1
Q
Q: What precautions should be taken when cleaning equipment used in compounding preparations that require special care, such as antibiotics and cytotoxic materials?
A
- Extra Care Required: Equipment used in compounding preparations that require special precautions (e.g., antibiotics, cytotoxic, and other hazardous materials) should be cleaned with extra care.
- Dedicated Equipment: Whenever possible, use dedicated equipment for these types of preparations to avoid contamination.
- Cleaning Procedures: If the same equipment is used for different drug products, ensure that appropriate procedures are in place for thorough cleaning before using it with other drugs.
- Disposable Equipment: Use disposable equipment when possible to minimize the risk of bioburden and cross-contamination.
2
Q
- <797> states, “When a CSP will not be released or dispensed on the day of preparation, a visual inspection must be conducted immediately before it is released or dispensed to make sure that the CSP does not exhibit any defects such as precipitation, cloudiness, or leakage, which could develop during storage.” Would this prohibit stocking CSPs on the floors in automated dispensing cabinets (i.e., Pyxis) to no more than a 24- hour supply?
A
No, releasing a CSP to the floor is similar to dispensing to a patient so a second check is not required by a pharmacist. Nurses should be educated to check all types of sterile preparations – manufactured, from a registered outsourcer, prepared by pharmacy, or those that they activate or mix – prior to administration to a patient.
3
Q
- After a CSP has been verified by a pharmacist and placed in an area to be picked up for a specific patient in a specified timeframe, does the CSP need to be re-checked by a pharmacist before going out to a patient?
A
<797> requires that “at the completion of compounding, before release and dispensing, the CSP must be visually inspected to determine whether the physical appearance of the CSP is as expected”. If the pharmacist has performed the release check and dispensed the CSP, and it is only awaiting pick-up or delivery, a re-check is not required.
4
Q
- Where do I find labeling requirements for HDs?
A
Labeling must be compliant with federal, state, and local regulations and the appropriate USP standards for compounding including USP or , if applicable. HDs identified by the entity as requiring special HD handling precautions must be clearly labeled at all times during their transport.
5
Q
- What kind of packaging containers can be used for prepackaging HDs?
A
Packaging containers and materials that maintain physical integrity, stability, and sterility (if needed) of the HDs during transport should be used. Packaging materials must protect the HD from damage, leakage, contamination, and degradation, while protecting healthcare workers. Prepackaging tablet and capsule forms of Table 1 Antineoplastic HDs for dispensing to patients should be done using a manual system to eliminate the risk of contaminating automated systems if the HD would break.
6
Q
- What kind of packaging containers can be used for packaging HDs for transportation within the healthcare institution?
A
Packaging containers and materials that maintain physical integrity, stability, and sterility (if needed) of the HDs during transport should be used. Packaging materials must protect the HD from damage, leakage, contamination, and degradation, while protecting healthcare workers who transport HDs. The entity’s SOPs should describe the practices for transporting hazardous drugs within the healthcare setting (e.g., use of cleanable transport containers) and ensure safe work practices (e.g., training, access to spill kits).
7
Q
Q: What are the requirements for containers and closures used for compounded drug preparations?
A
- Material Quality: Containers and closures must be made of suitable, clean materials to ensure they do not alter the quality, strength, or purity of the compounded drug preparation.
- Container Selection: The choice of container depends on the physical and chemical properties of the compounded preparation.
- Container-Drug Interaction: Consider potential interactions between the container and drug, especially for substances with sorptive or leaching properties.
- Storage and Handling:
- Containers and closures should be stored off the floor.
- They must be handled and stored to prevent contamination.
- Rotate stock to use the oldest items first.
- Inspection and Cleaning: Store containers and closures in a way that allows for inspection and cleaning of the storage area.
8
Q
Q: What are the training requirements for personnel involved in compounding, evaluation, packaging, and dispensing of compounded preparations?
A
- Training Requirements: All personnel must be properly trained for their specific roles in compounding, evaluation, packaging, and dispensing of compounded preparations.
- Training Program: The compounder is responsible for implementing and maintaining an ongoing training program.
- Evaluation Frequency: Compounding personnel should be evaluated at least once a year.
- Training Process:
- The compounder demonstrates the procedures to the employee.
- The employee practices the procedures under the compounder’s direct supervision.
- The employee must perform the procedure independently after training.
- Documentation: Once the compounder is satisfied with the employee’s knowledge and proficiency, the compounder will sign the documentation records to confirm the employee’s appropriate training.
9
Q
- What PPE is required for compounding HDs?
A
Gowns, head, hair, shoe covers, and two pairs of gloves that meet the American Society for Testing and Materials (ASTM) standard D6978 are required for compounding sterile and nonsterile HDs. ASTM has published F3267-22 (Standard Specification for Protective Clothing for Use Against Liquid Chemotherapy and Other Liquid Hazardous Drugs) standard for chemotherapy gowns which is gaining wide acceptance in the industry.
10
Q
- When compounding sterile preparations in a CACI, are three pairs of gloves required?
A
When compounding HDs, two pairs of gloves that meet ASTM standard D6978 are required. When using a CACI, that means one pair on the sleeve assembly and one pair passed through the antechamber and placed over the gloves on the sleeve assembly. Depending on the CACI used and your organizational policy, some entities use an additional glove to place on the hands prior to accessing the gloves on the sleeve assembly
11
Q
- What PPE is required for administering HDs?
A
For administering antineoplastic HDs, two pairs of chemotherapy gloves tested to American Society for Testing and Materials (ASTM) D6978 standard must be worn. For administering injectable NIOSH Table 1 antineoplastic HDs, gowns shown to resist permeability by HDs must be worn in addition to two pairs of chemotherapy gloves. ASTM has published F3267-22 (Standard Specification for Protective Clothing for Use Against Liquid Chemotherapy and Other Liquid Hazardous Drugs) standard for chemotherapy gowns which is gaining wide acceptance in the industry. For administering other HDs, the PPE requirements should be specified in the entity’s polices.
12
Q
Q: What is required to be documented for the visual inspection of CSPs and the container closure system?
A
- Visual Inspection of CSPs:
- Appearance Check: All CSPs must be visually inspected to ensure their physical appearance is as expected.
- Master Formulation Record: The master formulation record should list specific requirements for the CSP, including acceptable visible quality characteristics.
- Examples of Visual Quality Characteristics: These include checking for discoloration, visible particulates, or cloudiness.
- Visual Inspection of the Container Closure System:
- System Check: Inspect the container closure system for any issues.
- Examples of Issues to Check: Look for leakage, cracks in the container, or improper seals.
13
Q
- Can USP provide some clarity as to when a preparation needs to be prepared as sterile (CSP) as opposed to as nonsterile (CNSP)?
A
<795> and <797> both describe compounded preparations that are required to be sterile or can be prepared as nonsterile.
In general, preparations designed to be delivered to any body space that does not normally freely “communicate” or have contact with the environment outside of the body, such as the bladder cavity or peritoneal cavity, are typically required to be sterile. Additionally, ophthalmic products and compounded aqueous inhalation solutions and suspensions are required to be sterile. Otic preparations are not required to be sterile unless being administered to a patient with a perforated eardrum. Irrigations for the mouth, rectal cavity, and sinus cavity are not required to be sterile, nor are nasal spr
14
Q
- What are the requirements for dispensing final dosage form HDs (e.g., conventionally manufactured products that do not require further manipulation)?
A
Final dosage forms of HDs that do not require any further manipulation may be dispensed without any further requirements for containment unless required by the manufacturer or if visual indicators of HD exposure hazards are present (e.g., HD dust or leakage). These do not require any additional storage or handling requirements according to USP unless otherwise required by the manufacturer.
15
Q
- Our entity does not compound HDs but may handle final dosage forms. Are we required to have engineering controls (i.e., negative-pressure storage rooms, negative-pressure compounding areas)?
A
No. HDs that do not require further manipulation may be prepared for dispensing without further requirements for containment unless required by the manufacturer or if visual indicators of HD exposure hazards are present (see USP 12. Dispensing Final Dosage Forms).
16
Q
- What garb is required for nonsterile compounding?
A
Gloves must be worn for all compounding activities. Other garb (e.g., shoe covers, head or hair covers, facial hair covers, face masks, and gowns) should be worn as required by the facility’s standard operating procedures (SOPs). Garb is recommended for the protection of personnel and to minimize the risk of CNSP contamination. The garb must be appropriate for the type of compounding performed. The garbing requirements and frequency of changing the garb must be determined by the facility and documented in the facility’s SOPs.
17
Q
- Are gloves required to be wiped or changed before beginning to compound a CNSP with different components?
A
The chapter recommends wiping or replacing gloves before beginning to compound a CNSP with different components to minimize the risk of cross-contaminating other CNSPs and contaminating other objects. General Chapter <795> does not describe the use of specific wipes or agents to use for wiping gloves. Facilities must determine whether gloves should be changed or replaced and the appropriate wipe/agent to use if they are wiped.
18
Q
- Can gowns be reused for multiple days if not soiled?
A
If gowns are worn, they may be re-used if not soiled. If gowns are visibly soiled or have tears or punctures, they must be changed immediately. Facilities must determine the frequency for changing gowns.
19
Q
- Is a compounding space required to be in an enclosed room (i.e., with walls and doors)?
A
No. While a room may be used as the compounding space, the chapter does not require a separate room. The chapter requires a space that is specifically designated for nonsterile compounding. A visible perimeter should establish the boundaries of the nonsterile compounding area.
20
Q
- Can non-compounding personnel clean and sanitize the compounding space?
A
Facilities must determine the appropriate personnel for cleaning and sanitizing the compounding space. The chapter does not specify who may perform the cleaning and sanitization procedures. However, the chapter does specify that knowledge and competency must be demonstrated initially and at least every 12 months for those that are cleaning and sanitizing.
21
Q
- Is daily cleaning only required when nonsterile compounding has occurred?
A
Cleaning and sanitizing of the surfaces in the nonsterile compounding area(s) must occur on a regular basis at the minimum frequencies specified in Table 1 or, if compounding is not performed daily, it must be performed before initiating compounding.
22
Q
- When is the use of distilled water acceptable?
A
Purified Water, distilled water, or reverse osmosis water should be used for rinsing equipment and utensils. Note that Purified Water or better quality, e.g., Sterile Water for Irrigation, must be used for compounding CNSPs when formulations indicate the inclusion of water.
23
Q
- Can I use distilled water to compound CNSPs?
A
If the water meets the requirements of the Purified Water USP monograph, then it can be used to compound CNSPs.
24
Q
- If Sterile Water for Irrigation is used as a component in a CNSP, what is the BUD of the Sterile Water for Irrigation once opened?
A
Purified Water or better quality, e.g., Sterile Water for Irrigation, must be used for compounding CNSPs when formulations indicate the inclusion of water. Since sterility is not required, Sterile Water for Irrigation may be used until its labeled expiration date if it is stored in its original container per the manufacturer’s recommendations.
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42. Our Board of Pharmacy inspector is questioning our use of Sterile Water for Irrigation in place of Purified Water in CNSPs. Does USP reference this in other general chapters?
Purified Water or better quality, e.g., Sterile Water for Irrigation, must be used for compounding nonsterile drug preparations when preparations indicate the inclusion of water. Per <1231> Water for Pharmaceutical Purposes, 3.2.4, Sterile Water for Irrigation may be used in other applications that do not have particulate matter specifications, including where Purified Water is indicated but where access to a validated water system is not practical.
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50. Are all CNSPs required to be labeled, regardless of whether they are dispensed?
Yes. CNSPs must be labeled with the information specified in 9. Labeling regardless of whether or not they are dispensed. Labeling provides the information of the package contents.
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63. Do personnel of reproductive capability include both male and females since the chapter requires personnel of reproductive capability to confirm in writing that they understand the risks of handling HDs?
Yes, the requirement applies to anyone capable of reproduction (even if they dont want kids!)
28
29. Can non-compounding personnel clean and sanitize the compounding space?
Facilities must determine the appropriate personnel for cleaning and sanitizing the compounding space. The chapter does not specify who may perform the cleaning and sanitization procedures. However, the chapter does specify that knowledge and competency must be demonstrated initially and at least every 12 months for those that are cleaning and sanitizing.
29
66. What is the order and location of garbing?
General Chapter does not specify the order and location of garbing. The order and location of donning and doffing each article of required garb would depend on the type of garb used (e.g., sterile gowns) and the placement of the sink (e.g., if the sink is located inside or outside of the anteroom). The garbing order, location, and donning/doffing each article of required garb must be determined by the facility and documented in the facility’s SOP. For example, if a sink is located outside of the anteroom, a facility’s garbing policies and procedures may indicate that certain garb would be donned outside of the anteroom to more easily transition into hand hygiene procedures. Garb must be donned and doffed in an order that reduces the risk of contamination. Please note, sterile gloves must be donned in a classified room or SCA. Skin must not be exposed inside the ISO Class 5 PEC (e.g., gloves must not be donned or doffed inside the ISO Class 5 PEC exposing bare hands).
30
What should be included in the Compounding Record for prepration of a non-sterile product?
Mixing instructions should be part of the Master Formulation Record, not necessarily part of the Compounding Record (unless there is a deviation from the standards instructions, which should be rare)
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Compounded drug products, sterile or non-sterile, prepared by pharmacies
I. Must be FDA approved
II. Should be labeled with adequate directions for use when dispensed to patients
III. Are subject to Current Good Manufacturing Practice (CGMP) regulations
Correct answer - II. Should be labeled with adequate directions for use when dispensed to patients
Explanation:
FDA Approval: Compounded drug products are generally not FDA-approved. They are prepared by pharmacies in response to individual patient prescriptions, and thus do not need FDA approval.
Current Good Manufacturing Practice (CGMP): Compounded drug products are not subject to CGMP regulations. These regulations apply to commercial drug manufacturing but not to individual patient-specific compounded preparations.
Labeling with Directions for Use: Compounded drug products must be labeled with adequate directions for use when dispensed to patients. This ensures that patients have the necessary information to use the product safely and effectively.
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**Q: What distinguishes compounding by a licensed pharmacist or physician under section 503A from compounding by an outsourcing facility under section 503B of the FD&C Act?**
1. **Prescription Requirement:**
- **Section 503A:** Compounding by a licensed pharmacist in a State-licensed pharmacy or a Federal facility, or by a licensed physician, is done in response to an individual patient’s prescription. This requirement helps distinguish these types of compounding from other practices.
- **Section 503B:** Outsourcing facilities may or may not obtain prescriptions for identified individual patients. Section 503B(d)(4)(C) allows these facilities to compound drug products without a specific prescription for each patient.
2. **Regulatory Requirements:**
- **Outsourcing Facilities:** These facilities are subject to Current Good Manufacturing Practice (CGMP) requirements and other conditions. They can compound drug products to meet the needs of health care practitioners who need products on hand, not necessarily for identified individual patients.
- **Compounding under Section 503A:** Such compounding is specifically tailored for individual patients based on prescriptions and is not subject to CGMP regulations.
**Note:** The prescription requirement under section 503A ensures that compounded products are prepared for specific patients, while outsourcing facilities under section 503B have broader compounding capabilities and must adhere to CGMP standards.
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**Q: What are the guidelines for compounding office stock or compounding for office use?**
1. **Purpose of Compounding for Office Use:**
- Compounded drug products may be prepared and kept as office stock for immediate use by hospitals, clinics, or health care practitioners to address patients' immediate needs.
2. **Sources of Compounded Products:**
- **Outsourcing Facilities:** Hospitals, clinics, and health care practitioners can obtain non-patient-specific compounded drug products from outsourcing facilities registered under section 503B of the FD&C Act.
3. **Regulations for Outsourcing Facilities:**
- **CGMP Requirements:** Outsourcing facilities must adhere to Current Good Manufacturing Practice (CGMP) regulations.
- **FDA Inspections:** These facilities are subject to FDA inspections based on a risk-based schedule.
- **Adverse Event Reporting:** They must follow specific adverse event reporting requirements.
- **Prescription Requirement:** Outsourcing facilities may or may not obtain prescriptions for identified individual patients prior to distributing compounded drug products (as per section 503B(d)(4)(C)).
4. **Compounding and Distribution:**
- Outsourcing facilities can compound and distribute both sterile and non-sterile non-patient-specific drug products to hospitals, clinics, and health care practitioners for office use.
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**Q: What are the risks and regulatory considerations associated with compounded drug products compared to FDA-approved drugs?**
1. **Risk and FDA Approval:**
- **Higher Risk:** Compounded drugs generally pose a higher risk to patients compared to FDA-approved drugs.
- **No FDA Approval:** Compounded drug products are not FDA-approved, meaning they have not undergone the FDA's premarket review for safety, effectiveness, and quality.
2. **Regulations for Compounding:**
- **Section 503A Compounding:** Licensed pharmacists and licensed physicians who compound drugs in accordance with section 503A are not subject to Current Good Manufacturing Practice (CGMP) requirements.
- **FDA Interaction:** The FDA does not interact with most licensed pharmacists and physicians who compound drug products under section 503A because these compounders are not licensed by the FDA and usually do not register their compounding facilities with the FDA.
3. **FDA Awareness and Monitoring:**
- **Limited Awareness:** The FDA often does not know about potential problems with compounded drug products or compounding practices unless it receives a complaint, such as a report of a serious adverse event or visible contamination
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What is required for documenting a prescriber's determination when prescribing a compounded drug product?
1. Format for Documentation:
The FDA does not require a specific format for documenting the prescriber's determination. The prescription should clearly indicate the change made to the drug product and the significant difference it will produce for the patient.
2. Examples of Sufficient Documentation:
-“No Dye X, patient allergy” (if the comparable drug contains the dye)
-“Liquid form, patient can’t swallow tablet” (if the comparable drug is a tablet)
-“6 mg, patient needs higher dose” (if the comparable drug is only available in 5 mg dose)
3. Insufficient Documentation:
A prescription that only identifies the patient name and drug product formulation without specifying the relevant change or benefit is not sufficient.
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What is the significance of the change made to a commercially available drug product for a compounded drug to qualify for exemptions under section 503A?
1. Significant Difference:
The change made must produce a significant difference for the patient, as determined by the prescribing practitioner, between the compounded drug and the comparable commercially available drug.
2. Inadequate Factors:
Changes based solely on factors such as a lower price do not qualify as a significant difference. The change must affect the drug product formulation in a way that is meaningful for the patient.
3. Copy Restrictions:
Compounded drug products must not be essentially copies of commercially available drug products. Both sections 503A and 503B restrict such practices.
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What should a compounder do if a prescription does not clearly document the prescriber's determination for a compounded drug product?
Contact the Prescriber:
The compounder should contact the prescriber to confirm whether the compounded drug product contains a significant change that makes a difference for the patient.
.
Notation on Prescription:
If confirmed, make a notation on the prescription indicating that the compounded drug product contains a change that produces a significant difference for the patient. The notation should be specific and include the date of the conversation with the prescriber.
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**Q: What conditions must be met for a compounded drug product to qualify for exemptions under Section 503A of the FD&C Act?**
1. **Compliance with USP Chapters:**
- The compounded drug product must be prepared in compliance with the United States Pharmacopoeia (USP) chapters on pharmacy compounding.
- **Bulk Drug Substances:** The bulk drug substances used must comply with the standards of an applicable USP or National Formulary (NF) monograph, if one exists.
- If no monograph exists, the drug substance must be a component of an FDA-approved human drug product.
- If neither a monograph exists nor is the drug substance a component of an FDA-approved drug, it must appear on a list of bulk drug substances for use in compounding developed by the FDA through regulation (section 503A(b)(1)(A)(i) of the FD&C Act).
2. **Manufacturing Establishment Registration:**
- The bulk drug substances must be manufactured by an establishment registered under section 510 of the FD&C Act. This includes foreign establishments registered under section 510(i) of the FD&C Act (section 503A(b)(1)(A)(ii) of the FD&C Act).
3. **Certificates of Analysis:**
- The bulk drug substances must be accompanied by valid certificates of analysis for each substance (section 503A(b)(1)(A)(iii) of the FD&C Act).
4. **Ingredients Compliance:**
- Ingredients other than bulk drug substances used in compounding must comply with the standards of an applicable USP or NF monograph, if one exists, and the USP chapters on pharmacy compounding (section 503A(b)(1)(B) of the FD&C Act).
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**Q: What regulatory requirements must be met for drug products that meet the conditions of Section 503A of the FD&C Act?**
1. **Exemptions:**
- Compounded drug products meeting the conditions of Section 503A of the FD&C Act are exempt from the requirements under sections 501(a)(2)(B), 502(f)(1), and 505 of the FD&C Act.
2. **Potential Violations and Actions:**
- Despite the exemptions, individuals and firms may face regulatory actions such as warning letters, product seizures, injunctions, and/or criminal prosecution for violations of other FD&C Act requirements.
3. **Specific Requirements:**
- **Filthy, Putrid, or Decomposed Substances:** The drug product must not contain any filthy, putrid, or decomposed substances, nor be prepared, packed, or held under insanitary conditions that could lead to contamination or health risks (Sections 501(a)(1) and (a)(2)(A) of the FD&C Act).
- **Official Compendium Standards:** If the drug product is recognized in an official compendium, its strength, quality, or purity must not fall below the compendium standards unless the difference is stated on its label (Section 501(b) of the FD&C Act).
- **Drug Strength and Quality:** For drug products not subject to Section 501(b), the strength, quality, or purity must match what is claimed (Section 501(c) of the FD&C Act).
- **Packaging and Labeling:** Drugs recognized in an official compendium must be packaged and labeled according to the compendium's requirements (Section 502(g) of the FD&C Act).
- **Labeling and Promotion:** The drug product’s labeling, advertising, and promotion must not be false or misleading
40
52. Are compounders required to remove all PPE when leaving the compounding area?
Consider all PPE worn when handling HDs to be contaminated with, at minimum, trace quantities of HDs. The HD gown and outer pair of shoe covers need to be removed in the doffing area prior to leaving the negative pressure room. Other garb may remain, depending on the facility’s polices and work practices. The goal is to contain all hazardous contamination within the negative pressure room.
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53. When do HD PPE components need to be removed?
The outer pair of sterile HD gloves (tested to ASTM D6978) are removed inside the C-PEC prior to leaving the C-PEC. They must be placed in a trace HD container (such as a bag or small rigid yellow bin) inside the hood. Each negative-pressure room should have a doffing area, near the door leading to the anteroom (for a cleanroom suite) or the general area (if leaving a C-SCA). Remove the outer pair of shoe covers and the HD gown in the doffing area and discard it inside a trace HD container in the negative-pressure room just prior to leaving the room. Discard the remaining PPE in the anteroom (for a cleanroom suite) or just outside the general area (for a C-SCA) in a trace HD container.
.
TLDR Remove outer gloves inside the C-PEC, take off the outer shoe covers and gown in the doffing area of the negative-pressure room, and discard all remaining PPE in the anteroom or outside the general area.
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24. Can a single-dose container be used to prepare doses for more than one patient when compounding an immediate-use CSP?
No. One of the conditions of the immediate-use CSP provision specifies that any unused starting components from a single- dose container must be discarded after preparation for the individual patient is complete. Single-dose containers must not be used for more than 1 patient when used for preparing immediate-use CSPs.
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68. What are examples of methods to cover jewelry that cannot be removed?
Examples of jewelry that cannot be removed are dermal piercings (also known as a microdermal piercing), which is a piercing that is held in place with a dermal anchor that is installed underneath the skin. Facilities must determine the appropriate method for covering dermal piercings to minimize the risk of contaminating the CSP and the environment. For example, depending on the location of the piercing, an adhesive bandage or head cover may be used to cover the jewelry.
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A. Are wedding rings permitted to be worn under sterile gloves?
B. Are eyelash extensions allowed in the cleanroom?
C. Regarding Section 3.1, gum-chewing and mints are considered food. Why can’t compounders have anything in their mouths or put anything in their mouths while in the cleanroom suite?
69. Are wedding rings permitted to be worn under sterile gloves?
The chapter requires removing all hand jewelry that could interfere with the effectiveness of garbing or otherwise increase the risk of contamination of the CSP. Wedding rings may potentially compromise the integrity of the glove (e.g., tearing) and prevent adequate hand hygiene.
70. Are eyelash extensions allowed in the cleanroom?
No. Cosmetics are not permitted.
76. Regarding Section 3.1, gum-chewing and mints are considered food. Why can’t compounders have anything in their mouths or put anything in their mouths while in the cleanroom suite?
It is too easy to want to blow bubbles or move gum and candy around in the mouth that could spew additional wet into the mask and contaminate it. The candy or gum can also fall out of the mouth, out of the mask and onto a hood counter or floor and contaminate the area.
45
82. When should I apply sterile 70% IPA to gloves?
Application of sterile 70% IPA to gloves must occur immediately before compounding (e.g., before entering the ISO Class 5 PEC) and regularly throughout the compounding process
46
167. Can a CSP be administered beyond the assigned BUD?
Administration cannot begin past the assigned BUD; however, it is not intended to limit administration that began before the BUD lapsed (see 14.1 Terminology). For example:
* An intravenous preparation begins 1 hour before the BUD lapses; however, it is scheduled to continue infusing for a total of 2 hours. The BUD is not intended to limit the dose from being completed.
* An ophthalmic preparation is scheduled to be given once daily for 14 days; however, the BUD will lapse in 10 days. The medication can continue to be administered up until the assigned BUD in 10 days, beyond which the preparation must not be used and must be discarded.
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168. After the CSP has begun to infuse, does it need to be taken down and discarded after the BUD is met?
No. Administration must begin before the BUD. The administration process is outside the scope of <797>. Standard precautions such as the Centers for Disease Control and Prevention (CDC) safe injection practices apply to administration. See <800> for additional recommendations for the administration of hazardous drugs.
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Q: What is required for water-containing compounded sterile preparations (CSPs) that are nonsterile during any phase of the compounding procedure?
Objective: Water-containing CSPs that are nonsterile during any phase of the compounding procedure must be sterilized within 6 hours after completing the preparation.
Purpose: This requirement is to minimize the generation of bacterial endotoxins.
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60. Is an entity required to have two sets of equipment, one set for compounding HDs and a second set for compounding non-HDs?
Disposable or clean equipment for compounding (such as mortars and pestles, and spatulas) must be dedicated for use with HDs. Equipment (or parts of equipment) that comes in direct contact with HDs must be dedicated for use with HDs. Equipment that does not come in direct contact with HDs may be shared between HD and non-HD compounding areas provided it is deactivated, decontaminated, and cleaned before it is removed from the HD area. Equipment used in HD compounding must be operated in the C-SEC unless it is operated as a closed system (e.g., certain mixers, terminal sterilization using an autoclave, or convection oven).
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22. When compounding immediate-use CSPs, may more than three individual containers of a sterile products be used?
The immediate-use CSPs provision states that the preparation must not involve more than 3 different sterile products. Two or more of the same sterile components (product) may be used as long as there are not more than three different sterile components (products). For example, two vials of the same component (drug product) are reconstituted using two vials of Sterile Water for Injection (component products) and added to a single component product intravenous diluent bag such as NS or D5W. As another example, when the CSP requires combining 4 vials of the same component (drug product) into a single component product intravenous bag of diluent, only 2 different sterile components (products) are used to prepare the CSP. Both examples may be considered immediate use as long as the criteria listed in 1.3 Immediate-Use CSPs are met.
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No. One of the conditions of the immediate-use CSP provision specifies that any unused starting components from a single- dose container must be discarded after preparation for the individual patient is complete. Single-dose containers must not be used for more than 1 patient when used for preparing immediate-use CSPs.
24. Can a single-dose container be used to prepare doses for more than one patient when compounding an immediate-use CSP?
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39. Can immediate-use CSPs be made in a batch for more than one patient?
Compounders can prepare multiple doses of immediate-use CSPs intended for use in one or more patients in a single batch as long as the conditions in Section 1.3 are met.
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22. When compounding immediate-use CSPs, may more than three individual containers of a sterile products be used?
The immediate-use CSPs provision states that the preparation must not involve more than 3 different sterile products. Two or more of the same sterile components (product) may be used as long as there are not more than three different sterile components (products). For example, two vials of the same component (drug product) are reconstituted using two vials of Sterile Water for Injection (component products) and added to a single component product intravenous diluent bag such as NS or D5W. As another example, when the CSP requires combining 4 vials of the same component (drug product) into a single component product intravenous bag of diluent, only 2 different sterile components (products) are used to prepare the CSP. Both examples may be considered immediate use as long as the criteria listed in 1.3 Immediate-Use CSPs are met.
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25. Why does the immediate-use CSP provision allow for administration to begin within 4 hours following the start of the preparation?
The immediate-use CSP provision was revised to allow up to 4 hours for beginning administration to balance the need for ensuring CSP quality with timely access to medication in a variety of healthcare settings. The allowance of up to 4 hours was based on the 4-to-6-hour lag phase of microbial growth, during which potential bacterial cells are adjusting to their environment and change very little, and they do not immediately start reproducing.1 In the event bacterial cells were inadvertently introduced into a CSP during compounding, replication is unlikely and therefore there is a window of time in which a CSP can be held prior to administration.
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40. What does “directly administered” mean in 1.3 Immediate-Use CSPs?
“Directly administered” refers to the dose being prepared and then immediately administered by the person who prepared it, or administration is witnessed by the person who prepared it. In a situation where a CSP may be prepared for direct and immediate administration there is risk involved if a CSP is unlabeled and the person who compounded it is not administering or present for the administration.
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**Q: What are the guidelines for using single-dose and multiple-dose containers of sterile products and compounded sterile preparations (CSPs)?**
1. **Single-Dose Containers:**
- **Opened in Worse than ISO Class 5 Air Quality:**
- **Use Time:** Must be used within 1 hour after opening.
- **Discard:** Any remaining contents must be discarded.
- **Single-Dose Vials Exposed to ISO Class 5 or Cleaner Air:**
- **Use Time:** Can be used up to 6 hours after the initial needle puncture.
- **Opened Single-Dose Ampuls:**
- **Storage:** Shall not be stored; they must be used immediately and discarded if not used.
2. **Multiple-Dose Containers:**
- **Formulation:** Typically contain antimicrobial preservatives and are intended for multiple withdrawals.
- **Beyond-Use Date (BUD):**
- **Standard BUD:** 28 days after the initial entry or opening (e.g., needle puncture), unless otherwise specified by the manufacturer.
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44. Section 2.1 Demonstrating Knowledge and Competency of Core Skills states that personnel must complete training and be able to demonstrate knowledge of principles initially and at least every 12 months. Does this mean that each person needs written or electronic testing on each of the listed topics in addition to competency testing?
The written training program must describe the required training and the process for evaluating the performance of personnel, but personnel must both demonstrate knowledge of principles and competency of skill for performing sterile manipulations and achieving and maintaining appropriate environmental conditions as applicable to their assigned job functions.
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47. Do supervising pharmacists that do not compound have to undergo training and evaluation?
Yes. The following must be included: 1. Core skills: requires that personnel who do not compound, but supervise compounding personnel, have to be trained and demonstrate competency initially and at least every 12 months as outlined in Section 2.1 Demonstrating Knowledge and Competency of Core Skills. 2. Garbing Competency: Initially and at least every 12 months. 3. Aseptic Manipulation Competency: Personnel who have direct oversight of compounding must complete an aseptic manipulation competency evaluation at least every 12 months. The evaluation should correspond to the type of activities of the personnel they oversee but does not require the same quantities.
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13. Does docking and activation of a proprietary bag and vial system for immediate administration in accordance with the manufacturer’s labeling instructions have to occur under ISO 5 conditions?
No. Docking and activation of proprietary bag and vial systems in accordance with the manufacturer’s labeling for immediate administration to an individual patient is not considered compounding and may be performed outside of an ISO Class 5 environment.
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14. When does the chapter apply for docking a proprietary bag and vial system?
Docking of the proprietary bag and vial systems for future activation and administration is considered compounding and must be performed in an ISO Class 5 environment in accordance with , with the exception of 14. Establishing Beyond-Use Dates. BUDs for proprietary bag and vial systems must not be longer than those specified in the manufacturer’s labeling.
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36. If a device (e.g., a repeater pump) has undergone validation by the FDA, is the compounder required to verify the volumetric accuracy each day of use?
Yes. Before using automated compounding devices or other similar equipment, compounding personnel must conduct an accuracy assessment before the first use and again each day the equipment is used to compound CSPs.
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50. How many gloved fingertip and thumb sampling tests and media-fill tests must be done initially and subsequently?
In the revised chapter gloved fingertip and thumb samplings are taken during both the aseptic manipulation competency (i.e., immediately after media-fills) and the garbing competency evaluation (i.e., after garbing and gloving). The complete garbing competency evaluation, including gloved fingertip and thumb sampling, must be successfully completed no fewer than 3 separate times initially, and only 1 time on subsequent evaluations. All aseptic manipulation competency evaluations, including media-fill and gloved fingertip and thumb sampling after media-fill, must be successfully completed 1 time for the initial and 1 time for all subsequent evaluations.
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57. Do the three initial gloved fingertip tests need to be done on the same day?
Not necessarily. The organization can determine the interval for the three initial gloved fingertip tests. In any case, these need to be three separate instances of hand hygiene, garbing, and the gloved fingertip test. Garbing once and completing three sets of gloved fingertip tests does not meet the requirement for the initial testing. The 3 successful completions must be in succession—failure of any of the 3 initial garbing competency evaluations requires repeat testing until personnel successfully complete 3 evaluations in a row.
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61. Does the ongoing garbing competency include gloved fingertip and thumb sampling (GFT) after the visual observation of garbing?
Yes. Performing GFT after the visual observation of garbing ensures personnel can don sterile gloves without contaminating them.
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75. Can gowns be re-used?
Yes. If compounding Category 1 and Category 2 CSPs, gowns used for nonhazardous compounding may be reused within the same shift by the same person if the gown is maintained in a classified area or adjacent to, or within, the SCA in a manner that prevents contamination. Garb must be replaced immediately if it becomes visibly soiled or if its integrity is compromised. Additionally, gowns and other garb must be stored in a manner that minimizes contamination (e.g., away from sinks to avoid splashing).
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81. When must laundering be performed with a validated cycle?
For facilities that compound Category 3 CSPs, laundered sterile garb must not be reused without being laundered and resterilized with a validated cycle. The facility’s SOPs must describe this process.
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123. Does the equipment inside a PEC need to be cleaned?
yes...Yes, the chapter requires equipment inside of the PEC to be cleaned, disinfected, and a sporicidal disinfectant applied
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124. Are cleaning supplies required to be sterile?
Cleaning and disinfecting supplies used in the PEC must be sterile with the exception of tool handles and holders, which must be cleaned and disinfected prior to use in a PEC. The chapter states that all cleaning supplies (e.g., wipers, sponges, and mop heads) with the exception of tool handles and holders must be low lint. Further, the chapter recommends that wipers, sponges, and mop heads be disposable.
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125. Are cleaning agents required to be sterile?
Cleaning, disinfecting, and sporicidal disinfectants used within the PEC must be sterile. In classified areas outside of the PEC, sterile cleaning and disinfecting agents should be used.
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152. When is a compounding record needed for immediate-use CSPs?
If the immediate-use CSPs are prepared in a batch and are intended for use in more than one patient, then a compounding record as described in Section 11.2 Creating Compounding Records is required.
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171. Can the BUDs of Category 2 CSPs be extended beyond those in Table 13. BUD Limits for Category 2 CSPs?
**Q: How are Beyond-Use Dates (BUDs) determined for Category 2 and Category 3 CSPs?**
**A:**
- **Category 2 CSPs:**
- **BUD Determination:** Follow Table 13 unless a specific monograph provides a different BUD, in which case the monograph’s BUD applies if all requirements are met.
- **Category 3 CSPs:**
- **BUD Limits:** Can be assigned longer BUDs than Category 2 CSPs, not exceeding the limits in Table 14, provided all Category 3 requirements are met.
- **General Considerations:**
- **Assignment:** BUDs must be conservative and consider factors like stability testing, sterility, endotoxins, container closure integrity, and particulate matter.
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186. Is a conventionally manufactured single-dose container required to be stored in an ISO Class 5 PEC in order for it to be allowed to be used for up to 12 hours?
No, opened or punctured conventionally manufactured single-dose containers may be stored outside of an ISO Class 5 PEC. However, the chapter does require that the conventionally manufactured single-dose container be entered or punctured inside of an ISO Class 5 PEC. These containers may be used up to 12 hours after initial entry or puncture provided that the storage requirements (e.g., controlled room temperature, cold temperature) are maintained. Opened single-dose ampules must not be stored for any period of time.
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199. What are allergenic extracts?
Allergenic extracts are biological substances used for the diagnosis and/or treatment of allergic diseases such as allergic rhinitis, allergic sinusitis, allergic conjunctivitis, bee venom allergy, and food allergy. Allergenic extract prescription sets are combinations of licensed allergenic extracts which would be mixed and diluted to provide subcutaneous immunotherapy to an individual patient, even though these allergenic extract combinations are not specified in the approved biological license application (BLA) for the licensed biological products.
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200. Does 21. Compounding Allergenic Extracts apply to physician and pharmacy settings?
Yes, the provisions in 21. Compounding Allergenic Extracts apply regardless of where the allergenic extract is compounded when: 1. The compounding process involves transfer via sterile needles and syringes of conventionally manufactured sterile allergen products and appropriate conventionally manufactured sterile added substances, and 2. Manipulations are limited to penetrating stoppers on vials with sterile needles and syringes and transferring sterile liquids in sterile syringes to sterile vials.
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201. Why are the BUDs for compounded allergenic extracts longer than those required for Category 1 and Category 2 CSPs?
Because of certain characteristics of allergenic extracts and allergy practice (e.g., preservative systems and risk of anaphylaxis), preparation of allergenic extract for individual patient prescription sets is not subject to the requirements in this chapter that are applicable to other sterile CSPs. Further, FDA provides additional information for preparation of allergenic extracts in the FDA Guidance for Mixing, Diluting, or Repackaging Biological Products Outside the Scope of an Approved Biologics License Application.
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202. Does gloved fingertip and thumb sampling need to occur after media-fill testing for personnel who compound allergenic extracts?
No. Unlike personnel training for other CSPs, the goal of gloved fingertip and thumb sampling for personnel who compound allergenic extracts is to evaluate hand hygiene and garbing but not aseptic technique, due to the nature of the CSPs they compound. Therefore, personnel perform gloved fingertip and thumb sampling three times initially before compounding; thereafter gloved fingertip and thumb sampling is performed immediately after donning gloves at least once every 12 months. The action level for these samples is anything greater than 0 CFU per each hand.
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203. Can allergenic extracts be prepared for immediate-use?
Yes
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204. Can this section apply for vials that are made for multiple patients?
No. Compounding allergenic extracts is per individual patient prescription set only.
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17. Is more than one designated person permitted for <800>?
YES.
**Q: What is the role of the designated person in a facility for compounded preparations?**
**A:**
- **Role:** The designated person (or persons) is responsible and accountable for the facility’s operations and personnel involved in compounding preparations.
- **Responsibilities:** Facilities must choose and allocate responsibilities to the designated person(s). They can delegate tasks to an assigned trainer as per the organization's policies.
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8. Can a designated person be responsible for more than one site?
<800> does not restrict a designated person to one site. This must be determined by the facility’s SOPs.
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19. Does the designated person need to be a pharmacist?
There is not a requirement for the designated person to be a pharmacist.
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50. Can gowns be re-worn during the same day if a compounder leaves the HD compounding area?
No. Disposable PPE must not be re-used. Consider all PPE worn when handling HDs to be contaminated with, at minimum, trace quantities of HDs. PPE must be placed in an appropriate waste container and further disposed of per local, state, and federal regulations. PPE worn during compounding should be disposed of in the proper waste container before leaving the C-SEC.
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**Q: What records are required when compounding a drug preparation?**
**A:**
1. **Master Formulation Record:**
- **Creation:** Should be created before compounding a preparation for the first time.
- **Use:** Must be followed each time the preparation is made.
2. **Compounding Record:**
- **Completion:** Should be completed each time a preparation is compounded.
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48. Does a new master formulation record (MFR) need to be made for different batch sizes of final CNSP (e.g., same ointment of 120 grams and 60 grams)?
No, the quantity compounded is reflected in the compounding record (CR).
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Which of the following should be included in the Compounding Record for prepration of a non-sterile product? Select all that apply.
Choose ALL answers that apply.
A
Lot number of the product(s) used
B
Mixing instructions
C
Expiration dates of the product(s) used
D
Name of person who prepared the product
E
Documentation of any issues reported by the patient
All but B!!!
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Outsourcing facilities differ in compounding regulations from that of community pharmacies. Outsourcing facilities (Select all that apply)
Choose ALL answers that apply.
A
May obtain prescriptions to compound drug products for individual patients
B
May compound drug products in large batches, NOT for individual patients
C
Are subject to Current Good Manufacturing Practice (CGMP) regulations
D
May compound drug products for health care practitioners to have on-hand
ALL!!!!!!
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Immediate-use compounded sterile products are exempt from the requirements garbing and ISO 5 air as long as (Select all that apply)
Choose ALL answers that apply.
A
The compounding process involves no more than 3 different sterile products
B
Aseptic technique is followed
C
Administration begins no later than 4 hours following the start of the preparation
D
The product bears a label or is administered by the person who prepared it
ALL!
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True or False: If a compounded sterile product has a drug monograph that states a beyond-use-date beyond that which is stated in USP for that Category of compound, the longer beyond-use-date may be used.
True
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Compounding allergenic extracts
I. May be immediate-use
II. Are to be prepared for 1 individual patient maximum
III. May have longer beyond-use-dates than other category 1 compounds
All
