The Wave of the Future: Peptide APIs
By Dror Gefen, Site Quality Head, TAPI Plantex-Abic
Even though pharmaceutical peptides were first introduced decades ago, peptide production is still considered a young market with promising therapeutic capabilities and exciting potential for the API industry. Most APIs are manufactured with established processes and state-of-the-art technology. TAPI and its strategic partner Novetide are also pioneering a biologic approach to produce peptide APIs. Scientific advancements over the past several years have resulted in peptide APIs with more stable molecules, allowing them to be produced in larger quantities. With a greater supply of peptide APIs available, pharmaceutical companies have the possibility to develop new and potentially more effective drug treatments for larger markets.
What are peptides?
A peptide is a compound of two or more amino acids in which a carboxyl group of one is united with an amino group of another. Amino acids are the building blocks of life and are found in all living organisms. Peptides regulate critical functions such as burning fat, building muscle, and serve as hormones and neurotransmitters. Because some are able to pass through cell membranes, they can deliver drugs that fight cancer and other serious diseases affecting the cardiovascular, respiratory, gastrointestinal, and nervous systems.
Peptide-based drugs accumulate in low levels in body tissue, which reduce toxicity levels. They are highly selective which makes them effective at lower doses and, on such basis, with less serious side effects. However, they are short-lived and doses must be administered more frequently. Most are administered parenterally since their oral bioavailability is extremely low. More than 60 peptides are on the market today and hundreds more are in development.
TAPI - Novetide: a pioneer of peptide API production
Manufacturing peptide APIs is a complex process involving sophisticated technology and expert oversight. TAPI - Novetide was an early pioneer in peptide API development, and has accumulated a wealth of knowledge and experience in this highly-specialized field. The partnership offers a unique interface between classic solution-phase chemistry, solid-phase synthesis, fragment condensation and other novel technologies. State-of-the-art downstream processing (DSP) technologies and innovative methodologies enable us to address a wide range of customer needs. TAPI - Novetide produces a comprehensive portfolio of peptide APIs at five plants in Israel, and is able to deliver quantities at any scale, from several grams to hundreds of kilograms per year. The teams who manage production are highly qualified in analytical operations and are among the best trained in the industry.
As with every product that TAPI - Novetide manufactures, quality and compliance are top priorities. The partnership complies with current Good Manufacturing Practice standards (cGMP) and enforces rigorous end-to-end control from product development to delivery. Moreover, it strives to deliver quality beyond compliance, by setting internal standards that exceed current regulatory guidelines worldwide. TAPI-Novetide peptide manufacturing facilities have been inspected several times by regulatory agencies and successfully audited. TAPI’s Quality teams take these steps to ensure that the partnership consistently delivers peptide APIs that our customers can trust.
Peptide APIs production challenges
Producing peptide APIs is complex. In order to deliver a high quality product, many challenges must be addressed.
Characterization – Peptides have a secondary structure which may result in aggregation and an impurity profile with high similarity to the API and to each other. Bioactivity determination using complex methods to develop may be required.
Regulatory guidelines, such as the ICH Q3A, exclude peptides. Manufacturing peptide APIs is complex and no specific guidelines are in place to ensure high-quality production.
Thus, various tools are combined to address quality needs which will eventually enable the commercialization of our product by regulatory authorities, such as the FDA.
Quality by design
In order to achieve product quality through peptide production, we start with a well thought-out project management process. We define the framework of product quality through its quality attributes related to the expected route of administration and dosage, and the capacity of API production. When it comes to the quality of raw materials, we exercise strict control of quality attributes, which may eventually affect API quality, including diasteroisomers and other related impurities. Special attention is given to synthetic amino acids as building units.
The process involves design space with tools like DOE that enable control of product quality, and eventually ensure high quality and batch-to-batch high consistency. This is so important for such a multi- step complicated process, especially while implementing various complex dosage forms like depot formulations, etc.
Peptide synthesis is a multi-step complicated process which involves dozens of chemical steps followed by a rigorous purification campaign. Process automation, especially in large scale production utilizing hundred kg. capacity lines, enables our facilities to strictly control process parameters which provides for high batch-to-batch consistency.
Continuous improvement and collaboration build strong customer partnerships
The need for new, more complex peptide-based drugs is growing and TAPI - Novetide is taking a proactive approach to ensure it continues to meet customer demand. In TAPI – Novetide’s culture of continuous improvement, its processes are evaluated on an on-going basis to find ways to do things better. TAPI – Novetide is always looking for opportunities to expand its peptide API portfolio, improve its technology, work more quickly and efficiently, and increase capacity. The partnership strive to anticipate its customers’ needs and expectations throughout the entire product lifecycle and deliver outstanding support, including through their product development phase.
TAPI views customers for these products as long-term partners and collaborate closely with them to make sure their projects keep moving forward. Our Regulatory Affairs team is available to support them during the submissions process to help them receive on-time approval. If an issue arises during formulation or they need a different specification, we will help work through the issue and develop a joint solution.
Peptide therapeutics will continue to be a growth area for the pharmaceutical industry, and TAPI - Novetide is well-positioned to support it with industry-leading peptide-related services. With our specialized know-how, world-class team, cutting-edge technologies and fully-equipped production plants, we are excited about the role we’ll play transforming promising drug candidates into viable industrial-scale peptide products.
Dror Gefen is the Site Quality Head at TAPI’s Plantex-Abic plant in Israel, overseeing Quality Assurance in peptide production. He joined Teva Pharmaceutical Industries in 2007.
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