IPA/AAPS/FIP Workshop on Quality

Wednesday 20 and Thursday 21 February 2008 The Hyatt Regency Hotel, Mumbai, India Good manufacturing Practices for 21st Century

WHO-GMP Perspectives
By Dr Abdel Aziz Saleh Special Adviser to the Regional Director WHO/EMRO

WHO Constitution

International health standards

WHO Constitution Article 2: to act as the directing and coordinating authority on international health work.

FUNCTIONS OF WHO
To act as the directing and coordinating authority on international health work To develop, establish and promote international standards with respect to food, biological, pharmaceutical and similar products.

STANDARD SETTING FUNCTION The Health Assembly shall have the authority to adopt concerning:
Standards with respect to the safety, purity and potency of biological, pharmaceutical and similar products moving in international commerce; Advertising and labeling of biological, pharmaceutical and similar products moving in international commerce;

Strategy Components
Medicines policy Access Quality and safety Rational use

Quality System
Most developing countries lack the comprehensive set-up of a national quality system as defined by WHO An appropriate infrastructure, encompassing the organizational structure, procedures, processes and resources necessary to ensure adequate confidence that a product (or service) will satisfy given requirements for quality

Quality and Safety

The quality, safety and efficacy of all medicines assured by strengthening and putting into practice regulatory and quality assurance standards

Medicines regulation and quality assurance systems WHO Objective

Instruments for effective drug regulation and quality assurance systems promoted in order to strengthen national drug regulatory authorities.

Challenges
Three types of common imbalance have been identified in regulatory practice
Much more time is assigned to pre-marketing assessment than to post marketing surveillance While product registration is considered a major responsibility by all the drug regulatory authorities, the regulation of drug distribution channels and information does not enjoy the same level of attention In many countries, GMP inspection receives more attention and resources than inspection of distribution channels

Some examples of WHO technical support

With the technical support of WHO, a postgraduate university degree course on pharmaceutical good manufacturing practices (GMP) was developed in the Islamic Republic of Iran which can be used for capacity-building for countries of the Region. Technical support was provided for training workshops on good manufacturing practices in several countries.

Technical support was provided for fellowships for different issues related to quality assurance and safety of medicines and vaccines, a in addition to Who publications on quality and safety of medicines.

Quality assurance of Pharmaceuticals

A compendium of guidelines and related materials

Volume 2, 2nd updated edition Good manufacturing practices and inspection

The quality of pharmaceuticals has been a concern of the World Health Organization (WHO) since its inception. The setting of global standards is requested in Article 2 of the WHO Constitution, which cites as one of the Organizations functions that it should develop, establish and promote international standards with respect to food, biological, pharmaceutical and similar products.

World Health Assembly continues to express great concern about the quality, safety and efficacy of medicines, particularly those products or active pharmaceutical substances imported into, or produced in, developing countries. In recent years counterfeit products have infiltrated certain markets in disquieting proportions. Since the founding of WHO, the World Health Assembly has adopted many resolutions requesting the Organization to develop international standards, recommendations and instruments to assure the quality of medicines, whether produced and traded nationally or internationally.

In response to these resolutions, the WHO Expert Committee on Specifications for Pharmaceutical Preparations, which was originally created to prepare The International Pharmacopoeia, has made numerous recommendations relevant to quality assurance and control.

The recommendations are essential to all concerned with the quality assurance of medicines, but separate publications over a period of years has made it difficult to recognize them as complementary parts of a comprehensive system of quality assurance.

Volume 1 of Quality assurance of pharmaceuticals: a compendium of guidelines and related materials was published by WHO in 1997. Material relating to national drug regulations, product assessment and registration

Volume 2, first published by WHO in 1999, reproduces guidelines related to good manufacturing practices (GMP) and to the inspection of pharmaceutical manufacturers and drug distribution channels. This volume was updated in 2004, and the current version constitutes the second updated edition of Volume 2 including new texts and revisions adopted to date as WHO guidelines.

GMP are an important part of a comprehensive system of quality assurance. They also represent the technical standard upon which is based the WHO Certification Scheme on the Quality of Pharmaceutical Products Moving in International Commerce.

The first GMP text published by WHO was developed during 196769 upon request by WHOs Member States and was revised in 1975. In the 1980s and early 1990s, several national and regional drug regulatory authorities issued or revised guidelines reflecting the ongoing elaboration of the concept of GMP.

Revised and expanded GMP guidelines were prepared during 198990, approved by the WHO Expert Committee on Specifications for Pharmaceutical Preparations in late 1990 and subsequently published by WHO.

GMP guidelines published by WHO are to be regarded as advisory in nature and may need to be adapted to address specific conditions in individual countries. However, if any departures from recommended practices are introduced, the equivalence of such alternative approaches should be validated.

Specialized Guidelines
The GMP guidelines for biological products The GMP guidelines for the manufacture of investigational pharmaceutical products The specialized GMP guidelines for the manufacture of herbal medicinal products Radiopharmaceuticals close collaboration with the International Atomic Energy Agency (IAEA). Guidelines for inspection of drug distribution channels

Inspection is closely related to other

elements of the overall medicines quality assurance system: GMP, licensing of manufacturing facilities, product registration.

Provisional guidelines on the inspection of pharmaceutical manufacturers was published by WHO in 1992 along with the core GMP guidelines.

Additional guidelines dealing with the quality system requirements for national good manufacturing practice inspectorates were adopted by the Expert Committee.

WHO good manufacturing practices: main principles for pharmaceutical products

General considerations
Licensed pharmaceutical products (marketing authorization) should be manufactured only by licensed manufacturers (holders of a manufacturing authorization) whose activities are regularly inspected by competent national authorities.

Glossary
The definitions given below apply to the terms used in this guide. They may have different meanings in other contexts.

Quality management in the drug industry

The basic elements of quality management are:
an appropriate infrastructure or quality system,
encompassing the organizational structure, procedures, processes and resources; systematic actions necessary to ensure adequate confidence that a product (or service) will satisfy given requirements for quality. The totality of these actions is termed quality assurance.

Quality assurance
Quality assurance is a wide-ranging concept covering all matters that individually or collectively influence the quality of a product. It is the totality of the arrangements made with the object of ensuring that pharmaceutical products are of the quality required for their intended use. Quality assurance therefore incorporates GMP and other factors, including those outside the scope of this guide such as product design and development.

Good manufacturing practices for pharmaceutical products (GMP)

Good manufacturing practice is that part of quality assurance which ensures that products are consistently produced and controlled to the quality standards appropriate to their intended use and as required by the marketing authorization. GMP are aimed primarily at diminishing the risks inherent in any pharmaceutical production. Such risks are essentially of two types: cross-contamination (in particular of unexpected contaminants) and mix-ups (confusion) caused by, for example, false labels being put on containers.

National Drug Quality Assurance System

The quality of medicine Varies greatlyespecially in low-and middle-income countries. While most countries have a medicines regulatory authority and formal requirements for registering medicines, one-third of WHO Member Sates have either no regulatory authority or only limited capacity to regulate the medicines market.

Main Challenges
Legal framework Qualified national expertise in GMP inspection Teaching GMP and Quality Assurance at universities Continued education and on job training Quality system

Legal Framework
Many developing countries do not have the national expertise to develop national legal framework for GMP standard and GMP national inspection system

Developing countries usually adopt one of the recognized national, regional, or global GMP rules. WHO/GMP are generally accepted. The development of the National Inspection Manual and the Legal Framework of the GMP Inspection system needs additional technical support.

Qualified national expertise in GMP Inspection

Most of the national regulatory Authorities in developing countries lack the necessary personnel with the appropriate qualification and expertise in developing and running an efficient national system in GMP Inspection

The available facilities and working conditions do not attract competent personnel to work in the governmental sector

Teaching GMP and Quality Assurance System at universities

Only recently schools of pharmacy in developing countries started teaching basic principles of medicines Quality Assurance System and GMP inspection to the pharmacy under-graduate students

Continued education and on job training

Very few countries regularly organize continued education programme and on job training courses to GMP inspectors and other quality assurance system staff These activities are mainly dependent on external sources from donors and UN agencies

Recommendations and conclusions:

Establishment of national quality system Pharmacy education Professional development Partnership and collaboration

Quality systems requirements for national good manufacturing practice inspectorates

Administrative structure
The administrative structure, membership, operation and legal status of the GMP inspectorate should be described in the quality manual. The quality manual should show how all personnel working for the GMP inspectorate, including subcontracted staff or advisers, and persons serving on committees providing advice, can maintain their impartiality

Organizational structure
The GMP inspectorate should have an organization that enables it to maintain the capability to perform its technical functions satisfactory

The GMP inspectorate should have:

Documentation clearly identifying its legal status An organizational chart showing clearly the responsibility and reporting structure of the inspectorate and, in particular, the relationship between its inspection and authorization (licensing) functions A description of the means by which the inspectorate obtains financial support A description of the relationship between the GMP inspectorate and other departments within the drug regulatory authority and other government agencies, where they operate as separate bodies.

Inspection personnel
The credibility of the GMP inspection process will depend to a large degree on the technical competence and integrity of the inspectors. The quality manual should provide up-to-date details of the names, qualifications, experience and terms of reference (job description and duties to be performed) of each member of staff engaged in the GMP inspection process

Pharmacy Education
GMP and quality system courses should be part of the core curriculum of undergraduate pharmacy education

Partnership and Collaboration

More technical support to developing countries is needed from UN agencies and other partners Bilateral, subregional and regional collaboration has proven to be very successful in improving the national quality assurance system