Knowledge management has always been a key factor for the successful development and manufacture of pharmaceutical products. Understanding the chemical and physical processes underlying material interactions in dosage forms formulation, production processes, and product storage along its shelf-life is fundamental in assuring quality, efficacy, and safety of medicinal products. Knowledge has always directed the design of dosage forms (e.g., in terms of selection of excipients and primary packaging materials) and the development of production processes (e.g., in terms of process technology applied and process controls implemented).

Knowledge is normally assumed to be a combination of education and experience. Advanced education on chemistry, physics, microbiology, biology, analytics, materials properties, process technology, pharmacokinetics, pharmacology, toxicology, and physiology must be available in the pharmaceutical industry. Nowadays this ‘traditional’ form of education has to be integrated with a decent knowledge of information technology, data management, and processing. In addition, highly innovative and specialized areas, like biotech or advanced therapy, require specific knowledge of biochemistry, genomics, and cell engineering.

Pharmaceutical Technology’s October 2021 APIs, Excipients, and Manufacturing eBook

Alessandro Regola,* a.regola@libero.it, is the AFI vice president in Milan and coordinator of the AFI Quality Section, and Marco Adami is an AFI member in Milan and coordinator of the Validation Group within the AFI Quality Section. They both serve as pharmaceutical consultants in quality systems and research and development, respectively.
*To whom all correspondence should be sent.

When referring to this article, please cite it as M. Adami and A. Regola, “Pharmaceutical Knowledge Management: Experiences in Drug Development and Manufacturing,” 

Pharmaceutical Technology’s APIs, Excipients, and Manufacturing

Articles

Quality

Knowledge management has gained increasing importance in the pharmaceutical industry over the past 10–15 years

Pharmaceutical Knowledge Management: Experiences in Drug Development and Manufacturing

Advancements in technology combined with the rediscovery of new ‘reagentless’ activation methods—such as using light in photochemistry and electrons in electrochemistry—have changed the way researchers devise synthesis routes toward novel molecules and set up their experiments. Photochemistry has gained much recognition over the past 20 years, and this growing trend has led to the development of innovative, modular flow photochemistry systems that allow users to efficiently switch between chemistries.

Andrew Mansfield is flow chemistry leader at Syrris.

When referring to this article, please cite it as A. Mansfield, “Shining a Light on Photochemistry in Flow,” 

Development

The ever-increasing interest in photochemistry has inspired the development of innovative, modular flow photochemistry reactors.

Shining a Light on Photochemistry in Flow

In continuous pharmaceutical manufacturing, real-time assurance of critical quality attributes (CQAs) is highly desired. Among CQAs, control and assurance of tablet potency has been challenging due to lack of real-time measurement sensors tied to optimization programs. A modular self-contained toolbox developed using Python programming has been demonstrated to predict tablet potency based on a residence time distribution (RTD) model and apply a diversion strategy to divert out-of-specification tablets. The modular toolbox can be integrated with any commercially available tools to control tablet potency, can automatically calibrate the RTD model for different formulations and processes, and can be used to predict outlet concentrations, assuming accurately quantified inputs.

Ravendra Singh is Assistant Research Professor, NSF-ERC C-SOPS, Department of Chemical and Biochemical Engineering, Rutgers, The State University of New Jersey.

When referring to this article, please cite it as R. Singh, “Predicting Tablet Potency in Continuous Manufacturing,” 

Pharmaceutical Technology APIs, Excipients, and Manufacturing 

Manufacturing

A modular toolbox enables residence time distribution-based control for continuous pharmaceutical manufacturing. 

Predicting Tablet Potency in Continuous Manufacturing

The COVID-19 pandemic has drawn attention to pharmaceutical supply chains, notably increasing public awareness of how and where drugs and vaccines are made. While the United States and European Union (EU) retain the two top spots in terms of number of FDA-registered manufacturing plants, China and India, together, now account for 31% of these facilities. India alone supplies 40% of the world’s generic drugs but relies on China for 70% of the raw materials and APIs used to make them. This complex supply network has flexed rapidly and successfully to answer to the demands of the pandemic, with manufacturing plants switched to the production of hand sanitizer, manufacture of materials in short supply due to regional outbreaks, or, for the longer term, making respiratory drugs and vaccines. However, changes in supply chain or plant use are challenging for this heavily regulated industry, particularly given the criticality of product quality and safety.

Reliable specifications, for products and raw materials, provide a secure foundation for those navigating the global pharmaceutical supply network and are increasingly important as the industry regroups, drawing on lessons learned. Powders are particularly challenging in this regard, with conventional specifications often failing to successfully differentiate materials. This article explores reasons why specifications for products and raw materials fail, and experimental data illustrating how powder testing can be used to establish better, more robust specifications will be provided.

Jamie Clayton, jamie.clayton@freemantech.co.uk, is operations director, Freeman Technology (a Micromeritics company), Gloucestershire, UK.

When referring to this article, please cite it as J. Clayton, “Building Robust Specifications Using Powder Testing,” 

Excipients

Advanced powder testing is a useful tool to differentiate materials and optimize the supply chain.

Building Robust Specifications Using Powder Testing

Prior to the commercialization phase for API manufacturing, there is a lot to juggle as well as a tricky global regulatory landscape to navigate. API manufacturers must meet the standards for the country where the drug will be distributed, and every country has its own regulations as well as its own interpretation of those regulations.

When referring to this article, please cite it as M. Rivers, “Global Regulatory Approach to API Manufacturing," 

Navigating a complex global regulatory landscape involves upfront research into the expectations of the different regulatory bodies, thorough documentation of every step of the API manufacturing process, and good communication. 

Global Regulatory Approach to API Manufacturing

The advantages that enzymes have as biocatalysts are well known within the pharmaceutical manufacturing industry, not least that they can give excellent specificity and yields, and even facilitate reactions that are difficult with chemical catalysts. Their credentials towards improving sustainability are also increasing the levels of interest for process development, as biocatalytic reactions can be more efficient in terms of solvent and material use.

Mark Muldowney is head of technology, and innovation and Greg Holgate is biocatalysis chemist, both with Sterling Pharma Solutions.

When referring to this article, please cite it as M. Muldowney and G. Holgate, “Seeking Economies of Scale for Biocatalysis,” 

New enzymes and protein engineering have advanced biocatalysis processing toward commercial acceptance. Technology and economic roadblocks must be overcome for the process to be widely embraced by pharma.

Seeking Economies of Scale for Biocatalysis

Approximately 58% of drug products in development are small molecules, according to a Thermo Fisher article (1). Moreover, a 2021 report by 

 estimates that the small-molecule API market will reach US$279,697.1 million by 2027 (2). This includes both in-house manufacturing and contract manufacturing. Some of the drivers of this growth, according to the same report, include a “growing demand for newly developed small molecule drugs” and “the changing nature of drugs” (2).

But that isn’t the only upward prediction for the small-molecule API market. In a report by 

, an 8.05% compound annual growth rate market growth is predicted from 2021 to 2028, and technological advancement and innovations may lead to profitable opportunities for players in the small-molecule API market (3).

With this promising trajectory in mind, it’s no surprise that many companies are wondering what some of the potential advantages of working with small molecules (vs. large molecules) are in API manufacturing.

When referring to this article, please cite it as M. Rivers, “API Development and Manufacturing: Advantages of Working with Small Molecules," 

Between dosage form versatility, product stability, lack of storage restrictions or need to refrigerate, and an easier means of purification, small-molecule APIs present an appealing market niche.

API Development and Manufacturing: Advantages of Working with Small Molecules

Just in time (JIT) manufacturing aims to reduce flow times within manufacturing systems while cutting response times from suppliers and thence to customers. Under favorable circumstances, it’s a helpful tool for a manufacturer’s overarching strategy. With the emergence of additive manufacturing alongside rising software sophistication, JIT’s dominance of supply chain management appeared assured.

And then COVID-19 hit.

MJH Life Sciences sees CPhI’s global event in Milan, Italy as an ideal meeting place to rethink, recalibrate, and retool for the next decade of pharmaceutical manufacturing expansion. The ability to congregate face-to-face is a clear opportunity to build on that sense of community, which is so strong in the pharmaceutical industry. Among the many trends accelerated by the pandemic, the urgent requirement to build multiple additional supply partners into any future proofed supply and distribution chain has become clear. An anticipated vial shortage never became a critical bottleneck, partly because the raw materials themselves failed to arrive. Large companies had leveraged their outsized influence over suppliers—sometimes at the expense of customers, sometimes countries, and sometimes patients. This reinforces the necessity for face-to-face meetings, to rebuild trust, and to reduce hoarding and the threatening implicit bias of regionalism.

Rejoin the pharmaceutical community in Milan to engage with new partners, and to energize a supply chain infrastructure strategy with inherent adaptability and parallel inputs. Celebrate the obvious successes the industry had in meeting the COVID-19 challenge, and re-tool with a new understanding of how best to face common goals—together.

When referring to this article, please cite it as C. Spivey, “Rethinking, Recalibrating, and Retooling," 

From The Editor

CPhI is set to provide the pharma community with an ideal platform to engage with new value chain stakeholders post-COVID.

Pharmaceutical Technology, APIs, Excipients, and Manufacturing, October 2021