Manufacturers Look to Vaccines for Growth and Innovation - Pharmaceutical Technology

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Manufacturers Look to Vaccines for Growth and Innovation
Vaccine R&D is surging, but continues to raise manufacturing and regulatory challenges.

Pharmaceutical Technology
Volume 34, Issue 2, pp. 30-37

Eggs versus cells

Perennial difficulties in calculating flu vaccine demand and meeting production goals has generated efforts to shift from the use of fertile chicken eggs to produce flu vaccine, a method established in the 1930s, to cellular-based methods. The traditional system has remained in use because the influenza virus grows well in eggs, an important feature for fast production of a viral strain that changes every year. Manufacturers are beginning to augment egg-based vaccine production with cellular methods, but vaccine experts warn that the change is no panacea for the tricky process of producing a sufficiently potent and pure vaccine very quickly each year.

A shift to cell-culture vaccine will not transform influenza-vaccine production, but could lead to more reliable products and faster scale-up, noted Jesse Goodman, FDA chief scientist, at a December 2009 seminar on advances in influenza vaccine technologies at the National Institutes of Health (NIH). For years, there have been cell-culture vaccines for mumps, measles, polio, rubella, and other diseases, he explained, but the approach has not been adopted for influenza because it can take a long time to get a good yield out of cell cultures.

Shifting to cell culture doesn't cut off that much time, added Anthony Fauci, director of NIH's National Institute of Allergy and Infectious Diseases (NIAID), but he believes that it can establish a more flexible surge capacity. Making the transition from egg- to cell-based production "will take some time," Fauci said, "but eventually we will get there."

As part of its mission to fund research and production of public health medical countermeasures, HHS' Biomedical Advanced Research & Development Authority (BARDA) has awarded grants and contracts during the past five years to expand manufacturing capacity for pandemic influenza vaccine. For example, BARDA funds construction of new facilities and retrofitting of existing plants. The goal is to create more robust, flexible, and scalable manufacturing systems that can produce 150 million doses in six months, explained BARDA director Robin Robinson at the NIH seminar. Cell-based vaccine production, according to BARDA, could meet surge capacity needs more successfully because cells could be frozen and stored in advance of an epidemic.

BARDA's manufacturer grants, which total $1.3 billion, include $487 million to Novartis to construct a cell-based pandemic and seasonal-flu vaccine manufacturing facility. The new plant opened in late 2009 and is scheduled to be operational in 2011. The agency also is establishing a network of formulation and fill–finish manufacturers for emergency vaccine production and distribution.

New platforms

The real "endgame answer" to pandemic and seasonal-flu vaccine production problems, according to Fauci, is to develop a universal flu vaccine that could be administered in childhood and last a lifetime, as with most vaccines against infectious disease. Such a discovery could reduce the need to produce 120–150 million doses of a new influenza vaccine each year in the US, at a cost of $2.8–$4 billion. "It is doable," he says, noting that researchers already are identifying possible vaccine targets that don't change with each year's seasonal flu strain.

Scientists also are looking for innovative manufacturing platforms such as DNA-based and microbial-vector vaccines that can accelerate vaccine production. Protein Sciences (Meriden, Connecticut) developed a recombinant vaccine that places a flu virus gene into an insect virus called baculovirus, but the company has run into delays gaining FDA market approval for the resulting FluBlok vaccine due to safety concerns. Novavax (Rockville, MD) has reported promising clinical results for its virus-like particle vaccine being tested in Mexico.

Increased use of adjuvants to enhance patient response also could make influenza-vaccine manufacturing more efficient. Novartis and GSK produced H1N1 swine-flu vaccine more quickly last year in Europe where regulators have authorized vaccines with adjuvants that require less antigen for each dose. FDA is looking at the potential of new adjuvants to produce a more robust immune response from a vaccine, but there are concerns that adjuvants also may cause inflammation and autoimmune responses. FDA's Goodman seeks a better understanding of how adjuvants work and how they can boost the desired immune response without raising added safety issues.


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