Author name: suruchi

Home About Blogs Enlightenment Inventions Photography Press Writings Contact X FDA Accepts Our Filgrastim Biosimilar Application By Niazi April 21st, 2024 0 Comments Discussion It has been a long journey; I founded the company and grew it into a fully integrated, pure-play, US-based company biosimilars company. Our 351(k) application was accepted by FDA for review (Adello Biologics); several more products are underway, now that we have a great team in place. There is no substitute to learning it the hard way. Over next few weeks, I am giving several talks to share my experience and also plans on how to expedite development of biosimilars. niazi@niazi.com and www.niazi.com Our Recent Posts Hubri July 2, 2024 Letter to Kamala Harris July 2, 2024 Share it On:Copyright 2024 © Niazi | Developed By AssaptR

Home About Blogs Enlightenment Inventions Photography Press Writings Contact X Novel Approaches Of Demonstrating Bioequivalence By Niazi April 21st, 2024 0 Comments Discussion A Public Meeting was held by FDA on 17 July 2017 on Administering the Hatch-Waxman Amendments[1]: Ensuring a Balance Between Innovation and Access. The comments below were submitted as Comments on this Public Meeting Reference 1k1-8yz7-ttos The Drug Price Competition and Patent Term Restoration Act (Public Law 98-417) of 1984 has made drugs more accessible. One of the key elements of the Act is the demonstration of bioequivalence of generic products containing drugs that are not eligible for bioequivalence waiver. Bioequivalence testing originated in the early 1970s with the ±20 rule. According to a separate study, “the shortcomings of this approach were immediately evident, since such a criterion would theoretically allow the parameters of generic product A to differ from the reference (innovator) product by +20%, while allowing the parameters of generic product B to differ from the reference product by -20%. The net difference between the generic products A and B would then be as much as 40% and, therefore, beyond the limits of therapeutic equivalence as originally conceived.”[2] In response, the FDA adopted a powered approach in the early 1980s. However, both approaches were discontinued by the FDA in 1986 because of public concern about bioequivalence and were subsequently replaced by the 90% CI approach in 1992, which remains the current criteria for bioequivalence decisions.[3] How closely the FDA sticks to this guidance is seen in the current bioequivalence testing guidance that states[4] that “We recommend that applicants not round off CI values; therefore, to pass a CI limit of 80 to 125 percent, the value should be at least 80.00 percent and not more than 125.00 percent.” [The upper limit of 125.00 percent comes from the strict 20.00% limit on each end (100/125=0.80)]. Why is there a need to follow this limit so strictly? According to the FDA[5], this range is based on a clinical judgment that a test product with bioavailability that falls outside this range should be denied market access. A 90% CI is used, since a 5% statistical error is allowed at both the upper and the lower limits. Therefore, the total error is 10%, generating the 90% CI. Understanding a predefined range is much more intuitive and easier to grasp than the reality of multiple PK parameters having to fit within a narrow CI. Now that the FDA has initiated its efforts to bring innovation to the Act, I would like to suggest that we re-examine the current the guidance on how to meet the BA and BE requirements set forth in 21 CFR part 320 as they apply to dosage forms intended for oral administration or non-orally administered drug products when reliance on systemic exposure measures is suitable to document BA and BE (e.g., transdermal delivery systems and certain rectal and nasal drug products). A suggestion for this change comes in The Patient Protection and Affordable Care Act (Affordable Care Act), signed into law by President Obama on March 23, 2010, that amends the Public Health Service Act (PHS Act) to create an abbreviated licensure pathway for biological products that are demonstrated to be “biosimilar” to or “interchangeable” with a FDA-licensed biological product. This pathway is provided in the part of the law known as the Biologics Price Competition and Innovation Act (BPCI Act)[6]. Under the BPCI Act, a biosimilar product is a biological product that is approved based on a showing that it is highly similar to a FDA-approved biological product, known as a reference product, and has no clinically meaningful differences in terms of safety and effectiveness from the reference product. What I am proposing is that we add the consideration of “clinically meaningful” to the bioequivalence testing of generic products, instead of using a fixed range of bioequivalence, to make this test more relevant. An FDA analysis shows that for the submissions between 1996 to 2001 for highly variable drugs, the mean AUC varied by 10%,[7] while the range allowed was 20%. Such statements can be misleading since they do not represent the granularity of data where even 10% variability can be too much and the situations where a 30% variability will still yield a clinically equivalent product. The FDA has recently begun discussion of narrow therapeutic index (NTI) drug bioequivalence[8]. Four new draft guidances are posted online recommending replicate design studies for NTI drugs including tacrolimus, phenytoin tablet, levothyroxine, and carbamazepine. The movement from “one size fits all” to product-specific standards is a sign of the maturation of the generic drug program. However, the emphasis in these recent approaches has been on the statistical design and not the margin that remains an iron-clad acceptance criterion. Replicate design helps reduce the size of the study, yet it does not add a clinically meaningful component to the study. I am recommending that the FDA allow developers to justify margin that they can demonstrate to provide a clinically meaningful comparison that may include novel in vitro testing methods or any other approaches that have not been explored mainly because of the fixation of complying with the equivalence margins as currently mandated. The roots of this recommendation come from the 21 CFR Part 320[9] wherein: “(e) Bioequivalence means the absence of a significant difference in the rate and extent to which the active ingredient or active moiety in pharmaceutical equivalents or pharmaceutical alternatives becomes available at the site of drug action when administered at the same molar dose under similar conditions in an appropriately designed study.” Since the site of drug action as cited here is in most case not known and rarely sampled, blood level PK studies were suggested as a surrogate, not a primary test, to demonstrate bioequivalence. In fact, given that blood level studies add substantially more variability in the assessment of bioequivalence, better means of establishing bioequivalence are the in vitro means wherein a generic product is more likely to show a discernible difference. One such means is demonstration of thermodynamic equivalence for which a Citizens Petition is already filed and open

Home About Blogs Enlightenment Inventions Photography Press Writings Contact X On Leaving the Company I Founded Adello Biologics By Niazi April 21st, 2024 0 Comments Discussion More than a decade ago, I founded Therapeutic Proteins Inc (now Adello Biologics) with a vision of making affordable biosimilars in USA. Today, Adello has products under approval by the FDA, and uniquely that first therapeutic protein manufactured using a single-use technology that I invented.  I wish to thank the angel investors, who gave me a head start, Jim Berens who placed his trust in my passion to help me build clean rooms, Steve Einhorn for providing the first large funding, and Chirag, Chintu and Tushar Patel, who helped me complete a fully integrated GMP facility in Chicago. It was a challenging ride, but we came through. Now Adello is in good hands with Peter and Mike and it is about time that the baton is transferred to new hands, who are much better at handling supply chain issue than I could. I leave the company I founded with an experience of a lifetime and an immense sense of humility. Our Recent Posts Hubri July 2, 2024 Letter to Kamala Harris July 2, 2024 Share it On:Copyright 2024 © Niazi | Developed By AssaptR

Home About Blogs Enlightenment Inventions Photography Press Writings Contact X A Critical Analysis of the FDA Guidance on Clinical Immunogenicity Testing of Insulin By Niazi April 21st, 2024 0 Comments Discussion The Section 7002(e)(4) of the Biologics Price Competition and Innovation Act of 2009 (BPCIA) requires that on March 23, 2020, an approved application for a biological product under section 505 of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 355) will be deemed to be a license for the biological product under section 351 of the PHS Act (42 U.S.C. 262). In anticipation of the licensing of insulin products under the BPCIA in 2020, the FDA has recently issued draft guidance on the clinical immunogenicity testing as part of the biosimilarity determination for biosimilars. To be licensed as a biosimilar, an application submitted under section 351(k) must contain, among other things, information demonstrating that the biological product is biosimilar to a reference product based upon data derived from analytical studies demonstrating that the proposed biosimilar is highly similar to the reference product, animal studies, and a clinical study or studies (including the assessment of immunogenicity and pharmacokinetics or pharmacodynamics); the FDA has the discretion to determine that an element described in section 351(k)(2)(A)(i)(I) is unnecessary. The FDA has concluded that, because insulins are relatively smaller-sized biologics that are structurally uncomplicated and have few post-translational modifications, they can be well-characterized analytically to leave little residual uncertainty regarding the risk of clinical impact from immunogenicity. The FDA further states that there is minimal or no clinical relevance of immunogenicity with insulin product use. The FDA determination comes from: Recommendations from the European Medicines Agency, which published a revised guideline in 2015 that no longer recommends a clinical immunogenicity study to support a biosimilar marketing application Decades of insulin products’ listings in FDA’s Approved Drug Products with Therapeutic Equivalence Evaluations (the “Orange Book”) with little concern for any meaningful clinical impact of immunogenicity on the safety or efficacy of insulin product use Decades of clinical experience with approved insulin products, including the lack of a correlation between immunogenicity and safety or effectiveness as reflected in approved product labeling for insulin products, and published literature indicating a poor correlation between immunogenicity in insulin-treated patients and clinical impact on safety and efficacy Public comments received by the FDA in response to the May 2019 public meeting, “The Future of Insulin Biosimilars: Increasing Access and Facilitating the Efficient Development of Biosimilar and Interchangeable Insulin Products” Better purification methods developed over time that have reduced the concerns about the risk of clinical immunogenicity Based on the premise presented above, the FDA determined that the current analytical tools used to evaluate quality attributes for insulin products can support a comprehensive analytical comparison that leaves little residual uncertainty regarding immunogenicity and that has minimal or no risk of clinical impact from immunogenicity. In such cases, a comparative clinical immunogenicity study would generally not be necessary to support the licensure of a proposed biosimilar or interchangeable product. The FDA now recommends that, to secure licensing under the 351(k), the developers will need to provide: Adequate chemistry, manufacturing, and control information to fulfill product quality-related requirements described in 21 Code of Federal Regulations 601.2, including a validated manufacturing process, and to support an inspection of the facility that is the subject of the application (ie, a facility in which the proposed biological product is manufactured, processed, packed, or held) A comprehensive and robust comparative analytical assessment between the proposed insulin product and the proposed reference product demonstrating that the proposed insulin product is “highly similar” to the reference product A comparative clinical pharmacology study between the proposed insulin product and the reference product that provides a time-concentration profile and a time-action profile over the duration of action of each product based on reliable measures of systemic exposure and glucose response (eg, glucose infusion rate), using a euglycemic clamp procedure or another appropriate test An immunogenicity assessment justifying why a comparative clinical study to assess immunogenicity is not necessary to support a demonstration of biosimilarity; this justification may reference other data and information in the application, eg, a comparative analytical assessment with very low residual uncertainty. Where differences in certain impurities or novel excipients give rise to questions of residual uncertainty related to immunogenicity, these should be adequately addressed and may not require clinical testing. Of greatest significance is a clear direction to developers that a comparative clinical immunogenicity and efficacy study is not required if the analytical assessment supports high similarity. Further, the design of clinical pharmacology study need not be complicated if the duration of action is determined based on reliable measures of systemic exposure and glucose response. The draft guidance on clinical immunogenicity testing for insulin products is indeed a historic event: a bold step by the FDA that shows a determination that there is a need to bring into market lower-cost alternates to the reference products if the clinical studies that contribute to the majority of cost and time are not required. I anticipate FDA issuing similar assessments of other biological products like the cytokine inhibitors that too fall in a similar category of highly characterizable products, and particularly the products that have little immunogenicity risk, like the filgrastim. An ending thought remains: Why did it take the FDA 4 years to accept the thesis that is already practiced in European Union? Perhaps it was the inevitable pressure to make insulins more affordable. The fact is that, unless we have this level of clarity, it will be difficult to make biosimilars more accessible. Our Recent Posts Hubri July 2, 2024 Letter to Kamala Harris July 2, 2024 Share it On:Copyright 2024 © Niazi | Developed By AssaptR

Home About Blogs Enlightenment Inventions Photography Press Writings Contact X A Critical Analysis of the Final Guidance on Demonstrating Interchangeability of a Biosimilar With Its Reference Product By Niazi April 21st, 2024 0 Comments Discussion Introduction The FDA has issued its final guidance on demonstrating interchangeability of a biosimilar with its reference product to assist sponsors in showing that a proposed therapeutic protein product is interchangeable with a reference product for submitting a marketing application or supplement under section 351(k) of the Public Health Service Act (PHS Act) (42 U.S.C. 262[k]). In formulating the final guidance, the FDA had considered the comments provided in response to the invitation by the FDA when it posted draft guidance. There were 53 comments posted by the deadline of March 20, 2017, and these came from diversified sources, including a private consumer who suggested that the Affordable Care Act not be repealed to a physician suggesting the use of suffix to biosimilars, to organizations like Coalition of State Rheumatology Organizations, which suggested that a case-by-case approach is not satisfactory and that no extrapolation should be allowed unless a product is tested in patients for all conditions. The Parenteral Drug Association emphasized the role of human factor studies and need for new regulations to provide comparison; Johnson & Johnson opposed extrapolation and recommended that testing be done in each condition, and that the labeling of biosimilar products declare when they are not interchangeable. Apotex sought clarification on the meaning of immunogenicity and if a product is given at 2 doses; would it mean 2 separate studies? The Biosimilars Council questioned whether studies will be required in conditions that are not claimed or how extrapolation will be allowed; AbbVie and other reference product companies disagreed with almost everything in the draft guidance and suggested that the FDA does not have the authority to go around the Biologics Price Competition and Innovation Act (BPCIA) requirements. In addition to the above comments from stakeholders, there were several publications that pointed out the shortcomings of the FDA guidance in establishing biosimilarity and interchangeability. There were 2 citizen petitions and several testimonies that questioned the FDA guidelines on biosimilars. The final guidance on interchangeability took into account several recommendations that were made by me, including using biodistribution in pharmacokinetic (PK) and pharmacodynamic studies (PK) studies, de-emphasizing clinical efficacy studies, and allowing sponsors to propose novel approaches to licensing of biosimilars and interchangeable biologics. It is important to reiterate that the FDA guidelines are not binding, and for the same reason, they do not preclude a sponsor from making an alternate proposal to the FDA, even though most sponsors would hesitate to do so. In this paper, I am suggesting that sponsors exercise their privilege to question the guidance and fully exploit the opening provided by the FDA for alternate proposals. Overarching View ESSENTIAL DEFINITION Section 351(k)(4) of the PHS Act provides that an interchangeable product must be “biosimilar to the reference product” and additionally, it “can be expected to produce the same clinical result as the reference product in any given patient.” For a biological product that is administered more than once to an individual, the risk in terms of safety or diminished efficacy of alternating or switching between use of the biological product and the reference product is not greater than the risk of using the reference product without such alternation or switch. A sponsor may choose to file a new application for approval as a biosimilar or an interchangeable biosimilar; there is no requirement that the product must be first approved as a biosimilar. To demonstrate biosimilarity, the sponsor can refer to previously submitted data, but only after consultation with the FDA, since the FDA now requires that, in addition to the data required for demonstration of biosimilarity, developers should also include analyses of any differences in the expected PK and biodistribution, toxicities of the product, immunogenicity risk of the product, and any other factor that may affect the safety or efficacy of the product in each condition of use and patient population for which the reference product is licensed. The use of “differences in the expected” in the above description creates a dilemma for the sponsors: there is no such expectation, since the sponsor knows that the product is a biosimilar and therefore presents “no clinically meaningful difference” from the reference product in a situation in which the sponsor is filing for a change of status to the interchangeable product. Even in those situations in which the sponsor is making its first filing and anticipates receiving an interchangeable status, there are no expectations of differences, and none can be scientifically anticipated. A more appropriate language would be “any clinically meaningful observed differences.” I am suggesting that the sponsor make this assumption regarding the expectations of the FDA. It is noteworthy that the FDA has recognized biodistribution in PK studies as a critical parameter; I had provided details of the clinical importance of the distribution volume parameter during a testimony given to the FDA recently. More details on this subject are provided in the section on Advice to the FDA, below. STATUTORY LANGUAGE The BPCIA states that an interchangeable product “can be expected to produce the same clinical result as the reference product in any given patient,” and this statutory language forms the basis of an allowance made in the final guidance. The statement, which cannot be modified by the FDA, can be construed to state that a biosimilar interchangeable product is “capable of demonstrating the same clinical result as the reference product in any patient”; the description of the test subject as “any patient” may also mean “not necessarily the patient treated for a disease for which the product has been approved.” As a result, sponsors may use a patient population that is different from that used to support licensure of the reference product, or in healthy subjects, provided the sponsor also gives adequate scientific justification to support the fact that the study population is adequately

Home About Blogs Enlightenment Inventions Photography Press Writings Contact X Biosimilars: No Rationale for Clinical Efficacy Testing By Niazi April 21st, 2024 0 Comments Discussion The US FDA got its charter to approve biosimilar biologics in 2009,[i] once the patents expire on new biological drugs; the goal of this charter for the FDA is to expedite the entry of biosimilars to increase accessibility: availability and affordability. The FDA has issued ten regulatory guidance documents[ii], and it redrafted[iii] one pivotal guidance on analytical testing after the author pointed out inconsistencies in the original guideline.[iv] As of July 2020, the FDA has approved 27 biosimilar products, comprising 19 monoclonal antibodies, seven cytokines, and one fusion protein since the first biosimilar was approved in 2005. Data for one cytokine has not been reported by the FDA yet. The regulatory submissions that lead to these approvals provide a keen insight into how the developers are approaching the development and how the FDA is assessing the submitted data.  There are four key studies pivotal to the approval of biosimilars comprising analytical assessment, nonclinical pharmacology, clinical pharmacology, and clinical efficacy. The 26 approved products submitted over 1100 analytical similarity, 96 animal pharmacology, 42 in vitro/ex vitro pharmacology, 52 clinical pharmacology, and 32 clinical efficacy studies.  There was no consistency in the number of studies submitted for the same molecule; five adalimumab biosimilars submitted 31-105 studies; five trastuzumab biosimilars submitted 48-111 studies, and four infliximab biosimilars presented 48-80 studies. Dozens of animal toxicology studies were rejected by the FDA as being irrelevant. However, none of the accepted animal toxicology studies failed. All PK/PD studies also passed, a few requiring repeat testing due to the choice of wrong population acceptance criterion.  A few clinical pharmacology studies had to be repeated to meet acceptance criteria due to inappropriate choice of the study designs. Finally, no clinical efficacy study failed, and two products were approved without clinical efficacy testing. Biosimilarity is a judgment made by the regulatory agencies for a product that has a “clinically meaningful difference” with its reference product. There are several fundamental arguments against the use of clinical efficacy testing to establish biosimilarity. The FDA requires stepwise testing wherein the development reaches the clinical efficacy testing only after confirming analytical similarity, animal toxicology, and clinical pharmacology assessment. And even then, the FDA must identify a “residual uncertainty,” before extensive clinical efficacy testing is suggested. Since all except two products conducted clinical efficacy testing, it was not made clear by the FDA what was the “residual uncertainty?” Were these studies conducted voluntarily by the developers to support their marketing program, or they were required by the FDA remains uncertain. However, if we can establish that these studies are not necessary, then conducting these studies will be considered unethical for a variety of reasons. One strong argument against conducting clinical efficacy testing comes from the experimental design that is mostly a noninferiority testing requiring that the developer establish a range of differences between the biosimilar and the reference product as clinically acceptable. While the proponents of clinical efficacy argue that this acceptance criterion can be established on clinical judgment, the choice, nevertheless, remains arbitrary. The proof of this arbitrariness comes from the analysis of studies conducted on the same molecule with a highly variably acceptance criterion. The mode of action of biological drugs often leads to a broad dose-response relationship confounding any real difference. The assessment of clinical efficacy is straightforward in the case of a new drug, where a placebo control quickly establishes efficacy vis-à-vis the observed side effects. Further compounding the lack of utility of clinical efficacy comes from the current practice of testing a product in just one of several indications, leaving doubt, if the efficacy can be extrapolated among the indications. However, the FDA allows extrapolation of all indications, even if the testing is conducted in just one indication. Does this allowance leave much to doubt about the safety and efficacy of a biosimilar? However, requiring testing in all indications will defeat the purpose of the pathway to approve biosimilars leading to cost that may even be higher than developing a new drug. The validity of clinical efficacy testing can be challenged on a logical ground as well. So far, none of the efficacy testings failed provided the biosimilar product met all other stepwise similarity testings. Was it because all products were biosimilar, or the efficacy testing was not sensitive enough to identify differences? A more pressing concern arises if the FDA accepts the results of efficacy testing to overcome the lack of similarity in analytical, nonclinical, and clinical pharmacology assessment. Given that there will never be data available to judge relative safety and efficacy, the risk of approving products that are not biosimilar gets higher.  One factor that adds significant variability to clinical data is the selection criterion of the study population. In the case of oncology antibody testing, it is almost impossible to find naïve subjects or patients with similar prior treatment; additionally, the clinical markers cannot be established given the peculiarity of the disease for each patient. All of these observations establish a premise that it is not possible to create a testing plan that can be reasonably rational. In the case of monoclonal antibodies, the mechanism of action is generally known, allowing the use of in vitro/ex-vitro methods to compare efficacy; these tests can be more robust and reliable than the study of clinical responses in patients, particularly in the case of anticancer drugs, where it is almost impossible to secure a naïve patient population or even a sufficiently large number of population and the high variability of response; do these studies bring added confidence to the safety and efficacy of the biosimilar product? Responsible regulatory guidance should require minimal testing needed to assess the safety and efficacy of a product, and if clinical efficacy testing is not useful, these studies should be discouraged and not just added as supplementary proof. The same holds true for animal toxicology testing that is ruthlessly conducted by developers

Home About Blogs Enlightenment Inventions Photography Press Writings Contact X Response From the FDA on My Letter to Dr. Stephen Hann on COVID-19 Issue By Niazi April 21st, 2024 0 Comments Discussion Dear Dr. Sarfaraz: Thank you for your recent email to Dr. Stephen Hahn, Commissioner of Food and Drugs, concerning the development of vaccines to prevent coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2. We appreciate your interest in this important topic.  The FDA recognizes the urgent need to develop vaccines to prevent COVID-19, and we are working collaboratively with industry, federal, domestic, and international partners to accelerate this work. We are committed to working with these partners to efficiently advance the development of safe and effective vaccines intended to prevent COVID-19. The nature of a particular candidate vaccine and its intended use may impact the specific data required to advance the development and licensure of that vaccine. Please note that the goal of these development programs is to demonstrate safety and effectiveness of a vaccine for the prevention of COVID-19. We are committed to working with these partners to efficiently advance the development of safe and effective vaccines for COVID-19. We also recognize that transparency around the FDA’s review, evaluation and decision-making with respect to COVID-19 vaccines is likely to impact public confidence in these vaccines and we are committed to being as transparent as possible throughout the process. When making decisions about Emergency Use Authorization (EUA) or licensure of COVID-19 vaccines, we will apply the relevant statutory and regulatory requirements in the Federal Food, Drug, and Cosmetic Act and the Public Health Service (PHS) Act. FDA staff involved in the evaluation of vaccines are highly qualified scientists and physicians who are knowledgeable about the complexity of vaccine development. The same FDA scientists and physicians who routinely advise sponsors on vaccine development programs, manufacturing considerations, and assessment of safety and effectiveness of all vaccines are the experts who are focused on the work related to COVID-19 vaccine development. As with all vaccines, the FDA requires that vaccine developers provide sufficient data to the FDA to evaluate the safety and effectiveness of the vaccine for its intended use and population. The FDA is working with vaccine developers to help ensure that ongoing and planned clinical trials will provide sufficient data to support approval of safe and effective COVID-19 vaccines in the United States. We understand that there may be a perception that typical vaccine development steps are being skipped, but please know that FDA scientists will not allow corners to be cut in the fundamental steps required for vaccine development. In addition, the FDA will thoroughly evaluate the data submitted in support of a vaccine candidate’s safety and effectiveness and will only authorize or approve a vaccine for the prevention of SARS-CoV-2 infection and/or COVID-19 if the vaccine meets the Agency’s statutory and regulatory standards.  After issuance of an EUA or approval of a BLA for a COVID-19 vaccine by the FDA, FDA will continue to closely monitor the safety of COVID-19 vaccines various existing surveillance systems and, when appropriate, require the manufacturer to conduct post-marketing studies to further assess known or potential serious risks.  The FDA’s guidance entitled, Development and Licensure of Vaccines to Prevent COVID-19, addresses considerations regarding EUA of an investigational vaccine – and makes clear that an assessment regarding using any potential EUA for a COVID-19 vaccine would be made on a case-by-case basis considering the target population and the totality of the relevant, available scientific evidence, including preclinical and human clinical study data of the product.  The guidance reflects the recommendations and advice the FDA has been providing over the past months to companies, researchers and others, and describes the Agency’s current recommendations regarding the data needed to facilitate the manufacturing, nonclinical and clinical development, and approval of COVID-19 vaccines.  Additionally, the guidance provides an overview of key considerations to help manufacturers satisfy requirements for chemistry, manufacturing and controls, and nonclinical and clinical data needed for development and licensure and for post-licensure safety evaluation of vaccines. The guidance explains that, given our current understanding of SARS-CoV-2 immunology, the goal of development programs at this time should be to support traditional FDA approval by conducting studies to directly evaluate the ability of the vaccine to protect humans from SARS-CoV-2 infection and/or disease.  The guidance document provides transparency about the FDA’s current thinking about the scientific data needed to support approval of safe and effective COVID-19 vaccines. As part of these efforts to communicate about our expectations, we recently updated our guidance agenda to include an upcoming guidance on EUAs for vaccines to prevent COVID-19.  The new guidance will expand on our June guidance, and is intended to provide sponsors of requests for EUAs with recommendations regarding the scientific data and information necessary to support issuance of an EUA.  Also, on October 22, 2020, the FDA will convene its Vaccines and Related Biological Products Advisory Committee (VRBPAC), a panel of outside, independent, technical experts from various scientific and public health disciplines that provide input on scientific data and its public health significance in a public forum. The VRBPAC will meet in open session, to discuss, in general, the development, authorization and/or licensure of vaccines to prevent COVID-19. No specific application will be discussed at this meeting.  This advisory committee for the FDA is the appropriate advisory committee to obtain input on scientific issues related to the development of vaccines to prevent SARS-CoV-2 infection and/or COVID-19. Given the widespread potential use of these vaccines, transparent discussion at VRBPAC will help ensure clear public understanding of the evidence supporting vaccine safety and effectiveness. While the October 22nd meeting is not intended to discuss any particular vaccine candidates, the agency is also prepared to schedule additional meetings of the Committee promptly following submission of a request for an EUA or BLA for a COVID-19 vaccine to further ensure transparency.  Further details on this meeting are available on the FDA’s website at https://www.fda.gov/advisory-committees/advisory-committee-calendar/vaccines-and-related-biological-products-advisory-committee-october-22-2020-meeting-announcement.  We will continue to explore additional mechanisms to be as transparent as possible about our decision-making and general thinking regarding vaccines to prevent SARS-CoV-2 infection and/or COVID-19 disease.  We sincerely appreciate your concerns and interest in this topic, as well as the opportunity to provide this information to you. Our Recent Posts Hubri July 2, 2024 Letter to Kamala Harris July 2, 2024 Share it On:Copyright 2024 © Niazi | Developed By AssaptR

Home About Blogs Enlightenment Inventions Photography Press Writings Contact X An Open Letter to Hon. Justice Amy C. Barrett By Niazi April 21st, 2024 0 Comments Discussion Congratulations on your nomination to the Supreme Court. Consider yourself the luckiest person; you will soon have an opportunity to serve the country you love and the Constitution you adore, as you said in your acceptance speech. You have repeatedly stated that your personal beliefs do not enter your judgment making, and I believe it because you are a person of faith, a firm believer in whatever is your belief. You have a character. However, it is difficult to walk a delicate path when it comes to interpreting the law. You are first an English major and then a lawyer. Everything is written can be reinterpreted if it had been establishing a while ago; the intents do not change; their practice to apply changes frequently. An excellent example that you had offered is how sex discrimination will have to be interpreted today in trans-genders’ age. Laws may become obsolete with time. While this is the legislators’ job to keep the legislation updated, it does not happen as efficiently as it should, leaving the interpretation in the hands of the courts. If the Bible says, “Thou shall not…” there is never an interpretation required, but in the seat you will occupy, you will find that “shall” and “will” can be interpreted differently, as it happened in the Sandoz Inc v. Amgen Inc. case [No. 15–1039. Argued April 26, 2017—Decided June 12, 2017]. More problematic is decision-making that can have an enormous impact on the life of Americans. The Affordable Healthcare Act was voted in by the House, the Senate, and signed by the President. Did the three entities act following the Constitutional limits? The lawmakers, whoever they were, decided so. Now the ACA is coming to the Supreme Court for a challenge. I need not tell you how it will decimate the lives of millions of Americans. Even with the ACA, one of the worst countries to support its citizens for their ultimate healthcare needs. Taking down the ACA will have many more impacts, such as removing the BPCIA. This act created generic forms of biological drugs that save several trillion dollars and make expensive medicines accessible to all. So, when the ACA comes up for a judgment, it is not just an interpretation of the Constitution, capable of doing. Still, the Constitution does not teach you how to interpret its nuances—and it must be a nuance; otherwise, the lawmakers would not have voted it in. The filing to remove the ACA does not offer an alternative that must be required to consider repealing the ACA. A lot will depend on how you show that you love America for decades; you have the ultimate destiny for any human being—to able to serve. Now begins the hard part. Assure me that you will not politicize your opinions just as you have promised not to let your religious beliefs affect your decision. Good luck! Our Recent Posts Hubri July 2, 2024 Letter to Kamala Harris July 2, 2024 Share it On:Copyright 2024 © Niazi | Developed By AssaptR

Home About Blogs Enlightenment Inventions Photography Press Writings Contact X A Meaningful Dialog with a Young Pastor By Niazi April 21st, 2024 0 Comments Discussion The most joyful moments of my life come when I meet another human who is passionate about whatever there is to be passionate about! When I am spending time in Wisconsin, I run into a young pastor at Starbucks. The pastor owns the Lakewood Baptist Church. He is in his early thirties, an extremely handsome man with a great sense of respect for other human beings; he has adopted four infants of color in his early marriage [he does not have any children of his own, yet; yes, he is white] and extremely articulate in expressing his beliefs. Invariably, I never engage in any discussion on politics or religion, but he tempted me with his great smile. So, we decided to have a written dialog; here is an unedited exchange between a young pastor and an old man [me].  PASTOR:  As you know, we all view the world through our lenses; such is our worldview. From my understanding, yours is a rationalistic-scientific lens, which cannot itself be proven to be an accurate lens for all of life’s questions. In other words, one cannot prove the axiom, “everything that we believe must be verified by the scientific method,” because the scientific method itself cannot be used to prove the axiom in question. Science, as you know, has limitations; namely, it is limited to what is observable and repeatable. And so, when it comes to questioning, “how we came into existence,” science is actually the wrong tool because the event(s) of our origination is neither observable nor repeatable. Of course, this is no slight towards science, for the method can answer a great many important questions, just not this one. So, when you say, “To make a scientific discussion…we need a clean slate, to begin with,” I challenge the presupposition that any scientific discussion can have truly begun with a “clean slate.” To invoke a worldview that demands that all claims be verified by the scientific method is not really a clean slate at all, because it rests upon the unproven presupposition that all truth need to verify by a scientific authority (when, again, science itself cannot be used to prove that it is the required intellectual authority). I’m belaboring this point, however…   ME:  One assertion that was made clear is that whether there is anything to know; I agree that once we decide that there is a first cause, then it must have an existence raising the question of what and who. The reason we dwell on a first cause because our brain seeks out the first cause to everything and this is the pivotal reason why we need to invent god or a first cause; what I am saying is that even the desire to know the first cause is based on the faulty brain network that forces us into requiring an answer to our existence. A clean slate means to remove this desire as well, and then establish the need for creating god. It has little to do with science and deals with rationality. Now one can say being rational too is a presumption and again it is this dilemma that makes us vulnerable to accepting a divine existence. Our current stage of evolution is not advanced enough to provide us wisdom to assert that there has to be a starting point to everything. We should always leave science out of the discussion because it is indeed limited by the accuracy and precision of our observation and that is surely not either. So again, a clean slate would mean taking out the human thought to have a starting point—if you say otherwise then you are basing it on a scientific viewpoint that we both agree can only be as perfect as our observations. Your statement that not being knowable is a characteristic of god presupposes that there is an existence of an unknowable entity, a circular argument.PASTOR:  My dear Sarf, further, when you state that “we cannot know, ‘what’ or ‘who’ is this first cause,” you imply the positive assertion that the first cause is unknowable. Ironically, unknowability, then, is an attribute or quality of this first cause — the same first cause that you have already labeled as unknowable. Philosophically, this is a self-contradictory belief — that one can attribute certain qualities to that which is unknowable, without acknowledging that we must know something about that which we speak. Again, your discussion plate is not clean, because your unprovable presupposition is that the first cause is unknowable.              My foundational presuppositions are mainly these: (a) God exists, and (b) God has revealed Himself to His creation in a comprehensible manner. These presuppositions have led me to the meaningful evaluation and comparison of religious texts — not to sweeping out-of-hand dismissals that lack nuance, but sadly characterize much religious discussion in our world today. For example, I will not judge the merits of Islam based upon the horrific actions of radical jihadists, nor will I judge the merits of Catholicism based upon the crimes of the Crusaders or the modern priest molestation scandals. I actually reject them both on other bases altogether.   ME:  See the doctrines of belief to determine our behavior; it is intended to distinguish the believers for the same reason the foragers huddled together but broke the ranks when the size of the group increased to about 50-70; religion brought a possibility to expand this group by handing over the authority to an unquestionable ruler; later came empires to do the same and now we live in a “civilized” societies called nations. The motives of the human mind remain the same, and it could not change much in a 100,000 year, to control others—nothing does better than religion. It is a doctrine of politics that sells very well because our thinking comes to a halt once we begin questioning our existence

Home About Blogs Enlightenment Inventions Photography Press Writings Contact X Letter to VP – Elect Senator Kamala Harris By Niazi April 21st, 2024 0 Comments Discussion Dear Senator Harris: Congratulations on breaking so many barriers today. As a woman, you bear the torch to the suffrage movement. As a black person, you the have the burden of muting the racial discrimination. As an Asian gene holder, you assert that every American, except the American Indians, we are a land of immigrants. These are significant responsibilities, but with your passion and youth, I am confident you will serve as a role model, and you have the best wishes of millions behind you.  I am writing to you at the behest of Vice President Joe Biden, who, a few weeks ago, asked me to continue my advisory to President Barack Obama. I was able to educate President Obama about the biosimilars, and he engineered these into the AHCA. Now the AHCA is under attack, and my advisory is now focusing on making medicines affordable, particularly the essential lifesaving medicines like insulin. This was also the subject of my communications that we exchanged when you were a presidential candidate. My communications with President Obama are now present in President Obama’s library. And all my advisory submissions to the US FDA are cataloged by the US FDA in www.regulations.gov –all aimed at taking a creative approach to healthcare. Once you have established your transition office, I will be honored to meet with you and your team to share a possible strategy for making medicines affordable, particularly the lifesaving medicines like insulin, to all. However, this should not be a disincentive to the US pharmaceutical industry that has introduced almost all medicines used today. The cost of medicines is unaffordable to many—that is what we need to address it, and it is possible, as I will demonstrate in my thesis.  I was invited by the CMS early this year to suggest how to reduce the CMS budget and concluded that this require a legislative change; this is one of my advice I will submit to you.  Again, congratulations, and I look forward to meeting you soon. Our Recent Posts Hubri July 2, 2024 Letter to Kamala Harris July 2, 2024 Share it On:Copyright 2024 © Niazi | Developed By AssaptR