Medicines are important tools in improving and maintaining health. Whilst standards for ensuring the quality of medicines at international level are becoming increasingly rigorous, quality assurance within many countries still remains a major public health concern. In recent years, there have been numerous reports highlighting problems surrounding poor quality drugs including contamination by toxic substances, increase in counterfeiting, and presence of substandard medicines on the market. Very often, these cases can be avoided by strict application of good manufacturing practices (GMP) which has an essential role to play in the quality assurance of medicines.

The need for inspection is intimately linked to the success of quality assurance systems. Without a competent inspectorate operating to high professional standards, neither GMP compliance nor licensing provisions can effectively be enforced. In addition, inspection of manufacturing facilities is pivotal to operation of the WHO Certification Scheme on the Quality of Pharmaceutical Products Moving in International Commerce (1).

GMP Implementation Project

In 1998, the WHO Department of Essential Drugs and Medicines Policy received funding from the Government of Japan to operate a three-year project on Promotion of Implementation of GMP*. The aims of the project were:

• to improve the quality of locally manufactured pharmaceutical products by identifying obstacles to implementing GMP; and

• to develop tools and methods to assist countries improve implementation of GMP.

* Responsible officer, Dr Kazushige Morimoto, SPMI Project, Essential Drugs and Medicines Policy, World Health Organization, Geneva, Switzerland. edm@who.int

A WHO Working Group was established to plan, coordinate and evaluate project activities and oversee the development of training modules to be produced as a CD-ROM and aimed to build training courses on GMP and inspection (2). Material was focussed to the needs of government officials carrying out inspection of manufacturing facilities for either finished products, medicines or pharmaceutical starting materials.

Criteria for country participation in the project were to:

• sustain existing collaboration with WHO;
• be a developing country;
• have a functioning drug regulatory authority;
• be able to serve as regional centres for GMP training in the future; and
• have significant levels of local pharmaceutical production.

GMP training modules

GMP training material comprised 20 modules (see table on page 82), with slide presentations, tutorial notes, group session exercises, handouts, comprehension tests and answer sheets. Separate modules covered: Basic Principles of GMP, GMP Inspection Processes, and trainers’ notes for the setting up and running of the course. These were completed in November 1999 for testing at the first WHO Pilot Training Workshop held in Beijing in December 1999.

WHO pilot workshops

The first workshop was organized in collaboration with the State Drug Administration (SDA), China. Participants comprised government inspectors and administrative officers with a good knowledge of GMP inspection from eight countries in the WHO Western Pacific and South-east Asia Regions.

The resulting material was tested at a second WHO Pilot Training Workshop held in Pretoria, South Africa, in July 2000, along with a first viewing of the GMP Implementation video.

Two one-day courses were further held at the end of 2000 using finalized versions of two modules, and the GMP implementation video. Participants came from a broader range of backgrounds, such as government institutions, national and private pharmaceutical facilities and universities.

GMP implementation video

The 18-minute training video was developed during the first half of 2000 as part of the GMP modular package to serve as a stand-alone training tool. Film sequences and narrative illustrated examples show GMP-compliant and non-compliant situations in pharmaceutical manufacturing facilities and include scenes of manufacturing processes, premises and quality control procedures.

For the GMP-compliant footage, a facility was selected where a full range of pharmaceuticals was being produced. Illustrations of non-GMP compliance were taken from black and white film footage originally prepared by the US Food and Drug Administration during the 1970s. The persons and company featured in the scenes were fictional. However, the situations shown were based on true events and demonstrated the consequences of human error for product quality and end-user well being. The “compliant” example contained some “non-compliant” features for use as a case study exercise during training. The video was completed in June 2000.

GMP CD-ROM

Work on the production of a CD-ROM began in March 2000. The CD contains modular training texts, WHO published documents on good manufacturing practices and inspection (3), the GMP implementation video, and background project information. Copies have been distribued to drug regulatory authorities, WHO country and regional offices and participants of GMP workshops.

Project on Strengthening of Pharmaceutical Manufacturing Inspection

Upon conclusion of the GMP Implementation Project in December 2000, the Strengthening of Pharmaceutical Manufacturing Inspection (SPMI) Project was initiated to consolidate achievements of the former project and focus on strengthening pharmaceutical manufacturing inspectorates by promoting the global use of the completed training materials. The SPMI Project ended in March 2003.

Training workshops involving 134 participants from 31 countries were organized utilizing the GMP Implementation Project modules. Where possible, a visit to a pharmaceutical factory site or laboratory was included in the programme to enable participants to be exposed to practical aspects of GMP training.

Results of SPMI

Initial distribution of the CD-ROM in April 2001 was followed by a questionnaire to national drug regulatory authorities and participants of the workshops in June 2001. The questionnaire aimed to elicit feedback on the five components of the training package (slides, tutorial notes, group sessions, handouts and the GMP implementation video) in terms of technical content and user’s opinion on the usefulness of the materials for developing skills in GMP inspection and compliance. A total of 702 questionnaires were distributed between June and November 2001.

Course evaluation and feedback from participants has indicated a strong desire for further training for inspectors and for longer courses to be set up encompassing all the modules. At the workshops in Chong Qing, China, and New Delhi, India, there was a particular focus on promoting GMP in the manufacture of antituberculosis drugs, and participants expressed a desire for further training to be specifically aimed at inspectors and manufacturers of these products.

It is hoped that wide distribution of the CD-ROM, together with availability of the materials through the WHO Internet (http://www.who.int/medicines), will greatly enhance accessibility to training possibilities supporting GMP. For some countries, however, the viability of future training will depend on the availability of computer equipment, software and translation of materials. The modules have also been translated into Spanish and produced as a CD-ROM by the Pan American Sanitary Bureau (PAHO). Feedback to date has indicated that further translations into other languages are planned, including Chinese, German, Japanese, Portuguese, Russian and Turkish.

An article describing the two projects in more detail has recently appeared in the journal Quality Assurance (4).

References

1. World Health Organization. WHO Certification Scheme on the Quality of Pharmaceutical Products Moving in International Commerce. HTP/EDM/QSM 82.4 Rev 5 (1997).

2. World Health Organization. CD-ROM WHO Basic Training Modules on GMP: A resource and study pack for trainers. Essential Drugs and Medicines Policy, World Health Organization, 1211 Geneva 27, Switzerland. e-mail GMP@who.int

3. World Health Organization. Quality Assurance of Pharmaceuticals. A compendium of guidelines and related materials. Volume II. Good manufacturing practices and inspection (1999).

4. Morimoto, K., Curry, J., Kopp, S. et al. Promoting GMP implementation: developing training materials for the international audience. Quality Assurance, 10: 11 - 27 (2003).