Ask the Expert: Leveraging Quality Management Systems to Achieve Competitive Advantages

During a May 2021 “Ask the Expert” presentation, Jigisha Patel (vice president of global regulatory compliance and technical services at Spectrum Chemical Manufacturing Corporation) emphasized the need to minimize supply-chain contingencies that lead to variability across raw materials used in biopharmaceutical manufacturing. Deviations in raw-material specifications can jeopardize good manufacturing practice (GMP) compliance and reduce drug-product efficacy and stability. Patel explained how her company’s quality management system ensures that bioprocess materials will meet specifications and process needs.

Patel’s Presentation
Patel provided three examples of supply-chain uncertainties that cause production problems. In one case, a manufacturer of a parenteral drug product purchased dry-powder sodium phosphate, but the product that arrived was more granular than expected. It clumped easily and posed risks for the company’s mixing vessels. The user’s and supplier’s quality assurance (QA) teams found that the contracted product specifications did not stipulate particle sizes. The supplier ultimately provided new material, but the drug developer lost considerable time determining the reason for the raw-material variability. When finalizing quality agreements, drug companies must list specifications carefully and be clear about expectations for notification of control changes. Supplier QA teams need to be equally diligent in identifying cases where specifications need to be established or clarified.

Patel’s second example featured a biopharmaceutical research facility that observed a decrease in cell growth during upstream operations. The problem traced back to lots of a laboratory-grade reagent that came from a different source from that specified by its supplier. The lots contained a trace impurity that did not appear during initial testing. But because the chemical was not produced under GMP conditions, the supplier did not need to notify users about changes in the reagent’s source.

Patel also referenced factory shutdowns associated with the 2008 summer Olympics in Beijing, China, and a concomitant potash miners strike in Saskatchewan, Canada. Those events disrupted supply chains for precursors of amino acids and active pharmaceutical ingredients (APIs). Bioprocess suppliers did not investigate far enough up the supply chain to identify risks. Several manufacturing bottlenecks ensued, and production costs increased significantly during that period.

Such examples, Patel observed, should compel biopharmaceutical companies to ask how well they can mitigate supply-chain uncertainties. For instance, vendors can differ in their application of GMPs, and GMP audit programs can be difficult to develop and implement. Biopharmaceutical developers and manufacturers should ensure that suppliers of their raw materials can provide complete GMP audit reports, including documentation of noncompliance events and corrective and preventive actions (CAPAs). Users also should inquire into their suppliers’ product and process QA programs, sanitization procedures, operator-error rates, instrument calibration protocols, cross-contamination risks, change controls, and product-packaging requirements.

Spectrum’s bioCERTIFIED quality management system is designed to enhance supply-chain visibility and validate that raw materials will be safe and effective during production of biopharmaceutical products. Patel’s company ensures that its own suppliers’ operations comply with GMP and United States Pharmacopeia (USP) <797> guidelines. Spectrum also asks vendors to demonstrate fulfillment of compendial testing. Spectrum’s QA team confirms such data by performing extensive in-house testing for bioburden, endotoxins, elemental impurities, and residual solvents. Then the unit assembles complete documentation — e.g., of standard operating procedures (SOPs) and certificates of analysis (CoAs) — and performs packaging/labeling validation. Spectrum gathers all those data to develop further documentation for regulatory review and technical support. Such materials include product specification guides, safety data sheets, manufacturing-process flowcharts, general label information, and product stability and shelf-life guidance.

The bioCERTIFIED QA system yields a set of highly characterized and documented amino acids, buffers, salts, sugars, vitamins, and clean-in-place solutions, all of which can be produced at research and GMP grades. To support that process, Spectrum leverages three analytical testing laboratories that use several chromatographic and spectrometric methods and tests for microbial contamination.

Questions and Answers
Does Spectrum perform only monograph-specified testing of its products? In addition to required compendial testing, Spectrum can develop custom assays or implement a customer’s assay to assess parameters that are not specified in industry guidances.