European Regulatory Roundup: EMA Reviews Drugs Tested at Two Indian Sites

CHMP began reviewing drugs tested at Indian sites in the midst of GCP's concerns

The Committee for Medicinal Products for Human Use (CHMP) undertook a review of the trial on two sites Micro Therapeutics Research Labs India Drugs. The national regulatory authorities asked the CHMP to conduct a review after the Austrian and Dutch authorities found fault with these sites during a Good Clinical Practice (GCP) inspection.

Officials visited sites in February Micro Therapy reported concerns about the survey data used to support applications for marketing authorization in the European Union. This led to 18 national regulatory bodies to ask the European Medicines Agency (EMA) to check whether the findings of the GCP inspectors affected their position on the risks and benefits of the drugs tested on the sites. The CHMP also checks whether the data generated on the sites are used to support active applications and, if so, to determine whether the origin of the results should influence their evaluation.

The review involves a centrally licensed drug, a generic copy of Eli Lilly's erectile dysfunction drug Cialis sold by Mylan. EMA drug approved two years ago on the basis of data showing that it is bioequivalent to the reference product. The review will also assess the risks and benefits of drugs approved by national authorities in light of questions about data generated at sites in the Indian cities of the Chennai and Coimbatore regulatory bodies.

Previous suggests EMA will strongly act against any medication that has been approved based on data generated incorrectly. When EMA found evidence of manipulating electrocardiogram data from GVK Biosciences, he recommended the suspension of 700 products that were based on studies conducted by contract research agency in India for approval. More recently, the agency has suspended dozens of drugs, including many sold by Novartis and Teva Pharmaceuticals, after finding flaws in how the Semler Research Center conducted bioequivalence studies.

Scottish politicians criticize MHRA on transvaginal mesh implants

Politicians have criticized the UK Drug and Health Products Regulatory Agency (MHRA) for its treatment of transvaginal mesh implants. The Scottish government has asked the National Health Service (NHS) to stop using appliances in 2014, but the products remain on the market, it is reported that more than 400 women have received implants since.

Scottish politicians discussed implants after the BBC News reported the continued use of devices. Shona Robison, the ruling Scottish National Party, adopted the debate defining the powers or lack belonging to the government and MHRA and other politicians said a report to be released early next year will contain answers to your questions. However, with a political argument that implants cause "organ damage, loss of a kidney, bladder removal, constant chronic and unbearable pain" and other side effects, the Robison argument has not Managed to soothe all other loudspeakers.

"Due to the problems we are discussing, we have tended to speak on the subject in the most cautious tones. However, last month in the Australian Parliament, Senator Derryn Hinch delivered a speech absolutely Dull in which he criticized doctors And manufacturers neglect women and compared implant mesh scandal with thalidomide, "said conservative politician Carlaw Conservative Party said." I include the MHRA in my criticism. "

MHRA examined evidence of the risks and benefits of implants in 2014 after groups representing patients affected by devices come to him. The regulator concluded that "for most women, the use of vaginal mesh implants is safe and effective." Other regulators have come to similar conclusions.In January, the Food and Drug Administration (FDA) ) Reclassified mesh implants used to repair organ pelvic prolapse (POP) and increased risk devices, but left used to treat stress urinary incontinence products in Class II.

The position of the FDA is broadly aligned with that of the MHRA, which was more unequivocally its support for the use of POP SUI mesh. Despite this, and a requirement that all patients give their prior knowledge before proceeding to an authorization of the mesh implant, the question remains political

FDA Proposes New Rule on Bulk Substances Used to Compound Drugs

The US Food and Drug Administration (FDA) on Thursday issued a proposed rule to add six bulk pharmaceutical substances to a list of these substances that can be used in the composition and to remove four other bulk substances Included in the list.

If the proposed rule is finalized, the six bulk pharmaceuticals proposed to be included in the so-called bulk carrier list 503A. The FDA Pharmacy Advisory Committee (ABCP) discussed proposed additions and exclusions in 2015 and the committee met three times in 2016 to discuss the inclusion and exclusion of others Substances on the list.

"Due to the time elapsed between the publication of the proposed rule in 1999 and the promulgation of the DQSA [Drug Quality Security Act], the FDA considered it necessary to recommence the development of the 503A bulk carrier list," said The agency In the Federal register of Thursday.

In addition to new additions and exclusions, the FDA is also proposing, through this new rule,

"Due to the time elapsed between the publication of the proposed rule in 1999 and the promulgation of the DQSA [Drug Quality Security Act], the FDA considered it necessary to recommence the development of the 503A bulk carrier list," said The agency In the Federal register of Thursday.

In addition to new additions and exclusions, the FDA is also proposing, through this new rule,

1. 1 Physical and chemical characterization of the substance
2. 2 Safety Issues Raised with the Substance in Compounded Pharmaceuticals
3. 3 Available evidence of the efficacy or lack of efficacy of a drug product combined with the substance, if there is such evidence
4. 4 Historical use of the substance in compounded pharmaceutical products, including information on the medical condition (s) to which the substance was used to treat and any references in the peer reviewed medical literature.

The FDA proposes to examine each criterion and balance it on a substance-by-substance basis in order to decide whether a substance is appropriate for inclusion in the list.

The Federal Register's notice announcing the proposed rule provides additional details on the type of information proposed for each criterion and how the FDA proposes to weigh the information.

Inclusion in List 503A

Based on the FDA assessment and consultation with the Advisory Committee on Pharmaceutical Composition, the agency proposes to include six bulk pharmaceutical substances on the list:

1. 1 Brilliant Blue G, also known as Coomassie Brilliant Blue G-250, as a dye used for staining for visualization during ophthalmic procedures
2. 2 cantharidin (for topical use only), for the treatment of warts and molluscum contagiosum
3. 3 diphenylcyclopropenone (for topical use only) for the treatment of alopecia and non-genital warts
4. 4 N-acetyl-D-glucosamine (for topical use only) for the treatment of hyperpigmentation and other skin conditions
5. 5 dibutyl ester of squaric acid (for topical use only) for the treatment of alopecia areata and recalcitrant non-congenital warts
6. 6 thymol iodide (for topical use only) for ulcerations and skin infections, as well as intrapleural treatment for pleural effusions

Exclusion from List 503A

The FDA has proposed that the following four substances be included in List 503A:

1.  1 oxitriptan (evaluated as a treatment for depression and insomnia)
2.  2 piracetam (evaluated as a treatment to improve cognitive skills)
3.  3 light silver protein (for use as an anti-infective agent for ophthalmic use)
4.  It is approved in South Korea and Japan for the treatment of asthma, keloids and hypertrophic scars, and an ophthalmic solution for allergic conjunctivitis (4), transilast (for the treatment of allergic disorders, Arthritis, dry eye syndrome, keloids and hypertrophic scars )

Regulatory Action Against State Pharmacies

The FDA also notes in the proposed rule that it does not intend to take regulatory action against a government-approved pharmacy, a federal facility or a licensed physician to make a drug using a pharmaceutical Bulk that is not the object of a USP or NF

FDA Finalizes Drug Supply Chain Guidance, Seeks Comment on New Section

The Food and Drug Administration (FDA) issued final guidelines on the implementation of the Drug Supply Chain Security Act (DSCSA) on Thursday, but also asks for comments on a new section describing when manufacturers should notify the FDA High risk that an illegitimate product is

.

According to the new section, which is distributed "for comment only", the Agency offers its interpretation of paragraph 582 (b) (4) (B) (ii) of the Food, Drugs and (FD & C Act) , Which obliges manufacturers to make notifications under certain circumstances for products that present a high risk of illegitimacy.

"The FDA interprets this provision as requiring manufacturers to notify (1) the FDA and (2) the manufacturer's immediate business partners (which the manufacturer has reason to believe possesses in the possession of the trading partner a manufactured product or purported to be A product Manufactured by the manufacturer) in three general scenarios:

1. Within 24 hours of the determination or notification by the FDA or a trading partner that there is a high risk that the manufacturer has reason to believe in the possession of an immediate trading partner is a Product.
2. Within 24 hours of the determination or notification by the FDA or a trading partner that there is a specific high risk that could increase the likelihood that the illegitimate product will enter the supply chain of the US pharmaceutical distribution.
3. Within 24 hours of the determination or notification by the FDA or a trading partner that there is "other high risk" as determined by the FDA in the guidelines under paragraph 582 (h).

The new section, "For manufacturers: high risk of notifications of illegitimacy", also offers examples of scenarios involving high risks of illegitimacy in which the manufacturer should make a notification.

In addition to the added section, the FDA says it has made minor changes to FDA Form 3911 and instructions for completing the form.

The finalized parts of the guide, written for the first time in June 2014, are intended to help companies rapidly remove illegitimate drugs from the US market by notifying the FDA and trading partners after manufacturers determine or are notified by the FDA or the FDA Business Partner That there is a high risk that an illegitimate product is.

And as of next November, pharmaceutical companies will have to mark their products with National Drug Code (NDC), serial number, batch number and expiration date in both machine-readable and human-readable formats

Sanofi Halts Production of Bladder Cancer Drug as Others Fail to Win FDA Approval

Sanofi Pasteur has announced the completion of the manufacture of TheraCys, an important drug against bladder cancer, and shortages are expected, while the Food and Drug Administration (FDA) on Friday issued draft guidelines to help develop new treatments for non-invasive nonmuscular cancer NMIBC ).
Benjamin Davies, MD, associate professor of urology at the University of Pittsburgh School of Medicine, wrote in Forbes on Thursday, called on the government to step in and posted Sanofi's letter informing doctors of the decision.

Sanofi said production would cease at the Canadian manufacturing facility in mid-2017 and production will not resume.

In 2012, the Canadian facility received a warning letter from the FDA stating that "sterility for all batches of TheraCys, BCG Live (Intravesical) (BCG-IT) manufactured in the building (B) Method Validation in 2000 can not be insured. "

And when the facility closed in 2012, many patients either missed doses or received lower medications in place of BCG, according to another Davies article here.

The same Toronto facility later stated in October 2015 as a result of these molds and other problems Health Canada would allow it to resume production of drugs later in 2015, The FDA.

Sanofi said in his letter this week that no other company would take on the manufacture of the product and "the product will not be relaunched in the United States."

Rejection and draft guidance from the FDA

Separately on Thursday, Spectrum Pharmaceuticals said the FDA had rejected its NMIBC treatment, Apaziquone. "Based on the discussions, the Company is evaluating a new, more modest study that would replace the ongoing Phase 3 program in which enrollments were stopped," the company said in a fil filing.

Telesta Therapeutics also received a full response letter for its FDA NMIBC treatment in February, saying an additional Phase 3 clinical trial would be required.

Following these refusals, the FDA released Friday to 12-page draft guidelines to help pharmaceutical and biotech promoters try to develop drugs and biologics to treat patients with this form of high-risk bladder cancer.

"The alternative is radical cystectomy, the surgical procedure with significant morbidity and mortality," says the FDA.

"The preferred trial design to demonstrate the efficacy of drugs developed to treat NMIBC is a randomized, controlled trial with a survival time without recurrence. (BCG) in situ, with or without papillary using a complete end-of-response rate criterion (and duration) may be appropriate.

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EMA Recommends Nine Drugs for Approval

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) announced on Friday that I recommend nine drugs for its meeting approval in a This Week of Principles, including four new treatments, three and two generic biosimilars .

Regarding New Medicines, the CHMP Recommends Marketing Authorization for Afstyla (lonoctocog alfa) CSL Behring for the Prevention and Treatment of Hemorrhage in Patients with Haemophilia A, FIASP Novo nodisk (insulin aspart) for Diabetes, Suliqua Sanofi (Glargine / lixisenatide insulin) for the treatment of type 2 diabetes and Vemlidy (tenofovir alaphaenamide) Gilead for chronic hepatitis B.

Three of the four new treatments have been approved by the FDA and US Food and Drug Administration (FDA), including FDA approval Thursday Vemlidy. The US regulator has until last of this my sober decision for the Sanofi Treatment Request After Further Information on the Delivery Device.

In the Biosimilars Front, Lusduna Three New were recommended for approval by the CHMP Merck Sharp and Dohme (Glargine Insulin) for the treatment of diabetes, as well as STEMA Arzneimittel of Movymia not Gedeon Richter Terrosa (Both contain teriparatide) for Treatment of osteoporosis.

None of THESE Treatments Has Been Approved by the US FDA, Merck AGAINST in August A New Drug Application Presented for its biosimilar insulin biosimilar in the US, with Partial Funding Samsung Bioepis.

The CHMP also recommends return generic medications for approval: darunavir Mylan for Treatment HIV-1 Infection by Tadalafil and Mylan for Treatment of Pulmonary Arterial Hypertension. FDA for the First Time American Authorized Generic Darunavir Mylan in 2013, EVEN for Tadalafil, Best Known as in the US Cialis, there is no generic Generic Market.

In addition, EMA recommends extensions of the Indications Novartis Arzerra (ofatumumab), Genzyme Caprelsa (vandetanib) Abbvie Humira (adalimumab), Pfizer's Nimenrix (meningococcal Group A, C, W135 and Y conjugate vaccine) is UCB Pharma Vimpat (lacosamide) .

Complete CHMP also Scientific An evaluation of the Annual Marketing Authorization Renewal Conditional Conditional Treatment of Duchenne Muscular Dystrophy, Duchenne Dystrophy (DMD) from PTC Therapeutics Translarna (ataluren) recommending that you renew the conditional marketing authorization f. In the United States, the FDA sent the Past A decision of February my Refuse AFTER a PTC from the agency SAID the Company's Request for Treatment Was Not Completely Enough.

As part of the CHMP evaluation for Transplanna, the PTC Requester Regulator conducted a randomized, placebo-controlled eighteen-month study with patients in DMD, followed by an 18-month period in which all patients would change to have transplantation. If you expect the Study Results in the primer to be available quarter 2021.

Overall, by 2016, the CHMP has Issued Positive Opinions 73 Medications, Including New Treatments, Biosimilars Generics Y, And 50 Opinions ON THE POSSIBLE EXTENSION OF THERAPEUTIC REGISTRIES.

RAC US Exam Question No 46

Question No 46:

MDUFMA authorized 3rd party establishment inspections. All of the following are true about these inspections EXCEPT:

A. You need to market at least one device in the United States.
B. Participation is mandatory.
C. In order to be eligible, an establishment's most recent inspection must be NAI or VAI.
D. Establishments are not required to obtain clearance of a 3rd party in advance.

Answer: B

Health Canada Issues New Medical Device Recall Guide

Health Canada on Thursday issued new guidance on the medical device recalls in detail the responsibilities of sponsors under the Medical Devices Regulations (MDR) in the country, replacing the 2011 Guidelines of the organization.

Specifically, the guide provides advice on keeping medical records distribution, extraction devices instruments, submission to Health Canada recalls and drafting internal procedures for retirement.

The guide has also been rewritten to include support clubs and other language intended to provide clarity and other fund sponsors, including links to definitions, laws and regulations.

For example, in the section on the scope of the document, the agency added an explanation of why the regulatory requirements for reminders apply to different types of businesses:

The requirements to maintain distribution records under [section] 52-56 [Regulation of Medical Devices] and the recovery process in accordance with paragraph 58 (b) of the MDR (Part 1) s' apply to manufacturers, importers and distributors. The information requirements provided for in Articles 64 and 65 manufacturers and importers apply only.

The new guide also focuses more on the process and responsibilities related to the removal of the devices, while the previous version was more technical in nature, focusing on the different sections of the MDR and interpretation.

The new guide also includes additional annexes containing tables and checklists to carry out withdrawals and maintain distribution records.

Finally, the new guide includes detailed instructions for writing retirement procedures and reports of memory sections.

RAC US Exam Question No 45

Question No 45:

A physician reports to a manufacturer that a patient was hospitalized with acute sepsis after treatment with an approved device. This side effect is not listed in the package insert. This event must be reported by the manufacturer to FDA no later than:

A. 5 calendar days.
B. 15 calendar days
C. 30 calendar days.
D. The next quarterly or annual report.

Answer: C

FDA Approves First PFO Occluder From St. Jude

The Food and Drug Administration (FDA) approved on Friday, Minnesota-based St. Jude Medical Amplatzer PFO occluder, qui est intended to reduce the risk of stroke in some patients who previously had a stroke.

The device - qui was sold more than a decade under a Humanitarian Device Exemption (HDE) target ago was voluntarily withdrawn by St. Jude in 2006 after the FDA concluded that her goal was greater than 4,000 patients population - is specifically for Tal patients who previously had a stroke that is believed to be caused by a blood clot passing through a small hole in the heart, expired called patent foramen ovale (PFO), and then traveled to the brain.

Since 2006 (when the device was withdrawn from the market), this is the first occluder heart FDA approved It is especially indicated to close the PFO to reduce the risk of a recurrent stroke in patients with cryptogenic stroke before, qui is a type of stroke When medical tests can not identify the cause.

"The Amplatzer PFO occluder provides a non-surgical method for physicians to close a PFO," said Bram Zuckerman, M. D., director of the Division of Cardiovascular Devices at the FDA Center for Devices and Radiological Health. "Purpose as the device labeling clearly states, patients should be carefully evaluated by a neurologist and a cardiologist to rule out other causes known of stroke and help ensure that PFO closure with the device will likely help reduce the risk of a recurrent stroke . "

How does it work

The Amplatzer PFO occluder is inserted through a catheter placed in a leg vein and advanced into the heart. Here it is implanted near the hole in his heart between top right chamber (right atrium) and the left upper chamber (left atrium).

FDA said that the duties of devices can not be used in patients with an infection of the heart valves other infections untreated gold, gold heart tumor or blood clot in the implant site. The device is contraindicated in patients with other abnormal connection between heart chambers them or in which the anatomy or blood clots could interfere with the ability to move the catheter.

Assays for approval

FDA concluded device that demonstrated a reasonable assurance of safety and effectiveness after a Assessed randomized 499 participants aged 18 to 60 years who were treated with an Amplatzer PFO anticoagulants more drugs and compared with 481 participants who were treated with blood anticoagulant drugs.

While the rate of new beats in both treatment groups was very low, the FDA Said, the study found a 50% reduction in the rate of new stroke in participants who use the PFO Amplatzer occluder more drugs that thin the blood compared to those only take blood-thinning medications.

RAC US Exam Question No 44

Question No 44:

A company's supplier of the active drug substance for the company's OTC drug product informs the company that the supplier will be moving their production of the drug substance from the current plant to a new manufacturing plant in another state in 6 months. The supplier states that all manufacturing processes will remain the same and the specifications will not change. The company intends to qualify the change suitably. How should the company report the change to FDA?

A. The change only needs to be reported in an annual report because the company will qualify the change and the supplier said the process and specifications won't change.
B. The change should be reported in a pre-approval supplement (e.g., CBE, CBE-30 or full pre-approval supplement) because it is a change to the drug substance manufacturing location.
C. The change does not have to be reported because it is an OTC drug.
D. Not enough information.

Answer: D

ICH Proposes Two New Guidelines

The International Council on Harmonization (ICH) announced two new guidelines, with a (M9) to support the recommendations provided Biopharmaceutical Classification of drugs, while the other (M10) is applied to the validation of methods of bioanalysis and study no analysis sample preclinical and clinical studies.

The two new plans guidelines are part of efforts to harmonize regional differences in policy documents and were finalized by the ICH October 7. The publication of the guidelines document design and business plans on Thursday to continue the international expansion of the board last summer.

Biowaivers based on the Biopharmaceutics Classification system: M9

This proposed classification system that analyzes biopharmaceutical guide computer (BCS) based biowaivers is designed to help reduce the number and types of bioequivalence studies to be carried out, according to the targeted area / regional.

Currently, pharmaceutical companies must follow different approaches, particularly the United States, European Union, Japan, Canada and the World Health Organization at all times offer different advice, but overlapping biowaivers bioequivalence.

"Biopharmaceutics Classification System (BCS) biowaivers based computer may be applicable to BCS Class I and III drugs BCS but biowaivers basis for these two are not recognized worldwide classes," says ICH. "Also even the classification itself may be different. This means that pharmaceutical companies have different approaches in different regions."

ICH said that the main problems can be divided into information to support classification of drugs in one of the four BCS classes, and supporting information for the resignation itself.

The recommendations of the ICH guideline addressed:

• Supporting data for classification, treats, including solubility and permeability
• The data support a waiver, which could involve establishing criteria limits for dissolution of the drug is considered BCS BCS class I or III drugs

ICH said it expects to reach Phase 2 of the approval process of the Directive in the first half of 2018 STI, while approving the document Step 4 is likely to occur in the second quarter 2019

M10: Bioanalytical Method Validation

The new directive will provide recommendations on scientific regulatory requirements for the development of bioassays conducted during and biologics.

ICH bioassay defined as the quantification of drugs and metabolites in biological matrices His such as plasma, serum, blood, urine or other body fluids, which are performed in clinical and non-clinical studies.

EU, US and Japan have different regulatory guidelines or draft guidelines for validation of bioanalytical methods (BMV), which creates obstacles to the mutual use of data from bioassays in all regions.

The main technical and scientific issues can be classified BMV According ICH as method validation, analysis of the study sample and other issues. The recommendations outlined in the guidelines address issues taking into account the characteristics of the analytical methods used in bioassays, for example, the test and the chromatographic ligand binding.

ICH expect the adoption of the document Step 2 in the second quarter of 2018 and the adoption of the document in step four years later.

RAC US Exam Question No 43

Question No 43:

Which of the following federal laws includes information about ANDA submissions?

A. Antibiotic Amendments of 1945
B. Durham-Humphrey Amendment of 1951
C. Drug Amendments of 1962
D. Drug Price Competition and Patent Term Restoration Act
Answer: D

FDA, EMA Officials: Regulators Must Adapt to Effectively Regulate Precision Medicine

To effectively regulate medicine precision, regulators have to adapt to other testing methods produce, for example officials Food and Drug Administration US (FDA) and the European Medicines Agency (EMA) and the former President of medicines in the UK and Healthcare products Regulatory Agency (MHRA).

The call is made in a commentary published in the journal Nature Reviews: Drug Discovery Friday former president MHRA Alasdair Breckenridge, Third EMA medical officer Hans-Georg Eichler and Jonathan Jarow FDA, which serves as Senior Medical Advisor to the Director of Evaluation Center and drug research.

Specifically, the review authors say regulators should take into account factors through the generation of five key areas to test patient involvement, cost, access and security in order to advance the medical accuracy before risk.

Advances in medicine authors precision have allowed an approach in which genetic heterogeneity in patients and diseases can be used to optimize treatment by determining that patients see the most benefit, or larger risks of a particular treatment.

However, they argue that these advances also present a number of challenges that regulators face in order to facilitate further progress.

challenges

The authors argue that the advent of precision medical threat shake "the basis for regulatory decision making for the past 50 years," the randomized controlled trial (RCT).

In the development of traditional medicine, they say, ACE is considered the gold standard to support regulatory approval. However, precisely in medicine, the authors argue these tests "may not be possible," particularly in cases where a patient population is divided into several, often small, sub-groups.

In light of this, the authors argue that regulators must resort to other forms of evidence, such as adaptive clinical trials or observational studies of the wide range of digital data available through "electronic health records (EHR), patient records and the future of media, it can be social ".

However, the authors state that the use of these alternative methods should not completely replace ECR, "In our opinion, observational studies based on real-world data should complement and not replace ECR, and sometimes that can be the only source of information available, "the authors write.

The authors also argue that regulators should continue supporting a wider patient participation in making regulatory decisions.

"Instead of seeing patients as a large heterogeneous group, medicine precision offers the possibility of working with smaller populations needs of patients, more consistent and better informed to emergencies and potentially only they expressed clearly," write the authors.

For regulators, they say, then keep patient preferences in mind and the reported research results in other therapeutic areas such as oncology, which has traditionally focused on patient clinical outcomes reported.

Regulatory Recon: FDA Approves Humira for 10th Indication;

Regulatory Recon: FDA Approves Humira for 10th Indication; Unproven Stem Cell Centers Spreading Across the US (1 July 2016)

Headlines: US

• The clinics offer stem cell therapies unproved proliferate throughout the US (MIT Technology Review)
• copay coupons was making more expensive drugs? (ProPublica)
• FDA promises faster to the drug GMP warning letters shorter (Gold $ Detailed)
• Breakthrough therapies: FDA Official calls for greater transparency in nominations, Denials (Focus) ($ scriptures)
• Doctors, hospitals Americans paid billions for the drug, device manufacturers: the government (Reuters) (MassDevice)
• Fireproof: CRISPR takes the next step (bill Harvard Health)
• FDA warns Two Chinese medicines manufacturers for data integrity violations (Focus)
• Call for action on toxic chemicals (New York Times)
• A final medical school in the United States, even killed the animals to teach surgery. But no more. (Washington Post)
• The FDA issued new guidance on project Elemental Impurities (Focus)
• FDA approves Humira for non-infectious intermediate and posterior adults Panuveitis few weeks before Biosimilars Advisory Committee (Press) (Advisory Committee meeting)
• The difference between manufacturing and design defects (medications and right of the device)
• Reshaping the FDA Purpose To prepare the 'avalanche' of products cancer of senior officials (Forbes)
• The consequences for public health of updating the FDA to label drugs abortion (bio issues and blog)
• FDA approval at the barricade Place trajectory of the novel Cholesterol Drug (CardioBrief)
• More US babies with birth defects related Zika reported by the health agency (Reuters)

Headlines: International

• The final text travel by first impressions (MedicalDevicesLegal)
• Brexit: Guests find positives scientists (Financial Times)
• action plan to combat illegal therapies with fresh cells (Swissmedic)
• Swissmedic informs the risk of cervical cancer in women treated with Remicade and biosimilars (Swissmedic)
• AstraZeneca sells the rights to two dermatological drugs LEO Pharma (Reuters)
• WHO urges manufacturers to submit products for malaria prequalification scheme (WHO)
• UK regulatory approvals for testing medications stops cabinet of India (Reuters)
• Vaccine anti-couple found guilty in the death of young children should post on Facebook decision (vice)
• database sheds light on pharmaceutical payments to British doctors (Financial Times)
• Doctors want more details on labeling of biosimilars (GABI)
• Health officials to prevent yellow fever Congo career disaster (Reuters)

USA .: Pharmacy and Biotechnology

• International Supply Chain Pharmaceutical endangered as never before: Summary Webinar (FDA Law Blog)
• Top 5 winners and losers from Q2 2016 Biotech (Forbes)
• KaloBios emerges from bankruptcy, raises $ 14M in the recapitulation (fierce)
• NIH refused to march again in regulation and Human Challenge National Academies (Genomics Law Report)
• efforts by the NIH application uses scientific methods to reduce HIV transmission from mother to child (NIH)
• FDA to keep the workshop of PPE (BioCentury)
• Family history major predictor of heart attacks in people with psoriasis (Reuters)
• Advaxis manufacturing, security and development of key cancer drugs efficacy (BioPharmaReporter)
• Mother throws Serve daughter and others with poorly understood non-profit (Forbes)
• Update: The first clinical trials with live biotherapeutic: chemistry, manufacturing and control of information; Guidance for Industry (FDA)
• Bioequivalence recommendations paliperidone palmitate; Draft Guidance for Industry; Availability (FDA)
• Vulvovaginal candidiasis: drug development for treatment; Draft Guidance for Industry; Availability (FDA)
• Recurrent cold sores: the development of drugs for the treatment and prevention; Draft Guidance for Industry; Availability (FDA

United States: pharmaceutical and biotechnology products: results of clinical studies, documents and Designations

• The first patients included in the study post-approval Orberá US intragastric balloon (press)
• Phase III data: Merck KGaA Erbitux plus FOLFOX improved results in RAS wild-type metastatic colorectal cancer ($ PharmaLetter-)

Medical devices in the US:

• Turning FDA guidance Panels Project NGS (GenomeWeb)
• FDA panel for approval Medite OTC Factors Diagnosis of Infectious Diseases (detailed $ Gray)
• Sparo laboratories obtains FDA approval for its application connected monitor lung function, Ala (mobihealthnews)

United States: Assortment and government

• Warnings other prescription drugs making Preemption (Drugs and right of the device)
• PerkinElmer Faces game over 'Lousy' drug testing devices (Law360a- $)
• FDA fifth biennial report situation Judicious use of antimicrobials in food-producing animals (FDA)
• Federal Judge blocks law on abortion Indiana (Reuters)

Upcoming Meetings and Events

• Calendar of the Advisory Committee of the FDA
• Webinar - Update on the program of medical devices FDA clinical trials - July 14, 2016 (FDA)
• Provisional agenda: Part 15 Audience: Draft Guidelines for the regulation of cells, tissues or cell or tissue products based on September 12, 2016 (FDA)

Europe

• EMA: Strengthening interaction with the academic world (EMA)
• BIOTRONIK wins CE Mark for EDORA adaptive pacemakers MRI (MassDevice)
• Factors UK MHRA regulatory human Expectations Directive is aligned with the United States ($ CLINIC-)
• SRS Medical wins CE Mark for prostate Key stent (MassDevice)

Asia

• China expects the market for organic products in the fastest growing in the next decade (BioSpectrum)

India

• Torrent Pharma acquires Glochem unit in Vizag (Economic Times)
• Biosimilars are too expensive and do little to improve accessibility: Doctors (Economic Times)

Australia

• Fees and charges: Summary - July 1, 2016 (TGA)

Canada

• Draft Guidance Document - Canceling a Drug Identification Number (DIN) and notification of interruption marketing (Health Canada)

Zika

• The Zika fears are growing among women in the US ($ WSJ-)

General health and other interesting items

• US Transgender Estimated population doubles to 1.4 million adults (New York Times)

RAC US Exam Question No 42

Question No 42:

Devices that are exempt from premarket notification are:

A. All Class I devices
B. Some Class I devices
C. Most Class I devices and some Class II devices
D. All Class I devices and some Class II devices

Answer: C

Regulatory Recon: Brexit Fallout: How Will MHRA and EMA Handle the Split?

Headlines: US

• Medivation Sanofi slams 'deceptive' coup says the saga continues fusion (fierce) (Medivation)
• Why US consumers are of two minds when it comes to pharmaceutical companies (Forbes)
• FDA defends response to the final data of Medtronic Infuse (MassDevice)
• FDA committee vote whether reductions in medication for diabetes cardiac death (Reuters)
• White House veto threat Zika Republicans plan funding (Reuters) (STAT)
• A new report urges the FDA to clarify the use of real-world testing (Focus)
• What is the composition of the private sector to help fight Zika? (Blog of Health Affairs)
• Vote "possible cures Senate in July, President HELP Says (Bloomberg)
• Senator renews its opinion Pharma Ties on federal commission (ABC)
• asks the defective filter leukocyte reduction device Recall (Focus)
• Why we inherit mitochondrial DNA only our mothers? (New York Times)
• They are scientists fraudsters deserve a second chance? (STAT)
• PwC medical cost trend: Behind the figures of 2017 (PwC)
• Four ways to address ethical tensions around accelerated approval of new prescription drugs (Health Affairs blog)

Headlines: International

• Brexit Conundrum: How MHRA Working with EMA Moving Forward (Focus) (Reuters) (ferocious) (Political)
• Statements Brexit (EFPIA) (ABPI) (leaders of EU states) (EP Vantage)
• full coverage of the referendum on the EU (The Telegraph) (BBC)
• EMA warns that tablets and oral suspension NOXAFIL have different doses and are not interchangeable (EMA)
• Adempas not for use in patients with pulmonary hypertension caused by idiopathic interstitial pneumonia (EMA)
• EMA recommends six new drugs, including cell therapy for approval (EMA)
• Gavi committed $ 27.5 million for the Pilot Program candidate against malaria WHO as more funds (focus) vaccine
• ISO pharmaceutical sector gets new tool for drug identification (ISO)
• Soon regulatory reform in Thailand? ($ PharmAsiaNews-)

USA .: Pharmacy and Biotechnology

• Biogen in negotiations to sell the stainless steel plant in 2,000L MA (BioPharma-Reporter)
• BIO opposes HB to reduce Biological Exclusivity From 12 to 7 years (Focus)
• Fill a prescription? You might be better to pay cash (KHN)
• FDA extends comment period hepatitis C Guidance for Development (FDA)
• FDA extends comment period for the guide special protocol assessment (FDA)
• Warning Letters FDA: Warning signs are still there (Compliance Monitoring Pharmaceutical)
• AstraZeneca expects to save FluMist in the United States with foreign data (Pink information- $)
• precious sets late stage pipelines in 2017 for some major events (EP Vantage)
• "Shop" CBER Role: Mounting In the Oncology Center of Excellence ($ RPM Report)
• Ocaliva ICER report is an important step forward, but too expensive ($ PharmaLetter-)
• Bye, Bye exenatide Teva to take GLP-1 agonist generic two years before AstraZeneca (Pink detailed $)
• FDA life of influenza vaccine Flublok (DSN) extends
• Why Amgen biotechnology Goliath is strong long-term investment (Street)
• Diabetes medications are expensive worth? (MedPage)
• FDA approves changes (vigabatrin) Sabril® REMS Program (Press)
• Vibrant and flourishing of Life Sciences Ecosystem Home North Carolina Wilmington (Forbes)
• Focus Therapy - product amyloidosis is still Alnylam answers (EP Vantage)
• Agreement to combat Zika virus stimulates NIH, CDC's efforts, but offers no FDA Review Dollars ($ Detailed Gray)
• Epizyme NABS agreement with Genentech combined tests for the candidate of the NHL (fierce)
• biosimilar rituximab in patients naive biological rheumatoid arthritis (GABI)
• Q & A with rare mom and CEO of biotechnology Karen Aiach (Boston Biz Journal)
• Pharma veteran Stephen Friend Bites health data supply Apple (Xconomy)

United States: pharmaceutical and biotechnology products: results of clinical studies, documents and Designations

• FDA Approves Expanded Label for Avycaz (Pharmafile) Allergan
• A new study shows Baxter telemedicine to increase access to care and reduce hospitalizations (Press) Perception

Medical devices in the US:

• GI Dynamics data reveals EndoBarrier final completion of the test (fierce)
• Returns the table FDA MDUFA high and low resolutions ($ detailed Gray)
• rheumatoid arthritis market approach 400m test $ 2,022 (BioSpectrum)
• A new blood test is Epic Sciences patients with PARP inhibitors (MedCityNews)
• The future of the devices devices (as we know them today) (MassDevice)
• Odors are the last frontier of intelligent sensors (MassDevice)
• The evaluation of rapid tests commercially rage reveals serious problems with the accuracy (RGT)
• The first step to navigate Regulatory combination products Road: pmoa (GxP Lifeline)
• Roche receives FDA approval for procalcitonin (PCT) analysis to help physicians to effectively assess the risk of sepsis and treat patients with sepsis (Press)

United States: Assortment and government

• Appeals court confirms the victory over Thermomedic Exergen (MassDevice)
• Apotex litigation Drops counterclaims Sham Litigation Neupogen and Neulasta biosimilar (Biological Blog)
• Barred experts, he says patients have Bayer IUD cases ($ Law360-)
• Florida Physician pleads guilty to fraud - years after complaints about their prescription (ProPublica)
• Janssen accuses media provider HyClone Celltrion patent violation (BioPharma-Reporter)
• scheduled for wrongful death in the bone cement Norian XR judgment (MassDevice)
• Pharma accuses payers use money to influence the monitoring of expenditure of the United States (fierce)

Upcoming Meetings and Events

• Calendar of the Advisory Committee of the FDA
• Webinar for final FDA guidance: Use of existing clinical data for extrapolation to pediatric uses of medical devices - August 8, 2016
• EMA: Workshop on testing of one arm (SAT) in Oncology - June 30, 2016

Europe

• France plans to invest € 670 million in genomics, personalized medicine (GenomeWeb)
• CLL drugs Genmab receives negative opinion from the EMA Commission (Pharmafile)
• Astellas UK ABPI suspended for "deception" and other cultural defects (Pharmafile)
• Belle rejects Celgene drugs to treat cancer of the blood (Pharmafile)
• EC grants marketing authorization for HIV Odefsey (EPR)
• AstraZeneca rejects Belle Tagrisso for lung cancer in the preliminary recommendation (Pharmafile)
• Most Borderline / Combo products to escape the high risk rating in the EU ($ detailed Gray)
• St. Jude wins the CE mark, launches algorithm SyncAV CRT (MassDevice)
• Trulicity gets the seal of approval for Welsh NHS (PharmaTimes)

Asia

• Takeda (TKPYY) Returns some molecules, the products of Amgen (AMGN) (Biospace)
• Zhejiang Hisun anti-influenza drug market Fujifilm China ($ PharmaLetter-)
• Turkey Price Pressure hits profits and market growth ($ PharmAsiaNews-)

India

• Glenmark FDA approval for new generic bags (BioSpectrum)
• Ranbaxy Dinesh Thakur Whistle Blower prosecution suggests strict laws to fix the pharmaceutical industry (Economic Times)
• FDI in the pharmaceutical industry: drug supply NLEM to keep for 5 years (Economic Times)
• pharmaceutical sector grow 20 percent in the relaxed FDI rules: Ananth Kumar (Economic Times)

Australia

• Centinel Spine Australia wins the game STALIF The implant (MassDevice)

Zika

• Without federal funding, counties are prepared to face alone Zika (Washington Post)

Other international organizations

• The reasons for the success of a company in the generic drug market Sudan (GABI)

RAC US Exam Question No 41

Question No 41:

A sponsor intends to submit a Special Protocol Assessment (SPA) request for a clinical trial that will form the primary basis of an efficacy claim in an NDA. Which of the following is TRUE?

A. The sponsor should submit the SPA request within 30 days following the start of the trial to expedite FDA feedback
B. An SPA provides an opportunity to focus on general drug development issues
C. The SPA request will be handled as a request for a Type B meeting
D. A sponsor can submit a revised protocol while the agency is reviewing an earlier version of the same protocol

Answer: D

EMA Tries to Assuage Professors on Assumptions Linked to Adaptive Pathways Pilot

The European Medicines Agency Director (EMA) Executive Guido Rasi and high medical Hans-Georg Eichler sent a letter Thursday to clarify some assumptions put in doubt by a group of nine teachers That criticize aspects of track program pilot adaptation of the agency.

Background

First announcement in March 2014, the EMA pilot program seeks to accelerate patient access to medicines for patients with urgent medical needs and then of approval for a strong indication if waiting That clinical data and the additional real world That is used for assess if treatment is really as effective as expected. From November 2015, the EMA has selected 19 proposals to participate in the pilot program.

As Rasi there Eichler describe the of pilot adaptation "way seeks to maximize the positive effect of new drugs balancing timely access to That patients might benefit more from a new drug with the need for adequate information sober evolution benefits there risks . "

Three companies participating include Bluebird Bio, in 2015. That said May that it intends to request the conditional approval for gene therapy to treat beta-thalassemia LentiGlobin BB305 greater; September biotechnology company said in 2015 Immunocore also plans to seek approval conditional Addition lead IMCgp100 biological treatment of patients with metastatic uveal melanoma, a rare and fatal disease with few options available treatment; there August 2015, Pluristem Therapeutics, indicate if found using the guide EMA in the pilot to develop a cellular therapy product That heads a sub-group of patients with critical ischemia of the above tips of look you expand to other sub-groups of patients.

assumptions

In May, nine professors of Oxford, Cambridge, the Medical School London Hygiene and Tropical National French Academy of Medicine, Royal College of Physicians, Toronto, York University, as well as other Barcelona and Italy Copenhagen raised questions with some serious regarding the assumptions made by the development in the EMA pilot ways of adaptation.

"The evidence if based in these cases does not seem very convincing for us and it seems that there is a lot of uncertainty in their potential operational implementation" teachers wrote, noting a list of eight General assumptions, including:

• "New" or "innovative" drugs and biologicals STI more effective and safer That That current
• Current mechanisms of regulation postmarket suffocate market and the market entry and innovation retardation and "new" drugs "Innovator"
• Enter the market on time is beneficial for society
• To that patients have run you will return in a Town medication if the new one just failing regulatory obstacles or later you have marketing and doctors That sober act such subsequent warnings based sober marketing or use restrictions damages
• EU information systems can support the adaptation process with impartial way (or minimally slanted) a day as observation data information
• His acceptable alternative outcomes
• The notion of That "something is better than nothing" is an acceptable principle

And although teachers think That said in the notion of the way of adaptation has "great potential to benefit society," That also claim scientific terms "should be used and correctly, there's possibility That is a misinterpretation. The term "real-world evidence" are a euphemism for observation tests, is That comes from observations That experimentation has always precede production of empirical evidence there. "

They also say that before the use of a means of adaptation leads to the authorization of a new drug, "any subsequent plane to generate evidence must be agreed there legally binding on all parties Following Agreed protocol. This is should you need to ensure of the surrender of accounts by substantial sums of public money they have been and will That invested invested ".
EMA response

In response to the letter, there Eichler Rasi offer point by point summary if agree with the teachers there try of provide more support for adaptation That way form of works and moving forward will work in.

In the event of the "new" or "innovative" drugs could give the impression of That these more effective or safer That existing STI treatments, EMA says that the terms (new and innovative) That said His synonyms his "neutral" respect of a product if innovative or new more or less is given effective or safe That existing treatments.

"The aim of the ways of adaptación're lead to potentially beneficial treatments for the group of patients right as soon as appropriate" officials wrote. "Therefore, evaluation probable of sober benefit the existing treatment options heading of" novelty "must precede has decision to follow paths of adaptation. Note the EMA received 60 requests from sponsors its pilot program pathways of adaptation course, but we selected only 20. Our goal is to '' choose the winners, in the interest of patients No. unmet medical needs. "

And although officials clarified That "real-world evidence" art used by EMA "to refer you evidence from records, electronic health records (EHR) and insurance data, whether in studies specific observation or monitoring continuous use, the risks benefits there, "they also say That" his conscious That observational studies have produced results not reproducible or contradictory, however, also have done other methodologies, including RCTs [randomized clinical trials therefore the concept. pathways of adaptation makes Insisting in the necessity of harvesting planned the observation data, where it may be necessary to supplement trials testing. This collection is based on the advice of experts there Methodologic input of multiple stakeholders. on the other hand, repeated cycles of generation is quickly testing to refine or emphasize decisions when necessary right past. "

And as to be able to change a patient's drug again when the new one Town could become less effective, EMA recognizes the difficulties such a scenario.

"We are conscious disappointing experiences in the past, in fact, doctors have not always acted on post warnings to damage the sober marketing and use restrictions" Rasi there Eichler write. "However, recent experience with flat designed Prospectiva risk sample That is if properly managed, restrictions / warnings can be successful."

In the event of That "something is better than nothing" officials also make clear That "would be unethical and incompatible with the regulatory role of" selling hope rather than aid "[Bianco and Sipp Nature 2014. 510, 336- 337]. This is why special way of adaptation makes Insisting in early enough relevant evidence of patient benefit there a strict control of patient benefit after launch ".

RAC US Exam Question No 40

Question No 40:

The Food and Drug Administration Modernization Act (FDAMA) established two types of formal early collaboration meetings. Which of the following is one of those meetings?

A. PDP meeting
B. Agreement Meeting
C. Pre-IDE meeting
D. Type A meeting

Answer: B

FDA Kicks Pharma, Device Rule Finalizations Down the Road, Past Obama’s Presidency

The US federal government is notoriously slow to establish new rules and apply them. However, the Food and Drug Administration (FDA) is taking this slow to a new level for a variety of potentially controversial proposed and final rules, some of which have persisted for decades.

On Friday, the Department of Health and Human Services (HHS), which operates under the FDA released its semi-annual inventory of actions for the development of regulations under development, which lists a fraction of FDA standards or work propose or End and many of which have been delayed without explanation.

Security Subsequent Marketing

One of the first examples of such a prolonged delay a final rule is facing new requirements for reporting on the post-market drug products for human use and biological security. First proposed in 2003, the FDA now says HHS will need until 2017 last March under President Barack Obama in office, to take the final action of the rule, which further harmonize definitions and reporting formats with used by the International Conference on harmonization.

The final rule also add or revise the existing reporting requirements for drugs and biologics, to review certain deadlines for reporting and suggest further changes to improve the quality of safety reports received by the FDA.

Another rule, which has been persistent since the regulation of proposed rulemaking (NPRM) comment period ended in 2009 (and, last fall, the FDA said it would be completed two months ago in April) clarify how to describe the information requirements post-marketing combination products (combinations of a drug, device and / or biological) security. The completion of this rule is not even on the list of HHS 'on Friday.

Furthermore, it is not included in the list of HHS 'is the decision of the FDA to delay the completion of its rules on the labeling of generic drugs, which also deals with the post-marketing and widely covered approach to security. It is also expected that this rule to come post-Obama in April 2017 (after it was proposed in 2013, open to comments in 2015 and should be published in February). The house was still trying to force the FDA to rewrite the rule.

Test Devices

On the device side, the FDA proposed a rule proposed in February 2013 to ensure clinical investigations conducted outside the United States in support of an application for premarket approval, the request for exemption from humanitarian system, an application for exemption investigational device or submission notification for marketing will be carried out in accordance with good clinical practice.

According to the FDA, in the fall of 2014 that the rule that the device could be completed in January 2015, but now lists HHS (in the agenda published on 9 June) that it intends to terminate the rule sometimes the last month.

Another Delay

Meanwhile, another rule FDA first proposed in 2006, reorganize, consolidate, clarify and amend the rules governing what companies must register establishments and list of medicinal products for human use, there including some biological drugs and animal drugs , it has been postponed until next month times.

It also goes on sale in July 2016: the change in FDA regulations for good current manufacturing practices to clarify and strengthen requirements for the label, color, dedication and design of medical gas containers and closures (first proposed in 2006).

"Despite regulatory requirements and industry standards of medical gas, there have been repeated incidents in which the cryogenic vessels of harmful industrial gases have been linked to the systems of medical oxygen supply in homes hospitals nursing and then administered patients. These incidents resulted in death and serious injury, "says the FDA." there have also been several incidents with medical gas bottles high pressure that led to death and injury to patients.

These changes, as well as current regulations are intended to ensure that the types of incidents that occurred in the past are produced, as well as other types of medical gases and potentially fatal accidents not predictable in the future. "
The FDA also expected next December to propose regulations to define and implement certain legal conditions under which aggravate products are eligible for exemption from certain requirements. FDA had planned to make the proposal on 31 March.

Also Unregistered

Nor on the agenda of HHS is the rule proposed by the FDA to allow inclusion in labeling of the symbols of autonomous devices established via a standard developed by an organization of national or international standards, provided that these symbols are explained in the unit label. The rule also revises the rules on labeling of the unit in order to allow the use of the statement symbol "prescription only" on the label.

The rule was proposed in 2013 and expected to be finalized (last fall) 31 Mar 2016.

The complete list of rules and possible dates, many of whom rejected without any transparency or explanation, as Senate Republicans questioned how the FDA uses the project and the final orientation regular, rather than through d regulatory Action

RAC US Exam Question No 39

Question No 39:

In the development of a revised manufacturing procedure, which of the following is a critical step in ensuring that the product manufactured would not be adversely affected by this change?

A. Procedure qualification
B. Product verification and/or process validation
C. Quality control
D. Conformance inspection

Answer: B

Advanced Therapies: Stakeholders Call for EMA Changes on Regulations, Manufacturing

The European Medicines Agency (EMEA) on Friday issued a report with concerns and regulatory: modifications described by developers, manufacturers and investors in therapy products Medicines (Drugs Advanced Therapy), including gene therapies, products tissue engineering therapies and somatic cell, a UN meeting last week.

Note interpenetration What recurring themes include the need for early interaction with regulators and policy, a larger Executives Transparency larger Managers harmonization between Member States of the EU regulation ATMP, What and a proposal for Industry Being EMA calling more flexible converter Advanced Drug Reservations therapy manufacturing.

"While no decision has been bis prize, European Commission, national authorities and the EMEA and have a conversation Start From The feasibility of these proposals," said EMA.

Context

In the EU regulatory framework Verter Advanced Drug therapy was established by Regulation (EC) No 1394/2007, which has been in force since 2008.

Allows automatic regulation of the UN access to a central line for authorization of advanced therapy products in the EU and created the Committee for Advanced Therapies, which experience gathered and established, among other processes, classification procedures are Certification converter rescuer The early development of advanced therapy.

An EMA convened a meeting covering advanced therapy 27 May, 2016, attended ONT University and researchers, incubators and NGOs Consortium, and NGO representatives Patients and health care, small and large pharmaceutical companies, investors, Technology assessment Bodies health, national competent authorities (ANC) and the European Commission

Manufacturing Proposal

"A mayor proposal at the meeting was to licensing requirements reflect Vierten Special Unique Drugs for manufacturing Advanced Therapy," Specifies rapport. "For example, participants take into account the manufacturing ATMP can take place in different sitios and to pour certain products, further ethical Production may need to take place near the head Involvement What is all the sites concerned. - it including hospitals - would be needed to maintain the manufacturing license. "

However, with the lack of harmonization of the United Nations, only the level of the National Motor Vehicle some Member States allow hospitals hold a manufacturing license, interested parties "a request to the authorities to more flexible requirements pendant principles the years phases of maturation development. specific proposals for adaptation needs under gone up tone based products cells a included (no products handled significantly) could be If you take into account as falling on the border between the grafts and Drug Advanced therapy activate below.

"Similarly, more pragmatic approach should be used converter meet requirements Process Validation converter Many advanced therapy, given the difficulty to produce the required amount of batch conversion to CHARACTERISTICS pharmaceuticals," Specifies rapport.

Other proposals Promotion manufacturing technologies include (for example for manufacturing header and closed systems) and manufacturing models (for example, manufacturing decentralization), which would require more flexibility.

"Regulatory bodies could also stimulate the development of production sites, such as service, the use of small and medium enterprises (SMEs) and other funds, so that capacity is available converter multipart develop different advanced therapy medicinal" said the relationship. "These suggestions were considered timely, given the European Commission What is revising the Directive on GMP requirements Pour advanced therapy and will soon launch the public consultation."

GMO

Another important issue in the meeting focused on a genetically modified (GMO), which had a cool reception in the EU.

Interested parties have indicated that GMO directive (directive 2001/18 / EC) "are not designed specifically for your drugs and aggravated lacunar infarcts compared AEC is by discrepancies in the application in the Member States. From May Different requirements among States members, the integration of assessment of GMOs in the authorization of clinical trials of the United Nations is a challenge, especially in the context of multicenter clinical trials. "

Developers of these gene therapies have called for greater uniformity is suggested as a step premiere, the establishment of a central repository in Spanish, a list of requirements and deadlines for the assessment of GMOs in all Member States.

"Some speakers also called for: modifications directive has the OMG itself," says A good relationship. "Another area that could benefit from further harmonization concern cells and tissues as materials manufacturing EMPLEA premieres Drug Therapy Advanced with contradictory interested Applicant rational application over tissues and cells (Directive 2004/23 / EC) and other relevant laws" .

Other issues

Weighing also called for greater harmonization A "facilitate the movement of materials between the tiles with different requirements (inside and outside the EU) starting and reduce the burden of having a re-tester cells and tissue Before starting the manufacture of drugs . Advanced therapy the test puts itself can then focus on: aspects of the nature of the Advanced therapy Medicinal Products ".

The industry also asked for excipients A SPECIFIC guidelines and a system master file fluent Marketing authorization with respect to excipients and content premieres.

In addition, stakeholders have proposed new tools for Development (organelle eg transferor of extrapolation, modeling / simulation, biomarkers, etc.) to meet the needs of clinical no.

"On the question f risk-benefit ratio product development, stakeholders noted that the current practice is mainly focused on the risks and the call of the additional UN accent is put on the expected advantages, but realistic, particularly when patients have incurable diseases or treatments when appropriate default font "added the relationship.

"If advanced therapy should fulfill its promise to provide innovative treatments for patients, regulators should feed regulatory environment that the UN Promoting Innovation protect public health and, ultimately, the bill easily accessible when patients to appropriate new treatments" says interpenetration.

RAC US Exam Question No 38

Question No 38:

Which of the following federal laws includes information about ANDA submissions?

A. Antibiotic Amendments of 1945
B. Durham-Humphrey Amendment of 1951
C. Drug Amendments of 1962
D. Drug Price Competition and Patent Term Restoration Act

Answer: D

Expedited Compassionate Use for Investigational Drugs Coming Soon, FDA Says

The fight for patient access to experimental drugs via the process of compassionate use Should get a lot Easier in the near future, as (FDA) of the US Food and Drug Administration nonprofit arm, the Reagan-Udall Foundation (RUF), is working to build an online navigator to help Patients and physicians better Understand esta process.

Compassionate use, Also known as expanded access, is a process by Which doctors That May request the FDA Allows the use of an experimental drug outside of a clinical trial for a patient with a illness or no other treatment options terminal. But the process can be Initiated if the drug development company and the patient's treating physician AGREES to move forward and make the request of the FDA.

Speaking at the expanded access Navigator Public Workshop Monday, Richard Moscicki, MD, deputy director of the center for science operations at the FDA's Center for Drug Evaluation and Research (CDER), Said the agency will finalize a plane (more than a year after it was Proposed) "very, very soon" That Could reduces the time required doctors to fill out the forms for requests for access extended to 45 minutes, Which would be a significant change the previous form, Which, in some cases, Took over 100 hours to complete.

The agency plans to release three Present guidance documents related to the compassionate use and expanded access soon.

RUF Navigator

As Nancy Beck, Ph.D., Acting Deputy Director of the Reagan-Udall Foundation, Told Focus last month, the new online browser will help physicians Provide (as it is They Who must apply to expanded access) with a more complete picture of how to make a single Investigational New Drug (IND) application of the patient; the role of the FDA, manufacturers and Institutional Review Boards in the process; the principles of access expanded the eligibility criteria and decision making based on risk; the challenges of translating the results of early research on clinical outcomes; and Perhaps Most Important, a repository of information on the FDA and manufacturers' policies, Procedures and points of contact.

Jonathan Jarow, MD, Senior Medical Advisor to the Director of Center for CDER, Said at the workshop on Monday That the vast majority of applications are expanded access for non-emergency applications and IND single emergency,, Although the new browser will only process non INDs - Emergency INDs emergency as Requested by phone or e-mail and Requested by the FDA Usually in a few hours or less a day.

But the application process is heavy and difficult to Currently navigate, Michael Grimley, M.D., associate professor at the University of Cincinnati Department of Pediatrics, Said, offering an example of compassionate use browser Already used. He and others Also NOTED That the FDA Should make data available on expanded access requests, in terms of health Especially outcomes of These applications, but not for the browser details Were approved Monday.

Alison Bateman-House, PhD, MPH, MA, a postdoctoral fellow in medical ethics Rudin Division at New York University Langone Medical Center, Said the point that she did not think the FDA Should build "yet another independent resource" that requires financing, marketing and a chance for "a confusing message." She Said She Believes Also there is an opportunity to Improve clinicaltrials.gov, Which contains lists of all ongoing clinical trials execution in the United States, and She Said She Thinks Should be the first place Patients Should go for more information.

"Is there a reason why a browser Should not Be Executed by the FDA or the RUF? The FDA's budget is a perennial issue, and all the money spent running the browser shouldnt be taken from the Already Inadequate budget of the agency," wrote Bateman-House in comments on the browser project "the same Should be Said for human resources in the agency -. if a new navigation service is created, let rely on new recruits, not be added to the job description of staff Already loaded But the main argument Against Having a browser, in particular. one built around a web page, short of the FDA or the RUF is logistics. We do not want a webpage That has Thousands of links to web pages of the company That are inactive and must be maintained. We do not want a web page with lists of phone numbers That come out of service When Small Businesses are acquired by larger ones. We do not want a webpage That promises assistance for That causes frustration. We Already have one of them, and it is called ClinicalTrials.gov. "- See more at:

Right to try

The need for Such a browser comes as 28 states since 2014 Have passed "Right to Try" laws to circumvent process to help compassionate use FDA terminally ill Patients or Those With No treatment option to access potential drugs still in clinical trials. But what is unclear is acerca These new laws help Whether They whos access to experimental treatments Patients.

The Goldwater Institute, Which pushed for the passage of esta legislation as a way around What They believe is an abundance of red tape at the FDA, Said in recent weeks That I is aware of doctors and Patients an experimental drug Because of access right to try the legislation, none of the doctors, Although Patients or are ready to go out.

Senator Ron Johnson (R-WI) Also Introduced a bill last week That would not allow federal the government to interfere With state laws and to protect Businesses from new Commitments and stop FDA to use data on Patients WHO take medications Obtained under new laws to delay or negatively impact the FDA approval.

This bill Makes reverberations Monday as Goldwater representative Said That the institute factotum believes the federal government shouldnt be Involved in the process of compassionate use and shouldnt be a problem for doctors, Patients and Developing societies, new drugs.

However, Richard Plotkin, Vice President of the Max Cure Foundation, for many children Explained That and Adults with incurable diseases, experimental drugs use can reduce Their quality of life in end months and does not Their Provide all the advantages.

An AIDS activist Past Explained During the public comment portion of the workshop That in the 1980s, When Patients Requested the use of new treatments against HIV and AIDS, "We blame everything on the FDA, and it is not Their fault, it is Often the fault of companies "no company wants to block the development of the drug Because of a compassionate use.

Industry

Indeed, Often, requests for early access to a drug in development are refused Because Patients do not meet established criteria Certain by the company running the trial.

The difficulty for many of These Patients WHO have either run out of treatment options (or did not Have any to begin with) is not getting the FDA to sign-off on the use of the investigational drug (FDA signs off more than 99% of applications received expanded access), but to get the companies running clinical trials to allow New Patients to have access to experimental treatment while the trials are ongoing or earlier Begins the trial.

And companies, some of Which are just an expensive treatment Developing, have to make Concessions to the New Demands of Patients, Which can disrupt a trial Potentially, as in the past Happened.

Richard Klein, director of FDA Patient Liaison Program, Monday NOTED That an internal review of 10,000 Expanded Access INDs found only two trials That Have Been interrupted due to adverse events Observed in Patients received drugs WHO as part of requests for compassionate use.

However, the reverse can be true Present. At Least one drug, ganciclovir, used to treat Which is a viral infection of the eye That blinds many AIDS Patients, was approved based Solely out of use of the drug on a compassionate basis.

And one of the Reasons Why is so ready to sign on almost all requests for expanded access it Receives is Because all the work of serious things with getting a development company or an experimental biologic drug to sign on compassionate use a patient has Already Been terminated by FDA filing an expanded access request was Submitted to the FDA, Beck Told us earlier.

RAC US Exam Question No 37

Question No 37:

If a device failure is occurring with greater than expected frequency and investigation of the problem indicated improper use by the end user, which of the following should occur?

A. The labeling is revised
B. The product is recalled
C. The product is redesigned
D. A "Dear Doctor" Letter is issured

Answer: A

Expedited Compassionate Use for Investigational Drugs Coming Soon, FDA Says.

The struggle for patient access to experimental drugs through compassionate use process should get much easier in the near future, since (FDA) arm nonprofit US Food and Drug Administration of the Reagan Foundation Udall (FRU) is working to build an Internet browser to help patients and physicians better understand this process.

Compassionate use, also known as expanding access, is a process by which doctors may request that the FDA allows the use of an experimental drug outside of a clinical trial of a patient with a terminal illness or no other options treatment. But the process can be initiated if the company's drug development and patient's treating physician agrees to go ahead and make the request of the FDA.

Speaking at expanding access Navigator Public Workshop Monday, Richard Moscicki, MD, deputy director of the center for science operations at the FDA Center for Drug Evaluation and Research Drug (CDER), said the agency would finalize a plan (more than one year after proposed) "very, very soon" that could reduce the time physicians required to fill out forms for applications extended to 45 minutes access, which would be a significant change in the above manner, which, in some cases, it took more than 100 hours to complete.

The agency also plans to launch three guidance documents related to the compassionate use and greater access soon.

RUF Navigator

As Nancy Beck, Ph.D., Acting Deputy Director of the Reagan-Udall Foundation, this approach last month, the new online browser will help provide physicians (and they are the ones that should apply to expanded access) with a more complete picture of how to make a single application Investigational new drug (IND) of the patient; the role of the FDA, manufacturers and Institutional Review Boards in the process; the principles of access expanded the eligibility criteria and decision-making based on risk; the challenges of translating the results of early research on clinical outcomes; and perhaps most importantly, a repository of information on policies, procedures and contact points of the FDA and manufacturers.

Jonathan Jarow, MD, superior to the Center Director CDER medical adviser, told the workshop on Monday that the vast majority of applications access applications was extended are not emergency and IND emergency call, although the new browser only process non IND IND -Emergency as requested by phone or email and usually requested by the FDA in a few hours or less a day urgency.

However, the application process is currently heavy and difficult to navigate, Michael Grimley, M. D., associate professor of the University of Cincinnati Department of Pediatrics said, offering an example of compassionate use browser already used teacher. He and others also noted that the FDA should make available data on applications for expanded access, particularly in terms of health outcomes of these applications, but not for browser data were approved on Monday.

Alison Bateman-House, PhD, MPH, MA, a postdoctoral fellow in medical ethics Division Rudin at New York University Langone Medical Center, said the point he did not think the FDA should build "another independent resource" that requires funding, marketing and an opportunity for "a confusing message." she also said he believes there is an opportunity to improve clinicaltrials.gov, which contains a list of all ongoing clinical trials execution in the United States, and she said she believes should be the first patients should go for more information.

"Is there any reason why a browser should not be executed by the FDA or the RUF? The FDA budget is a perennial problem, and all the money spent running the browser should not be taken from the already insufficient budget of the agency, "Bateman-House wrote in comments on the project browser" the same is true of human resources at the agency -. if a new navigation service is created, let depend on the new recruits, not they added to the job description of staff already loaded But the main argument against having a browser, in particular. one built around a web page, below the FDA or RUF is logistics. we do not want a webpage which has thousands of links to web pages of the company that are inactive and should be maintained. we do not want a website with a list of phone numbers that come out of service when small businesses are acquired by larger ones. we do not want a page web that promises assistance for that cause frustration. We already have one, and is called ClinicalTrials.gov. "- See more at:

Right to try

The need for a browser, such as has 28 states since 2014 have passed "right to try to" laws to circumvent the process of compassionate use FDA to help terminally ill patients or those who have no treatment option for access potential drugs still in clinical trials. But what is clear about these new laws is whether they actually help patients access to experimental treatments.

The Goldwater Institute, which promoted the passage of this legislation as a way to avoid what they believe is a lot of paperwork at the FDA, he said in recent weeks that he is aware of physicians and patients an experimental drug because adequate access to treat legislation, although none of the doctors or patients are ready to leave.

Sen. Ron Johnson (R-WI) also introduced a bill last week that would not allow the federal government to interfere with state laws and to protect businesses from new commitments and stop FDA to use data patients taking drugs obtained under the new laws to delay or negatively affect FDA approval.

This bill makes reverberations Monday as representative Goldwater said the institute believes the federal government should not be involved in the process of compassionate use and should not be a problem for doctors, patients and the development of societies, new medicines.

However, Richard Plotkin, vice president of the Max Cure Foundation, explained that for many children and adults with incurable diseases, experimental drug use can reduce their quality of life in their last months and does not provide all the benefits.

An AIDS activist also explained during the public comment portion of the workshop in the 1980s, when patients require the use of new treatments for HIV and AIDS, "We blame everything on the FDA, and not the fault of they often it is the fault of companies "no company wants to block the development of the drug because of a compassionate use.

Industry

In fact, often, requests for early access to a drug developing refused because patients do not meet certain criteria established by the company in charge of the study.

The difficulty for many of these patients who have either run out of treatment options (or did not have any to begin with) is not getting the FDA to logoff in the use of investigational drug (signs of the FDA more than 99% of applications received expanded) access, but to get companies to conduct clinical trials to allow new patients have access to experimental treatment, while the trials are ongoing or previous trial begins.

And companies, some of which are only developing an expensive treatment, they have to make concessions to the new demands of patients, which can potentially disrupt a trial, as happened in the past.

Richard Klein, director of the Liaison Program Patient FDA said Monday that an internal review of 10,000 IND expanded access found only two trials have been discontinued due to adverse events observed in patients receiving drugs as part of applications compassionate use.

However, the opposite can also be true. At least one drug ganciclovir, which is used to treat a viral eye infection that blinds many AIDS patients, was approved based solely out of your use of the drug on a compassionate basis.

And one of the reasons why it is so ready to sign on almost all requests for expanded access receiving is because all the work of serious things with getting a development company or an experimental biologic drug to sign on compassionate use a patient who has already been completed by the FDA to submit an application for expanded access was submitted to the FDA, Beck told us before.

RUF still accepting written in the expanded browser.

RAC US Exam Question No 36

Question No 36:

While reviewing complaint files for a drug-eluting stent, a single entity combination product, it was noticed that an adverse event had occurred and a patient was hospitalized for two additional days. Such an adverse event was a foreseeable event and the mechanical features of the stent contributed to the occurrence. As a regulatory professional, your decision regarding the adverse event report would be?

A. Report to FDA in a 15 Day Alert Report
B. No action is needed as ADE reporting is only required for serious and unexpected adverse events; this ADE is expected so no reporting is needed
C. Report to FDA in Form 3500A (MDR) within 30 days
D. Report to FDA within 7 calendar days

Answer: C

FDA Finalizes Guidance on Postmarket Device Surveillance

The Food and Drug Administration (FDA) has finalized the guidance Friday (five years after the draft guidance was released) for device manufacturers in their interpretation of the law with regard to post-marketing surveillance of some devices class II or class III.

The guide is presented as the Office of the Government Accountability Office (GAO) said last October that 90% of post-marketing FDA studies have ordered in the past seven years were classified as inactive, although some of these studies, they have added other ongoing studies.

More recently, the FDA sent a warning letter to Argo Medical Technologies, based in Israel after its failure to carry out such monitoring studies after marketing your device to help people with spinal injuries spinal.

Background:

The Federal Food, Drug and Cosmetic (FD & C Act) gives the FDA the authority to require manufacturers to conduct a post-marketing devices of a certain class II or Class III monitoring, although the FDA says -Marketing that subsequent monitoring is not a substitute for obtaining necessary information before marketing to support 510 (k), PMA, HDE, PDP or approval, or to grant the order de novo.

In addition, the Act Food and Drug Administration Safety and Innovation (FDASIA) further clarified that the agency can issue a post-market prescription at the time of the approval of the device or at any time thereafter surveillance. Under what is called a "522 order" FDA may appeal to companies to carry out such studies postmarketing surveillance.

The order requires the manufacturer 522 begins subsequent marketing surveillance within 15 months after the date on which the order was issued.

Once comments on the draft guidance include AdvaMed industrial group criticizes the vagueness of the project, while Johnson & Johnson sought more information on the types of devices that will not be subject to such surveillance studies.

New Address:

According to the FDA, the guide is designed to help manufacturers of devices subject to section 522 orders post-marketing surveillance, providing:

•  An overview of the section of the law that allows the FDA to require such studies;
•  Information on how to order complete 522 obligations; Y
•  Recommendations on the format, content and review of post-marketing monitoring plans presentations.

In general, management, said the law allows the FDA to order "prospective post-marketing surveillance for a period of 36 months unless the manufacturer and the FDA agreed to extend this period or if there is no agreement, after completion of the differences. "

However, the law also authorizes the FDA to require a period of prospective follow-up of more than 36 months compared with a device that has an important use in the pediatric population, although the FDA said that in these cases the intention to work with the manufacturer to determine the time of placing a pediatric study.

The FDA also provides examples of situations that may arise subsequent to marketing issues, including:

•  Where the FDA to better understand the nature, severity or frequency of suspected problems identified in reports of adverse events or in the published literature.
•  For more information on device performance in clinical practice in the real world.
•  For the treatment issues or long-term safety and efficiency with rare implants and others who have contributed premarketing testing of more limited information. "For example, prior to marketing a device evaluation may have been based on indirect markers. Once the device is actually marketed, post-marketing surveillance may be appropriate to evaluate the effectiveness of the detection device or treatment the disease or condition, rather than the surrogate mother. data collected by the post-marketing surveillance can include failure rates or failure of a device for use incidents long term or resulting latent effects of use of the device "says the FDA.
• To better define the relationship between the problems and the devices when serious adverse events unexpected and inexplicable occur after a device is marketed, if there is a change in the nature of the serious adverse events (eg gravity) or if there an increase in the incidence of serious adverse events.

Upon issuance of an order 522, manufacturers must also submit a progress report every six months during the first two years of surveillance and every post provisional marketing, from the date of approval of the monitoring plan or year other date agreed separation, says the FDA.

Monitoring plans:

The FDA also states that follow evaluate all proposed plans to determine whether they will lead to obtaining useful data to answer questions surveillance or security.

Consequently, the FDA may issue a decision following letters:

1. Charter is not acceptable, that is when a submission is considered administratively complete (CDRH provides a checklist to determine if a request is administratively complete in the address).

2. Approval Letter

3. Minor Deficiency letter, citing small specific deficiencies that must be addressed by a plan to be approved;

4. Major Deficiency Letter, which would include serious deficiencies to be addressed;

5. Letter disagreement, which means that the FDA has determined that it is unlikely that the monitoring plan will result in obtaining useful data to answer questions post marketing. This letter also directs the manufacturer to provide a new declaration to answer questions post marketing.

"If the manufacturer does not agree with the FDA on the content of the plan or if the plan is rejected, describes the options for an appeal" in the law, the FDA said, noting that these include requesting a meeting with the Director the Office of the Office of surveillance and bio-metrics FDA requesting an internal review of the decision of the FDA 21 CFR 10.75, for an informal hearing, or to request a review by the Panel of medical Devices Advisory solution Committee dispute medical devices.

If a manufacturer does not meet the requirements for plan approval of post marketing surveillance and begin post-marketing surveillance in the 15 months following that order of 522, the agency said that inaction can result legal action