This document provides information on various pharmaceutical certification systems including WHO-GMP, ISO 9000, ISO 14000, and the WHO certification scheme. It explains that GMP certification focuses on consistent production of quality products according to standards, while ISO 9000 certification focuses on quality management across an organization. ISO 14000 provides environmental management standards. The WHO certification scheme facilitates international trade of pharmaceuticals between countries by issuing certificates for products, licensing status, and batches. Overall the document gives an overview of important certification systems for the pharmaceutical industry.

1. Prepared by: Diwakar Chudal
Institute of medicine, IOM

2. Pharmaceutical certification:
 Pharmaceutical Certification refers to the
confirmation of certain essential characteristics of
pharmaceutical industry which is required to
produce safe, efficacious and standard quality
pharmaceutical products.
 This confirmation is always provided by some
form of external review, assessment, or audit.

3. Most widely adopted certification system for
pharmaceutical sectors are:
 WHO-GMP certification
 ISO 9000 series
 ISO 14000 series
 WHO certification scheme

4. What is GMP ?
 Good manufacturing practice (GMP) is a system for ensuring that
products are consistently produced and controlled according to
quality standards and as required by the marketing authorization.
 GMP covers all aspects of production; from the starting materials,
premises and equipment to the training and personal hygiene of
staff.
 GMP requires detailed written procedures for each process that
could affect the quality of the finished product. Hence there must
be a system to provide documented proof that correct procedures
are consistently followed at each step in the manufacturing
process - every time a product is made.

5.  Sanitation and Hygiene
 Qualification and Validation
 Complaints
 Product recalls
 Self inspection and Quality audits
 Qualified personnel and Training
 Premises
 Equipments
 Materials
 Documentation

6.  The guiding principle of GMP is that quality is built into
a product, and not just tested into a finished product.
 Therefore, the assurance is that the product not only
meets the final specifications, but that it has been
made by the same procedures under the same
conditions each and every time it is made.
 GMP is designed to minimize the risks involved in any
pharmaceutical production that cannot be eliminated
through testing the final product.

7.  Many countries have legislated that pharmaceutical companies
must follow GMP procedures, and have created their own
GMP guidelines based on WHO-GMP that correspond with
their legislation. Therefore, complying with GMP is a
mandatory aspect in pharmaceutical manufacturing.
 GMP guidelines are not prescriptive instructions on how to
manufacture products. They are a series of general principles
that must be observed during manufacturing. When a
company is setting up its quality program and manufacturing
process, there may be many ways it can fulfill GMP
requirements. It is the company's responsibility to determine
the most effective and efficient quality process.

8.  The national regulatory authority of Nepal i.e
Department of drug administration (DDA) is
responsible for issuing and renewing the WHO-GMP
certificate to domestic pharmaceutical industries.
 DDA has it’s own GMP guidelines based on WHO-
GMP principles which is used as reference standard for
checking compliance with GMP system.

9.  Inspection department of DDA assigns auditors and sends them to
respective pharmaceutical industry for GMP audit.
 Upon completion of the audit, the auditors generates an audit
report identifying any non-conformances (NC’s) to the GMP
guidelines. At the same time auditors gives CAPA to the QA
manager.
 After receiving CAPA, QA manager works along with other
managers and HOD’s to resolve the NC’s in a given frame of time.
CONT….

10.  The auditors submits the audit report and NCs to the
Administrator/Director of DDA.
 The audit documentation is then reviewed by Director of DDA for
approval of GMP audit.
 Once the Director of DDA approves the closure of the NCs, the WHO-
GMP certificate is issued and sent to respective pharmaceutical
industry.
 GMP certification must be renewed by pharmaceuticals at a regular
interval of 2 years and same audit procedures will be carried out by
DDA.

12. What is ISO?
 The International Organization for standardization (ISO) is an
international standard-setting body composed of representatives
from various nation.
 Founded on 1947, ISO is an independent non-governmental
organization, the members of which are the standards
organizations of the 164 member countries with its headquarter
located in Switzerland. It is the world's largest developer of
voluntary international standards and facilitates world trade by
providing common standards between nations.
 Nearly twenty thousand standards have been set by ISO covering
everything from manufactured products, technology, food safety,
agriculture, healthcare, etc

13. Most commonly issued ISO certifications for
pharmaceutical industries are:
 ISO 9000 series
 ISO 14000 series

14. • The ISO 9000 Series is a set of international standards for
quality management and quality assurance by an
industry/company.
• They are not specific to any one type of industry or
company.

15. How ISO 9000 series was developed?
• ISO based the foundation of ISO 9001 in the content of a
British set of standards, BS5750, an older document for
military applications. BS5750 aimed at tightly controlling
the quality of products in factory that built bombs
in United Kingdom during World War II.
• With this encouragement from the British government,
ISO drafted the first version of these standards in 1987

16. • As opposed to ISO 9000 which was introduced in 1987,
ISO 9001,ISO 9002,ISO 9003 and ISO 9004 were gradually
developed.
 ISO 9001 – Standard for quality assurance in
design and development
 ISO 9002 – Standard for quality assurance in
production & installation
 ISO 9003 – Standard for quality assurance in final
inspection and tests
 ISO 9004 – Standard for Quality management.

17. • Later in the year 2000 AD, ISO 9001,9002,9003 and
9004 were combined together and was called ISO
9001:2000.
• ISO 9001:2000 was again updated in year 2008 AD
and was called as ISO 9001:2008. However the
changes were considered minor.
• Recently in the year 2015 AD, ISO 9001:2008 was
further updated and now called as ISO 9001:2015.

18. • ISO 9000, represents a standards for quality
management methodology which must be adopted
by pharmaceutical industries to deliver products and
services that meet customer expectations.
• ISO helps to facilitate international trade of drug
products by providing a internationally-accepted
standards for everybody's reference.
• ISO can be used to enhance a GMP based
Quality System.

19.  ISO 9000 certification gives world-class specifications
for products, services and systems. Hence it helps to
develop reputation of pharmaceutical industries.
 ISO standards acts as strategic tools that reduce costs
by minimizing waste and errors and increasing
productivity.
 ISO certification helps companies to access new
markets and level the playing field for developing
countries like Nepal.

20.  ISO 14000 series is the world’s most recognized
framework for environmental management systems.
 ISO 1400O series gives standard for organizations to
manage the impact of their activities on the
environment and to demonstrate sound environmental
management system.
 The ISO 14000 family of environmental management
standards can be implemented in any type of
organization in either public or private sectors.

21.  ISO 14000 has developed standards that helps
pharmaceutical industries to take a proactive approach to
manage environmental issues.
 ISO 14000 helps to overcome the challenge of climatic
changes.
 ISO 14000 further increases the degree of product’s quality
by encouraging the inclusion of environmental aspects in
product design.
 ISO offers a wide-ranging portfolio of standards for
sampling and test methods to deal with specific
environmental challenges. It has developed some 570
International Standards for the monitoring of such aspects
as the quality of air, water, soil, as well as noise, radiation,
etc

22.  ISO does not itself certify organization.
 Many countries have formed accreditation bodies to authorize
certification bodies, which audit organization applying for ISO
compliance certification.
 Both the accreditation bodies and certification bodies charge
fees for their services.
 The various accreditation bodies have mutual agreements
with each other to ensure that certificates issued by one of the
accreditation certification bodies are accepted worldwide
 The applying organization is assessed based on its sites,
functions, products, services and processes.
CONT……

23.  A list of problems/NC will be made
 If there are no major problems/NC, Certification body
will issue ISO certification to organization.
 An ISO certificate must be renewed at regular
intervals.

24.  One of the main problems of comparing GMP and ISO is that the
two standards are not the same and are not really trying to do the
same thing.
 GMP is a product quality standard, with a focus on consistently
getting the right quality product to the only customer of GMP –
the patient. ISO 9001 on the other hand is more about running a
whole business, a goal of which will be getting product of the
international standard quality globally.
 GMP mainly focuses on Production and Quality Control but ISO
focuses on the all departments and processes of an organisation.
Hence ISO is more encompassing than GMP.

25.  List of the clauses of ISO 9001 are below. Those in GREEN text are
requirements of ISO that are not specifially mentioned in GMP. From this
list we can see that there are a number of areas that ISO covers that are
not covered by GMP.
 Section 1 – Scope
 Section 2 – Normative Reference
 Section 3 – Terms and Definitions

 Section 4 – Quality Management System
 4.1 – General Requirements (Process Approach)
 4.2 – Documentation Requirements
 4.2.1 General
 4.2.2 Quality Manual
 4.2.3 Control of Documents
 4.2.4 Control of Records
CONT…


26. Section 5 – Management Responsibility
 5.1 – Management Commitment
 5.2 – Customer Focus
 5.3 – Quality Policy
 5.4 – Planning
 5.4.1 Quality Objectives
 5.4.2 Quality Management System planning
 5.5 – Responsibility, authority and communication
 5.5.1 Responsibility and authority
 5.5.2 Management Representative
 5.5.3 Internal Communication
 5.6 – Management Review
 5.6.1 General
 5.6.2 Review Input
 5.6.3 Review Output
CONT………….

27. Section 6 – Resource Management
 6.1 – Provision of Resources
 6.2 – Human Resources
 6.2.1 General
 6.2.2 Competence, awareness and training
 6.3 – Infrastructure
 6.4 – Work Environment
Section 7 – Product Realization
 7.1 – Planning of Product Realisation
 7.2 – Customer-related processes
 7.2.1 Determination of requirements related to the product
 7.2.2 Review of requirements related to the product
 7.2.3 Customer Communication
 7.3 – Design and Development
 7.3.1 Design and Development Planning
 7.3.2 Design and Development Inputs
 7.3.3 Design and Development Outputs
 7.3.4 Design and Developm ent Review
 7.3.5 Design and Development Verification
CONT…..

28.  7.3.6 Design and Development Validation
 7.3.7 Control of Design and Development changes
 7.4 – Purchasing
 7.4.1 Purchasing Process
 7.4.2 Purchasing Information
 7.4.3 Verification of Purchased Product
 7.5 – Production and Service provision
 7.5.1 Control of production and service provision
 7.5.2 Validation of processes for production and service provision
 7.5.3 Identification and Traceability
 7.5.4 Customer Property
 7.5.5 Preservation of Product
 7.6 – Control of Monitoring and Measuring Equipment
CONT….

29. Section 8 – Measurement, Analysis and Improvement
 8.1 – General
 8.2 – Monitoring and Measurement
 8.2.1 Customer Satisfaction
 8.2.2 Internal Audit
 8.2.3 Monitoring and Measurement of processes
 8.2.4 Monitoring and Measurement of product
 8.3 – Control of nonconforming product
 8.4 – Analysis of Data
 8.5 – Improvement
 8.5.1 Continual Improvement
 8.5.2 Corrective Action
 8.5.3 Preventive Action
 From the above list, we will see that there are certainly some
areas where ISO can be used to enhance a GMP based Quality
System.

30. What is WHO Certification scheme?
 It is a Scheme developed by the World Health
Organization (WHO) in response to the request
of WHO Member States to facilitate
international trade in pharmaceutical products
between Member States.
 was first developed in 1975. Since then it has
been revised in 1988, 1992 and in 1997.

31.  Any member state, which intends to participate in the scheme, should
write to the Director general of WHO
 of its willingness to participate in the scheme,
 name and address of national drug regulatory authority of the
country.
 A Member State intending to use the Scheme should first satisfy itself
that it possesses:
 an effective national licensing system, for pharmaceutical
products, manufacturers and distributors;
 Implementation of GMP requirements, recommended by WHO.
CONT……

32.  Effective control measures to control the quality of
pharmaceutical products registered or manufactured within its
country.
 Highly qualified staffs, who can investigate to ensure that
manufacturers conforms to these requirements.
 Administrative capacity to issue the required certificates and do
inquiries in case of complaint.

33.  Three types of certificates can be requested
under this scheme:
 A certificate of a pharmaceutical product.
 A statement of licensing status of
pharmaceutical products.
 A batch certificate of a pharmaceutical
product.

34.  CPP should Incude the following informations for each
product:
 Brand name
 Generic name (International Non-proprietary Name)
 Name and address of manufacturing facility,
 Formulation
 Product information for medical professionals and
for patients as approved in the exporting country,
 Labeling on retail and wholesale containers, and
 Packaging details.

36.  This attests only that a license has been issued for a specified
product, or products, for use in the exporting country.
 Example-
 No. of statement:
 Exporting (certifying) country:
 Importing (requesting) country:
 This statement indicates only whether or not the following
products are licensed to be put on the market in the exporting
country.
 Applicant (name/address):
CONT…….

38.  This certificate is issued by the manufacturer of
the exporting country.
 This certificate is used to provide an attention
concerning the quality and expiry date of a
specific batch of product which is to be
exported.

39.  Example:
1. No. of Certificate:
2. Importing (requesting) authority:
3. Name of product:
 Dosage form:
 Active ingredient and amount per unit dose:
 Is the composition of the product identical to that registered in the
country of export?
(yes/no/not applicable)
If no: please attach formula (including excipients) of both products.
4. Product-licence holder(name and address):
 Product-licence number:
 Date of issue:
 Product licence issued by:
 Product certificate number:
5.1 Batch number:
5.2 Date of manufacture: CONT…

40. 5.3 Shelf life (years):
5.4 Contents of container:
5.5 Nature of primary container:
5.6 Nature of secondary container/wrapping:
5.7 Specific storage conditions:
5.8 Temperature range:
6 Remark:
7 Quality analysis:
7.1 What specifications apply to this dosage form. Either specify the
pharmacopoeia or append company specifications.
In the case of a product registered in the exporting country, have these
company specifications been accepted by the competent authority?
(yes/no)
7.2 Does the batch comply with all parts of the above specifications? (yes/no)

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