Drug Policy Issue for Developing Countries

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LEGISLATION, REGULATION AND QUALITY ASSURANCE
ISSUES

• Drug Policy Issue for Developing Countries
• Yogyakarta - Indonesia
• 29 September 9 November 2001

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National Drug Policy
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Why Legislations and Regulation on Pharmaceutical
are Necessary ?

• Pharmaceutical concern the whole population
• Pharmaceutical involve many parties (patients,
  doctors, other health workers, manufactures,
  distributors, researchers etc)
• Pharmaceutical involve important health risks
  there are serious consequence from the lack
  or misuse of drugs
• Informal control are insufficient

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STAGES OF DRUG DEVELOPMENT
Pre-Clinical Study Stage
Clinical Study Stage
Research on New Molecule ( 5-10 yrs)
Pre-Marketing Evaluation Registration
Marketing Approval
PMS
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TREND ON DRUG RESEARCH DEVELOPMENT (RD)
Current Approach Molecular Biotech Research
Selection Gen Screening
R D
Drug Design
Biochemical Approach
Clinical Research
Active Substance Test/Analysis
Pre-Clinical Research
Effectiveness Study
Pharmacodynamic Pharmacokinetics Toxicology,
Teratogenicity Mutagenicity, Carcinogenicity
Phase I, II, III
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Element of a Comprehensive Drug law (1)

• General Provision
• Control of Availability and Marketing
• Drug Registration (Pre-Marketing Authorization)
• NED List/ National Formulary
• Scheduling, Prescription, and dispensing
  authority
• Labeling
• Generic Labeling, Manufacturing, and Substitution
• Information and advertising
• Public Education
• Imposition of fees
• Price Control
• Special Products (herbal medicines, orphan drugs)

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Elements of a Comprehensive Drug Law (2)

• Control of Supply Mechanism
• Importation of drugs
• Exportation of drugs
• Controls, incentives, disincentives for local
  manufacture
• Control of distribution, supply storage, and sale
• Drug control Administration/Drug Regulatory
  Authority
• Powers to Make Rules and Regulations
• Repeals and Transition Provisions
• Exemptions from provision of the law

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Stages in the Evolution of Legislative /
Regulation (1)

• Examples
• A Drug Registration/Pre-Marketing Authorization
  System
• Stage 1. Notification Procedure
• Standard information on all pharmaceuticals for
  sale ? enter into a register.
• No judgment is made regarding the appropriateness
  of drug for sale

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Stages in the Evolution of Legislative /
Regulation (2)

• Stage 2 Basic Authorization Procedures
• Drugs listed in the register are provisionally
  authorized to remain on sale
• All new drugs for sale require a license after
  assessment for E, S, Q and completeness of
  packaging information

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Stages in the Evolution of Legislative /
Regulation (3)

• Stage 3
• Full Registration or Licensing Procedures
• Evaluation of individual products is conducted
  by examining detailed data from the manufactures
  (and from the literature)
• ? to Assess Q, E, S.
• Stage 4
• Re-evaluation of Older Drugs
• All older drugs on the market are systematically
  reassessed.

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THE EVOLUTION OF U.S. DRUG LAW

• Food and drug Act (1906) required only that
  drugs meet standards of strength and purity. The
  burden of proof was on FDA on the drug labeling
  prior to marketing
• Federal Food, drug and cosmetic Act (1938)
  revised the 1906 drug law after the tragedy of
  107 people died caused by the elixir of
  sulfanilamide, required a manufacturer to prove
  the safety of drug prior to marketing
• Durham-Humphrey Amendment (1951) defined R/
  drugs as those unsafe for SM and should only
  under a doctors supervision

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THE EVOLUTION OF U.S. DRUG LAW

• Kefauver-Harris Drug Amendments (1962) tighten
  control over drug prior to marketing due to the
  Thalidomide reports, a manufacturer is
  responsible not only on safety, but also
  effectiveness for the intended use. After
  marketing, ADR must be reported to FDA, and
  complete information on risk and benefit must be
  available
• Orphan Drug Act (1983) encourage development of
  products which are for treating diseases. The law
  allows manufacturer to take tax deduction for ¾
  of the cost of CT

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THE EVOLUTION OF U.S. DRUG LAW

• Drug Price Competition and Patient Term
  Restoration Act (1984) expands the of drugs
  for ANDA make it less costly and time consuming
  for generics to reach the market
• Generic Drug Enforcement Act (1992) imposes
  debarment and other remedies for criminal
  convictions based on activities relating to the
  approval of ANDAs
• Prescription Drug User Fee Act ( 1992)
  regulates user fees for certain NDA and
  supplements, an annual establishment fee, and
  annual product fees.

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THE EVOLUTION OF U.S. DRUG LAW

• FDA Modernization Act (1997) contains
• some of the most significant changes to the
  Food, Drug and Cosmetic Act in 35 years, such as
• reauthorization of PDUFA through FY 2002
• changes of assessment and collection of user
  fee, i.e.waiver of fee for orphan products,
  pediatrics suppl.
• codifies FDAs accelerated approval and fast
  track.
• issuance of guidance for NDA reviewer

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DRUG / NATIONAL REGULATORY AUTHORITY (DRA/NRA)

• A network that administer the full spectrum of
  drug regulatory activities, including at least
  the following functions
• MA for new products and variation of existing
  authorization
• QC laboratory testing
• Adverse Drug Reaction
• Provision of any drug information and formation
  of RUD and other distribution channels
• Enforcement operations
• Monitoring of Drug Utilization

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PROVISIONS AND PREREQUISITS FOR REGULATORY CONTROL

• Political will and commitment
• Legislation
• Accountability
• Resources for MA function (Staff, Premises,
  Archiving, Computers, Experts Advising Body)
• Fees and Cost Recovery
• Inventory of existing products on the market
• Rational selection of products (public health
  need, number of interchangeable products, price)
• Special Access Scheme
• PMS

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Guiding Principles for Small DRA/NRA (1)

• Objectives
• To establish a frame work for drug regulation
• The primary responsibility of DRA/NRA (i) to
  operate a system of administration and
  enforcement so that drugs conform to acceptable
  Q, S, E, (ii) promotion and marketing of drug is
  similar to PI approved (iii) Manufacturing,
  distribution, Supplying, dispensing and use
  conform with the requirements

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Guiding Principles for small DRA/NRA (2)

• A Mandatory system of licensing/authorizing of
• All medicinal product (local or import)
• All manufacturer, importing and exporting agents,
  distributors
• All premises and facilities to manufacturer,
  store, distribute
• All stages of manufacturing and distribution of
  product are supervised by qualified personnel
• An efficient system of inspection with access to
  QC laboratory facilities
• The legislation is enforceable

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Guiding Principles for Small DRA/NRA (3)

• Example Pre Marketing Authorization
• With the limitation on human, financial,
  scientific, and technological resource
  decision may be guided by the regulatory status
  of the product in the country of origin based on
  information provided through the WHO
  Certification scheme on the Quality of
  Pharmaceutical products moving in International
  Commerce
• Need Knowledge of and acceptance of the standards
  and competence of the DRA/NRA of Exporting
  country by the DRA/NRA of the importing country

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BEST REGULATORY PRACTICES
GOAL Enhancing mutual understanding

• Should include procedures and outcomes
  transparent to applicant, health professional
  and the public
• The assessment products of pre-marketing approval
  of drug should be of a reasonable duration
  without compromising quality, safety and efficacy

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WHO has set up a new initiative the world
Alliance for Quality Pharmaceuticals in
International Commerce (WAQPIC)

• Strengthening national regulatory system
• Enhancing mutual understanding and collaboration
  at the international level
• Providing operational supports to global and
  regional harmonization efforts and
• Reducing circulation of substandard drugs

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WAQPIC

• Tools to assess regulatory capacity, training
  opportunities, information exchange mechanism and
  forum for discussion
• Partners
• National/regional regulatory bodies
• Pharmacopoeia Team
• Professional association
• Other UN organization

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REGULATORY HARMONIZATION IN ASEAN COUNTRIES
Brunei Darussalam
Vietnam
Cambodia
Thailand
Singapore
Indonesia
Lao-PDR
Philippines
Malaysia
Myanmar
HARMONIZATION SCHEMES OF PHARMACEUTICAL
REGULATION OF THE ASEAN COUNTRIES HAS BEEN
INITIATED IN 1999
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• THE SCOPE OF HARMONIZATION
• Includes harmonization of pharmaceutical product
  registration requirement in
• - Common Technical Requirement (CTR)
• - Common Technical Dossier (CTD)
• FOUR MAJOR AREAS ON CTR AND CTD AND THE LEAD
  COUNTRIES
• - Pharmaceutics (Quality) -
  Indonesia
• - Pharmacological and Toxicological
• data (Safety) - Philippines
• - Clinical data (Efficacy) -
  Thailand
• - Administrative data and Product
• Information - Malaysia

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REGULATION AND LEGISLATION ON PHARMACEUTICAL
INDONESIA EXPERIENCE
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LEGAL BASIS FOR NA DFC
ACT 8/99 CONSUMER PROTECTION
ACT 7/96 FOOD
ACT 23/92 HEALTH
CENTRAL GOVERMENT GR 25/2000
ACT 69/99 FOOD LABELING
GR FOOD SAFETY AND QUALITY
GR 72/98 PHARM. SAFETY
GR 81/99 SMOKING
DECENTRALIZATION PP 22/2000
DRUG AND FOOR CONTROL
NA-DFC DECREE ORG. STR
PRES DECREE 165/2000 MOH
PRES DECREE 166/2000 NA-DFC
MD ORG. ST.
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(No Transcript)
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ASPEK LEGAL BIDANG OBAT
Act 8/99Consumer Protection
Ordonant 419/49 Drugs
GR 72/98 Pharm. Med. Devices Control
Act 23/92 Health
GR 17/2001PNBP/Fee
NA-DFC Decree HK.00.063.00685 (7-03-01)
Guidelines on Drug Registration (old 1971,
1980, 1990,1993)
MOH Decree 949/2000 Drug Registration
Quality, safety efficacy requirement
Ch II
Ch 39
MOH Decree 2380 Reg. of Generic Drugs
To protect comm, quality, safety, efficacy of
product
Ch III
MOH Decree 140/91 Reg. of Med. Dev. Household
Ch II
Production
Reg. Procedure Pre-submission, Reg.
MOH Decree 5417/89 Revaluation
Ch IV
Ch 40
Ch III
MOH Decree 925/93 Schedule
Comply with FI and standards
Distribution
Data requirement
Ch IV
Ch V
Ch 41
Marketing approval
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lanjutan
Ch V
Reg. Dossier
Export - Import
GR 32/91
Attachments
MOH Decree 415/80
Ch VIII
Guidelines
DG Letter 2243/94
Labeling Advertisement
MOH Decree 2380/83
MOH Decree 2396/86
Ch VIII, IX, X, XIII, XIV
DG Letters 13650/739159/8235/835660/83
Quality Assurance
MOH Decree 43/88 GMP
DGD 5411/89 GMP Implementation
MOH Ins. 186/80 ADR AEFI
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REGULATORY SYSTEM ON DRUG REGISTRATION IN
INDONESIA

• Started in 1971. Criteria for the registration
  1980 up dated in 1990, 1993 and 2000
• Based On Risk Assessment (Quality, Safety
  Efficacy) and actual need of the public health
• Since July 2000
• To improve efficiency on drug registration
  process in anticipating Global Harmonization
  trend
• To accelerate drug evaluation process without
  compromising S, E Q
• To provide transparent and efficient communication

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NEW REGULATION

• REGISTRATION FEES APPLICABLE FOR ALL DRUGS
• Implementation of fee with the concept of cost
  sharing, in force with GR 17/2001
• FASTER APPROVAL IN THE DECISION MAKING PROCESS
• A NEW COMPUTERIZED SYSTEM HAS BEEN INSTALLED FOR
  DRUG REGISTRATION (FERO)
• To support 2 main functions
• - document tracking
• - evaluation process of certain copy products
  (template)

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National Committee on New Drug Evaluation

• Consist of experts in the field of clinical
  pharmacology, pharmacy, biology and relevant
  clinicians
• Recruited from Universities and other relevant
  institutions
• Conducting meeting regularly to discuss the
  result of evaluation on the safety, efficacy and
  quality of drugs

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THE IMPLEMENTATION OF GCP

• GOOD CLINICAL PRACTICES
• Adoption of ICH-GCP
• GCP requirements which are not stated in the
  ICH-GCP
• Preparation of CT procedure

• REGULATION ON CT PROCEDURE
• AMONG OTHERS
• GCP requirements
• Import license requirement

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ADVERSE DRUG REACTION (ADR) MONITORING PROGRAMME

• Was started in 1975 as a pilot project
• As national programme since 1981
• Voluntary reporting system ? yellow card
• Publishing bulletin Berita MESO
• To arise the interest (active participation) of
  health practitioner
• Contains ADR evaluation reports and other
  information associated with ADR
• Twice / year
• Distributed to hospitals, physicians and other
  health professionals

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POST-MARKETING QUALITY ASSURANCE

• SStandardization of quality of raw materials,
  finished products (Indonesia Pharmacopeiae, USP,
  BP)
• LLicensing of drug establishment
• IImplementation of GMP and Inspection on GMP
  Compliance
• SSampling and Analysis of drugs
• IInspection Supervision of Drug Distribution
  channel

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DRUG PROMOTION ADVERTISEMENT

• Advertising of drugs is subject to the
  regulation no. 386 of 1994 which ensures
  advertisements are truthful, appropriate and do
  not mislead consumer
• Advertisement of prescription drugs to the
  general public is prohibited
• Prescription drugs may be advertised only in
  medical and pharmaceutical journal
• O.T.C. Drugs, can be advertised based on the
  information approved at the time of registration
• Day to day monitoring of advertisement is
  conducted by the drug inspectors at the
  provincial levels
• A committee was established to evaluate an
  advertisement before it is approved
• Product samples are prohibited to be given to
  physicians

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THANK YOU