Amy Ritter was Scientific Editor, BioPharm International.

Amy Ritter, PhD

FDA approved Roche’s Kadcyla (trastuzumab emtansine or T-DM1) for the treatment of people with HER2-positive metastatic breast cancer who have received prior treatment with Herceptin (trastuzumab) and a taxane chemotherapy.  Kadcyla is an antibody-drug conjugate (ADC) composed of the monoclonal antibody, trastuzumab, and the chemotherapy, DM1, joined together using a stable linker.  The linker and toxin were developed through a licensing agreement with ImmunoGen, a Massachusetts-based biotech company specializing in targeted anticancer therapies.

, patients treated with Kadcyla had a median progression-free survival of 9.6 months compared with 6.4 months in patients treated with another chemotherapy drug, lapatinib plus capecitabine. The median overall survival was 30.9 months in the Kadcyla group and 25.1 months in the lapatinib plus capecitabine group.

Kadcyla is the first ADC to result from Roche and Genentech’s 30 years of HER2 pathway research and the third medicine Roche has developed for the treatment of HER2-positive breast cancer, according to Roche’s 

. In addition, Roche and Genentech currently have more than 25 antibody-drug conjugates in their pipeline.

Articles

FDA approved Roche?s antibody-drug conjugate, Kadcyla (trastuzumab emtansine or T-DM1), for the treatment of people with HER2-positive metastatic breast cancer.

Roche/Genentech Win FDA Approval for Antibody-Drug Conjugate

 that the Biomedical Advanced Research and Development Authority (BARDA) will continue to support the company’s influenza vaccines program. BARDA has agreed to modify its contract to support certain activities associated with scaling up manufacturing to meet the capacity metrics in the contract and to be able to expand the age indication of Flublok and Panblok influenza vaccines, according to the company press release. 

Protein Sciences expects to have approval for use of Flublok in people 50 years and above in time for the 2013/14 influenza season, while Panblok is being developed to protect against pandemic influenza. Both vaccines are manufactured using the company’s egg-free baculovirus expression vector system, a platform that enables rapid production of vaccine without the use of live influenza virus. Protein Sciences and BARDA entered negotiations to provide additional support for the establishment of Flublok large-scale manufacturing in Pearl River, NY and help fund clinical studies required to secure FDA approval of Flublok for use in populations not included in the initial approval. The company release says that 13 new employees have been hired to begin operations in Pearl River, and the company plans to add approximately 30 more within the next year.

Protein Sciences announced that the Biomedical Advanced Research and Development Authority (BARDA) will continue to support the company?s influenza vaccines program.

BARDA Continues to Support Protein Sciences' Cell-Based Vaccine Programs

	Researchers from Heriot-Watt University in Edinbugh and Roslin Cellab in the UK 

 for producing uniformly sized spheroids composed of human embryonic stem cells in the Feb. 4, 2013 issue of the journal 

. According to the authors, creation of uniformly sized spheres is essential to controlling differentiation of stem cells. Previous attempts to use 3-dimensional bioprinting to automate the process and thereby produce structures of more consistent size have been unsuccessful because of poor cell viability. Human stem cells, they say, are particularly fragile and often do not survive the printing process.

	In the current study, they use a valve-based cell printer to deposit two layers of liquid, or “bio-ink.” One layer consisted of cell-culture medium containing human embryonic stem cells, and a second layer contained medium alone. The volume of each ink droplet could be controlled independently, and varying the volume allowed control of the size of the resulting droplet and the number of cells contained within. A large-bore nozzle was used to reduce shear stress on the cells. After deposition into a microwell, the droplets were inverted, and the stem cells adhered to each other to form uniformly sized, spherical aggregates with cell viability of greater than 89% after 72 hours.

	The authors suggest that the combination of speed, reproducibility, and the high degree of cell viability afforded by the process make it a promising system for production of stem-cell derived tissue for 

 drug development, toxicity testing, or as clinical trial material.

Researchers from Heriot-Watt University in Edinbugh and Roslin Cellab in the UK describe a method for producing uniformly sized spheroids composed of human embryonic stem cells in the Feb. 4, 2013 issue of the journal Biofabrication.

Producing Stem-Cell Aggregates Using Bioprinting

 that it will discontinue its Phase III rheumatoid arthritis program for tabalumab, an anti-BAFF (B cell activating factor) monoclonal antibody, because of lack of efficacy.  The decision was not based on safety concerns. A Phase III program for tabalumab for systemic lupus erythematosus is ongoing and will continue as planned. 

"While we are obviously disappointed by these results in rheumatoid arthritis, we continue to believe that tabalumab could have significant potential for patients in other disease areas," said Eiry Roberts, M.D., vice-president of autoimmune product development at Lilly in the company press release. "Autoimmune disorders are highly individualized. We believe that targeting BAFF with a molecule such as tabalumab may still represent an important advance for patients, and therefore we will continue the ongoing Phase III tabalumab lupus program."

Eli Lilly and Co. announced that it will discontinue its Phase III rheumatoid arthritis program for tabalumab, an anti-BAFF (B cell activating factor) monoclonal antibody, because of lack of efficacy.

Lilly Discontinues Phase III Rheumatoid Arthritis Program

	According to FDA, 75% of the products in shortage are generic sterile injectables; low-margin products that must be manufactured in specialized facilities and that must meet stringent quality metrics. Recent lapses in quality from manufacturers including Ben Venue and Hospira have led to plant shutdowns and drug shortages. FDA has found itself squeezed between the necessity of ensuring that drugs on the market are safe, and ensuring that there is a sufficient supply of drugs on the market to meet crucial medical needs. For example, a 

 released in June 2012 by the House Committee on Oversight and Government Reform accused FDA of contributing to shortages by over-zealous enforcement. Yet House members also 

 FDA of contributing to the recent meningitis outbreak by under-zealous enforcement.

	To shed some light on the topic, FDA commissioner Janet Woodcock and Marta Wosinska, director of the analysis staff in the Office of Planning and Informatics at CDER, coauthored a 

. The paper discusses how the pressures faced by manufacturers of sterile generics to keep the cost of production low can affect quality, and thereby supply. The authors recommend that quality be a factor when considering the price of a sterile generic injectable, and suggest that the additional monetary incentive for producing a quality product will lead to more consistent manufacturing practices.

	The paper’s premise can be summed up by the following: “The drivers behind the quality problems we describe above are multifaceted, but we postulate that at their core is the failure of the market to sufficiently reward quality.” Generic manufacturers compete on price, and the lowest price wins. Low profit margins, the authors say, mean that manufacturers are reluctant to invest in the kinds of plant maintenance and improvement that would ensure dependable operations and consistent quality. If manufacturers were able to differentiate their products based on quality, and could charge more for a quality product, they would be more likely to make those investments, they argue.

	While their argument makes sense, it is difficult to see how a quality reward system could be implemented. Consumers will pay more for higher quality cars, washing machines, and produce because they derive some benefit or satisfaction from the higher-quality product that they purchase. But for sterile injectables, the purchaser of the product (e.g., a physician or a hospital pharmacy) is not the end user (i.e., the patient). In a system where the product’s buyer and the product’s end-user are not the same entity, where would the impetus to reward quality come from?

According to FDA, 75% of the products in shortage are generic sterile injectables; low-margin products that must be manufactured in specialized facilities and that must meet stringent quality metrics.

Balancing Supply with Quality

 of more than 50 guidance documents planned for 2013.  The list reflects guidance documents currently under development as of the date of the posting, Jan. 31, 2013. Planned documents relevant to cGMP and compliance include:  

Quality Systems Approach to Pharmaceutical cGMP Regulation (OMPQ)

Control of Highly Potent Compounds (OMPQ)

Contract Manufacturing Arrangements for Drugs: Quality Agreements

Submission of Field Alert Reports and Biological Product Deviation Reports (OMPQ)

Pre-Launch Activities Importation Request (PLAIR)

With regards to biosimilars, the agency plans a guidance on 

Submission of Clinical Pharmacology Data as Evidence of Biosimilarity for Biologics and Protein Products

Formal Meetings Between the FDA and Biosimilar Biological Product Sponsors or Applicants

Other guidance documents in the planning stage include 

Securing the Drug Supply Chain—Standards for Tracking and Tracing Prescription Drug Packages

, and a guidance on compounded medications titled 

Pharmacy Compounding of Human Drugs Under Section 503A of the Federal Food, Drug, and Cosmetic Act

FDA has released a list of more than 50 guidance documents planned for 2013.