IMPORTANCE OF HARMONISATION
DIVISION OF PHARMACEUTICAL MARKET
OVERVIEW OF EMERGING MARKET
DIFFERENCE BETWEEN REGULATED AND EMERGING MARKET
REGISTRATION REQUIREMENT FOR REST OF THE WORLD
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.
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.
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.
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 &
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,
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
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
REGISTRATION REQUIREMENTS FOR THE REST OF THE WORLD
Certificate of Pharmacopoeial Product
CHEMISTRY, MANUFACTURING AND CONTROL DOCUMENTS
API DMF Open part- Following data should be Open Part
Container Closure System
API Specification, Method of Analysis & COA of API by the Applicant
DRUG SUBSTANCE AND DRUG PRODUCT
Nature of the drug
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
MANUFACTURING FORMULAAND PROCESS
Batch Manufacturing Record
In Process Control
Description of in process control / test
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
It should be given as certificate of analysis
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
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
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
Published data on Clinical Trials & references are attached in dosier
Registration fees should be paid as per requirements of the agency of importing
STABILITY REQUIREMENTS FOR DIFFERENT COUNTRIES
Attrinute Market Numb
FWA &CA (Federal
Wide Assurance &
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;
6 m 12 m, SL,
3 Zone II 6 m 6 m
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 should be suitable for storage, transport and compatible
For both primary and secondary packaging detailed analysis and method of
specification is required
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
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
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
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.
Complete procedure for coating material is not provided
The information on some hazardious materials like reagent and solvent is hidden
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
Microbial Contamination results are missing
Pathogen Count and Total Count is not provided
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
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]