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Susan J. Schniepp is a fellow at Regulatory Compliance Associates, Inc. and a member of BioPharm International's Editorial Advisory Board.
Open communication channels between all the parties involved is key when outsourcing analytical methods, says Susan Schniepp, distinguished fellow at Regulatory Compliance Associates.
Q. I head up the quality control laboratory for a contract manufacturer. Business has been increasing and the laboratory operations are strained, so I am considering outsourcing some of the analytical methods. Can you offer some advice on what I need to consider in choosing a contract test laboratory?
A. When outsourcing any operation, the primary consideration should always be determining the capabilities of the service provider, in this case a contract test laboratory. This assessment depends on a number of factors including what methods for which products are being considered for outsourcing.
It is crucial to be transparent with your clients, so the first step is to inform them of your intent to outsource some of the analytical methods traditionally performed by your laboratory. They may have experience with outsourcing analytical methods and may be able to offer advice about what to review when choosing a testing facility. They might also have objections to the further outsourcing of their methods, and this concern should be considered when determining which methods are suitable for outsourced testing.
The next step should be to perform an audit of the facility you are thinking of using for this activity. During the audit, you want to focus on several areas including the support you will receive during the transfer and validation/verification activities for the methods being outsourced. Some of the methods to be transferred may be proprietary and some may be compendial; the detail involved in transferring them will vary. Either way, outsourcing testing for just one product means multiple methods will be involved during the transfer activities, so it is critical that the test laboratory has a process for onboarding new methods in a timely and efficient manner. Attention should also be paid to how the testing facility maintains and calibrates its equipment and the qualifications of the analysts that are responsible for the material testing.
Particular attention should be paid to how the contract laboratory handles out-of-specification (OOS) investigations. The general rule is that the laboratory that generated that data owns the analytical data, and therefore, they are responsible for performing any OOS investigations. What you need to focus on for an OOS evaluation is to determine if the contractor’s standard operating procedure is in compliance with FDA expectations (1) and what their communication scheme is for notifying clients when an OOS occurs. The laboratory that generated the data is really the only entity that can verify whether the OOS was a result of laboratory error or if the investigation into the result needs to be expanded to manufacturing. It is important that the contract test laboratory has an open and transparent relationship with their client and that the client has an open and transparent relationship with their client. A robust communication scheme and an open and transparent relationship are crucial for quickly determining the direction of the investigation and ultimately the determination of the final product disposition. All parties in the relationship should be willing to discuss and disclose any method issues that arise. Any reluctance in establishing open communication channels with all parties in the relationship should be considered a red flag.
Once the audit is complete and you have decided on the methods to be outsourced, you need to construct a quality agreement (2,3) with the laboratory. Defining the responsibilities that might come up over the course of the agreement is a critical step in establishing a long-term productive relationship. Some responsibilities that should be discussed include who will monitor the compendia for method changes and maintaining the stability of reference standards, as well as the proper receipt and handing of the testing samples. Another responsibility that needs to be discussed and clearly defined is who is responsible for initiating and approving change controls for method changes. Clearly defining responsibilities upfront will help to eliminate disagreements and testing delays when issues arise.
Another consideration that needs to be discussed is the handling and maintenance of the documentation that supports the suitability of the methods. Both the test laboratory and the client should have documentation that supports the use of the methods. If the testing being done has been contracted by a CMO on behalf of a client, the client should also have the documentation supporting the method. The documentation to be shared should include, but not limited to, method development reports, validation and technical transfer/protocol reports, change controls, final test results, OOS investigation reports, and documentation that supports the shipping, receipt, and proper handling of the test samples. The sharing of these data is crucial in establishing continuity between the parties in the event of regulatory inspections or inquiries.
Outsourcing analytical methods is a critical activity that can affect the operations of the contract test laboratory, the contract manufacturer, and the product owner. Assuring the veracity and the validity of the data is key in defining the success of the relationship and depends on open communication channels between all the parties involved. Establishing a robust quality agreement with the unambiguous delineation of responsibilities and an effective communication scheme will make the outsourcing of test methods a successful experience for the parties involved.
1. FDA, Guidance for Industry: Investigating Out-of-Specification (OOS) Test Results for Pharmaceutical Production (CDER, 2006).
2. FDA, Guidance for Industry: Contract Manufacturing Arrangements for Drugs: Quality Agreements (CDER, 2016).
3. EC, EudraLex Volume 4, EU Guidelines for Good Manufacturing Practice for Medicinal Products for Human and Veterinary Use, Chapter 7, Outsourced Activities (EC, Jan. 31, 2013).
Vol. 31, No. 6
Pages: 50, 49
When referring to this article, please cite it as S. Schniepp, "Outsourcing Analytical Methods," BioPharm International 42 (6) 2018.