USFDA has released GUIDANCE for Quality Attributes of *CHEWABLE TABLETS

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*CQAs of CHEWABLE TABLETS (CT)*
USFDA has released GUIDANCE for Quality Attributes of *CHEWABLE TABLETS*
According to this latest guideline, FDA has recommended sponsor/applicant should also incorporate following CQAs:
*1. PATIENT ACCEPTABILITY*
Acceptable Taste, Mouthfeel & Aftertaste With-
*2. HARDNESS / BREAKING FORCE / CRUSHING STRENGTH*
Hardness of CTshould be kept  low  (i.e.  <12 kp).
A higher hardness  value  (e.g.,  >12 kp)  may  be  considered if  justified.  An example  of  such justification could be  demonstrating  significant disintegration and/or  reduction in hardness  of  such  tablets  following  brief  i.e.  30 seconds  in-vitro exposure to simulated saliva (1 mL) before chewing to ensure patient compliance without  GI  obstruction (choking in throat / blocking bowel movement) in the case if patient swallow tablet without chewing due to high hardness
*3. CHEWING DIFFICULTY INDEX*
CDI is a value derived from the relationship between two methods used for measuring tablet strength: diametral compression (diametrical tensile strength) and flexural bending (flexure tensile strength test), to ensure patient compliance without damage to teeth or dentures
CDI should be also evaluated before & after in-vitro exposure to 1 mL of simulated saliva for 30 seconds
*4. DISINTEGRATION & DISSOLUTION*
CT should  typically  meet the  same  disintegration  and dissolution specifications  as _IR  tablets_. In vitro DT & Dissolution testing  should be  conducted on  _intact_ chewable  tablets since  _it is  possible  that some  patients  might swallow  the  tablets  without chewing_.
*5. Others*
If functional coated particles are present in chewable tablet then applicant has to ensure its functionality even after chewing tablets.
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FDA takes steps to foster greater efficiency in biosimilar development by reconsidering draft guidance on evaluating analytical studies

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FDA takes steps to foster greater efficiency in biosimilar development by reconsidering draft guidance on evaluating analytical studies

Today, the agency withdrew the draft guidance, “Statistical Approaches to Evaluate Analytical Similarity,” issued in September 2017. The draft guidance, if finalized as written, was intended to provide advice for sponsors developing biosimilar products regarding the evaluation of analytical similarity between a proposed biosimilar product and a reference product. After considering public comments that the agency received about the draft guidance, the FDA determined it would withdraw the draft guidance as it gives further consideration to the scientific and regulatory issues involved.

June 21, 2018

Media Inquiries

  Angela Stark
  301-796-0397

“Biosimilars foster competition and can lower the cost of biologic treatments for patients, yet the market for these products is not advancing as quickly as I hoped. I believe that the FDA can do more to support the development of biosimilars, as well as promote the market acceptance of these products. As the cost to develop a single biosimilar product can reach hundreds of millions of dollars, it’s important that we advance policies that help make the development of biosimilar products more efficient, and patient and provider acceptance more certain,” said FDA Commissioner Scott Gottlieb, M.D. “One of the central aspects of biosimilar development and approval is the analytical studies performed to demonstrate that a biosimilar is highly similar to the reference product. We’re taking a fresh look at our draft recommendations for evaluating analytical studies in order to ensure our guidance takes into consideration the most current and relevant science. We’ll continue to work directly with biosimilar developers on their programs as we develop new draft guidance in this area. By supporting the more efficient development of biosimilars over the long term and helping reduce barriers to bringing these products to market, we can help ensure patients get access to affordable, safe and effective treatment options.”

Today, the agency withdrew the draft guidance, “Statistical Approaches to Evaluate Analytical Similarity,” issued in September 2017. The draft guidance, if finalized as written, was intended to provide advice for sponsors developing biosimilar products regarding the evaluation of analytical similarity between a proposed biosimilar product and a reference product. After considering public comments that the agency received about the draft guidance, the FDA determined it would withdraw the draft guidance as it gives further consideration to the scientific and regulatory issues involved.

Comments submitted to the docket addressed a range of issues that could impact the cost and efficiency of biosimilar development, including the number of reference product lots the draft guidance would recommend biosimilar developers sample in their evaluation of high similarity and the statistical methods for this evaluation. The FDA believes that in better addressing these issues in the future, the agency can advance principles that can promote a more efficient pathway for the development of biosimilar products.

The agency intends to issue future draft guidance that will reflect state-of-the-art techniques in the evaluation of analytical data to support a demonstration that a proposed biosimilar product is highly similar to a reference product. The goal is for future draft guidance to address potential challenges faced by biosimilar sponsors in designing studies that are intended to demonstrate that a proposed biosimilar product is highly similar to a reference product, including consideration of appropriate methods to analyze analytical data to account for potential lot-to-lot variability of the reference product. Future draft guidance also will focus on providing appropriate flexibility for sponsors in order to help spur the efficient development of biosimilars without compromising the agency’s rigorous scientific standards for evaluating marketing applications for biosimilars.

The FDA continues to encourage sponsors of proposed biosimilar products to discuss product development plans with the agency, including the evaluation of analytical data intended to support a demonstration that the proposed biosimilar product is highly similar to a reference product. The FDA will continue to provide development-stage advice to sponsors of proposed biosimilar products or proposed interchangeable products through formal meetings and other interactions with sponsors.

The FDA will communicate publicly when new draft guidance is issued in relation to the evaluation of analytical data between a proposed biosimilar product and a reference product.

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FDA warns of fraudulent and unapproved flu products

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FDA warns of fraudulent and unapproved flu products

As part of the U.S. Food and Drug Administration’s ongoing efforts to protect consumers from health fraud, the agency is reminding consumers to be wary of unapproved products claiming to prevent, treat or cure influenza, or flu. This year’s severe flu season raises new concerns about the potential for consumers to be lured into buying unproven flu treatments, and even worse, buying counterfeit antivirals online from websites that appear to be legitimate online pharmacies. Continue Reading

FDA updates the label of Tasigna to reflect that certain patients with a type of leukemia may be eligible to stop treatment after sustained response

FDA updates the label of Tasigna to reflect that certain patients with a type of leukemia may be eligible to stop treatment after sustained response

Discontinuation in treatment marks a first in chronic myeloid leukemia 

The U.S. Food and Drug Administration today updated the product label for the cancer drug Tasigna (nilotonib) to include information for providers about how to discontinue the drug in certain patients. Tasigna, first approved by the FDA in 2007, is indicated for the treatment of patients with Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML). With today’s updated dosing recommendations, patients with early (chronic) phase CML who have been taking Tasigna for three years or more, and whose leukemia has responded to treatment according to specific criteria as detected by a test that has received FDA marketing authorization, may be eligible to stop taking Tasigna. Continue reading

 

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FDA clears stereotactic radiotherapy system for use in treating breast cancer

FDA clears stereotactic radiotherapy system for use in treating breast cancer
Today, the U.S. Food and Drug Administration cleared a new noninvasive stereotactic radiotherapy system intended for use in treating cancer in breast tissue. Continue reading.

December 22, 2017

Summary

FDA clears stereotactic radiotherapy system for use in treating breast cancer

Release

Today, the U.S. Food and Drug Administration cleared a new noninvasive stereotactic radiotherapy system intended for use in treating cancer in breast tissue.

“With today’s clearance, patients will have access to a treatment option that provides greater accuracy in delivering radiation therapy to breast tumors while saving surrounding breast tissue,” said Robert Ochs, Ph.D., acting deputy director for radiological health in the Office of In Vitro Diagnostics and Radiological Health in the FDA’s Center for Devices and Radiological Health.

Radiation therapy is an important treatment option for cancer patients. Approximately 60 percent of all cancer patients will be treated with some form of radiation therapy. During radiation therapy, tumor cells are killed when their DNA is damaged by the radiation being absorbed into them. While radiation therapy has the potential to kill tumor cells, it can also damage healthy tissue around the tumor.

The GammaPod system is intended for use in the noninvasive stereotactic delivery of a radiation dose to a portion (partial volume) of the breast in conjunction with breast conserving treatment. During the procedure, radiation is delivered to specific areas of the breast. The GammaPod has not been shown to be as effective as whole breast radiation therapy (WBRT) and is not intended to replace WBRT.

The GammaPod system is a dedicated stereotactic radiation therapy technology designed to treat breast cancer. GammaPod uses thousands of focused beams of radiation from 36 rotating radioactive Cobalt-60 sources in combination with a two-layer, vacuum-assisted cup that immobilizes the breast to achieve a more accurate delivery of radiation. The GammaPod design to immobilize the breast during treatment provides the benefit of minimizing the radiation dose to the surrounding healthy tissues in the breast, heart and lungs.

For today’s clearance, the FDA reviewed scientific evidence including a clinical study of 17 patients that tested the feasibility of accurately delivering the prescribed dose to the breast tumor while minimizing radiation to the healthy tissue. The clinical evidence supports delivering the prescribed dose to the breast tumor with minimal radiation-induced side effects such as skin redness or erythema.

The GammaPod system was reviewed through the premarket notification 510(k) pathway. A 510(k) is a premarket submission made by device manufacturers to the FDA to demonstrate that the new device is substantially equivalent to a legally marketed predicate device.

The FDA granted clearance of the GammaPod to Xcision Medical Systems, LLC.

Statement from FDA Commissioner Scott Gottlieb, M.D., on newsteps to advance medical device innovation and help patients gain faster access to beneficial technologies

Statement from FDA Commissioner Scott Gottlieb, M.D., on newsteps to advance medical device innovation and help patients gain faster access to beneficial technologies

Enabling patients and providers to have efficient access to new and innovative medical products that meet the FDA’s gold standard for safety and effectiveness is a core part of our mission. We’re advancing these goals as part of the Medical Innovation Access Plan that I announced earlier this year. While we’ve unveiled parts of that plan already, we’ll be releasing its full detail shortly. As one part of that effort, we’re announcing some additional steps we’re taking right now to promote beneficial medical device innovation. Continue reading.
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Report from the EMA-FDA QbD pilot program

Image result for QBDReport from the EMA-FDA QbD pilot program

In March 2011, the European Medicines Agency (EMA) and the United States Food and Drug Administration (US FDA) launched, under US-EU Confidentiality Arrangements, a joint pilot program for the parallel assessment of applications containing Quality by Design (QbD) elements.

The aim of this program was to facilitate the consistent implementation of QbD concepts introduced through International Council for Harmonisation (ICH) Q8, Q9 and Q10 documents and harmonize regulatory decisions to the greatest extent possible across the two regions.

To facilitate this, assessors/reviewers from US and EU exchanged their views on the implementation of ICH concepts and relevant regulatory requirements using actual applications that requested participation into the program. The program was initially launched for three years. Following its first phase, both agencies agreed to extend it for two more years to facilitate further harmonization of pertinent QbD-related topics.

The program officially concluded in April 2016. During this period, the agencies received 16 requests to participate. One submission was rejected because the approach presented was not limited to QbD applications, and another application was not reviewed because it was never filed by the applicant.

In total, two Marketing Authorisation Applications (MAA)/New Drug Applications (NDA), three variation/supplements and nine scientific advice applications were evaluated under this program. One MAA/NDA was assessed under the parallel assessment pathway, with the rest following the consultative advice route. Based on the learnings during the pilot, FDA and EMA jointly developed and published three sets of Question and Answer (Q&A) documents.

These documents also addressed comments from the Japanese Pharmaceuticals and Medical Devices Agency (PMDA), which participated as an observer, offering input to further facilitate harmonization. The objective of these Q&A documents was to generate review guides for the assessors/reviewers and to communicate pilot outcomes to academia and industry.

Additionally, these documents captured any differences in regulatory expectations due to regional requirements, e.g. inclusion of process validation information in the dossier. The following topics were covered in each of the three Q&A documents: –

Q&A (1) published on Aug 20, 2013 included the following topics: (a) Quality target product profile (QTPP) and critical quality attributes (CQA), (b) Criticality, (c) Level of detail in manufacturing process descriptions, and (d) QbD for analytical methods1 –

Q&A (2) published on Nov 1, 2013 on Design Space Verification, that included definition, presentation, justification (including potential scale-up effects) and verification of design spaces both for active substances and finished products2 –

Q&A (3) published on Dec 19, 2014 included the following topics: (a) Level of detail in the dossier regarding Risk Assessment (RA), (b) Level of detail in the dossier regarding Design of Experiments (DOE) and Design Space3 R

 

Additionally, the FDA-EMA pilot provided the agencies an opportunity to harmonize regulatory expectations for the following precedent-setting applications that were reviewed under the consultative advice pathway: – The first continuous manufacturing (CM) based application submitted to both agencies.

Based on the learnings from this application, the following areas related to CM were harmonized: batch definition; control of excipients; material traceability; strategy for segregation of nonconforming material; real-time release testing (RTRT) methods and prediction models; and good manufacturing practice (GMP) considerations for RTRT, validation strategy, models, and control strategy. – A post approval supplement that included a broad based post-approval change management plan/comparability protocol.

Both agencies were harmonized on the expected level of detail in the protocol and considerations for implementation of a risk based approach to evaluate the changes proposed in the protocol. In line with the scope of the QbD pilot program, joint presentations of key findings were publically presented and discussed with stakeholders at different conferences.

These included the Joint EMAParenteral Drug Association QbD workshop4 organized in 2014 which also included participation from FDA and PMDA.

Overall, it is concluded that, on the basis of the applications submitted for the pilot, there is solid alignment between both Agencies regarding the implementation of multiple ICH Q8, Q9 and Q10 concepts. The FDA/EMA QbD pilot program opened up a platform for continuous dialogue which may lead to further communication on areas of mutual interest to continue the Agencies’ support for innovation and global development of medicines of high quality for the benefit of patients.

Both agencies are currently exploring potential joint activities with specific focus on continuous manufacturing, additional emerging technologies, and expedited/accelerated assessments (e.g. PRIME, Breakthrough). Additionally, EMA and FDA are hosting experts from each other’s organisations to facilitate dialog and explore further opportunities.

References: 1. EMA-FDA pilot program for parallel assessment of Quality-by-Design applications: lessons learnt and Q&A resulting from the first parallel assessment http://www.ema.europa.eu/docs/en_GB/document_library/Other/2013/08/WC500148215.pdf

2. FDA-EMA Questions and Answers on Design Space Verification http://www.ema.europa.eu/docs/en_GB/document_library/Other/2013/11/WC500153784.pdf

3. FDA-EMA Questions and answers on level of detail in the regulatory submissions http://www.ema.europa.eu/docs/en_GB/document_library/Other/2014/12/WC500179391.pdf

4. Joint European Medicines Agency/Parenteral Drug Association quality-by-design workshop http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/events/2013/12/event_detai l_000808.jsp&mid=WC0b01ac058004d5c3