Contractee Responsibilities in Outsourced Pharmaceutical Quality Control Testing

aMethod Qualification (Verification and/or Validation)Once a contract testing laboratory has been given “approved” status, the actual methods to be used may be qualified for their purpose. If the contractor has a desired compendial method in place, the contractee is responsible for providing a sample of test material for verification according to compendial requirements. The US Pharmacopeia includes guidance on verification of compendial procedures (16). For noncompendial lot-release methods (e.g., viral and mycoplasma testing, which are driven by US FDA points to consider and ICH guidance documents), the methods will require validation if used for GMP purposes.
Validation is normally performed by a contract testing organization with a generic sample matrix, so it should not be confused with the product-specific qualification described below. Validation of compendial procedures is outlined in the US Pharmacopeia (17) as well as the International Conference on Harmonisation of Technical Requirements for the Registration of Pharmaceuticals for Human Use (ICH) (18). A contractee may wish to confirm the status of a given method by evaluating validation reports during an on-site visit. Contract testing labs may also be willing to provide copies of method validation reports or summary documents describing those results.
Commercial product lot release testing is expected to be performed using methods deemed suitable for a given product. This typically entails product qualification for the analytical method and evaluation of possible matrix interference. The contractee is responsible for commissioning such studies before routine use of any method and should maintain the resulting reports as evidence that the methods being used are suitable for their purpose. Such studies may need to be repeated if the processes involved in manufacturing a commercial product are modified significantly. Quality and Business Agreements Regulators expect that the relationship between a product sponsor and its contract testing partner be formalized by a quality agreement (7,8). Such agreements specify explicitly the responsibilities of each partner and provide the means by which a contractee extends its QC testing standards to a contractor. The agreement should list technical and/or quality contacts (names and phone numbers) at the contract testing organization as well as contact information for appropriate decision makers at the contractee organization.
Among the specifics to be detailed in a quality agreement are

• the types of compliance to be followed in contracted studies
• details on interactions between the contractor's and the contractee's quality systems
• requirements for equipment and assay validation, verification, and/or qualification
• assurance of quality and reporting requirements
• data recording and archiving practices
• conduct of investigations into nonconformances, deviations, unexpected, and OOS results (and timing of client notification)
• notification of regulatory inspection
• requirements for use of subcontracting laboratories
• use of debarred personnel
• availability of the contract testing laboratory for periodic technical and compliance as well as for-cause audits.

Business requirements should be addressed in a separate document and may take the form of a master service agreement, an agreement of scope, a pricing agreement, or a standard terms and conditions agreement supplied by the contractor. Such considerations may include assay pricing (including discount structures), assay initiation and report turn-around times, testing volume and exclusivity, availability of rush service and associated charges, and (in some cases) penalties for late reporting. These business agreements often specify the requirements of a contract testing laboratory with respect to contractee notification of impending sample submission, which are detailed below.