News & Press
By Patricia Van Arnum – DCAT® Editorial Director
CordenPharma Roundtable Contribution by
Fabio Stevanon, Global Injectables Platform, CordenPharma International
DCAT Value Chain Insights, October 23, 2019
Parenteral drugs, which may be a biologic or small molecule, refer to drugs using non-oral means of administration by injecting the drug directly into the body typically through three common routes of administration: intramuscular, subcutaneous and intravenous. The percentage of parenteral drugs approved as new molecular entities (NMEs) by the US Food and Drug Administration’s (FDA) Center for Drug Evaluation and Research (CDER) (see Table I at end of article) reached a recent high of 59% in 2016 and has since trended near 40% over the past several years.
To gain a perspective of the key trends in development and manufacturing of parenteral drugs, DCAT Value Chain Insights gained input from industry members. Providing perspectives were Claus Feussner, PhD, Senior Vice President Development Service, Vetter Pharma-Fertigung GmbH & Co. KG, and Fabio Stevanon, Director, Global Injectables Platform, CordenPharma International.
Generally, as the regulatory authorities’ scrutiny with regards to injectables / parenterals continues to increase, including ever tighter expectations with respect to facility and microbial controls, so does the burden to demonstrate the production of a safe and sterile product.
With respect to small molecules, while the regulatory process is well defined and stringent, there are incentives to developing biologics because these often target unmet medical needs or orphan diseases. In these cases, the regulatory pathway can be shortened, resulting in a more attractive development landscape for innovators to explore.
Parenteral drug manufacturing industry-wise, the effort to raise the compliance level of terminally sterilized drugs, which closely mimics the aseptic fill–finish standard, is a clear and evident trend. We also see the movement of aseptic fill–finish facilities toward operating more and more in an “automatic-robotized” environment to improve product protection, as well as operator and environmental protection in the case of highly potent compounds.
With reference to injectable technology, the terminally sterilized manufacturing trend adopts a C-class area close to compound and filling lines while aseptic formulation and filling is forced to adopt open-close restricted-access barrier systems (RABS)(EU GMP_ Annex I driven) or even isolator technology, as well as ready-to-fill technology to limit interaction with materials before the final filling closing step.
With regards to capacity, we have recently seen a significant investment toward high-speed filling lines to address the need for the traditional high-volume marketed drugs. The challenge here is that these high-speed lines are often inflexible with regards to variation or optionality as they are designed to fulfill demands of millions of units per annum.
The other end of the product-volume continuum is represented by the more innovative drugs or niche/orphan product areas, which demand greater flexibility with regard to volumes or components, and, therefore, ultimately require more flexible, slower filling lines. Here capacity and customers’ pricing expectations remain a challenge.
Within the injection-delivery scope, the evident increase of subcutaneous over intravenous delivery is driven by patient-centricity and system-friendly technology. In particular, the subcutaneous products are heavily dominated by pre-filled syringes, pens and auto-injectors while wearable devices are becoming more prominent where therapy has to be constantly monitored and data-driven. This is reflected in the implementation of new rules from the US FDA for combination product standards and revised medical device regulations by the European Medicines Agency.
As a consequence, injectable manufacturing is becoming overall less standardized, as seen, for example, in the different interaction between constituents and components, device and combination product testing, control strategy and analytics, and complex packaging diversity, all overseen by cGMP and new drug / device regulations.