As regulatory conditions internationally become more consistent and more predictable—thanks to harmonization initiatives—it’s important to consider the relative administrative demands and the business potential in the strategically important markets of Benelux, the Baltics, South Africa, and Canada.
The barriers to doing business in additional geographical markets are being reduced all the time, not least as global trading agreements are redrawn. Initiatives to bring international information and safety compliance standards into alignment, meanwhile, promise to reduce the administrative complexity for companies trading in multiple markets.
For large- and mid-sized organizations looking for new growth opportunities for existing product lines, or small but ambitious firms seeking to spread their risk and raise their profile globally, arguably there has never been a better time to broaden their horizons.
Harmonization of industry requirements isn’t quite there yet, however. So what are the best geographical opportunities to consider in 2018 and beyond, and what are the current regulatory peculiarities that companies need to be aware of as they contemplate setting up base in those markets?
As the home of European Union (EU) administration, the Benelux region of Belgium, the Netherlands, and Luxembourg is an important European market. Belgium is a major regulatory hub as well as an open environment that is research friendly.
Belgium’s language diversity makes it a useful base from which to support other European countries and to liaise with headquarters. Belgian teams typically manage regulatory filings on behalf of Luxembourg and the Netherlands.
For companies, the biggest challenge is the need to have a single responsible person for pharmaceutical information. This comprehensive role must be filled by a physician or pharmacist approved by a country’s ministry of health, and suitable candidates are hard to find.
The requirement can trip up companies that don’t consider it up front.
As a multilingual country that is strategically positioned geographically and that has a well-established and transparent regulatory environment, Belgium represents a progressive hub for European submission management.
Since joining the EU, Lithuania, Latvia, and Estonia have adopted relevant legislation; companies preparing local submissions must have authorization from each country’s local authority or from the European Medicines Agency (EMA) depending on the type of registration.
In Latvia, the State Agency of Medicines assesses medicines before issuing market authorizations. Estonia, too, has a State Agency of Medicines. Lithuania’s regulatory body is called the State Medicines Control Agency.
With a combined population of around 6.3 million, the Baltic region is not known as a significant producer of pharmaceuticals, and it lags behind other European markets.
EU legislation requires that a marketing authorization holder reside in the EU. None of the Baltic countries requires the presence of a regulatory person, nor is it necessary to have a native speaker within each country to work with authorities, which tend to communicate in English.
None of the Baltic countries requires the presence of a regulatory person, nor is it necessary to have a native speaker within each country to work with authorities.
However, it is advisable to have a native speaker for translations of summaries of product characteristics and packaging materials and to provide advice on product implementation.
Although the Baltic region has seen a marked decline in mortality rates in the last 15 years, the rates remain relatively high for Europe, which presents certain health-care challenges—as well as market potential. All three countries are experiencing pharmaceutical market growth, with promising potential for innovative companies that offer new medicines.[i]
Compared with more-complex European markets, the Baltics are relatively easy to manage from a distance. The regulatory authorities are easy to communicate with, and dossier submission can be managed electronically via the Common European Submission Portal/Platform (CESP), although in Latvia, a signed paper application form, a cover letter, and proof of payment are required via courier or post in parallel.
As the gateway to the African continent, South Africa is an important pharmaceutical market even though its regulatory regime remains in a state of flux. In June 2017, the government introduced the Medicines and Related Substances Amendment Act and is establishing the new South African Health Products Regulatory Authority to oversee medical devices and medicinal products. This will replace the Medicines Control Council.
Other moves have included a transition from the old Medicine Registration Form format to the Common Technical Document (CTD)—mandatory since 2016. Old dossiers can remain in their existing Medicine Registration Form format, but if a chemistry, manufacturing, and control variation is submitted, the entire submission must be converted to CTD and a fully updated Module 3 entered.
The South African regulatory environment is stringent, and firms submitting marketing authorization applications in South Africa must be locally based. Each company must have a responsible person in the form of a pharmacist registered with the South African Pharmacy Council to ensure adherence to medicine controls and be accountable for all technical and regulatory issues.
South Africa–based pharmaceutical companies and representatives commonly handle submissions for Botswana, Ghana, Kenya, Mauritius, Namibia, Tanzania, and Uganda, and satisfying each country’s regulatory nuances requires experts with relevant knowledge and good working relationships with in-country agents.
The national agency’s regulatory backlog is probably the biggest area of concern for companies targeting African markets. Although measures are being taken to tackle the backlog, the South African approval process currently takes around five years.
In 2015, South Africa initiated an electronic CTD (eCTD) pilot involving 18 products, which provided good insights into the eCTD process and helped speed the review process for some products. Even though eCTD applications are now accepted for both new chemical entities and generic applications, the time frame for compulsory submission in eCTD format has not yet been set.
As a pharmaceutical market, South Africa is the largest in sub-Saharan Africa—valued at €2.52 billion ($3.13 billion)—and is expected to grow at a compound annual rate of 7.4 percent up to 2019, according to IQVIA (formerly IMS Health). South Africa’s market follows ICH guidelines—similar to EU requirements. The use of South Africa as a base for building regulatory submissions for other African countries also is appealing.
As a member of ICH, Canada takes a regulatory approach and follows an eCTD submissions process that will feel familiar to global companies, although Health Canada has implemented certain country-specific regulations (see below).
The United States and Canada have established a Regulatory Cooperation Council Pharmaceutical and Biological Products working group to enhance regulatory harmonization between the two countries.[ii]
The pharmaceutical industry in Canada employs around 27,000 people directly and more than 100,000 people indirectly and is growing at a compound annual rate of 2.2 percent. Most of the country’s pharma companies are clustered in Toronto, Montreal, and Vancouver.
Among Canada-specific regulatory requirements is the product monograph, akin to EMA’s summary of product characteristics. Health Canada introduced plain-language labeling requirements in 2014 to ensure that patient materials are easy to understand. Another consideration is a requirement to publish a product monograph and all labeling in both English and Canadian French.
As a straightforward and transparent market, Canada poses few specific regulatory complexities for companies. However, understanding the local environment and developing a rapport with the local authority are important to avoid delays to market given that there is no predefined time limit in Canada for the question-and-answer review period.
Canada is the 10th-largest pharmaceutical market in the world; it ranks highly for cost-effective clinical trials and medical product testing[iii], and it is a leader in biotechnology and vaccines. Given its similarities to both the United States and Europe in regulatory terms, Canada presents few hurdles for companies—yet many advantages.
With regulatory differences between regions reducing all the time, the conditions are ripe for life sciences companies to broaden their geographic reach as a source of business growth.
[i] “Baltic states’ pharma markets continue to emerge from crisis,” IHS Market, 17 December 2013.
[ii] 2016 Top Markets Report Pharmaceuticals Country Case Study, Canada, International Trade Administration.