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January 16, 2014

FLH's Brian Malkin Quoted In The Pink Sheet on Generic Drug Review Changes

drugs.pngOn January 6, 2014, FLH Partner Brian J. Malkin was quoted in an article by Derrick Gingery in The Pink Sheet entitled "Generic Drugs 2014: OGD Creates Internal Review Goals, May Make OND-Inspired Changes".

Gingery's article focused on FDA's Office of Generic Drugs ("OGD") taking steps to meet review deadlines that will be imposed by the Generic Drug User Fee Act ("GDUFA"), and enacted by the Food and Drug Administration Safety and Innovation Act ("FDASIA") of 2012. For example, sixty percent of all applications accepted for filing in fiscal year 2015 must be reviewed within 15 months, which is included in a GDUFA commitment letter. According to the article, as of December 1, 2013, OGD's project managers started setting internal goals to help reviewers get used to a review clock--a new concept for OGD but something that has been around since the Prescription Drug User Fee Act ("PDUFA") first implemented in the 1990s for FDA's Office of New Drugs ("OND"). Acting OGD Director Kathleen Uhl, M.D. ("Cook") commented there, "We need to have all the reviewers practice the review to a goal date and then we need to monitor what's our predictability of meeting those goal dates." Uhl also told Gingery that the "primary purpose" of the goal dates was to help OGD determine the time it will take to complete various parts of the abbreviated new drug application ("ANDA") reviews and would not be shared with sponsors.

Malkin was asked to comment on the internal goals, which appeared in the article as follows:

Attorney Brian Malkin, of Frommer, Lawrence and Haug LLP, agreed that the internal goals likely would not be helpful to sponsors.
"They're not going to be able to react to FDA's deadlines unless FDA shares additional information with them, except perhaps to set some of their own timetables for what FDA may be doing on their end," Malkin said in an interview.
Malkin said the aim appears to be finding areas where the process can become more efficient.
"It's tied to FDA's realistic expectations of what they can do to meet their timeframes, but also ... it may not be exactly what industry thought they were getting," he said. "The concept would suggest shorter review times, but we'll have to see."

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December 10, 2013

Physical Attributes of Generic Tablets and Capsules Guidance Issued by FDA

troubleswallowingpills.pngOn December 9, 2013, FDA issued a new draft guidance: Size, Shape, and Other Physical Attributes of Generic Tablets and Capules. FDA said that it issued the guidance because it is concerned that patients perceive differences in the physical characteristics (e.g., size and shape of a tablet of capsule) of generic drugs in relation to its referenced listed drug ("RLD") counterpart. FDA believes that these perceived differences are "important" and "may affect patient compliance and acceptability of medication regimens or could lead to medication errors." FDA does not plan for the Guidance to apply to generic drugs that are already on the market, unless there are safety issues, or other oral dosage forms.

According to the Guidance, many individuals have difficulty swallowing tablets and capsules, perhaps as many as 40 percent of Americans. Of these individuals, most blamed the dosage form size as an issue. In some instances, the larger tablets or capsules have been "shown to prolong esophageal transit time," which may lead to disintegration of the product in the esophagus or cause injury to the esophagus, or more general adverse events such as pain, gagging, choking, and aspiration. In the industry, these larger tablets or capsules have been called "horse pills." Some tablet and capsule shapes are known to be easier to swallow and have faster esophageal transit times than similar dosage forms with the same weight, e.g., oval sizes are easier to swallow than round. In turn, patient compliance may be affected by the size and shape of a tablet or capsule. Other physical attributes that affect ease of swallowing include coatings, weight of the tablet or capsule, and surface area of the dosage form.

As a result, FDA recommends that as part of its quality initiatives for generic drug products, generic oral tablets and capsules should be of a similar size to their corresponding RLD. In particular:

  • If the RLD is less than or equal to 17 mm in it largest dimension, the generic product should be no more than 20 percent larger than the RLD in any single dimension (resulting dimention not to exceed 17 mm) and no more than 40 percent larger than the RLD in volume.
  • If the RLD is greater than 17 mm in its largest dimension, the generic product should be no larger than the RLD in any single dimension or volume.
  • We recommend the largest dimension of a tablet or capsule should not exceed 22 mm and that capsules should not exceed a standard 00 size

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December 5, 2013

Bioequivalence Guidance for ANDAs Released

FDA.bmpFDA issued a draft guidance Wednesday that provides its recommendations for generic-drug makers seeking to show bioequivalence to a reference listed drug. The document--Bioequivalence Studies with Pharmacokinetic Endpoints for Drugs Submitted Under an ANDA--does not represent a significant change or shift in FDA policy/opinion, but it covers many approaches and revises and replaces parts of two existing FDA Guidances (see here and here). And, most notably perhaps, the document is a consolidation of many of FDA's previous opinions and guidances on establishing bioequivalence that concludes with an attachment providing a summary of general approaches for the design and data handling of bioequivalence studies with pharmacokinetic endpoints. The document should provide would-be generic-drug applicants with a good starting place.

FDA's advice is very general, as the Agency states that companies should see FDA's product-specific guidances for information on individual drugs. But despite the lack of product-specific advice, the guidance provides significant detail about common study parameters. FDA starts with a general discussion of how best to establish bioequivalence. The Agency notes that applicants can establish bioequivalence using in vivo and/or in vitro methods, which include--in descending order of preference--pharmacokinetic, pharmacodynamic, clinical, and in vitro studies.

Regarding pharmacokinetic studies, FDA suggests that applicants use: (1) a two-period, two-sequence, two-treatment, single-dose, crossover-study design; (2) a single-dose-parallel-study design; or (3) a replicate-study design. To establish bioequivalence from the studies, FDA urges applicants to use the average bioequivalence method of analysis. The guidance provides that, if possible, the study population should consist of enough subjects--18 years and older and representative of the entire population, considering age, sex, and race--to provide adequate statistical power.

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November 25, 2013

Generic Drug Labeling May Include New Safety Information According to Proposed FDA Regulation

genericdrug.jpgFDA is proposing to amend its regulations to permit generic drug companies to add or strengthen safety warnings in labeling of their products on the basis of newly acquired safety information, even before the Agency has approved this safety information in the labeling of corresponding brand name drugs.

Under current rules, a generic drug must have the "same labeling" as its reference listed drug. This prevented an ANDA holder from inserting or altering a safety communication unless and until FDA has approved this information in the labeling of the brand name drug.

The purpose of the amendment is to "level the playing" field for generics, which arises from two conflicting Supreme Court decisions involving Federal preemption of safety warnings in prescription drug labeling. In Wyeth v. Levine, the Court held that a failure to warn claim in a Vermont personal injury action was not preempted by FDA labeling regulations, because the brand name drug company could have voluntarily amended its labeling to include a stronger safety warning even if FDA had not approved it. In contrast, the Court subsequently held in Pliva v. Mensing that a state failure to warn claim was preempted by FDA-approved labeling, since the generic company could not unilaterally add or strengthen its warning due to the same labeling requirement.

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November 7, 2013

GPhA's Fall Technical Conference Delivers Messages of GDUFA, Quality, and More - Day 2

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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November 6, 2013

GPhA's Fall Technical Conference Delivers Messages of GDUFA, Quality, and More - Day 1

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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October 29, 2013

FLH's Brian Malkin to Attend GPhA's 2013 Fall Technical Conference in Bethesda, Maryland

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")
• Quality metrics and how they are effectively used and reviewed
• FDA compliance, including inspections and enforcement
• FDA's thoughts on generic versions of complex drug products
• Clinical endpoint studies
• Microbiology and sterility
• The Office of Generic Drug's filing review
• Stability issues and testing
• How to handle different inactive ingredients
• Office of Generic Drug Director's Update

Mr. Malkin plans to attend the main conference from October 29-30, 2013, and looks forward to meeting you at GPhA's Fall Technical Conference and sharing with you his thoughts about the information shared and discussed. THe full agenda for the Conference may be found here.

October 24, 2013

Watson's Silodosin Petition Denied by FDA

rapaflo.jpgEarlier this month, FDA denied a Citizen Petition filed by Watson Laboratories Inc. (now part of Actavis, Inc. or "Actavis") on May 10, 2013, requesting that FDA deny any abbreviated new drug applications ("ANDAs") it receives for a generic version of Rapaflo® (silodosin) Capsules unless the applicant demonstrates bioequivalence for both silodosin and its metabolite KMD-3213G. Watson requested that bioequivalence for both the drug and its metabolite be measured using a strict statistical evaluation of the standard pharmacokinetic measures of area under the plasma concentration-time curve ("AUC") and peak drug concentration ("Cmax"). Watson further requested that FDA revise its draft guidance on bioequivalence testing for silodosin capsules to require a demonstration of bioequivalence for both silodosin and KMD-3213G.

On October 8, 2008, FDA approved Watson's new drug application ("NDA") for Rapaflo®, 4 mg and 8 mg, indicated for the treatment of the signs and symptoms of benign prostatic hyperplasia ("BPH"). BPH is a noncancerous enlargement of the prostate that makes urination difficult and uncomfortable. Sandoz Inc. ("Sandoz") recently filed an ANDA for generic Rapaflo®.

Silodosin is an alpha-1 adrenergic receptor antagonist and undergoes extensive metabolism. Its main metabolite is a glucuronide conjugate, KMD-3213G, which has been shown in vitro to be active. KMD-3213G has an extended half-life (approximately 24 hours) and reaches plasma exposure approximately four times greater than that of silodosin.

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October 8, 2013

Refuse-to-Receive ANDA Guidance Issued

refusetoreceive.pngOn September 30, 2013, before the federal government shut down hit, FDA published a new guidance, "ANDA Submissions-Refuse-to-Receive Standards". FDA's guidance explains many of the principles that have been articulated in FDA's "ANDA [Abbreviated New Drug Application] Checklist for Completeness and Acceptability of an Application" ("ANDA Checklist"), which is reviewed quarterly basis (calendar year) and updated on an "as needed" basis. The Guidance reported that refusal-to-receive decisions ("RTRs") "underscore the need for improvement in the quality of original ANDAs." Between 2009 and 2012, FDA's Office of Generic Drugs ("OGD") refused to receive 497 ANDAs, the Guidance explains. RTRs occurred with regard to original submissions, in 2009 - 12%; 2010 - 18%; 2011 - 15.5%, and 2012-9.4% (estimated). The most common reasons for RTRs included serious bioequivalence deficiencies and serious chemistry deficiencies, with other lead causes being format or organizational flaws, clinical deficiencies, and inadequate microbiology. As a result, FDA believes that it would help to clarify its RTR criteria to help improve ANDA quality.

First, FDA noted that as part of its threshold determination for filing, FDA reviews ANDAs following the ANDA Checklist, which is formatted to mirror the organization of the Electronic Common Technical Document ("eCTD"). As a matter of general policy, FDA will notify an applicant if it will issue a RTR and provide the applicant with the opportunity to withdraw its ANDA, amend to correct the deficiencies, or take no action. FDA intends to work with applicants if there are fewer than ten minor deficiencies, with such notification by phone, e-mail, or facsimile. If the applicant can correct the deficiencies within five business days and FDA so finds, then FDA will still receive the application from its original receipt date; if not so corrected, FDA will RTR the application. FDA will issue an RTR, however, if the application contains more than ten minor deficiencies or one or more major deficiencies.

The Guidance goes on to explain what FDA considers major deficiencies: failure to submit a completed FDA Form 356h, organizational/format failures, non-payment of Generic Drug User Fee Act payment obligations, lack of a U.S. agent for a foreign applicant, failure to provide an environmental assessment (or claim of categorical exclusion), failure to ensure the proposed labeling is consistent with the filed patent statement (i.e., the proposed method of use, with one exception where a patent is listed but the referenced listed drug ("RLD") does not include the claimed use (Here, OGD will advise if this approach was correct or if the labeling or patent statement need revision.), citing an incorrect or unfounded basis of submission, other labeling deficiencies (not electronic or not the same as the RLD with not appropriate explanation for certain allowed differences such as change of manufacturer name), drug master file deficiencies, chemistry deficiencies, and bioequivalence and clinical deficiencies. Where an applicant has questions, FDA encourages Control Correspondence for guidance, with the exception that applicants are to consult product-specific bioequivalence recommendations rather than sending FDA Control Correspondence except for further guidance to explain the public guidance. FDA will consider alternative bioequivalence or other criteria in some instances with adequate justification, the Guidance further explains.

As more GDUFA measures are implemented over time, as with this one, it will be interesting to see if FDA will report improved ANDA quality or if the problems persist.

October 1, 2013

FLH's Brian Malkin Quoted in "The Pink Sheet" Article on GDUFA Update

Thumbnail image for drugmoney.jpegOn September 30, 2013, FLH Partner Brian J. Malkin was quoted in an article in "The Pink Sheet" entitled "GDUFA Plus One: Stakeholders, FDA Confident As Review Goals Near" (subscription or article fee required). The article summarized progress since the Generic Drug User Fee Act ("GDUFA") was enacted last year. GDUFA permitted FDA to collect fees from generic drug applicants and holders of drug master files ("DMFs") in exchange for certain efficiency enhancements and the promise for considerably shorter review times for abbreviated new drug applications ("ANDAs") in coming years. While FDA does not have to meet any ANDA review deadlines this year, starting with applications received from the fiscal year beginning October 1, 2014, FDA will need to review 60% within 15 months, then 75% within 15 months the following fiscal year, and 90% within 10 months of submission the next year.

FDA has reported progress with collecting fees, hiring new reviewers, and beginning to train these reviewers, as well as making a dent in the ANDA backlog. Regarding fees, FDA reported collecting $255 million collected in fiscal year 2013, about $44 million less than the target. GDUFA required FDA to hire 231 new employees in fiscal year 2013 and on September 11, 2013, FDA said it had hired 234 GDUFA-tagged employees, which FDA is in the process of training. FDA also has reported that it has reviewed about 40% of the application backlog since GDUFA went into effect and has conducted completeness assessments for about 900 DMFs. At the same time, however, review times have remained at a mean of 30+ months and have appeared to now be even longer. FDA has attributed part of this to the need to train new reviewers, which takes seasoned reviewers away from ANDA reviews, with the new reviewers not up to speed yet. Malkin was quoted in two sections on early improvement and budget sequesteration. Excerpts from the full quotations in the article include, for example:

There also does not appear to be much evidence that inspection parity is evolving. Brian Malkin, an attorney at Frommer, Lawrence and Haug, said there continue to be delays getting facilities reviewed and approved for first-to-file generic applicants.

. . .

Budget sequestration may have hindered some implementation efforts, but Malkin said ultimately the changes taking place at FDA were necessary to improve its generic drug systems.

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September 13, 2013

ANDA Labeling / USP Featured at GPhA/FDA Conference Part 2 of 2

ANDA drugs.jpgThis is a the second part of the blog on the Generic Pharmaceutical Association ("GPhA") / FDA / United States Pharmacopeia ("USP") ANDA Labeling Workshop/USP User Forum held in Bethesda, Maryland on September 11-12, 2013. Following Rudy Wu, Pham. D., M.P.H., Team, Leader, Labeling Branch, OGD, Scott Dallas, R.Ph., Labeling Reviewer, OGD, provided an overview of OGD's view of medication errors, which has built upon several reports by the Institute of Medicine in 1999 and 2006. FDA has been working with a Merck labeling initiative to see how products can be modified to be more easily distinguished in particular on the pharmacist's shelf. Generic drugs, just like their innovator counterparts, may be confused by similar trade dress or packaging, which should be a consideration when filing an application, Dallas noted. In addition, specialty packaging, such as blister packs or clear parenteral doses have been an issue, Dallas explained, where space for labeling is tight and often difficult to read for practitioners.

Carrie Lemley, OGD's only current Labeling Project Manager, described OGD's labeling review as a multidisciplinary process. Regarding products with mandated risk evaluation and mitigation strategies ("REMS"), Lemley said OGD is tracking FDA's process to standardize REMS (see related blogs here and here). In particular, if generic applicants are supposed to use a single, shared system for the elements to assure safe use ("ETASU"), FDA expects the RLD sponsor and generic drug applicants to work together to develop the single, shared program.

To date, FDA has only granted one waiver (buprenorphine) to permit both an RLD and shared generic REMS, but FDA contemplates that waivers will only be granted with well-rationalized reasons, i.e., more than an inability to get along. ANDA applicants, however, are not responsible for developing a communication plan or assessments for REMS but is expected to update its REMS in line with the RLD, e.g., if FDA with draws the REMS requirement, a generic applicant should also request to withdraw its REMS (The process is not automatic.) In response to questions about the waiver process, Lemley stated that there is no formal process but the elements to include in a waiver request are:

  1. Description of efforts to negotiate and decision makers,
  2. Justification for waiver including inability to work out issues regarding control or finances,
  3. Explanation how a waiver would affect everybody in that system and how two systems could co-exist instead of one,
  4. Accounting of cost issues for implementation, and
  5. Anticipation of the burden on the healthcare system and consumers for the separate systems.

Continue reading "ANDA Labeling / USP Featured at GPhA/FDA Conference Part 2 of 2" »

September 12, 2013

ANDA Labeling / USP Featured at GPhA/FDA Conference Part 1 of 2

ANDA drugs.jpgOn September 11-12, 2013, the Generic Pharmaceutical Association ("GPhA") in coordination with FDA and the United States Pharmacopeia ("USP") hosted an ANDA Labeling Workshop/USP User Forum in Bethesda, Maryland. The first day featured FDA speakers from FDA's Office of Generic Drugs ("OGD") who focus on labeling and filing/approval issues, and the second day featured speakers from USP.

Peter Rickman, M.S., Director, Division of Labeling and Program Support, OGD, kicked off the program, noting that OGD had a lot of challenges implanting the efficiency goals of the Generic Drug User Fee Act of 2012 ("GDUFA"), including their new 10-month review goals. Rickman stressed that for OGD to meet those goals, abbreviated new drug applications ("ANDAs") will need to be high quality, which is why FDA is spending time educating industry about quality.

Rudy Wu, Pham. D., M.P.H., Team, Leader, Labeling Branch, OGD, explained that labeling reviews can take longer when a consult is needed, i.e., checking with another FDA office for labeling acceptability, including the Office of Chief Counsel ("OCC"), Office of New Drugs ("OND"), surveillance, epidemiology, pediatric, and other centers. When a consult is requested, OGD must wait for the other entity to respond, which may create additional delays. Wu said there are many reasons why labeling reviews may take longer than expected: waiting for a final United States Pharmacopeia standard to issue or be met, standardizing the generic risk evaluation mitigation strategies ("REMS"), consults, citizen petitions, pending regulations or guidances, new clinical experience, patents and exclusivity may cause generic applicants to submit formulations that differ from the reference listed drug ("RLD) or include labeling carve-outs, and nomenclature differences. For example, regarding nomenclature, Wu said sometimes the RLD may use non-compendia-standard terms where the Orange Book uses another term, and FDA is concerned that both the RLD and the generic versions include labeling to ensure that pharmacists understand that they are substitutable for one another.

Continue reading "ANDA Labeling / USP Featured at GPhA/FDA Conference Part 1 of 2" »

September 11, 2013

FLH's Brian Malkin to Attend GPhA/FDA's ANDA Labeling Workshop / USP User Forum

On September 11-12, FLH's Partner Brian J. Malkin will attend GPhA[Generic Pharmaceutical Association]/FDA's ANDA [Abbreviated New Drug Application] Labeling Workshop / USP [United Pharmacopeial Convention] User Forum. The Conference provides a unique opportunity for attendees to hear straight from FDA's Office of Generic Drugs ("OGD") Labeling Review Staff, who are responsible for reviewing and approving ANDAs. The Workshop will provide industry with current information on the ANDA labeling review process as well as the many issues facing the generic industry when submitting ANDA labels. Some key topics to cover include:

  • Recommendations for industry on handling last-minute labeling "carve-outs"
  • The impact of REMS on the ANDA labeling review process
  • MedGuide Requirements>
  • Risk management plan challenges
  • Pediatric exclusivity considerations
  • Best practices for ANDA labeling

In addition, the Conference features presentations from USP staff about recent trends in USP's monograph process and how changes in monographs can affect ANDA labeling and approvability. USP is a scientific, nonprofit organization that sets standards for the identity, strength, quality, and purity of medicines. Some of the topics USP staff will cover include pharmaceutical quality standards and the USP-NF standards- setting process, in addition to the following topics:

  • Pending Monograph process
  • Flexible Monographs
  • General Chapters Updates
  • Navigating the USP-NF
  • General Notices
  • USP Dictionary of USAN

In addition, USP will explain how members of the pharmaceutical community may get involved with the USP monograph process and more.

June 26, 2013

Court Denies Bartlett Relief for Generic Drug Design "Defects"

Thumbnail image for supreme court.jpgOn June 24, the U.S. Supreme Court decided to shield generic manufacturers from product liability suits in Mutual Pharmaceutical v. Bartlett. The Court held that a generic manufacturer could not be held liable for a design-defect claim on a small molecule, pharmaceutical product, because the claim was preempted by the Federal Food, Drug, and Cosmetic Act ("FD&C Act").

Karen Bartlett met with her physician to treat her shoulder pain. Her physician prescribed Clinoril® (suldinac), and she was dispensed a generic version marketed by Mutual Pharmaceuticals ("Mutual"). Unexpectedly, Bartlett suffered a rare and devastating reaction to the drug. Even after months of treatment, she was left severely disfigured and almost entirely blind.

As we blogged previously, Bartlett sued Mutual in New Hampshire under a state design-defect theory of product liability. Like many states, New Hampshire borrowed its design-defect cause of action from the Restatement (Second) of Torts. Under this theory, Bartlett alleged that the active ingredient sulindac was inherently and unreasonably dangerous.

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April 22, 2013

Generic Oxycontin®--Abuse Resistance Required Says FDA

mortar and pestle.jpgThe U.S. Food and Drug Administration ("FDA") announced last Tuesday that it would not approve any generic versions of the original formulation of the prescription narcotic painkiller OxyContin® ("original Oxycontin®"). OxyContin® is a brand name for oxycodone hydrochloride, an opiate-based pain medication. Original Oxycontin® has been marketed by Purdue Pharma since 1995 and is notorious for its user misuse and abuse.

OxyContin® contains a large amount of oxycodone because it is designed to release the pain-relieving drug over an extended 12-hour period. However, original Oxycontin® can easily be crushed and then snorted or injected (or even sprinkled on food) to produce a rapid and intense euphoric high. The abuse of original OxyContin® in this manner can lead to addiction and dependence and has reportedly earned the product the nickname "hillbilly heroin." Its accessibility has magnified abuse rates; FDA reports that half a million people over age twelve began using original OxyContin® for non-medicinal purposes in 2008 alone. According to the Center for Disease Control, the death toll from prescription painkiller overdoses tripled in the first decade of the 21st century, and such overdoses "now kill more Americans than heroin and cocaine combined."

In addition to a patent for original OxyContin, which expired on Tuesday, Purdue Pharma also owns a patent for a reformulated, abuse-deterring version ("reformulated Oxycontin®"). This newer version was designed to resist being crushed and to form a gel that is difficult to inject when dissolved. Notably, FDA approved an updated label for this product last week, specifying the tablets' crush-resistant properties and warning of the fatal risks of misuse. (The label information is available here.) Purdue withdrew original OxyContin® from the market when its new version was approved in 2010 but retained the trade name.

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