Atlanta, GA–(ENEWSPF)–October 11, 2012 at 3 p.m. ET
- Audio recording (MP3, 16MB)
OPERATOR: Welcome, and thank you for standing by. I would just like to remind all parties that the lines have been placed in a listen only mode until the question and answer session of today’s call. This call is also being recorded. If you have any objections, you may disconnect at this time. I would now like to turn the meeting over to Mr. Curtis Allen and sir you may begin.
CURTIS ALLEN: I thank everyone for joining the CDC and the FDA at the Massachusetts Department of Health joint telebriefing updating our investigation on the meningitis outbreak. We have three speakers available today, but there are also technical experts around the table who might be available to answer additional questions. First is J. Todd Weber, MD with CDC. And he’s the Incident Manager of the multistate meningitis outbreak and then we have Deborah Autor, and she’s the Deputy Commissioner for Global Regulatory Operations and Policy at FDA. And then Dr. Madeleine Biondolillo, Director, Department of Public Health, Bureau of Health Care and Safety and Quality at the Massachusetts Department of Public Health. We are going to do things slightly differently today. I will begin the introductions, and then after the introductions and then when we move to the Q&A, Erica Jefferson at FDA will take over the Q&A. So with that let me introduce Dr. J Todd Weber.
J. TODD WEBER: Thank you, Curtis. Today I would like to give you an update on CDC’s efforts to date on tracking down patients who may have been exposed to the medication in question, what we know from the laboratory testing about the fungus associated with these infections, what CDC is doing to ensure that patients are receiving the best possible treatment based on the latest clinical information from confirmed meningitis cases. What we know about patients who may have received this medication as an injection in a joint and how we are working with FDA to evaluate long-term strategies to protect patients from exposure to contaminated medicine. I’ll start with the update on the patient notification efforts.
On Monday, we stated that the CDC believed that approximately 13,000 patients may have been exposed to the three indicated lots of preservative-free methylprednisolone acetate produced by the compounding center which is frequently referred to by the acronym NECC, continuing investigations by state and local health departments have demonstrated that this number is now closer to 14,000 patients. The 14,000 patients received the medication as a steroid injection either into the spinal area or into a joint space such as a knee, shoulder or ankle. Through the tremendous efforts of our state and local public health departments and utilizing CDC’s Emergency Operations Center to staff a call center to contact patients, we are happy to say that together, we have successfully contacted over 12,000 or 90% of these nearly 14,000 patients. CDC and public health officials are referring any patients who have symptoms to possible meningitis or possible joint infection to their physician who can evaluate them further. However, we know we are not out of the woods yet.
In these notifications, we are making sure patients understand that should they develop symptoms of meningitis or joint infections in the coming weeks, they need to seek medical care immediately. Among people with meningitis for whom we have clinical information available, the onset of symptoms is typically between 1 and 4 weeks following injection. However, we want to emphasize that we know fungal infections can be slow to develop, and that there are indeed reports of longer periods of time between the injection and the onset of symptoms so patients and their doctors will need to be vigilant for at least several months following the injection. Patients with meningitis have presented with a variety of symptoms including fever, new or worsening headache, nausea or a new neurological deficit consistent with a deep brain stroke. Almost all patients have reported headaches and half have reported fever, back pain or nausea. Some of these patients’ symptoms were mild. Given the severity of the fungal meningitis, time is of the essence. We know we can save lives by identifying patients early and getting them on appropriate anti-fungal therapy.
Now I will talk about the infections that have been reported to us. As of October 11th, today, we have 169 meningitis cases that have resulted in 14 deaths across 11 states. Additionally, we have one joint infection case that has just been reported to us. This person received an injection from one of the three recalled lots. Laboratory results are not complete at the time so we cannot be sure if this is a fungal infection. A breakdown of the number of cases per state is available on CDC’s website.
Next, I would like to discuss in more detail what we know about the fungi that has been identified to date in this outbreak. As we reported a week ago, the first patient with fungal meningitis from Tennessee had an infection from a fungus known as Aspergillus, since that time the laboratory confirmed cases of fungal meningitis have all had infections caused by a different fungus known as Exserohilum and the spelling is on the website. To date CDC laboratories have confirmed the presence of fungus Exserohilum in ten people with meningitis, and the fungus Aspergillus in only one person with meningitis. That was our first patient. We are aware of three additional Exserohilum cases confirmed by other laboratories.
I am now going to walk you through some complex points regarding diagnosis and treatment. We know that fungus such as Exserohilum can be difficult to detect from samples from patients. Patients and their clinicians should not assume fungal testing that is negative, means there is no infection. In other words, patients who received an injection with one of the three recalled lots of steroids may be diagnosed with meningitis, but their fungal testing may be negative. In these cases, patients should still be treated for fungal meningitis. Similarly, curing these infections requires prolonged treatment and patients should adhere to the treatment recommendations of their physician. The CDC’s laboratory continues to get specimens for testing daily. Although we are not prepared to say that Exserohilum is the sole cause of these injections we are certainly seeing a predominance of that fungus among the patients with meningitis. Let me emphasize that historically fungal meningitis is very rare and Exserohilum has not been seen previously as a cause of fungal meningitis. This is new territory for public health and the clinical community.
So, you may be wondering, what does this laboratory testing mean for patients. Knowing the type of fungus causing these infections will directly impact the treatment regimen we are recommending for patients. CDC has convened a panel of the nation’s leading clinical fungal experts who are working with us to ensure that our diagnostic and treatment guidance is appropriate for identifying and treating these patients should they become ill. We initially started with a treatment recommendation that was narrow in scope. Once we had laboratory confirmation of Exserohilum infections we broadened the scope of the treatment guidance to ensure that we were giving the patients an appropriate regimen to fight these fungal infections. At the present time we are recommending that patients with confirmed fungal meningitis receive two anti-fungal drugs, — voriconazole and lipsomal amphotericin B. These drugs are very strong and can be very difficult for patients to tolerate over a long period of time. We are working with our clinical experts to determine the best dose and the best length of time to treat patients. As additional information comes in from CDC’s laboratory, and from FDA’s testing of the vials of medications that were in the facility, it is possible that our clinical recommendation will change. We are working quickly to gather as much information as possible to ensure that doctors and nurses who are treating any patients with fungal meningitis have the necessary information they need to appropriately care for these patients.
Next, I want to shift gears and talk about the patients who received the potentially contaminated medication as a steroid injection in a joint space such as knee, ankle or shoulder. As I mentioned, CDC and the Michigan Department of Community Health have confirmed today the first patient with evidence of joint infection following injection with the implicated medication. We are working to get additional information on this individual patient. To reiterate laboratory results are not complete at this time. We expected through our patient notification efforts we may see additional patients come forward with infections of the joints. These patients may present with symptoms including fever, increased pain, redness, warmth or swelling in the joint where they received the injection or at the injection site. CDC will be releasing guidelines for the clinicians to manage and treat patients with fungal joint infections.
I want to take a moment and acknowledge tremendous work happening across the country by state and local health departments during this investigation. Last week we mentioned the rapid work by the Tennessee Department of Health in piecing together the information from the initial cases and helping CDC and FDA crack open this investigation. Today, we talked about the work by the Michigan Department of Community Health in identifying the first case of fungal joint infection. I also would like to acknowledge the Virginia Department of Health was the first to identify that the patients presenting fungal meningitis was in the rare form cause by Exserohilum. Their laboratory was the first to make this connection and put CDC further ahead in the clinical investigation. Over the weekend, public health officials worked tirelessly to track down 14,000 patients in 23 states that had been exposed to the implicated medication. Additionally, CDC has stood up our Emergency Operations Center to better respond to this outbreak and is working 24/7 to ensure that patients are notified, clinicians have the necessary information to treat these patients, clinical specimens are tested and fungal isolates are promptly identified. These examples demonstrate the public health efforts to save lives and protect people.
This outbreak highlights the need to ensure that all products, processes and procedures used in healthcare are safe. CDC is committed to working with our federal partners at FDA to ensure that long-term strategies are put into place to prevent contaminated medication from entering our healthcare system. We want patients who access healthcare to be confident they are not going to get a potentially devastating illness as a result of their care. This is a necessary safety net that all Americans deserve.
Thank you – I would now like to turn it over to my colleague at FDA, Dr. Deborah Autor.
DEBORAH AUTOR: Thank you. Let me first start by saying we know how unsetting these recent events have been and we send our deepest sympathies to all who are impacted by this tragic situation. It is our goal here at FDA to understand and contain the health risk as quickly as possible. We consider this a top priority and we are dedicating many, many resources to this investigation. Once the immediate crisis is contained, we want to work with Congress, compounders, the states, and all other stakeholders to strengthen the system, to try to prevent tragedies like this in the future.
I’ll provide an overview of where we are today. First, FDA is working closely with the CDC and state partners, to investigate this meningitis outbreak. It has occurred among patients who have received an epidural steroid injection. The investigation into the exact source of the outbreak is still ongoing, but a contaminated product is suspected to be the cause of the outbreak. As you heard the suspected injectable steroid was compounded and distributed by New England Compounding Center – NECC — Framingham, Massachusetts. The process of producing sterile drugs is highly complex and must be done with great skill and care. Compounding pharmacies have a responsibility to have processes in place to ensure that they are producing quality drug products that are safe. Failure to do so puts patients at risk.
Here’s a brief timeline of our investigation into this matter. I want to point out these are some of the major milestones in our investigation. But this has been a 24/7 operation system the moment we found out about this and we are actively working with CDC and the states to contain this public health issue at all possibilities. On September 26, 2012, the Massachusetts Board of Pharmacy initiated an inspection at NECC. On October 1, 2012, FDA and the Massachusetts Board of Pharmacy together inspected NECC. On October 3, 2012, New England Compounding Center discontinued all operations and voluntarily surrendered its pharmacy registration to the Massachusetts Board of Registration in Pharmacy. No products have been produced or distributed by the facility since October 3, and none of the injectable steroid at issue has been produced since September 26. On October 6, 2012, the NECC, following an earlier recommendation by FDA that none of the firm’s compounded products be used, announced a voluntary recall of all products currently in circulation that were compounded at and distributed from this facility.
FDA and the Massachusetts State Board of Pharmacy are continuing with our joint inspection of NECC. As one part our inspection, FDA’s investigators are taking samples of materials from the NECC facility and testing those samples in an FDA laboratory. We are also reviewing the processes, procedures, and documentation at the facility. We are conducting a thorough investigation. FDA has also collected product samples from clinical facilities around the country that reported ill cases and/or had remaining quantities of methylprednisolone acetate supplied by NECC. FDA investigators also initiated an inspection on October 2, of Busse Hospital Inc., of NY, the firm that provided custom epidural trays to the TN pain clinic, which had an event. The epidural trays were used in conjunction with spinal injections administered at the TN pain clinic and initially considered one of the suspect items associated with the outbreak; they have since been ruled out. The inspection spanned October 2-10th included inspection of Busse’s sterilization firm in Long Island, NY. The firms have demonstrated good manufacturing practices. Concurrently, FDA inspectors in New Orleans collected epidural trays from the New Orleans pain clinic central to the outbreak. The epidural trays common to a number of the pain clinics have been analyzed by FDA’s Winchester Engineering and Analytical Center lab for fungus. The trays have been negative for fungus implicated in the outbreak.
FDA has confirmed fungal contaminant in multiple sealed vials of methylprednisolone acetate injection both at the pharmacy sites from samples collected around the country. FDA in partnership with CDC, is in the process of identifying the exact species of the fungus whether is similar to organism found in the patients. At this time, FDA labs have a number of ongoing analyses of samples taken from NECC and from around the country. These tests are in process, and we will share further information as soon as it is available.
Yesterday, also working closely with Massachusetts Board of Pharmacy, FDA launched a joint inspection at Ameridose, as part of our efforts to protect the public health. Because there appears to be a business relationship between Ameridose and NECC, and as a precautionary measure, FDA intends to determine whether certain aspects of compounding practices and facility conditions observed at NECC may also be present at the Ameridose facility. As part of this inspection, FDA will review whether Ameridose has procedures and facilities necessary to assess the firm’s ability to safely produce and provide sterile drug products. At the same time that we initiated the inspection with the Massachusetts Board of Pharmacy, the State was able to have Ameridose voluntarily cease operations until October 22.
Although NECC has recalled all products, we want to be sure that no product compounded by NECC remains on the shelves and we are urging clinics, doctors’ offices, and hospitals to check their drug supplies and purchasing records to determine if they have purchased products from NECC. They should immediately remove and isolate those products from their supply. NECC will be providing further instructions regarding the disposition of the products at a future date.
Finally, as I noted at the beginning of my remarks, we will continue working with CDC, state health authorities and boards of pharmacy and patient care clinics to notify the public if we determine any other NECC products pose any risks. Again, we give our heartfelt sympathy to all patients and family members who are affected by this situation. We hope that all who touch pharmacy compounding –pharmacists as pharmacies, doctors, regulators, law-makers, and others – can come together, work together, to try to prevent such tragedies in the future. Thank you.
MADELEINE BIONDOLILLO: Thank you, Dr. Autor and Dr. Weber. Good afternoon, my name is Dr. Madeleine Biondolillo, I am the Bureau Director for Health Care Safety and Quality at the Massachusetts Department of Health and Human Services. On behalf of the commonwealth, I want to express my deepest sympathy for each person and their loved one impacted by this tragedy.
The department of public health (DPH) continues to closely collaborate with the CDC, the FDA and the other state public health officials to investigate the exact cause of this outbreak of fungal meningitis. DPH took immediate action to protect the public health and safety when first notified of the outbreak late in the evening of September 24th. NECC voluntarily surrendered its license at the request of DPH and has recalled all medications. Yesterday the board of pharmacy issued an alert to all compounding pharmacies in the commonwealth to reinforce for them the rules they must abide by in Massachusetts. Our statutory and regulatory requirements stipulate that compounding can only be conducted upon receipt of a patient’s specific prescription. Additionally the board of pharmacy has issued an order requiring that all compounding pharmacies in the commonwealth sign an affidavit attesting compliance with all pertinent laws and regulations.
At the request of DPH, Ameridose, LLC, a manufacturing pharmacy in Westborough, Massachusetts, that shares principle ownership with NECC agreed to cease all manufacturing and compounding operation effective October 10th. And other pharmaceuticals have ceased manufacturer and distribution of any compounds from that company. Ameridose and its partnering distributor Alantos pharmaceuticals have cease distribution of all products manufactured and compounded by that company or any of the companies under shared ownership, for any kind of delineated period. The request for a temporary cessation of operations will facilitate a targetted joint DPH, FDA inspection. DPH has seen no evidence to suggest that there is direct concern for compromised products manufactured or compounded by Ameridose, and has not requested a recall at this time. We are working closely with the Massachusetts hospital association to ensure protection of medication supply chains, and we encourage state hospital associations across the country to similarly engage with their providers.
Our shared investigation with our federal partners at the FDA continues and will be comprehensive. This includes concerns for quality and safety across the corporate entity including but not limited to corporate ownership and governance structures at NECC and Ameridose. We urge congress to act quickly to address the needs for new laws on the federal level to fill in the regulatory gap so that there is clear authority over regulating these practices. DPH and FDA are jointly examining all root causes of these events and we are committed to ensuring that all responsible parties are held accountable. Thank you very much.
CURTIS ALLEN: Okay. We will open it up for questions but first let me turn it over to Erica Jefferson at the FDA. Erica?
ERICA JEFFERSON: Thanks Curtis. The one important ground rule before we get started, given the level of interest in this issue we want to make sure that we get to as many people on the phone as possible. So, I will be limiting reporters to one question and a related follow-up. A transcript of the telebriefing will be available after the call. With that, let’s begin. Calvin can we take the first question?
OPERATOR: Yes, thank you. At this time if you would like to ask the question, please press star one on the telephone keypad. The first question from David Morgan with Reuters and your line is open.
DAVID MORGAN: Thank you very much. I’d like to know given the 2006 warning letter from FDA to Dr., which talked about the managed manufacturing scale of production and concerns about health risks including a health risk associated with injectable sterile drugs, wasn’t there anything that FDA could have done under current law to prevent this outbreak from taking place?
ERICA JEFFERSON: Dr. Autor?
DEBORAH AUTOR: Thank you for the question. The FDA has done a lot together with the states to oversee NECC both being repeatedly inspected and sent a warning letter and NECC has been under consent agreement with the state. I want to point out first and foremost, it is the responsibility of NECC to ensure that they are making safe high quality products and they assured us that they were doing that, so we have taken some action, and I will say that the enforcement in this case and other compounding cases is complicated greatly by litigation and a lack of clarity in the law, and while we have done some with clear authority, we cannot do all.
DAVID MORGAN: Are you saying that the NECC misled the FDA and state authorities?
DEBORAH AUTOR: I would defer that question to the state, to the state.
ERICA JEFFERSON: Dr. Biondolillo?
MADELEINE BIONDOLILLO: This is Madeleine Biondolillo. So, you know, NECC under Massachusetts board of pharmacy licensing regulations was licensed to deliver compounded products in response to individual patient specific prescriptions. And it looks through the investigation as though they have violated that aspect of the state licensing regulation despite their assertion that they were operating under the regulations.
ERICA JEFFERSON: Great. Next question.
OPERATOR: Thank you. Our next question comes from Jon Lapook from CBS news. Your line is open.
JON LAPOOK: We want to know if the — this is a question directed to the Massachusetts Board of Health. So, how was it that you wouldn’t know that this company was shipping volume to a number of states in clear violation of the law? This is the main business as far as we can tell.
MADELEINE BIONDOLILLO: This is Dr. Biondolillo from Massachusetts. Under the Massachusetts licensing regulations for pharmacies including compounding pharmacies, there’s oversight in this capacity by four distinct bodies. The board of pharmacy supervises the adherence to practice requirements, the FDA supervises the integrity of drugs and active pharmaceutical ingredients, and the DEA and the drug control program at the state handle controlled substances, but the DEH regulatory function does not track the volume of medications that are prepared and distributed. There is an arena of intrastate licensing which goes on and following on to Dr. Autor’s comment about the need for the evaluation of the federal oversight, this is an area which businesses like NECC have expanded into, and certainly NECC was not operating as far as the investigation has seen so far in accordance with the Massachusetts licensing regulations. However, the intrastate aspect of that is something that bears looking at on a federal level.
ERICA JEFFERSON: Do you have a follow up, CBS?
JON LAPOOK: So, kind of the way it was set up nobody was looking?
MADELEINE BIONDOLILLO: So, as I mentioned, we have had regulatory authority over the company and as Dr. Autor mentioned, the FDA and board of pharmacy inspectors have been out on numerous occasions, and have been inspecting, and this organization chose to apparently violate the licensing requirements under which they were allowed to operate.
JON LAPOOK: Thank you.
ERICA JEFFERSON: Can we have the next question, please?
OPERATOR: Yes, the next question comes from Yamiche Alcindor from USA Today, and your line is open.
YAMICHE ALCINDOR: Hi. Several people online have expressed worry about getting the flu shot, because of this outbreak, and obviously the two are completely different, and completely different substances, but what advice or message do you have for people who are feeling scared about it, and people tweeting about whether or not they are going to get the flu shot because of the meningitis outbreak and anybody can answer that and I’m hoping that maybe the CDC could take a crack at that, please.
ERICA JEFFERSON: Dr. Weber?
TODD WEBER: Yes, we were having difficulty hearing what she said, and may the question be repeated?
YAMICHE ALCINDOR: Oh, hi. Can you hear me now?
TODD WEBER: Yes, better.
YAMICHE ALCINDOR: Sorry. Several people online have expressed worry about getting the flu shot because of the meningitis outbreak and obviously these are two different substances, but people are tweeting on Facebook and saying that they are scared to get the flu shot because of the meningitis outbreak and what advice or message do you have for people like that those who are feeling anxious about getting the flu shot and I would hope that Dr. Weber could take a crack at that from the CDC, and if anybody else wants to chime in, I would appreciate it. Thank you.
TODD WEBER: Okay. This is Todd Weber from the CDC, and we think that these are completely unrelated subjects, and follow the recommendations for getting a flu shot.
DEBORAH AUTOR: I would add on to that from the FDA perspective that the flu shots are FDA approved products for safety, whereas compounded products do not have FDA approval and are not approved for efficacy and quality, so this is not going the raise concern as to the quality.
YAMICHE ALCINDOR: Okay. Thank you.
ERICA JEFFERSON: May we take the next question, please.
OPERATOR: Our next question come from Mike Stobbe with the Associated Press. Your line is open.
MIKE STOBBE: Thank you. Dr. Autor said that the vials tested positive, but she did not say how much. How many of the vials tested positive at the NECC facility and you said some tested positive out across the country, and could you give us details?
DEBORAH AUTOR: There are more than 50 vials that have tested positive for fungus, and we have sent the vials and the samples to the CDC to see if it is connected to the meningitis.
ERICA JEFFERSON: Did you have a follow up, Mike?
MIKE STOBBE: I did. Where is it coming from? Any developments in the investigation about where in the plant? Was it a particular piece of equipment? Did you think it was from staff there, broken autoclave or anything about how this contamination got into the vial?
DEBORAH AUTOR: We continue to investigate that, and to take samples of products and environmental samples, and the facility and looking at records because we are concerned about the conditions at the facility, but at this point, we cannot speak about a definitive link.
MIKE STOBBE: You said 50 vials, 5-0, right?
DEBORAH AUTOR: Yes. That’s correct.
ILISA BERNSTEIN: And just to be clear, this is the FDA, but we have a number of samples ongoing in the process as fungus takes a while to grow out and culture. So things are at various different stages, so that we are still waiting to get results from the other testing.
ERICA JEFFERSON: Dr. Bernstein is the Director for the Center for Drugs and Office of Compliance. May we have the next question, please.
OPERATOR: Our next question comes from Danielle Dellorto with CNN News. Your line is open.
DANIELLE DELLORTO: Thank you. My question is going back into the whole misleading for the FDA and the state level, because records show that the department of veteran affairs actually placed eight different orders with the NECC totaling more than $20,000. These were all large batch orders, and dating back to 2006. So what is your response to that, and, you know, to claim that you didn’t know when a government agency was actually ordering drugs from them in bulk and not individual.
DEBORAH AUTOR: I think that at this point, we are continuing to investigate the facts to make sure we have a thorough understanding of exactly what was happening and exactly what we were and were not told. I will say that what this points out is that the practice of pharmacy has changed quite a bit. The world has changed a lot since the days of mortar and pestle, and this is the time for pharmacists, for lawmakers, for regulators and for doctors to sit down to grapple with this new model of pharmacy compounding and come up with a regulatory scheme that appropriately controls the risk.
DANIELLE DELLORTO: But you are saying that the government, the federal government didn’t know that NECC was making and distributing large batches, when the government, itself, actually gave them $20,000 and placed large orders with them.
DEBORAH AUTOR: I’m saying that this is an ongoing investigation and we have to understand all aspects of it, and we have potential criminal and civil remedies and we will continue to look into this.
ERICA JEFFERSON: And can we take the next question this is.
OPERATOR: Next question is from Maggie Fox with NBC. Your line is open.
MAGGIE FOX: Thanks very much. The sound on this call for some reason is very, very distorted. Can we ask that the transcript be made available as soon as humanly possible, and my questions are kind of follow-up. Can I ask if any other type of fungus have been found in any of the samples and also can we have more details on the one case, because it is hard to understand the one case of joint injection.
ERICA JEFFERSON: Dr. Weber.
TODD WEBER: Right. So —
ERICA JEFFERSON: Maggie, could you repeat the first question.
MAGGIE FOX: Yes. Dr. Weber, can you give us more details on the one case when the person was injected in the joint and not the spine. I could not understand what you were saying about that case.
TODD WEBER: Well, it has been reported to us because the person got an injection with the steroid lots that were recalled that have been the focus of the investigation, and so they need, and they are meeting the criteria for someone that we would want to investigate further, and they have symptoms in their joints, but we don’t have the final results of the laboratory testing, so we don’t know if it is a fungal infection.
CURTIS ALLEN: Did you have a follow-up?
MAGGIE FOX: Dr. Weber, I heard about half of that. Is everybody else having the same trouble hearing you?
TODD WEBER: Okay. So I’m not sure if it is on our end. But I will say it again. Can you hear me now?
MAGGIE FOX: Yes.
TODD WEBER: Okay. So, we know that, that patient got an injection into that joint with the medication that was, you know, one of the three lots that was recalled, and they have symptoms that indicate infection, but we don’t have the final results of laboratory tests that tell us whether this is a fungal infection or something else.
MAGGIE FOX: But they do have meningitis?
TODD WEBER: Pardon me?
MAGGIE FOX: They have meningitis? Or they have headaches?
TODD WEBER: No, no. Okay. Sorry. No, this is symptoms of an infection in their ankle.
MAGGIE FOX: An infection in the ankle. Okay.
TODD WEBER: And it is a joint injection and not a spinal injection.
MAGGIE FOX: Okay.
ERICA JEFFERSON: Are you clear on that now?
MAGGIE FOX: I’m sorry.
TODD WEBER: It is called a peripheral joint if that would help.
MAGGIE FOX: It is the ankle, and that I have an infection in the ankle and no symptoms of meningitis.
TODD WEBER: Correct.
MAGGIE FOX: And where is this case?
ERICA JEFFERSON: Maggie, this is Erica, and so we can continue, can you follow up with Curtis for the details. Calvin, can we take the next question, please.
OPERATOR: Yes, from Katie Moisse with ABC news, your line is open.
KATIE MOISSE: Hi, thanks very much. I was wondering if someone could comment on the attack rate and explain why some people are developing the infection whereas others are not. Is it a question of dose, if someone could elaborate on that?
ERICA JEFFERSON: Dr. Weber.
CURTIS ALLEN: Actually, Dr. Park will answer that question.
BENJAMIN PARK: Dr. Benjamin Park, at the CDC. What I would say is that the investigation is ongoing. There are different, there are different clinics and different states in various stages of patient notification and as well as patient follow-up so as this investigation continues to evolve, we will have better data about what the attack rate is. So, I would say that those numbers are yet to be determined right now.
ERICA JEFFERSON: And Dr. Park, can you provide the title for the participants on the call, please.
BENJAMIN PARK: Ah, sure, Medical Officer.
ERICA JEFFERSON: Can we take the next question.
OPERATOR: Yes. The next question comes from Sabrina Tavernise from New York Times. Your line is open.
SABRINA TAVERNISE: Hi, yes. Thank you for taking my question. Do we know anything about the source of the original materials that went into the compounded drugs? Where they came from? The country of origin? Whether they were generics or what, what was the source of what went into the steroid?
DEBORAH AUTOR: Yeah, hi. This is Deborah Autor at FDA, and let me go back to the previous question and with respect to the question of the attack rate one thing that is important to realize is that contamination is not necessarily uniform in a lot of the product, so I’m not saying that is or is not a factor here, but when considering the potential infections here, it may or may not be the case at all vials are equally contaminated with the methylprednisolone acetate source of contamination. With respect to the source of the ingredients, that is something we are actively looking into. We want to make sure that we have traced down every thread in this investigation, and one of those is what is the source of every ingredient in the compounded products that appear to be associated with this problem, and with rein the process of doing that.
ERICA JEFFERSON: Sabrina, did you have a follow up?
SABRINA TAVERNISE: I wanted to know why the company managers haven’t been, and why they were still involved in the recall.
DEBORAH AUTOR: When we conduct a recall, and the firm conducts a recall one of the things that is key is for the firm to be there to help us to understand the district shun of the product, and the customers and how the product was sent out and the FDA will oversee the recall and conduct audit checks to ensure that the customers have been notified about the recall, but it is key that the individuals at the firm be involved so that which can make sure that we are able to reach all possible products.
ERICA JEFFERSON: Can we take the next question, please.
OPERATOR: Our next question comes from Richard Knox with National Public Radio. Your line is open.
RICHARD KNOX: Hi. Thanks very much. Can you tell me about what is the longest interval between injection and symptom onset, and something about the distribution of those cases in terms of time?
ERICA JEFFERSON: Dr. Weber or Dr. Park.
BENJAMIN PARK: Dr. Park. I’m sorry, Richard, the first question was about the longest duration of time and the second part was what?
RICHARD KNOX: Excuse me. If you have any information about the distribution and the time of onset, and I think that many people out there who are worrying that i got the injection last may or july and i noticed earlier in the conference call you say that people have been alert for several months burk i am trying to get behind that and find out what you know about the time of injection versus onset.
BENJAMIN PARK: Okay. Richard, thanks. The median time which is the similar to the average, but about the middle time frame that we know of is about two weeks between the last injection that they received and when the symptoms began. Now, the longest that we have is about 42 days. But, again, as Dr. Weber mentioned, we want to emphasize that we don’t know what the longest will be, so we don’t quite know at this point how long people need to be vigilant for, but as Dr. Weber said, it is important to stay vigilant for a long time afterwards to make sure that they do not develop symptoms of infection.
ERICA JEFFERSON: Richard, did you have a follow up?
RICHARD KNOX: Yes, please. It is related. It is striking so far that 11 states out of 23 that got these potentially contaminated lots are reporting cases this far in. What are you thinking that signifies or what are the hypotheses about why it is unevenly distributed?
BENJAMIN PARK: I would say that there are possibly a lot of reasons as to why the, there are some cases that don’t have cases yet. As you know, the investigation is ongoing, and the other thing that we know is that there are some states that did not receive many lots of the medication, and there are some states for example, Tennessee we know received a lot of medication. So it probably has something to do with that.
ERICA JEFFERSON: Can we take the next question, please.
OPERATOR: Our next question comes from Jennifer Corbett with the Wall Street Journal, and your line is open.
JENNIFER CORBETT: Yeah, hi. This question is for Dr. Autor, and you mentioned that the phone was breaking up, and you mentioned some of the stuff that came back negative as to the epidural trays came back negative and can you explain to me what those are and where those were and my other question is of the 50 vials of the steroids, were those all at the facility in Massachusetts or were these taken from some of the clinics?
DEBORAH AUTOR:Sure. Thank you, Jennifer. We are spect to the epidural trays, we can easily i think walk you back through that after the call. Essentially, we were doing a comprehensive investigation to look at all of the components that could have been involved here and the epidural trays were among those, but we have at this point ruled that out as a cause of the problem. With respect to the vials that have tested positive, those were vials that we collected at the facility and also at clinics.
JENNIFER CORBETT: Okay. Thank you.
ERICA JEFFERSON: Now can we take the next question, please.
OPERATOR: The next question comes from Lena Sun from the Washington Post. Your line is open.
LENA SUN: Yes, hi, this question is for Dr. Autor, and I had two questions. One is that both you and Dr. Biondolillo mentioned the regulatory gaps and could you be specific where you feel that maybe you could answer the question this way — what is the FDA’s authority over compounding pharmacies like NECC and then i had a specific follow-up.
DEBORAH AUTOR: Okay. Well, it is incredibly complicated to explain what our authority is and is not and the nuances of that. There is for example differing court cases in different federal appellant courts in the country. I will say that the state boards of pharmacy that licenses pharmacies and oversee the day-to-day operations, and we have some authority, and we can initiate enforcement action against the compounded drug if it is misbranded in certain ways, but on the other hand, the law exempts these companies from compounded drugs not manufactured in United States, and they do not undergo premarket review. So it is very, very complicated. With respect to what needs to be put in place at this point, I think that what we need to do is to sit down with pharmacists, with lawmakers and with other regulators to think about how to put in place the schemes that recognize the practice of pharmacy and the industry of compounding have evolved over time, and there needs to be a risk-based scheme put in place to deal with those issues. It is really unfortunate that it takes a crisis to bring this kind of change, but that is often the case. It is in crisis that we have the opportunity to the make change, and i hope that we can do it together to prevent these kinds of tragedies in the future.
ERICA JEFFERSON: Dr. Biondolillo, would you like to add anything?
MADELEINE BIONDOLILLO: Well, I would certainly agree with what Dr. Autor just said, and say that the licensing regulations in each state are different. In this case, we have a company that was apparently operating in violation perhaps of the licensing regulations for our particular state, but there is, you know, difference between the states and so, working together with all of the states and with our federal partners is really going to be a key to ensuring public safety as this industry evolves.
LENA SUN: I had a follow up.
ERICA JEFFERSON: Okay.
LENA SUN: Okay. And the follow up was in 2006, the FDA sent a warning letters to NECC and you were explicit in those warning letters that when a compounding pharmacy acts like a drug manufacturer, then you can definitely take action against them. There was some specific issues. Are the issues that you raised in 2006, were they resolved, and if they were, what did you do to make sure that the company did what it said it was going to do?
DEBORAH AUTOR: Sorry. Could you restate the question?
LENA SUN: You sent warning letters to NECC in 2006. And in those letters, you said that the company was acting like a drug manufacturer, and that the compounding was resulting in, you know, adulterated stuff, and there were issues and they were acting like a manufacturer, raised a whole host of issues. I’m — I don’t know if that investigation is still ongoing, but if it has been closed, if the company said that it took corrective action, i guess my question is, what did the FDA do to make sure that those corrective actions were actually, you know, taken? That they did what they said they were going to do.
DEBORAH AUTOR: Yes, a there has been a series of actions including after the letter correspondence back and forth with the firm where they assured us that they were adequately protecting the patients and complying with the applicable laws and regulations and, again, we took some action, and it is very, very complicated and the ability to take action here. So, while we did some, and we will continue to remain vigilant with respect to compounding pharmacies, it is also an ongoing concern as to what NECC was and was not doing. I will point out that they had the obligation to appropriately compound products, and in fact under Massachusetts state law, they were bound the follow the United States phrma cospeed (inaudible) chapter on appropriate sterile compounding practices your issues, and they had to understand the facts and what was done when and we will hold people accountable as appropriate.
LENA SUN: So is that investigation still open or closed?
ERICA JEFFERSON: Well, we will have to move on to get to the next question. Calvin, can we take that, please?
OPERATOR: The next question comes from Anna Edney with Bloomberg news. Your line is open.
ANNA EDNEY: Hi, thanks. Dr. Autor, and in relation to the warning letters, was NECC ever, did the FDA ever visit them again? You are not counting the most recent ones, the most recent investigation or, you know, inspections that you have done?
DEBORAH AUTOR: The state came back and inspected NECC.
ANNA EDNEY: Can the state talk about that?
MADELEINE BIONDOLILLO: So during the time period after 2006, there were not complaints registered with the state. There was a visit and inspection made in 2011. So there was no complaint activated in between 2006 and 2011 and in ’06, there was with a licensing action that needed to be investigated which is the renovation in some space, and that was conducted. And then there was a complaint in March of 2012 which is currently still under investigation.
ERICA JEFFERSON: Thank you. We will take the next question.
OPERATOR: Our next question comes from David Pittman from Medpage Today. Your question?
DAVID PITTMAN: A lot off my questions have been answered or asked by the people, but i will try to ask something. Is there any way that you can talk about the kind of the number or the put in perspective the growth of the problem nationally, and like how the pharmacies can go from acting like a small compounders to small manufacturers like this and how you can work with states to, to keep an eye on these folks, or is that a problem with the lack of clarity and the regulations and the laws?
DEBORAH AUTOR: I’m not sure I totally followed the question, but I think that challenges there is a lack of clarity in the law, and this has I think that the pharmacy practice and industry has evolved a lot, and that needs to be taken into account in the future in coming up with an appropriate regulatory scheme.
ERICA JEFFERSON: David, did you have a follow-up?
DAVID PITTMAN: Yes, can you speak about how you mentioned earlier about the potential civil and criminal remedies in the situation, and can you elaborate on that?
DEBORAH AUTOR: Sure. Under the federal food and drug and cosmetic act we have the authority to seize products. We have the authority to put firms under injunction which is to obtain a court order which requires them to do or stop doing the certain things, and we have criminal prosecution abilities if people violate the federal food, drug and cosmetic act.
ERICA JEFFERSON: We have time for two more questions. Calvin, the next to last question, please.
OPERATOR: Yes. The next to last question comes from Alice Park with Time magazine.
ALICE PARK: Yes, hi. Thanks for taking the question. I just wanted to clarify with Dr. Autor, you talked in the 2006 letter to NECC, can you clarify, are there, on what did you base the, the complaint that they were acting like a manufacturer and had sort of moved beyond acting like a compounding pharmacy, and also I’d like Massachusetts to address that if there is anything in the state regulations that set a limit on volume or how do you determine when a compounding pharmacy is reaching that limit and starting to, you know, go beyond its, what it is allowed to do under the registration.
DEBORAH AUTOR: Well, let me speak to one of the complexities here which is that there is some legal dispute about our ability to look at records and pharmacies, and it is the records that help us to determine whether a pharmacy is acting as a pharmacy or as a manufacturer. And so, in some cases, we are blocked from the threshold determination of the regulatory ability with respect to the compounders, because the regulatory ability is limited and so it becomes a bit of a catch 22 in respect to the agency’s ability to effectively regulate the pharmacies.
ERICA JEFFERSON: did you have a follow-up?
ALICE PARK: Yes, I would like to hear from the Massachusetts side on whether the regulations or the registration when people apply for the registration is there, you know, anything in those requirements in the state that sets a volume or looks at it? It seems that is where it would need to occur and that is something that the state would keep track of.
MADELEINE BIONDOLILLO: So, the regulatory authority at the Massachusetts board of pharmacy does not include tracking volumes of medications. Our regulations are specific in saying that each dose of a medication produced as in compounding procedures has to be tied to a patient-specific prescription, but there is nothing that speaks to a volume question.
ERICA JEFFERSON: The last question, please.
OPERATOR: Yes. The last question comes from Mark Bell with the Daily News Journal in Tennessee.
MARK BELL: Yes, I had a question about the sterility test, and it is clear if NECC was performing any sterility testing on the tainted medications?
DEBORAH AUTOR: This is ongoing investigation and I don’t believe we can comment on that at this point. We are continuing to thoroughly investigate this issue, and track down all threads and work with all stakeholders to put in schemes to prevent this type of tragedy in the future and put together the facts to make sure that all people who are to be held accountable will be held accountable as appropriate
ERICA JEFFERSON: And this is going to close the Q&A portion of the call. And now I send it back over to Curtis to close this out.
CURTIS ALLEN: I believe it was Maggie, and we will try to get the transcript up as quickly as possible, it will probably be available within two hours. Also there is an audio file available, and you can access that by calling the press 404-639-3286. Again, thank you very much for joining us today, have a good evening.
OPERATOR: That concludes today’s conference call, and that concludes your participation. You may disconnect at this time.