Part 4 — How are Analytical Methods Exchanged in a Technology Transfer?

Posted by Norm Fong

Technology Transfer: Want To Get It Right?

[Editor’s note: Success in contract pharmaceutical manufacturing hinges on several critical factors, but chief among them is getting technology transfer right. This is part 4 of an in-depth, multi-part series on tech transfer.  Visit our blog page to view additional segments.]

As the principal means of assuring chemical identity and purity, instrumental analysis is the lifeblood of pharmaceutical development and manufacturing. In addition to standard instrumental methods, molecules may undergo enzymatic or cell-based assays to demonstrate some critical quality. Products often become “married” to analytical methods, and transferring this panel of tests during a technology transfer requires care.

Analytics tend to transfer more smoothly through internal projects because companies are more likely to standardize instrument platforms, instrument configurations and method transfer protocols across their laboratories.

Getting in Sync

Analytical method transfers can stall when instrumentation or skills at the two organizations differ, or if the contractor simply lacks certain expertise. CMOs try to duplicate the sponsor’s analytical capabilities as much as possible, but with the sponsor’s approval they may outsource esoteric assays to third parties.

Determining-Best-Manufacturing-Processes-Guide-For-Pharmaceutical-ProductsContractors need time to work out the kinks in an analytical method while simultaneously maintaining fidelity to the originator’s methods and goals. Both parties may wish to conduct parallel assays on the same test items at their individual sites, and to compare results. This adds time, but ensures that methods are consistent and robust. Equipment should be as well-matched as possible, as factors as seemingly trivial as the age of an HPLC column can produce different impurity profiles.

Problems are common in analytical method transfer because many methods are specific to the product or to the development group. Qualifying analytical methods depends heavily on the analyst’s skills, and sometimes on the source of a critical analytical reagent, especially antibodies. The solution is to employ a formal qualification/validation protocol to help identify potential variability and communicate it to the receiving laboratory.

A Vital Part of Tech Transfer

Analytical methods transfer more easily “on paper” than process methods, but problems still arise. Many methods for quantifying impurity levels have become standardized in biotech, particularly within drug classes or expression systems. By contrast, however, product-related assays are unique. Cell-based and enzymatic tests for potency for activity are highly user-dependent, and require more cross-checks than HPLC assays.

Transfer of analytical methods is time-consuming for CMOs and costly for sponsors. Most CMOs possess extraordinary competence at standard assays. However, even off-the-shelf methods require validation to assure that the product does not enhance or inhibit results. Successful technology transfer involves process understanding, a willingness to admit and document knowledge gaps, communication and trust. When executed intelligently, tech transfer adds value through the synergy of complimentary needs and competencies, and reinforces efforts at continuous improvement.

Next Time: Part 5 — The Cost of Technology Transfer

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Topics: CMO, analytics, analytical method transfer, chemical analytics, validation

Norm is the technical transfer manager, business development, for WellSpring. He has over 21 years in the pharmaceutical manufacturing industry and has held development, transfer and commercial manufacturing positions over the course of his career with Patheon, Global Pharm (formally Pharmacia Upjohn) and Genpharm (owned by Merck). Norm is responsible for overseeing technology transfer and all validation activities in the organization.

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