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Volume 2019 Supplement, Issue 1
Outsourcing of analytical testing and processes can help bio/pharmaceutical companies expand their product profiles.
Innovation in the bio/pharmaceutical industry brings success to pharma companies and new options for patients. New treatments and therapies, however, often come with new and/or additional analytical testing requirements. Many bio/pharmaceutical companies don’t have the knowledge, experience, instruments, or personnel to perform such testing; therefore, many analytical processes are outsourced to contract research, contract development, or contract manufacturing organizations (CROs, CDMOs, CMOs). And outsourcing of these and other services is expected to grow in the coming years (1).
So how can contract laboratories serve the pharma industry? Pharmaceutical Technology spoke with Kimberly McClintock, executive vice-president at Metrics Contract Services, which offers method development and validation for small-molecule drug substances and drug product stability and release testing including on-site microbial testing; and Patrick A. Tishmack, PhD, analytical services general manager at AMRI West Lafayette, which offers both small- and large-molecule analysis, about the benefits of outsourcing analytical processes and testing.
PharmTech: Why should pharmaceutical companies outsource their analytical processes?
McClintock (Metrics Contract Services): One of the main reasons to outsource laboratory testing is to access expertise and instrumentation. It may not be feasible for pharmaceutical companies to purchase and operate specialized equipment themselves for a limited number of programs. Contract labs support hundreds of programs, making significant investments worthwhile and enabling them to hire and retain qualified, experienced staff for specialized testing. Examples of this include inductively coupled plasma-mass spectrometry (ICP–MS) and inductively coupled plasma-optical emission spectrometry (ICP–OES), which are used to detect elemental impurities.
Working on a wide variety of programs gives contract labs an advantage for problem solving and regulatory compliance. Frequent inputs from global regulatory agencies and client quality departments give contract labs a strong sense of industry expectations and numerous examples of how to plan, execute, and report method development and testing that is acceptable for submission.
Tishmack (AMRI): Certain analytical techniques are more conveniently outsourced because they may be tedious or require significant overhead or training that could distract from a company’s focus. This might include potent compounds, controlled substances, or other special handling requirements such as inert atmosphere.
Virtual companies that do not have any internal analytical capabilities usually call on one or more contract research organizations to do all of their analytical testing.
Larger pharmaceutical companies may want to outsource certain types of analytical testing to be done in parallel to internal studies for validation or troubleshooting. Outsourcing is also a good way for a pharmaceutical company to expedite development timelines or to move lower priority development out of their laboratory so that there will be some progress when it eventually becomes a higher priority.
PharmTech: Which small-molecule analytical services should pharma companies consider outsourcing?
Tishmack (AMRI): Nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry are commonly outsourced because these capabilities are typically quite expensive to acquire and maintain. Both techniques usually require experts to properly maintain the instruments and to implement advanced applications that will obtain maximum value from the techniques.
Elemental analysis and metals analysis are very commonly outsourced, particularly if GMP compliance is needed. Carbon, hydrogen, nitrogen, and sulfur analyses are relatively simple to perform, which means that high volume is the only economical way to use the instrument. Metals analysis by ICP–MS or ICP–OES may be more conveniently outsourced due to the acid hydrolysis procedure needed for sample preparation and the instrument maintenance requirements.
PharmTech: Which large-molecule analytical services should biopharma companies consider outsourcing?
Tishmack (AMRI): Mass spectrometry is typically used for peptide mapping and protein sequencing, which requires a high-performance instrument and an experienced scientist.
NMR spectroscopy of large molecules is still a very specialized technique that requires a highly skilled scientist with specialized training to collect good quality data and to properly interpret the complex NMR spectra. Therefore, relatively few CROs have this capability.
Capillary electrophoresis, particularly combined with mass spectrometry, is a high-value analytical technique for most biologics and larger molecules. This technique is very useful for difficult separation and characterization procedures.
Cell-based assays can be quite difficult to develop and validate, so an experienced CRO will expedite biologics development and preclude the need to invest in the specialized infrastructure required for maintaining cell lines.
PharmTech: What are the downsides to outsourcing analytical services?
McClintock (Metrics Contract Services): Analytical methods and results are a critical part of product development, so outsourcing this work could create a gap for the pharmaceutical company. A strong contract lab partner will make sure the sponsor understands more than just the values reported. For example, the contract lab will convey observations made during dissolution since these can be critical to assessing whether the formulation and process are robust.
PharmTech: What are some best practices for data integrity and tech transfer when it comes to outsourcing analytical services?
McClintock (Metrics Contract Services): It is a tech transfer best practice to completely evaluate method(s) being transferred for method competency and successful transfer.
Tishmack (AMRI): A highly competent quality unit is a key indicator that the CRO knows what it takes for appropriate regulatory compliance. A good indicator that a CRO has adequate control over their processes is the existence of a laboratory information management system (LIMS), particularly if nearly all laboratory processes, data integrity, and quality assurance procedures are integrated into it. A critical consideration is determining if the CRO has electronic records that are created and maintained by software with rigorous user access control, extensive audit trailing, and secure archiving of data files. It is also very important to determine whether the CRO has experienced scientists with extensive training who can provide expert analytical method development and validation under GMP compliance.
PharmTech: Which outsourced analytical services are in high demand?
McClintock (Metrics Contract Services): We are seeing high client demand for residual solvents, elemental impurities, API solubility and dissolution method development, and API characterization.
Tishmack (AMRI): Unknown particle identification, NMR spectroscopy of solids and liquids, chromatography, and mass spectrometry have all been growth areas, especially non-routine testing to solve unusual problems.
PharmTech: Are there analytical processes not currently being outsourced that you anticipate will be in the future?
Tishmack (AMRI): Pharmaceutical companies typically adopt new analytical techniques rather quickly, but they tend to rely on them for release testing of drug substances and drug products only after significant assurance of reliability. Although nearly every common analytical technique can be outsourced if desired, many pharmaceutical companies are selective in the types of analyses outsourced to a CRO depending on their own experience and internal capabilities.
Selective outsourcing of biologics testing is quite common because pharmaceutical companies are reluctant to rely on potentially less experienced CROs to transfer or develop analytical methods for biologics that are difficult and expensive to make and test. Atypical analytical techniques that are still in the development stage may eventually be outsourced once they have been better established as suitable tests for pharmaceutical development.
1. R. Rader and E. Langer, “The Outlook for CMO Outsourcing in 2019, Pharmaceutical Technology 43 (1) 2019.
Supplement: Partnering for Bio/Pharma Success
When referring to this article, please cite it as S. Haigney, “Utilizing Analytical Services for Success in Innovation," Partnering for Bio/Pharma Success Supplement (February 2019).