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 2017
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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…..?

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Good regulation can offer competitive economic advantage
Supports development of dynamic, innovative and sustainable
healthcare system
Being too cautious can cause negative consequences
“Protect and enable” instead of “Protect or enable”

“It is the duty of government to

make it difficult for people to do
wrong, easy to do right.”
Smart
William E Gladstone
Regulator
Relevant, Responsive & Ready
 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 14
PERLU KESEIMBANGAN REGULATORY
(Regulatory Balance)

Flexibility

Transparency Empowerment

Accountability Risk management

Sumber: WHO
 KONSEP & BEBERAPA
PENGERTIAN GRP/GDRP

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SUMBER : APEC
Merupakan skim voluntari yang disusun suatu kelompok atau
organisasi dalam bentuk Code of Practice
Ruang lingkup mencakup topik antara lain Standar, Informasi
yang dibutuhkan dan Mekanisme untuk menyelesaikan masalah.
Code of Practice dapat efektif sebagai alat untuk peningkatan
kepercayaan konsumen, dan sarana komunikasi yang efektif
antara konsumen dan suplair.
Efektivitas Code of Practice tergantung pada peran aktif
pemangku kepentingan yang terlibat, sanksi bagi yang tidak
patuh (non-compliance), dan sampai seberapa jauh konsumen
dan pemangku kepentingan terlibat dalam proses monitoring dan
evaluasi.

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SUMBER : USA-EU Commission - High level Regulatory
Cooperation Forum Common Understanding on Regulatory Principles
and Best Practices
evidence based policy making dengan mempertimbangkan juga
pada Benefit/Cost Ratio,
adanya keterbukaan dan transparansi yang melibatkan semua
pemangku kepentingan,
adanya analisa akan alternatif regulatori dan best practices yang
relevan
adanya kegiatan monitoring dan evaluasi akan efektivitas
regulatory measure yang berlaku
pendekatan yang menekankan pada minimalisasi beban dan
mengarah pada sistem yang tidak rumit.

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SUMBER : WHO
Prinsip dasar Best Practices bidang obat dan produk kesehatan lain
harus menekankan bahwa upaya regulatori :
harus dilakukan melalui proses terbuka dan transparan
harus mendorong akuntabilitas dan partisipasi masyarakat dan
pemangku kepentingan
harus dilaksanakan dalam waktu yang memadai, dengan
kesempatan dan alat yang tepat pada setiap tahap, mulai dari
persiapan kebijakan sampai saat adopsi konsep final
harus disusun berdasarkan pertimbangan Benefit dan Cost
(kualitatif dan kuantitatif)
harus memiliki mekanisme monitoring dan evaluasi secara
berkala.

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SISTEM REGULASI YANG
BAIK DALAM KERANGKA
GRP/GDRP

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Pemanfaatan prinsip Risk Management
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
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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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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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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 records

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 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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 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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Be aware of, and prepare for, global impact & trends:
– Multinational clinical trials
– Harmonization
– 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
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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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 KERANGKA STRUKTUR FUNGSI REGULATORI UTAMA
DAN UNIT YANG BERTANGGUNG JAWAB
Administrative
elements

• Policy, legislation,
regulations
• Human resources
• Finance Regulatory functions
• Infrastructure

Technical
elements

• Standards Licensing of Inspection of Product Monitoring Control of Adverse drug

• Specifications premises, manufactures, assessment quality drug promotion reaction
• Guidelines practices & & &
• Procedures of drugs & advertising monitoring
persons distributors registration

*) Effective drug regulation, a multi country study, WHO 2002

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 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 37
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