Life sciences industry

Molecular diagnostics is emerging as an important component of the life sciences industry.

The biological and life sciences industry is concerned with many aspects of physiological and medical sciences, covering the entire range of plants, bacteria, and animals. As such, there are significant crossover opportunities, such as between fermentation based companies such as beer producers and genetically engineered protein pharmaceutical companies, or between genetic engineering and biofuels. Following are several types of organizations that can be grouped under the heading of life sciences.

Biorepository

Biorepositories, as their name implies, are essentially libraries of biological specimens. Frequently, biorepositories are focused on cancer research, as the type and variety of cancers require a significant bank of available tumor, tissue, and body fluid samples. Within the U.S. the National Cancer Institute (NCI) has established the Office of Biorepositories and Biospecimen research(OBBR), whose main objective is "developing a common biorepository infrastructure that promotes resource sharing and team science, in order to facilitate multi-institutional, high throughput genomic and proteomic studies."^[1]. As part of this, the OBBR has developed a best practices document^[2] addressing a broad range of topics associated with biorepositories. Of particular note is the call for the establishment of a Quality Management System (QMS). Although no specific model is dictated, several reference models are provided, among which is the FDA QMS guidance. As part of the QMS, there is the recommendation to establish a process for determining and measuring key process indicators (KPIs) - in essence calling for a quality control laboratory function. In addition, the best practices document also refers to the need for an informatics system to manage the data necessary for and generate by the biospecimen management process, although not much detail is provided in this version.

Other forms of biorepositories exist, as well, that are not primarily focused on supporting research, such as cord blood banks, which supply not only a long term cord blood storage bank, but also provide stem cells for research purposes.

Molecular diagnostics

The molecular diagnostics industry has arisen largely in response to the growing understanding of different cancers at the molecular level. As this understanding has developed, the diagnosis and treatment of cancer has equally evolved^[3].

In the past, most diagnosis centered on microscopic examination of specimens (typically tumor biopsies or in the case of leukemia blood samples) to determine if cancer was present. Treatment was based on the specific organ involvement, rather than on a more specific understanding of the biochemistry of the specific cancer cells.

Molecular diagnostics is focused on looking for either the presence of specific marker molecules within a specimen, or in some cases, levels of these markers. One well known example is that of the Her2 molecule.

HER2 is an orphan receptor molecule which is over-expressed in certain aggressive forms of breast cancer (and in other forms of cancer as well). Therapies that either bind to HER2, or interfere with its life cycle, have a remarkable success rate in treating the cancer^[4].

In some cases, the molecular diagnostic test developed can create a different testing workflow than is normally the case in a clinical environment. A good example of this is the Nadia ProsVue developed by the molecular diagnostics division of Iris International. Whereas most tests are focused on a single specimen, the Nadia ProsVue test is focused on the rate of change of the target molecule, PSA. The requirements for the test are that three samples drawn over a specified time period be tested together for slope determination^[5]. This drives a different workflow than normally encountered in either clinical or pathology laboratories.

Molecular diagnostics has grown, however, beyond the oncology market into a variety of disease states for which a molecular understanding can benefit treatment decisions. Thus, genetic markers are of as much interest in this field as are markers specific to cancer.

Molecular diagnostics firms can fall under two separate groups of regulations, depending on the precise scope of the organization. On the one hand, molecular diagnostics are, as the name implies regulated by the Food and Drug Administration (FDA) under 21 CFR 820 within the U.S., and various other regulations throughout the world. On the other hand, the development of a molecular diagnostic test can lead to a case where the manufacturer opts to commercialize the test within their own clinical laboratory^[6]. It is generally the case that the testing lab is maintained as a segregated facility within the organization, with the clinical laboratory falling under the Federal (within the United States) Clinical Laboratory Improvement Amendments (CLIA) regulation. Such organizations also frequently seek out certification from the College of American Pathologists (CAP).

Personalized medicine

Molecular diagnostics, as indicated above, is largely focused on analyzing the levels of specific biomolecules in patient samples as a means of determining the most effective treatment for the disease. Since the treatment regimen is then being adjusted on a person by person basis, the term personalized medicine has arisen to describe this approach.

Increasingly, pharmaceutical companies have entered into the field of personalized medicine, with some companies mandating that all new drugs in development have a biomarker associated with them^[7]. This is with the intent of having some form of diagnostic test available with these drugs as they enter into the market. On the other hand, a recent survey in the European Union has determined that pharmaceutical companies do a poor job of coordinating with clinical laboratories when they plan on launching a new diagnostic test alongside of a new pharmaceutical^[8].

The impact that this on the laboratories of molecular diagnostic companies remains unclear. If new assays are being developed, it is likely that new bioreagents are required to perform the test. This will, of course, require quality control methods be developed to support the manufacturing and release process for the reagents. In addition, if a unique processing workflow exists, it is possible that the company may wish to at least design the testing process along with appropriate software support (i.e. Lab Information handling).

Pharmaceutical/Biopharmaceutical

The pharmaceutical industry represents one of the oldest industries within the biological and life sciences space. The first know drug store was opened in the 8th century AD, with the most significant growth of the industry happening from the 19th century onwards^[9].

As the industry has developed, increasing regulatory requirements covering the development as well as the manufacturing and delivery of pharmaceuticals have grown up with them^[10]. This increasing regulation has driven both an increased need for laboratories to support the different development and manufacturing processes, as well as increasing the demands on those laboratories, in terms of record keeping and procedures.

Several different types of laboratories are in use within the pharmaceutical industry:

Research laboratories

These laboratories are involved with three primary activities: synthesis of molecules of interest, characterization of these molecules, and assessment of in vitro activity. Synthesis, in particular, is a very broad term that used to apply to purely organic/chemical synthesis. However, with the advent of biotechnology, synthesis also applies to biological manufacturing at a small scale. The characterization process depends on the compound being analyzed. If the compound is a protein, then standard protein characterization processes apply, such as sequencing, mass spectrometry, and crystallographic structure analysis. DNA based compounds also lend themselves to mass spectrometry and sequencing. Small molecules are typically easier to characterize, as an NMR spectra along with basic mass spec can allow the scientist to elucidate the structure with great fidelity. Both synthesis and assessment have shifted dramatically in recent years. Historically the paradigm was to develop one molecule, or perhaps a handful, and assess them individually. Many organizations, however, have undergone a paradigm shift toward a rational drug design approach. Along with this shift have developed the capacity to support high throughput screening in order to evaluate large numbers of molecules in one or few analysis. High throughput systems are typically capable of running as many as 100,000 samples/day, with ultrahigh throughput systems capable of running beyond that. Needless to say, such a volume of samples demands significant automation.

Toxicology and pharmacology laboratories

These laboratories are focused on assessing compounds in animal systems in order to assess toxicity, clearance rates, and partitioning, among other things. (flesh this out in much more detail)

Clinical research laboratories

Clinical research laboratories are, generally speaking, very similar to their commercial cousins. One exception would be that the testing being performed is likely to be non-standard. Otherwise, many of the same issues exist, such as compliance with privacy regulations, as well as the sorts of customized workflows typical within that laboratory.

Process development support and analytical development laboratories

Process development support laboratories perform a very similar role to the Quality Control laboratory. However, owing to their position in the drug development flow, certain significant complications can arise. Frequently, the analysis that is being performed is unique, having been developed in the research laboratory. Frequently, the analytical development process is somewhat separated from the support process. However, even when this is the case, the method is new to the support laboratory, and the overall robustness in the context of a routine testing environment is likely still being established. In addition to the challenges associated with a new method, turn around time can prove to be an issue. While not unique, the impact that poor turn around time can have on the expense and time for development is frequently underestimated. It is not unusual for process development scientists to continue forward with a process with less information than would be ideal. This can lead to either process failures, or a significant increase in the number of subsequent tests submitted to the laboratory in the interest of acquiring enough data to understand what is happening in the process.

Quality control laboratories

Quality control laboratories are focused on testing for conformance to pre-determined specifications for raw materials (including water), in-process materials, finished products, and environmental factors (air, surfaces, etc.). Quality control laboratories have to be concerned with conformance to with regulations, typically across multiple jurisdictions. For instance, a QC laboratory for an organization manufacturing products in California and shipping both domestically and internationally, will have to deal with the California Department of Health Services, the US Food and Drug Administration, and the regulatory agencies of all destination countries. This level of regulatory oversight creates an environment focused very much on well documented procedures, and limited tolerance for variability in processes.

Basic research

Basic research, when it occurs outside of the Pharmaceutical or Molecular Diagnostics/Personalized Medicine environment, most often occurs within the academic environment. Research of this sort can range from biological or chemical experiments that are focused on single experiments all the way up to the high volume experiments typical of proteomics and genomics, which also are frequently found within the pharmaceutical industry.

Proteomics

Proteomics is the study of the expression of proteins within an organism or system within an organism. This study includes not only the expression levels, but is also concerned with assessing modifications to the protein, such as phosphorylation, ubiquitination, or glycoslation. Similar to genomics analysis, and high throughput screening labs, proteomics lab are dependent on automation in order to be successful. It is estimated that in humans, the number of unique proteins number somewhere in the millions, and any analysis of the protein expression of a human system must be able to manage a significant volume of data.

Genomics

This discipline studies the genomes of organisms, in particular interested in the impact of genetic variation on certain disease states. Similar to proteomics, genomics can be very data intensive. The human genome contains approximately 3 billion bases^[11]. Some researchers working in this field, are pursuing NOSQL databases to handle the data volume^[12]. Even when working in a much narrower range of a given genome, the number of experiments that need to be run to track mutation frequencies and things of the nature can be substantive. IT solutions, then, need to deliver both performance and significant storage capacity.

Gene expression analysis

Gene expression laboratories focus on studying the expression products of specific genes (typically a series of genes involved in a specific physiological phenomenon or disease state). These products can be proteins, or functional RNA, such as tRNA or mRNA. Gene expression analysis also can focus on evaluating the expression of multiple different gene products that may be of interest in a particular disease state, as frequently these states are governed by multiple genes and their products.