BioTechLogic Perspectives on Oligonucleotide Therapies

Oligonucleotide: Opportunities, Pipeline and Challenges At Long Last, Nucleic Acid Therapeutics Are Coming of AgeRecently, I sat down with Tracy TreDenick, BioTechLogic’s Head of Regulatory and Quality Assurance, to learn more about her insights and experiences from the extensive oligonucleotide therapeutics work BioTechLogic has done.

Q: Briefly describe the types of work you have done within the oligonucleotide space?

A: BioTechLogic has done a great deal of working with oligonucleotide products in recent years, including process validation work for drug substance, drug product and an oligo adjuvant.

Just some of BioTechLogic’s oligonucleotide work has included:

  • CMO on-site support
  • Equipment qualification protocols
  • Commercial-ready batch records
  • Support validation protocols and studies
  • Process validation
  • Manufacturing support
  • Technical support
  • Facility validation reports
  • Microbial monitoring strategies
  • Commercialization plans
  • Formulation development reports
  • Process control strategies
  • Chromatography column troubleshooting
  • Multiproduct facility CV site policies and strategies

Q: What are the most common challenges you have confronted while working on oligonucleotide products, and how has BioTechLogic addressed these challenges?

A: One of the most common challenges is the environmental classifications for manufacturing this kind of product because in many situations, the product is not a finished product or an API, but an adjuvant. There are guidelines for drug products, and ICH Q7 for APIs, but not specific guidelines for adjuvants. BioTechLogic has had to evaluate the environmental requirements based on the needs of the product.

Another challenge is balancing the U.S. FDA filing requirements (macro-molecule) to the EU’s “centralized procedure” which is used for biologics. For the most part, this challenge has been addressed by applying the most stringent of the two requirements, allowing the given product to be filed both in the United States and in the European Union (EU).

Q: Share your views on the oligonucleotide product regulatory debate, including the likely issues that will surface on the regulatory landscape as these products mature.

A: The U.S. technical/regulatory experts for oligonucleotides say these are just macro-molecules, a type of large “small molecule,” as opposed to a biologic. A biologic is typically difficult to characterize using analytical procedures, while small molecules are far easier to characterize. There is some debate about impurities and quality assurance when manufacturing oligonucleotide products; however, via improved analytical instrumental technologies and new approaches, the industry has made a lot of ground here. But typically, the difference in regulatory environment amounts to what type of manufacturing support validation that you have to do for a biologic as opposed to a small molecule, and there is generally more complex work for a biologic.

Oligonucleotides: Opportunities, Pipeline and Challenges At Long Last, Nucleic Acid Therapeutics Are Coming of Age