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Vaccine provision: Delivering sustained & widespread use [Special Issue]b

Tuesday, 20th of December 2016

Vaccine provision: Delivering sustained & widespread use

Excerpts below; full text is at http://dx.doi.org/10.1016/j.vaccine.2016.10.079

Highlights

• 100–500 different Quality Control tests assess vaccine safety, potency and purity.

• 70% of time needed for manufacturing is dedicated to Quality Control activities.

• Vaccine development typically takes 10–30 years but can be expedited in emergencies.

• Single-dose vials avoid preservatives but significantly impact on supply and cost.

• Most vaccines require strict temperature control (cold chain) for continued potency.

Abstract

The administration of a vaccine to a recipient is the final step in a development and production process that may have begun several decades earlier. Here we describe the scale and complexity of the processes that brings a candidate vaccine through clinical development to the recipient. These challenges include ensuring vaccine quality (between 100 and 500 different Quality Control tests are performed during production to continually assess safety, potency and purity); making decisions about optimal vaccine presentation (pre-filled syringes versus multi-dose vials) that affect capacity and supply; and the importance of maintaining the vaccine cold chain (most vaccines have stringent storage temperature requirements necessary to maintain activity and potency). The ultimate aim is to make sure that an immunogenic product matching the required specifications reaches the recipient.

The process from concept to licensure takes 10–30 years. Vaccine licensure is based on a file submitted to regulatory agencies which contains the comprehensive compilation of chemistry, manufacturing information, assay procedures, preclinical and clinical trial results, and proposals for post-licensure effectiveness and safety data collection. Expedited development and licensure pathways may be sought in emergency settings: e.g., the 2009 H1N1 influenza pandemic, the 2014 West African Ebola outbreak and meningococcal serogroup B meningitis outbreaks in the United States and New Zealand.

Vaccines vary in the complexity of their manufacturing process. Influenza vaccines are particularly challenging to produce and delays in manufacturing may occur, leading to vaccine shortages during the influenza season. Shortages can be difficult to resolve due to long manufacturing lead times and stringent, but variable, local regulations.

New technologies are driving the development of new vaccines with simplified manufacturing requirements and with quality specifications that can be confirmed with fewer tests. These technologies could have far-reaching effects on supply, cost of goods, and on response timing to a medical need until product availability.

Abbreviations

CMC, manufacturing and controls;
HA, haemagglutinin antigen;
HPV, human papillomavirus;
MenACWY, meningococcal (serogroups A,C,W,Y) oligosaccharide conjugate vaccine;
NA, neuraminidase

1. Introduction

Human trials of a new or improved vaccine can only start when the manufacturer, study investigators, overseeing ethical committees and regulatory agencies are satisfied that the potential benefit of immunisation is likely to outweigh any risk. This is achieved through careful laboratory characterisation of the vaccine components, preparation of assays to measure the effect of the vaccine, in vivo testing in animal models, and development of production methods allowing scale up from the bench, to manufacturing, to producing the numbers of doses needed for clinical trials, and finally for commercial distribution.

Clinical development occurs in step-wise fashion such that by the time a vaccine reaches Phase III clinical trials, the dose, schedule, proof-of-concept and the preliminary safety profile when used in the target population are known (see [18]). Phase III studies establish efficacy (and/or immunogenicity) and safety in large numbers of subjects. In parallel, the final manufacturing process, including characterisation of all the materials used to manufacture the vaccine, and all tests used to ensure the final product matches the final specifications are defined. Detailed information on the chemical composition and structure of the vaccine, the results of all pre-clinical tests, clinical trial results, and extensive documentation of quality, are combined in the regulatory dossier that is used to support product registration by competent authorities.

Here we describe the scale and complexity of the processes that brings a candidate vaccine through clinical development and ultimately to the recipient. We consider the challenge of ensuring vaccine quality, how aspects of manufacturing impact supply, and the importance of the vaccine cold chain in making sure an immunogenic and safe product reaches the recipient. We also describe the comprehensive data package that is developed to support licensure of new vaccines and the processes instituted after licensure to ensure continual monitoring of vaccine benefit and potential risk.