Considerations for Determining Pharmacy-Specific Hazardous Drugs

As of January 1, 2017, California law requires pharmacies compounding with anti-neoplastic agents as classified by National Institute for Occupational Safety and Health (NIOSH) do so within the proper facilities and engineering controls as defined in CCR §1735.6(e) and 1751.4. The law also requires any other drugs, compounds or materials to require these same conditions if determined hazardous by the PIC. Each pharmacy must review their operations to ensure they are meeting this new mandate to protect their employees and the public. This document contains considerations for determining if any other drugs outside of the NIOSH anti-neoplastic agents require the same compounding conditions. 

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Final Compounding Regs for California: Hazardous Drug Compounding

New Pharmacy compounding regulations for California have undergone multiple iterations since last year, with the latest version set to be approved. In February the board of pharmacy voted for these regulations to take effect immediately upon being approved by the CA Office of Administrative Law (OAL) despite commentary from numerous stakeholders requesting a buffer period to account for operational lag time. Most of the push back came from the inclusion in the new regulations of certain parts of the newly published USP <800> for hazardous drugs in health care settings.  

The new California regulations for pharmacy compounding are expected to become law as early as January 1, 2017. This gives California compounders and CA-licensed non-resident pharmacies a little over six months to become compliant with the new laws. In addition to new definitions, CA has also added details for facilities and equipment needed for the safe handling and manipulation of hazardous drugs similar to USP <800>. The following is a summary of major highlights compounders should be aware of immediately in order to prepare for the January 1, 2017 live date. In this paper the language in the California regulations is examined to understand what these new requirements are, learn how facilities can be set up to comply with them, answer some frequently asked questions, and differentiate between the CA regulations and USP <800>. For complete information on all new compounding regulations, click here. 

READ: Final Compounding Regulations for California: Hazardous Drug Compounding PDF

FDA Draft Guidances Released for Industry

In mid-February the FDA issued 5 draft guidance documents regarding the practice of pharmacy compounding. Among these documents stood out a draft memorandum of understanding- a document that dictates the terms under which a state board of pharmacy is expected to communicate with the FDA at the direction of the Drug Quality and Security Act (DQSA). The terms described in this document also allow pharmacies an expected percentage of prescriptions which may be shipped out of state.  The major surprise however was seen in the document entitled "Mixing, diluting, or repackaging biological products outside the scope of an approved biologics license application".  While these documents reflect the agency's current thinking on the said topics, they are not yet enforceable law. They do however, pose a very serious threat to the livelihood of compounding pharmacies focusing on the repackaging of biologics. 

Draft Memorandum of Understanding (MOU) Between a State and the US FDA Addressing Certain Distributions of Compounded Human Drug Products

The memorandum of understanding seeks to define conditions under which state boards of pharmacy must alert the FDA when the practice of traditional (state-regulated or 503A) compounding potentially becomes outsourcing as defined by section 503B of the DQSA. The limit set forth in this document is 30% of distributed patient prescriptions, out of the total dispensed and distributed prescriptions. Per the FDA, "distribution" includes office use prescriptions as well as dispensing to individual patients or agents of patients. For many pharmacies, this 30% allowance may alleviate any concern about sending compounded medication out of state, but for others, the 30% is still well exceeded. Major concerns about this draft guidance are: 

1.  States that do NOT sign an MOU may in fact face greater FDA interference with state/tradition compounding practice
2.  States that do NOT sign an MOU may still be responsible for communicating information about interstate shipping to the FDA

States that enter into an MOU with the FDA will be given the duty of investigating pharmacies that receive complaints and are responsible for reporting complaints to the FDA within 72 hours. Therefore, regardless of a state's election to sign an MOU with the FDA, states still face greater federal involvement in the practice of tradition pharmacy compounding. 

Mixing, Diluting, or repackaging biological products outside the scope of an approved biologics license application 

The contents of this guidance document do not directly reflect any aspect of congressional intent during the writing and passing of the Drug Quality and Security Act. Yet ,the FDA has put forth strict terms for the repackaging, mixing, diluting of biological drugs. While many patients depend on repackaged drugs, the language in this document would greatly restrict patient access to critical compounded treatments. The major implications of this document are as follows: 

1. For Outsourcing Facilities, repackaged biological drugs may be repackaged, as long as the beyond use date does not exceed 5 days if appropriate sterility and packaging compatibility studies are conducted; otherwise a 24 hour beyond use date with microbial studies may not be exceeded
2. For traditional pharmacy compounders,  repackaged biological drugs may be repackaged, as long as the beyond use date does not exceed 24 hours if appropriate sterility studies are conducted; otherwise a 4 hour beyond use date may not be exceeded 

There are many other stipulations for the repackaging of biological products which can be read on the documents, however, these items represent the most significant restrictions on the practice. Despite numerous published studies available on the chemical stability and microbial profile of repackaged biological drug products, the FDA has established a means of effectively removing the possibility of pharmacies compounding biological products for patients and prescribers. Both physicians and pharmacists are left wondering how to combat these guidelines in order to preserve patient access to critical oncological, ophthalmological, and other therapies.  The comment period for this guidance is from Feb 13 - May 13, 2015. ITL Consulting is providing testimony from sterile compounders and prescribers in order to voice the concerns for patient access to the FDA. 

We urge all stakeholders to submit comments on these documents to ensure a positive effect in preserving patient access to repackaged biological drug products from pharmacy compounders.  

guidance documents can be located here

http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm434270.htm

Considering PCAB Accreditation? Here's a few tips!

In July 2014, the Pharmacy Compounding Accreditation Board (PCAB) became a service of the Accreditation Commission for Health Care (ACHC). ACHC is a large, nationally recognized agency that accredits health care practices spanning the industry. With this new change also came new standards for pharmacy compounding. Those familiar with the PCAB accreditation manual will no longer see this set of standards as their reference for practice. 

In recent news, PCAB made headlines after the Professional Compounding Centers of America (PCCA) announced the establishment of a preferred provider network of compounding pharmacies that are PCAB accredited. This network, called PersonalMed, will be the middleman between PCCA's member pharmacies and the PBMs handling claims for their compounded drugs. Like other preferred networks, pharmacies will pay a pre-negotiated fee to participate be included in the network and will be subject to the terms set forth by PersonalMed including reimbursable formulary, audits, credentials, and more. 

The popularity and number of PCAB accredited pharmacies has been steadily growing since the group's inception in 2007. The revised standards recently set forth by ACHC set the industry benchmark for quality in pharmacy compounding. Pharmacies striving to achieve this distinguished status invest significantly in time, energy and money. The ability to market and demonstrate a commitment to quality makes this investment worthwhile. 

ITL Consulting's pharmacists began consulting for PCAB accreditation in 2011. Since then, PCAB accreditation has become an integral part of our core services. Under ACHC, the accreditation process has undergone some key changes. In order to accelerate the process for our clients, we have developed a unique approach to the process in order to achieve accreditation goals in a minimal amount of time. Provided here are some key considerations for determining the readiness for your practice and some tips for facilitating the process. 

Apply  

To begin the process, you will need to logon to ACHC.org and register your practice. Along with creating a pharmacy profile an accreditation application must be completed along with detailed information about the business. An application fee will also need to be submitted along with agreements of terms. 

Download 

The ACHC standards for pharmacy compounding must be downloaded through the website. For pharmacies that are currently accredited through the PCAB standards, there is a cross-walk available to reference the new standards according to your own policy manual. 

Review 

The new ACHC standards should be reviewed by the party responsible for leading the accreditation process and examined to determine any financial requirements, staff changes, or other major operational considerations. Major changes will need to be considered in the overall project budget and often times become the deciding factor. 

GAP Analysis 

The policies and procedures manual is often the most time consuming part of the process. Each pharmacy is responsible for submitting a manual that it is in compliance for the accreditation applied for. The completion of this step is not required to be completed prior to the application process, but will allow for a head start on planning to meet the standards. To begin this process, a GAP analysis referencing the current policy manual should be performed. This analysis should be used to make a project timeline which will be the guiding tool for the project. 

A Preliminary Evidence Report that must also be submitted along with the initial application information. This is a checklist signifying to ACHC that the applicant meets the initial requirement of baseline policies and procedures prior to scheduling a survey. The list of these policies and procedures is including in the application info. 

Scheduling

Once the required application info and agreements have been submitted and approved, the applicant will be able to choose days which an ACHC representative will not show up for the initial survey. Each practice should consider which days are best in order to have the project leader available to answer questions and guide the representative during the visit. Consider blacking out days where high-volume is expected, key staff may be away, or other projects may interfere with practice workflow. 

These initial few steps should provide a solid foundation for efficiently launching the accreditation process. In small businesses, efficiency is as critical as ever, and misallocating human capital to nonessential tasks may pose a serious financial threat. A cost analysis of how great a financial burden an accreditation project may be using only internal staff  may be greater than expected due to the large time commitment and unknown logistical challenges. ITL Consulting works with pharmacies where this financial burden is simply too great to consider accreditation. Our pharmacists provide all the resources needed for the accreditation process in a single program. By allowing each organization to design their consulting program according to their needs, we take pride in making accreditation a reality for our colleagues. Contact a pharmacist consultant today to learn more about how you can benefit from PCAB accreditation. 

USP <795> Beyond Use Date Guidelines: An Accepted Standard or Unfair Restriction?

Ask the average compounding pharmacist what the USP <795> general guidelines state about stability and beyond use date (BUD) and they can pretty clearly explain it; for compounded formulations without stability information they can assign a BUD up to 30 days for water containing topical formulations, 14 days at cold temperature storage for water containing oral formulations, and 6 months for non-aqueous formulations. 

Unfortunately, the reality of how each pharmacy currently assigns BUDs for their formulations does not match their rhetoric.   Further, the reality of how each pharmacy board inspector understands these guidelines or even begins to enforce these guidelines is unclear and inconsistent.  Even further, the reality of how each accrediting organization inspector enforces these guidelines varies based on the inspector’s individual qualities and discretion. 

To take it a step further, here is the pertinent section from California pharmacy law, Article 4.5 section 1735.2(h):

“Every compounded drug product shall be given an expiration date representing the date beyond which, in the professional judgment of the pharmacist performing or supervising the compounding, it should not be used. This “beyond use date” of the compounded drug product shall not exceed 180 days from preparation or the shortest expiration date of any component in the compounded drug product, unless a longer date is supported by stability studies of finished drugs or compounded drug products using the same components and packaging. Shorter dating than set forth in this subsection may be used if it is deemed appropriate in the professional judgment of the responsible pharmacist.”

All throughout the country, California included, many compounding pharmacies are opening up based on the financial opportunities and unfortunately their pharmacists in charge are often not capable of determining a BUD by “professional judgment” as stated in the law.  But even well established and experienced compounding pharmacies do not have the capability to make these determinations based on the law and the current guidelines.  This forces law and guideline abiding pharmacies to put forth thousands of dollars to validate the BUDs for their compounded products. 

But wait… isn’t there any easy way out of this?  Many pharmacy owners think there is.

It is very common for a pharmacy owner to tell me something like, “We get our BUDs from our wholesaler who provides the formula and the BUD, and we use that as documentation.”

And let the debate begin… and then the anger… and then the frustration with having to comply with these standards.  First, I urge them to contact the wholesaler who provides them with the formula and ask for any credible documentation for the BUD and also any packaging information for the BUD studies so they can reasonably apply the BUD to their product.  Unfortunately, most of the provided formulas do not have the support necessary to use to truly comply with the law and standards, so this road leads us right back where we started.  The pharmacy cannot comply with the USP 795 guidelines without spending thousands of dollars.

So why is this discussion important when a large portion of the industry has been getting by for many years with using BUDs that clearly do not comply with USP 795?  The answer is simple, PCAB accreditation.  PCAB’s compounding industry influence goes well beyond just their accredited pharmacies. 

PCAB has been extremely successful in bringing these standards to the table and it has been the most successful organization at integrating USP into community compounding practices.  Pharmacies understand that to be PCAB accredited they will have to take clear steps to abide by USP, including the USP 795 BUD general guidelines.  

Unfortunately, these BUD guidelines are one of the most critical barriers preventing the majority of the industry from attempting PCAB accreditation.  Many compounding pharmacies are motivated and driven to move their pharmacy towards USP compliance in policies and procedures, training, cleaning and almost all other standards, but the financial burden required to implement the BUD guidelines is prohibitive. 

The industry is brought to a halt in progress by this cost restriction and it leaves me pondering a couple of key questions:

1) If these guidelines are considered enforceable standards, then how come only certain pharmacies are truly complying with them? 

2) And is it fair that many pharmacies spend thousands of dollars annually on stability indicating studies while their competitors spend nothing and just assume a longer BUD with no regard for USP?

As part of our ITL Consulting True Quality Partners program, there is a strong focus on ongoing compliance, quality assurance, and finding the optimal ways to approach these BUD guidelines and each pharmacy’s state specific laws.  We also provide guidance to pharmacy's considering PCAB accreditation and if it is right for their practice.  

Please contact us with your interest in having a free consultation with our pharmacists regarding these guidelines and your practice. 

USP <800> [Revised] - FACILITIES

The newly revised <800> addresses the numerous comments from the industry that were recently submitted. Some of these changes include word clarification, removal of the 'no acceptable level of hazardous drugs' statement, and the allowance for an entity to perform its own risk assessment in determining which hazardous drugs (HDs) must follow the chapter guidance.  

This post will provide a  practical summary of Section 5. FACILITIES, as this section may potentially have the biggest impact on the industry should regulatory agencies choose to actively enforce these new requirements. 

THERE WILL BE A SECOND ROUND OF PUBLIC COMMENTS FOR CONSIDERATION BY THE USP EXPERT COMMITTEE. PLEASE TAKE THE TIME TO REVIEW THE CHAPTER AND SUBMIT COMMENTS AS THEY PERTAIN TO YOUR PRACTICE! 

CLICK HERE FOR THE DRAFT OF <800> 

5. Facilities

The use of HDs must be considered in way that promotes safety for all employees, patients, and the surrounding environment. Along with restricted access limited to those who must access HDs, there must be a sign at the entrance indicating designated areas, which must be available for the following operations: 

• receipt and unpacking of antineoplastic HDs or HD active pharmaceutical ingredients 
• storage of HDs
• non-sterile HD compounding (if performed)
• sterile HD compounding  (if performed) 

RECEIPT

HDs may not be unpacked or removed from external shipping containers in sterile compounding areas or any positive pressure area. 

STORAGE

HDs must be stored in a manner that prevents spillage in the event the container falls and breaks. These may not be stored on the floor. 

Antineoplastic drugs that require manipulation (other than counting a final dosage form) must be stored separately from non-hazardous inventory and must be stored in a negative-pressure room. 

Only HDs used for sterile compounding may be stored in a negative-pressure buffer area. 

Refrigerated antineoplastic drugs require storage in their own dedicated refrigerator which must be located in a negative-pressure area, which may be a storage area, buffer-area, or other segregated area. If located in the buffer-area, the placement of an exhaust next to the compressor should be considered. 

COMPOUNDING

All compounding with HDs must be performed in a separate, negative pressure room with at least 12 air changes per hour and meet the following specifications: 

• externally vented through HEPA filtration 
• physically separated from other rooms
• have a negative pressure between 0.01 and 0.03 inches of water column 

If a containment workstation where direct manipulation of sterile compounding takes place, the unit must operate continuously. 

Sinks and eyewash stations for treating exposure to hazardous drugs must be available, with consideration for affecting ISO classification and applicable state laws. 

If both sterile and non-sterile compounding takes place, the containment devices for direct compounding must be located in separate rooms, unless the device for non-sterile is able to maintain the ISO 7 classification throughout non-sterile compounding operations. In this case, each compounding device must be placed at least 1 meter apart and no particle-generating activity can be performed during sterile compounding activities. 

NON-STERILE COMPOUNDING

A compounding containment device for the manipulation of non-sterile HDs is required for any compounding activity that generates particles, aerosols, or gasses. 

This device may be externally vented, which is the preferred mode, or use redundant HEPA filtration in series. Examples of these devices, which must provide personnel and environmental protection, may be a Class I or II biological safety cabinet (BSC), aseptic containment isolator or containment ventilated enclosure. 

For occasional non-sterile HD compounding, a containment device used for sterile compounding may be used, providing it is decontaminated and throughly cleaned and/or disinfected prior to using for sterile compounding. 

Any device used for non-sterile HD compounding is not required to have unidirectional airflow, as there is no ISO classification requirement for air quality with non-sterile compounding. 

Work surface requirements from <797> apply to the compounding of non-sterile HDs due to the difficulty of cleaning contamination. 

STERILE COMPOUNDING

<800> requires compliance with <797> standards for all sterile compounding activities. 

All containment devices for compounding of sterile HDs must be externally vented and contain ISO 5 air or better. Examples of these devices include, Class II or II biological safety cabinet, or aseptic containment isolator. For Class II BSCs, type A2, B1, or B2 are acceptable. 

Low and medium-risk (only) sterile compounding may be performed in a separate, negative pressure room with at least 12 air changes for hour, within a biological safety cabinet or aseptic containment isolator, provided the beyond use date does not exceed those denoted in <797>. This description is not an ISO 7 classified buffer area and also must contain a sink for hand washing not within 1 meter of the compounding device.

ISO 7 Buffer Area for HD Sterile Compounding 

•  Negative pressure between 0.01 and 0.03 inches of water column 
•  Minimum of 30 air changes per hour of HEPA filtered air
•  Hand washing sink 1 meter or more from the entrance into the room

The ante-area through which the buffer room is entered must contain: 

•  Minimum of 30 air changes per hour of HEPA filtered air
•  Positive pressure of a minimum of 0.02 inches of water column 
•  Maintain ISO 7 classification air quality or better 

These are some of the main practical considerations to observe when examining how your practice can comply with these new requirements. There are different configurations your practice may take when complying with <800>, and ITL Consulting can help your facility to meet compliance with this chapter with minimal disruption and maximum efficiency.

Click here to download this post as a PDF 

Contact a pharmacist consultant today to learn more about facility design and compliance with USP <800>.

USP <71> Sterility Tests: Table 2 & 3 Calculator

With the growing scrutiny on sterile compounding pharmacies and a push towards external accreditation and cGMP, USP <71> Sterility Tests is an extremely important chapter to understand and comply with.  The chapter discusses two forms of sterility testing: membrane filtration and direct inoculation.  It details two appropriate culture media that may be used for the sterility tests.  Fluid thioglycollate medium used primarily for culture of anaerobic bacteria and soybean casein digest medium suitable for both fungi and aerobic bacteria.  Another critical feature of the chapter is the incubation temperature and time, which are important factors for chapter compliance.  In a future post we will further discuss the aforementioned topics and other components of the chapter, including method suitability tests, and how these concepts will increase in prevalence across our industry going forward. 

At the core of the chapter are Tables 2 and 3 which define the minimum quantity to be tested and the number of articles to be tested for each batch that requires sterility testing.  ITL Consulting has created a free resource for the industry, which is two simplified version of these tables and an excel document that calculates the appropriate number articles and quantity to be tested for each batch.  These documents focus on specifically on liquid sterile preparations, including parenterals, ophthalmics, and non-injectable products.  

For a free copy of this resource, please email questions@itlconsulting.net or click the link below and complete the form - Subject: USP <71> Calculator 

Sterile Compounding Special Report

The California Board of Pharmacy inspected 578 sterile compounding pharmacies in hospital and community settings in a span of 3 months. Their report of these findings presented some basic points regarding violations. 

Because this represents a large portion of California's sterile compounding pharmacies, ITL Consulting has re-tabulated the same data to detect further trends for the purpose of citing practical data during the revision period of California's sterile compounding regulations. This report takes a detailed look at the findings, provides a brief analysis, and lists recent legislative initiatives in other states. 

Click here to download the report 

Pharmacy Law Brief - Federal Compounding Rules- 503A

Click here for the PDF version of this Pharmacy Law Brief

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Earlier this month the Food and Drug Administration released policy guidance documents explaining the agency's thinking on the two central sections of the recently amended Food, Drug, and Cosmetic Act (FDCA)- Sections 503A and 503B. These guidance documents provide more detail as to how the agency plans to implement the new provisions of the law pertaining to pharmacy compounding. For many stakeholders, these documents are critical in ensuring the agency is continuing to work with state boards of pharmacy and to continue protecting patients who depend on compounded medication.

Presented here is the digested language of the guidance document for Section 503A- one of two sections essentially bisecting the compounding industry. 503A defines 'traditional compounding' and 503B, outsourcing facilities. Although the agency expects state boards of pharmacy to continue their oversight and regulation of pharmacy compounding, the extent to which they will allow the state boards of pharmacy to regulate practice in accordance with their respective provisions cannot be known for sure. It is implied that the definitions and criteria set forth by these two sections of the FDCA will become the regulatory magnifying glass by which state boards of pharmacy must examine pharmacy compounding in their states. Furthermore, state boards and the FDA must work together to address pharmacy practices that fall outside the lines of these two sections. Provided here are the requirements the agency will enforce for compounding pharmacies not registered as outsourcing facilities.

Section 503A 

To qualify as a traditional compounding pharmacy, a pharmacy practice must: 

1. Compound a drug product for an identified individual patient pursuant to a valid prescription 

2. Have a licensed pharmacist compound drugs in a licensed state or federal facility 

3. Compound a drug in limited quantities prior to receipt of a valid prescription for an individual and based on a history of the pharmacist or physician receiving those prescriptions and there is an established relationship between pharmacist/physician and patient 

4a. Compound drugs in compliance with USP chapters on pharmacy compounding that comply with USP or NF monographs

•  If there is no monograph, the drug must be a component of an FDA-approved human drug

4b. If it is not a component of an FDA-approved human drug, it must be on the FDA approved list of bulk drug substances for use in human compounding 

5. Use bulk ingredients that are manufactured by a FDA registered entity 

6. Use bulk ingredients that have an accompanying certificate of analysis or purity 

7. Use ingredients that comply with USP/NF monographs, if applicable, and USP chapters on compounding

8. Not compound with bulk ingredients on the FDA 'do not compound' list 

9. Not regularly compound or compound in large amounts drugs that are essentially copies of commercially available drugs 

10. Not compound drugs identified by the FDA to be demonstrably difficult to compound 

11. Not ship a quantity of compounded drugs that represents more than 5% of total prescription orders out of state - unless the state has entered into a memorandum of understanding (MOU) with the FDA regarding interstate distribution of compounded medication.

Notes: 

- Provisions pertaining to physician compounding were not discussed

- These guidance documents and federal regulations apply only to compounded drugs for human use; drugs for veterinary use are not affected by these regulations. 

- Many of these provisions requiring submissions in order to establish a list of drugs will not be enforceable until the FDA announces an official list and sets forth implementation regulations. 

- A state may enter into a MOU with the FDA only after the FDA releases a draft MOU for comments and consideration. Following this release, the FDA will then enforce the 5% limit in states that have not signed and entered into the MOU. 

- In regulating pharmacy compounding in accordance with these provisions, a risk-based inspection criteria will be used, as described in the Drug Quality and Security Act and will place greatest importance on what is deemed to pose the greatest risk to public health. 

Executive Summary: California Proposed Compounding Regulations

The California Board of Pharmacy has released the language for the proposed regulations amending several sections of the law pertaining to pharmacy compounding for sterile and non-sterile practice. This executive summary focuses on summarizing the major changes put forth and less so on grammatical changes inserted for the purpose of distinguishing pharmacy compounding from manufacturing. Section titles are shown in their proposed language.

Click here to download the print-friendly PDF version 

Click here to read the full text proposal from the CA Board of Pharmacy

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Title 16 Article 4.5 

Section:

 1735.1. Compounding Definitions 

Amended to include definitions for: 

Ante-area

Batch - means compounding of two or more finished drug preparation units produced during the same continuous cycle of compounding and shall include any multiple dose vials prepared for administration to more than one patient

Beyond Use Date

Buffer area

Cleanroom

Controlled cold temperature

Controlled freezer temperature

First air

Gloved fingertip sampling

Integrity - all aspects of quality including sterility, packaging, chemical stability and potency, handling and transport and storage are maintained throughout the drug preparation process, and until the beyond use date provided on the label

Media-fill test

Parenteral

Personal protective equipment 

Potency - added reference to range specified by USP37-NF32, 37th revision 

Preparation

Prescriber's Office 

Process validation

Product

Primary Engineering Control (PEC) 

Segregated compounding area 

Smoke test

1735.2. Compounding Limitations and Requirements; Self-Assessment 

Amended to clarify provisions for prescriber's office compounding. An order for a compounded medication must be ordered and paid for by the prescriber using a purchase order or other order form that lists the number of patients seen or to be seen in the prescriber office for whom the drug is needed or anticipated, and quantity for each patient sufficient for treatment in the office or for furnishing of no more than a 72 hour supply. The order must be delivered to the prescriber office and signed for by the prescriber. The pharmacy may not dispense an amount beyond which they can reasonably and safely compound. 

Further limitations found in this section are inserted from the recently amended Section 503A of the Food, Drug and Cosmetic Act (FDCA). No pharmacy or pharmacist shall compound a drug that:

1. is classified by the FDA as demonstrably difficult to compound

2. appears on a FDA list of drugs that have been withdrawn or removed from the market because such drugs or components of such drugs have been found to be unsafe or not effective; or 

3. is a copy of essentially a copy of one or more drug products, unless that drug product appears on an ASHP or FDA list of drugs that are in short supply at the time of compounding and at the time of dispense. The pharmacy shall retain a copy of the documentation of the shortage in the pharmacy records for three years. 

Compounding master formula records must contain the rationale or reference source for determining the maximum allowable beyond use date. 

A compounding self-assessment must be completed for a change of location. 

Ingredients that lack a supplier's expiration date are subject to following limitations: 

1. such ingredients cannot be used for any non-sterile preparations more than 3 years after the date of receipt by the pharmacy unless documented inspection or analytical testing indicates that the ingredient has retained its purity and quality for use, considering the container in which it is packaged and the storage conditions. 

2. the same is stated for sterile preparations no more than 1 year after the date of receipt by the pharmacy, unless inspection or analytical testing indicates otherwise. 

1735.3. Recordkeeping for Compounded Drug Preparations 

Pharmacy records for compounded preparations must include storage information. Procuring ingredients should be, whenever possible, through FDA registered supplier. 

Certificates of purity or analysis must be matched to the product received. 

If records are stored only electronically, on magnetic media, or in any other computerized form, the records shall be maintained as specified by Business and Professions Code section 4070 subsection (c). 

1735.4. Labeling of Compounded Drug Preparations

Preparations packaged into unit-dose containers that are too small for a label compliant with all requirements should at a minimum contain the name of the compounding pharmacy and dispensing pharmacy, if different, in addition to currently established components. 

1735.5. Compounding Policies and Procedures 

The pharmacy shall follow its policies and procedures and failure to follow these policies and procedures shall constitute grounds for disciplinary action. 

The annual review of the policies and procedures by the pharmacist in charge shall be documented, signed and dated.  

There should be evidence that the staff has been educated and trained on all policies and procedures. 

A written plan for preparation recall to be included and proof that all affected doses can be accounted for as part of the recall. 

There should be procedures for evaluating, maintaining, certifying, cleaning, and disinfecting the facility used for compounding, and for training on these procedures as part of the training and competency evaluation process. 

Dates of any revisions to the policy and procedure manual shall be approved by the pharmacist-in-charge, signed and dated. 

There shall be policies and procedures for storage of compounded sterile preparations in the pharmacy and daily documentation of all room, refrigerator, and freezer temperatures. 

There shall be policies and procedures regarding ensuring appropriate functioning of refrigeration devices, monitoring refrigeration device temperatures, and actions to take regarding any out of range temperature variations. 

1735.6. Compounding Facilities and Equipment

Amended to specify definition of equipment to include any equipment that weighs, measures or transfers ingredients for compounding to be calibrated prior to use per manufacturer's specifications.
 

1735.8 Compounding Quality Assurance

Amended to include a written procedure for responding to out-of-range temperature variations, including for preparations furnished to patient care areas. 

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ARTICLE 7. STERILE COMPOUNDING 

1751. Sterile Compounding; Compounding Area; Self-Assessment 

The designated compounding area shall be in a restricted location where traffic has no impact on the performance of primary engineering controls (ISO 5).  All ISO classified environments must be certified at least every 6 months. 

Sinks and drains shall not be present in an ISO Class 7 or better environment, nor within three feet of an ISO Class 5 PEC or better located in a segregated compounding area. A sink may be located in an ante-area. 

1751.1. Sterile Compounding Recordkeeping Requirements 

The are amendments listing the required record keeping components for results of hand hygiene and garbing assessment, media fills, viable air sampling, and surface sampling.

Daily documentation of controlled temperature for all rooms and refrigerators / freezers for storage as well as air pressure differentials, and/or air velocity between adjoined ISO classified rooms/environments associated with PEC or containment isolators. 

Logs or documentation for inspection of expired and recalled products and/or ingredients.

Pharmacies compounding sterile preparations for future use pursuant to section 1735.2, in addition to requirements in 1735.3, must make and keep records indicating the name of the preparation, lot number, amount and date on which the preparation was provided to a prescriber.

Records maintained and stored electronically must comply with Business and Professions Code section 4070 subsection (c).

1751.3 Sterile Compounding Policies and Procedures 

There shall be written policies and procedures for proper use of equipment and supplies, training staff in all aspects of the preparation of sterile preparations including: 

- didactic training and knowledge/competency assessments including hand hygiene and garbing, cleaning and disinfection of controlled areas, proper aseptic technique

- an environmental sampling plan including viable air sampling, surface and gloved fingertip sampling, and nonviable particle sampling

- for compounding aseptic isolators and compounding aseptic containment isolators, documentation of the manufacturer's recommended purge time 

-media fill test procedure

- compounded sterile drug preparation stability and beyond use dating 

- visual inspection and other final quality checks

- conduct of personnel in controlled areas

- use and maintenance of primary engineering controls that create direct compounding area 

- daily and monthly cleaning and disinfection schedule for controlled environment 

- airflow considerations and pressure differential monitoring 

- temperature and humidity monitoring in compounding and controlled storage areas

- facility management including certification and prevention maintenance of controlled environments and related equipment 

- assigning of beyond use date requirements 

- use of automated compounding devices (if applicable) 

- hazardous drug employee training and safety program 

- hazardous drug handling, storage, labeling and transport

- hazardous drug compounding techniques

- hazardous drug spill, deactivation and waste management 

- preparing sterile solutions from non-sterile components (if applicable) 

- disposal of packaging materials, used syringes, containers, and needles to enhance sanitation and avoid accumulation 

- action levels for colony-forming units (CFUs) detected during viable surface testing, glove fingertip sampling and volumetric air sampling

(Pharmacies subject to an institutional infection control policy may follow that policy as it relates to cleaning schedules and the alternation of disinfectants in lieu of complying with requirements in this subparagraph)

For sterile batch compounding: 

- use of master formulas and compounding work sheets 

- appropriate documentation 

- appropriate sterility and bacterial endotoxin testing 

For non-sterile to sterile compounding: 

- sterilization methods 

- end-product evaluation and testing 

1751.4. Facility and Equipment Standards for Sterile Compounding 

Cleaning and disinfecting of surfaces in the ISO Class 5 PEC shall occur frequently, including the beginning of each shift, before and after each batch, after a spill and when surface contamination is known or suspected. 

Counters, cleanable work surfaces, and floors shall be cleaned with a germicidal detergent and water and disinfected with a suitable agent (i.e. isopropyl alcohol) daily. Walls, ceilings, storage shelving, tables and stools shall be cleaned in the same manner, at least monthly. 

Included provision for use of an aseptic containment isolator outside of an ISO 7 buffer area if the isolator provides ISO 5 air during a particle sampling count approximately 6-12 inches upstream of critical exposure site, not more than 3250 particles (0.5 microns and larger) per cubic meter during material transfer, recovery time to achieve ISO 5 air is documented and used to create procedures that allow for ample recovery time after material transfer before and during compounding operations. 

To compound sterile preparations containing hazardous drugs, a negative pressure PEC must be used and certified every 6 months by a qualified technician. Pharmacies utilizing a negative pressure buffer area and PEC for the purpose of compounding hazardous drugs must use this PEC exclusively for hazardous drugs, otherwise non-hazardous preparations compounded in this area must be labeled with the same requirements as hazardous drugs. A laminar flow hood may be installed outside of this negative pressure area, or on the clean side of the line of demarcation from the ISO 7 ante-room, at least six feet from the sink to be exempted from this r. 

All hazardous drug preparations compounded in an aseptic containment isolator must comply with the same provisions for personnel garbing in a controlled environment. 

Containment isolators that are certified to provide ISO 5 air during dynamic operation conditions during transfer and compounding may be placed in a non-ISO classified room. Compounding of this nature requires the same personnel garbing and hygiene requirements as if working in a laminar flow hood, including the donning of sterile gloves over the isolator gloves.  These sterile gloves must also be changed by each individual whenever continuous compounding is ceased and before compounding resumes. 

Viable air sampling and surface testing shall be performed at least monthly for low and medium-risk and at least weekly for high-risk compounding. All sampling tests should occur under similar conditions as routine compounding. When results exceed action levels, the pharmacy shall identify CFUs to at least the genus level, and conduct an investigation including review of cleaning and compounding operations. 

The pharmacy shall have a comfortable and well-lighted working environment of 20 degrees Celsius or cooler. Humidity levels should be consistent ASHRAE Standard 55 (30-65%RH). 

1751.5. Sterile Compounding Attire 

Personal protective equipment (PPE) includes facial hair covers when applicable. All PPE should be donned and removed within the ante-area. PPE should be applied from activities considered dirtiest to cleanest, beginning with shoe covers, head cover, face mask, washing of hands and elbows, then donning the non-shedding gown. Hand, wrist or finger jewelry shall not be worn. 

Sterile gloves that have been tested for compatibility with disinfection with isopropyl alcohol are required. Hands must be cleansed with a persistently acting alcohol-based product followed by the donning of sterile gloves in the ante or buffer-area. Gloves must be routinely disinfected with the agent (i.e. sterile 70% IPA) before entering the PEC and after contact with non-sterile objects. Gloves must also be routinely examined for holes, punctures or tears and replaced immediately if such are detected. 

Individuals with rashes, sunburn, weeping sores, conjunctivitis, active respiratory infections, or wearing cosmetics shall not be permitted into compounding areas until these conditions are remedied. 

1751.6. Sterile Compounding Consultation; Training of Sterile Compounding Staff 

Media fill test must be as complicated as the most complex manipulations performed by staff and contain the same amount of volume transferred during the selected manipulations. 

1751.7. Sterile Compounding Quality Assurance and Process Validation 

Media used for personnel media fill tests must have demonstrated the ability to support and promote growth. Samples must be incubated according to manufacturer's recommendations.  

The initial gloved fingertip test should be conducted after the initial hand hygiene and garbing procedure and demonstrate 3 successful test results prior to permission for sterile compounding (zero CFUs). 

Revalidating must include 3 media fill tests per day for 3 consecutive days for an annual revalidation. 

All personnel competencies must be revalidated at least every 12 months for individuals performing sterile to sterile (low and medium-risk) compounding and at least every 6 months for individuals compounding non-sterile to sterile (high-risk) ingredients, in addition to the currently established criteria for revalidating.

Batch produced (see proposed CA definition) sterile preparations from one or more non-sterile ingredient must follow USP definition for pyrogen testing. Testing must demonstrate sterility and an acceptable level of pyrogens prior to dispensing. 

In the circumstance where a 'high-risk' batch-produced preparation is needed for immediate dispensing, where failure to dispense may results in loss of life or intense suffering, the preparation may be dispensed prior to receipt of these test results if there are written procedures in place that include the following: 

1. Prior to dispensing: 

- the physician is notified of the inability to conduct the required testing 

- suggest an alternative preparation or product to the prescriber 

- procure the prescriber's written consent to dispense given the circumstances 

2. and subsequent to dispensing: 

- daily observation of the incubating test specimen are made 

and

- there is an immediate recall of the dispensed compounded sterile preparation's when there is any evidence of microbial or pyrogen growth resulting 

Any dispensing under these circumstances shall only be done in such a quantity as necessary to meet the immediate need and circumstance, and is documented according to written policies and procedures 

1751.8. Beyond Use Dating for Sterile Compounded Drug Preparations 

All sterile compounded preparation must have a beyond use date that does not exceed the expiration date of any individual component. The USP <797> risk level definitions are provided in this section, indicating that a preparation which falls into the USP classified risk level, in the absence of a sterility test, may not exceed its respective beyond use date. 

Guidelines are also provided for sterile preparations compounded in a segregated compounding area, restricted to using only sterile ingredients. 

Sterile preparations containing hazardous components that are prepared outside of a negative pressure environment are granted a beyond use date of 12 hours. 

Any sterile preparation that is compounded outside of an ISO 5 environment, or a PEC that does not meet the requirements for ISO 5 environment, the preparation must be labeled "for immediate use only" and granted a one-hour beyond use date. If not used within one hour, the preparation must be discarded. This type of compounding shall only be utilized in situations where there is an immediate need for compounded sterile preparations where failure to dispense such may result in loss of life or intense suffering, and only in a quantity to meet such a need. This compounding must be conducted according to written policies and procedures. 

1751.9. Single-Dose and Multi-Dose Containers; Limitations on Use 

This new section is added to include the USP <797> definitions, requirements, and limitations for storage of single-dose vials and ampules, and multi-dose vials. 

Is the FDA Meeting DQSA Expectations?

Since the Drug Quality and Security Act was signed into law last November, the Food and Drug Administration has chosen to selectively implement the law, leaving the industry perplexed. With the dust still settling from the nationwide meningitis outbreak of 2012,  U.S. Senator Lamar Alexander (R-Tenn.) requested that the Senate Appropriations Committee direct the FDA to meet with stakeholders in implementing the Drug Quality and Security Act. Thus far, the FDA has not met with patients, providers, or any other stakeholder affected by the DQSA. The intent behind the new law is to protect the public from potentially unsafe medications, with the consensus that affording the FDA with oversight of a new category of compounding pharmacies would help address major safety issues.

These outsourcing facilities, however, have been the great minority in the latest of those inspected by the FDA since the enactment of the law. For reasons currently unknown, the FDA has begun interfering with pharmacies not involved in compounding sterile medication. Pharmacies performing the compounding of non-sterile medication with state authorized provisions for office-use compounding have been the recent target of FDA's enforcement actions. In contrary action to the language of the industry guidance documents issued by the FDA, they have decided that they may apply federal standards the state-regulated practice of pharmacy, and use those standards in enforcement action. The following excerpt is taken from the Food Drug and Cosmetic Act Section 503A Industry Guidance, which reflects the FDA's thinking on  DQSA implementation: 

This lack of consistency has spurred groups like the International Academy of Compounding Pharmacists (IACP) to increase their voice on Capitol Hill and to issue a response to the FDA regarding these industry guidance documents. 

Commissioner Hamburg has made little effort to communicate to stakeholders on this topic as FDA inspectors continue to flout the intention of Congress. 

Pharmacies not registering as federally regulated outsourcing facilities for the purpose of compounding exclusively non-sterile medications may still face regulation by the FDA for the state-approved practice of office-use compounding. As of late, the blurring of these regulatory lines have left numerous pharmacies across the country reaching out for help and demanding answers. The pharmacy compounding community continues to intensify efforts to get answers from the administration, as any kind of legal precedent will not likely happen any time soon. 

Health-Systems & the New CA Sterile Compounding Law

Health-systems practitioners in California have begun the application process for obtaining a license for sterile compounding (LSC) from the Board of Pharmacy. Before Jan 1, 2014, health-systems accredited by the Joint Commission or other agencies were exempt by the board from obtaining a separate license for sterile compounding. IV manipulations and other parenteral medications prepared in a clean room or even satellite hoods will now require a LSC from the board. Initial inspections by the board have revealed a few common missing requirements that health-systems pharmacies do not yet have in place. In this piece I will discuss the issue of Personnel Training & Documentation that health-systems pharmacies performing sterile compounding, or the preparation of any parenteral medication, must implement before the board will grant a LSC. 

The Who, What, and How of Personnel Training & Documentation 

Who: All personnel engaging in sterile compounding or aseptic manipulation of parenteral medication, including technicians, pharmacists, intern pharmacists and possibly other hospital personnel. 

What: All personnel must pass an initial competency process evaluation prior to preparing sterile medications for patients. The initial competency required is also known as a media fill test. The media fill test is performed by preparing a sterile medication as usual for a patient, but instead of a delivery solution, a microbial growth medium is used and the sample is incubated to test for microbial contamination. 

Although CA law does not specifically state that the testing of gloves is required, a performance evaluation is required as part of the quality assurance program. In this instance, it is highly recommended to follow the USP <797> guidelines for initial and periodic gloved finger tip sampling of all personnel to ensure gloving technique is sound and does not increase the chance of touch contamination. 

Another part of a compliant and effective personnel training program is the didactic review of the pharmacy's policies and procedures and all requirements for ensuring safe aseptic technique. To implement this system, a written quiz containing information on aseptic technique, beyond use dating, disinfecting, storage, labeling, equipment, and facility requirements should be administered to and passed by all personnel. Additionally, issuing a copy of the policies and procedures for sterile compounding and a signed acknowledgement of reading and understanding the material should be documented. 

If the pharmacy prepares hazardous, namely cytotoxic, drugs for patients in the hospital, additional detailed training and documentation is required. 

For many health-systems, the annual review of this material is required. For facilities performing high-risk compounds (compounds from one or more non-sterile ingredients), a semi-annual review is necessary among several other requirements. 

How: The pharmacy must document all training and retain the training files for at least 3 years. One way to keep track of these documents is to assign each employee an individual training file which can be accessed easily by both personnel and regulatory authorities. Included in this files should be the previously mentioned requirements, signed acknowledgement of having received certain information, and other documentation that may be specific to the scope of the pharmacy's sterile compounding. 

Other requirements health-systems must review to ensure compliance with are :

• Facilities
• Equipment 
• Master Formula Records 
• Labeling of Preparations
• Beyond Use Dates 
• Quality Assurance Program 

Because heath-systems greatly vary in terms of size, infrastructure, facilities, and scope of compounding, so will the requirements for each. The CA Board of Pharmacy has increased the number of inspectors in hopes of meeting the demand to inspect and grant licenses to California's numerous health-systems applying for a LSC. 

Designing and implementing new requirements and major changes into a health-systems pharmacy is no easy task. The first, most critical step is deciding how the health-system will address the new requirement by the board of pharmacy. Often times, charging internal personnel to handle these issues is time and resource consuming. For certain types of health-systems, this may be an acceptable choice, and for others, the misallocation of human capital can have negative consequences on quality of care, finances, and department harmony. 

Visit ITLConsulting.net/hospitals to discover if streamlining this licensure process is the right decision for your health-system or pharmacy practice. 

Does the FDA Have Adequate Resources for Compounding Oversight?

The passing of HR 3204, the Drug Quality and Security Act (DQSA) has led many pharmacies to reconsider their business model. With a murky federal line drawn between "traditional" compounding pharmacies and outsourcing facilities, business owners around the country are making the decision to register as an outsourcing facility or restructure their operation to remain profitable while significantly blunting the scope of their operation to comply with these new requirements. While future outsourcing facilities are busy preparing applications, information and other paperwork required for federal authorities, a common question being asked by stakeholders is "Is all this work going to make the medication any safer?" FDA Commissioner Margaret Hamburg might answer the question with a resounding yes. Others may disagree. 

Historically, the FDA has never been able to regularly inspect all the facilities it grants licenses to. Its demand to Congress to grant them oversight of even more facilities has left many wondering how they are going to find the resources to carry out even more inspections. 

The DQSA describes the way the FDA plans to inspect outsourcing facilities. Their "risk-based" inspection frequency offers the following criteria: 

• compliance history of the outsourcing facility
• record, history, nature of recalls linked to the outsourcing facility 
• inherent risk of the drugs compounded at the outsourcing facility 
• the inspection frequency and history of the outsourcing facility, including whether the outsourcing facility has been inspected pursuant to section 704 in the last 4 years 
• whether the outsourcing facility has registered under this paragraph as an entity that intends to compound a drug that appears on the list in effect under section 506E (drug shortages) 
• Any other criteria deemed necessary and appropriate by the Secretary for purposes of allocating inspection resources 

Since March, around 35 pharmacies have registered as outsourcing facilities with the FDA. The President has asked for an additional $25 million dollar appropriation for the FDA, which they intended to use for the inspection and enforcement of traditional compounding pharmacies, according to budget notes. The FDA appears to be worried more about exercising their discretion against traditional pharmacies rather than inspecting and guiding outsourcing facilities. 

In addition to their recent questionable promotion of outsourcing facilities to lawmakers, hospitals, professional organizations, and countless others as a 'higher' standard drug provider, the FDA seems to lack an understanding of the Congressional intent of the DQSA, or just seems to blatantly ignore it. Numerous drug recalls from manufacturers occur on a daily basis and vastly outnumber those from compounding pharmacies. But manufacturers don't utilize the same "risk-based" inspection frequency set forth for outsourcing facilities. 

Furthermore, the FDA is now infringing upon the states' authority to regulate the practice of pharmacy compounding. The FDA has sent numerous warning letters to compounding pharmacies, finding them in violation of federal laws for engaging in office use compounding. According to their interpretation of the DQSA, they have taken section 503a to mean, no office compounding. Period. 

Through their subjective interpretation of the DQSA, the FDA is granting itself the authority to override the individual states which have provisions for office use compounding and cite pharmacies. Because of their string of actions, there are pending warnings which may evolve into court cases that could set new precedents for FDA's criteria of  inspections and authority.  

Until this happens, the FDA is likely to continue with their line of attacks against traditional compounding pharmacies, utilizing the resources they are being granted by Congress to abuse their discretion, rather than promote and encourage patient safety. Pharmacies have two choices: they can either follow their state laws, and be cited to be in violation of federal laws, or they may obey the FDA's warnings and turn patients and prescribers away. Regardless of this choice, this does not promote patient safety or find favor for the compounding pharmacist. 

Should Hospitals Seek Compounds from "Outsourcing Facilities"?

With the latest piece of major legislation to be passed by Congress, many pharmacies providing compounded sterile preparations to hospitals and other types of health care facilities are re-examining their practices in preparation for major changes. One major change is the creation of a new category of compounding pharmacy termed "outsourcing facilities". The Drug Quality and Security Act defines the terms of what constitutes an outsourcing facility and lists the numerous requirements that must be fulfilled. But does this laundry list of requirements make an outsourcing facility any safer than than a compounding pharmacy? The thought on Capitol Hill is that many hospitals and other facilities will start looking to outsourcing facilities as the new source for compounded sterile preparations and other compounds. Here are some facts to consider when examining the true safety standards of outsourcing facilities: 

1. The Drug Quality and Security Act Does Little More for Patient Safety

Many advocates of this new law, including some pharmacy associations, tout the bill as a win for patient safety and point toward the stronger federal oversight as added protection. While the bill may seem like a moral gesture, the most important fact to remember is that there were already adequate safety measures in place prior to the events stemming from the gross negligence of New England Compounding Center. During Congressional testimony, the FDA demonstrated a clear lack of sound judgement in exercising their long established authority after receiving reports of NECC's violations years earlier. Plain and simple, the safety measures in place were not executed as designed. This segues directly into the next important fact.  

2. Authority of Outsourcing Facilities are Only Overseen by the FDA

In the language of the Drug Quality and Security Act, an outsourcing facility does not need to be a licensed pharmacy. Pharmacy is historically a profession regulated at the state level, yet this law creates a new avenue of compounding that strays from the well established safety measures and statues of the states. The added problem of deciding which laws will take precedence in light of a statute (FDCA Section 503A) open to the discretion of the FDA will create ambiguity for state regulators and compounding pharmacies. At this point, the dialogue between these two bodies is not well developed in providing any answers.

3.  The Role of the Pharmacist is Unclear in Outsourcing Facilities 

A pharmacist must directly oversee the compounding operations in an outsourcing facility. This is the only mention of a pharmacist's role in this legislation. While many states have strict laws on the technician to pharmacist ratio, outsourcing facilities can bypass this safety requirement as a federally licensed facility. There are several other regulatory loop holes inherent to the creation of this category of compounding. 

4. Outsourcing Facilities May Compound Large Quantities of Non-Patient Specific Meds

This specific allowance is a main distinction between compounding pharmacies and outsourcing facilities. Until now, virtually all compounding pharmacies have prepared compounded medication for 'office-use' at the direction of a prescriber for use on a patient. Many different types of practices depend on this type of medication for the unique uses across various settings. Outsourcing facilities will be allowed to prepare large amounts of sterile compounded medication for distribution across state lines-almost similar to the scale of NECC. There is no defined limit on non-patient specific compounding in this bill. 

Each of these points lend to the fact that an outsourcing facility is not necessarily a 'safer' source of sterile compounded medication. This is not to say that an outsourcing facility can not maintain a perfect track record, but rather to examine the facts behind the logic. Regulation of these facilities by the FDA is being looked at as a 'fix' to the system, when we have established there was no fatal flaw to begin with. After all, the FDA was responsible for regulating NECC, as they acted as a manufacturer rather than a pharmacy. 

Real measures of quality come from practices with an established, respectable track record and few or no documented safety and/or quality issues. The pharmacies in the community that strive to uphold a higher level of quality are also denoted by such accreditations as PCAB or ACHC. With little research, a quality source of compounded medications is surely available to provide safe, effective medications at the direction of prescribers. 

HR 3204 Passes Senate, What Changes for Pharmacy Compounding?

This afternoon HR 3204 The Drug Quality and Security Act passed the US Senate via voice vote and is on its way to the President's desk. With the challenges of implementing the Affordable Care Act and its provisions, Obama is expected to quickly sign this bill into law. As soon as this law is enacted, the Food and Drug Administration will be looking to the Food Drug and Cosmetic Act (FDCA) Section 503A to impose action against compounding pharmacies not in compliance with this statute. Throughout the history of this bill, ITL Consulting has been tracking and discussing the possible outcomes of this bill with pharmacy owners, pharmacists and law makers. Provided below are links to main discussion points in examining where pharmacy compounding is headed. 

Will my pharmacy be targeted by the FDA? 

What exactly does the FDCA mean for pharmacy compounding? 

What are some potential ramifications of this bill? 

Will access for patients be affected by this bill? 

CA Hospitals & Home Health- Ready to get your LSC?

By July 1, 2014 community, hospital and other facilities preparing sterile parenteral compounds must have a LSC license from the California board of pharmacy to dispense in CA. The majority of community pharmacies doing sterile compounding have this license, but other facilities have been exempt from this requirement under CA B&P 4127.1 (d) and instead received accreditation through private agencies like the Joint Commission that have been approved by the board. Earlier this year, the board completed a round of inspections in hospitals accredited by the Joint Commission, the Pharmacy Compounding Accreditation Board (PCAB) and the Accreditation Commission for Health Care (ACHC). The findings of these inspections indicate a clear divergence between the accrediting body's requirements and the CA pharmacy laws. The following are just a few of many critical areas where pharmacy directors and staff can prepare their operations to be fully compliant with the CA regulations in preparation for an initial inspection by the board of pharmacy before July 2014.  

• Quality Assurance (QA) & Process Validation - Title 16 CCR 1751.7

The QA plan must be an exhaustive, integrated document housed within the policies and procedures. It is a living, dynamic document that must not only be well developed and unique to your pharmacy, but must also be constantly reviewed and updated as needed. Essentially, this document dictates all the quality assurance activities carried out by the pharmacists from the beginning to end of a process and must be performed as written and documented where required. 

• Regular Cleaning of Sterile Compounding Area - Title 16 CCR 1754.1

The controlled environment where sterile compounding is performed must be cleaned weekly. This includes the cleaning of walls, floors, ceilings, equipment and requires documentation as evidence. Many pharmacies opt to have a third party complete the full cleaning each week. Assigning a team member as the point of contact with the cleaning crew may be necessary to ensure proper documentation and compliance with this policy, of which alternation of disinfectants is also a requirement. 

• Master Formula & Compounding Records  - Title 16 CCR 1735.2

Whether sterile or non-sterile, a master formula containing all required components of the medication being compounded must be accessible and utilized during the compounding of any preparation as documented. This includes an appropriate beyond use date with written justification for arriving at that specified time, including citations of studies if used. Stability data relating to each ingredient and packaging material may be difficult to find for certain preparations and pharmacist judgement and/or USP guidelines may also need to be used. 

While the board found a great many shortcomings during these inspections, these represent some of the most common findings. Whether in the hospital, home health, or long-term care facility, the board of pharmacy will require a LSC license to compound sterile injectable drugs. The daily operational efficiency and pleasant environment of the work place does not need to suffer in undertaking this stretch goal. Strategically implementing the necessary changes in the pharmacy and seeking the expertise of a consultant are sound business tactics in such a scenario. 

How Do You Create Change in Your Pharmacy?

For the average pharmacy, optimizing and assessing processes occurs when conditions dictate it.  Major escalations transpire and signs of ineptitude force the pharmacy owner to shuffle the deck and re-evaluate methods.  More often than not, critical assessment is completed by one individual who may not even be responsible for the newly adapted procedures.  This presents a vast problem for pharmacy owners who are expecting to implement process improvements and have not thoroughly evaluated the necessary tools to successfully promote these changes.  This post will discuss a simple process pharmacy owners can use to implement change without costing themselves valuable financial resources.

When trying to make drastic improvements to your pharmacy it is not often feasible to invest large financial resources to increase the staff.  In fact, this option could be a detriment to your team’s advancement and may cover up flaws in your company’s growth towards being truly efficient.  True pharmacy leaders learn how to create more with less, creating an evolving environment poised for adaptation and efficiency.  Developing a focus on critical areas where the greatest impact and improvements can be made and re-allocating your resources to emphasize those improvements is key.

For example, a pharmacy owner, David, receives a complaint about one of his team member’s customer service.  A customer states that the pharmacy clerk, Jennifer, “seemed preoccupied and rude” when she came to pick up one of her compounded prescription medications.   David knows that Jennifer is a hard working team member who constantly tries her best in customer service, so he approached Jennifer to see what happened with this patient.  After a brief conversation, he found out that Jennifer was overwhelmed; she was responsible for answering the phones, helping patients at the register, filing all the prescriptions, and a few other tasks that David did not even realize.

David had considerable pride in his store’s customer service and held a team meeting the next day to address the issue.  He decided that alleviating the stress on Jennifer so she could provide optimal customer service was a critical area of focus for his store.  Following the discussion, the rest of the team was on board.  The plan was to re-allocate some of their resources from the compounding lab to assist Jennifer at certain times of the day when the front end workload was the highest. 

After developing a new project for your pharmacy, one of the most critical measures to make this new process into a success is creating a managing group to help with its execution.  Managing groups can be comprised of a key pharmacist, technician, or any team member who is critical to the new process.  Depending on the size of your pharmacy, it may start with one individual or it may be a large group.  The individuals in these groups should have some distinctive character traits that will not only help you develop the project, but that will help deter the possible naysayers from stopping potentially great plans from advancement. 

In our example of re-allocating resources to help Jennifer, it is extremely important to get the right managing group on board.  In this case, it was the lead technician in the compounding lab, Stacy, who David relied on to help assist Jennifer with the front end work.  David held a meeting with Stacy, Jennifer, and a compounding pharmacist, Sarah, uniting them as the project’s managing group.  Each individual in this meeting had a pivotal role in the new process.  Jennifer could provide feedback and ensure the process improved her ability to help patients.  Stacy was essential because she would assign technicians the time to assist Jennifer with front end work, but she also served a dual purpose. Stacy was a highly respected technician who had a strong rapport with the other technicians on the team, and David knew that made her a perfect fit for the managing group.  With Stacy involved, the technicians were unlikely to complain to each other about having to break their routine to help Jennifer because they knew how hard Stacy worked on a daily basis.  Having a team member like Stacy involved kept the potential naysayers quiet and allowed the plans to proceed.  Finally, Sarah was established as the authority figure who would be responsible for the project’s outcome and would report shortcomings to the owner when necessary.  

Each managing group should be unique based on the new process to implement, but the essential elements should always be present.  Even if the managing group is one or two people, those individuals should at the very least: share the same vision, have open communication with the team, have the respect of their colleagues so they can delegate tasks and deter the naysayers, and have a responsible party who will report to the owner frequently on the project’s progress. 

Developing a clear vision for change, getting your team on board, and creating the right managing group to execute the implementation of a new process are only a small part of creating change in your pharmacy.  There are countless other elements to consider depending on the scope of the change that needs to take place.  In this post, the concepts are extremely simplified, but the intention is to begin the discussion of how you institute change in your pharmacy.

New Sterile Compounding Requirements - SB 294

 Governor Brown signed a bill into law this month which will impact the practice of sterile compounding. The board of pharmacy supported SB 294 Sterile Drug Products authored by Senator Bill Emmerson (R-23) in an effort to maintain the safety of California’s supply of compounded sterile medications. 

This new law will preempt Joint Commission accreditation provisions for all hospitals, home health care and other facilities providing sterile compounding. These facilities will now be required to apply for a California LSC license, exclusively for compounding sterile medications. In addition to the initial application process, the facilities must comply with all state regulations pertaining to sterile compounding and undergo an inspection prior to receiving a license. 

Hospitals and other facilities will likely be charging their compliance officers and ad hoc committees with this task. Internal resources will need to be reallocated and changes to the workflow implemented. Preparing for an inspection can be a grueling process, as policies and procedures, facilities, documentation and training must all be up to par to obtain this license. Consulting with professionals to fill in these gaps and verify the accuracy of a pharmacy’s practice can prove time, resource and sanity saving. 

The board of pharmacy has spent more than half of its $14 million dollar expenditures on personnel alone, many being new inspectors. Additionally, they plan to hire more inspectors with the expectation of inspecting these new pharmacies applying for the LSC. California has been a national leader in patient safety for pharmacy compounding and continues to demonstrate this commitment through their legislative efforts and enforcement of sterile compounding. Let’s be sure our hospitals, home health care, and other facilities continue to uphold an exceptional level of quality as we move through the wake of the NECC calamity.

More Support for a Defective Bill

As activity reconvenes on Capitol Hill, pharmacy compounding lobbyists continue to engage lawmakers on the latest piece of legislation to come forward. The National Community Pharmacists Association (NCPA) and American Pharmacists Association (APhA) have both announced their support for the Drug Quality and Security Act. However, the professional group whose constituency represents almost exclusively pharmacy compounders, the International Academy of Compounding Pharmacists (IACP), remains stern in their opposition. Both the APhA and NCPA have stated they believe the bill will help protect the public, while also preserving important access to critical compounded medication. While these groups represent far less pharmacy compounders, their rationale for supporting this bill does not seem well developed in its potential outcomes. Here are a couple reasons demonstrating how patient access can be negatively affected under this law. 

The American Academy of Ophthalmology (AAO) is the world's largest association of eye physicians and surgeons. Daily, thousands of patients depend on the medication that compounding pharmacies provide for the urgent treatment of eye diseases and conditions. The AAO has come out in support of legislation that lends to the safety of compounded medication, while preserving their access to these sight-saving medications. 

"Safe, sterile compounded medications have long been essential tools available to ophthalmologists for urgent treatment of eye diseases and conditions, benefitting millions of patients" 

-David W. Parke II, M.D.  

CEO, American Academy of Ophthalmology  

Congress has turned a cold shoulder to groups like the AAO who understand that a name on the label holds no bearing in creating a safer sterile compounded drug. Under HR 3204, this type of "office-use" compounding is not recognized, and would therefore not be permitted by compounding pharmacies currently providing these drugs. The FDA has publicly expressed sentiment against permitting this type of office-use compounding for sterile drugs in compounding pharmacies, and more recently, aggressively contested HR 3089 for its allowance of office-use compounding. Unfortunately, if HR 3204 passes, the FDA will regulate this practice; physicians and patients may face a serious problem with access to these drugs. In order to continue this type of non-patient-specific compounding of sterile drugs, a pharmacy would need to comply with the numerous pages of requirements associated with registering as a federal "outsourcing facility"- a formidable process with an added tax of mandatory registration fees. 

Another ongoing battle the FDA will win under this new law is that against the compounding of bioidentical hormone replacement therapy (BHRT). In 2008, the FDA sent warning letters to pharmacies compounding with estriol, a form of estrogen with an important clinical role. According to the administration, estriol is not any part of a FDA approved drug and it should not be used for pharmacy compounding unless authorized by an investigational new drug application or IND. Still included in HR 3204 however, certain bulk drug substances must be approved prior to being used in compounding, whether sterile or non-sterile. Approval is dependent on the administration's and HHS secretary's determination of a "clinical need". 

Yet, most worrisome is the issue that in the plain language of this bill, the authority for the FDA to use their discretion in determining that a compounding pharmacy is acting contrary to the laws dictated by HR 3204 is clearly granted. If such a determination is made, the pharmacy can either stop compounding- limiting access for patients- or stop compounding, and opt to register as an outsourcing facility in order to continue. Regardless of the scenario, this bill is inherently set up to result in disruptions to patient and prescriber access to compounded medication. 

 For obvious reasons, no legislation will be 100% fail-safe in protecting the public. In the case of NECC, existing laws at the state and at the federal level were not to blame. Not only was the incident a blatant disregard for humanity and an outlier event, it was the execution and enforcement of existing laws that was at fault. The FDA will argue and continues to argue, or more accurately redirect the blame, to the tune of "unclear authority". By now, we all know this of course was never the case. Instead of joining the "we need new legislation" bandwagon and denying the potential negative impact of a knee-jerk, compromised bill spawned by a fractionated legislature, our professional representation needs to perform serious due diligence on the true source of the problem and consider supporting legislation that makes sense for those they represent. 

What Will Distinguish a Compounding Pharmacy?

Analyzing the language of the Drug Quality and Security Act does not provide a clear definition of a compounding pharmacy. What it does provide is a battery of requirements that pharmacies registering as outsourcing facilities must comply with. 

To understand the limitations of a compounding pharmacy we must look at the Food Drug and Cosmetic Act (FDCA). The Drug Quality and Security Act will reaffirm section 503A of the FDCA into law and clearly dictates the stipulations allowing a compounded drug to be exempted from being classified as a new drug. If these prerequisites are not met as defined in section 503A, then the FDA views the drug as a new drug which is subject to the FDA drug approval process prior to entering the market. 

Unfortunately, the best chance of understanding what defines a compounding pharmacy is found in the following. 

The language of section 503A states:  

Sections (pertaining to new drugs) of this title shall not apply to a drug product if the drug product is compounded for an identified individual patient based on the unsolicited receipt of a valid prescription order or a notation, approved by the prescribing practitioner, on the prescription order that a compounded product is necessary for the identified patient, if the drug product meets the requirements of this section, and if the compounding—

(1) is by—

(A) a licensed pharmacist in a State licensed pharmacy or a Federal facility, or

(B) a licensed physician, on the prescription order for such individual patient made by a licensed physician or other licensed practitioner authorized by State law to prescribe drugs; or

    (2)(A) is by a licensed pharmacist or licensed physician in limited quantities before the receipt of a valid prescription order for such individual patient; and

    (B) is based on a history of the licensed pharmacist or licensed physician receiving valid prescription orders for the compounding of the drug product, which orders have been generated solely within an established relationship 

between—

(i) the licensed pharmacist or licensed physician;

and

(ii)(I) such individual patient for whom the prescription order will be provided; or

(II) the physician or other licensed practitioner who will write such prescription

order.

In addition to reestablishing this language, HR 3204 also states that the HHS Secretary will require state boards of pharmacy to prepare submissions: 

• describing actions taken against compounding pharmacies 
• expressing concerns that a compounding pharmacy may be acting contrary to section 503A of the Federal Food, Drug, and Cosmetic Act

And finally,  

The Secretary shall immediately notify State boards of pharmacy when—

• the Secretary makes a determination that a pharmacy is acting contrary to section 503A of the Federal Food, Drug, and Cosmetic Act.

In summation, we know that the FDA has already openly stated that office use compounding is not expressly permitted under section 503A, and seen them forcefully oppose a bill that permitted office use and anticipatory compounding (HR 3089) with limitations. Given their position, it can be expected that the strict interpretation of this language will be the defining factor between compounding pharmacies and outsourcing facilities. The interpretation of the law pertaining to the former however will remain the discretion of the FDA as the state boards of pharmacy also look to them for guidance on this language to better fulfill their own reporting obligations.