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