Good manufacturing practice among packaging suppliers in asia pacific is crucial to the region’s ability to export products, and to the improved healthcare of millions of people.
The Association of South East Asian Nations (ASEAN) is a multi-cultural region of over 500 million people. Despite the diversity of culture and language, the ASEAN nations are making efforts to work cooperatively to improve the economy of the region. In addition to economic development, the region is striving to improve healthcare provision and these two factors have contributed to the development of its own pharmaceutical industry. This relatively new industry however is somewhat vulnerable, with India to the west, China to the east, Japan to the north and the global reach of the American pharmaceutical industry, but at the same time there are also compelling economic and healthcare drivers for growth. But what is involved in bringing about the developments required in such a highly regulated industry? How is the region responding to the challenges to its pharmaceutical industry and what other influences are forming the future of pharmaceutical production in the region?
While the supply of active ingredients, excipients and labels are equally important, this article examines the good manufacturing practice (GMP) of pharmaceutical packaging in the ASEAN region and considers how packaging suppliers are developed in the west and how the same development could happen in the ASEAN region.
Ten countries making up the ASEAN region: Singapore, Malaysia, Thailand, Philippines, Indonesia, Cambodia, Vietnam, Lao PDR, Brunei Darussalam and Myanmar. Of these countries, Singapore and Malaysia, are members of the Pharmaceutical Inspection Cooperation Scheme (PIC/S). This means that they manufacture medicinal products to the same set of GMPs as all other countries that are members of PIC/S. Currently PIC/S member countries include Australia, Canada and the whole of Europe, although not currently the USA. The US Food and Drug Administration (FDA) says that it will apply for membership of PIC/S in 2005.
PIC/S came into being because countries began to export medicinal products to other countries. In order to determine if the products were manufactured to the appropriate quality, government inspectors would travel to the exporting country and carry out an inspection of the company against the GMPs of the importing country. Following a successful inspection, the medicinal products could be imported. This type of control had a number of problems associated with it. Often there were language barriers, different countries operated different sets of GMP rules and also it demands a lot of time and money. Travelling to another country to conduct an inspection is not cheap, particularly if it is on a company-by-company basis. So the inspectors held a convention in Europe where the initial members agreed that if a company was inspected to the same set of GMPs, then there would be no need to send inspectors overseas to carry out inspections. The initial convention has developed into a cooperation scheme and member countries now benefit from a common set of GMPs and a common standard for inspections as well as the economic benefits that drove the initiative in the early days.
PIC/S is now made up of a select group of countries that enjoy trading medicinal products both between members and to non-members. But what about the non-members including eight countries in the ASEAN region? Medicinal products in these countries are produced under World Health Organisation (WHO) GMPs. These countries cannot sell their products to PIC/S member countries unless they are inspected and they therefore suffer a time and financial disadvantage in the global medicinal products markets.
Any discussion regarding the provision of medicinal products in the ASEAN region inevitably contains an element of economics. Generally, medicinal products produced in PIC/S countries and the USA are considered expensive for non-PIC/S member countries so these countries are driven to produce their own versions, especially to treat diseases that are epidemic in the region such as HIV/AIDS, tuberculosis and malaria. Cheaper medicinal products are being produced by India and China, but the GMP standards in these countries are at best variable, however these countries are growing incredibly fast in many industries including the pharmaceutical industry. While this growth creates opportunities, unfortunately, it also creates opportunities for the production of counterfeit medicines.
No one really knows the extent of the counterfeit medicine problem, but some attempts have been made to quantify it. Here are some figures from the WHO:
One of the main reasons why counterfeits are such a problem is that the packaging is often very easy to copy.
Despite the potential difficulties in bringing order to the ASEAN pharmaceutical industry, it is by no means hopeless, and the European Community in conjunction with ASEAN is rising to the challenge. There is a vision that by 2020 all ASEAN member countries will become members of PIC/S. This programme is already under way and inspectors in all ASEAN countries are being trained as one of the key activities in the region.
Governments cannot bring about the changes alone and there is a great deal that can be done by the industry. In particular, while companies are developing their own GMPs and growing in their own understanding of what is required, their suppliers have even less idea of what is required of them. The responsibility for developing suppliers therefore rests largely with the pharmaceutical companies. Fortunately, auditing and training are useful tools in a supplier development programme already well developed and widely used in the West.
A number of multi-national pharmaceutical and medical device companies have operations in the ASEAN region encouraged by government promotion of target industries such as the Economic Development Board (EDB) in Singapore. As a consequence, Pfizer, Schering Plough, Merck, Sharpe, Dohme, Sanofi-Aventis, GlaxoSmithKline, Wyeth and Ciba Vision all have facilities in the city state. Mainly locals work at these companies but there are often Western managers in many of the key positions, at least for the initial few years. They quickly realise that the way business is conducted in Asia is different to the way business is conducted in the west. So they need to understand the culture of their supplier before they can hope to ‘develop’ them and this sometimes cuts across some of the conventional wisdom of the West as well as some of the multi-nationals global policies.
Before embarking on a supplier development programme, it is important to understand the supplier. There are some multi-national suppliers in the region and while the parent company may well be leaders in their understanding of GMP, the Asian regional facility may have local employees that are much less familiar with GMP requirements. In addition, there are very many suppliers that are not specialists in the pharmaceutical industry including many label suppliers and secondary packaging suppliers. A pharmaceutical company’s ability to influence non-specialist suppliers is much lower and in some cases they have no ability to influence them at all. Nevertheless, audits and training remain two powerful tools in developing suppliers.
When auditing suppliers, there are two international standards that can ensure that audits are effective. Firstly, the auditor needs to be trained in conducting supplier audits. This training follows a formal training programme and requires an assessment at the end of the training. When trained, the auditor will be able to prepare, conduct and report audits in a professional, consistent and effective manner as described in ISO 19011:2002 – Guidelines for Quality and/or Environmental Management Systems Auditing. The second international standard is ISO 9000:2000 and in particular the pharmaceutical packaging variant, PS9000:2001 produced by the UK Pharmaceutical Quality Group of the Institute of Quality Assurance. This is the standard for a Quality Management System appropriate for a supplier to pharmaceutical manufacturers and is available from the PQG (www.pqg.org). There is currently no Asian equivalent although given the status of GMP in the region, supplier development is only a part of a long priority list.
Training of suppliers does not need to be too intense. In Europe it usually consists of a few modules conducted by the pharmaceutical company at the supplier’s premises a few times a year. There are normally no charges involved, as it is a mutually beneficial activity. There is always a basic GMP training module because many of the packaging suppliers do not know what GMP is.
There are a number of initiatives to try to prevent the problem of counterfeiting. Some examples include the use of holograms and radio frequency identification (RFID). However, the major barrier to implementing these anti-counterfeiting technologies is that they are expensive, especially for smaller manufacturers and re-packers. In addition to this, the US FDA points out that it is only through federal laws, enforcement and increased penalties for offenders that they control the extent of counterfeiting in the US. The experience in the US points to government intervention that is beyond the influence of the industry and individual companies.
The responsibility for ensuring that packaging supplies meet the requirements of GMP rests with the manufacturers. The tools they have available to them are well tested and they work well in the West. Their application in ASEAN and the rest of Asia needs to take into account the business culture and the current developments in the pharmaceutical and biomedical industry. Developing suppliers will contribute to the growth of the industry here and ultimately, patients and consumers will benefit from an industry that is growing and developing in this vast, multicultural group of nations.