Quality of pharmaceutical products: “Regulatory Science” – its illusions, obstacles and a potential solution.

“Regulatory Science” is a term often used to describe practices of national, sometimes international, bodies to establish and monitor quality of pharmaceutical products such as tablet and capsule, which would include safety and efficacy aspects. However, a clear description of “Regulatory Science” appears to be lacking. It may be considered a practice of setting standards (specifications) and protocols for describing and establishing the quality of products available for human use. The underlying concepts for setting standards/specifications and protocols usually come from the fundamental principles and laws of sciences, engineering, and mathematics, such as biology, chemistry, manufacturing, and statistics. “Regulatory Science” uses these scientific principles to set specifications and protocols rather than generating new scientific knowledge which is developed under the auspices of a specific scientific and/or engineering discipline. Therefore, regulatory bodies hardly ever generate new scientific knowledge but use it to generate specifications and standard procedures for implementation for the public good. The authorities are mandated to enforce the developed and suggested specifications and protocols – as they are intended to be followed. This mandate of enforcement results in the term “compliance,” i.e., the industry must adhere (“compliant”) to the standards and protocols for their manufactured products to be approved for marketing.

The authorities’ role may be explained with an analogy of a distribution company (e.g., Amazon, eBay, Costco) which acts as a go-between between a manufacturer and its consumers. These distributors hardly ever manufacture or develop any of the listed products they sell; however, they ensure the quality of the products and their appropriate delivery to the consumers or customers meeting well-described quality standards/specifications. The distributors’ role is limited only to providing or transferring quality products from manufacturers to consumers, nothing more. If a product has a fault or issue of quality/compliance discovered through the distributor’s internal audit or by a third party. In that case, the particular supplier or manufacturer of the item is informed. The manufacturer has to deal with the issue. The distributor does not start addressing the issue or advising the manufacturer on fixing the manufacturing problem as they would lack the needed expertise. If the manufacturer cannot resolve the issue, the product must be taken off the market.

The regulatory authorities’ mandate is that of a go-between, like a distributor described above, to ensure that the manufactured products available on the market are quality. For this, authorities have to define a “quality product” and then set its “quality attributes,” along with measurable specifications, in collaboration with the manufacturers. Unfortunately, the authorities do not provide a definition/criteria for the “quality product” but expect that the manufacturers must offer quality products – obviously, they can’t! Therefore, by default, manufacturers become guilty of not providing quality products, and thus they need to be “corrected or fixed.”

With this presumed lack of trust or capability of the manufacturers came the regulatory guidance and inspection-based system to guide and/or advise the manufacturers on how to manufacture quality products. Therefore, the mandated responsibilities of the authorities have completely deviated (metamorphosed) from establishing and monitoring quality of the products to the quality of the manufacturing. Considering the lack of competencies of the authorities in manufacturing, as they never manufacture or develop any product like the above-mentioned distributors, understandably, they would be unable to advise the industry appropriately and correctly, especially in the absence of a definition of quality products and their attributes. Rather than providing appropriate definitions and standards for quality products that which industry should follow, authorities frequently start a new fad of “science-based guidance” documentation such as SUPAC, IVIVC, QbD, ICH, cGMP, PAT, inspections, etc., commonly even violating well-established scientific principles, for enforcing a new set of requirements for manufacturing. This practice has resulted in perpetual cycles of more guidance documents, reorganizations, rebranding, and policing activities turning the authorities from facilitators to bullies blaming and/or punishing the industry for not following quality standards and practices. The industry can’t follow arbitrary protocols and/or employ non-validated tests and procedures, as recommended and required by the authorities, to provide a scientifically valid outcome and, by extension, quality products. This has put an enormous administrative and financial burden on the industry and society in general – without improvement in manufacturing or availability of quality products and/or addition of any other value.

Therefore, to resolve this issue, the regulatory authorities worldwide should reconsider focusing their role as the standards-setting organizations for the products and not providing guidance to the industry on how to manufacture products and market these to the public.

Some relevant links which would be helpful to read in this regard (1, 2, 3, 4)

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