Advancements in synthesis and analysis technologies are helping unleash the therapeutic potential of peptides and oligonucleotides, spurring the dialogue on how the CMC/quality regulatory expectations, guidance and standards should keep pace.
With this expanded technical capability and therapeutic potential, the past decade has seen a burgeoning of interest in the peptide/oligo arena.
The field of therapeutic peptides is more established, although it is growing to include emerging therapies such as personalized neoantigen-specific peptide vaccines. Oligonucleotides are a more nascent product class, with significant and expanding prospects. Both peptides and oligos represent complex molecules that are difficult to synthesize and characterize, are prone to impurities, and pose many regulatory challenges.
Considerable global efforts are being made to facilitate the discussion between manufacturers, regulators, pharmacopeias, academics and contract laboratories on these challenges, in the effort to establish best practices and guidance in the areas of analysis, standard setting, and regulation of these treatment modalities.
To contribute to this global dialogue, the United States Pharmacopeia (USP) held a workshop on peptide and oligonucleotide therapeutics at its headquarters in Rockville, Maryland in November 2019. The focus of the workshop, which in previous years targeted only peptides, was expanded this past year to include oligos – reflective of the rapidly expanding industry engagement in the field.
The objective was to help: ● inform public standard setting ● highlight novel advances in manufacturing, purification, characterization, and analytical method strategies, and ● promote regulatory understanding of the challenges and expectations.
Highlights of the workshop were provided at its conclusion by Eli Lilly Bioproduct Research and Development Distinguished Research Fellow Michael DeFelippis, who chaired the meeting. [A link to his summary is provided in below.]
DeFelippis has served as chair of the USP BIO1 Expert Committee on Peptides and Insulins during the pharmacopeia’s 2015-2020 cycle. At the USP 2020 Convention, held virtually on May 4-6, he was elected to serve another five-year term as chair of the committee, which will now encompass peptides and oligos, reflective of the latter’s growing significance. Insulins, in turn, have been placed under the purview of the BIO2 committee. [See IPQ July 16, 2020, for an in-depth review of the discussions and developments that took place at the USP 2020 Convention.]
The story that follows focuses on the opening session of the November workshop, during which three regulators and an industry expert explored the peptide/oligo regulatory considerations, developments and challenges.
The final section of the story offers a European perspective on the regulatory picture for oligos, which was provided at a DIA/FDA conference on oligonucleotide-based therapeutics, held the week before the USP workshop.
The story is divided into five parts, reflective of the focus of these five presentations:
● Part I explores FDA’s current thinking on the development of generic peptide and oligonucleotide drug products.
● Part II provides an overview of the CMC regulatory issues for the smaller oligonucleotides, such as anti-sense oligos, with particular reference to quality issues.
● Part III presents an FDA perspective on the rapidly developing area of personalized neoantigen-specific peptide vaccines for tumor immunotherapy.
● Part IV profiles an industry perspective on CMC/quality and regulatory strategies for the successful development of therapeutic oligonucleotides and includes a comparison of the US and EU requirements.
● Part V shifts the vantage point to that of a European regulator, with the focus on quality support for early access approaches for therapeutic oligos.