Protein Drugs: Manufacturing Technologies

Report Highlights

• Protein drugs for human therapeutic use are a 1,000 metric ton industry-more than one billion grams of bulk proteins that garnered formulation sales, on average, of $27.80 per gram in 1999. This study estimates 1,048,859,344 grams of bulk drug proteins were produced worldwide in 1999. Approximately 1,150,573,386 grams will be produced worldwide in 2004, representing an overall 1.9% average annual (compound) growth rate from 1999 to 2004.
• Recombinant biological methods provided only 0.1% of the worldwide total bulk drug protein production in 1999, but are projected to provide 0.6% of the total production in 2004.

INTRODUCTION

STUDY GOAL AND OBJECTIVES

The objectives of this study are: (a) to ascertain the manufacturing methods used commercially to produce bulk therapeutic proteins; (b) to estimate worldwide bulk production of drug proteins, in grams; (c) to forecast worldwide bulk production in 2004; (d) to place the contribution of recombinant DNA technology in context; and (e) to identify bulk drug protein producers, as opposed to formulation suppliers.

The goals of this study are to shed light on a partially obscure, yet important aspect of protein drugs, and to provide -oriented technical information useful to all those interested in protein drugs.

REASONS FOR THIS STUDY AND ITS CONTRIBUTION

Protein drugs have emerged from the shadows to become, in the last 20 years, significant products in the arsenal against illnesses. While conventionally made proteins are considerable, proteins resulting from the biotechnology revolution drive future growth of the protein drug industry.

The main contributions of this study are the estimation of individual bulk protein quantities and their grouping by principal manufacturing methods. While other published studies on protein drugs look at the more obvious sales aspects, this study looks specifically at how these proteins are made and how much is made. We forecast how the proteins likely will be made in the future, and in what quantities. Most published studies on the subject of protein drugs ignore the bulk manufacturing and quantity aspects because of the difficulties involved in finding or deriving the relevant information.

Also, this study analyzes the problems that affect protein drug manufacture, and considers the technical and opportunities that these problems suggest. We look at technical trends in protein drug manufacture and examine reasons why the state of the art is where it is today.

AUDIENCE FOR THIS REPORT

This study is written for manufacturers of formulated protein drugs and producers of bulk drug proteins, and for those at the research and clinical stages of protein drug development, planning protein drug manufacture. Also expected to derive benefit are contract producers and the vendors of raw materials and equipment needed for bulk protein manufacture.

SCOPE AND CONTENT OF THIS STUDY

This study covers the commercial manufacture of bulk proteins serving, or intending to serve, human therapeutic drug applications. We concern ourselves with how the proteins actually are made for medical commerce (or will be made, once approved).

This study takes up the broad categories of source extraction from human, animal and plant materials, microbial fermentation, cell culture and chemical synthesis as bulk protein manufacturing methods. However, we do not provide detailed recipes or procedures for specific proteins. Also, we do not offer advice or counseling on the manufacture of proteins. Both regular and recombinant (including transgenic) protein manufacture are included within the scope of this study. This study also discusses the actual production of recombinant proteins, but excludes the in-lab genetic engineering aspects.

While this study provides discussion of post-bulk production operations, and data on formulation volumes and excipients for protein drugs, we do not go into detail on post-bulk production.

Excluded from consideration in this study are the methods and quantities of proteins produced for laboratory use, the methods and quantities of proteins produced for clinical trials, the methods and quantities of proteins for in vitro diagnostic use and the methods and quantities of proteins for in vivo diagnostic use. Proteins for veterinary use, their methods of production, and quantities are excluded also, as are protein methods and quantities for other applications. This study focuses only on commercial methods of bulk manufacture for proteins of human therapeutic use or potential use.

This study does not analyze sales of formulated protein drugs to any significant degree. For detailed sales information and analysis, readers should turn to other BCC published studies (such as report C-065N in three volumes).

REPORT METHODOLOGY AND INFORMATION SOURCES

To do this study, we read and assessed extensive amounts of published scientific literature and patents dealing with the manufacture of drug proteins. We spoke with people in industry engaged in protein drug manufacture, especially to pinpoint commercial (as opposed to laboratory) production methods. We talked with suppliers of formulated drugs to ascertain whether they actually produced the bulk proteins and, if not, to ascertain who did the actual bulk production.

This study estimates worldwide bulk drug protein production in grams for 1999 and forecasts the worldwide bulk production to 2004. The data are broken down by manufacturing method and by protein category. The study includes conventionally made proteins as well as drug proteins commercially made (and to be made) through recombinant DNA technology. Where more than one method is used to commercially manufacture a protein, we show the quantity of production for each method.

In many instances, we derive estimates of bulk protein quantities by our own calculations. Appendix I of this report explains the methodology in detail.