INSPEKSI

TREND PENGAWASAN OBAT BEREDAR PROFIL INDUSTRI DI JAWA TIMUR

(31)

Deficiencies (Temuan)

• Deficiencies are descriptions of non-compliance with GMP requirements

• A distinction is made between deficiencies as a result of : - a defective system or,

- failure to comply with the system

• Deficiencies may be classified as :

- Critical Observation – potential risk harm to the user - Major Observation – major deviation from GMP

(32)

Common deficiencies during BPOM

Inspection

• Bangunan dan fasilitas (3.4, 3.14, 3.15, 3.29)

-

Lapisan dinding epoksi retak - Plavon rusak di ruang timbang

- AHU belum dilengkapi dengan HEPA Filter (H13) pada final filter di ruang produksi non beta laktam

- Potensi terjadinya mix up

• Produksi (6.7, 6.9, 6.11, 6.12)

-

Prosedur/Instruksi kerja yang telah ditetapkan tidak dilaksanakan secara konsisten

- Potensi terjadinya mix up

(33)

Common deficiencies during BPOM

Inspection

• Dokumentasi

- Pengisian dokumen yang tidak lengkap

- Perubahan yang tidak didokumentasikan

- Tidak ada logbook pemakaian alat

- Perbaikan pengisian dokumen tidak sesuai dengan

kaidah CPOB

(34)

Common deficiencies during BPOM

Inspection

• Pengawasan Mutu

- Tidak melakukan uji penetapan kadar (misal vit B1)

- Tidak melakukan Uji Kesesuaian Sistem KCKT

- Larutan titer belum ditetapkan masa simpannya

- Tidak dilakukan pengecekan pH dapar media disolusi

sebelum digunakan

- Baku pembanding yang digunakan adalah sampel

pertinggal bahan baku tapi tidak dibakukan terhadap

baku pembanding primer

(35)

Common deficiencies during BPOM

Inspection

• Kualifikasi dan Validasi

- Belum melakukan re-validasi metode analisa yang

mengalami perubahan

- Belum melakukan validasi metode analisa

- Laporan validasi tidak lengkap

- Kalibrasi alat sudah lewat waktu atau tidak

terdokumentasi dengan baik

- Sertifikat kalibrasi internal kurang memadai

- Kalibrasi dilakukan oleh personel yang tidak

terkualifikasi

(36)

Product Recall

(TMS Disolusi dan TMS Kadar)

PRODUCTION

or

QC LAB

or

BOTH

??

DEFECTIVE SYSTEM or

FAILURE TO COMPLY

??

ROOT CAUSE ANALYSIS

(37)

Out of Specification (HULS)

OOS results may indicate

a flaw in product or process design



Lack of robustness in product formulation



Inadequate raw material characterization or control



Substantial variation introduced by one or more unit

operations of the manufacturing process



Combination of these factors

Consider to redesign of the product or process be undertaken

to ensure reproducible product quality.

Don’t

forget the

regulatory aspect due to the change of the design.

(38)

CAPA & ROOT CAUSE ANALYSIS



Set in motion by :

- a laboratory investigation

- a manufacturing inconsistency

- a regulatory or internal audit

- a costumer complaint



The more comprehensive and structured the investigation

process is, the more effective it will be

Don’t make a

“band aid” CAPA

(39)

CAPA & ROOT CAUSE ANALYSIS (2)

The majority of companies initiate their CAPA processes once

a field failure is discovered

its too late because the patient is already at risk !!

(40)

TOPIK BAHASAN

CPOB DALAM PEMASTIAN MUTU PRODUK

TOPIK

BAHASAN

PENUTUP

HASIL PENGAWASAN INDUSTRI FARMASI DI JAWA TIMUR TREND PENGAWASAN OBAT BEREDAR

PROFIL INDUSTRI DI JAWA TIMUR DASAR HUKUM TERKAIT CPOB

(41)

The Cost of Non-Compliance (1)

The (Internal) Cost

• Direct Costs

- Related to Product Failure, Scrap, etc

• “Continual Crises” Costs

- Unexpected costs associated with Quality System / GMP non compliance

- Reactive (noncompliant) versus preventive (compliant) approaches

• Remediation Costs

(42)

The Cost of Non-Compliance (2)

The (External) Cost

• Regulatory Action Costs

- Related to legal, 3rd_{party, disgorgement, etc}

- Related to Recalls, Discontinuation, Suspended Operation, etc

• Market Share Costs

- Related to volumes, Supply availability/reliability, etc

• Reputational Costs

- Related to product spillovers, corporate spillovers, shareholder value, etc

(43)

The Benefit of Compliance (1)

• Improved Process Efficiency

- Related to higher yield, lower cycle time, lower

failure, etc

• Lower Investigations / Risks

- Related to deviations, rejects, OOS, etc

• Increased Customer Satisfaction

- Related to lower returns, lower complaints, etc

- Which translate to reputation, market share, etc

(44)

12. Compliance Program Regularly Reviewed and Improved

8. Culture of Compliance Behaviour

9. Compliance Control in place

Risk Assessment Conducted 10. Compliance Performance Monitored 11. Compliance Demonstrated and Documented

PENUTUP

3. Appropriate resources Allocated 7. Competency &

Training Addressed

Compliance program – 12 Building Blocks (AS 3806)

44 4. Objectives documented endorsed 2. Compliance policy 6. Responsibilities Assigned

5. Compliance Obligation Identified & Assessed

1. Top Management Commitment Commitment Organization & Standards Organization & Planning Implementation Maintenance and Improvement

(45)

PENUTUP



GMP IS COMMON SENSE



COMPLIANCE TO GMP

GOOD QUALITY PRODUCT



GOOD QUALITY PRODUCT

PATIENT SAFETY AND

EFFECTIVE MEDICATION

REDUCE HEALTH COST



NON-COMPLIANCE TO GMP INCREASE COST

REGULATORY

SCRUTINY

PUBLIC TRUST &

PRODUCT BRANDING

(46)

PUSTAKA

 CAPA and Root cause Analysis

http://www.pharmamanufacturing.com/articles/2006/145/

 Examples of critical and major observations from GMP inspections of Manufacturing, QC and Contract Research Organization, Ian Thrussel

 Good Manufacturing Practices Purpose and Principles of GMP, Tony Gould

 Good Manufacturing Practices in the Manufacture of Medicine

 Kebijakan Pengawasan Produksi Obat, Deputi Bidang Pengawasan Produksi Produk Terapetik dan Napza Badan POM RI

 Pedoman CPOB tahun 2012, Badan POM RI

 Pharmaceutical Quality Systems (ICH Q10) Conference – Business Case for Quality, Jeffrey Macher, PhD

 Risk Management, Soemarno

 White Paper PIC/S 10 Golden Rules of GMP

www.pharmout.net

(47)

(1)

The Cost of Non-Compliance (2)

The (External) Cost

• Regulatory Action Costs

- Related to legal, 3

_{party, disgorgement, etc}

- Related to Recalls, Discontinuation, Suspended Operation, etc

• Market Share Costs

- Related to volumes, Supply availability/reliability, etc

• Reputational Costs

- Related to product spillovers, corporate spillovers, shareholder

value, etc

(2)

The Benefit of Compliance (1)

• Improved Process Efficiency

- Related to higher yield, lower cycle time, lower

failure, etc

• Lower Investigations / Risks

- Related to deviations, rejects, OOS, etc

• Increased Customer Satisfaction

- Related to lower returns, lower complaints, etc

- Which translate to reputation, market share, etc

• Superior Return of Investment (ROI)

(3)

12. Compliance Program Regularly Reviewed and Improved

8. Culture of Compliance Behaviour

9. Compliance Control in place

Risk Assessment Conducted 10. Compliance Performance Monitored 11. Compliance Demonstrated and Documented

PENUTUP

3. Appropriate resources Allocated 7. Competency &

Training Addressed

Compliance program

–

12 Building Blocks (AS 3806)

44 4. Objectives documented endorsed 2. Compliance policy 6. Responsibilities Assigned

5. Compliance Obligation Identified & Assessed

1. Top Management Commitment Commitment Organization & Standards Organization & Planning Implementation Maintenance and Improvement

(4)

PENUTUP



GMP IS COMMON SENSE



COMPLIANCE TO GMP GOOD QUALITY PRODUCT



GOOD QUALITY PRODUCT

PATIENT SAFETY AND

EFFECTIVE MEDICATION

REDUCE HEALTH COST



NON-COMPLIANCE TO GMP INCREASE COST

REGULATORY

SCRUTINY

PUBLIC TRUST &

PRODUCT BRANDING

(5)

PUSTAKA

 CAPA and Root cause Analysis

http://www.pharmamanufacturing.com/articles/2006/145/

 Examples of critical and major observations from GMP inspections of Manufacturing, QC and Contract Research Organization, Ian Thrussel

 Good Manufacturing Practices Purpose and Principles of GMP, Tony Gould

 Good Manufacturing Practices in the Manufacture of Medicine

 Kebijakan Pengawasan Produksi Obat, Deputi Bidang Pengawasan Produksi Produk Terapetik dan Napza Badan POM RI

 Pedoman CPOB tahun 2012, Badan POM RI

 Pharmaceutical Quality Systems (ICH Q10) Conference – Business Case for Quality, Jeffrey Macher, PhD

 Risk Management, Soemarno

 White Paper PIC/S 10 Golden Rules of GMP www.pharmout.net

(6)