EMA proposes quality guidelines for synthetic peptides and oligonucleotides

Regulatory NewsRegulatory News | 22 September 2022 |  By 

The European Medicines Agency (EMA) want to set clear quality guidelines for drug companies manufacturing synthetic peptides and oligonucleotides.
EMA raised the idea of specific guidelines for such products in new concept papers published this week, explaining current requirements on impurities testing, specifications and the control of DNA-reactive chemicals either partly or fully exclude synthetic peptides and oligonucleotides.
According to the agency, the proposed guidelines would address aspects of peptide and oligonucleotide manufacturing, characterisation, specification and analytical control “not covered in the Guideline on the Chemistry of Active Substances (EMA/454576/2016) and Chemistry of Active Substances for Veterinary Medicinal Products (EMA/CVMP/QWP/707366/2017).”
In addition to the current lack of specific guidelines, EMA cited increased industry interest in the development of peptide and oligonucleotide-based medicines as a motivation for development of the proposed guidelines.
 “The number of clinical trial applications for human products and marketing authorisation applications [for synthetic peptides and oligonucleotides] … for both human and veterinary products has significantly increased over the last few years,” EMA wrote.
The agency added that, from a regulatory standpoint, synthetic peptides and oligonucleotides are “interesting since they present a link between products derived from biotechnology and small molecular chemical compounds.”
Synthetic peptides
Specific measures in the synthetic peptides guideline will include directions on the development of a control strategy to ensure consistent quality of both the peptides and the resulting medicinal products, based on relevant critical quality attributes.
The guideline will also specify how manufacturers define a “batch” and how they should detail any splitting, pooling and re-processing steps applied during the purification process.
A section on controlling the purity of the peptide being made will cover how manufacturers should go about avoiding both product and process-related impurities.
The guideline also will address conjugation – the process of adding a compound like polyethylene glycol to the peptide – which has emerged as a common mechanism to alter or enhance the properties of synthetic peptides.
EMA also referenced the EDQM’s Technical Guide for the Elaboration of Monographs on Synthetic Peptides and Recombinant DNA Proteins, which covers the elaboration of monographs for synthetic peptides and products of recombinant DNA (rDNA) technology, as a foundation.
”This guidance will need to be reflected during the drafting process of the proposed guideline. Ph. Eur. monographs are available for certain individual synthetic peptides and should be taken into account as relevant,” EMA wrote.
“Furthermore, specific limits are laid down in the Ph. Eur. Monograph ‘Substances for pharmaceutical use’ for synthetic peptides which need to be referred to/reflected in the guideline.”
Similarly, the proposed oligonucleotide guideline will be tailored to specific considerations applying to this class of therapeutics according to EMA, which wrote that it will “cover antisense and other single strand products, double strand products as siRNA and as a third subclass aptamers.”
As with the peptide document, sections in the oligonucleotide guideline will cover the development of control strategies as well as requirements on batch definition and the description of splitting, pooling and re-processing steps applied in the purification process.
EMA also intends to address the selection of starting materials, approaches for impurity characterisation as well as purity control strategies.
The guideline will also acknowledge the use of well-established production processes according to the agency. “Oligonucleotides have potential to use prior knowledge and platform technologies. Recommendations on how to justify applicability of prior knowledge and platforms will be provided,” EMA wrote.
EMA will also address oligonucleotide purity in the guideline. However, it did not go into details pointing out that “in contrast to synthetic peptides, no purity limits are stated in the Ph. Eur. Monograph ‘Substances for pharmaceutical use’ for synthetic oligonucleotides.
“Establishing harmonised limits could be considered in this guideline. However, additional discussions are needed as analytical methods and specific oligonucleotide type of products are not comparable per se. The public consultation may facilitate comments from different stakeholders in this regard.”
Both concept papers have been made available for a three-month consultation period.


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