From : Communities>>Regulatory Open Forum
Dear Roy, You do not mention any important functions of the syringe/applicator, other than the Primary Packaging function for which you have identified testing to assess impact. The determination of these functions (e.g. deliverable dose or dose accuracy) could provide important testing to verify that no impact on performance. Also, an assessment on the impact of the change on the usability could be required (particularly if the ergonomics/forces change) or patient risk would be prudent, which [More]

From : Communities>>Regulatory Open Forum
Great! Thanks Anna --------------------------------- Anna Alonzi MD Sr. Regulatory Associate Newtown PA United States ---------------------------------

From : Communities>>Regulatory Open Forum
Hi everyone, I just finished it, and it is a really simple task! Go ahead! Thanks Anna --------------------------------- Anna Alonzi MD Sr. Regulatory Associate Newtown PA United States ---------------------------------

From : Communities>>Regulatory Open Forum
From a clinical perspective, nothing will make your medical device "safe" as this word is defined in a dictionary.  Different jurisdictions will adopt what are essentially legal definitions of this word. Devices that meet this definition are "safe" only within the scope of that definition, which is more than just the words, but also includes the process the regulatory agency follows to determine whether the device meets that definition.  Two different jurisdictions may adopt the same literal definition, [More]

From : Communities>>Regulatory Open Forum
Thank you Dinar! ------------------------------ MARIA GUDIEL Brea CA United States ------------------------------

From : Communities>>Regulatory Open Forum
Thank you Richard! ------------------------------ MARIA GUDIEL Brea CA United States ------------------------------

From : Communities>>Regulatory Open Forum
The short answer is "yes" provided that the development cell bank was the source for the GMP bank and is comparable in terms of performance. However, the devil is in details and you need to evaluate "comparability" carefully between the development bank and the GMP bank with respect to the characterization data you plan to use for, e.g., to support GMP bank for production, etc. Two ICH guidance documents are useful to look at, Q7 Table 1 and Q5D. The US FDA generally follows ICH guidance but EMA [More]

From : Communities>>Regulatory Open Forum
Yes, exactly i asked same

From : Communities>>Regulatory Open Forum
This message was posted by a user wishing to remain anonymous Why not use Adobe to fill out the form?  You will need it to compile the submission anyway.

From : Communities>>Regulatory Open Forum
Hi Annie, I knew before that I wouldn't be able to attend to the webcast, so I did not register for it. But I am very curious on Dr. Akras insights. Is it possible to view a recording of it? Thanks, Britta ------------------------------ Britta Cyron Bochum Germany ------------------------------

From : Communities>>Regulatory Open Forum
Dear Lee & Spyros, Many thanks for your invaluable advice - really appreciate your time in considering and providing deep insight. Kind regards, Roy Jamieson (BPharm Hons) Regulatory CMC Consultant

From : Communities>>Regulatory Open Forum
Hi Beverly, To find out details on EUAs go to the FDA website central for EUAs at  https://www.fda.gov/medical-devices/emergency-situations-medical-devices/emergency-use-authorizations#coronavirus2019.    They are pumping out lots of them pretty quickly.  Each type of EUA has different requirements and FDA is flexible depending on the EUA you are looking for.  Timelines are not specific I just asked that question of one of my connections at the FDA today.  They are giving priority to more technically [More]

From : Communities>>Regulatory Open Forum
I have not seen anything, but during the interactive EUA process FDA were very clear that we need to continue with 510[k] preparation and offered supportive and constructive comments of where additional information would be needed. Although the EUA team are very busy, they see it as mutually beneficial, well actually in everybody's interests, to help us to a cleared status as soon as possible and the level of interactive engagement has been great. I am not convinced any general guidance would have [More]

From : Communities>>Regulatory Open Forum
This message was posted by a user wishing to remain anonymous Have you looked into PRA Health Sciences?

From : Communities>>Regulatory Open Forum
Hi All, Always appreciate and respect the great advice that comes through this forum: The scope of my question is CE Mark of a Class IIa medical device system under the MDD (and then eventually MDR): We have Class I devices which will be CE Marked through self-certification. These devices can be used with other CE marked products (not owned by us). One of which is not CE Marked as a medical device (conformity to machinery and low voltage directives). In terms of what we consider this vendor, what [More]

From : Communities>>Regulatory Open Forum
Thank you all for participating in our Tagging Project! We're glad to hear you enjoyed it. All volunteers were entered into a drawing for a $50 Amazon gift card. See a video of the drawing attached.  I'm happy to announce that the winner is ...  @Jonathan Amaya-Hodges ! Thanks again to all who participated. If you're interested in more volunteer opportunities, see our full list here .​​ ------------------------------ Danielle Fezell Manager, Chapter & Volunteer Relations, RAPS Rockville MD United [More]

Files Attached Document
RE: Sort It Out by participating in the RAPS Tagging Project

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
I disagree with Richard. I just had a conversation with the COVID-19 hotline (11:45 am, May 7) and asked about this issue after having read an update from the FDA that said UDIs for EUA devices are waived and GMPs are under limited enforcement. The person I spoke with said the update is correct and that UDIs are waived for EUA devices.  Feel free to contact me if you have any questions.  Bob Bard ------------------------------ Robert Bard JD, RAC [Managing Director] South Lyon MI United States - [More]

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
This message was posted by a user wishing to remain anonymous I'd recommend a statement that you are using these standards as general use. A Declaration of Conformity allows you to submit less testing information, but FDA still may request it. In the case of the standards you mentioned, FDA will require that information (e.g. software documentation, risk management, etc). So I would not bother with the DoC as you still have to submit all that material. Here was a nice thread discussing the topic [More]

From : Communities>>Regulatory Open Forum
This message was posted by a user wishing to remain anonymous When this was first issued we printed it out, filled in the answers with careful handwriting and then scanned it back in - which seemed to be perfectly acceptable. Since then we've converted their form to a fillable PDF.​

From : Communities>>Regulatory Open Forum
Bob, I stand corrected; if you confirmed with FDA that is good.  From what I was reading and seeing (I must have missed that update) there was nothing addressing UDI or no UDI.for EUA products.  (Personally I am a bit surprised at this since the whole concept of UDI is traceability and they waive this for emergency use products - when there is an issue this is where UDI becomes so important.  Shrugs.) ------------------------------ Richard Vincins RAC Vice President Global Regulatory Affairs --- [More]

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
Hello Richard, Yesterday, I received a follow up from the Hotline (CDRH-EUA-Templates ) to my query. I was reminded that the waiver to good manufacturing practice and labeling requirements were included in the individual authorization letter. The person responding to my question concerning the UDI requirement provided the following: UDI is not specifically noted; however we are not enforcing UDI during the emergency. The specific authorization letter I was reviewing was for [More]

From : Communities>>Regulatory Open Forum
Hello Anonymous  You will be generating software documents (which is data of a sort), in accordance  with  ANSI-AAMI IEC 62304, and there is output from ISO 14971 which goes into the submission.   I just think DoCs are wasteful busy time and would do as few as possible. Regarding IEC 62366-1, maybe if you want mention it and do a DoC, but if the device  usability  study is not required in a submission don't  put it in there unless asked.  Just my opinion. Biocompatibility if used, is generating test [More]

From : Communities>>Regulatory Open Forum
Hi, Willard - The Product code RHP won't show any 510(k)s because that is not a match for any regulated medical device. You can see the classification in the "Radiation Emitting Electronic Product Codes" page (https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPCD_RH/classification.cfm?PCD=RHP), where it also notes that for this Product Code, there are no applicable standards for these "UV Lamp, Germicidal" products.  If it were a medical device, it might fall under FDA's classification for certain [More]

From : Communities>>Regulatory Open Forum
Thank you!!! Good to know that everyone is having a wonderful interactive experience. --------------------------------- Beverly Whitaker Beaufort SC United States ---------------------------------

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
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
See FDA Guidance For Industry: When to submit a new 510(k) for an existing device.  It will walk you through a decision tree. ------------------------------ William Coulston PMP, MS, RAC Quality & Regulatory Manager San Antonio TX United States ------------------------------

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
Hello Shikha, This depends on whether the form, function, and operation of the medical device is affected by the change to the accessory.  Without knowing the device, the accessory, or the type of change, it is hard to say, but I refer you to the FDA Guidance document for when to complete a 510(k) for an existing device.  If you go through the flowchart and read the descriptors for each there is the item B.5 and then the sub-boxes 1 through 4.  There is the question whether a change to accessory [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
Hello, I agree with Ginger, when you look at standards there will most likely be an output of documents from following those standards, i.e. risk management file, usability report, all the software documentation.  These would be included in the different sections of the 510(k) so you can claim them as recognised standards you are following.  I have mentioned in previous posts, we take a simple approach for the declaration of conformity to standards that is a small table describing what we are complying, [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
Good morning, Willard. In the U.S., disinfectants fall under the jurisdiction of both the FDA and EPA.  The agencies have an MOU in place to better define there roles.  Accordingly, devices that are  intended for "trapping, destroying, repelling, or mitigating any pest or any other form of plant or animal life (other than man and other than bacteria, virus, or other microorganism on or in living man or other living animals). . ." are defined as "pesticide devices", under  FIFRA section 2(h),.    Pesticide [More]

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]

By Laurie Meehan

SOP revision. It falls somewhere between income tax prep and colonoscopy prep on the likability scale.  So why would you want to read about it?  Maybe you’re hoping someone’s figured out a way to make the process more efficient and less painful.  Maybe we have.

The SWAT Technique

Last month, we worked with a company to revise a set of SOPs using a technique we call SWAT.  (Any edgy appeal that name might have otherwise had will be immediately dulled by its acronym expansion: “SOP Working Analysis Team.”  It’s the best we could do.  Don’t judge.)

The goal of the SWAT technique is to revise the most documents in the least time, while preserving friendships, sobriety, and original hair color.  The heart of SWAT is an immersive, multi-day working session in which participants discuss SOP revisions and incorporate them in real time.  Careful planning, thorough preparation, and commitment from management and participants are keys to keeping the SWAT session productive.

It’s Not For Everyone

Up front, we need to say that SWAT won’t work for every organization.  While the size of the company may not be important, the size of the working team needs to be fairly small.  Also SWAT won’t work for every set of SOPs.  The documents need to be part of a natural grouping – a set of similar procedures – and not a random collection.

But in the right situations, SWAT works very well.  Last month, we conducted a 2-day SWAT session with a client’s QA department to revise a set of 10 auditing SOPs.  We’ve also successfully used the technique with ClinOps teams, for example, to revise sets of monitoring SOPs.

SWAT Planning and Preparation

The SWAT process begins with central planning.  A coordination team selects a logical grouping of SOPs to revise, and assembles a list of specific revisions to be made.  Where it’s not possible to provide specific revisions, instructions and guidelines are developed, such as “remove audit report distribution details” or “update to reflect new file safeguarding practices.”

Each SWAT participant is assigned an SOP from the revision set.  The participant doesn’t need to be the author of record, but must be knowledgeable enough to “represent” the SOP – to learn the document well and understand how it’s similar to the other SOPs in the revision set and in what ways it’s unique.  Based on this understanding, prior to the SWAT session, participants make applicable revisions to their individual documents using the information received from the coordination team.  Participants should also note questions and any open issues appropriate for SWAT discussion using inline comments. 

SWAT Session

The result of the SWAT session is a set of approval-ready SOPs.  The precise structure of the SWAT session to get you there depends on a variety of factors, such as how similar or dissimilar the SOPs are, the extent and complexity of the revisions, and whether subject matter expertise is concentrated or distributed among the group.  But all successful SWAT sessions we’ve conducted share these attributes:

• Duration of 2 to 3 days.  Just long enough to accomplish the aggressive goal, just short enough to keep everyone from diving out the window.
• Real-time revision.  The “SOP of the hour” is projected on a screen while participants sit in front of PCs and update their assigned SOPs accordingly.
• Rigorous facilitation. It’s natural for discussions about company procedures to morph into other topics, such as business strategy or staffing requirements.  Discussion *will* get off topic.  When it does, the facilitator must act quickly to table it.  You can maintain a list of tangent topics on a flip chart, schedule a meeting to discuss the most pressing items, ring a cowbell, blow an air horn, or drop a quarter in the “Diversion Jar” and move on, but keep those conversations out of your SWAT session.  Save the war stories for dinner.
• Commitment to the process.  Scheduling the session is one thing, but remaining dedicated to the session is an act of will. It’s so ridiculously easy for outside work to creep in.  Management and participants must be committed to carving out the time and keeping the barbarians at the gate.
• Of course: Plenty of caffeine and yummy treats.

If you’ve ever worked on SOPs, you know there’s a big difference between done and almost done.  To help ensure you emerge from the SWAT session with the former, time must be allotted for participants to format, polish, and conduct a quality review.  If it’s possible to scare up some on-site administrative support, that could help expedite the process.

SWAT Benefits

When you look on your team’s Outlook calendar and see 3 entire days blocked out, it can seem like an awful lot of time devoted to SOP revision.  But SWAT really doesn’t take any longer than the usual process, it’s just more obvious.  Does SWAT take significantly *less* time?  Mmmm, not sure, but SWAT brings with it other benefits.

SWAT produces a more consistent set of SOPs.  Since every document is compared to every other, it’s easy to notice and correct incidental differences.

SWAT is a cross-training opportunity.  Participants enter SWAT knowing their own SOP very well.  They leave knowing the whole SOP revision set very well.

SWAT gets it done.  Auditors, how many times have you cited facilities for failure to revise their SOPs within the specified window?  It’s not because there’s a willful disregard for SOP procedures.  It’s because, in the real world of work, revising SOPs is seldom prioritized highly enough to get on anyone’s schedule until the end of the revision window encroaches or – oops – has passed.  But schedule a SWAT and they will come. (And because the effort is so visible and so obviously resource-intensive, no one wants to be the one to drop the ball.  Participants come prepared and the resulting documents are the better for it.)

SWAT is a lot more fun.  Revising SOPs on your own is really boring.  Revising them in immersive sessions with colleagues is significantly more enjoyable.  Gallows humor reigns supreme.  Copious amounts of chocolate are consumed.  Air horns are blown in celebration.  Friendships, sobriety, and hair color remain intact.  Participants live to write another day.



_______________________________________________________________________
Photo Credit:  Tenaciousme CoffeeArt, under Creative Commons License

Impossible to write a love song about FDA warehousing regulations, you say?
Challenge accepted.

(Sung to the tune of Billy Joel's "She's Always A Woman.")

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.

Guangping Gao, the head of the Horae Gene Therapy Center at the University of Massachusetts Medical School, will partner with Philadelphia-based Spark Therapeutics to figure out better ways to get disease-curing genes into cells. The collaboration, announced this morning, gives Spark (Nasdaq: ONCE) the option for an exclusive, world-wide license for any intellectual property to come out of it. No financial terms were disclosed. Earlier this year, Gao was featured in Newsweek magazine for seemingly…

Third Rock Ventures, the Boston-based venture capital firm behind some of the Bay State’s most prominent biotechs, has reclaimed its title as the biggest life science-focused VC firm in the state with a new $616 million round, and has also named its first female partner in eight years. With the announcement of its Fund IV today — its largest ever — the firm now has raised $1.9 billion in the nine years since it was formed. That eclipses its rival across the Charles River, Flagship Ventures,…

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.

• 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

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

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.