Articles

Spring 2018 Newsletter - 05/03/2018

Newsletter – Spring 2018

NOTE FROM KINEXUM CEO

By Thomas Seoh

President and Chief Executive officer

This email address is being protected from spambots. You need JavaScript enabled to view it.

Dear Friends of Kinexum,

Welcome to the Spring 2018 Kinexum Newsletter!  Guest author Professor Philip Home of Newcastle, an international authority in diabetes, writes provocatively that excess food is toxic, and no medication or other intervention which does not either reduce calorie intake or disposal will have a major effect on secondary conditions such as type 2 diabetes or NASH. Kinexum pre-clinical expert Dave Edwards writes on common pitfalls in pre-clinical drug development and what a developer can do about them.  Brandon Jones, a Kinexum medical writer and electronic submissions specialist, unpacks the electronic Common Technical Document (eCTD) structure, history, rationale and advantages. 

 (read more) 

POISONOUS CALORIES

By Professor Philip Home, DM, DPhil

Professor of Diabetes Medicine, Newcastle University

www.staff.newcastle.ac.uk/philip.home

P This email address is being protected from spambots. You need JavaScript enabled to view it.

A poison is 'a substance that causes death or harm when introduced into or absorbed by a living organism' [Oxford English Dictionary].  Most of us conceptualize this as something toxic in small amounts, but in reality, damage is simply a function of quantity, and that quantity may have to be quite large.  Carrots may help our night vision if we do not get enough carotene from other sources, but if you eat vast quantities, sometime after your skin turns a peculiar shade of orange your liver will fail.  Iron is of course essential to every one of our cells, but iron overload will wreck nearly every organ in your body, given time.  I once rescued a man treated for too long with high doses of vitamin D – he was in kidney failure as a result and had calcified many body tissues – my case presentation was of 'calcified man'.   But even the very common elements and substances can be poisonous.  Oxygen can be poisonous to divers and to new born babies. 

(read more)

 

Kinexum Executive Chairman Zan Fleming, M.D. moderates the closing panel at the GTCbio 11th Diabetes Summit in Boston, on April 11, 2018 

 

The Preclinical minefield: a guide to the possible pitfalls

By Dave Edwards, Ph. D This email address is being protected from spambots. You need JavaScript enabled to view it.

From the moment a new compound is championed for drug development, the possibility of failure is continually present.  This article attempts to point out the likelihood of this occurrence and possible remedies.

(read more)

Electronic Submissions to Regulatory Authorities

By Brandon JonesBrandonJones@Kinexum.com

This overview describes the electronic submission process for regulatory documents.  Official, detailed guidance can be found at:   FDA Electronic Submission Guidances

Electronic submissions?  eCTD?  Module placement?  What do these all mean?

(read more)  

 

Note from Kinexum CEO (cont.) …

We also welcome new additions to the Kinexum team:  Grant Edwards, M.D., (former Deputy Director of the Division of Oncology Products at FDA), Michael Sharp, Ph.D. (medical devices), Joyce Reyes, (biologics and cell therapy CMC), Lana Pauls, MPH (strategic regulatory and project management), Brandon Jones (medical writer and eCTD specialist) and Anand Khedkar, Ph.D. (biosimilar expert).

Zan and I moderated separate panels at the GTCbio 11th Diabetes Summit in Boston April 9-11.  Kinexum is a sponsor of the Defined Health 29th Annual Cancer Progress conference in New York City May 8-9.  A number of us will attend the American Diabetes Association 78th Scientific Sessions in Orlando June 22-26, and Liz Whalley-Buono will present at the GTCbio Opioid Crisis and Alternatives conference in Los Angeles June 26-27.  We also hosted a public webcast on April 27 (along with Hogan Lovells) on drug regulation outlook for 2018 and beyond; our next public webcast will be on May 11 on targeting metabolism to attack metabesic diseases by Michael Zemel, Ph.D., co-founder and CSO of NuSirt Biopharma, and on June 8 on European Medicines Agency regulations and in July on Japanese medical product regulations.

###

 

Professor Philip Home, Poisonous Calories (cont.) …

At the extreme of potentially common poisons is water, which constitutes 60+% of the human body (less in obese people or females), but with which doctors kill a few people e every year (mistakenly) through inadvertent intravenous water overload.  But by far the most common poison in modern society is the group of substances which is collectively known as 'food', and its manifestations, when in excess, tend like other poisons to affect a diversity of organs.  Often, when talking about food, debates rage around the three main types (plus one), namely carbohydrates, protein, fats and ethanol. To avoid confusion in this article, and because the main effect is simply one of combined excess load, the term ‘poisonous calories' will be used.

That fact that the calories are the problem should also take us above specific aspects of food as a source of poisonous substances.  I am not referring to these, but it is helpful to list them to acknowledge them and to deny them individually as the problem discussed here.  Ethanol is of course consumed already in its fundamental form, but other foods are digested to toxic substances for the sake of gut absorption and transport in the blood.  Monosaccharides, like glucose, fructose and galactose, are toxic in anything above the concentrations normally found in the blood.  For glucose this is clearly evidenced by the ravages of high levels in diabetes, and by the extraordinary complex ways glucose is stored and later made available after a meal, processes which waste around 30% of the precious energy content in avoiding hyperglycaemia.  Galactosaemia, the inability to covert galactose to glucose, is toxic to infants.  The body also has complex mechanisms for limiting the effects of the toxic reactive oxygen species generated during glucose metabolism.

The body degrades any excess of amino acids from digestion of proteins, as can be determined from the colour of urine, except in those people with genetic defects of the enzymes responsible for those removal pathways – over 20 specific genetic disorders are known, some of which kill in infancy.  Fatty acids, one of the two breakdown products of fat, are highly toxic, and not just when they drive ketoacidosis in diabetic hyperglycaemia crises.  One prime, usually forgotten, function of the albumin in our blood and tissue fluid is to bind and transport fatty acids safely – the huge transport capacity is high affinity, and a small proportion can safely be taken up by acylated insulins and other medications. 

It might be worth noting why all these substances can be toxic.  Essentially, they are all fuels and highly reactive – you can burn oils, and sugar with oxidizing agents is a good explosive (try throwing sugar on a fire).  All fuels and powers are manageable in controlled amounts (gas/gasoline, nuclear, electricity, coal, hydrogen), and all are highly dangerous when not so controlled. The brain and heart burn glucose and fatty acids constantly and are dependent on them.       

Ideally the body packs away any excess of these toxic food products safely, or degrades them.  Notably, the liver will convert the carbon chains of these substances into fatty acids (if not already such) and in combination with glycerol in the peripheral tissues will store the excess away in a low turnover environment, adipose or fat tissue.  In more gross excess, we term this storage condition obesity.  Obesity is known from the last 2000-3000 years but is not a normal human state of hunter-gatherer communities, who have little peripheral fat whatever the season.  Further, some ethnic groups are resistant to laying down peripheral fat.  The regulatory signals from fat tissue which reduce feeding in rodents, notably the hormone leptin, do not operate in humans, where, for reasons that are unclear, but which include learnt behaviour in childhood, culture seem to override metabolism.  Leptin does operate in women, as a signal of female fitness to endure a future pregnancy. 

The regulatory biochemistry goes back billions of years and is therefore fundamental.  Bacteria and archaea had to be able to regulate their metabolism according to the wild swings in the availability of nutrients in the medium around them.  This would not simply be a matter of inducing uptake and metabolism if a particular nutrient was poorly available, but also protection in times of excess.  In humans, the liver products of glycolysis, the prime metabolic pathway of glucose and fructose, induce regulatory proteins that inhibit the enzymes that take up glucose, and enhance the enzymes that release glucose into the blood – this condition at its extreme is known as diabetes.  This effect makes the liver resistant to other metabolic modulators – hence insulin resistance.   Some glucose can be stored, but the liver has a low maximum capacity for glycogen and is quickly saturated by high food intake and lack of exercise.

But excess calories must go somewhere, and in the liver, they are converted to fat.  This is further driven by insulin which activates the enzyme that promotes fat synthesis, and, due to the insulin resistance noted above, insulin levels are high as the body tries to compensate.  In some people, large amounts of fat are packaged and stored safety in peripheral fat tissue, but in extremes and in those whose bodies have reduced capacity for that (notably many Asians), the fat is retained in the liver – referred to as a fatty liver.  Fat in the liver is not by itself toxic to the organ, but again there is limited storage capacity. If the supply chain backs up, toxic intermediates accumulate, resulting in liver and systemic inflammation (steatohepatitis or NASH) and eventually liver failure. 

The same processes appear to operate in other tissues, but our understanding of this is remarkably poor.  Skeletal muscle is the major immediate store of ingested glucose (to protect against high glucose levels in the blood), but again, storage capacity is limited, and since in muscle glucose cannot go anywhere else, the cells resist further uptake –  resulting in peripheral insulin resistance.  In the islet B-cell, which produces and secretes our insulin, the sensor for blood glucose concentration is glycolysis, and the same protective biochemistry is likely to operate, so insulin secretion is reduced in proportion to glucose level.  Further, the islet B-cell interacts with fatty acid concentrations, and the islets even lay down fat. There is evidence that fat metabolism is a key toxic mechanism for defective insulin secretion and islet cell death. 

One important question is how quickly these effects can be reversed.  If liver and islet damage has not gone too far then calorie deprivation will reverse diabetes in just one week.  Of course, at that point peripheral and liver fat levels are still high (obesity thus does not cause diabetes), emphasizing it is the acute metabolic toxicity of calories that is the problem, not stored fat. 

Does any of this help us with the metabesity epidemic?  At the least, it emphasizes that no medication or other intervention which does not either reduce calorie intake or disposal will be able to have major effects on a secondary condition like type 2 diabetes or NASH (non-alcoholic steatohepatitis).  Disposal such as by uncoupling agents, promotion of storage of peripheral fat (thiazolidinediones), or enhanced glucosuria (SGLT-2 blockers), has capacity limitations, which leads us back to regulating food intake.  With few exceptions, any adult who has tried to lose weight will know that they are programmed from childhood to maintain a particular body weight, but the brain-gut neurohormonal cycle which does this can be reset or interrupted, as gut by-pass surgery illustrates.  Damning particular foods is incorrect, except as so far that most animals are attracted to sweeter foods, and sugars, notably glucose and fructose, that are easily consumed in high quantities, and as noted above have a fundamental role in the dysregulation of metabolism in humans. 

In conclusion, excess food is toxic.  This can be a useful media message.  The reasons for this toxicity are reasonably well understood and obey the laws of physics (overload must go somewhere), as well as biology.  Ultimately, we will only overcome the toxic food epidemic, metabesity, by controlling calorie intake. 

Copyright:  The copyright is retained by the author.  This article may however be reproduced but only in its entirety and without redaction (except with explicit permission), with acknowledgement to the current publisher, and when not in support of a commercial medical or food product (except with written permission), and with copyright retained by the author. 

###

Dave Edwards, Ph. D, The Preclinical Minefield (cont.) …

Investigational New Drug Submission (IND)

The typical preclinical pathway to an IND submission involves the following studies covering Safety Pharmacology, Genotoxicity and Toxicology:

Safety Pharmacology

            Rat Behavioral Study

            Rat Respiratory Study

            Non-rodent Cardiovascular Study (non-rodent encompasses canines or non-human primates)

            In vitro Human ether-a-gogo related gene Assay (hERG)

Genotoxicity

            In vitro Reverse Bacterial Mutation Assay (Ames Test)

                In vitro Chromosome Aberration Assay

                In vivo  Rodent Micronucleus Assay

Toxicology

            Rat Range Finder via intended therapeutic route (p.o., i.v. s.c. etc.)

            Non-rodent Range Finder via intended therapeutic route

            14/28 Day Rat Toxicity Study

            14/28 Day Non – rodent Toxicity Study

Thus, there are at least eleven (11) opportunities for an adverse result to hinder the progress towards an IND submission.

As the candidate drug would have undergone extensive pharmacological evaluation prior to nomination, the likelihood of significant issues arising from the rat behavioral and respiratory studies are minimal unless the compound exhibits unexpected profound neurological problems.  Occasionally these types of issues do arise but are commonly evaluated in relation to the pharmacological profile of the compound and rarely affect further development of the compound.

The latter two studies in the Safety Pharmacology package however, can pose more serious problems.  The Non-rodent cardiovascular study involves using telemetered animals and can pick up subtle changes in cardiovascular parameters that could raise issues for the compound while the hERG assay is a sensitive predictor of QT prolongation and possible Torsades de Pointes that can lead to sudden cardiac death.  Thus, any adverse finding in these two studies need careful evaluation before proceeding further with the development of the compound.

However, if these hurdles are successfully cleared one moves on to the Genotoxicity package.  A positive finding in the Bacterial Reverse Mutation Assay is probably the biggest compound killer in Pharmaceutical development as it provides an easy GO/NOGO decision point in the life of the drug.  In the case of big Pharma where the drug is one of several, the choice is easy – a positive finding kills the compound and proceed with a compound that is negative in the assay.  For smaller companies for whom the drug is their “only child”, the decision is far harder and, given that the test can throw out false positives, alternative defining tests such as the Comet Assay can be utilized to support the false positive argument.

The Chromosome Aberration Assay is known to show false positives either alone or with metabolic activation and is not as common a showstopper.  However, in all of these genotoxicity cases the positives can act like an albatross around the development of the compound as, in the eyes of the regulators, they never go away.  In this case it is always good to try and add to the package with additional studies such as the Comet Assay which, if negative, will provide further evidence that the original assay had provided a false positive.

Overall, in genotoxicity, the take-home message is that three negatives ensures progression, two of three really needs to become three of four by the addition of a further assay to ensure progression.

Having gone so far, the next move is to define the toxicity of the compound thereby enabling the therapeutic index to be established so that dosing in the clinic (probably in Human Volunteers) can begin.

Range finders in two species (rat and non-rodent) are performed to set not only the dose levels for the definitive toxicology studies, but also to establish the limits (Maximum Tolerated Dose – MTD) at which the animals can be dosed.  Occasionally, surprising adverse findings are seen at unexpectedly low levels that would disqualify the compound because toxicity was seen at levels that were considered to be the efficacious clinical dose.  Again, given the extensive nature of pharmacological studies performed prior to nomination, this is unlikely in a study of this duration (typically 7 days).

The IND-enabling toxicity studies can be either of 14 or 28 days duration depending on the intended dosing envisaged in the clinic as regulators view the toxicology in comparison to clinic dosing on a like-for-like basis i.e. 14 day toxicology study enables 14 days in the clinic, etc.  The doses are set based on the prior range-finders and consist of undosed controls, low, intermediate and high dose levels.  The high dose level is set such that some evidence of toxicity is apparent; the low dose is set at around the anticipated therapeutic dose and the intermediate dose is normally the geometric mean between the two doses.

Ideally, the intermediate dose level will be considered the No Observed Effect Level (NOEL) and should provide a suitable therapeutic margin to enable safe dosing in the clinic.  Setting the NOEL lower than that however, would require much thought on the part of the clinicians as to whether lowering the intended human dose would still provide efficacy, or whether the development should be abandoned.

New Drug Application (NDA)

Assuming that all went well with both the IND application and the early clinical trials, the compound now has to embark on the long journey towards final submission driven by both the needs of the clinicians and the regulators.  Besides the longer-term studies required in the toxicology area, reproductive studies are also needed along with carcinogenicity studies in two species and are outlined below:

Toxicology

            3 Month Rat Toxicology

            3 Month Non-rodent Toxicology

            6 Month Rat Toxicology

            9 Month Non-Rodent Toxicology

Reproductive

                Rat Fertility (Male and Female)

            Rat Embryotoxicity

            Rabbit Embryotoxicity

            Rat Peri- and Post-natal Toxicity

Carcinogenicity

            2 Year Rat Study

            2 Year Mouse Study

            OR

            6 Month Transgenic Mouse Study

The longer-term studies are designed to detect issues related to continuous exposure.  Thus, what might appear to be a slightly elevated liver enzyme in the short-term studies could manifest itself as liver disease over a prolonged period.  However, as biomarkers are becoming more and more sensitive, the “unexpected” findings in these longer studies are becoming less prevalent.  Once completed, these become the definitive studies and clinical studies can now be dosed as long as necessary to establish primary endpoints, efficacy and safety.

Any compound that could be dosed to women of child-bearing potential (WOCBP) has to be evaluated for effects on reproductive parameters such as fertility and teratogenicity.  Adverse effects here could have implications for the product if it is intended to be dosed to WOCBP.  However, if the product is intended for an older population then a so-called “Black Box Warning” may be applied such as seen in the major Pfizer product, Lipitor which carries the following statement:

“Do not take LIPITOR if you are pregnant or think you may be pregnant, or are planning to become pregnant, LIPITOR may harm your unborn baby. If you get pregnant, stop taking LIPITOR and call your doctor right away.”

The final part of the NDA jigsaw puzzle relates to the potential for tumorigenicity.  For many years regulators insisted on whole lifespan studies in both rat and mouse.  These studies involved large numbers of animals exposed to the drug for approximately 2 years with histopathological review adding at least another six months to this timespan.  More recently, the use of a transgenic mouse model dosed for six months has been accepted as a replacement for the 2-year mouse study allowing a much faster decision point regarding carcinogenicity.  Adverse effects at this late stage in development can prove catastrophic, but again the margin of safety needs to be considered and a risk/benefit analysis performed before terminating the program.

The take-home message here is encapsulated in a quote by Paracelsus (1493-1541):

“Poison is in everything, and no thing is without poison. The dosage makes it either a poison or a remedy.”

Thus, it is no surprise that adverse effects may be seen in this journey towards an NDA.  However, they need not be showstoppers.  By evaluating mechanisms of action, risk/benefit analysis, therapeutic margins, clinical requirements and population targeting, the path to an NDA may still be achieved.

###

Brandon Jones, Electronic Submissions to Regulatory Authorities (cont.) …

Industry professionals may have some understanding of the process, but may not be aware of the full extent, details and the requirements behind the process.  The process is intricate enough that the FDA has issued eighteen (18) Guidance documents on the subject.  This article describes some details and considerations for electronic submissions.

The electronic Common Technical Document (eCTD) is a categorized database and folder structure consisting of five (5) main Modules, that are further divided into multiple sub-sections to which documents are assigned during the publishing process and submitted to regulatory agencies through an electronic portal:

Module 1:  Administrative information, such as cover letter, information about the sponsor, authorizations, history of meetings and correspondence with FDA, etc.

Module 2:  Summaries of the major substantive subject matter categories of a drug application as it pertains to the                              product candidate:  quality, non-clinical and clinical

Module 3:  Quality, covering Chemistry, Manufacturing and Controls (CMC)

Module 4:  Non-Clinical Study Reports, covering topics such as pharmacodynamics, pharmacokinetics and toxicology

Module 5:  Clinical Study Reports

These five Modules are sometimes visually depicted as a pyramid:

Reports and literature references are assembled, attached and electronically linked to documents within the Modules.  The eCTD structure is used for marketing authorization applications for a medical product for human use in the United States, European Union and Japan (the parties of the International Conference on Harmonisation (“ICH”).

The complete list of documents under each Module is extensive, but can be seen in this table of contents at:  https://www.fda.gov/downloads/drugs/ucm163175.pdf.

A major objective of eCTD submissions is to group common documents from multiple submissions into specific sections for ease of access for review and approval of the specific medical product.  This greatly reduces the time for reviewers at the agency in reviewing amendments and subsequent submissions (e.g., Changes in Protocol, Investigation Brochures amendments, Periodic Safety Reports, or Annual Reports), in sharp contrast to the previously used cumbersome paper filing system.  In addition, this database structure systematically structures the accumulating body of knowledge about a product candidate, from the initial filing of an Investigational New Drug application (IND), through various amendments to the filing of the New Drug Application (or equivalent marketing authorization application), which reduces duplicative work for the sponsor and enables easy retrieval of knowledge for regulators.

Document Generation and Approval Process

Documents destined for their designated places within the eCTD submission are generated by internal functions of a medicinal product developer, or by its consultants and/or Contract Research Organization (“CRO”).  After going through some document approval process (which varies from organization to organization), the final, proposed submission documents are prepared by an electronic publishing specialist for formatting and linking and submitted to the electronic Publisher (which may be an in-house function, or an external vendor).

Care and quality control in arriving at the ‘content-lock’ version for sending to the electronic publishing function will repay itself multiple-fold, for example to avoid post-publication/pre-submission edits, and also to avoid unnecessary Requests for Information (“RFI”) from a regulatory agency post-submission.  Often, drafters of sections of a submission filing are very close to the content, from multiple, rushed revisions.  It is important to take the time and effort for several sets of eyes to do a final substantive review, through the eyes of regulatory reviewers, as well as QC review.  It’s astonishing how often it becomes clear, after a RFI is received, that some simple clarification or supplementation could have avoided such additional delay.

Publishing the Submission Package (Dossier)

The publishing process electronically ‘builds’ the submission package, typically as a pdf dossier, to be submitted through the Electronic Submissions Gateway (“ESG”) to the FDA, or Health Canada or other regulatory agencies through other electronic portals, or as an email attachment.

History of Electronic Submissions

‘Action is the foundation of all success.” – Pablo Picasso, Spanish Artist

With advancing technologies of document creation and processing, it was logical to replace the time-intensive paper submission process with an electronic process.  Version 1.0 of eCTD was introduced in 1999.  Subsequent advances in the Internet, connectivity and program interfaces have accelerated the adoption of electronic submissions.

United States

On May 5, 2015, the U.S. Food & Drug Administration published a final, binding guidance document requiring certain submissions in eCTD format within 24 months.  Electronic submissions became mandatory for New Drug Applications (NDAs), Biologic License Applications (BLAs), Abbreviated New Drug Applications (ANDAs) and Drug Master Files (DMFs) on May 5, 2017.  Starting May 5, 2018, Commercial Investigational New Drug Applications (INDs) and DMF must be submitted using eCTD format.

European Union

The European Union (“EU”) and its European Medicines Agency (“EMA”) began accepting eCTD submissions in 2002.  In February 2002 the European Union (“EU”) implemented their Version 2.0 of eCTD – an upgrade over the original eCTD – this was upgraded and version 3.0 was finalized in October of the same year.  It applies the ICH Common Technical Document (CTD), ICH M2 specifications to the European region and supplements this with the European Module 1 (http://esubmission.ema.europa.eu/eumodule1/index.htm).  In February 2004, the EU released eCTD version 3.2, and Version 3.2.2 in June 2008 was implemented (http://estri.ich.org/eCTD/eCTD_Specification_v3_2_2.pdf)

In February 2015, the EMA announced it would no longer paper application for products applying to "human and veterinary centralized procedure applications" and that all electronic application forms would have to be eCTD by January 2016.

EMA eSubmission Guidance for veterinary medical products, has also been developed (http://esubmission.ema.europa.eu/tiges/vetesub.htm).

Post-Publishing Review

“It ain’t over till it’s over.” – Yogi Berra, American Baseball Player

Anyone who has suffered (yes, ‘suffered’) through an eCTD submission process understands that there always seems to be one more requested revision; one more person to review; one more format change, or one more change to document placement.  Often, authors of documents are so close to the data and document content that results are transcribed incorrectly to the submission documents, or material is omitted. 

Until the document is submitted through the portal, and Acknowledgements of Receipt received, revisions are always possible.  However, post-electronic-publishing revisions will add materially to cost, so careful reviews by multiple pairs of eyes are invaluable in minimizing such last-minute changes. 

While it’s possible to view post-published documents in pdf format, viewing the assembled submission, as seen by FDA reviewers, will require an eCTD Viewer application.

Sponsor Obligations, Responsibilities and Best Practices

Legal Responsibility

Sponsors are ultimately legally responsible for the content, data and documents submitted to the regulatory authorities, the storage thereof, and responding to agency requests in a timely manner.  It is essential to provide final documents to the submitting entity with enough time to allow for re-review, re-approval and re-publishing of the submission package.

Document Transfer

Documents are provided to the submission and publishing departments in various ways; as email attachments, zipped folders, through company SharePoint sites, File Transfer Protocol (“FTP”) servers, or even via USB-flash drives and discs.  The important takeaway is that they’re provided in the agreed-upon format.

 Document Templates

“You don’t have to reinvent the wheel, just attach it to a new wagon.” – Mark McCormack, American Lawyer

It is recommended that document templates be followed (or created) for each type of regulatory document submitted as they are drafted.  Certainly, it would be cumbersome and unnecessary to produce templates of document types that will not be required but having the templates of previous submitted documents will reduce production time for subsequent submissions and ensure that the proper content is included. 

It is not extraordinary for the same FDA Project Manager to be assigned to the same Sponsor for multiple product submissions, contingent on the medical therapeutic area.  Once it is known that a particular project manager prefers a specific format, use this in your template and make note of this preference.

Conclusion

Sponsors superficially may encounter electronic publication (with its formats, bookmarks and hyperlinks) as an additional step that can add some weeks to a submission timeline.  However, the eCTD process has significantly reduced the time, effort and cost for Sponsors to provide documentation to regulatory agencies, and enabled regulators to conduct faster, higher quality reviews.  These benefits multiply as amendments are filed to the original submission, culminating in the marketing approval application.  Through proactive planning, mindful preparation and thoughtful execution and quality control, the eCTD process can become another opportunity for Sponsors to accelerate their achievement of corporate objectives through operational excellence.

###

Upcoming Conferences

 

A screenshot of a cell phoneDescription generated with high confidence

A close up of a logoDescription generated with high confidence

Dear Colleagues,

Kinexum executives and leading expert will attend the conferences in this section.  Anyone interested in meeting one or both of them during that time, please contact This email address is being protected from spambots. You need JavaScript enabled to view it.

 

Upcoming Webcasts

A close up of a piece of paperDescription generated with high confidence

 

 

New Kinexum team Members

Grant Williams, MD

Clinical Development & Regulatory Affairs

To learn more about Grant

Lana Pauls

Regulatory Affairs & Project Management

To learn more about Lana

Michael Sharp, Ph. D

Medical Device

To learn more about Michael

Brandon Jones

Medical Writer

To learn more about Brandon

Joyce Reyes

Regulatory Affairs

To learn more about Joyce

Anand Khedkar, Ph. D

CMC, Formulation/Process Development & Sourcing

To learn more about Anand

 

Kinexum provides strategic regulatory, clinical and non-clinical, manufacturing and other translational advisory services for life science product development.

Our experts typically have decades of experience in government, industry and/or academia, and have broad experience with a range of modalities (including small and large molecules, devices and digital health) and therapeutic areas (including diabetes, cardiovascular, GI, oncology, neurology, wound healing and infectious diseases). We manage and salvage complex assignments, and file regulatory submissions and negotiate with the FDA and agencies in other major markets.

If you would like to learn more about how Kinexum can help you, please contact us at: This email address is being protected from spambots. You need JavaScript enabled to view it. , Kinexum Services LLCPO Box 1260, 550 East Ridge Street, Harpers Ferry, WV 25425, (p) +1 (304) 535-3037, (f) +1 (304) 535-3166,  www.Kinexum,com.Follow us on Outlook Logo LinkedIn

To unsubscribe please email This email address is being protected from spambots. You need JavaScript enabled to view it.