Kuliah 2

PRINSIP CARA
REGULATORI OBAT
YANG BAIK
(GRP- Good Regulatory
Practices)
Lucky S Slamet

Mata Kuliah Regulasi dan Etika Farmasi

Program Pasca Sarjana Studi Ilmu kefarmasianUNIVERSITAS PANCASILA
Tahun Akademik 2019
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PENDAHULUAN

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1. Medicines: underuse of
generics and higher than
necessary prices for
medicines
2. Medicines: use of
substandard and
counterfeit medicines
3. Medicines: inappropriate
and ineffective use
4. Health-care products and
services:
overuse or supply of equipment,
investigations and procedures
5. Health workers: inappropriate or
costly staff mix, unmotivated
workers
6. Health-care services:
inappropriate hospital admissions
and length of stay
7. Health-care services:
inappropriate hospital size (low use
of infrastructure)
8. Health-care services: medical
errors and
suboptimal quality of care
9. Health system leakages:
waste, corruption and fraud
10. Health interventions: inefficient
mix/
inappropriate level of strategies
R&D and clinical trials R&D
priorities
Patent Conflict
of interest
Manufacturing Tax evasion
Registration Counterfeit/ High prices
substandard
Cartels Inspection
Selection Pressure
Unethical
donations Collusion Procurement & import
Over-
Thefts
Distribution invoicing
Waste
Falsification
Losses
Pricing
safety/ Bribery
efficacy data Prescription
Inappropriate
use Unethical
Dispensing
State Capture Promotion
promotion Pharmacovigilance
Mengapa GRP/GDRP sangat
penting dalam Regulasi
Farmasi/ Bidang Obat…..?

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KEDUDUKAN OBAT DALAM
PELAYANAN KESEHATAN
PEMERINTAH bertanggung jawab
atas ketersediaan,
keterjangkauan dan pemerataan
obat esensial yang dibutuhkan
masyarakat serta jaminan agar
pasien mendapat pengobatan
yang rasional dengan produk
obat yang aman, berkhasiat dan
bermutu

MASYARAKAT KESEIMBANGAN
memiliki hak atas ANTARA FUNGSI PELAKU USAHA
informasi obat yang SOSIAL, PERAN bertanggung jawab
benar, lengkap dan TEKNOLOGI, &
UNSUR
penuh atas khasiat,
tidak menyesatkan keamanan dan mutu
dan perlu terlibat EKONOMI
obat sesuai dengan
dalam pengambilan fungsi usahanya.
keputusan
pengobatan
 PERUBAHAN
KRISIS KEUANGAN
GLOBALISASI
TEKANAN
EPIDEMIOLOGI DAN
DEMOGRAFI
KEMAJUAN TEKNOLOGI
KOMUNIKASI
PERUBAHAN ARAH R&D
REFORMASI YANKES
ERA 2011-2020++
ERA 1980 - 2000
EKONOMI YG BERFLUKTUASI 7.6-
STABILITAS EKONOMI
9.4 %
6 -6.9% PRODUK
OBAT POPULASI GLOBAL BERUMUR 65+
POPULASI GLOBAL
BERUMUR 65+ EPIDEMIK OBESITAS

MEDIA : CETAK, TV, SITUS, MEDIA SOSIAL : FB, Instagram,

WEB twitter dll

BISNIS MODEL BLOCKBUSTER BISNIS MODEL SPECIALIST

MEDICINE
PENGOBATAN KONDISI
KRONIS PENGOBATAN PENY LANGKA
/AKUT
PEMASARAN OBAT KE
PEMASARAN PRODUK KE HEALTH
PRIMARYPHYSICIAN CARE
CARE PAYER
 JAMINAN BERKESINAMBUNGAN
MUTU, KEAMANAN dan EFEKTIVITAS (EFIKASI)
LANDSKAP PENGEMBANGAN, PRODUKSI & DISTRIBUSI OBAT BERUBAH SECARA DRAMATIS

• SKEMA ASURANSI
KESEHATAN
• COST-EFFECTIVENESS
(HTA, RW BIG
DATA/RWE)
• TEROBOSAN EVALUASI
PRE MARKET KESEIMBANGAN
• QA BERBASIS IT
•PERAN SERTA
PASIEN/MASY.

PENINGKATAN
vs
JAMINAN AKSES OBAT UPAYA EFISIENSI
YANG AMAN, EFEKTIF PENGEMBANGAN,
DAN TERJANGKAU – PRODUKSI dan
UNIVERSAL HEALTH DISTRIBUSI OBAT
COVERAGE (UHC)
 Perubahan PARAGDIGMA sesuai Cara Regulatori yang Baik
(GRP: Good Regulatory Practices)
Melindungi masyarakat secara purna dari produk obat yang tidak memenuhi
persyaratan (Jaminan KKM dan Penegakan Hukum/Law Enforcement)
Produk Obat dapat memberikan keuntungan ekonomi yang kompetitif (Competitive
Economic Advantage)
Mendukung pengembangan sistem pelayanan kesehatan yang dinamis, inovatif dan
berkesinambungan
Penerapannya perlu dilakukan dengan profesional, untuk tujuan perlindungan publik
dengan jaminan KKM. (“Protect and enable” instead of “Protect or enable”)

Jaminan Khas, Peningkatan Yan-Publik

Kam, Mutu (KKM) (Transparansi,integritas, “It is the duty of
utk Melindungi kompetensi,akuntabilitas) government to make it
KesMas
difficult for people to do
Keseimbangan wrong, easy to do right.”
Risk Based Approaches William E Gladstone
 Values & Principles Focus on Impact & Results

Traditional Less reliance

• Accountable, on output
Transparent measures

New Greater focus on risk

• Effective, management
Resource • Identify important
efficient problems and fix them
• Organize tools around
work, not vice versa
 Products Premises/Players Users/Consumers
(Manufacturers/Dealers/ (Healthcare Professionals/
Healthcare Professionals) Patients/Consumers)

Inherent Risks Knowledge Level Knowledge Level

Extrinsic Risks Operational Mgt Risk Appetite

Inherent risks
Mostly known based on disclosures by players or current scientific
knowledge
Managed by pre-market controls and post-approval conditions

Extrinsic risks
Usually unknown but may be predicted from trends/experience or
minimized through process controls
May be managed by post-market tools
 Products Premises/Players Users/Consumers
(Healthcare Professionals/ (Healthcare Professionals/
Manufacturers/Dealers) Patients/Consumers)

Inherent Risks Knowledge Level Knowledge Level

Extrinsic Risks Operational Mgt Risk Appetite

Different competencies of practitioners, manufacturers & dealers

Desired competencies linked to practice & product risks
Influencing factors:
Realities of prevalent business practices & supply chains
Communication & cost strategies
Resource considerations
Appropriate mix & calibrated applications of regulatory tools
 Products Premises/Players Users/
(Manufacturers/Dealers/
Healthcare Professionals)
Consumers
(Healthcare Professionals/
Patients/Consumers)
Inherent Risks Knowledge Level Knowledge Level
Extrinsic Risks Operational Mgt Risk Appetite

For certain high risk products (e.g. cell & tissue therapy, medical
devices)
No direct patient access - not able to make informed risk
decisions
Physicians act as main gatekeepers
Regulatory approach & interaction focused on gatekeepers
For certain low risk products
Caveat emptor & minimal pre-market oversight appropriate
Can lower evidence based treatments be allowed with conditions/
oversight, e.g. “adaptive licensing”?
 Risk linked to Impact

Risk
Assessment High IMPACT RATING

• Inherent Risks
Resources Impact
• Internal controls
Assessment
• External controls
• Systemic Impact
• Reputational
RISK RATING Low Impact
Low High
 Over- Under-
regulation regulation

Smart Regulation
“test of reasonableness”
1. Lisensi untuk industri, impor, ekspor,distribusi, dan
promosi/iklan
2. Penilaian Khasiat, keamanan, dan mutu produk
dan pemberian persetujuan pendaftaran
3. Inspeksi dan surveillance industri, importir,
distributor dan apotek
4. Kontrol dan monitoring mutu dan keamanan
(Pharmacovigilance) obat di pasar
5. Kontrol dan monitoring promosi dan iklan obat
6. Pemberian informasi independen tentang obat

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 Rangkaian Dinamika Obat dan Vaksin
Jaminan Khasiat, Keamanan, KEAMANAN MUTU
Mutu & keabsahan KEABSAHAN

CPOB di
KHASIAT IND FARM

RS Apotek Toko Obat

KEAMANAN (Obat Resep/ Obat bebas
Bebas)

MUTU
Izin Edar

KEABSAHAN DIST

PENGGUNAAN OBAT YANG

BERKUALITAS / RASIONAL
CDOB di SRN DIST 17
PERLU KESEIMBANGAN REGULATORY
(Regulatory Balance)

Flexibility

Transparency Empowerment

Accountability Risk management

Sumber: WHO
 SISTEM REGULASI YANG
BAIK DALAM KERANGKA
GRP/GDRP :
BEBERAPA PRINSIP UTAMA

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(Pemanfaatan prinsip Risk Management)
Science-based risk management, with risk-based
decision-making
Precautionary principle: “absence of full scientific
certainty shall not be used as a reason to postpone
decisions when faced with the threat of serious or
irreversible harm”
Proactive – take initiative to address and prevent public
health & safety concerns, such as Bovine spongiform
encephalopathy/Creutzenfeldt-Jakob disease
Know own strengths and weaknesses:
– Consult with experts on complex
scientific, medical, or regulatory issues
– Implement and make use of scientific advisory committees
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(Penetapan regulasi yang mempertimbangkan peluang
fleksibilitas dengan scientific evidence based)

Regulations should:
– Cover principles broadly
– Provide sufficient protection to the public
– Strike a balance between protection of the
public and enabling R&D
– Be forward-looking, allowing flexibility for
regulating in the current and future
environment

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Adopt international guidelines when
appropriate
Develop SOPs:
– Good guidance practices (e.g GMP, GLP)
– Good review practices
Develop and implement guidelines to address
regional issues
Be aware of drivers, such as globalization
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( Pemberian Informasi dan manajemen pencatatan yg
efisien)
Develop and implement tools to manage documents
and information submitted by sponsors
– Maintain accurate records with a numbering system for
sponsor and products submissions
– Clinical trial / standardization applications, amendments
and notifications
– PMS/PMV database for integration and analysis
– Submission allocation database
– Clinical trial inspection database
System to manage other information such as general
enquiries
Ensure security and maintain confidentiality of 23
(Kawalan terhadap kinerja, transparansi,
akuntabilitas dan Good Governance)
Measure workload and performance at periodic
intervals (e.g., quarterly)
Use information on workload and performance
to develop/revise business plans
Publish performance measures periodically
(e.g., annually)
– Number of clinical trials, protocol amendments,
notifications, ADRs, types of trials, etc.
– Submission processing and review times

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Provide opportunities for dialogue with sponsors
and stakeholders formally and informally (e.g., pre-
clinicaltrial meetings, telephone conferencing, informal
email enquiries)
Provide for appeal processes and opportunities for
reconsideration of final decisions
Consult with all stakeholders before implementing
or adopting new regulations, policies, and guidelines
Consult with stakeholders as early as possible
Communicate horizontally within organization
Seek lessons learned through impact analyses

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(Perimbangan antara riset dan akses produk
kesehatan untuk masyarakat - regional)
Analyze regional factors:
– Population (e.g., demographics, disease prevalence)
– Health care system and infrastructure
– Available expertise
– National support in research funding
– Regulatory frameworks for importation and sale of
health products
– Geographic location and neighbouring countries

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 (Perimbangan antara riset dan akses produk
kesehatan untuk masyarakat -Global)
Be aware of, and prepare for, global impact & trends:
– Multinational clinical trials
– Harmonization and Convergence
– Decreased number of blockbuster drugs & exponential
rise in generics
– Personalized medicine, pharmacogenomics
– Rising costs and emerging markets
– In choosing to place a clinical trial, companies will
look for countries with the appropriate laws, along with the
required population, disease prevalence, health care
system, qualified investigators and staff, with high
standards of professional integrity and ethics 27
BAGAIMANA
IMPLEMENTASINYA?

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 3 PILAR UTAMA CARA REGULATORI OBAT YANG BAIK
(GRP/GDRP)

Cara Uji Klinik yang Baik (GCP) CPOB terkini (cGMP)

Cara Distribusi Obat

CPOB terkini (cGMP) yang Baik (GDP)

Spesifikasi dan mutu BBO,

Cara Sampling Obat
Obat jadi, kemasan
yang Baik (GSmP)
(Farmakope dan
non-kompendia) GRP/
GDRP
Cara berlaboratorium
Penegakan hukum (law yang baik (GLP)
enforcement) dengan efek jera
tinggi

Cara berlaboratorium
yang baik (GLP)
Inspeksi Penyidikan dan pro-justicia Audit Komprehensif

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 Diperlukan
LEGAL BASIS
berupa Undang
Undang

Diperlukan
KOMPETENSI SDM
& KOMITMEN
dalam
IMPLEMENTASI

Source : WHO Effective Drug Regulation, a Multicountry study – 2002

( Ms Sauwakon Ratanawijitrasin and Mr Eshetu Wondemagegnehu)
 SUMBER DAYA KOORDINASI
(MANUSIA & DANA) KEBIJAKAN PUBLIK -
DASAR KEWENANGAN
dan INTERNAL &
FULL SPECTRUM
HUKUM EKSTERNAL
INFRASTRUKTUR
(OTORITAS OTONOMI)

Apabila pelaksanaan tugas dan fungsi NRA Organisasi dan

dilakukan oleh beberapa institusi pengawas Infra-Sruktur NRA harus
yang berbeda dimana jenis struktur organisasi, dirancang sedemikian rupa
komando dan kontrol yang dilakukan sehingga ada koordinasi
tidak terkoordinasi maka tugas dan fungsi NRA yang pusat-daerah di seluruh
dimandatkan dalam legislasi dan regulasi terkait akan negara dengan
terfragmentasi sehingga tujuan keseluruhan yaitu tanggung jawab
melindungi masyarakat secara menyeluruh tidak tercapai. dan akuntabilitas
*)Source : WHO Effective Drug Regulation, a Multicountry study – 2002
(Ms Sauwakon Ratanawijitrasin and Mr Eshetu Wondemagegnehu)
 Conceptual spheres of regulatory control

A Global sphere
Violations not B Regulatory
monitored G Sphere
Violations C Monitoring Sphere
monitored but F
not discovered D Violation
Sphere
Violations E Sanction
discovered Sphere

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Conceptual spheres of the
four main regulatory
functions

# facilities
requiring licensing

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GRP TOOLS :
RIA - REGULATORY 1. ISU
IMPACT ANALYSIS STRATE 2. TUJUAN
GIS UTAMA

6. 3.
KOMUNIKASI MEKANISME
RISIKO & PENCAPAIAN
KONSULTASI
RIS (REG & NON
REG)
REGULATORY
IMPACT 4. KAJIAN
STATEMENT MANAJEMEN
RISIKO

7.
OPSI USULAN/ 5.
REKOMENDASI KAJIAN
PELAKSANAAN COST/BENEFIT
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Agar terjadi perimbangan regulasi bidang farmasi Pre-Post Market
yang efektif dan efisien maka diperlukan upaya yang berdasarkan
konsep B/R Assessment dalam kerangka GRP/GDRP
Prinsip GRP mencakup antara lain Pemanfaatan prinsip Risk
Managemen; Penetapan regulasi yang mempertimbangkan
peluang fleksibilitas dengan scientific evidence based; Panduan
pengambilan keputusan yang konsisten dan efisien; Perimbangan
antara riset dan akses produk kesehatan untuk masyarakat;
Kawalan terhadap kinerja, transparansi, akuntabilitas dan Good
Governance
Penetapan GRP perlu mempertimbangkan lessons Learned
penerapan sistem regulatori dengan alat RIA dan penetapan RIS

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 GRP/GDRP Adalah suatu panduan cara regulatori
yang baik untuk menjamin bahwa produk obat yang
beredar memenuhi persyaratan terkini untuk aspek
mutu, keamanan dan khasiat sejak dari proses
pembuatan di pabrik; penyimpanan dan distribusi;
sampai diterima oleh end-users (pasien/konsumen)

GOALS :
1. Efisiensi : Keputusan yang cepat tetapi didasarkan bukti yang sahih dan
dapat dipertanggung jawabkan (Evidenced Based)
2. Efektivitas/produktivitas : Penggunaan resources yang ada dengan
optimal, cost effectiveness
3. Peningkatan kinerja : Pencapaian mutu yang diharapkan dan tetap dapat
mempertahankan kinerja 36
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