TigerTox

Potential Academic Contributions to Drug Development

cdavenport — Mon, 14 May 2012 14:00:25 +0000

Dr. Janet Woodcock (CDER, FDA) stated that for every 10 drugs that enter Phase I clinical trials, only 1 drug is approved. The cost of bringing an innovative drug to market often requires a decade and a billion dollars of investment. The paradigm where pharmaceutical companies invest heavily in research and development yet garner few drug approvals is unsustainable.

Woodcock suggests that academic researchers can contribute better methods and technologies to enable faster/better preclinical and clinical decisions to be made during drug development. Recommendations given include:

Development of biomarkers that help identify not only safety risks but also identify patients most likely to benefit from a new, targeted therapy

Greater emphasis on applied science (e.g., drug manufacturing and scale-up enhancements)
Identification of biochemical pathways causal to disease states
Identification of proof-of-concept/surrogate endpoints
Enhanced understanding of how the body handles a drug
Take a lead on developing orphan drugs, which have historically not been a priority for pharmaceutical companies
Develop and implement new ways to conduct clinical trials (e.g., use of early biomarker identification to guide patient selection) with the goal of developing faster, better, smaller clinical studies to gain critical information more quickly ( e.g., work being done at Stanford University)
To extend clinical trials into the community and region surrounding academic medical centers to facilitate patient access, recruitment, and to enhance compliance

The public has a decreased tolerance for risk, as evidenced by increased regulatory requirements for premarket evaluation of drug safety and efficacy. The hope is that academic researchers can drive changes in the required testing paradigms (nonclinical and clinical) to enable faster, better, and cheaper drug approvals.

Sources: Lecture by Dr. Janet Woodcock at the California Institute for Quantitative Biosciences (qb3), UCSF and HealthCanal.com.

Drug Safety: IOM Pharmacovigilance Report

cdavenport — Mon, 07 May 2012 14:00:08 +0000

An Institute of Medicine (IOM) committee report, recommends that the FDA take proactive steps to continue monitoring drug safety after initial approval and throughout the market lifecycle. Post-market evidence is far greater than what the FDA has when deciding upon initial approval. The IOM recommendation is that the initial approval is viewed as just one early step in a process that requires continuous, long-term monitoring (the “lifecycle approach”). The report makes recommendations about how post-market research should be conducted. The committee found that while randomized controlled trials remain the gold standard for studying drug effectiveness, observational studies have ethical and practical benefits over clinical trials post-approval. Safety results can be obtained more quickly, therefore regulatory action can be initiated earlier. One of the key report recommendations is that upon approval, each drug will have a single, publicly available Benefit and Risk Assessment Management Plan (BRAMP) to serve as a central, evolving repository of side effects and other information. As a centralized comprehensive record, the BRAMP will include a description, a benefit/risk assessment of any safety questions that exist when a drug is approved as well as any that emerge over the course of its market lifecycle, and details on any regulatory actions taken and their results. Furthermore, it was recommended that the FDA’s drug surveillance systems could be improved through use of various technological and methodological advances (e.g., use of natural language processing for review of electronic medical records). The possibility was also raised that with a more robust post-approval monitoring process, the more flexible regulatory authorities could be in the pre-approval stage.

Source: Medical News Today, and HealthCanal.com

Preclinical Offshoring Anticipated to Continue: Survey

cdavenport — Tue, 24 Apr 2012 14:00:17 +0000

In the next 2-5 years, large pharmaceutical companies plan to increase outsourcing of preclinical work, with emphasis on Discovery and non-GLP Toxicology. This trend is driven by the reductions in internal preclinical capability within Big Pharma. In an apparent reversal of the current trend towards use of a limited number of preferred providers, capacity will necessitate increasing the number of contract research organizations (CRO) involved. An offshore trend is anticipated despite the rapidly narrowing price differentials between Chinese and Western CROs for nonclinical work. A survey suggested that the offshore CROs best positioned to secure the early-stage drug development business from large pharmaceutical companies are Covance, WuXi, BioDuro, and ShangPharma. As an example, ShangPharma recently opened a new facility to accommodate a multi-year contract with Eli Lilly, with emphasis on in vivo pharmacology, oncology, and metabolic disease work.

Sources: Outsourcing-Pharma.com 11 Jan 2012, 17 Apr 2012, 19 Apr 2012

High-throughput ADME Screening Technologies

cdavenport — Mon, 16 Apr 2012 14:00:26 +0000

High throughput (HT) Absorption, Distribution, Metabolism, and Excretion (ADME) screening technology is the current push from Big Pharma to be outsourced through contract research organizations (CROs). Shifting also is the ADME regulatory emphasis; the FDA has released a draft guidance (17 Feb 2012) that includes specific wording around what needs to be done with respect to transporter drug-drug interactions (both efflux and influx). The guidance will start to drive significant changes in how ADME screening is performed. Two assays that are routinely being utilized in pharma are the Caco-2 cell-based assay and the PAMPA (parallel artificial-membrane permeation) assay. As currently practiced, predictive ADME screening is made even more difficult given the variety of transport mechanisms available. In toxicology screens (ADME-tox), however, one is not looking for altered aspects of the drug, which is generally initially unknown, but changes in known, endogenous parameters. Thus ADME-tox lends itself more easily to HT platforms. New platforms for high throughput ADME screening are available, and discussed in this article.

Source: Drug Discovery and Development

Drug Safety: Global Regulatory Authorities Encouraged to Share Inspection Results

cdavenport — Mon, 09 Apr 2012 14:00:21 +0000

To make best use of its limited resources, the Institute of Medicine (IOM) concludes that the US Food and Drug Administration (FDA) should direct resources to improve the regulatory systems of developing nations to better ensure the safety of the global pharmaceutical supply chain. Rather than try to inspect all foreign establishments itself, the FDA and its technologically advanced counterparts in the European Union, Canada, Japan, Norway, Iceland, Switzerland, Australia, and New Zealand are encouraged to plan a system for mutual recognition of inspections, which would eliminate the wasteful duplication of effort. Along these lines, an active pharmaceutical ingredient (API) inspection program involving many of the world’s premiere global regulatory bodies (FDA, the European Medicines Agency (EMA), Australia’s Therapeutic Goods Administration (TGA), the World Health Organization (WHO), the European Directorate for the Quality of Medicines & Healthcare (EDQM), and the Council of Europe (CE)) has formed to facilitate international collaboration and information sharing to enhance inspection capacity. Since data review and interpretation is already being shared between some global regulatory authorities in the nonclinical safety arena, it will be interesting to see if such global harmonization efforts extend to nonclinical safety inspections in the near future.

Sources:

RAPS – Regulatory Focus: IOM – Boost Foreign Regulatory Capacity and Global API Inspection Scheme

Nonclinical Toxicology: FDA Guidance Agenda for 2012

cdavenport — Mon, 26 Mar 2012 14:00:19 +0000

The Federal Drug Administration (FDA) Center for Drug Evaluation and Research (CDER) has issued a list of planned draft and final guidance documents for release in 2012. There are about 50 such guidances planned. Below are a few select highlights relevant to the preclinical safety space, with emphasis on the drug development of small molecules.

Electronic Submissions

Providing Regulatory Submissions in Electronic Format – General Considerations
Providing Regulatory Submissions in Electronic Format – Human Pharmaceutical Product Applications and Related Submissions. Using the eCTD Specifications
Providing Regulatory Submissions in Electronic Format – Study Data
Providing Regulatory Submissions in Electronic Format – Standardized Study Data

Procedural

Integrated Summary of Safety
Investigational New Drug (IND) Applications prepared and submitted by Clinical Sponsor Investigators

Nonclinical Toxicology Sector Predictions for 2012

cdavenport — Thu, 22 Mar 2012 14:00:13 +0000

Growth in demand for nonclinical toxicology services will be weak for the foreseeable future analysts said after the Society of Toxicology (SOT) annual meeting in San Francisco this past week. “Most agree that the industry is not merely going through a prolonged cyclical slowdown, but has also structurally changed, with less of an emphasis by clients on maximizing the number of drug candidates flowing into preclinical testing,” stated John Kreger, equity analyst at William Blair. In addition, chronic toxicity testing is being delayed until the later stages of compound development; this reduces preclinical development costs for compounds that fail. Among other factors, this has led to excess capacity at contract research organizations (CRO), price restrictions, and site closures. Tim Evans, senior analyst at Wells Fargo, expects the overall nonclinical toxicology market to grow by 2% in 2012 due to higher outsourcing penetration. In their selection of preferred service providers, global bio/pharmaceutical companies generally favor large CROs with broad capabilities. These “strategic partnership” deals, which are the cornerstones of global bio/pharmaceutical companies’ current outsourcing strategies, seek to leverage their massive buying power, reduce the cost of overhead, and improve coordination with the CRO. Sourcing models will continue to evolve, however, and will eventually threaten the business model upon which the recent megadeals are based.

On a related note due in part to ongoing capacity cuts, large pharmaceutical companies are seeking co-development deals with CROs and biotechnology firms to handle excess intellectual property. Shared risk and reward features are found in some of the more creative models. CROs that have made major acquisitions in order to leverage capacity, however, could be outmaneuvered by evolving sourcing models.

Sources: Outsourcing-Pharma.com 12-Mar-2012, 15-Mar-2012; BioPharm International

FDA Pre-IND Meetings: Why, When and How

cdavenport — Fri, 24 Feb 2012 14:00:52 +0000

The pre-IND phase of drug development is the foundation upon which all development-related activities (including registration) depend. It is, therefore, essential to give proper forethought and attention to this initial, all-important step of the drug-development process. In the United States, a pre-IND meeting can add considerable value to the overall process and maximize efficient use of both Sponsor and FDA resources. Although pre-IND meetings require considerable planning and preparation on the part of both the Sponsor and FDA, if warranted and properly conducted, the meeting can provide the Sponsor with valuable insight as to the FDA’s expectations regarding initial- and later-stage development and registration strategies. This presentation provides a high-level introduction to U.S. FDA pre-IND meetings ─ why and when a Sponsor should consider having a meeting and how the Sponsor approaches the process.

Source: Outsourcing4BioPharma

Outsourcing4BioPharma is designed to facilitate business transactions between the clients in health science industries and the contract service providers.

USA · http://www.outsourcing4biopharma.com

About the Author:

Grace Furman, Ph.D.

TigerTox: RT @esterlbarle: Toxicokinetics = what does the body do to the substance? Toxicodynamics = What does the substance do with the body?

Twitter / TigerTox — Fri, 28 Oct 2011 15:00:45 +0000

TigerTox: RT @esterlbarle: Toxicokinetics = what does the body do to the substance? Toxicodynamics = What does the substance do with the body?

TigerTox: Analyst calls for Covance to cut early development capacity http://t.co/lJiPvo1m #in #preclinical #nonclinical

Twitter / TigerTox — Thu, 27 Oct 2011 15:00:47 +0000

TigerTox: Analyst calls for Covance to cut early development capacity http://t.co/lJiPvo1m #in #preclinical #nonclinical