There has been a lot of press recently regarding the methotrexate shortage and there is talk that the crisis might be short lived. There are five manufacturers of methotrexate injection and they are apparently stepping up production in response to requests by the FDA and other health care officials. As a former pediatric oncology pharmacist, I can only hope this is the case. I am concerned that the time line to get enough product into physicians’ hands to treat patients could result in spot shortages.
There have been reports in the press that one company, that has shut down all production, is releasing product that was manufactured before its facility halted production. Additionally, the product being released has a very short shelf life and may only help patients for a few weeks. If the shortage does become a crisis, companies like JCB Laboratories, that specialize in compounding injectable drugs and chemotherapeutic agents, can help supply much-needed doses of these shortage drugs. For the last 12 months, JCB has been actively working to act as a stopgap when critical injectable drugs are unavailable. With a new state-of-the-art facility and a clean room dedicated solely to making dangerous chemotherapeutic agents, JCB really is a valuable resource in today’s environment of critical drug shortages.
For more on the methotrexate shortage, read:
Hospitals scramble to get scarce kids' cancer drug
Catheter-related bacteremia (CRB) is a major cause of morbidity and mortality among patients receiving hemodialysis. These catheter-related blood stream infections (CRBSI) often lead to hospitalization and can lead to other serious infections including osteomyelitis and endocarditis.
In a past blog I spoke about sodium citrate as an efficacious alternative to heparin as a catheter locking solution. A recent study presented at the American Society of Nephrology’s Kidney Week 2011 meeting addressed adding the antibiotic gentamicin to sodium citrate catheter locking solutions.
Prophylactic antibiotic locks have been proven to be a safe and effective way to prevent CRB. The ideal locking solution for a hemodialysis patient would prevent clotting in the catheter and be effective against a broad spectrum of microorganisms while not leading to resistance. One such combination discussed at Kidney Week 2011 was gentamicin 320 micrograms/milliliter in sodium citrate 4%. In the study using the combination, the overall CRBSI rate was significantly lowered and the time to first CRB event was significantly delayed. In addition, no increase in gentamicin resistance was observed.
Additional studies on this potentially ground-breaking combination are currently under way. Your dialysis center should consider the potential benefits and keep a close eye on the ongoing studies. A sterile compounding pharmacy with experience in dialysis products, such as JCB, can help you explore this interesting development.
Over the past five years, the United States has seen record high drug shortages each consecutive year. In fact, in 2011 there were over 250 drug shortages compared to 211 in 2010. More alarming is that roughly 75% of the drugs are injectables that are used in life saving procedures. Everything from anesthesia for surgery to critical cancer treatments were affected. In a country where excess is the norm, the obvious question is, “why are there so many drug shortages”? The answers are pretty straightforward but may be surprising. According to a recent FDA webinar regarding drug shortages, the top three reasons are:
- 54% due to product quality/significant cGMP issues (e.g., particulate, contamination, impurities)
- 21% due to delays or capacity issues at the manufacturing facility
- 11% due to discontinuations of drugs
It is alarming that the majority of drug shortages are due to quality issues. Over the last 12 months, several generic drug manufacturers have completely shut down their processing lines while working to fix their problems. With major drug manufacturer consolidation happening in the pharmaceutical market today, this leaves few companies as viable options to pick up where another company left off.
So, what is the FDA doing to help alleviate the drug shortage problem? The FDA has been very proactive in working with drug companies to help relieve the shortages. They are working with individual firms to address the quality issues and have been uncharacteristically flexible in order to divert any significant risks to patients. The FDA can expedite clearance of alternative supplies of drugs from unapproved sources. For example, when propofol was unavailable, the FDA approved temporary importation of propofol from non-U.S. sources. Overall, the strategies used by the FDA have led to the prevention of shortages for over 100 drugs in 2011.
Drug manufacturers are not required to notify the FDA or wholesalers of impending drug shortages. However, manufacturing firms are getting better at alerting the FDA when the possibility of a drug shortage arises. The proactive roles of both the FDA and the manufacturers are helping curtail further drug shortages that will ultimately save lives and hopefully avoid yet another record setting year for shortages in 2012.
Most of you have a main medication supplier, typically one of the three major wholesalers. Studies have shown that “normally”, about 95% of your medication needs are met by one of these large medication suppliers. However, we have not seen “normal” medication supply in many years; a result of record shortages five years in a row. More and more of our time is spent looking for critical medications from other suppliers.
How do you vet these alternative suppliers? Three critical areas that must be addressed:
- Licensure. Your supplier should carry the appropriate licensure to handle and ship medication to your facility. The supplier should either be licensed by the FDA or hold pharmacy/distribution licenses in their home state as well as the state where you reside. Ask for copies.
- Pedigree. Can the supplier provide documentation that your medication originated at the licensed manufacturer? They should be able to prove who handled the medication from the time it left the manufacturer to the time it arrived in your facility. Sometimes the med will come to your supplier directly from the manufacturer and other times there are middlemen.
- Storage conditions. Make sure the supplier properly stores and secures the medication prior to shipping it to you. Temperature and humidity should be monitored 24 hours a day. Drug products should not be co-mingled with other non-drug items. Only trained, authorized personnel should have access to medications. Ask the supplier for proof of required environmental monitoring.
If you are the person in charge of ordering medications at your facility, you understand that once the med arrives in your facility, you are responsible. Make sure you have performed adequate due diligence in selecting all of your medication suppliers.
1. Manufacturing integrity
- Do they comply with the requirements of USP 797?
- Is their clean room monitored and validated?
- Has Ribo-typing been performed?
- Has the equipment been validated to perform within its specifications?
- Can the clean room conditions be matched to time of drug compounding?
- Manufacturing procedures:
- Are there standard operating procedures in place?
- Can they be produced for verification?
- Can they electronically validate all weights of powders in each formula?
- Can photographic evidence be produced for all liquid measurements in each formula?
2. Third-party validation
- Do they serve national accounts (AmSurg, etc.) or are they vendors for GPOs?
- What other companies or agencies have inspected them (pharma, independent cGMP audits, etc.)?
- Can they provide references from other customers?
3. Leadership/customer service
- What are the resumes of top management? Are pharmacists leading the company?
- Who is available for technical questions and how fast are they answered?
- What are the qualifications of the staff and technicians at the facility?
--Origianal article by Rob Kurtz in Becker's ASC Review
1. Regulatory problems and other challenges are going to continue to create shortages for critical drugs. Drug shortages are at an all-time high. There are three primary reasons for today's drug shortages: raw material shortage (powder is not available), regulatory issues (manufacturing plant has an FDA compliance issue) or financial/economic reasons (a company decides to discontinue producing a drug). While there are a few legislators trying to enact laws to help ease the situation, there’s no doubt drug shortages will continue to be an industry problem.
2. When drugs become scarce, outsourcing is an option worth exploring. Most healthcare facilities have primary wholesalers from whom they order the majority of their drugs. In cases where drugs are unavailable or in short supply from primary vendors, secondary or tertiary wholesalers are often contacted. Alternative sources should be qualified and they should be able to provide pedigree information for the products. When wholesalers can’t meet demand, compounded drugs may be a reasonable option.
3. Alternative drugs and wholesalers can carry significant costs. While purchasing an alternative drug or using an alternative wholesaler are means of overcoming the lack of availability of a commonly used drug, ASCs may see a noticeable increase in cost. Markups as high as 3,000-4,000 percent are not uncommon. It's a significant issue when it comes to dollars.
4. Dosing and concentration differences can create safety problems. The need to switch from a familiar drug to an alternative can do more than just raise costs — it can also create safety problems. If you have to use an alternative drug that has different dosing and concentration from the traditional drug, double check the dosing and communicate any differences to your staff.
5. Lack of drug availability can hinder efficiency. At many ASCs, a staff nurse, clinical nurse manager or director of nursing is responsible for ordering. With all their other responsibilities, the last thing they need is to spend 2-3 hours trying to source unavailable drugs. If an alternative drug is found, it often requires retraining of staff to ensure proper dosing and administration. This can create inefficiencies during patient cases, which will inevitably decrease throughput.
6. Outsourcing not always an appropriate option. Outsourcing should not be considered when patient safety is questioned. If forced to look at alternative options for securing drug products, patient safety should be the first priority. Some unscrupulous “gray market” drug providers are more interested in making a quick buck than protecting patient safety. If there is any question about the credibility of drug suppliers then the choice should be made to not use them. Partnering with a company that can help locate credible alternatives is important.
Reprinted with permission of ASC Review. Copyright ASC Communications. For the original article, please click
here.
As a dialysis professional, you routinely use catheter locking solutions to maintain patency in hemodialysis catheters for your long-term dialysis patients. Heparin has traditionally been used for this purpose. However, some of your patients will experience an allergic reaction to heparin or a more serious complication known as heparin-induced thrombocytopenia (HIT). Sodium citrate has been shown to be an efficacious alternative to heparin as a catheter locking solution. Additionally, some studies show that sodium citrate acts as an antimicrobial.
30-mL Multiple Dose Vials of Sodium Citrate 4% Solution Offer a Safe Alternative to Large Single-Use Bags.
Sodium citrate from a manufacturer is currently only available in 250-mL bags and is labeled as single-use only, which means only one entry into the bag is allowed. Unlike a 250-mL bag of solution, you can withdraw solution from a multiple-dose vial repeatedly and the risk of contaminating the vial is dramatically decreased. This means less chance of causing an infection in your patients.
When choosing a pharmacy to compound sodium citrate, look for a proven sterile compounding pharmacy with a history of serving dialysis centers. Ask if they have experience in compounding sodium citrate. Are they a preferred provider for national dialysis groups?
Your dialysis center should consider the increased safety associated with sodium citrate as a catheter locking solution as well as the cost effectiveness and additional safety of a 30-mL multi-dose vial.
If you are a podiatrist or an ophthalmologist, or you work with either of these specialists, dehydrated alcohol injection is most likely a staple in your practice. It’s so common, in fact, that it’s easy to take it for granted. That is, until a recent shortage made it hard to find or all together unavailable. The reason for the shortage is simple: there was only one manufacturer supplying this med and quality issues at the manufacturing site forced them to shut down production. The shortage will continue until the FDA is satisfied the manufacturer meets requirements for good manufacturing processes.
Dehydrated alcohol for injection is indicated for neurolysis in patients as a way to treat chronic pain, especially in patients for whom surgery is not a good option. Ophthalmologists also use it for delamination of the corneal epithelium. Dehydrated alcohol Injection consists of not less than 98% by volume of ethanol (ethyl alcohol). Whether you dilute the alcohol to treat Morton’s Neuroma or use it full strength for ophthalmic procedures such as Recurrent Corneal Erosion Syndrome (RES), supply of this critical agent is extremely limited.
So, what are your options? Your most reliable option is a proven, experienced sterile compounding pharmacy. A Google search is just the beginning. Once you have found some sterile compounding pharmacies, call them. Ask to speak with a pharmacist and find out how they comply with USP <797>. Will they send you copies of their Standard Operating Procedures? Are you welcome to audit their compounding facilities at any time? When you have medication shortages or other medication related needs, the right sterile compounding pharmacy partner can be a tremendous asset to your practice.
Q&A With Brian Williamson of JCB Laboratories - by Rob Kurtz
Brian Williamson, PharmD, is president & CEO of JCB Laboratories.
Q: Can you explain the 60-minute rule for compounded medications per USP 797 and how organizations need to meet this rule?
Brian Williamson: The principle concern of the USP Sterile Compounding Committee was minimizing the risk to patients from medications drawn up from single-dose vials in ambient air or under less than ideal conditions. I'm sure that you have heard of the incidents of contamination from the misuse of single and multiple-dose vials in Las Vegas. There are studies that show microbial growth in media when simulated compounding activities occurred in ambient air environments. In the case of microbial contamination under the immediate-use conditions, one hour is nearly 100 percent guaranteed to not result in colonization or microbial population increase (i.e., not cause patient harm) based on the typical lag time of up to 4-6 hours for many microbial inoculations under ideal growth conditions.
Validating the efficacy of this practice is not easily tested at the individual patient level because the rates of failures are often low. Because of this, we need to understand that the traditional evidence-based approach cannot be the sole source of information for advancing patient safety. Many of the improvements in medicine, particularly anesthesia practices and aviation safety, were not built on evidence that certain practices reduced the frequency of errors or crashes. It relied on the widespread implementation of hundreds of small changes in procedures, equipment, training and organization that aggregated to establish a strong safety culture and amazingly effective practices. These changes made sense; were usually based on sound principles, technician theory, or experience; and addressed real-life problems, but few were subjected to controlled experiments. The one-hour timeframe was one of those small changes targeted at preventing contamination.
How do organizations meet this rule? Logistically, it has some challenges but they can be overcome with staff training and understanding why the rule is in place. Many facilities are outsourcing activities such as drawing up syringes for cases or mixing products together. Reputable compounding pharmacies are able to perform many of these activities and those that specialize in preparing sterile products should have the facilities to ensure longer shelf life dating.
Note: Thank you to Eric Kastango, who served on the USP Sterile Compounding Committee, for providing some of the information referenced in this response.
Reprinted with permission of ASC Review. Copyright ASC Communications. For the original article, please click here.
You are probably using Mitomycin C for various procedures, most often reconstituting it for ophthalmic, urologic, and chemotherapy treatment. Since it is a cytotoxic agent, proper procedures must be taken to prevent exposure to the drug during reconstitution. This common but hazardous process has prompted some surgery centers to outsource compounded mitomycin. To make matters worse, mitomycin is on national back order, prompting many more surgery centers to consider outsourcing.
Save Time
There are some distinct advantages if you outsource mitomycin for your ophthalmic and urologic cases. The mitomycin will arrive at the facility in solution ready for administration to the patient. You don’t need to manipulate the product beyond taking the cap off and placing a needle or urethral tip on the syringe. Stability is another benefit. Verified data shows that the mitocycin JCB reconstitutes in syringes is stable for 42 days when refrigerated and 11 days at room temperature. This stability allows you to have several weeks supply on hand rather than ordering within a couple days of every procedure.
Reduce Risk
What are the drawbacks to outsourcing? (1.) Be prudent when choosing your sterile product pharmacy. Some outsourcers have supplied frozen mitomycin. Be aware that current literature does not support storage of mitomycin in a frozen state. Studies show that when frozen, mitomycin will form a fine, pink, needle-like precipitate that does not dissolve when thawed in a microwave. Precipitate in the product can cause physical damage to the eye or pain upon injection or instillation in the bladder. (2.) Your outsourcing pharmacy should package the mitomycin in bags clearly marked with cytotoxic labeling. Make sure all your personnel understand the hazardous nature of the drug and how to properly handle the product. (3.) Finally, be sure to dispose mitomycin waste properly in yellow cytotoxic waste containers. You can then contact hazardous material disposal companies to pick up the containers and provide documentation of proper disposal.
Outsourcing Mitomycin can be a time and risk saving measure. Just make sure your outsourcer is familiar with proper preparation, storage and packaging.