Information regarding the regulatory requirements in Rest of the world

1. REGULATORY
REQUIREMENTS IN ROW
(REST OF THE WORLD)
PRESENTED BY:- JEEL PARAG JOSHI
M.Pharm Sem 1
Subject:- REGULATORY AFFAIRS
SAL INSTITUTE OF PHARMACY
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2. CONTENTS
 ROW COUNTRIES
 IMPORTANCE OF HARMONISATION
 INTRODUCTION
 DIVISION OF PHARMACEUTICAL MARKET
 OVERVIEW OF EMERGING MARKET
 DIFFERENCE BETWEEN REGULATED AND EMERGING MARKET
 REGISTRATION REQUIREMENT FOR REST OF THE WORLD
 CONCLUSION
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3. ROW COUNTRIES
 ROW refers to the Rest of the World countries, also known as the emerging
market or semi-regulated market
 These regions consist mainly of the countries from the Asia Pacific, Latin
America, Eastern Europe, Africa & Gulf countries
 Countries from Asia Pacific & Gulf have harmonized their regulatory
environment up to some extent through The Association of Southeast Asian
Nations (ASEAN) & Gulf Co-operation Council (GCC) organizations.
 ROW countries need to harmonize regulations in their respective regions.
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4. IMPORTANCE OF HARMONISATION
 Reduction in the cost involved in the availability of drugs.
 For maintaining quality requirements of the premise.
 Because of the regional registration requirements.
INTRODUCTION
 Regulatory Requirements are harmonized in regulated countries by
Common Technical Document (CTD) filling, while there is a diversity of
requirements in emerging countries.
 There are different requirements in different countries for registration. It is
difficult for any company to develop products for each region. Therefore
one needs to consider the majority of requirements during technical data
submissions which will help in export registration.
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5. THE PHARMACEUTICAL MARKET IS DIVIDED INTO THE FOLLOWING GROUPS
1. Regulated Market:
US, EU (UK, Germany,, France, Ireland & Sweden etc) Japan, Canada, Australia, New Zealand &
South Africa.
2. Semi Regulated Market:
(a) Asia: (Sri-Lanka, India, Bangladesh, China, Pakistan, Bhutan, Nepal).
(b) ASEAN: 10 countries group – Philippines. Vietnam, Singapore, Malaysia, Thailand, Indonesia, Laos,
Cambodia, Brunei Darussalam & Myanmar.
(c) African countries : (Algeria, Zambia, Ethiopia, Ghana, Kenya, Malawi, Zimbabwe etc.)
(d) Latin America: (Mexico, Brazil, Panama, Peru, Chile etc.)
(f) CIS (Common Wealth of Independent States) : Russia, Ukraine, Armenia, Tajikistan, Kazakhstan,
Uzbekistan etc.
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6. EMERGING MARKET OVERVIEW
 The optimization in requirements is mandatory keeping in mind the incidence of higher costs
involved in the availability of drugs, research and development facilities.
 The WHO & other developed countries’ drug regulatory authorities, should be encouraged and
supported so that they can expand their current programs which are supporting to developing
countries.
DIFFERENCE BETWEEN REGULATED & EMERGING MARKET
 There is a difference in the degrees of implementation of regulations.
 Intensity of conducting audits & inspections is different.
 In case the GMP is violated, then penalties both are different
 Regulated market guidelines are very clear unlike that of emerging markets.
 Regulated market adheres 100% to the guidelines whereas no such adherence is observed in the
emerging market as the regulations are not harmonized.
 There is a difference in their region.
 They also differ in certain aspects such as the regulation of Pharmaceuticals, using different
guidelines for registration, registration fees, requirements to maintain registration, duration of
registration, Patent Regulation & legislation for the drug
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7. REGISTRATION REQUIREMENTS FOR THE REST OF THE WORLD
ADMINISTRATIVE DOCUMENTS
 Certificate of Pharmacopoeial Product
 Product Permission
 Manufacturing Licence
 WHO-GMP Certificate
CHEMISTRY, MANUFACTURING AND CONTROL DOCUMENTS
API DMF Open part- Following data should be Open Part
 Nomenclature
 Genral Properties
 Structural Elucidation
 Impurities
 Container Closure System
 API Specification, Method of Analysis & COA of API by the Applicant
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8. DRUG SUBSTANCE AND DRUG PRODUCT
 IUPAC Names
 Nature of the drug
 Polymorphism
 CAS number (Chemical Abstract Service)
JUSTIFICATION OF LIMITS
The following factors are to be considered while fixing the specification limits
 API impurity and data limit
 API stability data
 Check ICH requirements
 Finished Product Stability Data
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9. MANUFACTURING FORMULAAND PROCESS
 Manufacturing Formula
 Master Formula
 Batch Manufacturing Record
 In Process Control
 Description of in process control / test
BATCH ANALYSIS
 Results of least one batch should be given
 It should be preferrably of the batch of which the samples will be submitted for
registration or it can be of the latest batch, as required by the agency in the
respective country
 It should be given as certificate of analysis
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10. EXCIPENTS
 For Excipeints of natural origin microbial limits should be specified
 Permitted & approved Colours & Flavours should be used
 Information on Adventitious Agents should be provided such as Asbetos in Talc
 For Excipients descibed in Compendia, copy of Monograph along with copies of
the methods reffered to monoraph but not appearing in monograph should be
provided
 Excipients Certificate of Analysis tested against the full set of specifications
METHOD VALIDATION FOR FPAND API
 In few countries Validation of analytical methods is still not mandatory if the
Pharmacopoeial method is followed
 Non-Compendial method needs to be validated if required by the Agency
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11. FINISHED PRODUCT SPECIFICATION AND METHOD OF ANALYSIS
 If not as per Pharmacopoeial Specifications, it should be prepared as per ICH Q6A.
Method of Analysis should be described in details.
 If based on Pharmacopoeia additional product related specifications should be
included as in house specifications (eg. Friability, Dimensions, MLT etc.). Method of
the additional tests should be given.
 If a test is based on compendial monograph, a cpoy of the monograph + any of
the methods referenced in the monograph must be submitted.
 Details of any specifications and test methods additional to those in the
Pharmacopoeia must be submitted.
PHARMACOLOGICAL TOXICOLOGICAL DATA
 Published references on Toxicological & Pharmacology studies are attached in
dossier.
 Published data on Clinical Trials & references are attached in dosier
REGISTRATION FEES
 Registration fees should be paid as per requirements of the agency of importing
drugs
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12. STABILITY REQUIREMENTS FOR DIFFERENT COUNTRIES
PACKAGING MATERIAL
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Attrinute Market Numb
r of
batche
s
Stability
Condition
Long Term
Min Duration
ACC
(Accelerated
Stability
Studies)
Min Duration
Long Term
FWA &CA (Federal
Wide Assurance &
Canada
3 Zone II 3 m 3-6 m
ASEAN 3 Zone IV-B 6 m 12 m
LATAM (Latin America
& the Caribbean)
3 Zone IV 6 m 6 m Vene-12 m
Mid-East 3 Zone IV;
Jordan-Z-III
6 m 12 m, SL,
Jordan-24 m
CIS
(Commonwealth of
independent states)
3 Zone II 6 m 6 m

13. where,
Z I - Temperate Zone
Z II - Mediterranean / Subtropical Zone
Z III - Hot Dry zone
Z IV- Hot Humid / Tropical Zone
Z IV b -ASEAN testing conditions hot / higher humidity
PACKAGING MATERIAL
 Packaging Material should be suitable for storage, transport and compatible
 For both primary and secondary packaging detailed analysis and method of
specification is required
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14. DESCRIPTION OF RAW MATERIAL REQUIRED IN MANUFACTURING PROCESS
 Name and complete contact details of each API-Vendor are not given even though
it is manufactured from 2 different manufacturers.
 Manufacturers complete address for manufacturing plant & Head office with
contact of Quality person not mentioned
 For sensitive Excipients eg. Mg-stearate TSE (Transmissible Spongiform
Encephalopathies) / BSE (Bovine Spongiform Encephalopathies) declaration is
provided ( stating it does not contain any material from animal origin and only
synthetic materials are used for manufacturing)
CONTROL OF MATERIALS
 Residual material from the reaction procedure are poorly addressed
 In FP (Finished Product) specification microbial limit is not included
IMPURITIES
 Potential impurities are not described in the impurity profile
 Hazardous Reagents and toxic substances residual limits are not given
 In the synthesis raw materials and intermediates are used. Their specification are
not described
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15. CONTROL OF DRUG SUBSTANCE
 The quality of the API’S meet only the requirements of specific monographs but
does not meet to specifications described in general monographs as per
pharamcopoeia
ANALYTICAL PROCEDURES
 The Limit of Quantification (LOQ) and the Limit of Detection (LOD) are
provided for GC and HPLC methods used to control residual solvents and
impurities in drug substance
 This method is used for the study of Drug Substance is not specific. For the analysis
of impurities specific method is used which is not provided
 Certificate of Analysis (COA) and the other Quality Control (QC) documents are not
signed, dated and certified by Quality assurance (QA) department.
BATCH ANALYSIS
 Complete procedure for coating material is not provided
 The information on some hazardious materials like reagent and solvent is hidden
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16. STABILITY DATA
 Zone-conditions for Real time stability studies is not considered
 Instability report the packaging details are missing
 The actual studies for stability are not provided
 Microbial Attributes test not provided
CONTAINER CLOSURE SYSTEM
 Primary packaging material Certifucate of Analysis (COA) & Standard Test
Procedure (STP) are not given
 Pack style & Pack size disvussion is not provided
 For Final Packaging the extractable and leachable study for the plastic containers
and stoppers used for drug product is not provided
MICROBIALATTRIBUTES
 Microbial Contamination results are missing
 Pathogen Count and Total Count is not provided
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17. ROW REGULATORY FILLING
PROCEDURE
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18. CONCLUSION
 Any export market demands good quality dosier which can be generated through
systematic formulation development
 The proper planning and execution of Formulation development will help in quality
dossier & in answering queries from Regulatory Authorities.
 Now the concepts have changed from ‘developing’ to ‘emerging’ and now to
growth markets.
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19. REFERENCE
 Badjatya Jitendra Kumar*, Bodla Ramesh (Dept. of Pharmacy, J.J.T University,
Chudela Jhunjhunu, Raj. India) (Dept. of Pharmaceutical Chemistry, DIPSAR New
Delhi, India) [Drug Product Registration in semi regulated market]
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