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Susan Haigney is managing editor of BioPharm International, firstname.lastname@example.org.
USP is preparing for 2021 while also supporting the development of vaccines and treatments for COVID-19.
The race for the development and approval of treatments and vaccines for COVID-19 is well under way, and regulators and other organizations are working with the bio/pharmaceutical industry to get these products into the hands of the public. As ever, pharmacopoeias play a role in providing a standards framework for the development, manufacture, and quality of these life-saving medicines.
With the current challenges facing industry and regulators, how has the US Pharmacopeia (USP), which publishes the United States Pharmacopeia–National Formulary (USP–NF), been assisting in the development of COVID-19 treatments and how has the pandemic affected the organization’s operations?
USP, like many other organizations, has been ensuring the safety of its staff and shifted the majority of its staff to working remotely in March 2020, according to Jaap Venema, PhD, chief science officer at USP.“Critical lab functions continued in a way that minimizes the risk to on-site staff,” says Venema. “Similar measures were taken for USP’s expert volunteers, who now regularly meet virtually to advance their standard-setting work.”
For USP, building trust in the effectiveness of COVID-19 vaccines and treatments, ensuring global access to these treatments, and combating falsified and substandard medicines are the focus, according to Fouad Atouf, PhD, vice president, USP Global Biologics. USP has been offering free resources and technical expertise to developers of COVID-19 vaccines and treatments since early 2020, says Atouf, including free and discounted education, limited-time free access to the USP–NF, and free samples of USP monoclonal antibody reference standards.
“Scientists and manufacturers working on developing new vaccines and treatments, increasing the production of approved drugs, and advancing other projects to tackle COVID-19 can access the USP–NF Online free for six months. Also, we have extended implementation dates and comment periods for our compendia, recognizing the challenges that the pandemic has brought to drug developers and manufacturers,” says Atouf.
“USP’s role in the wake of COVID-19 is multi-pronged: we are helping to accelerate the work of scientists and manufacturers in developing vaccines and treatments; supporting front line workers who will administer COVID-19 vaccines and treatments and who have been affected by shortages of critical drugs and personal protective equipment; and working on developing insights on current supply chain vulnerabilities and ways to strengthen it,” says Atouf. “Our expert volunteers and scientific staff can advise on novel vaccines, monoclonal antibody therapies, antiviral and cell therapies, and immunoglobulins or convalescent plasma treatments. And for existing and new therapies, USP compendial tests and methods address common issues shared by all drug manufacturers, such as suitability, validation, contamination control, stability testing, and qualification of raw materials,” he adds.
One of the key topics USP is planning to address in 2021, according to Edwin Gump, PhD, vice president, USP Small Molecules, is the detection and control of nitrosamine impurities, which are known carcinogens that have been found in some medications. USP has proposed General Chapter <1469> Nitrosamine Impurities that identifies sources of nitrosamines and risks associated with each source. The proposed chapter, says Gump, will give recommendations on a nitrosamine risk assessment and control strategies. It will also provide different test methods for controlling nitrosamines at levels below acceptable intake limits in angiotensin II receptor blockers.
According to Horacio Pappa, PhD, director of USP General Chapters, USP is also developing a chapter on supplier qualification that will provide a quality risk-based approach to the selection, assessment, approval, and monitoring of suppliers. “Suppliers for pharmaceutical ingredients, medical devices, as well as dietary supplement manufacturing companies and compounding pharmacies will be within the scope of the chapter,” says Pappa. “The current thinking is to develop the chapter around the supplier qualification lifecycle—a five-step process that includes identification/selection, evaluation/acceptance, performance, monitoring, and disqualification—along with discussions about expectations and a rationale for each step,” he says.
Proposed USP General Chapter <1220> Analytical Procedures Life Cycle offers “an alternate framework for analytical procedures that holistically incorporates the events that take place over the procedure life cycle,” says Pappa. “It is designed to demonstrate that a procedure is, and remains, fit for the intended purpose.”
The proposed chapter also seeks to build the connections between validation, verification, and transfer through the life cycle approach, says Pappa. At the same time, the International Council for Harmonization (ICH) has started the revision of the Q2 Validation of Analytical Procedures: Text and Methodology guideline on validation and proposed the creation of a complementary guide (Q14 Analytical Procedure Development) on the development of analytical procedures. “These guidelines will incorporate some of the concepts presented in <1220>,” says Pappa.
In 2021, USP also will propose procedures based on inductively coupled plasma spectroscopy (ICP) to element-specific general chapters, which impact USP General Chapters <206> Aluminum, <211> Arsenic, <241> Iron, <251> Lead, <291> Selenium, and <261> Mercury, according to Pappa. “This will give our stakeholders the option to continue using the classical wet chemistry tests as currently included in these chapters, or to adopt the use of an ICP-based procedure for analysis of the element in question, as similarly outlined in USP <233> Elemental Impurities—Procedures. This ensures the same approach is used throughout USP–NF regarding the analysis of individual metals with elemental impurities. This revision will provide stakeholders with an option for a single analysis to meet both monograph and chapter requirements, rather than multiple procedures,” says Pappa.
USP also is planning a chapter on batch release testing. “USP is aware that many of our tests are commonly used for batch release, but the procedures and acceptance criteria in General Chapter <905> Uniformity of Dosage Units refer only to the units tested, so any passing results should not be extrapolated to larger populations. The approach to release the batch (with respect to content uniformity) based on passing the <905> requirement is neither appropriate nor acceptably rigorous,” says Pappa.
When it comes to large molecules, USP added additional performance standards for monoclonal antibodies, according to Atouf. “These reference standards can be used as independent control materials for method development, training, method transfer, and internal assay control support, standardization of physicochemical testing, such as intact mass, charge heterogeneity, size variants, purity, and glycan analyses. These types of standards will have a positive impact on access to these critical drugs,” says Atouf.
In addition, a Plasmid DNA Expert Panel has been formed under USP’s Advanced Therapies Expert Committee to develop a new general chapter on the use of plasmid DNA in cell and gene therapies, according to Atouf. USP will also be developing a lentiviral vector copy number standard to “standardize the quantitation of viral vectors in cellular genomes. This is important because the number and persistence of inserted genes in patients may lead to health complications, and quantifying vectors efficiently in preclinical studies for gene therapies and vaccine development may prevent adverse events in patients,” says Atouf.
Susan Haigney is Pharmaceutical Technology's managing editor.
Vol. 44, No. 12
When referring to this article, please cite it as S. Haigney, "USP, COVID-19, and Plans for the Future," Pharmaceutical Technology 44 (12) 2020.