Pharmaceutical Technology Editors

FDA has published a draft guidance on Dec. 5, 2022, with recommendations to sponsors and applicants who intend to use equivalence criteria in analyzing 

 bioequivalence (BE) studies for investigational new drug applications, new drug applications, abbreviated new drug applications, and supplements to these applications.

The guidance discusses statistical approaches for BE comparisons and focuses on how to use these approaches both generally and in specific situations. After being finalized, it will replace the Guidance for Industry, 

Statistical Approaches to Establishing Bioequivalence

, which was originally issued in February 2001.

In addition to covering some of the topics in the 2001 guidance, subjects discussed in the new guidance will include missing data, intercurrent events, narrow therapeutic index drugs, variable drugs, and data preparation.

The draft guidance can be viewed in full 

Articles

The guidance discusses statistical approaches for BE comparisons and focuses on how to use these approaches both generally and in specific situations.

FDA Publishes Draft Guidance on Statistical Approaches to Establishing Bioequivalence

The US Pharmacopeia (USP) announced the opening of the USP Advanced Manufacturing Technology Lab in Richmond, Va., as a part of their launch of a suite of R&D analytical solutions to continue to support the efforts of drug manufacturers seeking to adopt advanced manufacturing technologies, such as pharmaceutical continuous manufacturing (PCM).

PCM is a continuous flow of materials through a process pipeline in which two or more unit operations are directly connected and there is a sequential transformation of the materials. The process output, such as an API or drug product, is collected as the input materials are being fed in, and the entire process happens in a single facility.

"Reducing technical and training barriers to adoption of advanced manufacturing technologies like PCM will help strengthen resilience by allowing medicines to be made in more places. This diversifies sources of supply and strengthens the medicines supply chain," said Ronald T. Piervincenzi, PhD, CEO of USP, in a press release. "Our new analytical laboratory service offerings extend USP's capability to assist manufacturers considering the adoption of PCM, and will help ensure availability of trusted, quality medicines made with PCM alongside those made with traditional batch manufacturing technology."

The R&D analytical solutions will consist of analytical lab services that use USP’s in-house scientific expertise and state-of-the-art facilities at the USP Advanced Manufacturing Technology Lab in Richmond and the USP headquarters facility in Rockville, Md.

The areas of focus that will be used to characterize materials and help ensure the quality of medicines made with PCM include:

Drug assays, including stability-indicating tests

Methods to control impurities (including mutagenic, process, and unknown impurities, as well as residual solvents)

Material isolation, identification, and characterization

Spectrometric and other process analytical technology applications.

USP is focused on R&D analytical solutions and quality measurements specific to PCM and is focused on addressing the challenges of PCM adoption and helping to strengthen medicines supply chain resilience.

In addition, USP is working with partners and stakeholders to address PCM knowledge gaps through educational programs, creating an online continuous manufacturing Knowledge Center, and launching a flow chemistry R&D lab to investigate novel routes of synthesis for APIs using PCM and develop new analytical techniques to ensure product quality.

PCM has the potential to allow flexibility and efficiency in manufacturing, lower production costs, cut environmental footprints, accelerate production and scale-up in response to emergencies, and reduce potential quality issues through real-time monitoring.

USP Advanced Manufacturing Technology Lab Opens for Further Developments in R&D Analytics

FDA announced the approval of Ferring Pharmaceuticals’ Rebotya for the prevention of recurrence of 

 infection (CDI) in individuals 18 years of age and older on Nov. 30, 2022. Rebyota, administered as a single dose rectally, is the first fecal microbiota treatment to be approved by FDA.

“Today’s approval of Rebyota is an advance in caring for patients who have recurrent C. difficile infection,” said Peter Marks, director, Center for Biologics Evaluation and Research, FDA, in an agency press release. “Recurrent CDI impacts an individual’s quality of life and can also potentially be life-threatening. As the first FDA-approved fecal microbiota product, today’s action represents an important milestone, as it provides an additional approved option to prevent recurrent CDI.”

According to the release, CDI is a potentially life-threatening disease resulting in diarrhea and significant inflammation of the colon; it is associated with 15,000-30,000 deaths in the United States annually. After recovering from CDI, individuals may get the infection again — this is known as recurrent CDI. The administration of fecal microbiota is thought to facilitate restoration of gut flora (also known as gut microbiome) that can prevent further episodes of CDI.

FDA based its decision on two randomized, double-blind, placebo-controlled clinical studies (as well as open-label clinical studies) conducted in the US and Canada, where participants had a history of one or more recurrences of CDI. Patients received either Rebyota or placebo 24 to 72 hours after completion of antibiotic treatment for CDI. An analysis of the results from these studies found that prevention of recurrent CDI through eight weeks was significantly higher for patients who received Rebyota (70.6%) vs. placebo (57.5%).

Ferring Pharmaceuticals’ Rebyota was approved for the prevention of recurrence of Clostridioides difficile infection.

FDA Approves First Fecal Microbiota Product

GSK, Sanofi, and Takeda announced a partnership with Singapore’s Agency for Science, Technology, and Research (A*STAR) and various Singapore universities on Dec. 6, 2022. The goal of this partnership, formalized through the Biologics Pharma Innovation Programme Singapore (BioPIPS), is to boost Singapore's biologics manufacturing capabilities, including recombinant therapeutic proteins and vaccines.

According to an agency press release, the partnership will bring together the companies and Singaporean researchers to enhance manufacturing productivity, improve operational efficiency, and reach sustainability goals. It will be composed of three workstreams:

The Sensing and Modelling workstream, focused on machine learning and mechanistic workflows to enable simplified and faster workflows,

The Sustainability workstream, focused on tackling sustainability challenges in biologics and vaccines manufacturing via exploration of novel materials, circular economy approaches, and models promoting more sustainable and resilient supply chains,

The Compliant Agility workstream, focused on removing manual tasks to improve productivity while retaining compliance.

“New opportunities will emerge as the biomanufacturing industry undergoes major changes brought about by the rapid pace of digitalization, Industry 4.0, and the need for greater sustainability,” said Lim Keng Hui, assistant chief executive, Science and Engineering Research Council, A*STAR, in the release. “As Singapore makes biopharma production a priority area in its Research, Innovation and Enterprise 2025 Plan, A*STAR aims to contribute our R&D capabilities through BioPIPS to help make the local biomanufacturing industry become more agile and better positioned to benefit from new products and technologies.”

“The objectives of BioPIPS are aligned to Takeda’s ambitions of being net carbon zero in our operations by 2035 and how we can tap on data, digital and technology to transform our manufacturing site. We look forward to this partnership with Singapore’s research ecosystem to further strengthen our capabilities and discover new and sustainable ways to develop and manufacture innovative medicine to deliver on Takeda’s commitment to Patient, People and Planet,” said George Lam, site head, Takeda Manufacturing Singapore, in the release.

The partnership will see the pharma giants partner with researchers from A*STAR and various Singapore universities.

GSK, Sanofi, and Takeda Partner With Singapore to Boost Biologics Innovation

Reaction Biology Corporation announced on December 2, 2022 that their closure on a definitive agreement for Reaction to acquire Bioassay Labor für biologische Analytik GmbH (Bioassay GmbH), including its wholly owned subsidiary, Peptide Specialty Laboratories GmbH (PSL), located in Heidelberg, Germany.

Bioassay offers good manufacturing practices (GMP)-accredited potency assays and functional bioassays, good laboratory practices (GLP)-compliant services, and through PSL, peptide synthesis services, including peptide-specific antibody production and neoantigen synthesis.

In addition, personnel, equipment, and facilities from the acquired companies will expand Reaction Biology’s presence in Germany while enabling its global customers to leverage Bioassay’s expansive portfolio of regulated clinical and commercial services.

“Market demand is increasing globally for large-molecule services as biopharmaceutical companies search for new treatment options for patients suffering with cancer and other serious diseases,” said John H. Johnson, chief executive officer of Reaction Biology, in a press release. “This transaction enables Reaction Biology to add Bioassay GmbH’s impressive clinical phase and post-approval infrastructure, which includes large molecule capabilities, as well as its GMP and GLP accreditations, to our expanding suite of drug discovery and development services. We can now provide our customers with even broader offerings to meet their research and development goals.”

Reaction Biology Acquires Bioassay GmbH for Increasing Large Molecule Capabilities 

The ROSS Vertical Blender is designed for reliable, gentle mixing of friable solids, abrasive materials, and shear-sensitive products. It consists of a low-speed auger that orbits the periphery of a conical vessel while gently lifting material upward. This agitation is intended to allow product from top portions of the batch to cascade to the bottom while blending with the material being drawn upwards by the auger.

The Vertical Blender is angled steeply to allow for efficient blending of batches as small as 10% of maximum working capacity while also enabling the quick discharge of the finished blend. It does not require bearing or packing glands in the product zone and is designed to promote 100% discharge. In addition to solid blends, the product can mix wet applications, such as flowable slurries and pastes. The machine can be jacketed for heating or cooling with water, oil, or steam.

The ROSS Vertical Blender enables mixing of friable solids. 