What You Need to Know About the FDA’s May 5th Deadline

The FDA has mandated that by May 5th, 2018, most file submissions to the agency MUST be in the electronic Common Technical Document (eCTD) format. The FDA states that all organizations must obtain a digital certificate for each person sending files through the ESG. We’ll cover a high-level overview of the mandate, review which files are affected, and cover how to buy the correct digital certificate.

Last May 5th, 2017 the FDA required that eCTD become “the standard format for submitting applications, amendments, supplements and reports to FDA’s Center for Drug Evaluation and Research (CDER) and Center for Biologics Evaluation and Research (CBER) (Weiler, 2017).” This rule applies to all New Drug Applications (NDAs), Abbreviated NDAs (ANDAs), and Biologics License Applications (BLAs).

This May 5th, 2018 the FDA is extending that requirement to Commercial Investigational New Drug Applications (INDs), Drug Master Files (DMFs) and Biological Product Files (BPFs). Additionally, any new submissions to the existing DMF must be done in eCTD format -- the same DMF number can be used.

So WHAT exactly, is the ESG? From the FDA’s website:

The Food and Drug Administration (FDA) Electronic Submissions Gateway (ESG) is an Agency-wide solution for accepting electronic regulatory submissions. The FDA ESG is a … secure exchange point for FDA and its partners to transact a variety of documents and submissions over industry-standard protocols. The FDA ESG enables the secure submission of premarket and postmarket regulatory information for review. The FDA ESG enables the FDA to process regulatory information automatically, functioning as a single point of entry for receiving and processing all electronic submissions in a highly secure environment. (Electronic Submissions Gateway, 2018) 
 

Simply put, the ESG is facilitating the agencies move from paper to digital and standardizing the process across industry submissions. The ESG supports Public Key Infrastructure (PKI) and requires a digital certificate in order to provide some level of security; the FDA provides a comprehensive document (ESG Appendix C: Digital Certificates, 2018) regarding certificate basics and how to acquire one, which we’ve summarized below.

Organizations must choose to pursue either an in-house or outsourced solution. In-House solutions can be costly to implement and maintain, requiring PKI subject matter expertise.  However, an in-house PKI gives the organization granular control over security policies and procedures – if you’re part of a large organization it’s very possible you already have an in-house PKI.  You’ll want to reach out to someone on your Identity, IT, or Regulatory Affairs teams to be sure.

Outsourced vendors spare your organization the headache of standing up and maintaining a PKI – it can be argued that outsourcing is cheaper and more effective than issuing trustworthy digital certificates in-house.  If you choose to go this route, the FDA recommends purchasing a three year certificate. Exostar is one such external vendor recommended by the FDA.

And it’s important to mention that by having an Exostar DCS certificate, you become a member of their Life Science Community of over 200,000 identities spanning more than 3,000 life science organizations.  The username and password you create during the DCS onboarding process can be used to access applications across the entire Exostar Life Science community. A single credential leads to faster user onboarding and more efficient collaboration with your business partners

Still have questions? Worried your organization isn’t compliant with the May 5th deadline? Feel free to give us a call or shoot us an email – we’re happy to help. 

Justin Flechsig

justin.flechsig@exostar.com

Works Cited

Electronic Submissions Gateway. (2018, 3 28). Retrieved from FDA: https://www.fda.gov/ForIndustry/ElectronicSubmissionsGateway/default.htm

ESG Appendix C: Digital Certificates. (2018, 3 26). Retrieved from FDA: https://www.fda.gov/forindustry/electronicsubmissionsgateway/aboutesg/ucm334781.htm#4

Weiler, K. (2017, April 25). FDA Says Adios to Paper Filing. Retrieved from Pharmaceutical Manufacturing: https://www.pharmamanufacturing.com/articles/2017/fda-says-adios-to-paper-filing/

Written on behalf of Exostar, published 4/24/2018 link pending

Three Ways the DSCSA Will Unlock Value in Your Supply Chain

Government regulation of industry often has unintended consequences that impact or strain the businesses involved. The Drug Supply Chain Security Act (DSCSA) is radically changing the pharmaceutical landscape; fortunately, the regulation is likely to improve the value companies are getting out of their pharmaceutical supply chain.

The purpose of the law is to improve the security of the pharmaceutical channel and reduce the risk of contaminated or counterfeit product reaching patients. It is the second piece of legislation contained in the Drug Quality and Security Act, signed into law in 2013 after an avoidable meningitis outbreak killed 64 people.

Many firms within the pharmaceutical industry are dragging their feet and scrambling to meet deadlines, but it's very likely the DSCSA will prove beneficial to their supply chain:

1.     Improving traceability and the patient experience

The DSCSA mandates that the pharmaceutical industry serialize and trace all pharmaceutical product in the channel. Serialization refers to a process wherein products are affixed with a unique ID that can be traced through the supply chain. Today, individual products are largely indiscernible from their peers -- this makes pinpointing illegitimate product during a recall expensive or impossible.

Counterfeit products represent a $163 billion to $217 billion global industry, and are responsible for an estimated one million deaths a year internationally. The US is not immune to the counterfeiting epidemic, as cancer patients prescribed Avastin may attest. In 2012, the FDA was forced to intervene when the illegitimate firm “Montana Health Care Solutions” offered Avastin at a discount of almost 25%; the Avastin knockoff did not contain the main ingredient, bevacizumab, and resulted in patients not receiving needed therapy.  Years earlier, counterfeit Heparin from China killed 81 Americans.

By improving traceability you reduce the impact of counterfeit product, improve the patient experience, and (potentially) reduce or isolate the threat of litigation.

2.     Gets rid of blinded and blocked data

Product serialization has the potential to revolutionize the pharmaceutical supply chain, offering a depth of data-insight that has not been previously possible. Historically, trade managers have visibility into demand at distribution center locations, but that visibility quickly fades at the pharmacy level due to blinded and blocked data.  Serialization has the potential to replace EDI 852 and 867 (product activity) data and may completely illuminate data that was previously blinded or blocked.

Serialized product data is very likely to supplement or replace expensive sales data, ultimately leading to our third point: the DSCSA may lead to a reduction in revenue leakage.

3.     Decreases revenue leakage

Serialized product data would empower Pharmaceutical organizations and their data partners to improve shipment forecasts, better meet demand, and identify leakage in the channel. Manufacturers could potentially marry their channel data to sales/Rx data and support the marketing arm of their organization, for example shipments to a pharmacy could feed a promotional lift calculation. Sales into outlets could be reliably used as a means of sales force compensation. Serialized product data would support returns management and reduce the cost of managing that process.

As the DSCSA moves towards its final deadline in 2023, manufacturers would be wise to consider who owns the serialized data and how they intend to marry it to their existing processes; serialized product data has the potential to flip existing means of processing trade and sales data on its head.

Justin Flechsig is the Life Sciences Product Marketing Manager for Exostar, A Gartner Cool Vendor for Identity and Access Management services in highly regulated industries.

Original Source: 3 Ways DSCSA Improves the Value of Your Supply Chain

"SAT" Scores and College Major Gender Composition

Original Post: Randal Olson, Average IQ of Students by College Major and Gender Ratio

Criticism:  The original post compares "IQ" with 'women as a percent of total students' and reaches the conclusion "the more female-dominated a college major is, the lower the average IQ of the students studying in the major".  However, it is likely that the original "IQ/SAT" source is in fact GRE data. Remember, the SAT is taken by college applicants in high school, while the GRE is taken in preparation for graduate school. This casts suspicion on the original conclusion and subsequent discussion of intelligence in the author's comment section/ Reddit submission. 

I hypothesize that the observed negative correlation between female-heavy disciplines and lower IQ (or in this case, GRE scores) is explainable through an undefined preceding event (e.g. self-selection, societal pressure) prior to adoption of a major. Following this, these individuals do not go on to receive advanced mathematical training and tend to score lower on the quantitative portion of the GRE. It's not unreasonable to think that a humanities graduate might not have performed advanced calculus since high school! 

We plot the percentage of women in a given major (W%T Ratio) against the total, verbal, and quantitative GRE scores.

Average GRE Score vs. % Women in a Major
We are able to recreate the same general trend the original author stated: there is a negative correlation between GRE score and the percentage of women in a given major.  We supplement each node with the 'number of individuals in a given major' -- this is reflected in the size of a given node. We note that the top-left quadrant focuses on mathematics, while the bottom-right quadrant leans toward liberal arts.

Educational Testing Services, http://www.statisticbrain.com/iq-estimates-by-intended-college-major/
National Center for Education Statistics, http://nces.ed.gov/programs/digest/d13/tables/dt13_318.30.asp
R-Squared = .61, P Value < .0001

Average Verbal GRE Score vs. % Women in a Major
We investigate the trending seen in the total GRE score by examing the verbal and quantitative components separately.

We note that the distribution in the verbal score appears random. We posit that the differences in GRE score are not explainable by the verbal section (supported by the R-Squared and P Values). 

Educational Testing Services, http://www.statisticbrain.com/iq-estimates-by-intended-college-major/
National Center for Education Statistics, http://nces.ed.gov/programs/digest/d13/tables/dt13_318.30.asp
R-Squared = .039, P Value = .145

Note: Major labels are only visible where possible, all data nodes are present in all three graphs.

Average Quantitative GRE Score vs. % Women in a Major
By digging into the quantitative scores we almost identically reproduce the trend in our first graph: there is a negative correlation between GRE score and the '%women in a major.'

Educational Testing Services, http://www.statisticbrain.com/iq-estimates-by-intended-college-major/
National Center for Education Statistics, http://nces.ed.gov/programs/digest/d13/tables/dt13_318.30.asp
R-Squared = .752, P Value < .0001

Conclusions:

My analysis differs from the original author as I believe that the GRE is undertaken predominately by individuals who have either completed college or have at least finished a substantial portion. As such, you would expect that majors with a heavy focus on mathematics (e.g. Engineering, Sciences) require completion of mathematical courses and subsequently outperform those majors with little-no emphasis on math (e.g. Arts, Education).

There is no statistically significant trend in the verbal scores and the negative correlation observed in 'total GRE' is driven by the quantitative scores. The original author's conclusion "the more female-dominated a college major is, the lower the average IQ of the students studying in the major", is simply not true or supported by the data.  I believe the difference in quantitative scoring is due to the mathematical training individuals enrolled in those majors receive. 

What's most interesting here is that women, assuming a uniform distribution of major choice, are underrepresented in STEM and as such receive less exposure to advanced mathematics during their time at college.

Charting & Data Source: 
Produced in Tableau 8.1 by Justin Flechsig
ETS + Statistic Brain, IQ/"SAT" Score
NCIS, Degree/Sex of Student
Data was joined via Excel's fuzzy logic plugin + manual cleaning.