On November 8, 2013, FLH’s key FDA/Regulatory Partners Charles J. Raubicheck and Brian J. Malkin will present on a variety of FDA/Regulatory topics at the 3rd Annual Korea-Maryland, USA Bio Expo. The Expo will showcase the best opportunity meet with Korea’s leading pharmaceutical, biotechnology, and medical device companies. The main show dates including these and other presentations are November 7th and 8th at the Universities at Shady Grove Conference Center in Rockville, Maryland. Specifically, Mr. Raubicheck and Mr. Malkin will present on: Guidelines for Current Good Manufacturing and Quality Control, Generic Pharmaceutical Development Manufacturing, Discussion of Current Drug Shortages Affecting the U.S. Market, Current Initiatives for Underserved Diseases, Current Initiatives for Repurposing Pharmaceuticals and New Development, Biosimilar Strategies and Current Guideline Discussion, and Biosimilars/Follow-on Biologics, Pertinent FDA Guidance.

The Expo features:

  • Korea’s regional officials from the Gangwondo, Jellonamdo, Kyeongsangnamdo, and Chungcheonbukdo Provinces will be in attendance.

gpha-headerLogo.gifDay 2 of the Generic Pharmaceutical Association (“GPhA’s”) annual Fall Technical Conference focused on RTR issues, FDA’s efforts to update the inactive ingredient database, stability, Uhl’s OGD update, and closing remarks.Some of the key take aways for RTRs is that once year three of GDUFA kicks in, FDA will take a closer look at RTR issues such as DMFs, which need to be accepted for referencing rather than just filed prior to the ANDA. In the past, many sponsors had filed their ANDAs close in time–and sometime simultaneously–with the ANDA to prevent competitors and referenced drug holders alike from suspecting their ANDA filing in advance of a patent challenge notice. Now FDA is recommending that DMFs be filed at least six months in advance to permit a completeness assessment for filing. FDA’s recommendation is based on an observation that it typically takes between two to five months for DMF holders to address submission deficiencies.

Johnny Young, M.A.L.A., Regulatory Health Project Manager, OGD, explained that OGD has been viewing excipients more critically than before, e.g., ophthalmic drugs need to be Q/Q even though the current regulations provide certain exceptions, based on what has been learned. Young also noted that there are new microbiology and stability requirements for ANDA that may also lead to RTRs, and he recommended that industry take a careful look at the new RTR guidance as well as ANDA checklist, which is regularly updated. Representing industry’s viewpoint, Robert Pollock, M.S., R.Ph., Senior Advisor and Member of the Board, Lachman Consultant Services, Inc. said that the proposed five-day turn around to remedy a RTR prior to its issuance (from the current 10-day scheme) may prove to be difficult for industry to meet. Pollock also thought that it would be important for ANDA applicants to submit higher-quality ANDAs at the onset rather than hoping to fix them later, even when there is a rush to be the first patent challenger for 180-day exclusivity, because a RTR could remove that incentive.

During a question-and-answer period, FDA explained that its new RTR guidance put into writing many of the policies it had been following, so not that much in it was particularly new. Ian Margand, R.Ph., Regulatory Support Management, OGD, explained that for GDUFA to work, ANDA applicants have to take a greater responsibility for their DMF holders. In particular, ANDA applicants need to provide time for their DMF holders to provide an adequate DMF for their ANDA to be filed. Regarding labeling carve-outs to attempt to avoid certain Orange Book-listed patents with method-of-use claims or unexpired exclusivity, Young said that like other RTR issues, FDA will provide ANDA applicants with five days to fix prior to receiving an RTR, if the carve out is not in line with the Agency’s expectations of appropriate carve outs.
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gpha-headerLogo.gifOn October 29-30, 2013, the Generic Pharmaceutical Association (“GPhA”) held its annual Fall Technical Conference that featured a Keynote by Director, Center for Drug Evaluation and Research (“CDER”), Janet Woodcock, M.D., the Acting Office of Generic Drugs (“OGD”) Kathleen “Cook” Uhl, M.D., and a variety of other FDA and industry speakers. While the Conference included typical fare such as bioequivalence issues, a predominant topic was FDA’s implementation of the Generic Drug User Fee Act (“GDUFA”).

Starting with Woodock’s Keynote, her message was OGD’s reorganization, including the development of the Office of Product Quality (“OPQ”) to help drive home the message that abbreviated new drug applications (“ANDAs”) need to be high quality for OGD to meet its GDUFA goals. Some of the changes Woodcock spoke about included reviewing generics by dosage form by specialized groups and centralizing elements of the generics program in 2015: microbiology, project management, and a policy office with policy functions for chemistry, manufacturing, and controls, quality issues, and inspections. Woodcock described OGD as having assembled “SWAT teams” to handle specific types of ANDA applications in the backlog, noting that next year will be critical to control the backlog before GDUFA measures kick in 2015.

Next a barrage of quality presentations from FDA and industry followed, emphasizing the need to develop quality metrics, methods to develop internal audit programs to continuously monitor identified quality issues, and FDA’s expectations for quality going forward. FDA said that Quality by Design (“QbD”) needs to be second nature, focusing on metrics that are clinically relevant to patient safety and health. Some metrics suggested included: batch/lot failure rates (rejected, reworked), right the first time, demonstration of active pharmaceutical ingredient/excipient compatibility and stability, and standards for sampling/acceptance plans. Rather than just include passing bioequivalence studies, FDA explained that sponsors need to explain how they arrived at a bioequivalent drug product and their scale-up plans.
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korea-MD Bio Expo.jpgOn November 6-9, 2013, the 3rd Annual Korea-Maryland, USA Bio Expo will showcase the best opportunity meet with Korea’s leading pharmaceutical, biotechnology, and medical device companies. The main show dates are November 7th and 8th at the Universities at Shady Grove Conference Center in Rockville, Maryland. Some of the major events associated with this Expo include:

  • Korea’s regional officials from the Gangwondo, Jellonamdo, Kyeongsangnamdo, and Chungcheonbukdo Provinces will be in attendance.
  • Evening Reception with presentations from Korean companies and their technology development on November 7th from 6:00pm-8:30pm.

lingual.jpgOn October 31, 2013, FDA responded to a Citizen Petition filed by G. Pohl-Boskamp GmbH & Company KG (“Pohl”) on December 16, 2010. The petition requested that FDA require particular showings prior to approval of an abbreviated new drug application (“ANDA”) for a generic version of Pohl’s Nitrolingual® Pumpspray (nitroglycerin lingual spray). Nitrolingual® Pumpspray is a metered dose spray indicated for acute relief of an attack or prophylaxis of angina pectoris, i.e., chest pain, due to coronary artery disease.

In its Citizen Petition, Pohl requested that FDA require ANDA applicants to show in vivo bioequivalence studies evaluating the concentration of active ingredient (nitroglycerin or “TNG”) and its two metabolites, 1,2- and 1,3-glyceryl dinitrate (“1,2-DNG” and “1,3-DNG”, respectively) in plasma. FDA “effectively granted” Pohl’s request in 2012 with issuance of revised Draft Bioequivalence Recommendations for Nitroglycerin Metered Spray/Sublingual products (“the 2012 Revised Recommendations”). FDA recommended that data for TNG as well as 1,2-DNG and 1,3-DNG be submitted as supporting evidence since these metabolites may contribute to the pharmacological activity of Nitrolingual® Pumpspray.

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Written by Shelly Fujikawa. Ph.D

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FDA also effectively granted, in the 2012 Revised Recommendations, Pohl’s request for in vivo bioequivalence studies to use a confidence interval approach for TNG, the parent substance. This ruling thereby prohibited substitution for a confident interval approach only for the active metabolites, 1,2-DNG and 1,3-DNG. Pohl argued and FDA agreed that TNG can reliably and accurately be measured using analytical methods employing gas chromatography.
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electronicclinicaldata.jpgOn October 28-29, 2013, Q1 Productions hosted a conference on Clinical Data Management Innovation. On October 29, 2013, FLH’s Brian J. Malkin and Julie Kurzrok presented an “Update on FDA’s Draft Guidance for Electronic Source Data in Clinical Investigations”. The two-day Conference featured a look at innovative strategies and technologies affecting forward-thinking companies involved in clinical studies and clinical data management. The Conference included topics of interest to clinical data managers (“CDMs”) as well as individuals who supervise or support CDMs to better understand the evaluation and selection of new technologies to meet FDA’s and other regulatory requirements for collecting and managing clinical data. The focus was on information relevant to industry executives and included discussions how to select vendors for running clinical trials and managing clinical data.

First, Colleen Cox, Senior Manager, Data Management, Infinity Pharmaceuticals, provided an overview of the function of a CDM in a pharmaceutical/biotech company and how CDMs ensure that clinical data is accurate, logical, consistent, and complete. Dan Ringenbach, Sr. Enterprise Architect, AstraZeneca, Research and Development Information, then provided an overview of existing and future technologies that may be used in clinical data management, including “the Cloud”, mobile platforms, as well as ways to manage the increasing trend towards electronic clinical data information. With the goal of “seamless integration”, various technologies may be used to create data dashboards that have the potential to deliver increased data quality and reliability. With the increased information, organizations such as the Clinical Data Interchange Standards Consortium (“CDISC”) have emerged to help develop standards for the acquisition, submission, and exchange of clinical research data, as was explained by Shannon Labout, CDISC Expert and Authorized Instructor. FDA wants data that conforms to CDISC standards, Labout said, which may be required in the near future.

Jason Raines, Head, Global Data Operations, Alcon Laboratories, Inc., provided a comprehensive look at how to select, negotiate, and contract electronic data capture (“EDC”) vendors that are frequently utilized in clinical trials. Once an EDC provider is selected, it is important to develop an effective implementation and roll-out plan to provide a structured approach for success. Raines suggested testing an EDC vendor with a pilot before committing resources to one vendor and to develop metrics to demonstrate value from the vendor’s program going forward. Hand-in-hand with selecting an EDC, Anne C. Hansen, Senior Study Data Manager, Genetech, Inc. and Roche Ltd., explained how the EDC vendors can work with contract research organizations (“CROs”).
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On October 29, 2013 FLH’s Brian J. Malkin and Julie E. Kurzrok will present an “Update on FDA’s Draft Guidance for Electronic Source Data in Clinical Investigations” at Q1 Productions Conference Clinical Data Management Innovation held in Alexandria, Virginia. The two-day Clinical Data Management Innovation Conference (October 28-29) will take a look at innovative strategies and technologies affecting forward-thinking companies involved in clinical studies and clinical data management. Executives in clinical data management for the life sciences industry face increasing challenges managing the level of data increasingly demanded by regulatory authorities and third-party payors. In addition, many later-phase studies are now multi-center studies being conducted simultaneously, where clinicians want immediate access to cross-center data.

The Conference will focus on topics of interest to clinical data managers (“CDMs”) as well as individuals who supervise or support CDMs to better understand the evaluation and selection of new technologies to meet FDA’s and other regulatory requirements for collecting and managing clinical data. In addition to presentations on FDA’s requirements, such as the one FLH is providing, the focus will be on industry executives rather than consultant or vendor corporations providing real-world insights into the pros and cons of a wide variety of technologies, as well has how they have been implanted on site. As with other Q1 conferences, there will be ample opportunities for education and knowledge sharing, as well as interaction and peer-to-peer networking throughout the program.

Key Conference Takeaways include:

FLH Partner Brian J. Malkin will join more than 700 generic industry professionals and FDA staff who attend the Generic Pharmaceutical Association’s (“GPhA’s”) Fall Technical Conference in Bethesda, Maryland from October 28-30, 2013. This unique educational conference has become the vehicle for key FDA officials to disclose and discuss the key regulatory and technical issues affecting pending or yet-to-be-filed generic products. Here, more than a dozen top FDA officials, including a keynote from the Director of the Center for Drug Evaluation and Research (“CDER”), Janet Woodcock, M.D., and panel discussions will discuss the issues affecting the generic drug industry and ultimately innovators and all of us in FDA regulatory affairs in a meaningful way.

Topics to be discussed include:

• The impact of the Generic Drug User Fee Act (“GDUFA”)

duelingsquirrels.jpgOn October 24, 2013, FLH Partner Brian J. Malkin was quoted on an Inside Health Policy article “FDA Denies Shared REMS Petition; But Guidance, Rulemaking A Possibility”. Some background on this topics may be found in a previous blog here.

Building upon a recent presentation made at the FDA public meeting on Standardizing and Evaluating Risk Evaluation and Mitigation Strategies (“REMS”) held in FDA’s White Oak campus on July 25-26, 2013, Mr. Malkin suggested another way that FDA could find the resources to assist in the collaboration between innovator and generic companies to develop shared REMS programs: user fees from generic drug companies to help fund the process and development of guidance and initiate a notice-and-comment rulemaking.

FDA’s decision to the Prometheus Citizen Petition said FDA may consider regulation or guidance as it gains more experience with the development of shared REMS, particularly in an environment where there is only the innovator’s product prior to generic entry. FDA’s response, however, denied the request for rulemaking at the present moment. FDA’s response suggested that FDA thought a shared REMS was possible because it has been accomplished before, despite the innovator’s concerns for resource commitments and potential risks arising from antitrust law and product liability. To the extent that FDA listed examples where a shared REMS worked, however, there were few contentious issues concerning patents such as patents on the REMS itself or complexities involved in obtaining the innovator’s product without circumventing or avoiding the REMS for bioequivalence testing purposes. FDA also denied Prometheus with an opportunity to directly participate in the process to determine whether FDA would waive the requirement for ANDA applicants to agree to a single, shared REMS with the innovator for a product with a REMS with elements to assure safe use. In this regard, FDA said that it would invite comments, however, from both innovator and generic companies on the process to develop a single, shared REMS. FDA reserved the right to determine by specific request or on its own whether a waiver should be granted based on its evaluation of the burdens and benefits to create a single, shared REMS.
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Thumbnail image for Thumbnail image for Thumbnail image for Thumbnail image for Thumbnail image for Thumbnail image for Q1 ProductionisAddressing Industry Concerns Regarding FDA Regulation and Compliance While Improving Utilization of Clinical Outcome Assessments through Increased Instrument Efficiency and the Utilization of Innovative Technologies to Ensure FDA Label Inclusion

Clinical Outcome Assessments within the pharmaceutical industry provide critical data to researchers to support a variety of claims, from safety to cost-effectiveness, to regulatory bodies as well as healthcare providers and third-party payers. While outcomes information has been collected for some time, and both from a wide variety of sources and in varied formats, there has been little harmonization in the ultimate reporting and utilization of this critical information. The Q1 Maximizing Clinical Outcome Assessments Conference will provide an opportunity for executives throughout the industry for high-level education and networking, blending perspectives from academia, industry-veterans, and regulatory authorities.

This conference will take place in Alexandria, Virginia on January 13-14, 2014. For organizations addressing challenges in maximizing clinical outcome assessments, the first step is to understand regulatory hurdles faced by the industry, and the evolving expectations from FDA for reporting and communicating research findings. Additional sessions will cover a range of topics, including presentations highlighting various instruments that can be utilized to collect reported outcomes, as well as new applications and mobile technologies, modernizing the methods through which this information is gathered. Insightful commentary will also provide detail on validation methods, as well as methods for working with the range of observers and with the most appropriate tools for those populations.


  • Addressing FDAs Perspective On Utilizing Clinical Outcome Assessment
  • Focusing On Implementation Strategies That Will Affect Label Claim Submissions
  • Review Costly Compliance Concerns That Effect The Pharmaceutical Industry
  • Sharpening Techniques And Methodologies To Maximize COA Utilization
  • Validating COAs Through The Power Of Social Media
  • Optimizing The Use Of Critical COA Evidence Beyond The Label
  • Evaluating The Considerations For COAs In Children And Adolescents

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