Vol. 45, No. 39 FDA Furlough Freezes New Filings; Oct. 7, 2013 ‘Emergency’ Tasks Take Precedence With Congress unable to agree on a fiscal 2014 government-funding INside this issue plan, the FDA has largely limited its operations to “emergency work” FDA approves new treat- and enforcement activities — strictures that have forced the agency to ments for psoriatic arthritis, freeze regulatory submissions for fiscal 2014 supported by new user fees. depression...... Page 2 Regulatory submissions for which a user fee was paid before FDA Calendar...... Page 2 Oct. 1 will still be accepted and/or reviewed during the government shutdown, however, including those assessed a FY 2014 user fee. Perjeta first to gain acceler- In a notice to industry, the FDA said the government shutdown ated approval via new FDA has restricted non-essential activities to those that are funded by pathway...... Page 3 “carryover user fee balances” under PDUFA and GDUFA. PhRMA sues HHS in bid The FDA also does not expect to receive any user fee money to repeal 340B orphan drug under the Biosimilar User Fee Act of 2012 (BsUFA) and therefore rule...... Page 3 will only be accepting BsUFA applications for emergency INDs. BI shutters Ben Venue unit, (See Furlough, Page 6) citing rising remediation price tag...... Page 4 Comings & Goings....Page 4 House Approves Track-and-Trace, CMS decision on diagnostic Compounding Pharmacy Reform Bill drug highlights new study challenges...... Page 5 A nationwide pharmaceutical track-and-trace program inched closer to reality Sept. 28 on House approval of legislation introduced Bioequivalence, chemistry by leaders in both houses of Congress. gaps top out FDA’s ANDA The bill, known as the Drug Quality and Security Act (H.R. refusals...... Page 5 3204), would also give the FDA new authority over large compound- More restructuring for ing pharmacies — albeit with certain key caveats (WDL, Sept. 30). Merck as key product pat- The House version of the bill, which passed on a voice vote, mir- ents expire...... Page 7 rors a Senate version of the bill that will move to the floor of that PhRMA asks FDA to let body as soon as Congress concludes its battle over how to fund the industry self-regulate trial government into the new fiscal year, which began Oct. 1. transparency...... Page 9 That fight notwithstanding, sources close to the legislation say Briefs...... Page 10 the Senate is expected to act quickly and there appears to be no sig- nificant opposition in the upper chamber blocking its path. The Buzz...... Page 11 (See Compounding, Page 12) Page 2 Washington Drug Letter Oct. 7, 2013

FDA Approves New Treatments maintenance study in which Brintellix showed For Psoriatic Arthritis, Depression patients taking the drug experienced significantly longer times between recurrences of depressive The FDA Sept. 30 approved two new treat- episodes than those on placebo. ments for adults with psoriatic arthritis and major depressive disorder (MDD), saying “it is impor- Takeda and Lundbeck said Brintellix will be tant to have a variety of treatment options.” available in 5 mg, 10 mg, 15 mg and 20 mg tab- lets by the end of 2013. The agency approved UCB’s Cimzia (certoli- zumab) for the treatment of active psoriatic arthri- Additional treatments for MDD include anti- tis, a chronic, inflammatory condition affecting the convulsants such as carbamazepine and valpro- joints and tendons. The nod falls on the heels of last ate, lithium and other antidepressants. week’s approval of Janssen’s Stelara (ustekinumab) — Melissa Winn for the same indication. The approval of Cimzia was supported by data FDA calendar from a Phase III trial showing the drug rapidly improved symptoms of enrolled active psoriatic Upcoming meetings through Nov. 14: arthritis patients, UCB’s chief medical officer and executive vice president Iris Loew-Friedrich said. ●● Oct. 16: The Endocrinologic and Metabolic Drugs Advisory Committee will meet to The new indication is Cimzia’s third in the U.S. discuss Amarin’s sNDA for Vascepa (icos- The drug is also approved for the treatment of certain apent ethyl) capsules. Silver Spring, Md. adults with rheumatoid arthritis and Crohn’s disease. ●● Oct. 17: The Anti-Infective Drugs Advisory Along with Stelara, Cimzia also faces mar- Committee will meet to discuss susceptibil- ket competition from AbbVie’s Humira (adalim- ity interpretive criteria for systemic antibac- umab) and Janssen’s Remicade (infliximab) and terial drugs and for dosing recommenda- Simponi (golimumab). tions in product labeling. Silver Spring, Md. ●● Oct. 18: The Anti-Infective Drugs Ad- UCB is also seeking a fourth U.S. indication for visory Committee will meet to discuss the drug, but the FDA asked its advisors to weigh Paladin’s NDA for miltefosine capsules. in on the proposal. A conflicted advisory panel in Silver Spring, Md. July voted 7-6 in favor of recommending approval ●● Oct. 21-22: The FDA will hold a public of Cimzia to treat axial spondyloarthritis, including workshop on Gastroenterology Regulatory ankylosing spondylitis, with one abstention (WDL, Endpoints and the Advancement of Thera- July 29). Many of the panel’s yes voters voiced con- peutics (GREAT II). Bethesda, Md. cerns about the drug’s broadly proposed indication ●● Nov. 12-14: The FDA will hold a training and hoped the FDA and UCB would narrow it. course for clinical investigators. College The FDA is still reviewing that filing. Park, Md.

Brintellix Approved in MDD Comment deadlines through Oct. 28: The agency also approved Takeda and Lund- ●● Oct. 25: Comments due on the draft guid- beck’s new antidepressant Brintellix (vortioxetine) ance Bioequivalence Recommendations for the treatment of adults with MDD. The mental for Risperidone Injection, docket no. health illness affects about 14 million adult Ameri- FDA-2007-D-0369-0244. cans a year, according to the companies. ●● Oct. 28: Comments due on the draft guid- The drug’s approval was supported by a ance ANDAs: Stability Testing of Drug large global clinical program, including six posi- Substances and Products, Questions and tive short-term studies, as well as one long-term Answers, docket no. FDA-2013-D-0938. Oct. 7, 2013 Washington Drug Letter Page 3

Perjeta First to Gain Accelerated percent of patients that received Perjeta in com- Approval via New FDA Pathway bination with trastuzumab and docetaxel chemo- therapy achieved pCR, compared to about 21 per- Genentech’s Perjeta Sept. 30 became the first cent who received the drugs without it. drug to win approval under the FDA’s new accel- erated approval pathway carved out for early- Additional safety data from a second Phase II stage breast cancer before surgery. study, as well as longer-term safety data from a Phase III study supporting a previous indication The pathway makes the treatment available for the drug, were also submitted to win approval. “several years earlier than previously possible,” Hal Barron, Genentech’s chief medical officer, said. A full review of data from an ongoing Phase The FDA in 2012 issued a draft guidance on using III study will be required for the accelerated pathologic complete response (pCR) as an endpoint approval to be converted to a full approval, the to support accelerated approval of a drug for neoad- FDA and Genentech said. Results from that trial juvant treatment (before surgery use) of high-risk, are expected in 2016. early-stage breast cancer (WDL, June 4, 2012). The FDA’s Oncologic Drugs Advisory Com- The agency said at the time that drugmakers mittee last month voted 13-0, with one absten- using randomized neoadjuvant trials assessing a tion, to urge approval of Perjeta as a preopera- pCR endpoint could predict clinical benefit within tive treatment in combination with trastuzumab months of initiating treatment, instead of years. and docetaxel for patients with HER2-positive, Perjeta’s (pertuzumab) approval is based on locally advanced, inflammatory or early stage data from a Phase II study that showed about 39 breast cancer (WDL, Sept. 16). — Melissa Winn

PhRMA Sues HHS in Bid to overlooked by drug companies seeking to market Repeal 340B Orphan Drug Rule blockbuster drugs. Congress intended the orphan drug exclu- PhRMA has launched a lawsuit to shoot sion to apply to any orphan drug use, including down a requirement that drugmakers provide for conditions not associated with rare diseases, orphan drugs to hospitals and healthcare provid- PhRMA argues, and it is asking the United States ers at drastically reduced prices under the federal District Court for the District of Columbia to 340B discount drug program. Orphan drugs were invalidate the final rule and bar the federal gov- previously exempt from the program. ernment from enforcing it. The suit against HHS challenges a final rule The Health Resources Services Administration issued by the agency that went into effect Oct. (HRSA), the HHS agency tasked with regulating 1 (WDL, July 29). The rule, which now exempts the 340B program, interprets congressional intent orphan drugs from 340B discounts only when differently. “The purpose of issuing this rule was used for the rare condition or disease for which to provide clarity in the marketplace and main- they were designated, expands the program tain the 340B savings and interests of newly-eli- beyond what Congress intended, PhRMA says. gible covered entities while ensuring the financial In general, the 340B program requires drug- incentives of the manufacturers of orphan drugs makers to provide certain outpatient drugs at are protected,” HRSA spokesman David Bowman a sizeable discount to hospitals and clinics that told WDL when the rule was issued in July. treat low-income and uninsured patients. Con- PhRMA “strongly supports the 340B pro- gress excluded orphan drugs from the program in gram” and is committed to working with all an effort to preserve incentives for orphan drug development for rare diseases, which often get (See PhRMA, Page 8) Page 4 Washington Drug Letter Oct. 7, 2013

BI Shutters Ben Venue in the told WDL that its drug shortages team is work- Face of Remediation Price Tag ing during the government shutdown to prevent a situation that could result in a shortage. Boehringer Ingelheim (BI) has decided to close Ben Venue Laboratories, its beleaguered It is unclear how the Ben Venue shut- generic injectable drugmaking unit, by the end down will affect the supply of necessary drugs, of the year, saying the subsidiary’s remedia- although one expert called it “huge” and likely to tion efforts will total about $1 billion and are not have a profound impact. worth the cost of keeping it open. Ben Venue was operating under a consent The decision will also affect Bedford Laborato- decree that hampered production but that had ries, which markets injectable drugs. Bedford will allowed it to continue making 108 medically nec- continue to market Ben Venue’s portfolio of available essary drugs (WDL, Jan. 28). products. BI spokeswoman Marjorie Moeling told Among those pharmaceuticals is Janssen’s WDL Oct. 4. Meanwhile, Bedford is “exploring stra- ovarian cancer drug Doxil (doxorubicin HCl lipo- tegic options to try to continue the supply of its port- some injection). Last month, manufacturing “dif- folio of products to patients long-term,” she added. ficulties” with Ben Venue resulted in another “The effort, magnitude of investment, and addi- potential Doxil shortage. — Robert King tional years required to remediate the facility before Ben Venue could return to sustainable production Comings & Goings is not feasible,” BI said. The German-owned drug- K-V Pharmaceutical has appointed Joseph maker projects it will be hit with approximately $700 Mahady chairman of its board of directors. Mahady million in cumulative operating losses over the next previously served as senior vice president of Wyeth five years — an estimate that comes on top of more and president of Wyeth Pharmaceuticals. than $350 million already invested to address reme- diation projects tied to long-standing quality issues at INC Research has named former Pfizer execu- its older and aging facilities (WDL, Sept. 2). tive James Taylor to be its new vice president of clinical development. The company recently tried to ramp down Olivier Brandicourt has been appointed production at two older Ben Venue facilities in chairman of the board of management of Bayer an effort to reorganize. Now BI will lay off about HealthCare and member of the Bayer AG Execu- 1,100 Ben Venue employees and cease production tive Council effective Nov. 1. Since March 2013, at all of its facilities. Wolfgang Plischke has led Bayer HealthCare on Ben Venue said Oct. 3 it notified the FDA of an interim basis in addition to his existing duties the shutdown. Agency spokesman Stephen King as a Bayer AG Board Member.

FDA FOIA Log

The FDA received 198 FOIA requests the week of Aug. 26 including the following. View the complete FOIA log for the week of Aug. 26 at www.fdanews.com/ext/files/10-03-13-FOIALog.pdf. Date Requester Requested Information Establishment inspection reports for the last five years for Cayman Chemical Company’s Ann Arbor, Mich., facility; Bio-Concept Labora- 8/26/2013 Aerie Pharmaceuticals tories’ Salem, N.H., facility; and Catalent Pharma Solutions’ Philadel- phia, Pa., facility. 8/26/2013 Fresenius Medical Care Safety reports on the NDA for Abbott Labs’ inpersol/delflex safe lock. 8/28/2013 Cempra Pharmaceuticals Form 483 for Wockhardt’s India plant. Oct. 7, 2013 Washington Drug Letter Page 5

CMS Decision on Diagnostic Drug Bioequivalence, Chemistry Gaps Highlights New Study Challenges Top Out FDA ANDA Refusals The Centers for Medicare & Medicaid Ser- Most ANDAs rejected by the FDA have defi- vices (CMS) decision to limit coverage of a diag- ciencies with either submitted chemistry or bio- nostic imaging drug for Alzheimer’s disease not equivalence data, new draft guidance on the only threatens the development of such drugs, but agency’s “refuse-to-receive” standard states. illustrates how industry must rethink clinical trial The Office of Generic Drugs (OGD) refused design, stakeholders say. to receive 100 ANDAs in 2012. Of those, 40 CMS last week said it would consider cover- were returned due to bioequivalence deficiencies, age for beta-amyloid imaging drugs such as Eli 36 had serious chemistry shortfalls, four were Lilly’s Amyvid (florbetapir F 18 injection) only in returned for inadequate sterility data and one was limited circumstances: for clinical trials that must sent back for referencing the wrong listed drug. be approved in advance by CMS. These critical deficiencies not only slow In its final decision, CMS said there is insuf- approval, but also can result in forfeited GDUFA ficient evidence that the use of such drugs is “rea- fees. The draft guidance, posted Sept. 30, clari- sonable and necessary” for the diagnosis or treat- fies what should be included in an ANDA and ment of Alzheimer’s. how to avoid an initial rejection. CMS will reconsider its decision only if a new Much of the information should be well- clinical study is conducted that meets certain cri- known to sponsors, including requirements that teria and proves the drug warrants coverage. The generic drugmakers have no outstanding user fee agency wants the trials to be comparative, lon- obligations and ensure that a product’s proposed gitudinal and involve patients “from appropriate labeling is consistent with a patent statement. populations.” Where appropriate, trials should be In clarifying the agency’s expectations around “prospective, randomized, and use postmortem bioequivalence and chemistry data, the draft guid- diagnosis as the endpoint,” it added. ance recommends “ANDA filers consult the bio- Amyvid was approved by the FDA in April equivalence recommendations (BE) webpage” for 2012 and is the only such product currently avail- product-specific guidance on conducting recom- able in the U.S. (WDL, April 16, 2012). The drug mended in vivo and/or in vitro studies. Agency is used with positron emission tomography imag- regulations also require applicants to submit infor- ing to detect levels in the brain of beta amyloid, a mation on failed in vivo BE studies. Questions protein that creates brain plaques believed to be about such studies can be directed to the Division the leading cause of Alzheimer’s. of Bioequivalence, the FDA says.

(See CMS, Page 6) (See ANDAs, Page 12)

FDA warning letter(S)

FDA Warning Letters Posted on Oct. 1, 2013 Letter Issue Close Out Date Company Name Issuing Office Subject Date C.P.M. Contract Pharma 9/17/2013 CDER GDUFA Requirements Not issued GmbH & Co. New Orleans Labeling/False & Mislead- 9/19/2013 Dolgencorp Not is­sued District Office ing Claims/Misbranded Florida District 9/24/2013 Nephron Pharmaceuticals New Drug/Misbranded Not issued Office Page 6 Washington Drug Letter Oct. 7, 2013

Furlough, from Page 1 increasingly being made to design clinical trials not only to meet regulatory standards, but also An HHS contingency plan released ahead of those imposed by payers, Andrew Stephens, vice the shutdown said the agency would have to “cease president of clinical research and development for safety activities such as routine establishment Piramal Imaging, told WDL Oct. 2. inspections, some compliance and enforcement Research techniques and trial endpoints must activities, monitoring of imports, notification pro- now include “health economics” measurements grams, and the majority of the laboratory research such as changes in treatment management that necessary to inform public health decision-making.” translate into improvement in patient outcomes Some 55 percent of the agency’s 14,779 and quality of life, he said. employees are expected to stay on the job under George Vradenburg, chairman of UsAgain- the contingency plan. stAlzheimer’s, called the move “anti-patient and Steve Niedelman, a consultant with King & anti-innovation.” Spalding urged drugmakers to continue to try Stephens agreed, saying the decision risks and meet regulatory deadlines. reductions in new investments in novel molecular “I would not use the government shutdown imaging agents. “In the end, it is the patients who as an excuse for not providing a timely submis- will suffer the most from CMS’ decision as they sion to FDA, for example responses to FDA 483s, will not be able to benefit from future innova- warning letters and the like,” he said. tions in molecular imaging,” he added. Meanwhile, Rep. Robert Aderholt (R-Ala.) Piramal’s florbetaben F18 product is currently introduced H.J. Res. 77, a fiscal 2014 appropria- being reviewed by the FDA and the European tions bill singularly designed to keep the FDA Medicines Agency. — Melissa Winn funded through the ongoing government shut- down. President Barack Obama promised to veto FDA Recordkeeping, the bill, saying it restores only “very limited” Dangerous Documents and agency activities. — Johnathan Rickman Writing for Compliance™

CMS, from Page 5 An Conference

Other companies such as GE Healthcare, Nov. 13–14, 2013 • Doubletree Bethesda Navidea and Piramal Imaging are developing Hotel • Bethesda, MD similar imaging drugs. GE and Navidea joined Every day, we write casual emails, meeting minutes and Lilly in expressing disappointment with CMS. sticky notes, never anticipating that an FDA inspector or other third party will read them. But these are exactly the types of Piramal, seeking clarification about how to dem- correspondences that are often used to determine an orga- onstrate outcomes in the requested trials, issued a three nization’s overall compliance profile. And thanks to product page response to CMS’ draft decision in July asking liability lawyers, these notes also need to be defensible…from criminal actions and lawsuits. the agency to establish a clear standard of the level of evidence required to expand coverage. The response But you don’t need to be afraid to write your next email. Join us on Nov. 13-14 for a two-day intensive workshop. Instead also questions whether coverage will be extended of sitting and being lectured to, you will engage in case stud- to the drugs upon meeting the trial endpoints, or ies, role playing, real-life examples and exercises designed to whether companies will additionally be required to ensure that your written word not only properly reflects your compliance initiatives, but also prevents trouble. navigate the “national coverage determination” pro- cess, again delaying access to the drug for patients. Register online at: www.FDARecordkeeping.com Piramal sees many hurdles ahead in light Or call toll free: (888) 838-5578 (inside the U.S.) of the CMS final decision. Drugmakers are or +1 (703) 538-7600 Oct. 7, 2013 Washington Drug Letter Page 7

Drugmakers Question FDA Thinking The Biotechnology Industry Organiza- On ‘Subjective’ New Inspection Powers tion commented that companies and the FDA often negotiate to allow photographs of certain The FDA’s interpretation of what consti- areas. This helps protect intellectual property tutes delaying or denying an inspection is far and trade secrets. The group asked the agency too subjective, and highlights the need for an to amend the draft guidance to loosen its provi- appeals process for pharma companies flagged as sion on photos by inserting language regarding obstructionist, drugmakers say in comments. “prior discussions” about photos. Celgene asked Violations outlined in recently published draft the FDA to provide a list of situations or scenar- guidance on the issue could be interpreted differ- ios where a company can expect an investigator ently from investigator to investigator, they said. to take a photograph. Such violations include situations where a facility’s contact ignores the agency, postpones a scheduled The comment period on the draft guidance, inspection start time or fails to produce requested docket no. FDA-2013-D-0710, is now closed. records, according to the July guidance, Circum- — Robert King stances that Constitute Delaying, Denying, Limiting or Refusing a Drug Inspection (WDL, July 15). More Restructuring for Merck As Key Product Patents Expire “The level of subjectiveness has the potential to lead to a disharmonized approach to inspec- Facing significant patent cliff pain, Merck tion expectations and management,” Celgene said Oct. 1 it plans to refocus its research around wrote. “Is it possible to provide clarity or defini- new therapies that present the “best opportuni- tive times for examples of reasonable justifica- ties:” vaccines, oncology, diabetes and acute care. tions so that both inspectors and companies are aware of what is expected?” The planned restructuring, which also includes job cuts and a new home base address, In cases where definitions in the draft guid- is intended to adjust to rapidly declining sales ance are disputed, Celgene asked for a “mecha- in asthma and allergy drug Singulair (montelu- nism to resolve the dispute” prior to a determi- kast sodium) and other Merck products beset by a nation and any associated consequences, which sudden surge of generic competition this year. could include criminal penalties. Recent regulatory disappointments have also Merck also asked for an appeals process, refer- compounded those patent problems, said Ken- encing a provision that an investigator must not be neth Frazier, the pharma giant’s chairman, presi- left in a conference room without access to necessary dent and CEO, on a conference call with analysts. documentation for “an unreasonable period of time.” FDA rejections of suvorexant and suggamadex There is no definition for what consti- occurred back to back this year. tutes “unreasonable,” Merck said. Sometimes a requested document could be stored off site and With an eye to recovering ground by the end “it may take time to locate and retrieve records (in of 2015, Merck plans to let go an additional 8,500 some cases over 24 hours),” the drugmaker added. employees on top of previous layoffs, as well as move its headquarters to Kenilworth, N.J. Merck Other commenters took aim at a provision sur- hopes to regain $2.5 billion in annual net cost rounding the taking of photographs by an FDA savings under the plan. investigator. The guidance states that not allow- ing photography may be considered a limita- To advance MK-3475, an anti-PD-1 antibody tion if “such photographs are determined by the that has shown initial success in treating mela- investigator(s) to be necessary to effectively con- noma, Merck plans to establish an integrated duct that particular inspection” (WDL, July 29). oncology unit, he added. — Lena Freund Page 8 Washington Drug Letter Oct. 7, 2013

Drugmakers Warned: 340B Program “I can’t imagine anybody abusing the program,” Da- Rules Not Excused By Ignorance vid Ivill, a partner at McDermott Will & Emery told WDL. Still, since its creation, “the 340B program Sen. Charles Grassley (R-Iowa) last week repri- has expanded” and involves more hospitals and manded two drugmakers for failing to provide price providers and thus more monies and suspicions. discounts or rebates on certain drugs as required under the federal 340B discount drug program. “The lack of transparency in both manufacturers’ pricing of 340B drugs and hospitals’ use of 340B In letters to Pacira Pharmaceuticals and CSL savings causes each group to suspect that the Behring, Grassley asks the drugmakers to ex- other is not playing by the rules,” a recent report plain conflicting comments they made to health- on the program states (WDL, July 22). care providers in Iowa and the Health Resources Services Administration (HRSA), the HHS Grassley has given both companies until Oct. 9 agency tasked with regulating the 340B program. to respond to the letters.

If drugmakers participate in state Medicaid pro- Pacira is reviewing the letter and “will provide grams, they must provide the discounts under 340B. further updates, as appropriate, in the future,” a Grassley made clear that ignorance of the oft- spokesperson told WDL. misunderstood program’s requirements would not excuse the drugmakers from reimbursing any 340B A spokesman for CSL told WDL Kcentra is providers they failed to provide discount pricing to. available at the Iowa facility for purchase at the mandated 340B drug discount price. “We recog- If they have not already made the reimbursements, nize the importance of this program and collabo- then they should explain “why not” and when the rate with qualified covered entities to ensure that reimbursements will be processed, Grassley said. product is made available,” he said.

Manufacturers are required to provide discounted Senator Grassley’s letters to the company can 340B pricing even if the pharmaceutical pricing be read at www.fdanews.com/ext/files/09-27-13- agreement (PPA) mandating the discount has Pacira.pdf and www.fdanews.com/ext/files/09-27- been acquired through an acquisition or a merger, 13-CSL.pdf. — Melissa Winn Grassley explained in his Sept. 25 letter to Pacira.

The 340B PPA conveys with any transfer of own- PhRMA, from Page 3 ership, he wrote in the letter, which was prompted by the complaints of an Iowa hospital that in- stakeholders to improve the program, Mit Spears, formed Grassley the drugmaker was not offering PhRMA’s executive vice president and general Exparel (bupivacaine liposome) at the 340B price. counsel, said Oct. 2. Pacira told the hospital it “does not participate” in the “To achieve this important objective, it is crit- 340B program, even though it does, according to ical that the [340B] program operates in a man- the letter. Pacira does not participate in Medicaid. ner consistent with the clear and unambiguous The hospital also complained CSL Behring direction of Congress,” he added. claimed its Kcentra (prothrombin complex con- centrate) was not available at 340B pricing “be- HHS Tuesday moved to stay the proceedings cause it is an in-patient biotherapy.” in the case until the ongoing government shut- down is resolved. PhRMA said it would agree to The drug, however, is used by hospitals in emergen- cy settings to stop acute bleeding when the patient a stay if HHS would also suspend implementa- first arrives and prior to being admitted as an inpa- tion of the final rule while the shutdown is under- tient, thus qualifying as an outpatient drug covered way. The government agency has so far declined under the 340B program, Grassley explains. to do so, prompting PhRMA to oppose the stay The misunderstandings identified by Grassley due to the “significant and irreparable harm” to “underscore the need for HRSA to issue clearer its members that “mounts on a daily basis.” guidance and to begin auditing manufacturers to ensure they are being compliant,” Ted Slafsky, To view PhRMA’s lawsuit, go to www. president and CEO of Safety Net Hospitals for fdanews.com/ext/files/10-02-13-PhRMA.pdf. Pharmaceutical Access told WDL Sept. 27. — Melissa Winn Oct. 7, 2013 Washington Drug Letter Page 9

PhRMA Asks FDA to Let Industry PhRMA and its EU counterpart the Euro- Self-Regulate Trial Transparency pean Federation of Pharmaceutical Industries and Associations responded to the EMA’s push with The drug industry itself is in the best position a joint set of industry principles for “responsible” to decide how to make preclinical and clinical trial sharing of clinical trial data (WDL, July 29). data more widely available, according to PhRMA. PhRMA reiterated those principles in its In comments to the FDA, the trade group response to the FDA, saying they justify industry points to limited agency resources as one impor- self-regulation of clinical trial transparency. tant reason for leaving transparency initiatives in While PhRMA outlined the potential road- the hands of industry, as well as industry’s expe- blocks to increased trial transparency, the Bio- rience with de-identifying data to protect the pri- technology Industry Organization offered a vacy of study subjects. potential roadmap for instituting an EMA-style The FDA in June issued a request for com- initiative. The three-step plan involves FDA ment on the topic, generating almost three dozen evaluation of existing data-sharing initiatives, responses from various stakeholders (WDL, June to learn what does and doesn’t work; develop- 10). Responding to the rush of replies, the agency ment of a pilot program based on what it learned, said Oct. 1 the comment deadline has been preferably focused on a disease area troubled by extended out to Oct. 31. past trial failures; and the publication of another request for comment on its trial transparency Around the time of the solicitation, FDA Com- plan before making any final decisions. missioner Margaret Hamburg said the agency was watching efforts by the European Medicines A Federal Register notice on the solicita- Agency (EMA) to oversee publication of trial data tion, docket no. FDA-2013-N-0271, is available “with great interest,” but stopped short of express- at www.fdanews.com/ext/files/09-30-13-data- ing support for a similar initiative in the U.S. sharing-notice.pdf. — Ferdous Al-Faruque

Feeling Patent Pain, Eli Lilly Places Meanwhile, the company is crossing its fin- Hopes on Pipeline Prosperity in 2014 gers that its long-term innovation strategy will begin bearing fruit by at least mid-2014 — hopes Eli Lilly is hoping to win several drug shared by some Wall Street analysts, who appear approvals next year to weather expiring patents, particularly bullish about Lilly’s ramucirumab as but for now it plans to cut back on operating a therapy for gastric cancer. expenses to stay competitive. Sluggish growth in certain emerging markets has put a damper on The company pointed to U.S. and European sales, the pharma giant noted Oct. 3. regulatory submissions for two Type 2 diabetes drugs empagliflozin, which it is developing with The new cost-cutting plan comes despite the Boehringer Ingelheim, and dulaglutide. It also drugmaker having the strongest pipeline in the touted positive results for necitumumab for patients company’s 137-year history, with 13 candidates with metastatic squamous non-small cell lung can- in Phase III or in regulatory review. But patents cer, and expects a regulatory submission next year. for two Lilly blockbusters are expected to expire before the pipeline produces drugs ready to mar- Phase III outcomes from Eli Lilly’s ramucirumab ket: the anxiety drug Cymbalta (duloxetine HCl) showed the drug was effective in treating gastric can- and osteoporosis drug Evista (raloxifene). cer, but failed to show the same for breast cancer. Lilly told investors it plans to reduce operat- Lilly is also committed to advancing its ing expenses and incrementally repurchase $5 Alzheimer’s drug, solanezumab. Fresh Phase III tri- billion in company stock. als are just now getting underway. — Robert King Page 10 Washington Drug Letter Oct. 7, 2013

briefs

Glass Issues Continue to Plague Hospira The bill, which now goes to the Senate, would Hospira late last month recalled one lot of require special licenses for compounding phar- metoclopramide injection, USP and two lots of macies and require by law that they be subject to ondansetron injection, USP due to glass issues. unannounced inspections. This time a supplier is to blame, Hospira said. The bill also includes whistleblower protec- The market correction was made due to a tion for pharmacy workers; a requirement that the confirmed vial defect where glass strands were state track all sterile compounded drugs made by observed affixed to the inside of the vial walls, state-licensed pharmacies and; a requirement that the generic injectable drugmaker said Oct. 1. compounding pharmacies report adverse events, such as illnesses or unintended drug reactions. The problem lots were distributed nationwide between June and September 2013. Upsher-Smith, Lundbeck Research PKAs Upsher-Smith Laboratories said Oct. 1 its UK The recall is the latest in a string of market cor- subsidiary Proximagen has entered into a preclinical rections related to glass particulates and overfills for development agreement with Denmark-based Lun- the company. The recalls come amid efforts to fix dbeck to expand its protein kinase (PKA) inhibitors manufacturing shortfalls at Hospira’s Rocky Mount, research program. The transaction is part of Upsher- N.C., plant and elsewhere (WDL, Aug. 27, 2012). Smith’s strategy to expand its current product port- folio of branded drugs, the company said. Specific Mass. Lawmakers Pass Compounding Bill terms related to the deal have not been disclosed. The Massachusetts House Oct. 2 unanimously approved a bill that would mandate tougher state Erbitux Shows New Promise regulations on drug compounding pharmacies. Merck KGaA said Sept. 28 that new data from The state’s New England Compounding Center a Phase III trial of its colon cancer drug Erbitux was at the heart of last year’s deadly meningitis (cetuximab) extended the lives of a sub-group of outbreak that sparked a national debate over regu- patients with advanced colon cancer on average lating compounders (WDL, Oct. 29, 2012). seven and a half months longer than those taking competitor Roche’s Avastin (bevacizumab). The legislation, approved by state lawmakers in a 155-0 vote, incorporates several recommendations The findings showed new promise for Erbitux in made by Gov. Deval Patrick (D) in the aftermath of a sub-group of patients with a certain type of “wild- the outbreak, including a requirement that compound- type” tumors. Merck announced earlier this year its ers report their drug production by type and volume. drug had failed to shrink tumors more than Avastin. t Court Actions Recent federal court actions involving the FDA and drug industry: Party Case Date Most Recent Most Recent Name Court Number Filed Action Date Action Case Topic United States PhRMA opposed HHS PhRMA v. 340B orphan District Court motion for stay of pro- HHS, HRSA 13-01501 9/27/13 10/1/13 drug exclu- for the District ceedings during govern- et. al. sion rule of Columbia ment shutdown U.S. Court of Eisai filed reply to Scheduling Appeals for the 13-1243 8/19/13 9/4/13 memorandum of law of controlled Eisai v. District of Co- and fact substance DEA lumbia Circuit Oct. 7, 2013 Washington Drug Letter Page 11

the buzz

Lynne Yao is associate director, when a problem arises it’s something the FDA Pediatric and Maternal Health Staff can hear about, consider and help the sponsors (PMHS), in CDER’s Office of New work through. Drugs. PMHS oversees initiatives Other issues unique to drug development for that promote and necessitate the children include formulation and metabolism of study of drugs and biological prod- the drug. For example, a young child who can’t ucts in the pediatric population and swallow a pill and the formulation that is cur- improve pregnancy and lactation- rently being evaluated for approval is a pill form. related information in product labeling. You’re going to have to develop a formulation, if WDL: How has the FDA tried to incentivize necessary, that would be appropriate to use in a more pediatric drug development? younger child. Pharmaceutical labels for approximately Also, children are not just little adults and 80 percent of drugs prior to 1997 had no infor- they may metabolize or absorb a drug in a differ- mation for children at all in any pediatric age ent way than an adult does. So it is important that group. Laws were passed to address that gap we know those characteristics, the pharmacoki- — the Food and Drug Modernization Act of netic and pharmacodynamics considerations that 1997 (FDAMA), which ultimately led to the may be different in children. That will lead to the Best Pharmaceuticals for Children Act (BPCA) ability to identify the appropriate dose for a child. and the Pediatric Research Equity Act (PREA). WDL: What are some ways sponsors can These two pieces of legislation have changed improve their ability to get more drugs for chil- the landscape of pediatric drug development and dren on the market? provided both incentives and requirements for One of the things we have the ability to do, companies that were developing drugs to con- which is different than adults and I think helps sider for children. to speed the development of drugs for children, BPCA provides an incentive for drug compa- is this concept of extrapolation. We can extrapo- nies to conduct FDA-requested pediatric studies late the efficacy if we know that the pathogene- by granting an additional six months of market- sis of the disease is similar in adults and children, ing exclusivity. and the mechanism of action of the drug would be similar in adults in children. So, there’s an abil- PREA requires drug companies to study their ity to not have to do full-blown double-blind, pla- products in children under certain circumstances. cebo-controlled efficacy trials in children if there’s When pediatric studies are required, they must an ability to extrapolate from adult efficacy. be conducted with the same drug and for the same use for which they were approved in adults. Importantly, you can’t extrapolate dosing or safety. You still have to have that data collected WDL: What are some key issues drugmak- in children and evaluated. But the ability to ers should take into consideration in pediatric extrapolate really decreases the time, money and drug development? effort required for pediatric trials. As with any development program, in order Under PREA, the FDA can waive studies in to be successful, it requires careful planning. children if the studies are not necessary. In some The other piece which I think is true is early and cases, the agency has also allowed sponsors to defer consistent communication with the FDA, so that pediatric studies, depending on the circumstances. Page 12 Washington Drug Letter Oct. 7, 2013

Compounding, from Page 1 pharmacy documents and to require com- pounders of high-risk drugs to register with the In the wake of the House’s approval of the agency and report adverse events. bill, various industry stakeholders have voiced To view the House version of the bill, go support for the proposal’s track-and-trace provi- to www.fdanews.com/ext/files/09-30-13-House- sions, including PhRMA, GPhA and the Health- Bill.pdf. — Johnathan Rickman care Distribution Management Association, which represents large drug wholesalers. Michael Rose, vice president of supply chain ANDAs, from Page 5 visibility for Johnson & Johnson, praised House and Senate lawmakers Sept. 30 for keeping the The agency warns that ANDAs backed by issue alive, telling WDL congressional leaders a single failed study will be stamped “refuse to played a key part in helping stakeholders reach receive,” as will applications submitted with a “alignment” on a once-elusive federal solution. non-recommended in vivo study that lacks ade- quate justification. The legislation would immediately preempt state laws and require all stakeholders along If an application contains fewer than ten the supply chain to develop an interim pedigree minor deficiencies, or those the agency consid- system that keeps track of product transactions ers to be easily remedied, the FDA will notify the within one year of enactment. Within a decade applicant by phone, fax or e-mail. Those ANDAs after its enactment, pharmaceutical companies with 10 or more minor deficiencies or one or would be required to develop an electronic and more major deficiencies will be considered unfin- interoperable unit-level traceability system. ished by the FDA and will receive “refuse-to- receive” designation. Reaction from pharmacies to the bill’s com- pounding component was less uniform, ranging “The sponsor may decide to submit additional from hostile to “neutral” — a position the Profes- materials to correct the deficiencies, but the result- sional Compounding Centers of America settled ing amended ANDA will be considered a new on. The group lauded the bill’s centerpiece pro- ANDA submission … and requiring a new GDUFA vision, making it voluntary for compounders to fee,” the draft guidance states. It also spells out the become an “outsourcing facility” governed by appeals process for “refuse-to-receive” letters. the FDA. However, the group said the legisla- The deadline to comment on the draft guid- tion needs “additional improvements” to provide ance, docket no. FDA-2013-D-1120, is Oct. 31. exemptions for certain kinds of pharmacy practice. Read ANDA Submissions — Refuse-to-Receive The FDA says it supports efforts to Standards at www.fdanews.com/ext/files/09-30- give agency inspectors the power to review 13-ANDA.pdf. — Melissa Winn

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Copyright © 2013 by Washington Business Information Inc. All rights reserved. Washington Drug Letter (ISSN 0194-1291), an executive briefing on the regulation of pharmaceuticals, is published weekly, 50 issues, for $1,347. Photocopying or reproducing in any form, includ- ing electronic or facsimile transmission, scanning or electronic storage is a violation of federal copyright law and is strictly prohibited with- out the publisher’s express written permission. Subscribers registered with the Copyright Clearance Center (CCC) may reproduce articles for internal use only. For more information, contact CCC at www.copyright.com or call (978) 750-8400. A Summit on FDA Inspections FDA Inspections Skyrocket … All to Feel the Impact: Drugs, Devices, Policies … Practices … and Biologics … Global Push for Drug and Device Safety … How Will Plans for the Future Presented by FDAnews Industry Cope? … The Eighth Annual FDA Inspections Summit

Oct. 23–25, 2013 • Bethesda North Marriott Hotel & Conference Center • Bethesda, MD

EIGHTH Annual FDA Inspections Summit 300 N. Washington St., Suite 200 Falls Church, VA 22046-3431 10 Distinguished FDA Representatives

John Taylor III Counselor to the Commissioner and Acting Deputy Commissioner for Global Regulatory Operations and Policy, OC, FDA (invited)

DR. Leslie Ball David Glasgow Erin McFiren Assistant Commissioner for Director, Division of Domestic Consumer Safety Officer, ORA, FDA, International Programs, Deputy Field Investigations, ORA, FDA Baltimore District Director, Office of International (invited) Grace McNally Programs, Office of Global Rachel Harrington Senior Policy Advisor, OC, CDER, Regulatory Operations and Policy, CSO, Drug Specialist, ORA, FDA, FDA (invited) FDA Baltimore District Diane Amador Toro Elizabeth Dickinson Brian Hasselbalch District Director, ORA, FDA, Chief Counsel, OC, FDA (invited) Acting Associate Director, Parsippany District Rick Friedman Policy and Communication, OMPQ, Kimberly Trautman Associate Director, Office of CDER, FDA (invited) Associate Director, International Manufacturing & Product Quality, Lori Lawless Affairs, Medical Device International CDER, FDA (invited) SCSO, Medical Device Specialist, Quality Systems Expert, Office of the ORA, FDA, Baltimore District Center Director, CDRH, FDA (invited)

Barbara K. Immel Chair, President, Immel Resources LLC A leading consultant in quality systems, regulatory compliance and training for more than 27 years, Barbara K. Immel is one of the most listened-to voices in FDA-regulated industry. She chaired last year’s Summit. “Barbara was simply fantastic,” said attendee Nicole Landreville, Xltek.

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SPECIAL PRECONFERENCE WORKSHOPS Wednesday, Oct. 23 • Registration 12:00 p.m. – 1:00 p.m. • Workshops 1:00 p.m. – 4:00 p.m.

Drugs and Biologics— Proven Procedures for Prepar- Medical Devices— QSIT Then and Now: Tips and Tools ing for Drug and Biologic FDA Inspections: From Intro- for FDA Compliance and Building Stronger Internal ductions to What Not to Say Quality Systems In this session, Frederick Branding will take attendees through an Tim Wells, who led the CDRH team that wrote QSIT, will pro- interactive mock inspection. In this exercise attendees will learn vide best practices on how industry should use this inspection about model procedures to handle nearly every aspect of a stan- tool. In this workshop, attendees will break into groups focus- dard inspection, including introductions, phone trees, escorts, ing on three key issues: positive and negative experiences with documentation, photographs and tapings. They’ll find out about FDA’s use of QSIT; suggestions on how to improve QSIT; and when to provide records access and when not to. And maybe what tools should industry use for internal audits. one of the most important lessons during this half-day seminar? Attendees will learn: When to say no and how to say no to an FDA inspector. n The highs and lows of QSIT from an industry perspective You’ll also take away: n Is QSIT still applicable as a quality system audit tool? n Developing inspection procedures n What are the best tools used today for successful audits? n Tips for handling a difficult inspector n The shortcomings of using QSIT for internal audits n Following up after an FDA inspection n Responding to inspectional observations Tim Wells, President, QualityHub; former Team Leader for the n The closeout meeting with management QSIT Project, CDRH, FDA

Frederick Branding, Principal, Olsson Frank & Weeda SUmmit agenda Day One: Thursday, Oct. 24 n How borders are no longer the primary Panelists: line of defense for drug safety standards David Glasgow, Director, Division of 8:00 a.m. – 8:45 a.m. Registration and n FDA efforts to combat counterfeit and Domestic Field Investigations, ORA, Continental Breakfast substandard drugs FDA (invited) Elaine Messa, Executive Vice President of the John Taylor III, Counselor to the Com- Medical Device Practice, Becker & Associates 8:45 a.m. – 9:00 a.m. missioner and Acting Deputy Com- Opening Comments by Chairperson Consulting; former Director of the Los Angeles missioner for Global Regulatory Operations and District, FDA Barbara Immel, President, Immel Resources Policy, OC, FDA (invited) LLC (Chairperson) 10:00 a.m. – 11:00 a.m. 11:00 a.m. – 11:20 a.m. Refreshment Break 9:00 a.m. – 10:00 a.m. The 10 Best — and 10 Worst — Things to Do FDA KEYNOTE — FDA’s Strategy for Protect- When FDA Staff Are on Site to Conduct an 11:20 a.m. – 3:30 p.m. ing the Global Supply Chain Inspection: Panel Discussion Two Concurrent Breakout Tracks Today, nearly 40 percent of finished drugs The behavior of drug or device company staff n Track 1 — Drugs & Biologics are imported, and nearly 80 percent of active during an inspection can run the gamut from su- n Track 2 — Medical Devices ingredients come from overseas sources. The US premely professional to downright comical. There imports from more than 150 different countries, are the stories of crack teams of QA/RA profes- 3:30 p.m. – 4:15 p.m. Networking Break many with less sophisticated and strict stan- sionals who have every document and every dards. In the past 10 years, the number of FDA- answer an investigator needs, and then there are 4:15 p.m. – 5:30 p.m. regulated shipments at more than 300 US ports stories of firms that refuse to let the investigator Plenary Panel Discussion has quadrupled, and there are now more than 24 into the plant. This panel takes the best and worst million shipments annually. This has dramatically of the industry’s performance and combines it 5:30 p.m. – 6:30 p.m. Networking Reception impacted international inspections, with a 168% into one great lesson for you and your staff. This increase in foreign inspections since 2008. In this year’s panelists have seen it all and are here to Drug & Biologics Track talk, John Taylor III dissects the FDA’s globalization give you the skinny on how to pass your upcom- strategy for implementing the new authorities ing inspection with flying colors. 11:20 a.m. – 11:30 a.m. under FDASIA and how it will impact companies’ Special Focus: On July 12 the FDA issued a draft Moderator Comments inspections and importing standards. guidance entitled, “Circumstances that Constitute Moderator: Attendees will learn: Delaying, Denying, Limiting, or Refusing a Drug John Avellanet, Managing Director & Principal, n How the FDA plans to implement FDASIA Inspection.” Attendees will be provided a copy Cerulean Associates LLC on a global scale of the guidance and panelists will go through the n Challenges of globalization of FDASIA for guidance and its examples and offer their insights 11:30 a.m. – 12:15 p.m. imports into the US and how the FDA will into how industry can best comply. FDA’s Clinical Trial Inspections in China — respond to these issues Lessons Learned From the First 5 Years n Threats throughout the drug supply chain Moderator: FDA established its China office in 2008, with the and global supply chain risks David Chesney, Vice President and Practice goal of strengthening cooperation with Chinese n Why the FDA is transforming from a Lead, Strategic Compliance Services, PAREXEL regulatory officials, providing relevant Chinese domestic safety agency to an agency fully pre- Consulting; former FDA District Director for the entities information about FDA requirements, and pared for a rapidly changing global environment San Francisco office increasing FDA inspections in China. Since then,

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FDA has made great strides in deepening its rela- erized systems in regulated activities n Should the company involve regulatory at- tionship with Chinese counterparts and increasing n Part 11 and Annex 11: a common approach torneys or consultants? If yes, at what stage? its understanding of the Chinese regulatory system to computerized systems validation compliance n Once the warning letter was issued, for medical products in China. In this presentation, n Understanding data integrity as the what should the company have done within Dr. Leslie Ball will dissect the findings of her recent cornerstone for future inspections the first 24 hours? trip to China and what lessons have been learned n How should the company respond to from the first five years of the China FDA office. Gilda D’Incerti, CEO, Pharma Quality Europe the warning letter and how far up the chain Attendees will learn: of command should the response to the n Which trial sites are directly regulated 2:45 p.m. – 3:30 p.m. warning letter be sent? and inspected by the FDA Warning Letter Recovery Strategies — n Should the company ask to have the n Challenges in ensuring the integrity of What to Do When You’ve Been Hit with warning letter rescinded? clinical trials conducted in China Repeat Violations n Lessons learned from a three-part training Recently, the FDA has been cracking down Connie Hoy, Vice President, Global Regulatory program with CFDA on repeat offenders and offering up tough talk Affairs, Palomar Medical Technologies n Common mistakes and risk factors for within 483 and warning letters. Firms dinged for noncompliance multiple and repeat violations at the same facili- 12:15 p.m. – 1:00 p.m. ties are deemed high risk and will face years of Update on the International Medical Device Dr. Leslie Ball, Assistant Commission- FDA scrutiny. If you’ve been cited for multiple or Regulators Forum’s Single-Audit Program er for International Programs, Deputy repeated violations it’s time to employ a warning The FDA’s representative to an important new Director, Office of International Programs, Office letter recovery strategy. But where to begin? international forum will give you a fresh insider’s of Global Regulatory Operations and Policy, FDA Drawing on decades of experience, this presen- take on what it will demand of auditors of medi- (invited) tation will provide a roadmap to recovery. cal device manufacturers’ quality management Attendees will learn: systems. The forum, which represents Austra- 12:15 p.m. – 1:00 p.m. n How to convert your root cause analysis lia, Brazil, Canada, China, the European Union, Kiss & Tell: How to Prove to the FDA Investi- investigations into actionable operational Japan and the US, will create the framework for gator that Your Outsourcing Oversight Works compliance strategies a single-audit program. How will these changes With the enforcement of FDASIA in full swing n Best practices for interacting with the impact the way you do business? Where and and new warning letters citing firms and execu- FDA after the agency has placed you in a when should you weigh in to make certain your tives under the Park Doctrine for poor supplier high-risk status concerns are heard? In this session, you’ll hear oversight, learn what you need to prove to an n Tips for managing staff that must work the latest developments and get a better under- FDA investigator that you are in control of your under consent decrees and third-party standing of how to make this work for you. outsourced, regulated activities. auditors Attendees will learn: Attendees will learn: n Results from the March IMDRF meet- n Key questions FDA investigators ask to Marie McDonald, Senior Director, Quality & ing and the latest on the work items in the uncover weak or missing supplier oversight Compliance Consulting, Quintiles pipeline and newly proposed items n Specific supplier oversight elements n Roadmap for global implementation of to clearly document in your annual quality 3:30 p.m. – 4:15 p.m. Networking Break the UDI system system management review or annual n MDSAP WG Update — with results from product review Medical Device Track the September meeting n Documents to obtain and retain from n Details on the slated January 2014 pilot your suppliers every year 11:20 a.m. – 11:30 a.m. program in which four regulatory authori- n Components of a supplier dossier that Moderator Comments ties (Australia, Brazil, Canada and US) will will show every FDA investigator that you Moderator: conduct inspections that will be recognized are in control Dan O’Leary, President, Ombu Enterprises LLC by all four authorities n How to document accountabilities in your contracts to please the FDA and 11:30 a.m. – 12:15 p.m. Kimberly Trautman, Associate Director, frustrate product liability lawyers Case Study: Domestic Importer Hit with International Affairs, Medical Device Warning Letter Thanks to Overseas Supplier International Quality Systems Expert, Office of John Avellanet, Managing Director & Principal, A US-based company received a warning letter the Center Director, CDRH, FDA (invited) Cerulean Associates, LLC for problems identified in a facility inspection. The company is registered with the FDA and 1:00 p.m. – 2:00 p.m. Lunch 1:00 p.m. – 2:00 p.m. Lunch acts only as an importer. All the complaint investigation and MDR filings occur at its par- 2:00 p.m. – 2:45 p.m. 2:00 p.m. – 2:45 p.m. ent company outside the US The US. company An FDA Investigator’s Viewpoint: How to EU and US Joint Inspections: Data as the received a very strong 483, and responded with Assure Your Seven Subsystems are in Compli- Cornerstone for the Future corrective action. In addition, it applied for an ance and Linked Together It’s never been more important for pharmaceuti- MDR exemption and it was granted (meaning it In 15 years, FDA medical device specialist Lori cal companies to comply with both Annex 11 does not have to file MDRs because it would be Lawless has seen every violation of the medical and Part 11. Today, computerized automation is a duplicative). In spite of this, it received a warning device QSR that you can think of. This top-rated key element of any manufacturing and distri- letter. Could the company have done anything speaker will create a lively and informative discus- bution area of pharmaceutical manufacturing; differently to avoid the warning letter? What can sion about the Quality Systems Inspection Tech- therefore, the requirements for data integrity are it do going forward to prevent this from happen- nique (QSIT) approach to inspections. Lawless will now considered a fundamental expectation for ing in the future? This interactive presentation describe how she asks for information, analyzes all types of systems, including laboratory and will assess this nuts-and-bolts case study. that information and writes EIR and Form 483 process control systems. Attendees will learn: reports using the QSIT and QSR framework. Attendees will learn: n When to push back during the FDA Attendees will learn: n Differences between European and US inspection n What elements of QSIT the FDA fo- regulations addressing the use of comput- n How to respond to the 483 cuses on and why

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n Common mistakes firms commit and n What research – both internal and external how they can be avoided – do they use to prepare themselves for your n Red flags that investigators notice that company, plant and products? typically go unnoticed by quality assurance n What do they look for once inside your and compliance managers plant? n How QSIT violations appear in EIRs, n How they apply QSIT and other inspec- and a well-written report. Barbara Immel, with 483s and warning letters tional techniques to the QSR 31 years of industry experience in quality as- n Why they include items in the EIR and surance, regulatory compliance and training, Lori Lawless, SCSO, Medical Device Form 483 and how they take into account will provide a roadmap on how to successfully Specialist, ORA, FDA, Baltimore District your comments write and ensure a good investigation to prevent future citations. 2:45 p.m. – 3:30 p.m. Moderator: Attendees will learn: Assuring Your ISO 14971 Risk Management Lori Lawless, SCSO, Medical Device n How to use the “CAPA starburst” Strategy Adopts a Holistic Approach Specialist, ORA, FDA, Baltimore District approach to quality data trending US devicemakers have recently experienced n Examples of recent FDA inspection findings shock, disappointment and downright anger Panelists: n 22 great investigation tools for a suc- because of failed EU audits. As of August 1, Tim Wells, President, QualityHub; former Team cessful investigation 2012, all US devicemakers that want to sell Leader for the QSIT Project, CDRH, FDA n Roadmap to inverted pyramid writing style products in the EU must be in compliance with Diane Amador Toro, District Director, n How to determine root cause EN ISO 14971:2012 and in particular Annexes: ORA, FDA, Parsippany District n The three key sections of a good ZA, ZB and ZC. These Annexes are commonly Larry Spears, Director, Deloitte & Touche LLP, investigation overlooked by devicemakers — but not by EU former Deputy Director for Regulatory Affairs at auditors. Failure to understand the nuances of CDRH, FDA Barbara Immel, President, Immel Resources the Annexes and how they need to be account- LLC (Chairperson) ed for in your risk management and Quality 5:30 p.m. – 6:30 p.m. Networking Reception Management Systems assessments can find 10:45 a.m. – 11:00 a.m. Refreshment Break you in noncompliance. This presentation, led DAY TWO – Friday, Oct. 25, 2013 by BSI’s Technical Director, Dr. Ibim Tariah, will 11:00 a.m. – 12:00 p.m. assure that the requirements found in the An- 8:00 a.m. – 8:45 a.m. Continental Breakfast FDASIA Year 2: Where Are We and What’s Ahead nexes are incorporated into your risk manage- for Supply Chain Regulation? Panel Discussion ment programs. 8:45 a.m. – 9:00 a.m. It’s been a year since FDASIA required formal Attendees will learn: Opening Comments by Chairperson control over the pharma supply chain. But n How to assure the EU’s holistic approach Barbara Immel, President, Immel Resources the agency still hasn’t modified the regula- to risk management and QMS assessment LLC (Chairperson) tions to reflect the change in the law. This are covered in your risk management strategy panel discussion, moderated by an ex-FDAer n What auditors are looking for and ways 9:00 a.m. – 10:00 a.m. and consisting of current FDA officials, will to assure that your documentation meets FDA KEYNOTE — Top Inspection-Related provide answers. EN ISO 14971:2012 and hence the MDDs Legal Issues to Watch Attendees will learn: requirements The FDA expects industry to comply with regula- n What should firms be doing now to com- n Pointers to how firms can properly plan tions. But sometimes the agency and industry ply with the new legal requirements? for and document their QMS assessments just can’t agree, and the courts have to take n What are investigators being told to look to ensure compliance with the MDDs over to settle disputes. For example, there’s a brewing controversy on whether the FDA has at during inspections, and what sorts of gaps might lead to a 483 observation today Dr. Ibim Tariah, Technical Director, BSI Health- the legal right to take photographs within your that would not have previously? care Solutions facility. The FDA is confident it can. Industry and outside counsel say no. Might this come to a n How far down the supply chain must companies now audit API companies, excip- 3:30 p.m. – 4:15 p.m. Networking Break head in a legal battle? Only time will tell. This and many other disputes are handled by the ient suppliers, container manufacturers and precursor chemicals? PLENARY SESSION PANEL DISCUSSION FDA’s chief counsel’s office. This presentation, by the FDA’s top legal officer, will highlight the Moderator: 4:15 p.m. – 5:30 p.m. agency’s current legal thinking on the industry’s David Chesney, Vice President and Practice A Day in the Life of FDA’s Field Investigators— most pressing topics. Lead, Strategic Compliance Services, PAREXEL Current and Former Field Investigators Explain Attendees will learn: Consulting; former FDA District Director for the What They Look for and Why and What’s on n What compels the FDA to initiate legal San Francisco office the Horizon: Plenary Panel Discussion action and how it works with the DOJ or Ever wonder what an investigator is thinking state authorities Panelists: when they receive their next inspection assign- n What current inspections related cases Rick Friedman, Associate Director, ment? Investigators typically review their assign- is the FDA currently pursuing and why Office of Manufacturing & Product ments, research the company or plant they are n How recent enforcement cases could Quality, CDER, FDA (invited) about to inspect and call on colleagues to help have been avoided Brian Hasselbalch, Acting Associate them with any questions. Then their training kicks Director, Policy and Communication, in and they follow a framework for inspections. Elizabeth Dickinson, Chief Counsel, OMPQ CDER, FDA (invited) This presentation will give you a glimpse into OC, FDA (invited) Grace McNally, Senior Policy Advisor, the inner workings of an investigator’s mindset OC, CDER, FDA (invited) before, during and after your inspections: 10:00 a.m. – 10:45 a.m. Attendees will learn: Writing (And Ensuring) Good Failure Investi- 12:00 p.m. Conference Adjournment n What does an investigator’s prep pack- gations and CAPA Reports age contain? A good CAPA starts with a solid investigation

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The FDA Inspections Summit — now in its eighth year — has fast become the “go-to” event for regulatory, compliance and quality assurance professionals and the one place to discover the tools and techniques to improve your inspectional readiness.

Can’t make it to the Eighth Annual FDA Inspections Summit? LIVE STREAM IT! We know that not everyone can travel to the Eighth Annual FDA Inspections Summit, so we have decided to stream it live! It’s a great way to see sessions as they happen. Registration is quick, and accessing the live sessions is as simple as clicking your mouse.

Benefits include: n The live stream is available from your computer or mobile device. n Watch the live-streaming video of the presenter and view the presentation materials in real-time. n Easily download presentation materials and any other supporting documents provided. n Ask questions of the speakers during the live conference from your home, office or on the go with your mobile device. n BONUS: A streaming video registration includes six-month access to archived session recordings after the conference.

TESTIMONIALS WHo should attend

“Excellent conference. Thank you for putting it together!” n Executive Management — Stephanie Hendrickson, Life Sciences Quality n Regulatory Affairs and Compliance, Accenture n Quality Assurance/Quality Control “The summit was very informative. There were powerful n Legal and Compliance Officers insights about FDA that I took away from the summit. It n Clinical Research Directors will be helpful in setting strategy for my organization.” n Consultants/Service Providers — Raghu Jainapur, Director of Quality Assurance, Roche TEAM DISCOUNTS “I liked the breadth and knowledge of the speakers.” Significant tuition discounts are available for teams of — Daniel Bolle, Manager, Supplier Quality, Baxter two or more from the same company. You must register Healthcare at the same time and provide a single payment to take “Very well rounded; included most recent FDA develop- advantage of the discount. ments; interesting as always.” Call (888) 838-5578 for details. — Johanna Stamates, Executive Director, Regulatory Support and Quality Assurance, University of Miami

About the Conference Chair Sponsors Barbara K. Immel is president of Immel Silver: Resources LLC, a management consulting firm specializing in quality systems, regula- tory compliance and training. For more than 30 years, Ms. Immel has been one of the most listened-to voices in FDA-regulated industry. She has taught at the Universities of California-Berkeley, Wisconsin, Georgia and Stanford; authored more than Bronze: 50 articles in industry journals; and written the Quality Assurance chapter in Dekker’s Encyclopedia of Phar- maceutical Technology. She is a former compliance columnist for BioPharm Magazine and is currently the editor of the Immel Report™ newsletter.

© Copyright 2013 by FDAnews EIGHTH Annual FDA Inspections Summit Oct. 23–25, 2013 • Bethesda North Marriott Hotel & Conference Center • Bethesda, MD

Registration and Hotel Details PreConference Workshop Only Bethesda North Marriott Hotel & Conference Center Tuition includes preconference workshop, workshop materials 5701 Marinelli Rd. and refreshments. Bethesda, MD 20852 Toll free (800) 859-8003 Cancellations & Substitutions Tel: +1 (301) 822-9200 Written cancellations received at least 21 calendar days prior to the http://www.bethesdanorthmarriott.com start date of the event will receive a refund — less a $200 adminis- Room Rate: $209 single or double (plus 13% tax) tration fee. No cancellations will be accepted — nor refunds issued Hotel reservation cutoff date: Oct. 1, 2013 — within 21 calendar days of the start date of the event. A credit for the amount paid may be transferred to any future FDAnews Exhibit and Sponsorship Opportunities event. Substitutions may be made at any time. No-shows will be For exhibit and sponsorship opportunities at this event, please contact: charged the full amount. In the event that FDAnews cancels the Jim Desborough, Business Development Director event, FDAnews is not responsible for any airfare, hotel, other costs Phone: +1 (703) 538-7647 or losses incurred by registrants. Some topics and speakers may be Email: [email protected] subject to change without notice. Complete Summit FOUR EASY WAYS TO REGISTER Tuition includes preconference workshop, all conference Online: www.FDAInspectionsSummit.com sessions, conference and workshop materials, two breakfasts, Fax: +1 (703) 538-7676 one luncheon, one reception and refreshments. Phone: Toll free (888) 838-5578 (inside the U.S.) Conference Only or +1 (703) 538-7600 Tuition includes all conference presentations, conference materials, Mail: FDAnews, 300 N. Washington St., Suite 200 two breakfasts, one luncheon, one reception and refreshments. Falls Church, VA 22046-3431 U.S.A.

I want to attend the EIGHTH Annual FDA Inspections Summit. Ye s! Sign me up for the option(s) I've selected below: 300 N. Washington St., Suite 200 Early Bird Fee No. of Regular Fee No. of Falls Church, VA 22046-3431 through Sept. 23, 2013 Attendees Sept. 23 – Oct. 25, 2013 Attendees Complete Summit $1,797 $1,997 Conference Only $1,597 $1,797 Preconference Workshop Only $597 $697 Livestreaming Full Conference $1,297 $1,497 (including 24/7 access to the content for six months after the event)

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© Copyright 2013 by FDAnews Managing Contract Manufacturers and Testing Labs

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