The Challenges of Crossing Regulatory Borders

by Gemma Verma

world regulation

Many pharmaceutical companies perform their research and manufacturing operations across international borders, and ship their goods to people around the world. However, operating between different countries and continents poses significant challenges, not least when it comes to obeying different sets of regulations for safety and GMP.

Growing Regulatory Pressure

Companies of all sizes are facing increasing pressure from a growing number of increasingly complex regulatory systems, put in place at global, regional and national levels. The rising number of cGMP violations being handled by the FDA is, at least in part, a symptom of this tangled regulatory maze and the growing importance that is being placed on GMP compliance. The FDA is paying more attention to procedural flaws that could result in future safety issues, with a large proportion of the 67 warning letters sent out between 2010 and 2013 citing lapses in procedure or problems with data integrity as the reasons for the warning. The added pressures that individual regulators like the FDA are increasingly placing on manufacturers is being compounded by the fact that they are often dealing with a larger number of regulators too. The risk of confusing the requirements of different regulators, and the additional pressure placed on manufacturers, could make compliance problems more likely. Crossing between the main markets has always added pressure, as companies have needed to meet slightly different demands from each regulator, but health authorities in the enticing emerging markets are also adding their own regulations to the load.

The Global Picture

Drug companies are working with increasing numbers of regulators, each with their own particular demands for GMP. A global company might need to work with the regulations of the FDA, the EU, individual countries in Europe and the rest of the Western world, and with individual developing countries that are busy creating their own regulations. Some, like Brazil, are gradually matching the standards set in the US and EU, and signing regional agreements to coordinate their requirements. Others, like China and India, two major producers of APIs for the global market, do not yet set the same GMP standards for their manufacturers. Companies can seek confirmation from their national regulators that their products meet international requirements, but it is a complicated business.

Dealing With Complexity

Succeeding within this complicated world of regulation takes great care. Companies need to devote sufficient time to understanding and keeping up to date with the different sets of regulations they need to follow. Sometimes they will need to adapt to a new regulatory culture or to a shift in a regulator’s perspective, like the FDA’s increasing demands for GMP. Action needs to be taken to make sure the company adapts to the differences and changes that are detected, and companies also need to invest in proper training to ensure that employees understand the regulations that they are supposed to be following. A well trained employee will not only know what they should be doing, but will also understand why it is important to complete procedures in the right way.

It is also important that regulators recognize how difficult it can be for companies to process the vast amounts of constantly updated information that they are being presented with. A successful system is not just one with excellent regulations and effective enforcement, but one in which the regulator is at pains to state their requirements as clearly as possible and to quickly disseminate details of any changes being made.

Simplifying and Saving Lives

Although complying with GMP regulations is likely to become more complicated for many companies in the near future, there is some light at the end of the tunnel. Efforts are underway that could help to harmonize regulatory systems across borders. The WHO has been developing standard GMPs that are already used in more than 100 countries, mainly in the developing world, while networks such as the Pharmaceutical Inspection Convention and Pharmaceutical Inspection Cooperation Scheme are encouraging thecoordination of GMP regulations across international borders.

Such efforts could make life much easier for companies operating internationally, but they will also help to ensure that all of the new regulations being put in place in the emerging markets will give consumers the right level of protection. The current standards are shockingly low in some countries, such as Nigeria, where recent testing revealed potentially dangerous pathogens lurking in many pharmaceutical products. Products manufactured in such an under-regulated system are barely safer than the contaminated substances that so frequently result in illness, infection, or even death, when taken recreationally, or the counterfeit medicines that are manufactured with no intention of meeting adequate safety standards.

It took the deaths of almost 300 people, killed by tainted sulfathiazole tablets, in the 1940s for the FDA to start creating strict quality controls and to write the first examples of what would come to be known as GMPs. Emerging markets face the prospect of similar tragedies if they do not implement adequate regulation, but they also risk losing out on valuable international trade if they cannot satisfy the requirements of the US and European markets. The importance of GMP, quality control and data integrity were key topics at the first Indian Pharmaceutical Association Pharmexcil Technical Conference in November 2014, and according to Ajit Singh, Chairman of ACG Worldwide, the need to work with the FDA to gain access to the US market is a key driving factor in the development of India’s own regulations. Whatever the motivation,better safety measures can only be a good thing for consumers all around the world, even if the multiplication of regulators poses a challenge for manufacturers.


1. Drug Regulatory Scrutiny and the Pharmaceutical Industry, Dilip Shah, CPhI Annual Report 2013
2. The Global Implementation of GMP, Michael Glessner, Specialty Chemicals Magazine
3. WHO Good Manufacturing Practices, WHO
4. Role of the Pharmaceutical Inspection Convention and Pharmaceutical Inspection Cooperation Scheme, PIC/S
5. Microbiological Contamination in Counterfeit and Unapproved Drugs, Dieter Pullirsch, Julie Bellemare, Andreas Hackl, Yvon-Louis Trottier, Andreas Mayrhofer, Heidemarie Schindl, Christine Taillon, Christian Gartner, Brigitte Hottowy, Gerhard Beck, Jacques Gagnon, BMC Pharmacology and Toxicology, 2014, 15:34
6. IPA, Pharmexcil Organises Technical Conference, November 11 2014, Express Pharma


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