Pharmaceutical companies of all sizes outsource at least some quality control (QC) testing to contract analytical testing laboratories. Virtual and smaller companies may not have the staff to conduct such testing, whereas mid- to large-size companies may outsource testing that they do not wish to perform in-house. In the relationship between a pharmaceutical company and its outsourcing partner, each partner has clearly delineated responsibilities, both business and compliance related. In May 2010, we discussed a contractee's (contract giver's) responsibilities (1). Here, we focus on those of the contractor (contract acceptor), limiting our attention to responsibilities in the contractee– contractor relationship. Neither discussion addresses purely business-related concerns such as revenue growth, development and retention of staff, and shareholder reward.

Compliance

The laboratory to which a pharmaceutical company outsources QC testing in effect becomes an extension of that company's own QC organization. Its compliance requirements must therefore be matched by those of the contractor. In most cases, therefore, the contract testing organization must meet good manufacturing practice (GMP) requirements. For a testing organization, that generally entails clearly defined quality systems, including sample chain of custody, organization and personnel, buildings and facilities, equipment, control of components, laboratory controls, change control, and records and reports.

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Evidence of a sufficient level of GMP compliance can be proven by the results of regulatory inspections, especially those conducted by the US FDA and the EMEA. With the former, satisfactory performance is evidenced by the absence of an unresolved FDA Form 483 (“Notice of Inspectional Observations”). The EMEA recognizes satisfactory performance by issuing a GMP certificate. Regular compliance visits conducted by sponsoring pharmaceutical companies contribute to a contract testing organization's ongoing steady-state level of GMP compliance. The nearly continuous flow of inspectors through a laboratory certainly provides ample opportunity for continuous improvement in compliance.

Long-Term Partnerships

When a pharmaceutical company decides to outsource QC work, it selects a contract laboratory on the basis of several criteria (1,2,3). Aside from compliance, method, and quality considerations, the sponsoring company must have assurance that outsourced methods will remain available at a contract laboratory over the long term. So the contractor must be financially secure and willing to commit to maintaining trained staff, secured facilities, reagents, and calibrated equipment necessary for performance of those methods for as long as they are requested. Should a contractor determine that it is not in its own best interest to maintain a given assay in its portfolio, sponsor companies using that method must be given sufficient advance notice to pursue other options.

Responsiveness and Adherence to Quality Agreements: A contract testing laboratory must make itself available to a sponsoring company's contacts. Poor responsiveness endangers the partnership. So it is advantageous for a contractor to set up a single contact for each client. That contact may better reside within a client services or program management group than in the testing laboratory itself.

A contract testing laboratory's contacts and responsibilities are specified within its quality agreement with each sponsoring company. The content of that agreement is described elsewhere (1,3). A quality agreement specifies clearly (from the sponsor's point of view) the contract laboratory's responsibilities in quality systems; compliance; equipment, reagent, and method characterization/validation; data recording and archival; sample receipt, storage, and retention; interactions with client and regulatory inspectors; conduct of investigations into unexpected and out of specification (OOS) results; and change control. During contract laboratory oversight, sponsor companies typically evaluate a contractor on the basis of its performance against the terms of the quality agreement. A sponsor can expect to address deficiencies in its periodic compliance audits of the contractor.

Organization and Personnel

Contract testing laboratories are expected to maintain a high caliber of scientific expertise in their staff who direct assay performance and operators who conduct assays. This level of expertise will be called upon in the event of unexpected or OOS results. Rapid troubleshooting of problems that invalidate assays and identification of OOS root causes require a high degree of expertise with a given assay system. In addition, scientific credibility comes into play for assay designs complicated by factors not normally encountered (e.g., viral testing for infectious viral vaccines or oncolytic viruses).

In some cases, scientific expertise in a specific method is reflected by participation of contractor staff in national/international consortia establishing or revising guidance or standards pertaining to that method (e.g., US Pharmacopeia, European Pharmacopoeia, American National Standards Institute, and the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use). Accessing this level of expertise is always beneficial to a sponsoring company because it can lend a higher degree of credibility to the work being performed.

In addition to scientific expertise, a robust quality assurance (QA) unit is essential to a contract laboratory's success. Responsibilities of the QA unit — as well as management's responsibilities and commitment to quality — should be clearly defined and described in documents such as a quality manual or quality policy (4). Personnel should be made aware of such documents, and proof of training on them should be made available to sponsor companies during audits.

Typical QA responsibilities include review and approval of procedures such as standard operating procedures (SOPs) and analytical methods, as well as validation and transfer protocols and reports. QA also participates in execution of nonconformances, deviations, and OOS investigations; approval of change control records; and hosting of regulatory inspections and client audits, including follow-up and closure. In some companies, QA staff are involved in routine data review, which is good practice. At a minimum, QA should review and approve certificates of analysis before their issuance to clients. Management awareness of quality issues (e.g., nonconformances, OOS results, and invalid assay trends) is a GMP requirement (5). To facilitate satisfaction of that requirement, QA representatives may compile periodic summaries and submit them to management.

A well-established training program is critical to the success of all contract laboratories. In addition to technical training, all personnel involved in testing and generation of data must be trained on GMP requirements. This includes consultants and contractors (5), those who are often overlooked by contact laboratories. Such training must be documented and available for review during regulatory inspections and client audits.