China Outlines Plan to Encourage Innovation, Speed Drug Approvals

The China State Council is calling for sweeping reforms of the country’s drug regulatory system, including accelerated approv-als of novel drugs, specified timelines for deciding applications and increased public access to applications and information.

The Council wants the China Food and Drug Administration to establish timelines for approving or rejecting applications by 2018, according to a plan released Aug. 18. The CFDA would also establish a special review and approval system to spur develop-ment of innovative drugs to combat AIDS, cancer, major infec-tious diseases and rare diseases. Small and micro-enterprises would be given approval priority.

Institutions involved in researching and developing new drugs would be allowed to apply for registration of those prod-ucts, and once approved and transferred to manufacturing facili-ties, no further appraisal would be required.

The plan also calls for simpler applications so that drugs, their labeling, packaging and materials can be approved simultaneously.

At the same time, transparency around the approval process would increase, with timely release of information on registra-tion applications and drug supply and demand. Sponsors would be informed of the status of application reviews and the public would be able to view and inquire about product approvals.

The Council also wants Chinese hospitals and academic cen-ters to increase their participation in multinational clinical trials that adhere to international standards to gather test data that can be used to support regulatory submissions.

Meanwhile, responsibilities of sponsors, clinical sites and ethics committees to protect study subjects would be strength-ened, and the clinical trial process would be more closely scru-tinized to ensure data integrity and reliability. Any fraudulent activities concerning research or data would be severely pun-ished, the Council says.

The plan also outlines steps to improve the quality of generic drugs and speed up generic quality conformance evaluations by the end of 2018. Generic drugs that don’t pass a quality confor-mance assessment would not be reregistered.

China Outlines Plan to Encourage Innovation, Speed Drug Approvals ....................... 1

U.S. FDA Proposes Naming Convention For Biosimilars, Reference Products ..................... 2

Proposed Rule Would Change Names Of Six Biologicals, Including Neupogen ................ 3

EMA Endorses Roadmap For Regulatory Reforms ......................................... 3

European Regulators Seek Input On Updated GCP Guidance ................................... 5

EU Revises Postauthorization Safety Studies Guideline ......................................... 5

EMA: QMS, AE Reporting Top 2014 Postmarketing Inspection Deviations.................... 5

EMA Adverse Event Monitoring Service Now Fully Operational .............................. 6

U.S. FDA’s Authority to Enforce Quality Metrics Questioned ................................... 7

U.S. Industry Seeks Clarity On CMC Draft Guidance ...................................... 7

India Approves $270 Million Plan To Upgrade Drug Regulations................................ 8

Drug Industry Slams French Law Promoting Off-Label Use ............................... 8

Two More Tropical Diseases Eligible For Priority Review Voucher in U.S. .................... 9

Saudi FDA Releases Guidance On Registering Clinical Trials ............................... 9

IPEC Urges Use of Industry Guidance On Stability Testing of Excipients ......................... 9

Viral Shedding Studies Focus Of U.S. FDA Final Guidance ............................... 10

Editor’s Note: The International Pharmaceutical Regulatory Monitor is available in an electronic edition, which includes web access to nine years of archived issues. For information on convert- ing to an electronic subscription, contact us at (888) 838-5578.

INTERNATIONAL PHARMACEUTICAL REGULATORY

A Monthly Alert to RegulationsAffecting the Pharmaceutical

and Biotech Industries MONITORIn This Issue

Volume 43, Number 9 September 2015

September 2015Page 2 INTERNATIONAL PHARMACEUTICAL REGULATORY MONITOR

Mark Barnes, an attorney with Ropes & Gray, says the measures, which have been put out for public com-ment, are likely to take effect, as State Council propos-als are typically adopted.

The long registration timeline in China has been a sore topic for multinational pharmaceutical companies, and even made it to the senior-level U.S.-China Joint Commission on Commerce and Trade dialogue, says Helen Chen, head of L.E.K. Consulting’s China life sci-ences practice.

One of the processes rumored to be streamlined is the IND application, which, if adopted, would move China toward a US-style process of approval, she tells IPRM. The duration may be 60 days, compared with 30 days in the U.S., but it’s substantially shorter than the one to two years drugmakers now wait for clinical trial authorization.

Plans that would allow R&D institutions to apply for registration of new drugs could open up the contract manufacturing market in China, Chen notes. This would foster start-ups, which could use CMOs rather than hav-ing to raise and invest capital in a manufacturing facil-ity, and would give the larger drugmakers more flexibil-ity, she adds. — Kellen Owings

U.S. FDA Proposes Naming Convention For Biosimilars, Reference Products

The U.S. Food and Drug Administration released long-awaited draft guidance on Aug. 27 on naming biological products, proposing that both reference products and bio-similars have nonproprietary names comprised of the core drug substance name and a different four-letter suffix.

Under this system, applicants would propose up to three suffixes to be included in the proper name desig-nated by the FDA at the time of licensing.

The suffix would consist of four lowercase let-ters that are unique and devoid of meaning, and should not make any misrepresentations about safety or effi-cacy, or be mistaken with the name of a currently mar-keted product, according to the guidance. For example, the nonproprietary name of a reference product could be replicamab-cznm, while a biosimilar to that product could be replicamab-hixf.

The proposed naming convention is meant to pre-vent inadvertent substitution for products that are not interchangeable, and make it easier to track usage of products after they are on the market.

Using a shared core name would indicate a rela-tionship among products, the FDA notes. By placing the identifier as a suffix, instead of a prefix, biological products with the same core name would be grouped together in electronic databases.

Applicants would request FDA review of a proposed suffix during the IND or BLA phase. If drugmakers later wanted to change the suffix, they could do so via a prior-approval labeling supplement, the guidance says.

Industry Reaction

For interchangeable biological products, the FDA is seeking industry feedback on whether the nonpro-prietary name should include a distinct suffix or should share the same suffix as the reference product.

Release of the guidance dovetailed with a proposed rule to designate nonproprietary names for six previously approved biological and biosimilar products (see story, page 3). One of those is Sandoz’s Zarxio biosimilar of Amgen’s chemotherapy drug Neupogen, which was approved in March using the placeholder name filgrastim-sndz.

The Generic Pharmaceuticals Association was quick to slam the proposed guidance.

Bertrand Liang, chairman of the group’s Biosimi-lars Council, said biologics and biosimilars should be

Document Index

The following documents covered in this issue of the Interna-tional Pharmaceutical Regulatory Monitor are available for download at www.fdanews.com/IPRMdocs.

U.S. FDA’s Nonproprietary Naming of Biological ProductsU.S. FDA’s Proposed Rule on Naming BiologicalsEU’s Telematics Strategy and Implementation Road-map 2015-2017EMA’s Guideline on Good Clinical PracticeEMA’s Draft Guideline on PostauthorizationEMA’s Addendum on Safety StudiesEMA’s Guidance on Pharmacovigilance AuditsEMA Pharmacovigilance Inspectors Working Group’s 2014 ReportEMA’s Manual on Medical Literature Monitoring ServiceEMA’s Question & Answer Document on MLMU.S. FDA’s Draft Guidance on CMC ChangesU.S. FDA’s Final Order on Tropical DiseasesSaudi FDA’s Guidance on Clinical TrialsIPEC-America’s Position Paper on ExcipientsU.S. FDA’s Final Guidance on Shedding Studies

INTERNATIONAL PHARMACEUTICAL REGULATORY MONITORSeptember 2015 Page 3

required to have the same international nonproprietary name with no added FDA-designated suffix. Adverse events and product recalls for small-molecule and bio-logic drugs are already successfully identified using the national drug code, lot number and company name, and there’s no compelling evidence that biosimilars should be handled differently, he tells IPRM.

Liang adds that there is already a precedent for shared names — e.g., erythropoietin, somatropin, interferon — that has not resulted in any known patient safety issues.

He also points out that shared INNs without suffixes are used in the EU, Canada, Australia and Japan with no ill effects. Adding a random collection of letters to the product’s nonproprietary name confers no additional safety benefit and, in fact, would require healthcare pro-fessionals to be armed at all times with a code-breaking reference, Liang says.

BIO and the Biosimilars Forum welcomed the guid-ance. The distinct suffixes support the Biosimilars Forum’s argument that biosimilars should have separate codes for Medicare reimbursement purposes, the group says.

Comments are due by Oct. 27. Read Nonproprietary Naming of Biological Products at www.fdanews.com/8-15-Biological-Naming.pdf. — Jonathon Shacat

Proposed Rule Would Change Names Of Six Biologicals, Including Neupogen

Just days before Sandoz launched Zarxio, its bio-similar of Amgen’s chemotherapy drug Neupogen, the U.S. Food and Drug Administration issued a pro-posed rule changing both drugs’ official names, at least temporarily.

The proposed rule affecting Neupogen, Zarxio and four other biological products was published in Aug. 28’s Federal Register, alongside the agency’s much-anticipated draft guidance on biological product naming. In both cases, the naming system attaches a nonidentifi-able four-letter suffix to the biological product’s official nonproprietary name (see story, page 2).

Under the proposed rule, Neupogen’s proper name, filgrastim, would add the suffix jcwp to become filgras-tim-jcwp. Zarxio, which had been given the placeholder name filgrastim-sndz, a suffix that could identify San-doz, would become filgrastim-bflm.

The other four biological products are Sicor Biotech UAB’s Granix, which would change from tbo-filgrastim

to filgrastim-vkzt; Janssen Biotech’s Remicade (inflix-imab), which would become infliximab-hjmt; Amgen’s Epogen and Procrit (epoetin alfa), which would be epo-etin alfa-cgkn; and Amgen’s Neulasta (pegfilgrastim), which would be pegfilgrastim-ljfd.

The rush to assign names for the six products ahead of final guidance on biologicals naming was prompted by the need to better detect product-specific safety sig-nals and class effects, as well as to distinguish between reference, biosimilar and related biological products, the FDA says.

The proposed names could change depending on the outcome of the final guidance on naming. The agency says it is considering several citizen petitions on the naming convention and is seeking comment on whether alternative approaches, such as suffixes derived from the name of the license holder — as in filgrastim-sndz — would be a better fit.

To minimize manufacturing or distribution disrup-tions, the FDA would allow drugmakers to implement new labeling reflecting the name change at the time of the next manufacturing run and to use up existing inventories of their products.

Sandoz is marketing filgrastim-sndz under the Zarxio name pending final guidance from the FDA regarding the naming process.

Comments on the proposed rule are due Nov. 11. Read it here www.fdanews.com/08-28-15-proposedrule.pdf. — John Bechtel

EMA Endorses Roadmap For Regulatory Reforms

The European Medicines Agency is planning to develop an EU portal and database as a single entry point for clinical trial data submissions by May 2016.

By July 2016, the EMA plans to finalize a guideline supporting the adoption of ISO standards for identifica-tion of medicinal products.

Other projects included in a three-year EMA road-map include upgrading the Eudravigilance clinical trial module to provide electronic reporting of annual safety reports and suspected unexpected serious adverse reactions. The module will address postmarket safety through simplified and centralized reporting, bet-ter quality data and improved analysis and tracking of labeling changes.

September 2015Page 4 INTERNATIONAL PHARMACEUTICAL REGULATORY MONITOR

INTERNATIONAL PHARMACEUTICAL REGULATORY MONITORSeptember 2015 Page 5

Looking to 2018, drugmakers will be able to submit applications electronically via a single submission portal.

The EMA’s management board endorsed the EU Telematics Strategy and Implementation Roadmap 2015-2017 in early August.

View it at www.fdanews.com/8-15-EMA-IT.pdf. — Jonathon Shacat

European Regulators Seek Input On Updated GCP Guidance

The European Medicines Agency is seeking feed-back on the International Conference on Harmoniza-tion’s revised E6 guideline, which adds new recommen-dations for sponsors on developing risk-based quality management systems for clinical trials.

Risks to critical study processes and data integ-rity should be identified and evaluated during proto-col development, taking into account the likelihood of errors occurring, the probable impact and the extent to which they’d be detectable, the guideline says.

Sponsors should incorporate risk-mitigation activi-ties in protocol design, monitoring, training and stan-dard operating procedures.

“Detection of deviations from … predefined quality tolerance limits should trigger an evaluation to deter-mine if action is needed,” the guideline says.

All quality management activities should be doc-umented and shared with stakeholders, and risk con-trol measures should be periodically reviewed to ensure their continuing effectiveness.

The ICH also updated the standards for maintaining electronic records and essential documents. Standard operating procedures for electronic data systems should describe validation and functionality testing, data col-lection and handling, system maintenance and security measures, change control, data backup and recovery, and contingency planning.

The revisions are intended to encourage efficient and improved approaches to trial design, conduct, evaluation, recording and reporting using advances in technology, and risk-management processes that have become avail-able since the guideline was finalized in 1996.

Comments are due Feb. 3, 2016. Read the ICH E6(R2) here: www.fdanews.com/8-15-EMA-GCP.pdf. — Jonathon Shacat

EU Updates Postauthorization Safety Studies Guideline

European regulators on Tuesday released two guide-lines clarifying certain requirements for pharmacovigi-lance in the EU.

A draft guideline on postauthorization safety studies describes procedures for reporting adverse events and submitting study protocols. If suspected adverse events resulting in death are not subject to expedited report-ing as individual case safety reports, drugmakers should explain their rationale for not reporting them, the Euro-pean Medicines Agency says.

Study protocols should include procedures for collect-ing, managing and reporting adverse events, according to Module VIII – Post-Authorisation Safety Studies (Rev 2). The draft also clarifies that the EMA or a national compe-tent authority can require drugmakers to conduct postau-thorization safety studies if there are risk concerns.

An addendum accompanying the draft contains new information on how study protocols and reports on non-interventional postauthorization safety studies should be reported to member states. Trial protocols and reports for centrally authorized products should always be sent to the EMA.

A final guideline, Module IV – Pharmacovigilance Audits (Rev 1), clarifies when activities don’t require an audit.

Comments on the draft guideline and addendum are due Oct. 9. They will take effect in the first quarter of 2016. Read the documents at www.fdanews.com/8-15-EMA- PASS1.pdf and www.fdanews.com/8-15-EMA-PASS2.pdf. The guidance on pharmacovigilance audits is available at www.fdanews.com/08-12-15-audit.pdf. — Jonathon Shacat

EMA: QMS, AE Reporting Top 2014 Postmarketing Inspection Deviations

Lapses in quality management systems and adverse event reporting topped the list of major deviations found during EU postmarking inspections last year, with 18 sites cited for QMS issues and 13 for AE reporting.

The EMA conducted 167 pharmacovigilance inspec-tions in 2014, down from 195 in 2013. Of those, 58 involved centrally authorized products — 15 more than the previous year, according to a report by the Pharma-covigilance Inspectors Working Party.

The report, which focuses on the 58 CAPs, notes that 10 of those inspections were requested by the EMA’s

September 2015Page 6 INTERNATIONAL PHARMACEUTICAL REGULATORY MONITOR

Committee for Medicinal Products for Human Use, three more than in 2013, turning up 79 deficiencies. Only one, involving organizational structure, was deemed critical.

The rest were split about equally — 40 versus 38 — between major and minor violations, and involved prob-lems ranging from clinical trials and safety data analysis to descriptions of pharmacovigilance systems or master files, computerized systems and archiving.

Only one of the 10 inspections CHMP requested involved more than one EU member state.

Pharmacovigilance inspections can be initiated by a member state’s inspection program or by the EMA and are usually product-specific.

Read the report at www.fdanews.com/08-13-15-Ph VReport.pdf. — Kellen OwingsEMA Adverse Event Monitoring Service Now Fully Operational

The European Medicines Agency’s medical litera-ture monitoring service kicked into full operation Sept. 1, allowing drugmakers to easily search for information on adverse reactions associated with their products.

The service, which launched a test run July 1 cover-ing 50 active substances, now monitors information on 300 chemical and 100 herbal active substances. Infor-mation on suspected ARs is entered into the EudraVigi-lance database by the EMA — relieving drugmakers of having to enter it themselves.

Individual cases of suspected ARs will be made available to marketing authorization holders so they can include them in their safety databases and meet report-ing obligations outside the European Economic Area, the EMA says.

Other expected benefits include enhancing the qual-ity and consistency of adverse event data, and reducing the number of duplicate reports.

Drugmakers should check to see if their medicines are covered by the service, the EMA says.

Read New Functionalities in Support of the Medi-cal Literature Monitoring Service here: www.fdanews.com/9-15-EMA-Manual.pdf. A Question & Answer doc-ument is available at www.fdanews.com/9-15-EMA-QA.pdf. — Jonathon Shacat

Think Fresh.Comprehensive healthcare regulatory learning delivered when you want it, where you want it. RAPS Online University offers online learning, developed by regulatory experts.

• Individual courses • Certificate programs• Immersive format with real-life scenarios

Step away from stale, static online learning and embrace a fresh approach with Online University. Your brain will thank you for it.

Dish up Online University via laptop, iPad or Android tablet.

RAPS.org/online

2015 OnlineU Fresh Ad 7.25x5.indd 1 7/22/15 10:09 AM

INTERNATIONAL PHARMACEUTICAL REGULATORY MONITORSeptember 2015 Page 7

U.S. FDA’s Authority to Enforce Quality Metrics Questioned

Industry groups questioned whether the U.S. Food and Drug Administration has the legal authority to enforce its quality metrics guidance during an Aug. 24 public meeting on the draft document.

To ask for quality data, the FDA would need to add the quality metrics to current good manufacturing prac-tices, PhRMA told agency officials. GPhA echoed that concern, saying there’s no statutory authority to require manufacturers to generate new records. The generics trade group also wondered whether the FDA’s authority would extend outside the U.S.

GPhA also had grave concerns with the agency’s stance that failure to supply metrics would be equivalent to refusing an inspection, which could cause products to be deemed adulterated.

Seven industry groups spoke at the Request for Quality Metrics public meeting at the FDA. The groups’ comments were precursors to formal comments they will submit in response to the FDA’s June 28 draft guid-ance. The Sept. 28 deadline for submitting comments has been extended until Nov. 27.

Quality Metrics Requirements

Stakeholders also urged the agency to require fewer metrics initially and to focus on collecting data at the site level, rather than the product level.

The guidance identified 10 quality data points that finished dosage form and active pharmaceutical ingredi-ent makers would collect for each product they produce. Any firm involved in the manufacture, preparation, propagation, compounding or processing of a finished dosage product or API would have to submit quality metrics data, which would be used to decide how often firms are inspected.

Both ISPE and GPhA urged the agency to collect quality data at the site level, as it is more representative of how industry collects and reports data. It would also reduce the burden of starting up the program, as compa-nies would be tasked with sorting through and present-ing data in ways they typically do not, ISPE said.

GPhA also asked the FDA to request metrics directly from contractors instead of making it the application holder’s responsibility to gather the metrics from them.

On implementing the program, ISPE recommended a phased introduction, with Diane Hagerty saying the FDA should “start small, learn and evolve.” Hagerty, who is vice president of global technical operations for quality systems and processes at Roche, suggested start-ing with higher-risk facilities or products that are medi-cally necessary with no alternatives. She also suggested an initial voluntary reporting stage with finished dosage facilities and deferring API reporting to a later phase.

ISPE also wants the FDA to use a smaller starting set of three metrics, and reiterated its position that the annual product review on time rate metric should not be included. Not only did ISPE not see any correlations or outcomes from that metric in the first phase of its pilot program, but the group is concerned about unintended consequences, such as firms focusing on timeliness of the review over quality or thoroughness, Hagerty said.

The FDA is also underestimating how long it will take companies to collect the data, ISPE said, noting drugmakers that participated in the pilot program had to adjust their IT systems and incorporate additional review and data retention methods.

GPhA asked for a safe-harbor period to allow com-panies to prepare accurate, meaningful metrics. The group also suggested the process is being “unduly rushed,” considering the significance of the initiative.

Russell Wesdyk, acting director of the CDER’s Office of Surveillance, said the final guidance will come out in 2016.

Full implementation of the quality metrics program is “several years away,” Christine Moore, acting director of the Office of Product Quality’s Office of Process and Facilities, told attendees at the recent GMP by the Sea Conference in Cambridge, Md. — Kellen Owings

U.S. Industry Seeks Clarity On CMC Draft Guidance

Drugmakers want to know when changes to chem-ical, manufacturing and controls in NDAs, ANDAs and BLAs must be reported to the U.S. Food and Drug Administration, saying draft guidance lacks clear crite-ria and examples.

AstraZeneca argues that changes to the maintenance strategy for a process or equipment should be considered part of continuous quality improvement and not subject to reporting. The company was among 13 that weighed in on the May guidance.

September 2015Page 8 INTERNATIONAL PHARMACEUTICAL REGULATORY MONITOR

The confusion centers on the FDA’s definition of an “established condition,” which, if changed following approval, must be reported to the FDA.

As part of the application process, the FDA said it will assess established conditions in conjunction with the level of understanding about the product and pro-cess, the applicant’s risk assessment activities and the proposed control strategy.

Glenmark Pharmaceuticals wants to know how this will apply for products awaiting approval and how the FDA will communicate assessments to applicants.

AZ also wants to know whether approval might be delayed if applications don’t include a summary of established conditions.

Drugmakers also raise harmonization concerns. AZ questions the timing of the guidance, noting the Interna-tional Conference on Harmonisation is developing ICH Q12, covering similar issues. And Pfizer points out that the guidance talks extensively about control strategy without referencing ICH Q8, 10 and 11, which address this concern.

Pfizer also disagrees with a requirement that updated batch records be submitted following changes to the process or control strategy. These are not con-sidered established conditions and shouldn’t need to be submitted, especially as they are available during FDA inspections, the drugmaker says. The company also wants the FDA to provide an example of when an estab-lished condition would no longer be necessary.

Legacy Products

The FDA should also define “legacy product” and how established conditions for these drugs would be described in applications, drugmakers say.

Leo Pharma says the definition should include the month and year a product could be classified as legacy, and criteria to determine whether a legacy product must be reported to the agency.

AZ suggests it might be more practical to delineate the established conditions after legacy products have been approved when additional data is available to show risk mitigation. In general, legacy products are ones that are no longer under development but haven’t been retired from a company’s drug development program.

The FDA has not indicated when it will issue final guidance. To view the draft guidance, go to www.fdanews.com/05-29-15-CMCguidance.pdf. — Kellen Owings

India Approves $270 Million Plan To Upgrade Drug Regulations

India’s prime minister has approved a $270 million plan to strengthen the country’s drug regulatory system, including establishing new drug testing laboratories and a training academy for regulatory and drug testing officials.

Under the three-year plan, existing laboratories will get additional equipment and manpower, and new mobile testing labs will be deployed throughout the country.

D.G. Shah, secretary general of the Indian Phar-maceutical Alliance, says the addition of testing labs in each state should reduce the time required to test drug samples — reducing the current bottleneck and allowing results to become available immediately.

Other upgrades include adding more personnel to handle stem cell, regenerative medicine and biological submissions and implementing organization-wide e-gov-ernance and information technology services, accord-ing to the Cabinet Committee on Economic Affairs. The Central Drugs Standard Control Organization will get $140 million for the improvements, with the remaining $130 million going to state regulators.

Amy Hariani, director and legal policy counsel of the U.S.-India Business Council, says the decision to invest in the pharma regulatory system demonstrates India’s long-term interest in growing its drug export business and aligning with global regulatory standards.

India supplies more than 40 percent of U.S. generic drug imports, based on volume, and patients have a vested interest in ensuring that the medicines they con-sume from India remain safe and effective, she tells IPRM. — Jonathon Shacat

Drug Industry Slams French Law Promoting Off-Label Use

EU biopharma groups have lodged a complaint with the European Commission opposing a French law that promotes off-label use of medicines, saying it puts cost ahead of patient safety.

The complaint comes in response to a June deci-sion by French medicines regulator ANSM to authorize the use of Roche’s Avastin to treat age-related macular degeneration in hospital patients under strictly super-vised conditions.

Minster of Health Marisol Touraine approved reim-bursement of Avastin for the unapproved use, effective Sept. 1, saying the decision “will achieve significant savings.”

INTERNATIONAL PHARMACEUTICAL REGULATORY MONITORSeptember 2015 Page 9

Avastin (bevacizumab), at $50 per dose, is signifi-cantly less expensive than alternatives such as Novar-tis’ Lucentis (ranibizumab), which retails at nearly $2,000 per dose, according to the American Macular Degeneration Foundation.

The complaint — filed jointly by the European Fed-eration of Pharmaceutical Industries and Associations, European Confederation of Pharmaceutical Entrepre-neurs and European Association for Bio-industries — argues that off-label prescribing should only occur in very specific situations where there is no therapeutic alternative, and not for purely economic reasons.

Novartis spokesman Eric Althoff says the drugmaker is evaluating possible consequences on patients’ health.

Roche could not be reached for comment.

EFPIA challenged a draft of the law when it was approved by the French National Assembly last sum-mer (IPRM, Aug. 26, 2014). The measure was ultimately adopted in December. A similar law passed the Italian legislature last year. — Jonathon ShacatTwo More Tropical Diseases Eligible For Priority Review Voucher in U.S.

The U.S. Food and Drug Administration has added Chagas disease and neurocysticercosis to the list of treatments for tropical diseases eligible for priority review vouchers, bringing the number to 19.

The list can be expanded to include any infectious disease that has no significant market in developed nations and disproportionally affects poor and marginal-ized populations.

Leaving Chagas disease and neurocysticercosis off the priority review list was an oversight that needed to be cor-rected, says Peter Hotez, dean of the National School of Tropical Medicine at Baylor College of Medicine in Houston.

The voucher mechanism will directly benefit the poorest Americans, as well as those living abroad, since an estimated 12 million Americans live with a neglected tropical disease, including the two just added to the list, he tells IPRM.

Neurocysticercosis is caused by a tapeworm and can lead to epileptic seizures. It affects up to 1.4 million peo-ple in Central and South America and up to 4.6 million people in sub-Saharan Africa, according to the FDA.

Chagas disease, a vector-borne parasitic disease, afflicts roughly 9.4 million people, the vast majority liv-ing in the Americas. Read the final order here: www.fdanews.com/8-15-FDA-PRV.pdf. — Jonathon Shacat

Saudi FDA Releases Guidance On Registering Clinical Trials

All sponsors planning to conduct clinical trials in Saudi Arabia for the first time must register their studies through the Saudi Clinical Trials Registry, under new guidance issued Aug. 30.

Phase 2 and 3 trials also require approval from the Saudi Food and Drug Administration, which car-ries a $4,000 evaluation fee. For Phase 4 trials, only the approval of an institutional review board is required. Phase 1 trials just require registration.

Companies must submit a yearly progress report on ongoing trials and inform the SFDA within 60 days of completing, terminating or suspending a trial, followed by a final report within 12 months.

Trial-related adverse reactions must be reported within 15 days if they are serious and within seven days if they are fatal or life-threatening.

The guidance also covers requirements for export-ing biological samples from trial participants and inves-tigator qualifications.

Read the guidance here: www.fdanews.com/8-15-SaudiTrials.pdf. — Jonathon ShacatIPEC Urges Use of Industry Guidance On Stability Testing of Excipients

IPEC-Americas is urging excipient makers to follow its voluntary guideline on stability testing in the wake of recent requests by foreign regulators for stability data.

During the first quarter of 2015, IPEC says sev-eral companies were told to provide authorities in South America and Asia with data on excipients stored under stressed conditions — those with higher temperatures and higher relative humidity — in addition to long-term stability data on their products.

That puts companies in a bind since there are no formal guidelines for excipient stability, says Phil Mer-rell, technical market manager for excipients maker Jost Chemical.

In the absence of formal guidance, most excipient makers currently use the International Conference on Harmonisation’s Q1A(R2) guideline to test for stability, even though it’s meant for finished drug products and active pharmaceutical ingredients, and not excipients. But Merrell questions the point of separate stability test-ing for excipients since any problem would be revealed when the finished drug was tested.

September 2015Page 10 INTERNATIONAL PHARMACEUTICAL REGULATORY MONITOR

IPEC’s guidelines address stability studies under likely — not stressed — conditions. As one option, the group suggests using historical data from batches stored by the manufacturer.

The other option — which IPEC prefers — is to study the excipient in its commercial packaging, placed in a commercial warehouse with a known and monitored tem-perature. The packaging container/closure system should be defined, and the general conditions under which sam-ples or containers are stored should be known.

If an excipient is meant to be stored at room temper-ature, then manufacturers can use ICH Q1A(R2), IPEC says. For excipients stored in an uncontrolled ware-house, stability data need to show that such conditions don’t adversely affect the product.

Merrell, who chairs the IPEC subcommittee deal-ing with the issue, says that because the stability of most excipients is supported by years of data, the guidelines will be most important for new excipients.

The U.S. Pharmacopoeia’s Excipient Verification Program and NSF/IPEC/ANSI 363: Good Manufactur-ing Practices for Pharmaceutical Excipients, which the U.S. Food and Drug Administration endorses, focus on good manufacturing practice and quality of excipients, not their stability. And while the USP’s verification pro-gram is designed to provide third-party confirmation of excipient quality for manufacturers, there has been lim-ited interest in the program.

The European Commission has developed GMP guidelines for excipients, which take effect next March, but they, too, make no mention of stability testing.

Merrell disputes the need for comprehensive stability testing in most cases, saying excipients have been shipped around the world and stored in a variety of conditions for decades with virtually no failures. As long as products are stored in proper containers, stability — for the vast major-ity of excipients — won’t change, Merrell says. Those

excipients that are known to be unstable are already stored and shipped in special temperature- and humidity-con-trolled refrigerated containers, he tells IPRM.

An IPEC position paper with a link to the guidelines is available at www.fdanews.com/08-07-15-Excipient PostionPaper.pdf. — Kellen OwingsViral Shedding Studies Focus Of U.S. FDA Final Guidance

Biologics makers developing drugs based on bacte-ria and viruses should conduct preclinical and clinical studies to determine if infection could be unintention-ally transmitted from treated patients to other individu-als, the U.S. Food and Drug Administration says.

While product-based viruses and bacteria are gen-erally not as infectious or virulent as the parent strain, transmission can occur, and sponsors should design a sampling plan to collect shedding data in clinical studies, according to final guidance that contains only minor changes from a 2014 draft.

The collection should begin in Phase 1 trials for virus or bacteria-based gene therapy products and onco-lytic products classified as replication competent. Spon-sors may need to continue collecting shedding data dur-ing Phase 2 and Phase 3, since replication competent products have a higher likelihood of releasing infectious viruses or bacteria, the FDA says.

For products based on bacteria or viruses that can infect a host but not spread, the data can be collected later in drug development, such as Phase 2 studies, after determining dose and regimen.

BLAs should include a comprehensive shedding report.

Read Design and Analysis of Shedding Studies for Virus or Bacteria-Based Gene Therapy and Oncolytic Products here: www.fdanews.com/8-15-FDA-Shedding Studies.pdf. — Jonathon Shacat

Reporters: Kellen Owings, Elizabeth Hollis, Michael Cipriano

President: Cynthia Carter; Editor-in-Chief: Meg Bryant; Managing Editor: John Bechtel

Copyright © 2015 by Washington Business Information Inc. All rights reserved. International Pharmaceutical Regulatory Monitor (ISSN 1934-600X) is published monthly, 12 issues, for $795. Photocopying or reproducing in any form, including electronic or facsimile transmission, scanning or electronic storage is a violation of federal copyright law and is strictly prohibited without 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.

300 N. Washington St., Suite 200 • Falls Church, VA 22046-3431 • Phone: (888) 838-5578 • +1 (703) 538-7600 • Fax: +1 (703) 538-7676www.pharmaceuticalmonitor.com

Customer Service Editor: Jonathon Shacat Ad Sales: Jim Desborough(888) 838-5578 • +1 (703) 538-7600 (703) 538-7663 (703) 538-7647customerservice@fdanews.com jshacat@fdanews.com jdesborough@fdanews.com

2 Days, 200 Tips For Improving Your Advertising and Promotion Review ProgramFDA marketing scrutiny no longer is limited to magazine and TV ads. Now the agency is poking around, checking signage in tradeshow booths… checking in on Twitter and Facebook….and listening to the physicians and other healthcare professionals you’ve paid to speak or train.

Come to Raleigh in May for two days of intense learning. You’ll arrive back home with a bag full of tricks and tips to keep all your marketing efforts squeaky-clean.

� Understanding Pre-Approval Communications Don’t get on the FDA’s or SEC’s radar screens before your product is even approved. Learn how to properly disclose information and remain in compliance.

� How To Maximize Disease Awareness Communications Take away valuable tips and tricks for using disease awareness communications pre- and post-approval.

� Hurray! You’re Approved Building the most aggressive – but compliant – campaign from first day of approval to commercial launch.

� Assuring Your Promotions Meet FDA Off-Label Standards Successfully navigating 4 major traps that can earn you a warning letter fast.

� Itching To Do More With Social Media? Discover how to get your message out there … without crossing the line.

YOUR EXPERT SPEAKER: NOV. 17-18, 2015 HILTON WASHINGTON DC/ROCKVILLE MD HOTEL AND EXECUTIVE MEETING CENTER

BUILDING A WORLD-CLASS ADVERTISING AND PROMOTION REVIEW PROGRAM

PRESENTS THE

AN INTERACTIVE WORKSHOP PRESENTED BY PHILLYCOOKE CONSULTING AND FDANEWS

Multi-attendee discounts are available!

DALE A. COOKE Owner, PhillyCooke Consulting

Mr. Cooke’s practice specializes in helping FDA-regulated companies develop compliant promotional tactics and improve the promo-tional review. He is the author of Effective Review and Approval of Digital Promo-tional Tactics and is currently at work on a book about compliant social media usage for prescription product manufacturers.

www.fdanews.com/advertisingpromotion | (888) 838-5578

“Dale is easy to listen to. The material covered is comprehensive. The sessions covered what I believe is beneficial to those responsible for ad/promo review” — Tim Williams, VP of Regu-latory Affairs, CR Bard

DAY ONE I NOV. 17

8:00 a.m. – 9:00 a.m.

Registration and Continental Breakfast

9:00 a.m. - 9:45 a.m.

Pre-approval Communications � How to meet your SEC requirements for

disclosing information while not running afoul of FDA pre-approval promotion prohibitions

9:45 a.m. - 10:30 a.m.

Disease Awareness Communications � A review of FDA’s help-seeking guidance

� Keys for using disease awareness communications prior to approval. Essential information for continuing communications efforts post-approval compliantly.

10:30 a.m. - 10:45 a.m.

Break

10:45 a.m. - 11:15 a.m.

From Day of Approval through Commercial Launch � Understanding the timeline and key dates for

communications

� Minimizing the pain, while maximizing the impact of initial promotional communications

11:15 a.m. 12:00 p.m.

Essential Advertising & Promotion Regulations � A review of all of the requirements for product

promotion, including product name usage, fair balance, directions for use

12:00 p.m. – 1:00 p.m.

Lunch

1:00 p.m. - 1:45 p.m.

Format-Specific Promotional Requirements � DTC television promotion

� Brief summary requirements for print promotion

1:45 p.m. - 2:30 p.m.

Substantial Evidence & Other Standards � A review of the substantial evidence standard,

what fails to meet that standard, and when other standards apply

2:30 p.m. - 2:45 p.m.

Break

2:45 p.m. – 4:00 p.m.

Off-Label Information � Avoiding off-label promotion

� Scientific exchange exemption

� Responding to unsolicited requests

� Distributing off-label reprints

4:00 p.m. - 4:30 p.m.

The Promotional Review Process � An overview of a the standard promotional

review process

� Essential traits for any effective process

� Key decisions in establishing or improving performance

� Effective use of metrics for evaluating performance

4:30 p.m.

Session Wrap-Up, End of Day One

DAY TWO I NOV. 18

8:30 a.m. – 9:00 a.m.

Continental Breakfast

9:00 a.m. - 9:45 a.m.

Integrating Digital Promotion � Key considerations for evaluating the

compliance of digital promotional tactics and their integration into the overall promotional mix

9:45 a.m. - 10:15 a.m.

Social Media Part 1 � Overview of the platforms, issues, and a

review of the status of FDA guidance

10:15 a.m. - 10:30 a.m.

Break

10:30 a.m. - 12:30 p.m.

Social Media Guidances � A review of the three social media guidances

released in 2014: 2253 Filing, Presenting Risk Information in Space-Limited Contexts, & Correcting Misinformation on Third-party Sites

12:30 p.m. - 1:30 p.m.

Lunch

1:30 p.m. - 3:15 p.m.

Promotional Review Board Practicum � Workshop participants will apply the lessons

from the earlier part of the workshop to specific product promotions. They will work in teams to evaluate specific promotional tactics, determine what (if any) parts of the promotion are problematic, and how to provide direction to a brand marketer to make the promotions compliant.

3:15 p.m. - 3:30 p.m.

Break

3:30 p.m. - 4:15 p.m.

Continuing Regulatory Intelligence: Staying Abreast of Ad/Promo News � Ad/Promo is an area of ongoing

developments. This session will cover the most prominent sources for keeping up with these developments.

4:15 p.m. - 4:30 p.m.

Wrap-up and Adjourn Workshop

www.fdanews.com/advertisingpromotion | (888) 838-5578

BUILDING A WORLD-CLASS ADVERTISING AND PROMOTION REVIEW PROGRAM

“Dale was very engaging and informative. I like the interactive

portion where we reviewed actual ads.”

— 2014 Workshop Attendee

Course Binder Materials:Full slides from the PowerPoint presentationsReference documents:

FDA Advertising & Procedural Guidances• Help-Seeking Guidance• DTC Broadcast Guidance & Q&A• FDAAA Pre-Dissemination Review Requirements• Product Name Guidance (All three versions from 1999, 2012, and 2013)• Presenting Risk Information Guidance• Social Media Guidances

- Postmarketing Submissions Requirements - Responding to Unsolicited Requests for Off-label Information - Presenting Risk Information in Space-limited Contexts Correcting Third-party Misinformation

• Distributing Off-Label ReprintsRelevant Sections of Code of Federal Regulations Form 2253PhRMA Principles on DTC AdvertisingPhRMA Principles on Interactions with Healthcare ProfessionalsPre-approval Promotion ChecklistEffective Review & Approval Process ChecklistKeys to Evaluating Promotional Review Systems List of Key Resources for Continuing EducationArticles by Dale Cooke

• Developing Compliant Search Engine Marketing Campaigns (Publication Date of September 2014)!

• Industry Standards for Linking Disease Awareness Websites to Product Promotion!

• Patient Testimonial Videos: FDA Actions on Risk Information Presentation!• Presenting Risk Information on Websites!• Where Things Stand on FDA Guidance on Social Media (Publication Date of

September 2014)

BUILDING A WORLD-CLASS ADVERTISING AND PROMOTION REVIEW PROGRAM

WHO WILL BENEFIT?

� Advertising and marketing managers

� Social media teams

� Promotion review committee members

� Medical affairs

� Continuing education and tradeshow organizers

� Regulatory compliance officers

� PRC coordinators

� Legal counsel

� Compliance

� Executive management

� Outside ad agencies and marketing consultants

www.fdanews.com/advertisingpromotion | (888) 838-5578

“[Dale is] an animated speaker who seems to know

something about everything and has no shortage of opinions.

This is potentially very dry and dull material. Dale brings out the exciting and humorous

aspects especially well. It’s an engaging two days.”

— Michael Benedetto, Editorial Group Leader, FCB Health

“This is normally a dry topic, but with Dale it was anything but

dry. Dale gave one of the best, most engaging presentations. Dale is highly knowledgeable and also very entertaining.”

— Ellen Derrico, Global Head, Market Development - Life

Sciences & Healthcare, QlikTech

“As a fellow regulatory professional, Dale is one of the most deeply knowledgeable experts I’ve heard on this complicated subject. As the

pharmaceutical industry is experiencing, digital promotional tactics can trip up even experienced regulatory professionals, but Dale showed how basic

principles can be applied to develop compliant promotional materials.”— Kathleen Koons, Sr Regulatory Affairs Manager,

DJA Global Pharmaceuticals Inc.

HOTEL INFORMATION INFORMATION:

Nov. 17-18, 2015

Hilton Washington DC/Rockville Hotel and Executive Meeting Center 1750 Rockville Pike Rockville, MD 20852

Toll Free: (800) HILTONS +1 (301) 468-1100

www.RockvilleHotel.com

Room rate: $215 plus 13% tax Reservation cut-off date: Oct. 26, 2015

TEAM DISCOUNTS:

Significant tuition discounts are available for teams of two or more from the same company. You must register at the same time and provide a single payment to take advantage of the discount. Multi-attendee discounts are available and will be calculated at check out.

2-4 attendees – 10%5-6 attendees – 15%7-9 attendees – 20%10+ attendees – 25%

TUITION:

Tuition includes all conference presentations, conference materials, two breakfasts, two lunches and refreshments.

CANCELLATION AND SUBSTITUTION:

Written cancellations received at least 21 calendar days prior to the start date of the event will receive a refund — less a $200 administration fee. No cancellations will be accepted — nor refunds issued — within 21 calendar days from the start date of the event. A credit for the amount paid may be transferred to any future FDAnews event. Substitutions may be made at any time. No-shows will be charged the full amount. In the event that FDAnews cancels the event, FDAnews is not responsible for any airfare, hotel, other costs or losses incurred by registrants. Some topics and speakers may be subject to change without notice.

Sign me up for the Building a World-Class Advertising and Promotional Review Program

INFORMATION:

Name ________________________________________________________________________________

Title ______________________________ Company __________________________________________

Address _______________________________________________________________________________

City __________________________________________________ State ________________ ZIP_______

Phone ______________________________________ Fax ______________________________________

Email ________________________________________________________________________________

PAYMENT OPTIONS:

c Check Enclosed: payable in U.S. funds to FDAnews

c Charge my: c Visa c MasterCard c AmEx

Card # _________________________________________ Exp. Date ____________________________

Signature ___________________________________________________________________________

Complete Workshop

Subtotal

Name ................................................................................................................................

Title ............................................................... Phone .........................................................

E-mail ................................................................................................................................

$1,797

Name ................................................................................................................................

Title ............................................................... Phone .........................................................

E-mail ................................................................................................................................

Call for

Discounts

Name ................................................................................................................................

Title ............................................................... Phone .........................................................

E-mail ................................................................................................................................

TOTAL: ________________www.fdanews.com/advertisingpromotion

Toll-free: (888) 838-5578

PRESENTS THE

Yes!

BUILDING A WORLD-CLASS ADVERTISING AND PROMOTION REVIEW PROGRAM

Call for

Discounts

Cut Drug Approval Time with a 505(b)(2)

Yes, you can speed up your company’s drug approval time — by using the 505(b)(2) process.

In a nutshell, Section 505(b)(2) allows you to obtain approval of NDAs containing investigations of safety and effectiveness that were not conducted by or for your com-pany, but for which the FDA has already issued an approval.

A 505(b)(2) can provide relatively fast-track approval for a wide range of products, especially for those that represent a limited change from an existing or approved drug. Ideal candidates include:

• New chemical entities (NCEs)/new molecular entities (NMEs)• Changes to previously approved drugs• Changes in dosage form, strength or route of administration• Changes from prescription (Rx) indications to over-the-counter (OTC) indications.

Unsure of how to use the 505(b)(2) process? Here’s an opportunity to get all the details in a new report available from FDAnews. Readers will learn:

• How the 505(b)(2) is similar to and differs from the 505(b)(1) standardNDA and the 505(j) ANDA

• How drugs approved under the 505(b)(2) process can obtain eitherthree or five years of patent exclusivity

• How to choose a listed drug for a 505(b)(2) application• And much more!

Name _________________________________________________________

Title __________________________________________________________

Company ______________________________________________________

Address _______________________________________________________

City________________________ State _____________ Zip code _________

Country _______________________________________________________

Telephone _____________________________________________________

Fax ___________________________________________________________

Email _________________________________________________________

METHOD OF PAYMENTq Check enclosed (payable to FDAnews)

q Bill me/my company. Our P.O.# _______________________

q Charge my credit card:q Visa q MasterCard q American Express

Credit card no. _______________________________________

Expiration date _______________________________________

Signature ___________________________________________

qYes!

Add $10 shipping and handling per book for printed books shipped to the U.S. and Canada, or $35 per book for books shipped elsewhere. Virginia customers add 6% sales tax.

15FLYR-N

Please send me ____ copy(ies) of Cut Drug Approval Time with a 505(b)(2) at the price of $397 each for the format I’ve selected: q Print qPDF

1. PHONE: Toll free (888) 838-5578 or +1 (703) 538-7600

2. WEB: www.fdanews.com/46768

3. FAX: +1 (703) 538-7676

4. MAIL: FDAnews 300 N. Washington St., Suite 200 Falls Church, VA 22046-3431

FOUR EASY WAYS TO ORDER

3

(Signature required on credit card and bill-me orders)