Angie Drakulich was editorial director of Pharmaceutical Technology.

Angie Drakulich

	What’s the best way to reach first-in-man studies when you have little to no information?   Bioavailability issues, financial constraints, and pressure to meet accelerated deadlines can affect development, so having a firm plan in place is key. PharmTech is hosting a free educational 

 on this topic next week, Oct. 3. Check it out for insight into the signs to look for when finalizing a plan and how to achieve the best outcomes. A detailed case study about a molecule that has successfully navigated through development to commercial success will be presented.

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What’s the best way to reach first-in-man studies when you have little to no information? Bioavailability issues, financial constraints.

How to Reach First-in-Man Studies Successfully

 and Patheon are partnering to provide you-our readers-with CMC advice from some of the leading formulation scientists and pharmaceutical manufacturing experts in the world. To get started, we need to know what plagues your CMC strategies and daily work. Email your questions directly to Editorial Director Angie Drakulich at 

adrakulich@advhttp://adrakulich@advanstar.com

. (*Note: We will keep your name and company affiliation anonymous.)

	Answers will be provided by the Patheon Certified Consultants team beginning in the January 2013 print and online editions of PharmTech. These experts have collectively brought more than 200 pharmaceutical products to market, including some of the world’s largest blockbusters.

	• I have a BCS Class II compound for which amorphous solubility is easily sustained, but I can’t get the compound to rapidly dissolve. What are some solutions, particularly with respect to excipient selection?
	• I have a compound that is non-ionizable and does not form a stable salt. Are co-crystals my best option and what are the key criteria in identifying a suitable co-crystal?
	• I am having trouble maintaining product stability when scaling up a lyophilization process. What are the likely factors causing the problem?

Pharmaceutical Technology and Patheon are partnering to provide you-our readers-with CMC advice from some of the leading formulation scientists and pharmaceutical manufacturing experts in the world.

CMC Troubles  Send Us Your Questions

	On July 9, 2012, the Generic Drug User Fee Act (GDUFA) was passed by the US Congress. The Act, to be implemented from Oct. 1, 2012, is designed to streamline the generic-drug review process and has been welcomed by the pharmaceutical industry. However, there have been a lot of unanswered questions regarding the general outcome of GDUFA and how it will impact the industry.

	The GDUFA agreement includes application fees for original Abbreviated New Drug Applications (ANDAs), prior approval supplements (PAS), and Type II Drug Master Files (DMFs) for APIs. Based on the fee structure, Type II DMFs will account for 6% and the API manufacturing facilities will account for about 14% of the GDUFA fees, respectively. To fulfill the GDUFA requirements and to streamline the DMF review process, the FDA Office of Generic Drugs (OGD) has established a DMF Review Team, with a future possibility of a division, which will be dedicated to review of API information submitted in Type II DMFs. With all the changes in the Type II DMF review processes that are covered in the GDUFA legislation and given the fact that there is currently a lack of adequate information available to the industry, there have been many industry questions and speculations regarding the impact of GDUFA on the submission and review of Type II DMFs.

 of PharmTech, former OGD reviewer Dr. Aloka Srinivasan, now with Parexel, answers some of these common questions.

On July 9, 2012, the Generic Drug User Fee Act (GDUFA) was passed by the US Congress.

GDUFA’s Effect on Drug Master Files

	Earlier this week, on Sept. 12, 2012, the Pharmaceutical Research and Manufacturers of America (PhRMA) honored nine individuals for their research into and fight against Alzheimer’s Disease (AD) as part of the association’s new Research and Hope Awards. The event was at the Washington, DC, Newseum and featured as keynote speakers Marc Kennedy Shriver, who wrote a book about his father’s experience with Alzheimer’s, and Meryl Comer, an Emmy award-winning journalist.

	The evening was about inspiration and motivation to keep up the fight against AD, whether as caregivers, patient advocates, health professionals, or scientists.

	It’s no secret that ongoing as well as recent setbacks have challenged research and discovery scientists working to find a treatment for AD. “Years of research has yielded five medicines that provide some symptomatic relief in some cases but has not yet resulted in an approved disease-modifying medicine,” states a new PhRMA report on researching AD, released in connection with the awards. “What sets AD apart from other diseases is that scientists still do not know what causes it. We may very well find a treatment first, that leads us back to the cause,” PhRMA President and CEO John J. Castellani told Pharmaceutical Technology in an interview before the award recipients were unveiled on Sept. 7, 2012.

	There are two additional key challenges to developing AD medicines listed in the PhRMA research report: the limited utility of current models of the disease, which creates a barrier in preclinical testing of drug candidates; and the absence of validated noninvasive biomarkers of disease activity and progression, which delay diagnosis until patients become symptomatic. As a result, long and expensive clinical trials have become the mainstay of human studies.

	This past summer, Johnson & Johnson, Pfizer, and Eli Lilly all released reports of failed clinical trials targeting the beta-amyloid protein, which is known to form brain plaques in AD patients. Some reports have alluded to lost confidence and momentum in the fight against AD as a result, not to mention potential decreases in R&D investment, but Castellani hopes that these ups and downs are just part of the biopharmaceutical discovery process. “…Researchers take the findings from the unsuccessful projects and use that new information to step forward and continue their quest,” states the PhRMA research report.

	Castellani acknowledges that AD is particularly challenging and complex, with 101 unsuccessful drug trials targeting AD since 1999 and a success ratio of 1 in 34 compared with most new medicines, which have a 1 in 5 chance of moving forward. The fact that traditional animal models cannot be used in trials for AD and that human trial recruitment is difficult only add to the complexity of finding a successful AD therapeutic. Castellani has high hopes, however.

	He points to the fact that there are nearly 100 new medicines in development right now for AD and dementias, boasting a full pipeline that has potential to reverse, treat, and hopefully prevent this catastrophic disease. These drugs include a medicine that inhibits the formation and accumulation of amyloid-beta and tau protein deposits; an intranasal medicine that is able to penetrate the blood-brain barrier for mild cognitive impairment, a precursor to AD; and a gene therapy, according to a second PhRMA report on medicines in development that was released this week.

	PhRMA is encouraging increased public understanding and awareness of AD and its unique challenges as well. The association has issued a list of 108 ongoing clinical trials for AD patients. Many caregivers of AD patients simply don’t have the energy or time to enroll their loved ones in a trial and the patients themselves often do not have the cognitive ability to enroll themselves, Castellani told Pharmaceutical Technology, but PhRMA hopes this may change as more information about the disease and about the research being done to help treat it reaches the public.

	For a list of the 2012 PhRMA Research and Hope Award recipients, including the Merck BACE team, see the PharmTech awards announcement 

Earlier this week, on Sept. 12, 2012, the Pharmaceutical Research and Manufacturers of America (PhRMA) honored nine individuals for their research into and fight against Alzheimer’s Disease (AD) as part of the association’s new Research and Hope Awards

PhRMA Awards Ceremony Inspiring for Alzheimer’s Workers, Researchers

, researchers from MIT’s Center for Biomedical Innovation (CBI) describe the interim results from recent research into 34 commercial-scale biopharmaceutical products at 11 international sites. The comprehensive survey on topics related to site characteristics, quality approaches, quality activities, perception of relative consistency of regulators, product-level process details, and product-level compliance performance was deployed over the past 18 months as a secure web-based questionnaire directly to biopharmaceutical manufacturing sites through several different channels. The individuals targeted for inclusion as survey respondents have been manufacturing plant managers or their representatives.

	Read the interim results and if you haven’t yet, the survey can be taken on behalf of a biomanufacturing site usin this 

In the September PharmTech issue, researchers from MIT’s Center for Biomedical Innovation (CBI) describe the interim results from recent research into 34 commercial-scale biopharmaceutical products at 11 international sites.