I had been working with a large CMO on a commercial injectable product for a couple of years; the CMO had a terrific support structure, including a fully functioning laboratory. Its quality systems met my team’s needs and its regulatory team provided appropriate support for our program. However, when we tried to bring in a clinical trial drug product, we found several limitations in using the CMO: there was not agility in meeting rapid timelines; also, process losses were acceptable for large-scale batches but represented significant issues for small batches. We needed some preclinical batches as well, so GLP manufacturing was part of our base needs.

So, we were compelled to find a different CMO to support preclinical and early-phase batches. We wanted to find an organization that could provide appropriate manufacturing services and laboratory support appropriate for early-phase clinical GMP requirements. The trouble is, CMOs in this space often do not invest in laboratory capabilities to support GLP and GMP testing. It is expensive to purchase and maintain complex equipment, and it’s even more expensive to keep trained personnel on staff; developing and transferring test procedures requires high technical experts. CMOs that specialize in clinical trial manufacturing often outsource testing or rely on innovators to arrange analytical aspects of their programs.

At early-phase manufacturing, the regulatory strategy for testing drug substance and drug product depends strongly on determining that the right quality attributes are measurable and in control. Further, understanding the regulatory lines between the GMP testing requirements for a clinical product and a commercial product is itself a specialization.

When selecting a site for commercial manufacturing, taking laboratory capabilities into consideration is expected. As an outsourcer, we didn’t want to manage multiple contract facilities; this requires audits and supplier quality management, and an out-of-specification, out-of-trend, or unexpected result obtained in a separate laboratory complicates an investigation. However, for sites that manufacture for clinical and preclinical work, laboratory capabilities may be only adequate to provide direct manufacturing support. Laboratory equipment, maintenance, and expertise are expensive, and procedures used for clinical and preclinical manufacturing runs are often undeveloped and unreliable.

The hurdle we needed to jump was finding a laboratory partner that could support our program. To accomplish preclinical work, we needed a laboratory that understood the differences between GLP and GMP; GMP testing is not only expensive but also requires procedure validation, which is not necessary for preclinical work. Further, when the clinical trials begin, there are different qualification requirements for a test procedure supporting Phase 1 compared with later-phase studies. Formulations and presentations change, and to keep agility, we needed a laboratory that was agile enough to react quickly. Typically, timelines for clinical trials are short and changes need to be addressed quickly and effectively.

Another issue is the testing itself. Especially for an innovative new drug, a laboratory research scientist may have developed a test procedure for measuring content. However, the scientist may not have evaluated suitability or robustness of the assay, and so when a testing laboratory attempts the assay, it is unsuccessful. Development may be required, which interferes with timelines and causes anxiety. Further, especially for virtual organizations, there may be no scientific expertise, so there is just a request to find an appropriate test procedure and qualify it.

So, how did we go about finding the right laboratory?

To begin, we evaluated our testing needs. We did this by examining the specification documents for drug substance and drug product, and then listing the techniques that need to be in place for the quality attributes. We wanted to limit the number of individual outsourced laboratories to have in place. Having multiple laboratories that do one or two tests each would require oversight for each lab, which is costly and complicated. A laboratory investigation that requires additional testing may mean involving two or more laboratories, a complicated task with multiple quality systems impacting the investigation. So, a list of all the test procedures and the techniques used in each is a start.

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Next, we evaluated the equipment used in developing the test procedures. Equipment and detectors vary across the board. Many assays are technique driven, and so instructions and precautions taken in one laboratory may not apply to another. In some cases, a piece of equipment needs to be purchased to support a product; in that case, there are timeline considerations and maintenance and calibration programs need to be implemented.

Next, we selected contract laboratories that could meet as many of our needs as possible, hoping to have a single competent laboratory. From the list of selected laboratories, we narrowed the list to the most desirable, considering capabilities, cost, and quality systems. We completed due diligence examinations of the labs. This included a quality audit but also included contacting colleagues and reaching out to knowledgeable technical people for informed opinions. A laboratory may have all the capabilities listed, but you may find that others have struggled with the laboratory teams with errors, gaps in experience, gaps in knowledge, or poor investigations. Surveying others for this experience may save you from putting your carefully-manufactured product at risk.

Finding a contract laboratory to fit the needs of your product is often challenging. Especially in the clinical and preclinical space, laboratory support is critical to presenting a foundation to the agency that your product is of the right quality and safety, and the basis of this before validation batches have been made depends wholly on the quality controls in place.

About The Author:

Barbara Berglund is COO of CMC Turnkey Solutions, where she applies over 20 years of experience in finished pharmaceutical, API, and medical device manufacturing. In particular, she has direct experience with quality assurance and manufacturing of commercial and clinical trial sterile liquid and lyophilized parenterals, microencapsulated products, intravitreal products, suspensions, and solid dosage forms. She has held strategic leadership positions in quality assurance, quality control, sterile manufacturing, and project management and has a particular interest in technical transfers both of processes and analytical procedures.

Berglund has an undergraduate degree in chemistry and postgraduate degrees in chemistry and pharmacological and physiological science. She received her PMI PMP (Project Management Institute Project Management Professional) certification in 2007 and her ASQ CQA (American Society for Quality Certified Quality Auditor) and ASQ CMQ/OE (Certified Manager of Quality/Organizational Excellence) certifications in 2015.

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