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Susan Haigney is managing editor of BioPharm International, email@example.com.
The European Pharmacopoeia is preparing for 2021 while also supporting the industry to develop 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 patients. As ever, pharmacopoeias play a role in providing a standards framework for the development, manufacture, and regulatory approval of these life-saving medicines.
With the current challenges facing industry and regulators, how has the European Directorate for the Quality of Medicines and HealthCare (EDQM), which publishes the European Pharmacopoeia (Ph. Eur.), been assisting in the development of COVID-19 treatments and how has the pandemic affected the organization’s operations?
EDQM has revised its production planning to adapt its approach as the pandemic crisis develops, according to EDQM Director Susanne Keitel. “We also reorganized our production process. These changes have enabled us to maintain an uninterrupted supply of reference standards throughout the crisis, which I consider to be a significant achievement since our portfolio covers more than 3000 different standards,” Keitel says.
EDQM has relied on virtual meetings to communicate with international partners since the pandemic started and has organized several online conferences. “These have included training on the new European Pharmacopoeia approach to the Management of Extraneous Agents in IVMPs and special information sessions for new chairs of groups of experts of the European Pharmacopoeia Commission,” says Keitel.
EDQM is working closely with the European Medicines Agency (EMA) to provide COVID-19 vaccine developers access to guidelines, resources, and applicable pharmacopeial texts, says Keitel. “The EDQM, for its part, has made available European Pharmacopoeia texts that are relevant for developers in the context of Marketing Authorisation Applications for candidate vaccines,” she says. Some academic institutions and small- and medium-sized enterprises involved in COVID-19 vaccine development, according to Keitel, may not be aware of all the applicable regulatory requirements.
“More than 40 quality standards relevant for vaccines have been published on our website. Developers can take them into account to help build appropriate analytical control strategies for their COVID-19 candidate vaccines and ensure the quality and safety of the final product,” says Keitel. “Furthermore, a document compiling selected training materials related to vaccines was also published to help accelerate users’ understanding of the European Pharmacopoeia and how to apply relevant texts. To bridge a gap, the EDQM has also drafted and published a non-binding guidance document on viral vectored vaccines, one of the new technology platforms of special interest for COVID-19 candidate vaccines.”
EDQM is also coordinating the European Network of Official Medicines Control Laboratories (OMCLs) for official control authority batch release (OCABR) to prepare for the additional release test for COVID-19 vaccines independent from the manufacturer, in line with European Union legislation. “This work includes a guidance document on the transfer of relevant tests, which, in order to save time, will not depend on the final validation of the analytical methods; and an information table on the testing capabilities of the different OMCLs, so that manufacturers can easily select the most appropriate OMCL for their products,” says Keitel.
“And of course, we have also continued to meet regularly with various stakeholders. We met with National Pharmacopoeia Authorities (NPAs) on a weekly basis during the first half of the year, and we now meet on a monthly basis in addition to the traditional annual meeting. We also have frequent meetings with industry associations and representatives of the OMCL system. Last but not least, we have liaised regularly with other international pharmacopoeias to help co-ordinate the public health response in Europe with that of the other world pharmacopoeias,” she says.
Several updates were made to Ph. Eur. in 2020, according to Keitel, including a new general chapter (2.6.32. Test for bacterial endotoxins using recombinant factor C) in Supplement 10.3 that offers an alternative to limulus amoebocyte lysate (LAL)-based testing methods. Supplement 10.3, which was published in July 2020, also included a revision to general chapter 2.9.19. Particulate contamination: sub-visible particles. This allows for alternative procedures for small-volume biologics. “The new general chapter, 5.17.2. Recommendations on testing of particulate contamination: visible particles, provides clarity on how to interpret the requirement to be ‘practically free from particles’ in production and quality control, including during stability studies,” says Keitel.
“A revised dosage form monograph on Nasal preparations (0676) was aligned with EMA guidelines for uniformity requirements for nasal sprays, number of deliveries and leak rate. Similarly, for oromucosal preparations, dental preparations were added and the sections on sprays and drops were separated. Chapter 2.2.2. Degree of coloration of liquids, revised by the Pharmacopoeial Discussion Group (PDG) with the addition of a harmonized instrumental method, also came into force in 2020,” says Keitel.
In 2021, EDQM plans to continue to implement the International Council for Harmonisation (ICH) Q3D guideline on individual monographs. There are also plans for a revision of the general notices for the dissolution test, a new technical guide on finished product monographs, and a general chapter on the analysis of N-nitrosamine impurities in active substances and finished products, according to Keitel.
“Depending on our harmonization work conducted with the US Pharmacopeia and the Japanese Pharmacopoeia in the Pharmacopoeial Discussion Group, we expect to finalize the revision of chromatographic separation techniques, the Ph. Eur. chapter 2.2.46,” says Keitel. “Other updates will concern requirements for parenteral preparations on visible and sub-visible particulate and bacterial endotoxin text/endotoxin testing. In addition, medicated plasters will be covered by a dosage form monograph and the disintegration method
for large tablets in general chapter 2.9.1. Disintegration of tablets and capsules will be adapted to allow stepwise testing.”
Susan Haigney is managing editor of Pharmaceutical Technology and Pharmaceutical Technology Europe.