Amy Ritter was Scientific Editor, BioPharm International.

Amy Ritter, PhD

At the end of February, sunny southern California will be the site for a week-long conference devoted to the development and production of biopharmaceuticals. IBC’s Biopharmaceutical Development and Production Week will be held in Huntington Beach, California, and runs from February 25-March 1. The conference is exceptionally broad in its coverage, ranging from sessions on raw material characterization and risk assessment, through sessions focused on development and production of particular product types.

		As well as technical sessions devoted to upstream and downstream processing, tech transfer, process validation, and protein analytics, the conference will cover regulatory issues surrounding biopharmaceuticals. Jeffrey C. Baker from FDA’s Office of Biotechnology Products will be on hand to deliver a keynote talk on emerging issues in the regulation of biopharmaceuticals. Within the Viral Safety for Biologicals track, representatives from and EU and FDA will discuss regulatory issues for adventitious agent testing.

		The second half of the week delves more deeply into production challenges for specific product classes. An entire track is devoted to antibody drug conjugates, with a keynote talk on characterization and comparability strategies being given by Fred Jacobson, PhD, from Genentech (a member of the Roche group). In addition, scientists from ImmunoGen, Pfizer, and Seattle Genetics will discuss analytical strategies for antibody-drug conjugates, and scientists from Ambrx, Sutro BioPharma, and Mersana Thersapeutics will give presentations on novel conjugation strategies.

		Barry Walsh, Conference Director and Project Leader at IBC Life Sciences spoke with me in detail about the organization of the conference. You can listen to his podcast to hear a more complete description of the sessions that will be presented.

Articles

At the end of February, sunny southern California will be the site for a week-long conference devoted to the development and production of biopharmaceuticals.

From Raw Materials to Lifecycle Management: IBC’s Biopharmaceutical Development and Production Week

 that it has voluntarily entered into a consent decree with FDA over violations of cGMP. Under the terms of the consent decree, Ben Venue is still permitted to manufacture and distribute more than 100 drugs that are essential for patient care. Ben Venue is also permitted to continue drug-development activities, and may file abbreviated new drug applications (ANDAs), and, as remediation progresses to FDA’s satisfaction, receive ANDA approvals and manufacture other products.

In November 2011, Ben Venue voluntarily suspended manufacturing at its Bedford, Ohio facility because of significant manufacturing and quality concerns. The Bedford site manufactured sterile injectable products, including the cancer drug Doxil, which was in critically short supply as a result of the suspension. 

According to Ben Venue’s press release, the company has invested more than $300 million to upgrade its facilities, making necessary improvements and changes to processes to address the manufacturing-related issues that resulted in the company’s decision to halt manufacturing. Ben Venue has demonstrated progress in improving manufacturing processes and announced in October 2012 that limited production had resumed. Since that time, production has resumed on additional manufacturing lines.

Ben Venue Laboratories announced that it has voluntarily entered into a consent decree with FDA over violations of cGMP.

Ben Venue Laboratories Enters Consent Decree

 issued by the Federal Trade Commission (FTC), FTC analysts reported that the number of potentially anticompetitive patent dispute settlements between branded and generic drug companies increased from 28 in 2011 to 40 in 2012.  According to the report, companies filed a total of 140 final patent settlements.  Of those, 40 settlements contained a payment to a generic manufacturer and also restricted the generic’s ability to market its product. In addition, the study found that in 19 of these settlements, branded firms may have used the promise that they would not develop or market an authorized generic as a payment to stall generic drug firms from marketing a competing product.

, that patent settlements that include a payment delay generic entry by 17 months longer, on average, than those that do not include some form of payment. By delaying the entry of cheaper generics, they say, pay-for-delay deals cost Americans $3.5 billion annually and will add to the federal deficit.  The FTC supports legislation that would restrict pay-for-delay settlements.

The Generic Pharmaceutical Association (GPhA) took issue with the FTC report. In a strongly worded 

, Ralph G. Neas, President and CEO of GPhA, said, "The FTC is wrong on the facts, wrong on the public policy and wrong on the law.”  According to GPhA, settlements actually help bring affordable generic medicines to market sooner, resulting in billions of dollars in savings to consumers.

Neas concludes, “Like the FTC, we oppose anti-competitive and anti-consumer settlements. That's why we support provisions in the 2003 Medicare Modernization Act that require FTC review of all brand-generic patent settlements. An outright ban would have the unintended consequence of preventing pro-consumer settlements that actually allow generic competition sooner than if the generic company took the case to conclusion and lost—which is a possibility in every single patent case." 

According to the Federal Trade Commission, the number of potentially anticompetitive patent dispute settlements between branded and generic drug companies increased between 2011 and 2012.

FTC Reports an Increase in Anticompetitive Activities Among Drug Makers

 an expansion of its antibody-drug conjugate (ADC) manufacturing capacity at its site in Visp, Switzerland. According to a company press release, Lonza will invest CHF 14 million ($15.1 million) to double the existing large-scale manufacturing capacity in Visp.  The company expects the expansion to be completed in the second quarter of 2014, and says there is the potential to add jobs at the site.

Facilities that manufacture ADCs must be equipped to handle both biologics and high-potency, small-molecule APIs.  Lonza began investing in ADC manufacturing suites and associated R&D and quality-control laboratories in 2006.

“We have witnessed significant growth in the ADC market in the past 24 months and this investment is necessary to continue to support the growing product demands from our customers” said Stefan Stoffel, head of Lonza’s chemical manufacturing business unit, in the release. “Lonza Visp will continue to offer a fully integrated end-to-end development and manufacturing solution for ADCs, including the cytotoxic small molecules used in these products and all associated analytics.”

Lonza will invest CHF 14 million ($15.1 million) to double the existing large-scale manufacturing capacity in Visp, Switzerland.

Lonza Expands Antibody-Drug Conjugate Manufacturing Capacity

With the release of a draft guidance on the evaluation and labeling of abuse-deterrent opioid formulations, FDA is one step closer to clarifying its thinking on acceptable formulations for this product class.

		FDA’s actions in recent months with regards to opioids have been inconsistent: in December 2012, they 

 the market entry of generic oxymorphone that was not formulated to be abuse-resistant. Endo Pharmaceuticals, who reformulated their branded product, Opana, to be abuse-resistant, filed a lawsuit against FDA to block approval of the generic drugs, claiming that the reformulation was done for reasons of safety, and that generic manufacturers should be held to the same safety standards. Shortly thereafter, however, an FDA approval committee 

 approval of an extended-release hydrocodone made by Zogenix, because of its potential for abuse. So, while FDA was clearly considering abuse potential in its approval process, an abuse-deterrent formulation was not a prerequisite for approval.

 from FDA Commissioner Margaret A. Hamburg to Rep. Fred Upton  contains more insight. In the letter, Hamburg says, “FDA has concluded that if FDA determines that a formulation of a product significantly deters abuse, we have legal authority, under the drug approval and drug safety provisions of the federal Food, Drug, and Cosmetic Act, to require generic version of that product to have abuse-deterrent formulations as well.” FDA is still considering whether to act on that authority, according to the letter. Hamburg tells Upton that FDA is evaluating data on opioid formulations to determine whether abuse-deterrent formulations do, in fact, deter abuse and will base their policy accordingly.

Abuse-Deterrent Opioids-Evaluation and Labeling

, contains a section on designing and conducting premarketing studies to demonstrate abuse-deterrence, a clear first step in being able to evaluate a product. As the data roll in, we should see more consistent policy regarding opioid formulations.

FDA’s Position on Abuse-Deterrant Opioid Formulations Becomes Clearer

AbbVie, a research-focused, specialty biopharmaceutical company that was spun off from Abbott, was officially launched on Jan. 2, 2013.  The new company will employ approximately 21,000 people in more than 40 countries, according to AbbVie’s 

The new company’s portfolio includes both growth brands and durable performers, including HUMIRA (adalimumab), AndroGel (testosterone gel), Lupron (leuprolide), Synagis (palivizumab, manufactured by MedImmune), Creon (pancrelipase), Synthroid (levothyroxine sodium), Kaletra (lopinavir/ritonavir), Norvir (ritonavir), and Zemplar (paricalcitol). In addition, AbbVie’s pipeline contains compounds in more than 20 mid- to late-stage clinical programs as well as discovery efforts in diseases including Hepatitis C, rheumatoid arthritis, psoriasis, multiple sclerosis, Alzheimer's disease, Parkinson's disease, spondyloarthropathies, multiple myeloma, and endometriosis.

"Our commitment at AbbVie is to build on Abbott's 125-year heritage and address some of the world's most serious health issues," said Richard A. Gonzalez, AbbVie’s chairman of the board and chief executive officer, in the press release. "We intend AbbVie's enduring legacy to be one of finding treatments for patients with serious health care needs."

AbbVie, a research-focused, specialty biopharmaceutical company that was spun off from Abbott Pharmaceuticals, was officially launched on Jan. 2, 2013