Thanks to significant advances in discovery science, there is a dramatic increase in the number of new compounds moving from discovery into biopharmaceutical product development. The goal of nonclinical testing is to eliminate poor candidates while moving quality candidate drugs into clinical development as quickly as possible. At any given time, there are 3,000-4,000 compounds in nonclinical testing that have made the cut from discovery into development. Ongoing incremental improvements in the discovery and selection process continue to occur, which should result in a higher rate of success for compounds entering the expensive clinical development phase.

Given today’s time pressures and the high cost of discovery and development in biopharmaceutical research, it is more important than ever that supporting services, such as bioanalysis, are optimized for speed and success. Bioanalysis, simply stated, is the quantitative measurement of an active drug in a biological matrix; it is required for evaluation of a therapeutic entity throughout the entire drug development cycle. In the early stages of discovery, lead selection/optimization and nonclinical development, the focus is on science: creating and refining analysis methods that will accurately and efficiently assess the drug level in a variety of species and biological matrices. As development moves from nonclinical to clinical investigations, the bioanalytical support required also undergoes a transition. In the later stages of development (Phases II-IV), the challenges of sample transport and handling from complex, multi-site, often multi-country trials, along with substantial data management needs, add a requirement for logistical excellence in addition to scientific capability (see Figure 1).

Figure 1. Bioanalytical Analysis Across the Development Spectrum

Bioanalytical sciences such as feasibility and method development support critical pharmaceutical evaluations, including toxico- and pharmacokinetics, bioavailabilty, drug-drug interaction studies and other systematic assessments. Due to the sheer volume of work required in nonclinical and clinical product development, lead times must be carefully managed to keep projects on track. Today, many pharmaceutical and biotech companies utilize outsourcing to accomplish at least a portion of their bioanalytical needs. Outsourcing of bioanalytical services may be done strategically or tactically and depends on business, financial and technical factors.

Using outsourcing as a strategy helps manage the ebb and flow of projects entering or leaving product development due to toxicity, economics or changing priorities. It may amortize the strengths of a particular outsourcing partner and provide additional scientific and operational excellence that can help provide information to make go/no-go decisions. Depending upon the specific type of project and compound, commercial bioanalytical laboratories can often quickly develop and validate scientifically robust methods, then smoothly integrate those methods into sample runs within weeks or sometimes even days of the initial project inquiry. Project initiation may begin immediately for established, validated assays, depending on the laboratory’s capacity. Bioanalytical outsourcing often provides sponsors with more flexibility, global reach and less investment in personnel and capital infrastructure, while expanding scope and capabilities that may not be available internally.

Strategic Vs. Tactical
Strategic outsourcing generally involves a corporate commitment to a vendor partnership for value-added benefits, with a focus on each partner’s strengths as a long-term strategy. It entails a decision to leverage the sponsor’s internal resources so that it adds maximum value for the discovery, development, and commercialization of new pharmaceutical or biological products. More commonly, capital- and/or labor-intensive development activities are outsourced, so the sponsor’s focus is on the evaluation of incoming compounds and which entities are the most promising candidates for development. Benefits that may be gained from strategic partnerships include: effective leveraging of investment in methods and science across the life-cycle of the product development program; consistent, customized services; enhanced communication; and specific scientific talent and expertise. Strategic outsourcing relationships generally yield financial benefits that range from maintaining tight control of fixed costs to leveraging fixed-cost investments toward activities that occur earlier in the discovery-development sequence—activities that are usually more of a unique “core” strength of the sponsor organization.

Companies that take a more tactical approach are often faced with short-term workloads that exceed their internal human resources or capacity. Tactical outsourcing is more “deliverable-focused” as opposed to value-added. Outsourcing the bioanalytical component helps them gain additional capacity when internal capacity is unavailable, streamline workflow and validate claims for additional internal resources. Often, these encounters are transactional one-time events to manage peak work volume and complete projects more quickly than the sponsor could internally. Neither the sponsor nor the contractor derive or amortize the longer-term benefits that may result from effectively working together over time. Of course, many companies find themselves somewhere along the continuum between strategic and tactical outsourcing and thereby derive some of the advantages and limitations of each approach. In either case, it may be important to evaluate which approach predominates in order to assess and choose a bioanalytical partner that will best meet a sponsor’s unique needs.

Bioanalytical Laboratory Assessment
The process of contract laboratory selection starts with the sponsor’s request for proposal (RFP). The RFP details the scope of work and includes all the pertinent information necessary for a contract bioanalytical laboratory to estimate the time, talent and costs associated with the potential project. Internally the sponsor should have an unambiguous understanding of the project scope (is it research-focused method development or production with thousands of samples?) and clearly communicate that to the laboratory under consideration. While the vocabulary may sound similar, meanings from organization to organization often differ, so expectations and terminology should be well defined in order to maximize efficiencies and cost-effectiveness.

A number of quantitative and qualitative elements should be examined when making a commercial bioanalytical laboratory assessment. The analysis should, of course, include assessments of capabilities, capacity and scientific talent. A deeper investigation should reveal a clear understanding of the laboratory’s quality processes, turn-around times, regulatory compliance, communication vehicles and other underlying factors that ultimately contribute to a laboratory’s “ease of use” factor and ability to consistently deliver over time.


Capacity
It is vital that method development, transfer and validation be coupled with sufficient “production” capacity to keep a product on the critical development path. These activities are frequently conducted using different resources, so it is useful to evaluate the capacity of a laboratory in each area. Acquire insight on whether any of the needed resources are assigned “double duty” (e.g., resource committed to work in both method development and production) and develop a clear understanding of the effectiveness of communication and interaction among resources. Discover whether any bottlenecks exist in the process. There are always times when sponsor companies need more instruments or staff. Understanding what personnel, equipment and facility resources are available and how they are managed, allocated and scheduled to projects is crucial. A commercial bioanalytical laboratory typically runs high sample volumes (particularly for later stage development) and is uniquely equipped to rapidly provide additional capacity. Typical questions that may help evaluate commercial laboratory capacity are listed below:

• How many samples does the analytical laboratory analyze per year?
• What is the laboratory’s capacity to store samples or expand services on demand?
• How much of a laboratory’s total capacity would the work being considered for   placement occupy?
• What types of analytical equipment does the laboratory have? How often is the   equipment calibrated and maintained? Are the technologies and systems   compatible with the sponsor company’s systems?
• How many [type of test of interest] does the contractor do in a week? A month? A   year?
• How many [specify type of equipment of interest] are available and in what   geographic locations?
• How quick are turnaround times for [type of test or results]?
• How flexible is the laboratory if a project is added or cancelled?
• How are resources managed and scheduled? Describe the policies and processes   in place for scheduling work. How does this differ for method development versus   production work?
• Does the laboratory provide dedicated resource services to accommodate large   capacity needs over longer periods of time?


Experience
No sponsor can afford to put a development program at risk. A commercial bioanalytical laboratory should have the talent and experience it takes to execute the project or it should decline the work. Examine the organization’s peripheral experience in regulatory, quality systems and information technology. Has the laboratory identified opportunities to improve quality and efficiency and installed methods to drive those changes? Look for an organization that is focused on amortizing the experience it has within and is willing and able to leverage that experience for a sponsor’s program.

• Does the laboratory have experience with the class of compounds or technique of   interest?
• How many methods are validated each year? How many are originated at the   laboratory and how many involve technology transfer?
• How many scientists/technical experts will be devoted to the project in question?   What are the policies and processes on how those experts are engaged and   scheduled?
• What are the scientific credentials of the study director, study monitor or principal   investigator assigned to the project?
• What is the training process for scientists? For technicians?
• What is the staff turnover in each department?
• Do the study directors, study monitors or principal investigator have the necessary   experience relative to the project in question?
• Does the laboratory have experience in method transfer? Do they provide efficient   systems for doing so?


Quality
Quality is paramount in pharmaceutical product development. How a bioanalytical laboratory approaches quality is a statement about its priorities. The FDA requires nonclinical bioanalytical work for regulatory submissions to be in compliance with GLP. While a recently communicated FDA guidance explicitly omits GLP compliance for bioanalytical work related to human clinical trials, the importance of these studies requires quality beyond compliance.

Quality systems should be “built in” to prevent errors or to catch them in real time. If a laboratory’s systems and procedures are well set up, quality control and quality assurance should not cause delays. Look for process auditing and process controls that minimize time delays or escalation of costs.

• What quality systems, SOPs, GLP or auditing procedures are in place?
• Is quality proactive or reactive and how is that demonstrated?
• What critical review procedures or peer-review steps are performed?
• Does the QA/QC process in the bioanalytical laboratory contribute or cause delays   or bottlenecks to receipt of the deliverable?
• What regulatory expertise does the laboratory have and how does it keep abreast of   the changing regulatory environment?
• How long has the laboratory operated in a regulatory environment?
• How many regulatory agency and/or client audits has the laboratory had and what   were the results?
• What plans are in place or steps are being made to ensure electronic records and   signatures comply with 21 CFR part 11?
• What type of quality control talent is dedicated to each project?

Performance and Productivity Measures
Each study is ultimately unique, but the performance and track record of a commercial bioanalytical laboratory will provide insight and help set expectations for future work. Ensure that the laboratory has mechanisms in place to track performance.

• What are the on-time delivery performance metrics? How are they assessed against   client expectations?
• How is customer satisfaction assessed?
• What is the laboratory’s error rate (including error severity and corrective action   plans)?
• How are errors tracked and followed up?
• What productivity measures does the laboratory track in development? In   production? Are these shorter or longer than sponsor company internal metrics (if   available)?
• How quickly does the laboratory develop and validate a method (on average)?
• How focused is the organization on maximizing efficiencies and minimizing costs?
• Does the promised turn-around time match the requirements of the sponsor?
• Where are the typical bottlenecks and slow points in any particular bioanalytical   assessment? How likely are they to affect turn-around time?


Information Technology &Data Management
The information technology infrastructure and level of automation within a contract laboratory should be examined. Highly automated organizations may have replaced labor intensive repetitive work, which may provide more consistency from run to run and/or result in more rapid delivery of cost-effective services.

Contract laboratories should also demonstrate efficient, robust data management and data processing systems, particularly when data-intensive studies such as Phase II-III studies are under consideration. Strong science capabilities are moot if the contractor is unable to meet deadlines because reports or deliverables are stalled by data delays. Look for automated data processes from sample receipt to final deliverable.

Highly IT-enabled bioanalytical units should be able to simultaneously maximize their ability to work efficiently, provide exceptional sample tracking and integrity, maintain superior regulatory compliance, minimize turnaround times (particularly from the collection of the last data point to the report), streamline client communication and access to data and continuously address areas of inefficiency through analysis of business metrics.

• What functions have been automated and where has this resulted in efficiencies or   reduction of development costs?
• What IT strategies are in place for study management (tracking, data transfer,   processing and accuracy)?
• Have IT systems been properly validated?
• Are data systems compatible with the sponsor systems?
• Are data systems capable of handling large quantities of data?
• How sophisticated are the data management processes?
• What sample management system is employed?
• What company-specific systems are there (e.g., LIMS-laboratory information   management system) and what do they do?

Communication
Success in bioanalytical outsourcing is probably more dependent on good communication than any other single factor. Detailed communication plans are essential for meeting expectations and keeping projects on track. Some contract laboratories provide a single point of contact, while others allow the sponsor to contact anyone within the organization who is involved with the project. Most contractors provide a customized communication plan to meet sponsor requirements. The value of face-to-face interactions to establish a strong working relationship cannot be underestimated, particularly when deadlines are critically tight.

• What expectations exist for reports, formats and/or timing?
• What elements comprise the communication plan and how is it executed?
• Who are the key contacts responsible for the project and how available are they?
• How flexible is the contract laboratory with regard to report formats, file types and   style standards?
• With what frequency is communication between sponsor and contract laboratory   maintained? Using what methods?
• How flexible is the laboratory with respect to communication protocols? How   effective are their communication protocols when “customized” to fit a sponsor?
• How often are face-to-face client meetings scheduled or allowed?
• How is contingency planning handled?
• What (if any) direct communication links can or will be provided as part of the   contract (e.g., secure e-mail)?

Financial Stability
It is important to know that the contractor is financially viable and will be in business when the sponsor needs it, particularly when late-phase, multi-year studies are under consideration. Assess the laboratory’s level of commitment to the field and to refining and extending its support services.

• What is the financial and business position of the bioanalytical laboratory?
• Does the laboratory have the financial means to invest in quality people, equipment,   and facilities?


Ease of Use
The answers to these questions are extremely important as evaluation tools. However, a less readily defined element—”ease-of-use”—may be critical in the final decision. Services must be crisp and clean. Problems have to be quickly communicated and solutions to those problems should be recommended. Information must be free-flowing, but at a pace and frequency desired by the sponsor. Flexibility should be applied to accommodate the sponsor’s shifting needs and priorities. Each sponsor will have a unique collection of requirements that add up to “ease-of-use” and the answer to that set of questions will factor prominently in the final selection of a contracting partner. In the end, a good outsourcing partner will provide a combination of capabilities, services and processes that instill confidence and save the sponsor time and money.


Contracting Bioanalytical Services
Contracts are the tools used to establish a framework for the working relationship between the sponsor and the contract laboratory. A clear understanding of project scope and specifications, including details of the essential activities to be outsourced, is necessary. While a large number of pharmaceutical and biotechnology companies have accepted outsourcing as a strategy, a small but rapidly growing number of organizations have put processes in place to broadly and systematically identify, select and manage bioanalytical laboratory contractors. Both business and technical input are required for the contracting process to be fully successful.

In larger companies, the sponsor generally assembles a cross-functional team to make the outsourcing decision that, at a minimum, includes the project manager, a bioanalytical scientist, a quality assurance representative and a contracts (or purchasing/procurement) manager. In smaller organizations, a single individual and a quality assurance (QA) representative may be responsible for selecting a contract lab. Project managers responsible for overall clinical programs may be focused on big-picture logistical concerns (e.g., sample management or how soon data is available). Bioanalytical scientists, on the other hand, very often have worked on the proprietary methods that will be used. Science is paramount and they may be more focused on the experience of the scientists or technicians at the contract laboratory who will perform the work. The QA representative will focus attention on quality systems and processes and assess the laboratory’s regulatory compliance program. The contract manager’s focus may be on the protection of the sponsor’s legal and financial interests (outlined in the contract), as well as the company’s proprietary interests (delineated in a Confidential Disclosure Agreement). Balancing competing interests around the outsourcing decision can often be challenging.

The most successful outcomes, however, typically occur when the contracting group or the individual that contracts the service has worked in a bioanalytical laboratory and/or is very familiar with the processes and services in these organizations. This familiarity may help prevent “scope creep” and ensure a fair agreement on timelines and compensation. Sponsor companies are best served by a contracting individual or group that is able to make judgments on the bioanalytical component of drug development for the particular product, understands the difficulty or simplicity of method development or transfer and the decisions that impact timelines.

The Contracting Process
Contracts may be simple or complex and are highly variable from one bioanalytical project to another. Contract pricing models vary according to the type of work under consideration. Method development may involve hourly fees, based on an estimate of the time it will take to come up with a viable, scientifically robust assay. Production bioanalytical work may be priced at a fixed fee per sample, with a sliding fee schedule based on volume. Nearly any element of a project is fair game for negotiation, from method runs to equipment, or from the people assigned to the project to payment schedules.

Contracts may be negotiated in less than a day or take much longer. One of the primary delays to quick study start-up is working through the legal verbiage that must necessarily go back and forth between the contract laboratory and sponsor. To a certain degree, master service agreements (MSAs) or preferred provider agreements (PPAs) address those bottlenecks, and facilitate the contracting process by covering common contractual elements including liability and confidentiality. MSAs and PPAs are particularly useful when strategic outsourcing is employed; the contract laboratory has a commitment for repeat business and can start pre-study work while project specific details are under negotiation.

Fair prices and the costs of bioanalytical services require a certain amount of reflection and consideration. While it may be prudent to challenge high prices for the sake of saving money, for the sponsor using bioanalytical services strategically, it may be just as important to challenge very low prices. The acquisition and retention of good talent, the timely introduction of modern technology and the implementation of adequate data systems are not sustained by low pricing.

Once a contract is signed, work is scheduled and initiated. Adequate supplies of test material and references should be provided to the contract laboratory with all the pertinent documentation well in advance of the study initiation date. Should the scope of the project change or should study delays or cancellations occur, the price quotation may change accordingly.

Not all commercial contract bioanalytical laboratories are created equally. Each drug development program has its own unique requirements and those requirements change as the stages of development unfold. Identifying a laboratory with too narrow a match with one drug or stage of development will likely produce inefficiency later in the program as those needs change. Conversely, identifying a laboratory with a broader range of capabilities may provide a less effective match with the needs of “today.”

Finding a laboratory with the breadth and depth to match the various talent, expertise, capacity and speed requirements of a drug development program can be a daunting challenge. Method development may be fraught with technical difficulty in crafting a scientifically robust, consistent, transferable assay. Full-scale production bioanalysis may be more fast-paced, requiring quick turn-around, plenty of capacity and logistical excellence. It is important to fully understand what present and future needs are or will be in order to find a complementary partner for outsourcing bioanalytical services.

The right combination of capacity, experience, quality, performance, communication and other attributes must be carefully assessed for “ease of use” in the evaluation of a contract laboratory. The contracting process is also an important consideration and must be factored into the overall planning process and timelines. A vigilantly nurtured bioanalytical outsourcing relationship has many benefits, including expanded resources, enhanced communication, global reach and the flexibility to accommodate time-critical product development. Fully understanding the scope, depth and breadth of what a commercial contract laboratory offers can provide the necessary information to make an informed decision and establish an outsourcing relationship that extends across time with a wide range of services for sponsor support.