spacer
home > pmps > winter 2010 > delivering biologics
PUBLICATIONS
Pharmaceutical Manufacturing and Packing Sourcer

Delivering Biologics

Recombinant biologics have been mainstream therapeutics since the 1990s. This success was largely initiated through replacement proteins (such as insulin), and biologics now generate around $70 billion in worldwide revenues. After the very first generation of biologics, originating from animal or human body fluids, protein and peptide drugs are now available from recombinant technologies, either as copies or Due to the chemical nature and size of biologics, even the most modern representatives of this drug class are still large molecules with secondary and tertiary structures, making them more sensitive to external factors (such as temperature, shear stress and interfaces) compared to small molecules. They are also still sensitive to digestive enzymes and are either not easily or not at all permeable through biological membranes. Therefore, they still need to be administered mainly via the parenteral route. An approach such as inhaled insulin worked technically, but was not successful commercially, had some safety concerns, and was withdrawn from the market after a brief commercialisation phase. So, innovative delivery or new strategies to improve the effects of biologics upon their targets are still needed to make full use of this interesting and innovative class of therapeutics.

DEVICES

Besides the dream of applications of biologics not requiring injections, real and already marketed improvements in the delivery of biologics were achieved mainly through two means. Devices and modifications of the therapeutic proteins leading to improved, pain-reduced injections and reduced injection frequencies was the first. Also, devices like prefilled syringes, double chamber syringes or cartridges, and injection systems such as pens or auto injectors allow improved application by the patient or the healthcare professional. Modern subcutaneous application systems provide small needles (29G/30G), siliconised, where no or only very little pain at the injection site is associated with the treatment, thus improving patient compliance. Protein formulations therefore need to tolerate the high shear forces associated to this thin needle passage and higher protein concentration formulations may be required, since subcutaneous application volumes are limited to about 1ml. Changes from vial to double chamber syringes or prefilled syringes will have the form of microparticles, implants and in situ forming implants (see Table 1) are established, but are only applicable for small peptide drugs (1). Novel delivery systems are under development, using different matrix materials and claiming superior properties, as listed in Table 2 (2).

Chemical modification of the therapeutics is a means to obtaining a reduction in injection frequency, which is especially beneficial for intravenous drugs like cytokines used for hepatitis treatment.

In some cases, structural modifications may even lead to a change in the application route from intravenous to subcutaneous, which will come as a relief for patients who are, in most cases, chronically ill. Subcutaneous injections can now be facilitated by co-administration of an enzyme (hyaluronidase), temporarily breaking the structure of the collagen network in the skin. This breakdown is claimed to be fully reversible, and allows on the one hand the application of larger volumes of subcutaneous drug solution (subcutaneous infusions), and may also allow bioavailability of subcutaneous drugs which are normally not administrable via that route of administration (for example, due to their high molecular weight). At present, collaborations between halozyme and several other companies have been published, studying, for example, subcutaneous application of antibody drugs (Herceptin) and immunoglobulins (Gammagard).

 


Read full article from PDF >>

Rate this article You must be a member of the site to make a vote.  
Average rating:
0
     

There are no comments in regards to this article.

 You must be a member of the site to make a comment.
spacer
Dr Carsten Olbrich studied Pharmacy at the University of Heidelberg and continued his qualification at the Free University Berlin, completing a PhD in Pharmaceutical Science. The title of his PhD thesis was ‘Optimized lipid nanoparticles and their biological testing’, focusing on nanoparticulate delivery systems for various purposes. Carsten joined Schering AG in 2000 as a Laboratory Head in diagnostic research, working on antibody attachment to surfaces of intravenous injectable polymeric particles, and quality methods for targeting specific imaging agents. In 2004, he joined the Pharmaceutical Development Department, where he acted as Associated Director in the CMC Technology Office and Drug Delivery Systems department as a scout for new technologies for CMC. In 2006, he joined the Parenteral Development Group of Bayer Schering Pharma AG as a director and is now a Senior Scientist in the Liquid Dosage Form development department, where he is responsible for drug product development of parenterals and expecially biologicals. Email: carsten.olbrich@bayerhealthcare.com
spacer
Carsten Olbrich
spacer
spacer
Print this page
Send to a friend
Privacy statement
News and Press Releases

Introducing Signant Health [Formerly CRF Bracket] and the Industry’s Most Comprehensive Patient-Centric Suite for Clinical Research

Philadelphia and London – June 10, 2019: CRF Bracket, formed by the 2018 merger of CRF Health and Bracket, today launched as Signant Health (signanthealth.com). Uniting eCOA, eConsent, Patient Engagement, IRT, Clinical Supplies and Endpoint Quality into the industry’s most comprehensive patient-centric suite, Signant makes it easier to participate in – and sites and study teams to run – clinical trials. This intense focus on the patient experience, deep therapeutic area expertise and global operational scale enable sponsors and CROs to extend the reach of drug development, expand patient opportunities and improve data quality.
More info >>

White Papers

Clinical Trial Labelling – More Than Just Labels

Faubel & Co. Nachfolger GmbH

Deciding which label is best for a particular trial project is not always easy. Labels have become multifunctional tools which are able to convey variable data in different languages, indicate first opening, product originality, support ease of use or blind study drugs. They are no longer used as mere carriers of specified contents.
More info >>

 
Industry Events

CPhI Worldwide

5-7 November 2019, Frankfurt, Germany

Join the World's Largest Pharma Event As it Celebrates its 30th Anniversary! Taking place from 5-7 November 2019 in Frankfurt, Germany, the event will bring together more than 45,000 visiting pharma professionals from around the globe and over 2,500 exhibiting pharma companies from every stage of the pharmaceutical supply chain - from ingredients and machinery to outsourcing services, packaging and more!
More info >>

 

 

©2000-2011 Samedan Ltd.
Add to favourites

Print this page

Send to a friend
Privacy statement