From : Communities>>Regulatory Open Forum
Thank you RAPS, what a pleasant surprise! I appreciate the opportunity to contribute to the project! Now, if only Amazon had any toilet paper in stock... ------------------------------ Jonathan Amaya-Hodges Associate Director, Regulatory Affairs CMC Combination Products and Medical Devices Cambridge MA United States ------------------------------

From : Communities>>Regulatory Open Forum
Hi everyone, As currently drafted,  the 2020 Chinese Pharmacopeia, the benchmark publication on the safety and efficacy of pharmaceuticals legally available in China, includes 319 new entries. The publication includes more than 5,500 traditional Chinese and Western medicines. The official compendium of the standards of purity, description, test, dosage, precaution, storage, and the strength for each drug legally marketed in China is published by the Chinese Pharmacopoeia Commission. It is designed [More]

From : Communities>>Regulatory Open Forum
Hello,  I can see many unapproved combinations of Minoxidil as topical solution like minoxidil+ Azelaic Acid; Minoxidil + Finasteride; Minoxdil+ niacin+retinol+caffeine that are available online for sale in US but these drug products are not approved by FDA as visble from USFDA website.  Can anyone explain that is there any mechanism or guideline to allows to sell such unapproved drug products online in US and also in EU? Or is this totally illegal practice?  Thanks Ankur RAC

From : Communities>>Regulatory Open Forum
Hi, Ankur - Some may be "legal," others not. It's a big industry, and it is fair to be cynical. Combination products for sale that have not been approved-as the combination-by FDA are just that, unapproved drugs. I assume you checked for the approval status in FDA's "Orange Book" (https://www.accessdata.fda.gov/scripts/cder/ob/index.cfm). Even if both active pharmaceutical ingredients in a 2-drug mixture were approved separately on their own, it does not mean the combined product is approved for [More]

From : Communities>>Regulatory Open Forum
These are all unapproved new drugs. Many people who have very limited knowledge of our OTC drug system, assume that if it is sold OTC, it is a monographed drug and they can change the formulation. They do not know that there are two types of OTC drugs allowed-compliance with a monograph or NDA. Minoxidil is one and chlorhexidine antiseptic wash is another. ------------------------------ David Steinberg,FRAPS President Steinberg & Associates, Inc. Pompton Plains NJ USA 609-902-8860 -------------- [More]

From : Communities>>Regulatory Open Forum
The only  possible way I can see any of these products being legally marketed in the US without going the OTC NDA route would be if the ingredients  other than Minoxidil are considered "inactive" and have some purpose (other than their active ingredient purposes) in the formulation.  That said, this might work for the last combination in your listing because all of these can and are often used in OTC products as inactive ingredients with understood and current reasons for existing in a formulation [More]

From : Communities>>Regulatory Open Forum
This message was posted by a user wishing to remain anonymous For device-lead drug combination products, is there any difference in the quality (grade) of API used compared to a pure drug product? The cGMP guidance for combination products does not seem to specify, and since drug claims cannot be made on device-lead drug combination products, it was not clear what quality of drug is required. Thank you!

From : Communities>>Regulatory Open Forum
Hi @Britta Cyron , Thanks for your question. Let me connect with m​y RAPS colleagues on this to get you an answer and then I will follow-up with you directly. Best, Annie ------------------------------ Annie O'Brien Community Manager Regulatory Affairs Professional Society regex@raps.org ------------------------------

From : Communities>>Regulatory Open Forum
​I doubt FDA would have any willingness to change the requirements or expectations for a drug product based on whether it is in a strictly drug product versus in a combination product.  The fact also that there is not a published allowance for this is further evidence that FDA expects that the drug will meet the requirements as expected for drug products without providing any allowed changes or classes of changes.  Remember, FDA expects that drug products meet specific requirements.  Things like [More]

From : Communities>>Regulatory Open Forum
Hello, The EUA is much faster than the 510(k) process.  However, the EUA intended uses are only authorized during the state of emergency.  Once the state of emergency ends so does your authorization for the EUA intended uses.  The 510(k) clearance is permanent and authorizes the product with its cleared intended uses, to be put into interstate commerce. Hope that helps. ------------------------------ William Coulston PMP, MS, RAC Quality & Regulatory Manager San Antonio TX United States -------- [More]

From : Communities>>Regulatory Open Forum
Annie: Thank you for sharing this news.  I am curious whether the Board considers this a limited exception or a potential new normal option going forward? Scott ------------------------------ Scott Bishop Houston TX United States ------------------------------ ------------------------------------------- Original Message: Sent: 04-May-2020 08:50 From: Annie O'Brien Subject: New: Take the RAC Exams Online this Summer! The RAC board has been working hard to find solutions offering more flexibility [More]

From : Communities>>Regulatory Open Forum
Yes, you will need to achieve a 510(k) clearance after the emergency use has been officially ended by the FDA as William mentions.  Much of the information is the same, but the review process is intended to be expedited.  If you want to continue selling the product in the United States after the emergency use, you should really submit a 510(k) now; while the virus issue may continue for a few months it will take a few months for 510(k) clearance.  And if you have an EUA Approval this really is not [More]

From : Communities>>Regulatory Open Forum
Thank you for posting this here Annie as the webcast was excellent (as would be expected from Dr. Akra haha) - but really it was great to have this publicly available as there was nice information about the EU MDR conveyed. ------------------------------ Richard Vincins RAC Vice President Global Regulatory Affairs ------------------------------

From : Communities>>Regulatory Open Forum
These types of products and combinations you mention are all unapproved drugs and unapproved combinations.  Unless the specific combination is approved or listed in an OTC monograph, it is a new drug and requires a NDA to market it.  Minoxidil is a Rx to OTC switch product so it requires a NDA or ANDA to market this drug in the US, even as a OTC drug.  Thus any combination with minoxidil is a new drug. In the past the FDA has also specifically stated that combining different types of products (drug [More]

Anx·i·ety (noun)
The state of uneasiness caused by apprehension of possible misfortune.

Yep.  That’s the word that comes to mind whenever anyone mentions FDA inspections.

But anxiety often stems from a lack of control, and in a regulatory inspection, you have more control than you might think.  There are many steps you can take -- before, during, and even after an inspection is over -- that can give you a fair degree of control over the outcome.   Here, Polaris auditors Lauren Kelley and Michele Commins share some of those steps with you.



Pre-inspection Preparation
For-cause inspections may be unannounced, but routine FDA inspections of submission data are scheduled in advance*.  That means most inspections are not pop quizzes; they’re final exams.
Remember how happy you were when a teacher gave you access to a prior year’s exam to study from?  You knew the type of questions that would be asked.  You knew how to prepare.

So this is the first tip we’d like to share.  FDA has, indeed, given you a copy of their exam in advance, in the form of its Compliance Program Guidance Manual, CPGM 7348.811.  This is the document all FDA field investigators use to conduct inspections at clinical sites.  It outlines in great detail what documents investigators will review, what dates they’re going to verify, what processes they’ll evaluate, what data they’ll collect, and what records they’re going to compare.  Despite its rather uninspired title, this is your copy of the final exam.

You know cramming is a risky strategy, so the earlier you get familiar with the CPGM the better.  Inspection readiness is a state of preparedness more than it is a laundry list of activities; it takes some time to get there.

When the Inspector’s in the House
According to the CPGM, one of the first pieces of information the FDA investigator will obtain is a list of all of the studies performed by the clinical investigator, including protocol number, sponsor, and study dates.  So even though FDA has scheduled its inspection with you, and has told you what study the investigator is coming to inspect, any study is fair game.  An FDA investigator can look at any document she wants, or talk to any staff member he chooses, whether related to the “assigned” study or not.

Most of your preparation will have been study-specific; questions about other studies will catch your staff off-guard, and a review of records for other studies may find them less than inspection-ready.  So here’s our second tip.   Avoid anything that might pique the investigator’s curiosity about a study that is not the original subject of the inspection.  Make sure the room you reserve as your investigator’s “home base” is free of any documents, reports, notes, phone lists, and post-its.  Make sure you tidy up offices, workspaces, and facilities site-wide, and keep extraneous chatter in check.

After the Visit
If your FDA inspection resulted in zero observations, then stop reading, thank your awesome staff members, and go celebrate.  If, however, you did receive a Form FDA 483, it’s probably not the end of the world, but you do have some work to do.  Our third tip is this:  remember that the sponsor/CRO is your ally here.  They have as much invested in FDA’s assessment of your study data as you do, and they have the regulatory, QA, even legal resources that you might not.   You’re not required to formally respond to 483s, but if you do, you’re likely to receive a more favorable Establishment Inspection Report (EIR) in the end.  Let your sponsor/CRO help you with your response.

Tips Do Not a Plan Make
Tips are helpful, but you’ll need more than that to ensure a successful FDA site inspection.  You need an inspection readiness plan -- a plan that you document and keep current.  All site staff members need to train on the inspection procedures and the individual roles they will play.  (Fourth tip: don’t forget to train your temporary employees; an office temp working at the receptionist desk could be the first person your FDA investigator speaks with.)

A Last Thought
Inspections are stress-inducing events, and nervous people make mistakes.  Investigators know this, and expertly exercise the “pregnant pause,” knowing how difficult it is for people to withstand an excruciating silence without volunteering unsolicited information.

So one last tip:  conduct a mock inspection before the FDA comes to visit.  It will stress test your procedures and identify improvements you need to implement.  A thorough mock inspection will give staff members an opportunity to rehearse their roles and interview techniques so they can execute your plan and speak to the FDA investigator with confidence.

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* For-cause inspections are also known as Investigator-oriented, and routine inspections are also known as study-oriented.

 A version of this article originally appeared in InSite, the Journal of the Society for Clinical Research Sites

What can small sponsors do to secure the outsourcing resources they need as large CROs form strategic alliances with Big Pharma?

Partenships between large pharmaceutical companies and large CROs have become the norm.  The advantages for sponsor companies include shared risk, knowledge transfer, dedicated resources, shorter time to market, and the ability to implement the massive data integration that clinical development requires.  Strategic alliances are arguably as advantageous for their outsourcing partners, providing a steady pipeline of work that’s larger in scope and longer in duration than is typical under traditional arrangements.



Strategic Partnerships in Big Pharma: Implications for the Rest
Advantages for one segment of the industry can introduce disadvantages for another.  Alliances among the large players increase competition for top-drawer CRO resources. Smaller sponsors may find it more difficult to receive the quality of service and level of commitment they might otherwise expect.  A large CRO is likely to assign their most talented personnel to projects associated with their strategic partners.  And if a partner study were to run into trouble, it would be hard to fault a CRO for pulling experienced staff members off a smaller project in order to help out with the big client.  Though a reputable CRO wouldn’t jeopardize the relationship with the smaller client, their responsiveness to routine requests might suffer.  It might take longer to get a question answered, receive requested documentation, making the job of vendor oversight difficult.

Though selecting a large, well-established CRO at the outset may have seemed like the safe bet, what do you do if you’re a small sponsor or biotech start-up who is dissatisfied with the level of service you’re receiving?

“Let’s Bring It In-house.”
Put off by a negative experience, many companies decide to curtail outsourcing, and bring functions like monitoring and project management in-house.

This response is understandable, but it rarely goes well.  There’s good reason to outsource study functions to a CRO, especially if you’re small, or new, or both.  Mid-study is a terrible time to realize you’re in over your head.  You may find it difficult to contract with the service providers you want in the timeframe you need them.  Services you would have preferred be performed by a single company may now have to be farmed out piecemeal, which has the overhead of multiple contracts and makes vendor oversight more difficult to manage.  You don’t have time to go through a thorough qualification process.  You’re not in a good bargaining position; you’re trying to buy a new car after they’ve towed away your old one.  And now you have to rely on your new service provider(s) – the ones who may not be your first choice, whom you had to choose in haste, whom you didn’t get to thoroughly vet – to jump in midstream and pick up a study that is already in trouble.

Options for Small Sponsors and Start-ups
So what’s the answer?  You have several good options we’ve seen work well for smaller organizations.

(1) Go smaller.  Look beyond traditional outsourcing choices and consider selecting smaller vendors who may well be in a better position to focus on individual projects and give priority to shorter term engagements.  After all, a project that’s small to a big CRO will be comparatively big to a small CRO.

(2) Go long-term.  Consider establishing strategic partnerships of your own.   Doing so would increase the expertise and technology to which you’d have ready access, and could extend your global reach.

(3) Go big, but go vigilantly.  There’s a reason companies hire big, reputable CROs.  ‘Big’ means the CRO has an impressive set of resources at its disposal.  ‘Reputable’ means it has a proven record of successfully completing studies, producing reliable data, and preserving subject safety.  Smaller sponsors can still take advantage of everything a big CRO offers if they can commit to conducting very strict vendor oversight.  They need to closely monitor the quality of the work the CRO performs, frequently assess adherence to the many written study plans, and make sure deadlines are being met.  Service contracts should guarantee a certain level of responsiveness (by specifying maximum turn-around times, for example), especially for those requests that enable these oversight activities.


Qualification is Key
While the key to Option 3 is effective vendor management, the key to Options 1 and 2 is effective vendor qualification.  Resources are tight in a small company, so you need to direct them where your exposure is greatest, where they’ll do the most good.  What could be more essential to the success of your study than choosing the right company to conduct it?   Many sponsors conduct on-site vendor audits.  That’s good.  That’s necessary.  But it’s not sufficient.  To consistently choose the best possible CRO for your study, sponsors need to:

• Formally document and maintain vendor selection criteria and qualification process
• Form selection committees that represent all sides of your business – finance, contracting, operations, finance, QA, data management, pharmacovigilance, biostatistics, etc.
• Conduct on-site audits with well-trained, well-prepared QA auditors
• Track the resulting CAPA activities
• Ensure outstanding issues are resolved before the contract is signed
• Periodically re-evaluate vendors to make sure they can continue to deliver the same level of quality they’ve delivered in the past

Strategic partnerships among large companies have reshaped the research environment for industry players of every size.  Small and mid-sized companies who take the time to review current outsourcing arrangements, assess alternative models, and thoroughly qualify new vendors and partners will fare the best.

Photo Credit: FreeImages.com/Svilen Milev

Year in and year out, protocol deviations are the most common FDA Site Inspection finding. Why does this keep happening?

If you’ve seen FDA’s Inspectional Observation Summaries, you know that in 2015 the most frequently cited violation in clinical research by far was “failure to conduct research in accordance with the investigational plan.”  Do you know this finding also topped the list the year before that?  And the year before that?  In fact, deviating from the protocol has been the most common observation every year for the last decade.

Why does this keep happening?



The Nature of Protocols
This will come as a surprise to no one: not all protocols are well written.  Important procedures can be hidden in the most obscure places.  Charts depicting Time and Events Schedules are famous for carrying dozens of footnotes that appear nowhere else in the protocol, yet convey important study procedures.   For instance, a pre-dosing column may include a footnote that provides a timeframe for performing a physical exam; a post-dosing footnote might specify the interval at which vitals must be taken.   Failing to follow study procedures compromises subject safety and data integrity; FDA won’t care whether the procedures were in big bold italics or 7-point font.

This, too, may come as no surprise, but not all protocols are error-free.   Information in charts may not match the narrative.  Procedures in Section A may conflict with procedures in Section B.  When the FDA investigator spots an inconsistency, you’ll be asked which of the two conflicting procedures you followed and why.  If you performed procedure A only because you didn’t even notice there was a B, it will be clear you didn’t read the protocol as thoroughly as you needed to.  The FDA investigator may become concerned that your study execution differed from the sponsor’s intention.  This is not a concern you want to trigger.

For these reasons, it’s imperative that study staff read and understand the protocol.  Study team members need to ask questions about anything they’re unsure of, seek clarification on protocol inconsistencies, and get responses that satisfy before starting the study.   A PowerPoint overview is not sufficient training.

One more irksome attribute of protocols that can make them difficult to follow -- they change.  While most study sites allocate time and resources for initial protocol training, many lack a plan for training staff on protocol amendments.   A disproportionate number of protocol deviations occur in amended procedures, and it’s often because staff members have been insufficiently trained on them.  (And when you do train on protocol amendments, don’t forget to document it.)

Deviation Temptation
A protocol is not a suggestion; PIs cannot substitute their own judgment for prescribed procedures, no matter how well-intentioned the departure.  The protocol for a psoriasis study might call for the PI to perform a series of punch biopsies, very invasive procedures.  After the first biopsy, an empathetic PI might be tempted to skip a second if he observes the plaque is clearing up; the drug is working.  But this would be a protocol deviation.  The protocol for another study might preclude the use of a particular drug, even though the drug is routinely used throughout the practice to treat a symptom that a study participant is exhibiting.  But the study protocol trumps standard of care; prescribing the drug would be a protocol deviation.

A PI who feels she must deviate from the protocol for some reason must obtain prior approval, since failure to follow the protocol can jeopardize the reliability of the study data, if not subject rights and safety.



Deviations Happen
So you’ve thoroughly read the protocol, you’ve asked your questions and received the necessary clarifications, you’ve trained your staff on the protocol and its amendments, and you do your best to follow them.

Despite all your preparation and vigilance, protocol deviations happen.  They just do.  And when they do, here are two don'ts.

(1) Don’t panic.

(2) Don’t let an FDA investigator find them first.
Take the time to fully document any protocol deviations.  Be sure to record why they happened, how they were corrected, and what was submitted to the IRB.

[Note: IRBs have different requirements about what types of protocol deviations should be communicated.  Out-of-window visits are common and are frequently considered too minor to report.  But nothing’s black and white.  If the missed visit resulted in missed doses, that would probably change the calculus. The PI needs to determine whether to notify the IRB, and if no submission is thought necessary, it’s a good idea to document why not.]

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A version of this article originally appeared in InSite, the Journal of the Society for Clinical Research Sites.

You know you need a computer systems audit, but that’s literally the extent of what you know.
Has this ever been you?

Yes, you use computers on a daily basis, and you may even use the system that needs to be audited. But you don’t spend your day thinking about where all the system components are located, how services and software are combined, and what Part 11 requirements apply. Terms like “cloud computing” make you feel slightly queasy. You’d rather get a root canal than discuss “distributed processing.” Your expertise is in manufacturing. Or clinical research. Or non-clinical lab operations. And somehow it’s your job to make sure an effective and properly-sized system audit is conducted. Great.



Yet your Quality Assurance colleagues -- whether they’re from your internal QA department or an external compliance company -- need your input. They need to understand what software is being purchased, what services are being contracted, how and where components of the system are being implemented, and how the system will be used.

The good news is that the QA auditors can help you. They know that FDA favors a risk-based approach to validation and Part 11 implementation, and they even know what that means. They love to talk about configuration management and change procedures. They love gathering evidence that demonstrates your system works correctly and is in a state of control, and they know what rocks they should look under to find and fix vulnerabilities.

What follows are examples of the types of information you need to convey to QA – and that they should be asking you about – to properly size and scope an audit.

How do You Plan to Use the System?

Suppose you need to audit the supplier of a new Document Management System. The first thing an auditor would need to understand is how you plan to use the system. How mission critical are the documents you’re looking to store?  Are they covered under regulatory scope?  Maybe you plan to use the system as a collaboration environment for developing new SOPs. That would require a relatively low level of scrutiny, especially if you only plan to print out the finalized documents for wet ink signature. (As a point of comparison, if you plan to use the system to finalize SOP approval, the auditor would need to check that Part 11 requirements for electronic signatures are properly implemented.) What if the Document Management System will be housing critical GxP documents, such as Trial Master Files, Master Schedule Sheets, or Master Batch Records? In these cases, the validation would have to be far more thorough, and Part 11 electronic record features, such as audit trails and archiving functionality, would have to be implemented and verified.

Here’s another “use” example. Similar to the term “Document Management System,” the term “Analytics System” does not tell the whole story. From a business perspective, study start up (SSU) metrics may be vital for sponsors and CROs to collect and analyze. But since they have no regulatory impact, the FDA would not require an SSU analytics system to be validated. (That doesn’t necessarily mean you might not want to, though.) On the other hand, a system that performs statistical analysis on study data for regulatory submission is about as critical as it gets, and would require thorough validation and Part 11 implementation. Other analytics systems, such as dashboards that pull data from critical systems, might fall somewhere between these two extremes.

What is the Vendor Providing? And How? And Where?

If you need to audit a complex system, the questions QA will ask you will go beyond system use. The auditors will need to understand the combination of software and services the vendor is providing, and where the software and data reside.

• Does the software and data reside internally at your company or does the vendor provide a hosting service?
  If the vendor is hosting, the auditor needs to tour the facilities and review SOPs and records to evaluate physical security, staff training, environmental controls, backup procedures, disaster recovery plans, data retention, computer infrastructure, and change control.
  
  
• Does the hosting vendor own its own servers or does it, in turn, outsource that function to a 3rd party hosting company, (possibly even in the cloud)?
  If the hosting is outsourced, ideally an auditor would be able to visit the hosting site. Failing that, the auditor would ask questions about the vendor’s qualification processes and review SOPs that govern vendor selection/management procedures. If the vendor outsources other services beyond hosting, those services might need to be considered, as well.
  
  
• Is the vendor providing any other services?
  Many EDC vendors will provide study-specific services such as screen development and data entry validation edits. Auditors would need to review SOPs for providing these services and understand how the vendor tests and manages modifications to these components as the study proceeds.
  Sometimes computer systems vendors provide ancillary services, such as help desk functions and user account management. That would mean additional SOPs and training records for the auditor to look through.

Other Considerations

There are many. For example, where are you in the product life cycle? You ask different questions about a new system than you would about one that has been operating for a few years. Is the product Commercial off-the-shelf (COTS) or highly customized? COTS systems vendors often have their own validation package which auditors would review, and then ensure proper operation in the sponsor/CRO’s specific environment. A highly customized or custom-built system would require a more extensive validation process.


The Take Away

CSV/Part 11 audits will never be standardized, cookie cutter type activities; there are simply too many factors -- in too many combinations -- to consider. You want your QA efforts to be worth the money you spend and be able to answer the questions FDA says you need to be asking. If you’re unsure how to do that, that’s ok. Other people know, as long as you can help them understand how you plan to use the system, what software and services are being supplied, and how components of the system are being implemented.

In case you missed it, our previous post was Notes 2 Fix Your Notes 2 File.
_______________________________________________
Many thinks to Lisa Olson for sharing her insights with me.

Protocol trumps practice. This principle seems clear enough, but complying with it is not always as straight-forward as it sounds. Years of practicing medicine has reinforced the way a physician responds to medical situations. But do these responses run counter to the investigational plan? Can a site’s commitment to standard of care affect its ability to meet enrollment targets?


There’s a lot to consider.



What’s Your Standard of Care?
When deciding whether or not to conduct a particular study, a PI needs to verify that the protocol is aligned with practice norms. For example, an early phase trial might exclude a medication that is part of a practice’s routine therapy. Is the study placebo-controlled? Does it feature a specific comparator drug? Will it include a washout period? Any of these elements could present enrollment challenges or preclude a site from accepting a study at all. Responsible sites want to make thoughtful decisions about study suitability; they want to provide realistic enrollment estimates. Sponsors want this too, and can help sites do both these things by providing them a sufficient level of detail about protocol procedures as early as possible.


The Road to Deviations is Often Paved with Good Intentions
Therapeutic misconception – a well-documented phenomenon in clinical research – occurs when a study participant “fails to appreciate the distinction between the imperatives of clinical research and of ordinary treatment.”* Study participants are not alone in this. Researchers blur the distinction themselves when they conduct procedures that are consistent with clinical care but deviate from the protocol. This may be particularly true for PIs who recruit participants from their own practices. An endocrinologist might ordinarily reduce dosage for a particularly diminutive patient. A pulmonologist would often skip a scheduled chest x-ray she felt wasn’t needed to avoid exposing her patient to unnecessary radiation. An orthopedic surgeon may decide his patient needs more recovery time than usual before attempting her first walk. In a clinical care setting, these decisions are sound, made in an individual patient’s best interest. In a clinical trial, if they differ from the investigational plan and haven’t been approved by the Sponsor, they’re protocol deviations.**

It May be Par for the Course, But It's Still an AE
Specialists who have experience treating particular conditions are also familiar with the complications that ordinarily accompany them. A nephrologist, for instance, knows that a patient with end-stage renal disease frequently experiences bloat from a buildup of fluid between dialysis sessions. Though useful for a doctor treating patients, this knowledge can actually work against a doctor running a trial. How? A PI may fail to report a stomach ache as an AE because it’s so typical, so expected. “Bloat is common for renal patients. If I recorded every GI incident, I’d be recording AEs all day.” At its surface, this PI’s argument sounds reasonable, but what if the study drug itself is contributing to the participant’s discomfort? In order to assess the drug’s gastrointestinal effect, the PI must document the frequency and severity of all GI events.

Lab values that are either above or below normal range are also prime candidates for AE underreporting. “Of course the participant’s liver enzyme is high – we’re testing a cholesterol drug.”

The Importance of Study Oversight
Any GCP course worth its registration fee will discuss the distinction between standard of care and the study protocol. In practice, the distinction is not always as obvious as training sessions might suggest. This is where well-trained CRAs come in. As site monitors, CRAs are in a position to catch deviations that result from lapses into standard of care. Reading through progress notes, a monitor can ensure that any untoward medical event has been reported as an Adverse Event. They can verify that procedures conducted by the PI and site staff are compliant with the protocol. Then, by reviewing which types of data must be collected and emphasizing the importance of following certain protocol procedures, monitors can take the opportunity to re-educate study personnel and help them avoid these common pitfalls.

_______________________________________________________________________
* Lidz CW, Appelbaum PS (2002) The therapeutic misconception: problems and solutions. Med Care 40: V55-V63.

**Andrew Snyder of the HealthEast Care System wrote a thoughtful piece describing the compatibilities that do exist between clinical care and clinical research. His arguments provide a useful counterpoint to the issues we’re raising here. https://firstclinical.com/journal/2017/1707_Research_vs_Care.pdf

A version of this article originally appeared in InSite, the Journal of the Society for Clinical Research Sites.

True or False:

(1) eSource in clinical trials means eliminating the possibility for transcription errors.

(2) Data collected in Electronic Data Capture (EDC) systems is eSource.

Strictly speaking, both statements are false. If that surprises you, it’s probably because many casual uses of the term “eSource” actually differ from the formal definition laid out by FDA. If the participants in any discussion share the same interpretation of “eSource”, or if it’s clear from context how “eSource” is being used, then no harm, no foul. (Contemporary translation: “Meh.”) BUT…and you know where we’re going with this…when a term can be interpreted in multiple ways, there’s always a possibility for miscommunication and cross talk.



FDA Guidance on eSource in Clinical Investigations
FDA defines eSource as *any* data initially recorded in electronic format. That’s a broad definition, one that includes:
     a) equipment-generated data, such as digital imaging and labs
     b) electronic Patient Reported Outcome (ePRO) transmissions
     c) data streams from mobile health devices, such as Apple ResearchKit
     d) data entered directly into an EDC, known as Direct-Data-Entry (DDE) solutions
     e) data entered into an Electronic Health Record (EHR) or electronic Medical Record (EMR) system


Discussion of Direct-Data-Entry (DDE)
DDE systems allow research staff members to use portable devices to enter study data directly into an EDC system. DDEs have been garnering a lot of industry attention of late, and a number of companies offer solutions that offer a DDE data flow. As independent 3rd party auditors, we don’t want to play favorites by mentioning specific systems as examples, but if your company sells or uses a DDE system that you want to highlight, feel free to add a comment below to give it a shout out.

Discussion of EMR/EDC Integration
Not long after finalizing its e-Source guidance, FDA hosted a webinar that encouraged companies to explore direct EMR/EDC integration. While a few industry players have taken up the effort, movement has been slow. One difficulty: generally EMRs are built with healthcare in mind, not clinical research. Secondly, with so many EMR and EDC vendors, ensuring that EMR data from one system is mapped to appropriate EDC fields in another system relies heavily on data standards that are still being defined and need to be implemented on both sides. 

Source Data Verification (SDV)
If data is transmitted directly from the source system to an Electronic Data Collection (EDC) system, SDV is not required, since the source data isn’t being transcribed manually. (Note: other types of Source Data Review (SDR) activities are still necessary, even if SDV isn’t. SDR must be conducted to verify ALCOA-C data principles such as attribution, originality, accuracy, completeness, etc.) Direct transmission from source system to EDC system is the typical pathway for items (a) – (d) above, and so SDV is not required for these types of eSource.


Common Confusions
SDV. Unless there is EMR/EDC integration – Item (e) above – source data from an EMR system needs to be manually transcribed. This is what makes T/F question #1 false. Just because source data originates in an EMR, it does *not* suggest SDV checks are superfluous. You could argue, as many have, that SDV is not a high-value activity and uncovers only a small percent of data error. That argument may well influence how much SDV is conducted, but whenever data is transcribed from original source into an EDC system, SDV is a relevant discussion.

EDC Data. It’s not unusual for someone to refer to data stored in EDCs as eSource. Data stored in EDCs are electronic, and may be source, but only if the EDC is the first place the data is recorded. This is what makes T/F question #2 false.

In Summary
If you’re ever in a discussion about eSource and things start going sideways, it may be time to haul out the formal definition of eSource -- in all its tedious detail -- to make sure everyone is using the term the same way. 

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Image Credit: Paradox by Brett Jordan

Trying to comply with the GDPR got you down?
Maybe our parody will cheer you up.

(Sung to the tune of Lennon-McCartney's "Back in the U.S.S.R.")

Q: Do study site personnel need to be able to answer questions about sponsor-provided computer systems during an inspection?

A: Yes, and there’s a simple thing that sponsors and CROs can do to prepare their sites.

This excerpt was lifted from an online, interactive course entitled “Developing a Part 11 Compliance Plan in Clinical Research.” While the course mainly targeted sponsors and CROs, who have the heaviest regulatory burden in this area, sites also have Part 11 and validation concerns, as demonstrated by this question.

Presenter Lisa Olson, a CSV/Part 11 expert with Polaris Compliance Consultants, briefly described her recommendation, which is both simple and effective. (And since that is total catnip to a compliance blogger, I interviewed her after her presentation to develop the following piece.)

So here it is. Here’s what she said...

Clinical research sites rely heavily on technology to store and manage study data, so regulators are focusing on computer systems and electronic data more than ever before. Many of the systems – such as Electronic Data Collection (EDCs), Interactive Response Technology (IRTs), and e-diaries – are selected and largely controlled by sponsors, CROs, and/or third-party vendors. That doesn’t mean, however, that site staff won’t be expected to answer questions about these systems during a regulatory inspection. Quite the contrary: site personnel are responsible for the integrity of the data these systems house. They need to be able to demonstrate the knowledge required to meet their regulatory obligations.

No one is expecting site staff to be computer specialists; the expertise on these systems resides within the sponsor/CRO/vendor organizations. But the better a site can satisfy a basic, frontline inquiry into the systems it uses, the less likely it is that an inspector will pursue additional lines of questions.

So how can sponsors and CROs help?

They can provide a set of short summaries (one page per system) that answer the questions regulators are likely to ask site staff members. Filed in the Investigator Site File (ISF), ready for use, these summaries will be valuable resources.


The Basics

First, sponsors/CROs should supply identifying information: the name of the system, the vendor, the version of the system currently being used, and a few sentences that describe what the system does.
User Access and Control

To ensure both data integrity and compliance with Part 11 e-record/e-signature regulation, it’s essential that access to a system be controlled and data entry/updates be traceable to a specific person. To that end, the one-pager should describe how unique logins are assigned and how users are restricted to activities appropriate to their roles in the study. A monitor requires read-only access to an EDC system. A study coordinator needs to be able to enter and change EDC data. A Principal Investigator must be able to sign electronic Case Report Forms (CRFs). The role determines the access. Staff should also be able to briefly describe how an audit trail captures metadata that show what data were entered/altered, by whom, and when. (And someone, though not everyone, needs to be able to demonstrate how the audit trail can be used to piece together the “story of the data.” That, however, is too much to ask from our one-pager.)

Validation 101

It would be unusual for site personnel to have detailed knowledge of Computer System Validation (CSV) activities. Nevertheless, the one-pager could include a single line that confirms that the system was validated and by whom. A contact number could be included in case a regulator asks for more information or wants to see validation documents.

Where’s The Data?

Regulators will often ask where system data are stored. The answer to that question can be a simple sentence: The data are hosted by the EDC vendor at such-and-such location, or stored at the CRO, or sit on a local server within the site’s IT department.

Finally, the last line of our one-pager could be a simple statement prepared by the sponsor, CRO, or vendor, confirming that the data are protected wherever they are being stored. The data center is secure and environmentally controlled; the data are backed up to protect against loss; the system is accessed via the web through an encrypted channel -- whatever protections apply.

Conclusion

Regulators are increasingly focused on the integrity of study-related data, and that means added scrutiny of electronic systems and records. More inspections are being conducted mid-study so regulators can evaluate and ask about live systems in current operation. It’s very difficult for sites to field these questions without help from the organizations who make the decisions and have the expertise.

It’s okay to tell an inspector, “I don’t know.” (And it’s always preferable to admit that than to improvise an answer.) But say it too many times, and it casts doubt on a site’s ability to produce and maintain reliable study data. That’s in no one’s interest.

It shouldn’t be overly burdensome to develop a one-page summary sheet for each system so site personnel can address an inspector’s questions on the spot. The Investigator Meetings or Site Initiation Visits would be a good opportunity for sites to raise this point with their sponsors/CROs.

Lisa Olson will be giving an encore presentation of “Developing a Part 11 Compliance Plan in Clinical Research,” on March 24th. She describes all the elements that regulators and clients will be expecting, and since sponsors and CROs can’t implement everything all at once, Lisa prioritizes the activities necessary for developing your plan. You can register for the online course, sponsored by the Life Science Training Institute, here. Use the promotion code olson to receive a 10% discount.

Guest Blogger: Greg Weilersbacher
Founder & President, Eastlake Quality Consulting

All companies outsource. It’s a humbling fact that you simply can’t do it all yourself. This often has to do with resource allocation; your company may allocate dollars to build and sustain some activities in-house while choosing to contract higher-cost operations to qualified suppliers who already have the expertise and equipment. 

You may outsource the manufacturing of tablets, sterile injectable, or topical dosage form, or the GMP release and stability testing of your product. Once the production and testing is complete, the product may need to be stored under controlled temperature and humidity conditions and then distributed to locations around the globe. The Contract Development and Management Organizations (CDMOs) who execute these critical operations are of paramount importance to your company’s success. Choosing the right suppliers will also help to minimize stress-induced headaches throughout your organization. Here are the top five ways to get the most out of a supplier audit.



1.  Come to the Audit Prepared
This seems obvious. However, more often than not, quality auditors step into the supplier’s lobby without doing their homework. Ask yourself the following questions: Why am I auditing this supplier? Is this supplier new to my company or one that we have used before? If used previously, have I read over the audit observations as well as the supplier’s responses and do I understand them? Which audit observations do I suspect would be the most challenging for the supplier to address and which are most important to my company’s requirements for this product? Have I reviewed previously executed production batch records and testing data and are there issues that need to be resolved? Are their deviations and CAPAs to follow up on?

Your understanding the supplier’s work proposal is of great value in refining the scope of the audit. Ask yourself:  Which of our products may be manufactured and tested here and which strengths (e.g., potency) will be produced? Which equipment is likely to be used? For a tablet production, the equipment train could include balances, blenders, roller compactor, spray dryer, solvent-rated oven, comils, tablet press and tooling, gravity feeder, coating systems, de-duster, weight sorter, metal detector, tablet counter, etc. This list of equipment will assist you in requesting equipment records during the audit. 

2.  Stay On Point
Proper audit planning will help to keep the audit organized and adhere to the audit timeline. In advance of the audit, provide the audit host with a list of the technical, lab, and manufacturing staff you wish to speak with and the records you need to review. A well-organized host will have this available for your review. Stick to your audit agenda. This is critical. The best way to derail your progress is to spend precious time chasing down minor issues while glaring problems get little to no attention. Continually refer back to the audit agenda and remember to keep the content of your audit report in mind while executing the audit.


3.  Know Your Technical Expertise and Limitations
Many auditors have led previous lives in the laboratory or in manufacturing while others started their careers in quality assurance and may have little technical background with regard to equipment, manufacturing processes, GMP utilities and laboratory testing. Know your limitations and if necessary strengthen them by hiring an expert consultant to assist you during the audit.

A common problem area that is at best glossed over and at worst completely ignored during an audit is the CDMO’s compliance with GMP utilities requirements. All too often, this is due to the auditor’s lack of understanding of the operation, inputs and outputs, validation parameters, and periodic testing and maintenance requirements for utilities such as HVAC, clean or pure steam, purified water and WFI systems, autoclaves, clean compressed air, nitrogen and other gases used for operating equipment or used during processing activities in manufacturing. Typically, these areas are also less well understood by the CDMO’s employees and as a result noncompliance abound. 

Some GMP utilities may be connected to the facility’s building management system, while others may be stand-alone equipment. In either case, the CDMO should have records of alarms (e.g., out of specification or out of range conditions), an acknowledgement of each alarm by designated staff members, and documentation of corrective actions. The last item is key. This is where the execution of quality systems tends to fail. Make a point to request documentation of corrective actions for each utility alarm. 

Additionally, purified and WFI water systems along with gases, such as clean compressed air and nitrogen, require periodical sampling/testing at each point-of-use. Verify that the timelines (monthly, quarterly, or annual) for sampling and testing were performed as directed by the CDMO’s procedures. These timelines are typically not well adhered to. A clear understanding of all the operations of the supplier’s GMP utility management process will keep your thoughts clear during the audit and help identify areas that are in need of improvement. 

4.  The Auditor’s Job is to Identify the Good and the Bad (Not to Win the Debate)
An important goal of a supplier audit is to identify the supplier’s strengths and weaknesses and come away from the audit with a compliance assessment that your company can use to make important decisions. It is of no value to your company if the goal of the auditor is to show the supplier how much he or she knows by debating the fine points of compliance. GMP auditors with decades of experience generally avoid this competitive exchange as it is unproductive. Rather, it is more important to the spend the necessary time identifying compliance issues, making them known to the audit host in a professional manner, and taking detailed notes that assist in writing the audit report. Your company’s senior managers need to know the supplier’s good and not-so-good points; detailing all of these provides the greatest value. 

5.  Interview the CDMO's Lab Staff, Manufacturing Operators, and Shipping/Receiving Personnel
CDMO’s quality systems are generally written by managers and directors who have many years of industry experience. It is of utmost importance that staff members who execute these systems understand them if your company’s product is to be manufactured, tested, stored, and distributed in a compliant manner. Request to speak with manufacturing staff members who work on the production floor and are likely to work on your product. Ask them about the process they would follow to conduct lines clearance, charge powders to a blender, operate a spray dryer, use a comil, set-up of a tablet press, inspect tablets, use metal detectors, etc. Compare the information they provide to the CDMO’s SOPs to determine if the staff understands their jobs. Listen for phrases such as “I usually do it this way…” or “it’s a different every time but I typically set up the equipment like this…” These phrases reveal a lack of control and adherence to procedures. 

The Take Away
The audit itself lays the foundation for a relationship with the supplier and the take-away message should address the following questions: Will the supplier work to resolve the issues I’ve identified? Am I confident that the supplier will immediately notify and involve my company’s representatives when deviations occur during production or testing? Do the supplier’s quality systems and records meet my company’s requirements and those of regulatory agencies? How confident am I that the supplier will produce and/or test a quality product that my company can stand behind? Is the supplier simply a pair of hands or are they committed to be my partner in this product’s success? The answers will provide you with a comfort level in making the decision to move forward with the CDMO or to look to the their competition.  

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A version of this article was first published in Outsourced Pharma.

 About the Author
Greg Weilersbacher is the Founder and President of Eastlake Quality Consulting, a GMP consulting firm based in the Southern California area. Over the last 25 years, he has held director and vice president positions leading Quality Assurance, Quality Control, Analytical Chemistry, Materials Management, GMP Facilities, and Product Manufacturing in biotech and pharmaceutical companies. His unique experiences and technical background have led to the manufacture and release of hundreds of solid oral, sterile, and biologic investigational products to clinics in the U.S. and abroad. Email Greg at weilersbacher.greg@gmail.com.

Over the years, attendees of MAGI Clinical Research Conferences have collected a set of practical, actionable suggestions for improving clinical trials. More than eighty such tips appear in the July 2019 edition of Journal of Clinical Research Best Practices*.  In this post, Polaris auditors weigh in on some of their favorite MAGI suggestions. Surprising no one, they also were eager to share some of their own.

Our Favorites Tips from MAGI

So how does a clinical trial tip earn a spot on our exalted Faves List?  First, it must be something we don’t see too often, or not as much as we’d like.(If most organizations already do a useful thing, it doesn’t really qualify as a helpful tip; it’s really just a common practice.) Second, the effort to implement the tip can’t be too onerous. If a practice requires too much interdepartmental coordination, change management, training, money, or resources, it’s not a tip. It’s a full-blown initiative.

So here they are. Each tip from MAGI attendees is in bold font. Our accompanying commentary is in plain text:

• To help ensure quality study conduct, clinical sites should prepare protocol-specific quality checklists for each study. We’ve written about quality checklists from the auditing perspective before. They’re not a panacea, certainly, but that doesn’t mean they can’t be very useful.
  
  
• After study close-out, sponsors and CROs should consider holding conference calls with groups of sites to capture lessons learned. This in turn could be used to improve training, SOPs, SIVs, etc.
  
  
• As a recruitment aid, clinical sites should create pocket-sized, laminated study cards that list the inclusion/exclusion criteria for a study.  Site staff members can keep these cards in their lab coat pockets and quickly refer to them when treating a patient who could be a potential subject.
  
  
• CROs should share risk assessments and mitigation plans with Sponsors. We agree, but would also encourage CROs to keep the sites involved and aware of risks so they can anticipate them and proceed accordingly.
  
  
• Sponsors/CROs should ensure proper qualifications of vendors prior to executing contracts. It’s hard to argue with this logic, but we don’t see it as much as we should. Too often qualification audits come after the paperwork has been signed. Should the audit uncover noncompliance or quality risks at the vendor site, it’s much harder to get the vendor to make necessary changes after the contract is in place.
  
  
• CROs should align 3rd party contracts with the Sponsor/CRO contract and the Clinical Trial Agreement. Yep.

Additional Tips from Polaris QA/Compliance Auditors

The MAGI list of clinical trial tips brought others to mind that we wanted to share. We applied the same criteria to these suggestions as we did to the MAGI contributions: (1) not necessarily rare, but not as common as it could be, and (2) not overly complex or expensive to implement.

• When evaluating outsourcing partners and clinical sites, Sponsors and CROs should make sure to look at personnel turnover rates. Frequent turnovers may suggest underlying problems that could jeopardize study conduct and quality.
  
  
• Sponsors and CROs should make sure their Monitoring Report templates are consistent with the Clinical Monitoring Plan (CMP). For example:
  
  
• The CMP calls for a focus on a particular set of critical variables, but the report template only has a place for recording that 100% SDV was completed. This means that there’s no way to document that the monitor put special emphasis on anything.
• The CMP requires bi-direction review of study data – a confirmation that what is in the CRF can be verified in the source, and all pertinent data in the source can be found in the CRF – but the report template only allows for the former to be documented.
  
  
• Every member of the site team has valuable input. It’s important to include the study PI, CRC, pharmacist, and other key personnel in the discussions. In 2017, we wrote an article about the important, yet often overlooked, input that the pharmacist on site can provide.
  
  
• There are many reasons that trial participants leave a study, many of which can’t be remedied with improved site practices. But sites that demonstrate they value the participation of their study volunteers, and honor the time they’re spending and contribution they’re making, tend to have better retention results. To that end:
  
  
• To help participants schedule their time, sites can prepare calendars that include all study visit dates and indicate the activities and procedures they entail. (This, of course, needs to be approved by the IRB).
• When participants arrive, they shouldn’t have to sit in a waiting room or empty exam room; they should be seen immediately so they don’t feel their time is being wasted.
• Sites can provide beverages and light snacks to their study participants who especially appreciate them immediately after a fasting blood draw (protocol permitting, naturally). It’s a small courtesy, and not difficult to do. Whose day isn’t brightened by a proffered nosh?**

Uh oh. Now we got you all thinking about mini muffins and cheddar popcorn. Go ahead. Grab a treat. We'll talk later.

________________________________________________________________
 * Journal of Clinical Research Best Practices, July 2019

** Proffered Nosh™ would be a really great name for a restaurant. Or a fictional Scotland Yard Inspector -- legendary for his wit, brilliance, wine pairings, and fashion sense.

The nation’s largest pharmacy serving elder care facilities will pay Massachusetts nearly half a million dollars to settle allegations that it got kickbacks more than eight years ago from Abbott Laboratories to promote the anti-seizure drug, Depakote. The settlement was signed by Omnicare, a pharmacy services company that was acquired by CVS Health Corporation (NYSE: CVS) in August 2015. The $476,216 payment to Massachusetts is part of a $28 million multi-state settlement that included 47 states…

Wednesday’s initial public offering for Cambridge-based Ra Pharmaceuticals marked the ninth biotech startup to go public this year, tying the number in 2013 but still less than either of the two years since. Ra (Nasdaq: RARX), which has 40 employees in one of the former Pfizer buildings in Alewife, ended up with the third-largest IPO size for any Massachusetts-based biotech in 2016, with a total of $92 million raised from the sale of 7 million shares for $13 each. That’s more than the $86 million…

On Friday, 21 emerging medical device companies will present their technologies and business plans to a group of local investors at the annual MedTech Showcase, hosted by the Massachusetts Medical Device Industry Council. More than 300 venture leaders and business leaders are expected to attend the event tomorrow, Oct. 28 from 8 a.m. to 2 p.m. at the Westin Waltham, 70 Third Ave. As a main event, John McDonough, president and CEO of Lexington-based T2 Biosystems (Nasdaq: TTOO), will be interviewed…

Today, Shire plc confirmed it won’t make any new investments from Baxalta Ventures, the short-lived venture capital arm of the drug company Shire acquired in June.

The results of a 33-patient study conducted by a Burlington biotech suggest its long-acting steroid injection for osteoarthritis of the knee may be safer for the large percentage of those patients who also have type 2 diabetes. Flexion Therapeutics (Nasdaq: FLXN) has for years been developing its lead drug candidate, Zilretta (formerly called FX006), a reformulation of a common corticosteroid that’s used with osteoarthritis patients. Flexion’s version combines the drug with a employs proprietary…

Latest innovation in quadrivalent meningococcal vaccination designed for use in persons 2 years of age and older in the U.S.

• Independent Data Monitoring Committee recommended continuing ongoing Phase 3 trial only in the more advanced “critical” group with Kevzara higher-dose versus placebo and discontinuing less advanced “severe” group

- Libtayo decreased the risk of death by 32.4% compared to chemotherapy

Objective responses seen in 29% of patients with locally advanced basal cell carcinoma (BCC)

US-based drugmaker Mylan and partner India-based biologicals specialist Biocon have announced the launch of their pegfilgrastim biosimilar, Fulphila, in Australia. The drug can be used to treat neutropenia (a lack of white blood cells) in cancer patients.

There are major regulatory lapses in the manufacturing of similar biologics in India. The use of scientific audits could strengthen the regulatory system and improve the provision of high quality biosimilars in the country, according to a recent opinion piece [1] by Dr GR Soni, which was published in GaBI Journal.

An online educational course has been published by Medscape in collaboration with the Association of Diabetes Care & Education Specialist.

In response to the COVID-19 pandemic, authorities in Australia and the European Union have allowed drug producers to collaborate to ensure medicine production and supply.

On 7 April 2020, China’s Center for Drug Evaluation (CDE) published draft guidance on clinical trials for the approval of bevacizumab copy biologicals. This guidance is the second specific guideline released by the CDE in April. The agency also released guidance on adalimumab on 1 April 2020 [1].

US-based drugmaker Mylan and partner, India-based biologicals specialist Biocon, announced on 28 April 2020 the launch of their pegfilgrastim biosimilar, Fulphila, in Canada. This is the second biosimilar from the pair to be launched in the country.

The Alliance met (virtually) on April 15 with Dr. Caitlin Boon, FDA Associate Commissioner for Food Policy and Response and several of her colleagues. She described CFSAN’s and CVM’s role in responding to the current pandemic, as well as how the agency is assuring a continued safe food supply. About 50% of food spending in the […]

FDA — along with NIH, CDC, and other front-line public health agencies — is caught up in the urgent COVID-19 efforts. Appropriately, enormous resources are being devoted to fighting the pandemic and more funding will come, if needed. At the same time, we are getting positive reports on the FDA’s efforts to carry out the […]

Congress is starting to consider ways to address the budget cap problem that hangs over the entire FY 21 appropriations process for non-defense discretionary (NDD) programs. Last year, Congress broke a long-running stalemate by agreeing to budget caps for FY 20 and FY 21. They decided to front-load the increases, making spending decisions (relatively) easier […]

WASHINGTON, D.C. – Five lawmakers introduced a bipartisan bill giving a full range of medical services to families with children who have life-limiting illnesses and who qualify for Medicaid, which currently has gaps in such coverage.

The Children’s Program of All-Inclusive Coordinated Care (ChiPACC) Act (H.R. 6560) would let states create comprehensive care programs for these children. Its authors are the Co-Chairs of the Congressional Childhood Cancer Caucus: Representatives Michael McCaul (R-TX), Jackie Speier (D-CA), G.K. Butterfield (D-NC), and Mike Kelly (R-PA), together with Representative Diana DeGette (D-CO), a senior member of the House Energy and Commerce Committee.

“Families with children facing life-limiting illnesses need all the support they can get, and they should be empowered to seek out that support,” the bill’s sponsors said in a joint statement. “We owe it to these kids and their loved ones to help ensure more compassionate care in their most trying times.”

Gaps in Medicaid coverage of hospice and palliative services have deprived many beneficiaries of the care they need because the program does not cover some of children’s unique medical needs.

Under this bill, the family of every child who qualifies for Medicaid will receive a specialized care plan covering a range of services – palliative, counseling, respite, expressive therapy and bereavement – providing them and their families greater comfort and peace of mind.

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Sangamo plans to utilize Mogrifyâs cell conversion technology to develop CAR-Treg cell therapies.

J&J agrees a manufacturing partnership with Emergent, as it looks to hit its target of one billion doses.

Takeda in global licensing agreement with ProThera to develop plasma-based therapies for inflammatory conditions.