As much as one-third of the world's population lacks access to essential medicines, and in the poorest regions of Africa and Asia, this figure rises to one-half (1). Along with other organizations, Medicins sans Frontieres (MSF, Doctors Without Borders) advocate for a combination of global and regional policies to lower drug prices sustainably, including local drug manufacturing. At this year's annual meeting of the Biotechnology Industry Organization (BIO), during a session on building vaccine capacity in developing countries, Martin Friede of the World Health Organization (WHO) told the audience, “It is not only essential to manufacture vaccines locally, but we must allow each region to make its own decisions.”

One of the biggest barriers to meeting this objective is the lack of manufacturing capacity in developing regions. During the same BIO session, Eric Iverson of the Gates Foundation stated that the lack of capacity is “a rate-limiting constraint to achieving global health objectives.” Although Martin agreed the need is far beyond capacity, he also pointed to a lack of interest by industry and a lack of technical know-how and expertise in these regions. Thus, he concluded, there is a need to provide technology from public sources within intellectual property constraints. Manufacturing, supply chain, regulatory policy, training, and surveillance are other “monumental” issues, said Iverson.

But the concept of local production is gaining popularity in the private sector, especially in India, China, and Brazil. Manufacturing in a region where their products will be distributed makes economic sense, especially if costs can be minimized. Nonetheless, the presence of both public and private markets in these regions can complicate matters, especially for vaccine production and distribution. “For organizations such as WHO and UNICEF, a dollar per dose is the maximum they can spend, so there is a lot of pressure on the price of vaccines from those agencies on manufacturers. Manufacturers respond to that by keeping their costs of manufacturing to a bare minimum,” says Eric Patzer (president and founder of Aridis Pharmaceuticals), who adds that his company has had discussions with the nonprofit groups regarding production of its rotovirus vaccine.

Global Thinking

Public or private markets aside, most experts would agree that establishing local manufacture in a developing region isn't trivial. “I don't think people appreciate what some of the challenges are in being able to do that kind of localized manufacturing,” says Matthew K. Hudes, US managing principal, biotechnology, at Deloitte Services LP. “There are certainly incentives for investment, so it makes sense in the grand scheme, but people have had some difficulty going into a particular region and trying to manufacture when they don't understand some of the capabilities, skill sets, and regulatory differences that occur in different places.” For example, a product or innovation that comes from the United States must comply with the Foreign Corrupt Practices Act (FCPA) in addition to other local and regulatory issues. “FCPA is not to be underestimated,” says Hudes, “Serious fines have been paid for violations and for going gobal without truly understanding those impacts.”

The industry's move toward localized manufacturing and establishing truly global markets means companies will need to change the way they handle their operations from the beginning. “It starts with global thinking,” says Hudes. He suggests companies should think about technology transfer early and design manufacturing processes to enable that transfer. Such designs are not site or facility specific, and some expertise at transferring that process around the world will be required. Addressing technology transfer and other logistics issues at the beginning is a lot easier than trying to globalize an existing product or process,” he adds.

Anticounterfeiting

As global markets emerge, the need for protecting the supply chain and finished products grows ever more critical. The rise in the number of counterfeit drugs is not only a huge business concern, but also a great concern for public health. In 2005, more than 500,000 counterfeit pharmaceutical products were discovered by customs officials in the European Union alone. In 2006, that number skyrocketed to more than 2.7 million (2).

According to Christopher Wolf, director at Arvato Services Healthcare, the main industrial areas of interest in Europe are the “Big Five” countries of Germany, UK, France, Spain, and Italy. Many companies, however, are not fully aware of the complexities of the various regulations for each country, says Wolf. For example, although serialization with two-dimensional barcoding is already a widespread practice in most of Europe, the systems to apply and detect these codes are different and depend on the country of origin (3).

The biopharmaceutical industry continues its current discussions regarding global technologies and standards to combat counterfeits. Overall, serialization with 2D unit-level barcoding is gaining popularity as the preferred strategy, even over more expensive radio-frequency identification (RFID) tags. Most industry experts agree that solutions combining global standards and item-level serialization (e-pedigree) are most effective. “One example would be to have 2D barcoding at the unit level and then have RFID on pallets. The RFID tags would contain all of the unit barcodes that should be on that pallet,” says Rainuka Gupta, group manager of medical technology at Cambridge Consultants. Combinations of overt (e.g., holograms, color-chaning inks), covert (e.g., taggants), and forensic technologies can then provide authentication.

As part of their logistics planning, local manufacturers will need to become familiar with local policies already in place for serialization. Italy was one of the first European Union nations to implement a bar-code based system. In 2005, the country introduced the “bollini,” which is a label that features the Italian product license number and a sequential number (4). Brazil, another emerging biologics hot spot, also has leveraged innovative solutions to supply chain protection. In January 2009, the Brazilian government passed a law mandating that drug manufacturers and distributors act on specific serialization and track-and-trace requirements. The deadline for compliance is January 2012 (3). In addition, Germany, France, and Turkey have either passed legislation or will soon pass legislation that will require a data matrix code encoded with the GS1 data standard (www.gs1.org). France instituted a labeling requirement that the global trade identification number (GTIN, developed by GS1), expiration date, and lot information must be marked on every product, preferably with a 2D data matrix bar code (compliance date is January 2011) (3).

In the United States, the FDA maintains an online information page on counterfeit medicines as well as reports from its Counterfeit Drug Task Force (5). In March, the agency issued new guidelines for labeling on prescription drug packaging that recommend inclusion of a serialized national drug code (sNDC, compatible with the GS1 data standard) on each package. The FDA's previous guidelines required an NDC, so the addition of a serial number enables item-level traceability for prescription drugs for the first time in the country.