STATE OF COLORADO

State PHARMACY Board	Department of Regulatory Agencies
Wendy L. Anderson,  Program Director	D. Rico Munn
	Executive Director
1560 Broadway, Suite 1300	
Denver, Colorado 80202-5146		Division of Registrations
Phone (303) 894-7690		Rosemary McCool
Fax (303) 894-7692		Director
TTY:Dial 711 for Relay Colorado				
www.dora.state.co.us/pharmacy	
	Bill Ritter Jr.
	Governor

NOTICE OF RULE MAKING HEARING

Pursuant to Colorado Revised Statutes, Title 12, Article 22 and Title 24, Article 4, CRS (2007), you are hereby advised that the Colorado State Pharmacy Board will hold a public rule making hearing on Thursday, January 17, 2008, at 9:30 a.m., at the Denver Post Building, 1560 Broadway, Suite 1380 Conference Room, Denver, Colorado 80202, for consideration of the following:

Hearing Regarding Repeal, Modification, Amendment, Revision or Adoption of:
Rule 3.01.20 (3 CCR, 719-1)
Rule 3.02.00 (3 CCR, 719-1)
Rule 10.00.00  (3 CCR, 719-1)
Rule 21.00.00 (3-CCR,719-1)

The proposed rules under consideration are attached to this notice and fully incorporated herein.

The Board encourages interested parties to submit written comments to the letterhead address regarding any of the above-listed rulemaking matters no later than December 20, 2007.  In addition, at the time and place designated in this notice, the Board of Pharmacy will afford interested parties an opportunity to submit written information, data, views or arguments.  The Board also will afford interested parties an opportunity to make brief oral presentations unless the Board in its discretion determines that such oral presentations are unnecessary.  All submissions will be considered.  The rules under consideration may be changed or modified after public comment and hearing.

BY ORDER OF THE COLORADO STATE BOARD OF PHARMACY

_______________________________________
Wendy Anderson, Program Director

Dated this ___________ day of __________________, 2007

COLORADO STATE BOARD OF PHARMACY
Rulemaking Hearing, January 17, 2008

Proposed Changes with Statement of Basis, Purpose, and Authority

Basis and Purpose:		Rule 3.01.20 is being amended to allow the identification of the manufacturer or distributor to not appear on the labeling of a packaged product when a suitable internal record is maintained.

Statement of Authority:	The Board is granted authority to promulgate rules pursuant to CRS sections 12-22-108 and 110 and 24-4-103.

3.01.20  Each packaged container, whether for use in a unit dose distribution system or a traditional dispensing system, shall be labeled in accordance with this regulation.  Any packaged unit dose, single dose or unit of issue container for which return for restocking and redispensing, pursuant to 3.00.80, is anticipated, shall be labeled in accordance with this regulation.  Additionally, any packaged container from which subsequent dispensing may occur, shall be labeled in accordance with this regulation.  Such labeling shall include at least the following:

a.	If a suitable internal record is maintained in the prescription drug outlet or other outlet, the requirements of (D), (e), (f), (g), and (h) of this rule may be omitted from the labeling and maintained in such record.  An internal lot number shall be assigned and shall appear in the labeling.  In a prescription drug outlet the record shall be signed by the pharmacist responsible for each lot packaged.  In another outlet the record shall be signed by the person specified in the Board approved protocol.  The record shall be retained for two years from the date of packaging unless otherwise required by law or regulation.

b.	Name and strength of the medication, and, in the case of a single dose package, the total number of individual tablets or capsules per dose;

c.	A suitable expiration date, which shall be not later than the expiration date on the manufacturer’s container, or one year from the date the drug is packaged, whichever is less;

d.	The identity of the manufacturer or distributor;

e.	The manufacturer's or distributor's lot number;

f.	The manufacturer’s or distributor’s expiration date;;

g.	The date the product was packaged;

h.	The identity of the pharmacist responsible for packaging in a prescription drug outlet, or, in the case of an other outlet, the identity of the non-pharmacist permitted to do so pursuant to protocols approved by the Board;

COLORADO STATE BOARD OF PHARMACY
Rulemaking Hearing, January 17, 2008

Proposed Changes with Statement of Basis, Purpose, and Authority

Basis and Purpose:		Rule 3.02.00 is being repealed and incorporated instead into new Rule 21.00.00, Compounding.

Statement of Authority:	The Board is granted authority to promulgate rules pursuant to CRS sections 12-22-108 and 110 and 24-4-103.

3.02.00  Compounding.

The purpose of this regulation is to provide information to pharmacists to enhance the pharmacist’s ability to compound preparations that are of acceptable strength, quality and purity.

If the pharmacist compounds a preparation according to the manufacturer’s labeling instructions, then further documentation is not required.  All other compounded preparations require further documentation.

3.02.10	Limitations.  

a.  No preparation shall be compounded in advance in such quantity as may exceed a 90 day supply or is necessary to accurately compound the preparation.  A 90 day supply shall be determined by the average number of dosage units dispensed or distributed of said preparation during the previous 6 month period.

b.  No expired components may be used in compounding.  No component may be used which will expire prior to the beyond-use date of the final compounded product.

3.02.20  Formulation Record.  For each compounded preparation, a uniform, readily retrievable formulation record shall be maintained, documenting:

a.  The name, strength, and dosage form of the preparation compounded;

b.  All ingredients and their quantities;

c.  The equipment used to prepare the preparation, when appropriate, and mixing instructions;

d.  The formulation assigned expiration date;

e.  The container used in dispensing;

f.  The storage requirements;

g.  Procedures for quality control.

3.02.30  Compounding Record.  For each compounded preparation, a record shall be maintained on the original order, or on a separate, uniform, readily retrievable record documenting:

a.  The name and strength of the compounded preparation;

b.  The formulation record reference for the preparation;

c.  The sources and lot numbers of each ingredient;

d.  The manufacturer’s expiration date of each ingredient when applicable;

e.  The total number of dosage units compounded;

f.  The name of the person who prepared the preparation;

g.  The name of the pharmacist who approved the preparation;

h.  The date of preparation;

i.  The assigned internal identification number if applicable;

j.  The assigned expiration date which, in the absence of stability information that is applicable to a specific drug and preparation,

(1)  For nonaqueous and solid formulations

(a)  Where the manufactured drug product is the source of the active ingredient, shall not exceed 25% of the time remaining until the product’s expiration date or 6 months, whichever is earlier;

(b)  Where a USP-NF substance is the source of active ingredient, shall not be greater than 6 months;

(2)  For water-containing formulations prepared from ingredients in solid form, shall not be greater than 14 days when stored at cold temperatures;

(3)  For all other formulations, shall not be greater than the intended duration of therapy or 30 days, whichever is earlier;

k.  The prescription number, if appropriate;

l.  The results of quality control procedures.

3.02.40  Labeling of Dispensed Compounded Prescriptions.

a.  Labeling shall comply with CRS 12-22-123.  In addition, the label shall contain the beyond-use expiration date of the product.

3.02.50  Casual Sales/distribution of Compounded Products.

a.  A pharmacy may only distribute a compounded product to a practitioner authorized by law to prescribe the drug.  

b.  The pharmacy must retain the following information on a current basis for each practitioner to whom it distributes compounded products:

1.  Verification of practitioner’s license from the jurisdiction in which licensed;

2.  Verification of practitioner’s current DEA registration, if controlled substances are distributed to the practitioner;

3.  If the products are distributed to practitioners located outside of Colorado, the pharmacy shall verify that the practitioners legally authorized to prescribe the drug in the jurisdiction in which the practitioner is licensed;

4.  If the products are distributed outside of the United States, the pharmacy shall maintain written documentation of the above in English; and

5.  Controlled substances may not be distributed outside of the United States unless the pharmacy has obtained registration with DEA as an exporter.

c.  Labeling of compounded products which are distributed shall contain at least the following:
1.  Name and address of the outlet;
2.  Name and strength of the drug(s);
3.  Total quantity in package;
4.  Quantity of active ingredient in each dosage unit;
5.  Beyond-use date;
6.  Batch (lot) number;
7.  Specific route of administration;
8.  Storage directions;
9.  “RX only”;
10.  “This product was compounded by the pharmacy”.

d.  Records of distribution shall comply with regulation 11.07.20.

COLORADO STATE BOARD OF PHARMACY
Rulemaking Hearing, January 17, 2008

Proposed Changes with Statement of Basis, Purpose, and Authority

Basis and Purpose:		Rule 10.00.00 is being repealed and readopted to allow for automated emergency kits and to modify outdated terminology.  An emergency kit is a kit containing emergency drugs which, by statute, a prescription drug outlet may provide to an approved facility, licensed hospice or certified home health agency.

Statement of Authority:	The Board is granted authority to promulgate rules pursuant to CRS sections 12-22-108 and 110 and 24-4-103.

10.00.00  EMERGENCY KITS.

10.00.10  Application.  Nursing homes, home health agencies, hospices, extended care facilities or intermediate care facilities licensed or certified by the Department of Public Health & Environment may maintain an emergency kit.  Such kit is to provide an emergency supply of drugs, both controlled and non-controlled as provided below.  The drugs maintained in the emergency drug supply shall remain the property of the pharmacy to whom the approval was issued.  Emergency kits and the contents thereof shall meet the following requirements:

10.00.20  Access.  Access to the contents of the kit shall be limited as follows:

a.  In the case of an approved facility, only a pharmacist employed by the prescription drug outlet which provides the kit, the consulting pharmacist, and any nurse employed at the facility shall have access.

b.  In the case of a certified home health agency or a licensed hospice, only a pharmacist employed by the prescription drug outlet which provides the kit or a nurse employed by the certified home health agency or licensed hospice shall have access.

10.00.30  Categories and Limits.  The Board shall establish therapeutic categories for drugs to be placed in the kit.

a.  In the case of an approved facility (i.e. nursing homes, intermediate and extended care facilities, etc.) the medical director of the facility, or equivalent, and the consulting pharmacist shall determine the specific drugs to be kept in the kit.  The number of drugs allowed in the kit shall be limited to sixty (60).  Of the 60, twelve (12) may be controlled substances.  The kit may contain no more than thirty (30) doses of any separate drug dosage form or strength for each drug.  The container size for each drug shall be limited to unit dose or unit of issue packaging.  Only an approved facility shall be permitted to have oral dosage forms of drugs in the kit.

b.  In the case of a certified home health agency or a licensed hospice, the director of nursing of the certified home health agency or of the licensed hospice, or designee, and a pharmacist employed and designated by the prescription drug outlet providing the kit shall determine the specific drugs to be kept in the kit.  A certified home health agency or licensed hospice may not have oral dosage forms of drugs or controlled substances in the kit.  The container size for each injectable drug shall be limited to unit dose or unit of issue packaging.  The number of drugs allowed in the kit shall be limited to sixty (60).  The kit may contain only thirty (30) doses of any separate drug dosage form or strength for each drug.

c.  The responsibility for stocking and restocking the emergency drug kit is that of a licensed pharmacist.

10.00.40  Notification.  A pharmacy which supplies an emergency drug kit to an approved facility or certified home health agency or licensed hospice shall notify the Board in writing within seven days that it has done so, specifying the name and address of the facility.

Notification must be repeated, within 30 days:

a.  If there is any change of ownership of the kit,

or 

b.  If there is a change of the consulting pharmacist, in the case of an approved facility, or of the designated pharmacist in the case of a certified home health agency or a licensed hospice.

10.00.50  The kit shall be sealed in such a manner that the seal must be broken to remove a drug.  Paper or tape seals are unacceptable.

10.00.51  The following information shall be placed on the outside of the kit and shall be readily visible and up-dated as required:  name, address and telephone number of the prescription drug outlet providing the contents of the kit; the date of sealing; a suitable expiration date which shall be the earliest expiration date of any drug in the kit, but in no event shall it be more than one year from the date of sealing; and, in the case of an approved facility, the name of the consulting pharmacist, or, in the case of a certified home health agency or a licensed hospice, the name of the designated pharmacist. A copy of the kit contents shall also be attached to the outside of the kit.

Use of automated storage units must comply with current pharmacy rules and follow the procedures outlined in these regulations, except as provided below:

a.  No seal is required on the unit, but a code is required in order to access it;

b.  The unit shall be restocked by a licensed pharmacist only at the facility in which it resides.

10.00.60  Inspection.  A pharmacist employed by the prescription drug outlet providing the kit shall inspect and inventory the contents of the kit at least annually and within 72 hours after being notified that the seal was broken.  Inspection shall be documented by that pharmacist, and such documentation shall be maintained and available for inspection at the prescription drug outlet for a period of two years.

10.00.70  Records.  The prescription drug outlet providing the kit shall maintain a separate record of use for each drug placed in the kit, and for each kit provided, which shall state the name and address of the approved facility, certified home health agency, or licensed hospice; the name and strength of the drug; and the container size and the quantity initially placed in the kit.  When a drug is removed for administration the prescription drug outlet shall obtain a prescription order for the drug within 72 hours after being notified that the kit was opened and the drug was used.  The order shall indicate the total number of doses administered.  The order shall be assigned a serial number and the order shall be retained as required by Regulation 11.04.10.  Additionally, the separate record required for each drug in the kit shall reflect the following information:  date and quantity administered; names of both the patient and practitioner; date the drug was replaced in the kit; the quantity of the drug replaced, which shall not exceed the quantity administered or removed for administration; and the prescription order number assigned.

10.00.80  Use.  The drugs shall only be administered to patients of the approved facility, certified home health care agency, or licensed hospice pursuant to the order of a practitioner.

10.00.90  Withdrawal of approval.  The possession or disposition of the drugs in contravention to these regulations shall result in the Board withdrawing approval of the drugs in the kit and may be deemed to be in violation of CRS 12-22-125.

10.00.00  EMERGENCY KITS.

10.00.10		A PRESCRIPTION DRUG OUTLET OR A HOSPITAL OTHER OUTLET MAY PROVIDE AN EMERGENCY KIT TO ANY OF THE FOLLOWING FACILITIES THAT ARE LICENSED OR CERTIFIED BY THE COLORADO DEPARTMENT OF PUBLIC HEALTH AND ENVIRONMENT:  LONG-TERM CARE FACILITIES, HOSPICES, AND HOME HEALTH AGENCIES.  Such kit is to provide an emergency supply of drugs, both controlled and non-controlled as provided below.  The drugs maintained in the emergency drug supply shall remain the property of the PRESCRIPTION DRUG OUTLET OR THE HOSPITAL OTHER OUTLET WHO SUPPLIED THE DRUGS. 

A.	ONLY ONE PRESCRIPTION DRUG OUTLET OR HOSPITAL OTHER OUTLET MAY PROVIDE A KIT TO ANY OF THE ABOVE FACILITIES.  MULTIPLE PHARMACIES OR HOSPITAL OTHER OUTLETS MAY NOT SUPPLY EMERGENCY KITS TO THE SAME FACILITY.

B.	THE PHARMACIST MANAGER OF THE PRESCRIPTION DRUG OUTLET SUPPLYING THE KIT OR THE CONSULTANT PHARMACIST OF THE HOSPITAL OTHER OUTLET SUPPLYING THE KIT SHALL BE RESPONSIBLE FOR THE ACCURATE STOCKING OR RESTOCKING OF THE KIT.  HE/SHE MAY DELEGATE THIS FUNCTION TO NON-PHARMACIST PERSONNEL, BUT THE PHARMACIST MANAGER OR OTHER OUTLET CONSULTANT PHARMACIST ASSUMES RESPONSIBILITY FOR THE ACCURACY OF THE CONTENTS OF THE KIT.

10.00.20		Categories and Limits.  

A.	FOR LONG TERM CARE FACILITIES AND INPATIENT HOSPICES, THE MEDICAL DIRECTOR OF THE FACILITY, OR EQUIVALENT, AND THE CONSULTING PHARMACIST SHALL DETERMINE THE SPECIFIC DRUGS TO BE KEPT IN THE KIT.  THE NUMBER OF DRUGS ALLOWED IN THE KIT SHALL BE LIMITED TO SIXTY (60).  OF THE 60, TWELVE (12) MAY BE CONTROLLED SUBSTANCES.  THE KIT MAY CONTAIN NO MORE THAN THIRTY (30) DOSES OF ANY SEPARATE DRUG DOSAGE FORM OR STRENGTH FOR EACH DRUG.  THE CONTAINER SIZE FOR EACH DRUG SHALL BE LIMITED TO UNIT DOSE OR UNIT OF ISSUE PACKAGING.  

B.	IN THE CASE OF A CERTIFIED HOME HEALTH AGENCY OR AN OUTPATIENT HOSPICE, THE DIRECTOR OF NURSING OF THE CERTIFIED HOME HEALTH AGENCY OR OF THE LICENSED HOSPICE, AND A PHARMACIST EMPLOYED AND DESIGNATED BY THE PRESCRIPTION DRUG OUTLET OR HOSPITAL OTHER OUTLET PROVIDING THE KIT SHALL DETERMINE THE SPECIFIC DRUGS TO BE KEPT IN THE KIT.  A CERTIFIED HOME HEALTH AGENCY OR OUTPATIENT HOSPICE MAY NOT HAVE ORAL DOSAGE FORMS OR CONTROLLED SUBSTANCES IN THE KIT.  THE CONTAINER SIZE FOR EACH INJECTABLE DRUG SHALL BE LIMITED TO UNIT DOSE OR UNIT OF ISSUE PACKAGING.  THE NUMBER OF DRUGS ALLOWED IN THE KIT SHALL BE LIMITED TO SIXTY (60).  THE KIT MAY CONTAIN ONLY THIRTY (30) DOSES OF ANY SEPARATE DRUG DOSAGE FORM OR STRENGTH FOR EACH DRUG.

10.00.30	THE KIT SHALL BE SEALED WITH A TAMPER-EVIDENT SEAL OR  AN ELECTRONIC SYSTEM WHICH NOTIFIES THE PHARMACY WHEN THE KIT HAS BEEN ACCESSED.  PAPER OR TAPE SEALS ARE UNACCEPTABLE.  IF AN ELECTRONIC SYSTEM IS UTILIZED, THE PHARMACY AND FACILITY MUST MAINTAIN A WRITTEN PROCEDURE FOR HOW THE KIT CAN BE ACCESSED IN THE EVENT OF DOWNTIME.

10.00.40	THE FOLLOWING INFORMATION SHALL BE READILY RETRIEVABLE AND UP-DATED AS REQUIRED:  

A.	NAME, ADDRESS AND TELEPHONE NUMBER OF THE PRESCRIPTION DRUG OUTLET OR HOSPITAL OTHER OUTLET PROVIDING THE CONTENTS OF THE KIT; 

B.	THE DATE OF SEALING OF THE KIT;

C.	 A SUITABLE EXPIRATION DATE WHICH SHALL BE THE EARLIEST EXPIRATION DATE OF ANY DRUG IN THE KIT, BUT IN NO EVENT SHALL IT BE MORE THAN ONE YEAR FROM THE DATE OF SEALING;

D.	IN THE CASE OF A LONG-TERM CARE FACILITY OR INPATIENT HOSPICE, THE NAME OF THE CONSULTING PHARMACIST, OR, IN THE CASE OF A CERTIFIED HOME HEALTH AGENCY OR AN OUTPATIENT HOSPICE, THE NAME OF THE DESIGNATED PHARMACIST. 

10.00.41	A COPY OF THE KIT CONTENTS SHALL ALSO BE ATTACHED TO THE KIT.

10.00.50	ACCESS.  ACCESS TO THE CONTENTS OF THE KIT SHALL BE LIMITED AS FOLLOWS:

A.	IN THE CASE OF A LONG-TERM CARE FACILITY OR INPATIENT HOSPICE, ONLY A PHARMACIST EMPLOYED BY THE PRESCRIPTION DRUG OUTLET OR HOSPITAL OTHER OUTLET WHICH PROVIDES THE KIT OR HIS/HER DESIGNEE, THE CONSULTING PHARMACIST, AND ANY NURSE EMPLOYED AT THE FACILITY SHALL HAVE ACCESS.

B.	IN THE CASE OF A CERTIFIED HOME HEALTH AGENCY OR AN OUTPATIENT HOSPICE, ONLY A PHARMACIST EMPLOYED BY THE PRESCRIPTION DRUG OUTLET OR HOSPITAL OTHER OUTLET WHICH PROVIDES THE KIT OR A NURSE EMPLOYED BY THE CERTIFIED HOME HEALTH AGENCY OR AN OUTPATIENT HOSPICE SHALL HAVE ACCESS.

10.00.51	NOTIFICATION.  A PRESCRIPTION DRUG OUTLET OR HOSPITAL OTHER OUTLET WHICH SUPPLIES AN EMERGENCY DRUG KIT TO A LONG-TERM CARE FACILITY, HOSPICE, OR HOME HEALTH AGENCY SHALL NOTIFY THE BOARD IN WRITING WITHIN SEVEN DAYS THAT IT HAS DONE SO, SPECIFYING THE NAME AND ADDRESS OF THE FACILITY.

NOTIFICATION MUST BE REPEATED, WITHIN 30 DAYS:

A.	IF THERE IS ANY CHANGE OF OWNERSHIP OF THE KIT,

OR 

B.	IF THERE IS A CHANGE OF THE CONSULTING PHARMACIST, IN THE CASE OF A LONG-TERM CARE FACILITY OR INPATIENT HOSPICE, OR OF THE DESIGNATED PHARMACIST IN THE CASE OF A CERTIFIED HOME HEALTH AGENCY OR A OUTPATIENT HOSPICE.

10.00.60	Inspection.  A pharmacist employed by the prescription drug outlet OR HOSPITAL OTHER OUTLET providing the kit OR THAT PHARMACIST’S DESIGNEE shall inspect and inventory the contents of the kit at least annually and within 72 hours after being notified that the KIT HAS BEEN ACCESSED. Inspection shall be documented by that pharmacist, and such documentation shall be maintained and available for inspection at the prescription drug outlet OR HOSPITAL OTHER OUTLET for a period of two years.

10.00.70	RECORDS.  THE PRESCRIPTION DRUG OUTLET OR HOSPITAL OTHER OUTLET PROVIDING THE KIT SHALL MAINTAIN A SEPARATE RECORD OF USE FOR EACH DRUG PLACED IN THE KIT, AND FOR EACH KIT PROVIDED, WHICH SHALL STATE THE FOLLOWING:

A.	THE NAME AND ADDRESS OF THE LONG TERM CARE FACILITY, CERTIFIED HOME HEALTH AGENCY, OR HOSPICE;

B.	THE NAME AND STRENGTH OF THE DRUG; 

C.  THE CONTAINER SIZE AND THE QUANTITY INITIALLY PLACED IN THE KIT.  

10.00.71	WHEN A DRUG IS REMOVED FOR ADMINISTRATION THE PRESCRIPTION DRUG OUTLET OR HOSPITAL OTHER OUTLET SHALL OBTAIN A PRESCRIPTION ORDER OR LTCF CHART ORDER FOR THE DRUG WITHIN 72 HOURS AFTER BEING NOTIFIED THAT THE KIT WAS OPENED AND THE DRUG WAS USED.  THE ORDER SHALL INDICATE THE TOTAL NUMBER OF DOSES ADMINISTERED.  THE ORDER SHALL BE ASSIGNED A SERIAL NUMBER AND THE ORDER SHALL BE RETAINED AS REQUIRED BY REGULATION 11.04.10.  ADDITIONALLY, THE SEPARATE RECORD REQUIRED FOR EACH DRUG IN THE KIT SHALL REFLECT THE FOLLOWING INFORMATION:  

A.	DATE AND QUANTITY ADMINISTERED; 

B.	NAMES OF BOTH THE PATIENT AND PRACTITIONER;
 
C.	DATE THE DRUG WAS REPLACED IN THE KIT; 

D.	THE QUANTITY OF THE DRUG REPLACED, WHICH SHALL NOT EXCEED THE QUANTITY ADMINISTERED OR REMOVED FOR ADMINISTRATION; AND 

E.	THE PRESCRIPTION ORDER NUMBER ASSIGNED.

10.00.80	Use.  The drugs shall only be administered to patients of the LONG TERM CARE facility, certified home health care agency, or hospice pursuant to the order of a practitioner.

COLORADO STATE BOARD OF PHARMACY
Rulemaking Hearing, January 17, 2008

Proposed Changes with Statement of Basis, Purpose, and Authority

Basis and Purpose:	Rule 21.00.00, “Compounding,” is being proposed with the rules from 3.02.00 being incorporated into Rule 21.00.00.  Rule 21.00.00 codifies the proper compounding of medications, both sterile and non-sterile to conform with United States Pharmacopeia (USP) requirements.

Statement of Authority:	The Board is granted authority to promulgate rules pursuant to CRS sections 12-22-108 and 110, and 24-4-103.

21.00.00	COMPOUNDING.

THE PURPOSE OF THIS REGULATION IS TO PROVIDE INFORMATION TO PHARMACISTS TO ENHANCE THE PHARMACIST’S ABILITY TO COMPOUND PREPARATIONS THAT ARE OF ACCEPTABLE STRENGTH, QUALITY AND PURITY.

FOR THE PURPOSES OF THIS REGULATION 21.00.00, PREPARATION OR PRODUCT MEANS A DRUG DOSAGE FORM, A DIETARY SUPPLEMENT, OR A FINISHED DEVICE.  IT IS THE FINISHED OR PARTIALLY FINISHED PREPARATION OF ONE OR MORE SUBSTANCES FORMULATED FOR USE ON OR FOR THE PATIENT.

IF THE PHARMACIST COMPOUNDS A PREPARATION ACCORDING TO THE MANUFACTURER’S LABELING INSTRUCTIONS, THEN FURTHER DOCUMENTATION IS NOT REQUIRED.  ALL OTHER COMPOUNDED PREPARATIONS REQUIRE FURTHER DOCUMENTATION.

21.00.10	LIMITATIONS.  

A.	NO PREPARATION SHALL BE COMPOUNDED IN ADVANCE IN SUCH QUANTITY AS MAY EXCEED A 90 DAY SUPPLY OR IS NECESSARY TO ACCURATELY COMPOUND THE PREPARATION.  A 90 DAY SUPPLY SHALL BE DETERMINED BY THE AVERAGE NUMBER OF DOSAGE UNITS DISPENSED OR DISTRIBUTED OF SAID PREPARATION DURING THE PREVIOUS 6 MONTH PERIOD.

B.	NO EXPIRED COMPONENTS MAY BE USED IN COMPOUNDING.  NO COMPONENT MAY BE USED WHICH WILL EXPIRE PRIOR TO THE BEYOND-USE DATE OF THE FINAL COMPOUNDED PRODUCT.

21.00.20	CASUAL SALES/DISTRIBUTION OF COMPOUNDED PRODUCTS.

A.	A PRESCRIPTION DRUG OUTLET MAY ONLY DISTRIBUTE A COMPOUNDED PRODUCT TO A PRACTITIONER AUTHORIZED BY LAW TO PRESCRIBE THE DRUG.  

B.	THE PRESCRIPTION DRUG OUTLET MUST RETAIN THE FOLLOWING INFORMATION ON A CURRENT BASIS FOR EACH PRACTITIONER TO WHOM IT DISTRIBUTES COMPOUNDED PRODUCTS:

1.	VERIFICATION OF PRACTITIONER’S LICENSE FROM THE JURISDICTION IN WHICH LICENSED;

2.	VERIFICATION OF PRACTITIONER’S CURRENT DEA REGISTRATION, IF CONTROLLED SUBSTANCES ARE DISTRIBUTED TO THE PRACTITIONER;

3.	IF THE PRODUCTS ARE DISTRIBUTED TO PRACTITIONERS LOCATED OUTSIDE OF COLORADO, THE PHARMACY SHALL VERIFY THAT THE PRACTITIONER IS LEGALLY AUTHORIZED TO PRESCRIBE THE DRUG IN THE JURISDICTION IN WHICH THE PRACTITIONER IS LICENSED;

4.	IF THE PRODUCTS ARE DISTRIBUTED OUTSIDE OF THE UNITED STATES, THE PHARMACY SHALL MAINTAIN WRITTEN DOCUMENTATION OF THE ABOVE IN ENGLISH; AND

5.	CONTROLLED SUBSTANCES MAY NOT BE DISTRIBUTED OUTSIDE OF THE UNITED STATES UNLESS THE PHARMACY HAS OBTAINED REGISTRATION WITH THE DRUG ENFORCEMENT ADMINISTRATION (DEA) AS AN EXPORTER.

C.	LABELING OF COMPOUNDED PRODUCTS WHICH ARE DISTRIBUTED SHALL CONTAIN AT LEAST THE FOLLOWING:
1	 NAME AND ADDRESS OF THE OUTLET;
2.	NAME AND STRENGTH OF THE DRUG(S);
3.	TOTAL QUANTITY IN PACKAGE;
4.	QUANTITY OF ACTIVE INGREDIENT IN EACH DOSAGE UNIT;
5.	BEYOND-USE DATE;
6.	BATCH (LOT) NUMBER;
7.	SPECIFIC ROUTE OF ADMINISTRATION;
8.	STORAGE DIRECTIONS;
9.	“RX ONLY”;
10	 “THIS PRODUCT WAS COMPOUNDED BY THE PHARMACY”.

D.	RECORDS OF DISTRIBUTION SHALL COMPLY WITH REGULATION 11.07.20.

21.10.00	 COMPOUNDING OF NON-STERILE PRODUCTS

21.10.10 	DEFINITIONS.  WHEN USED IN THIS REGULATION 21.10.00, THE FOLLOWING WORDS AND TERMS SHALL HAVE THE FOLLOWING MEANINGS, UNLESS THE CONTEXT CLEARLY INDICATES OTHERWISE.
A.	ACTIVE INGREDIENT: CHEMICALS, SUBSTANCES OR OTHER COMPONENTS OF PREPARATIONS INTENDED FOR USE IN THE DIAGNOSIS, CURE, MITIGATION, TREATMENT, OR PREVENTION OF DISEASES IN HUMAN OR OTHER ANIMALS OR FOR USE AS DIETARY SUPPLEMENTS.
B.	BATCH (LOT):  MULTIPLE UNITS OF THE SAME COMPOUNDED PREPARATION IN A SINGLE DISCRETE PROCESS, BY THE SAME INDIVIDUALS, CARRIED OUT DURING ONE LIMITED TIME PERIOD.  
C.	BEYOND-USE DATE: A DATE AFTER WHICH A COMPOUNDED PREPARATION SHOULD NOT BE USED AND IS DETERMINED FROM THE DATE THE PREPARATION IS COMPOUNDED. 
D.	COMPOUNDING: THE PREPARATION, MIXING, ASSEMBLING, PACKAGING, OR LABELING OF A DRUG OR DEVICE:
1.	AS THE RESULT OF A PRACTITIONER’S PRESCRIPTION DRUG ORDER, CHART ORDER, OR INITATIVE, BASED ON THE RELATIONSHIP BETWEEN THE PRACTITIONER, PATIENT, AND PHARMACIST IN THE COURSE OF PROFESSIONAL PRACTICE; OR
2.	FOR THE PURPOSE OF, OR AS AN INCIDENT TO, RESEARCH, TEACHING, OR CHEMICAL ANALYSIS AND NOT FOR SALE OR DISPENSING.
3.	COMPOUNDING ALSO INCLUDES THE PREPARATION OF DRUG OR DEVICES IN ANTICIPATION OF PRESCRIPTION ORDERS BASED ON ROUTINE, REGULARLY-OBSERVED PRESCRIBING PATTERNS.
E.	OFFICIAL SUBSTANCE: AN ACTIVE DRUG ENTITY, A DIETARY SUPPLEMENT, OR A PHARMACEUTICAL INGREDIENT OR A COMPONENT OF A FINISHED PREPARATION.
F.	QUALITY ASSURANCE: SET OF ACTIVITIES USED TO ENSURE THAT THE PROCESSES USED IN THE PREPARATION OF NON-STERILE DRUG PRODUCTS LEAD TO PRODUCTS THAT MEET PREDETERMINED STANDARDS OF QUALITY.
G.	QUALITY CONTROL: SET OF TESTING ACTIVITIES USED TO DETERMINE THAT THE INGREDIENTS, COMPONENTS AND FINAL NON-STERILE PRODUCTS PREPARED MEET PREDETERMINED REQUIREMENTS WITH RESPECT TO STRENGTH, IDENTITY, QUALITY, AND PURITY.
H.	REPACKAGING: THE SUBDIVISION OR TRANSFER OF A COMPOUNDED PRODUCT FROM ONE CONTAINER OR DEVICE TO A DIFFERENT CONTAINER OR DEVICE.
I.	SOPS: STANDARD OPERATING PROCEDURES.
J.	STABILITY: EXTENT TO WHICH A PREPARATION RETAINS, WITHIN SPECIFIED LIMITS, AND THROUGHOUT ITS PERIOD OF STORAGE AND USE, THE SAME PROPERTIES AND CHARACTERISTICS THAT IT POSSESSED AT THE TIME OF COMPOUNDING.
K.	USP/NF: THE CURRENT EDITION OF THE UNITED STATES PHARMACOPEIA/NATIONAL FORMULARY.
L.	VALIDATION: DOCUMENTED EVIDENCE PROVIDING A HIGH DEGREE OF ASSURANCE THAT SPECIFIC PROCESSES WILL CONSISTENTLY PRODUCE A PRODUCT MEETING PREDETERMINED SPECIFICATIONS AND QUALITY ATTRIBUTES.
21.10.20  	POLICY AND PROCEDURE MANUAL.
A.	A MANUAL, OUTLINING POLICIES AND PROCEDURES ENCOMPASSING ALL ASPECTS OF NON-STERILE COMPOUNDING SHALL BE AVAILABLE FOR INSPECTION AT THE PHARMACY.  THE MANUAL SHALL BE COMPLIED WITH AND SHALL BE REVIEWED ON AN ANNUAL BASIS.  SUCH REVIEW SHALL BE SIGNED AND DATED BY THE PHARMACIST MANAGER.  IN THE EVENT, THE PHARMACIST MANAGER CHANGES, THE NEW MANAGER SHALL REVIEW, SIGN, AND DATE THE MANUAL WITHIN 30 DAYS OF BECOMING PHARMACIST MANAGER.
B.	THE POLICY AND PROCEDURE MANUAL SHALL ADDRESS AT LEAST THE FOLLOWING:
	1.	RESPONSIBILITY OF COMPOUNDING PERSONNEL;
	2.	VERIFICATION OF COMPOUNDING ACCURACY;
	3.	PERSONNEL TRAINING AND EVALUATION IN COMPOUNDING SKILLS;
	4.	ENVIRONMENTAL QUALITY AND CONTROL;
	5.	PROCESSING;
	6.	LABELING AND RECORDKEEPING;
	7.	FINISHED PREPARATION RELEASE CHECK AND TESTS;
	8.	STORAGE AND BEYOND-USE DATING;
	9.	ADVERSE EVENT REPORTING AND RECALLS; AND
	10.	QUALITY ASSURANCE PROGRAM.
21.10.30  	PERSONNEL EDUCATION, TRAINING AND EVALUATION.
A.	 ALL PHARMACY PERSONNEL PREPARING NON-STERILE COMPOUNDED PRODUCTS MUST RECEIVE SUITABLE DIDACTIC AND EXPERIENTIAL TRAINING.
B.	DOCUMENTATION OF TRAINING OF PERSONNEL SHALL BE RETAINED AT THE PHARMACY AND BE AVAILABLE FOR INSPECTION.
C.	PHARMACISTS INVOLVED IN COMPOUNDING NON-STERILE PRODUCTS SHALL OBTAIN CONTINUING EDUCATION APPROPRIATE FOR THE TYPE OF COMPOUNDING DONE BY THE PHARMACIST.  DOCUMENTATION OF THE COMPLETION OF THIS CONTINUING EDUCATION SHALL BE MAINTAINED ON-SITE AT THE PHARMACY AND BE AVAILABLE FOR INSPECTION.
21.10.40  	ENVIRONMENTAL QUALITY AND CONTROLS.

A.	THE AREA USED FOR COMPOUNDING SHALL HAVE ADEQUATE SPACE FOR THE ORDERLY PLACEMENT OF EQUIPMENT AND MATERIALS TO PREVENT MIXUPS BETWEEN INGREDIENTS, CONTAINERS, LABELS, IN-PROCESS MATERIALS, AND FINISHED PREPARATIONS.

B.	THE COMPOUNDING AREA SHALL BE DESIGNED, ARRANGED, USED, AND MAINTAINED TO PREVENT ADVENTITIOUS CROSS-CONTAMINATION.

C.	NON-STERILE COMPOUNDING AREAS SHALL BE SEPARATE AND DISTINCT FROM ANY STERILE COMPOUNDING AREA.

D.	THE ENTIRE COMPOUNDING AREA IS TO BE WELL-LIGHTED.  HEATING, VENTILATION, AND AIR CONDITIONING SYSTEMS ARE TO BE CONTROLLED TO AVOID DECOMPOSITION OF CHEMICALS.

E.	STORAGE AREAS SHALL PROVIDE AN ENVIRONMENT SUITABLY CONTROLLED TO ENSURE QUALITY AND STABILITY OF BULK CHEMICALS AND FINISHED PREPARATIONS.

F.	PURIFIED WATER SHALL BE USED FOR COMPOUNDING NONSTERILE DRUG PREPARATIONS WHEN THE FORMULATIONS CALL FOR THE INCLUSION OF WATER.

G.	PURIFIED WATER SHALL BE USED TO RINSE EQUIPMENT AND UTENSILS.

H.	COMPOUNDING AREAS SHALL BE MAINTAINED IN A CLEAN AND SANITARY CONDITION.  ADEQUATE WASHING FACILITIES ARE TO BE PROVIDED, INCLUDING HOT AND COLD RUNNING WATER, SOAP OR DETERGENT, AND AIR DRIERS OR SINGLE-SERVICE TOWELS.

I.	SEWAGE, TRASH, AND OTHER REFUSE IN THE COMPOUNDING AREA IS TO BE DISPOSED OF IN A SAFE, SANITARY, AND TIMELY MANNER.

J.	SPECIAL PRECAUTIONS SHALL BE TAKEN TO CLEAN EQUIPMENT AND COMPOUNDING AREAS METICULOUSLY AFTER COMPOUNDING PREPARATIONS THAT CONTAIN ALLERGENIC INGREDIENTS.

21.10.50  	EQUIPMENT.

A.	EQUIPMENT SHALL BE OF APPROPRIATE DESIGN AND CAPACITY, AND BE OPERATED WITHIN DESIGNED OPERATIONAL LIMITS.
	
B.	EQUIPMENT SHALL BE OF SUITABLE COMPOSITION SO THAT SURFACES THAT CONTACT COMPONENTS, IN-PROCESS MATERIAL, OR DRUG PRODUCTS SHALL NOT BE REACTIVE, ADDITIVE, OR ABSORPTIVE SO AS TO ALTER THE SAFETY, IDENTITY, STRENGTH, QUALITY, OR PURITY OF THE DRUG PRODUCT BEYOND THE DESIRED RESULT.

C.	EQUIPMENT USED IN COMPOUNDING SHALL BE THOROUGHLY CLEANED PROMPTLY AFTER USE TO AVOID CROSS-CONTAMINATION OF INGREDIENTS AND PREPARATIONS.

D.	EQUIPMENT SHALL BE CLEANED AND SANITIZED IMMEDIATELY PRIOR TO EACH USE.

E.	WRITTEN PROCEDURES OUTLINING REQUIRED EQUIPMENT, CALIBRATION, ANNUAL MAINTENANCE, MONITORING FOR PROPER FUNCTION, CONTROLLED PROCEDURES FOR USE OF THE EQUIPMENT AND SPECIFIED TIME FRAMES FOR THESE ACTIVITIES SHALL BE ESTABLISHED AND FOLLOWED.  RESULTS OF EQUIPMENT CALIBRATION, ANNUAL MAINTENANCE REPORTS, AND ROUTINE MAINTENANCE SHALL BE KEPT ON FILE AT THE OUTLET FOR THE LIFETIME OF THE EQUIPMENT.  THESE RESULTS SHALL BE AVAILABLE FOR INSPECTION.

21.10.60	PROCESSING.

A.	A WRITTEN DESCRIPTION OF SPECIFIC TRAINING AND A PERFORMANCE EVALUATION PROGRAM FOR PERSONNEL INVOLVED IN THE USE OF TECHNIQUES FOR THE PREPARATION OF COMPOUNDED PRODUCTS SHALL BE DEVELOPED FOR EACH OUTLET.

B.	COMPOUNDING PERSONNEL SHALL UTILIZE TECHNIQUES DESIGNED TO PRECLUDE CONTAMINATION OF DRUGS, PACKAGING, AND EQUIPMENT DURING PROCESSING.

21.10.70  	COMPONENTS.

A.	COMPOUNDING PERSONNEL SHALL ASCERTAIN THAT INGREDIENTS FOR COMPOUNDED PRODUCTS ARE OF THE CORRECT IDENTITY AND APPROPRIATE QUALITY USING THE FOLLOWING INFORMATION:  VENDORS’ LABELS, LABELING, CERTIFICATES OF ANALYSIS, DIRECT CHEMICAL ANALYSIS, AND KNOWLEDGE OF COMPOUNDING FACILITY STORAGE CONDITIONS.  NO EXPIRED COMPONENTS MAY BE USED IN COMPOUNDING.  NO COMPONENT MAY BE USED WHICH WILL EXPIRE PRIOR TO THE BEYOND-USE DATE OF THE PREPARATION.

B.	ACTIVE INGREDIENTS USED IN A COMPOUNDED PREPARATION SHALL ONLY BE PROCURED FROM AN ENTITY REGISTERED BY THE COLORADO STATE BOARD OF PHARMACY AND SHALL BE A USP/NF GRADE SUBSTANCE THAT IS FDA-APPROVED.

C.	INACTIVE INGREDIENTS USED IN A COMPOUNDED PREPARATION SHALL PREFERABLY BE A USP/NF GRADE SUBSTANCE THAT IS FDA-APPROVED. 

D.	IF USP/NF GRADE SUBSTANCES ARE NOT AVAILABLE FOR INACTIVE INGREDIENTS, OR WHEN FOOD, COSMETICS, OR OTHER SUBSTANCES ARE, OR MUST BE USED, THE SUBSTANCE SHALL BE OF A CHEMICAL GRADE IN ONE OF THE FOLLOWING CATEGORIES:

1.	CHEMICALLY PURE (CP);
2.	ANALYTICAL REAGENT (AR); OR
3.	AMERICAN CHEMICAL SOCIETY (ACS); OR
4.	FOOD CHEMICAL CODEX.

E.	IF AN INACTIVE INGREDIENT IS NOT FDA-APPROVED, THE PHARMACIST SHALL ESTABLISH PURITY AND STABILITY BY OBTAINING A CERTIFICATE OF ANALYSIS FROM THE SUPPLIER.

F.	A MANUFACTURED DRUG PRODUCT MAY BE A SOURCE OF ACTIVE INGREDIENT.  ONLY MANUFACTURED DRUGS FROM CONTAINERS LABELED WITH A BATCH CONTROL NUMBER AND A FUTURE EXPIRATION DATE ARE ACCEPTABLE AS A POTENTIAL SOURCE OF ACTIVE INGREDIENTS.  WHEN COMPOUNDING WITH MANUFACTURED DRUG PRODUCTS, THE COMPOUNDER MUST CONSIDER ALL INGREDIENTS PRESENT IN THE DRUG PRODUCT RELATIVE TO THE INTENDED USE OF A COMPOUNDED PREPARATION.

G.	DRUG PREPARATIONS THAT APPEAR ON THE FDA LIST OF DRUG PRODUCTS WITHDRAWN OR REMOVED FROM THE MARKET FOR SAFETY REASONS MAY NOT BE COMPOUNDED.

21.10.80  	FINISHED PREPARATION RELEASE CHECKS AND TESTS.

A.	PHYSICAL INSPECTION

1.	FINISHED COMPOUNDED PREPARATIONS SHALL BE INDIVIDUALLY INSPECTED AFTER COMPOUNDING PURSUANT TO WRITTEN PROCEDURES.  IMMEDIATELY AFTER COMPOUNDING, AND PRIOR TO DISPENSING OR DISTRIBUTION, EACH PRODUCT SHALL BE INSPECTED FOR EVIDENCE OF PARTICULATES OR OTHER FOREIGN MATTER, CONTAINER-CLOSURE INTEGRITY,  AND ANY OTHER APPARENT VISUAL DEFECT.  DEFECTIVE PRODUCT SHALL BE SEGREGATED FROM OTHER PRODUCT AND SHALL NOT BE DISPENSED OR DISTRIBUTED.

B.	COMPOUNDING ACCURACY CHECKS

1.	WRITTEN PROCEDURES FOR DOUBLE-CHECKING COMPOUNDING ACCURACY SHALL BE FOLLOWED FOR EVERY COMPOUNDED PRODUCT DURING PREPARATION AND IMMEDIATELY PRIOR TO RELEASE.  OUTLETS WHICH COMPOUND SHALL HAVE AT LEAST THE FOLLOWING WRITTEN PROCEDURES FOR VERIFYING THE CORRECT IDENTITY AND QUALITY OF COMPOUNDED PRODUCTS PRIOR TO DISPENSING OR DISTRIBUTION:

a.	VERIFICATION OF LABEL FOR ACCURACY; AND

b.	CORRECT IDENTITIES, PURITIES, AND AMOUNTS OF INGREDIENTS HAVE BEEN USED BY COMPARING THE ORIGINAL WRITTEN ORDER TO THE WRITTEN COMPOUNDING RECORD FOR THE COMPOUNDED PRODUCT.

21.10.90  	STORAGE AND BEYOND-USE DATING.

A.	COMPLETED COMPOUNDED PREPARATIONS THAT ARE NOT IMMEDIATELY DISPENSED OR DISTRIBUTED SHALL BE STORED ACCORDING TO THE GUIDELINES IN THE FORMULATION RECORD. 

B.	IN THE ABSENCE OF STABILITY INFORMATION THAT IS APPLICABLE TO A SPECIFIC DRUG AND PREPARATION, THE FOLLOWING MAXIMUM BEYOND-USE DATES ARE TO BE USED FOR NONSTERILE COMPOUNDED PREPARATIONS THAT ARE PACKAGED IN TIGHT, LIGHT-RESISTANT CONTAINERS AND STORED AT CONTROLLED ROOM TEMPERATURE UNLESS OTHERWISE INDICATED.

1.	FOR NONAQUEOUS LIQUIDS AND SOLID FORMULATIONS

a.	WHERE THE MANUFACTURED DRUG PRODUCT IS THE SOURCE OF THE ACTIVE INGREDIENT, THE BEYOND-USE DATE SHALL NOT EXCEED 25% OF THE TIME REMAINING UNTIL THE PRODUCT’S EXPIRATION DATE OR 6 MONTHS, WHICHEVER IS EARLIER;

b.	WHERE A USP-NF SUBSTANCE IS THE SOURCE OF ACTIVE INGREDIENT, THE BEYOND-USE DATE SHALL NOT BE GREATER THAN 6 MONTHS;

2.	FOR WATER-CONTAINING FORMULATIONS PREPARED FROM INGREDIENTS IN SOLID FORM, THE BEYOND-USE DATE SHALL NOT BE GREATER THAN 14 DAYS WHEN STORED AT COLD TEMPERATURES;

3.	FOR ALL OTHER FORMULATIONS, THE BEYOND-USE DATE SHALL NOT BE GREATER THAN THE INTENDED DURATION OF THERAPY OR 30 DAYS, WHICHEVER IS EARLIER;

4.	THE BEYOND-USE DATE LIMITS MAY BE EXCEEDED WHEN THERE IS SUPPORTING VALID SCIENTIFIC STABILITY INFORMATION THAT IS DIRECTLY APPLICABLE TO THE SPECIFIC PREPARATION.  THIS INFORMATION SHALL BE RETAINED ON-SITE AT THE OUTLET AND BE AVAILABLE FOR INSPECTION.
21.11.00	FORMULATION RECORD:	FOR EACH COMPOUNDED PREPARATION, A UNIFORM, READILY RETRIEVABLE FORMULATION RECORD SHALL BE MAINTAINED AND AVAILABLE FOR INSPECTION FOR TWO YEARS FROM THE DATE LAST UTILIZED, DOCUMENTING:
A.	THE NAME, STRENGTH, DOSAGE FORM, AND ROUTE OF ADMINISTRATION OF THE COMPOUNDED PREPARATION;

B.	ALL INGREDIENTS AND THEIR QUANTITIES;

C.	THE EQUIPMENT USED TO PREPARE THE PREPARATION, WHEN APPROPRIATE, AND MIXING INSTRUCTIONS;

D.	THE BEYOND-USE DATE;

E.	THE CONTAINERS USED IN DISPENSING;

F.	STORAGE REQUIREMENTS; AND

G.	PROCEDURES FOR QUALITY CONTROL
21.11.10	COMPOUNDING RECORD. FOR COMPOUNDED PRODUCT PREPARED, A RECORD SHALL BE MAINTAINED AND AVAILABLE FOR INSPECTION FOR TWO YEARS ON THE ORIGINAL ORDER, OR ON A SEPARATE, UNIFORM, AND READILY RETRIEVABLE RECORD DOCUMENTING THE FOLLOWING:
A.	NAME AND STRENGTH OF THE COMPOUNDED PREPARATION;

B,	FORMULATION RECORD REFERENCE FOR THE PREPARATION;

C.	SOURCES AND LOT NUMBERS OF EACH INGREDIENT;

D.	MANUFACTURER’S EXPIRATION DATE OF EACH INGREDIENT, WHEN APPLICABLE;

E.	TOTAL NUMBER OF DOSAGE UNITS COMPOUNDED;

F.	NAME OF THE PERSON WHO PREPARED THE PREPARATION;

G.	NAME OF THE PHARMACIST WHO APPROVED THE PREPARATION;

H.	BATCH (LOT) NUMBER ASSIGNED, IF MULTIPLE UNITS COMPOUNDED;

I.	DATE PREPARED;

J.	BEYOND USE DATE;

K.	PRESCRIPTION NUMBER(S), IF APPROPRIATE;

L.	RESULTS OF QUALITY CONTROL PROCEDURES; AND

M.	SAMPLE LABEL.
21.11.20	LABELING OF NON-STERILE COMPOUNDED PREPARATIONS
A.	LABELING OF NON-STERILE COMPOUNDED PREPARATIONS DISPENSED PURSUANT TO AN ORDER SHALL INCLUDE AT LEAST THE FOLLOWING:

1.	ALL REQUIREMENTS OF CRS 12-22-123;
2.	BATCH (LOT) NUMBER, IF APPROPRIATE;
3.	BEYOND-USE DATE;
4.	STORAGE DIRECTIONS; AND
5.	“THIS PRODUCT WAS COMPOUNDED BY THE PHARMACY”

B.	LABELING OF NON-STERILE COMPOUNDED PRODUCTS DISTRIBUTED TO PRACTITIONERS OR MADE IN ANTICIPATION OF ORDERS SHALL INCLUDE AT LEAST THE FOLLOWING:

1.	NAME AND ADDRESS OF THE OUTLET;
2.	NAME AND STRENGTH OF THE DRUG(S);
3.	TOTAL QUANTITY IN PACKAGE;
4.	QUANTITY OF ACTIVE INGREDIENT IN EACH DOSAGE UNIT;
5.	BEYOND-USE DATE;
6.	BATCH (LOT) NUMBER;
7.	SPECIFIC ROUTE OF ADMINISTRATION;
8.	STORAGE DIRECTIONS;
9.	“RX ONLY”; AND
10.	“THIS PRODUCT WAS COMPOUNDED BY THE PHARMACY.”
	
C.	LABELING OF NON-STERILE COMPOUNDED PRODUCTS DISTRIBUTED WITHIN HOSPITALS AS FLOOR STOCK SHALL INCLUDE AT LEAST THE FOLLOWING:

1.	NAME AND ADDRESS OF THE OUTLET;
2.	NAME AND STRENGTH OF THE DRUG(S);
3.	TOTAL QUANTITY IN PACKAGE;
4.	QUANTITY OF ACTIVE INGREDIENT IN EACH DOSAGE UNIT;
5.	BEYOND-USE DATE;
6.	BATCH (LOT) NUMBER;
7.	SPECIFIC ROUTE OF ADMINISTRATION; AND
8.	STORAGE DIRECTIONS.

21.11.30	PATIENT MONITORING, ADVERSE EVENTS REPORTING, AND PRODUCT RECALL
A.	OUTLETS WHICH COMPOUND SHALL PROVIDE PATIENTS AND OTHER RECIPIENTS OF COMPOUNDED PREPARATIONS WITH A WAY TO ADDRESS THEIR QUESTIONS AND REPORT ANY CONCERNS THAT THEY MAY HAVE WITH THESE PREPARATIONS. 
B.	THE OUTLET SHALL HAVE WRITTEN POLICIES DESCRIBING SPECIFIC INSTRUCTIONS FOR RECEIVING, ACKNOWLEDGING; AND FOR RECORDING, OR FILING, AND EVALUATING REPORTS OF ADVERSE EVENTS AND OF THE QUALITY OF PREPARATION CLAIMED TO BE ASSOCIATED WITH COMPOUNDED PREPARATIONS.
C.	COPIES OF ADVERSE EVENT REPORTS SHALL BE SUBMITTED IN WRITING TO THE BOARD AND TO THE FOOD AND DRUG ADMINISTRATION (FDA) WITHIN THREE BUSINESS DAYS.
D.	IF A COMPOUNDED PREPARATION IS BELIEVED TO BE DEFECTIVE IN ANY WAY, THE OUTLET SHALL IMMEDIATELY RECALL ANY PRODUCT DISPENSED OR DISTRIBUTED.  ANY PRODUCT REMAINING IN THE OUTLET SHALL BE IMMEDIATELY QUARANTINED AND SHALL NOT BE DISPENSED OR DISTRIBUTED.  THE OUTLET SHALL IMMEDIATELY NOTIFY THE BOARD AND FDA IN WRITING OF PRODUCT RECALLS.  SUCH RECALL NOTIFICATION SHALL INCLUDE AT LEAST THE FOLLOWING:

1.	PRODUCT NAME, STRENGTH, DOSAGE FORM;
2.	REASON FOR RECALL;
3.	AMOUNT OF PRODUCT MADE;
4.	DATE MADE; AND
5.	AMOUNT OF PRODUCT DISPENSED OR DISTRIBUTED.

E.	THE OUTLET SHALL CONDUCT APPROPRIATE TESTS ON THE RECALLED PRODUCT TO IDENTIFY REASON PRODUCT WAS DEFECTIVE.  RESULTS OF THESE TESTS SHALL BE SUBMITTED TO THE BOARD UPON RECEIPT.

F.	ADVERSE EVENT REPORTS AND PRODUCT RECALLS SHALL BE RETAINED AND AVAILABLE FOR INSPECTION AT THE OUTLET FOR AT LEAST TWO YEARS.
21.11.40	QUALITY ASSURANCE PROGRAM.
A.	OUTLETS THAT MAKE COMPOUNDED PREPARATIONS SHALL HAVE A FORMAL WRITTEN QUALITY ASSURANCE (QA) PROGRAM WHICH SHALL PROVIDE A MECHANISM FOR MONITORING, EVALUATING, CORRECTING, AND IMPROVING THE ACTIVITIES AND PROCESSES REGARDING THE COMPOUNDING OF MEDICATIONS.  
B.	AT A MINIMUM, THE QA PROGRAM SHALL INCLUDE THE FOLLOWING:
1.	CONSIDERATION OF ALL ASPECTS OF THE PREPARATION, DISPENSING, AND DISTRIBUTION OF PRODUCTS, INCLUDING ENVIRONMENTAL TESTING, VALIDATION RESULTS, ETC.
2.	DESCRIBE SPECIFIC MONITORING AND EVALUATION ACTIVITIES.
3.	SPECIFICATION OF HOW RESULTS ARE TO BE REPORTED AND EVALUATED.
4.	IDENTIFICATION OF APPROPRIATE FOLLOW-UP MECHANISMS WHEN ACTION LIMITS OR THRESHOLDS ARE EXCEEDED; AND
5.	DELINEATION OF THE INDIVIDUALS RESPONSIBLE FOR EACH ASPECT OF THE QA PROGRAM.

21.20.00	COMPOUNDING OF STERILE PRODUCTS (CSPS)

21.20.10	DEFINITIONS.  WHEN USED IN THIS REGULATION 21.20.00, THE FOLLOWING WORDS AND TERMS SHALL HAVE THE FOLLOWING MEANINGS, UNLESS THE CONTEXT CLEARLY INDICATES OTHERWISE.
A.	ANTEROOM:	AN ISO CLASS 8 (CLASS 100,000) OR BETTER AREA WHERE PERSONNEL PERFORM HAND HYGIENE AND GARBING PROCEDURES, STAGING OF COMPONENTS, ORDER ENTRY, LABELING, AND OTHER ACTIVITIES WHICH GENERATE PARTICULATES.  IT IS A TRANSITION AREA THAT PROVIDES ASSURANCE THAT AIR FLOWS FROM CLEAN TO DIRTY AREAS.
B.	ASEPTIC PROCESSING:  THE TECHNIQUE INVOLVING PROCEDURES DESIGNED TO PRECLUDE CONTAMINATION OF DRUGS, PACKAGING, EQUIPMENT, OR SUPPLIES BY MICROORGANISMS DURING PROCESSING.
C.	BATCH:  COMPOUNDING OF MULTIPLE STERILE PRODUCT UNITS IN A SINGLE DISCRETE PROCESS, BY THE SAME INDIVIDUALS, CARRIED OUT DURING ONE LIMITED TIME PERIOD.  
D.	BEYOND-USE DATE:  A DATE OR TIME AFTER WHICH A COMPOUNDED PREPARATION SHOULD NOT BE STORED, USED, OR TRANSPORTED AND IS DETERMINED FROM THE DATE AND TIME THE PREPARATION IS COMPOUNDED. 
E.	BIOLOGICAL SAFETY CABINET:  A VENTILATED CONTAINMENT UNIT FOR PERSONNEL, PRODUCT, AND ENVIRONMENTAL PROTECTIONS HAVING AN OPEN FRONT WITH INWARD AIRFLOW FOR PERSONNEL PROTECTION, DOWNWARD HEPA FILTERED LAMINAR AIRFLOW FOR PRODUCT PROTECTIONS, AND HEPA FILTERED EXHAUSTED AIR FOR ENVIRONMENTAL PROTECTIONS.
F.	BUFFER AREA:  AN ISO CLASS 7 (CLASS 10,000) AREA WHERE THE PRIMARY ENGINEERING CONTROL IS PHYSICALLY LOCATED.  ACTIVITIES CONDUCTED IN THIS AREA INCLUDE THE PREPARATION AND STAGING OF COMPONENTS AND SUPPLIES WHEN COMPOUNDING STERILE PRODUCTS.  THIS AREA MAY ALSO BE REFERRED TO AS A BUFFER OR CORE ROOM, BUFFER OR CLEANROOM AREAS, BUFFER ROOM AREA, BUFFER OR CLEAN AREA.
G.	CLASS 100 ENVIRONMENT (ISO CLASS 5):  AN ATMOSPHERIC ENVIRONMENT WHICH CONTAINS LESS THAN ONE HUNDRED (100) PARTICLES 0.5 MICRONS IN DIAMETER PER CUBIC FOOT OF AIR, ACCORDING TO FEDERAL STANDARDS.
H.	CLASS 10,000 ENVIRONMENT (ISO CLASS 7):  AN ATMOSPHERIC ENVIRONMENT WHICH CONTAINS LESS THAN TEN THOUSAND (10,000) PARTICLES 0.5 MICRONS IN DIAMETER PER CUBIC FOOT OF AIR, ACCORDING TO FEDERAL STANDARDS.
I.	CLASS 100,000 ENVIRONMENT (ISO CLASS 8):  AN ATMOSPHERIC ENVIRONMENT WHICH CONTAINS LESS THAN ONE HUNDRED THOUSAND (100,000) PARTICLES 0.5 MICRONS IN DIAMETER PER CUBIC FOOT OF AIR ACCORDING TO FEDERAL STANDARDS.
J.	CLEAN ROOM:  A ROOM IN WHICH THE CONCENTRATION OF AIRBORNE PARTICLES IS CONTROLLED TO MEET A SPECIFIED AIRBORNE PARTICULATE CLEANLINESS CLASS.  MICROORGANISMS IN THE ENVIRONMENT ARE MONITORED SO THAT A MICROBIAL LEVEL FOR AIR, SURFACE, AND PERSONNEL ARE NOT EXCEEDED FOR A SPECIFIED CLEANLINESS CLASS.
K.	COMPOUNDING ASEPTIC ISOLATOR (CAI):  A CLOSED SYSTEM MADE UP OF SOLID WALLS, AN AIR-HANDLING SYSTEM, AND TRANSFER AND INTERACTION DEVICES.  THE WALLS ARE CONSTRUCTED SO AS TO PROVIDE SURFACES THAT ARE CLEANABLE WITH COVERING BETWEEN WALL JUNCTURES.  THE AIR-HANDLING SYSTEM PROVIDES HEPA FILTRATION OF INLET AIR.  TRANSFER OF MATERIALS IS ACCOMPLISHED THROUGH AIR LOCKS, GLOVE RINGS, OR PORTS.  TRANSFERS ARE DESIGNED TO MINIMIZE THE ENTRY OF CONTAMINATION.  MANIPULATIONS CAN TAKE PLACE THROUGH EITHER GLOVE PORTS OR HALF SUITS.   A BARRIER ISOLATOR IS DESIGNED FOR COMPOUNDING STERILE PRODUCTS.  IT IS DESIGNED TO MAINTAIN AN ASEPTIC COMPOUNDING ENVIRONMENT WITHIN THE ISOLATOR THROUGHOUT THE COMPOUNDING AND MATERIAL TRANSFER PROCESS.  AIR EXCHANGE INTO THE ISOLATOR FROM THE SURROUNDING ENVIRONMENT SHOULD NOT OCCUR UNLESS IT HAS FIRST PASSED THROUGH A HEPA FILTER.
L.	COMPOUNDED STERILE PRODUCTS (CSPS):	A STERILE DRUG OR NUTRIENT COMPOUNDED IN A REGISTERED PRESCRIPTION DRUG OUTLET OR OTHER OUTLET.  SUCH PRODUCTS MAY INCLUDE, BUT ARE NOT LIMITED TO, IMPLANTS, INJECTABLES, PARENTERAL NUTRITION SOLUTIONS, IRRIGATION SOLUTIONS, INHALATION SOLUTIONS, INTRAVENOUS SOLUTIONS AND OPHTHALMIC PREPARATIONS.
M.	CRITICAL AREA:	AN ISO CLASS 5 ENVIRONMENT
N.	CRITICAL SITES:	INCLUDE STERILE INGREDIENTS OF CSPS AND LOCATIONS ON DEVICES AND COMPONENTS USED TO PREPARE, PACKAGE, AND TRANSFER CSPS THAT PROVIDE OPPORTUNITY FOR CONTAMINATION.
O.	CYTOTOXIC DRUGS:  A PHARMACEUTICAL PRODUCT THAT HAS THE CAPABILITY OF DIRECT TOXIC ACTION ON LIVING TISSUE THAT CAN RESULT IN SEVERE LEUCOPENIA AND THROMBOCYTOPENIA, DEPRESSION OF THE IMMUNE SYSTEM AND THE ALTERATION OF A HOST’S INFLAMMATORY RESPONSE SYSTEM.
P.	DISINFECTANT:	AN AGENT THAT FREES FROM INFECTIONS.  IT IS USUALLY A CHEMICAL AGENT BUT SOMETIMES A PHYSICAL ONE.  IT DESTROYS DISEASE-CAUSING PATHOGENS OR OTHER HARMFUL MICROORGANISMS BUT MAY OR MAY NOT KILL BACTERIAL SPORES.  IT REFERS TO SUBSTANCES APPLIED TO INANIMATE OBJECTS.
Q.	EMERGENCY DISPENSING:  IS A SITUATION WHERE A RISK LEVEL 3 PRODUCT IS NECESSARY FOR IMMEDIATE ADMINISTRATION OF THE PRODUCT AND NO ALTERNATIVE PRODUCT IS AVAILABLE AND THE PRACTITIONER IS INFORMED THAT THE PRODUCT IS BEING DISPENSED PRIOR TO APPROPRIATE TESTING.  DOCUMENTATION OF THE DISPENSING OF THE PRODUCT, THE PRACTITIONER’S APPROVAL FOR DISPENSING PRIOR TO THE RECEIPT OF TEST RESULTS AND THE NEED FOR THE EMERGENCY MUST APPEAR WITHIN THE PRESCRIPTION RECORD.  A SEPARATE AUTHORIZATION FROM THE PRACTITIONER IS REQUIRED FOR EACH EMERGENCY DISPENSING.
R.	HIGH-EFFICIENCY PARTICULATE AIR (HEPA) FILTER:  A FILTER COMPOSED OF PLEATS OF FILTER MEDIUM SEPARATED BY RIGID SHEETS OF CORRUGATED PAPER OR ALUMINUM FOIL THAT DIRECT THE FLOW OF AIR FORCED THROUGH THE FILTER IN A UNIFORM PARALLEL FLOW.  HEPA FILTERS REMOVE 99.97% OF ALL PARTICLES THREE-TENTHS (0.3) MICRONS OR LARGER.  WHEN HEPA FILTERS ARE USED AS A COMPONENT OF A HORIZONTAL-OR VERTICAL-LAMINAR-AIRFLOW WORKBENCH, AN ENVIRONMENT CAN BE CREATED CONSISTENT WITH STANDARDS FOR A CLASS 100 CLEAN ROOM.
S.	MEDIA-FILL TEST:	A TEST WHICH IS USED TO QUALIFY ASEPTIC TECHNIQUE OF COMPOUNDING PERSONNEL OR PROCESSES AND TO ENSURE THAT THE PROCESSES USED ARE ABLE TO PRODUCE STERILE PRODUCT WITHOUT MICROBIAL CONTAMINATION.  A MICROBIOLOGICAL GROWTH MEDIUM SUCH AS SOYBEAN-CASEIN DIGEST MEDIUM (SCDM) IS SUBSTITUTED FOR THE ACTUAL DRUG PRODUCT TO SIMULATE ADMIXTURE COMPOUNDING.
T.	MULTIPLE-DOSE CONTAINER:	A MULTIPLE-UNIT CONTAINER FOR ARTICLES OR PREPARATIONS INTENDED FOR PARENTERAL ADMINISTRATION ONLY AND USUALLY CONTAINS ANTIMICROBIAL PRESERVATIVES.
U.	PARENTERAL:  A STERILE PREPARATION OF DRUGS FOR INJECTION THROUGH ONE OR MORE LAYERS OF SKIN.
V.	PHARMACY BULK PACKAGE:	A CONTAINER OF A STERILE PREPARATION FOR PARENTERAL USE THAT CONTAINS MULTIPLE SINGLE DOSES.  THE CONTENTS OF THE PACKAGE ARE INTENDED FOR USE IN A PHARMACY ADMIXTURE PROGRAM AND ARE RESTRICTED TO THE PREPARATION OF ADMIXTURES FOR INFUSION, OR, THROUGH A STERILE TRANSFER DEVICE FOR THE FILLING OF EMPTY STERILE SYRINGES.  THE CLOSURE SHALL BY PENETRATED ONLY ONE TIME AFTER CONSTITUTION WITH A SUITABLE STERILE TRANSFER DEVICE OR DISPENSING SET, WHICH ALLOWS MEASURED DISPENSING OF THE CONTENTS.  SUCH CONTAINER SHALL BE LABELED WITH THE FOLLOWING:
1.	THE STATEMENT “PHARMACY BULK PACKAGE—NOT FOR DIRECT INFUSION;”
2.	INFORMATION ON THE PROPER TECHNIQUE TO ASSURE SAFE USE OF THE PRODUCT; AND
3.	A STATEMENT LIMITING THE TIME FRAME IN WHICH THE CONTAINER MAY BE USED ONCE IT HAS BEEN ENTERED, PROVIDED IT IS HELD UNDER THE LABELED STORAGE CONDITIONS.
W.	PRIMARY ENGINEERING CONTROL:	A DEVICE OR ROOM THAT PROVIDES AN ISO CLASS 5 ENVIRONMENT FOR THE EXPOSURE OF CRITICAL SITES WHEN COMPOUNDING CSPS.  SUCH DEVICES INCLUDE, BUT ARE NOT LIMITED TO, LAMINAR AIRFLOW WORKBENCHES (LAFWS), BIOLOGICAL SAFETY CABINETS (BSCS) AND COMPOUNDING ASEPTIC ISOLATORS (CAIS).
X.	PROCESS VALIDATION OR SIMULATION:  MICROBIOLOGICAL SIMULATION OF AN ASEPTIC PROCESS WITH GROWTH MEDIUM PROCESSED IN A MANNER SIMILAR TO THE PROCESSING OF THE PRODUCT AND WITH THE SAME CONTAINER OR CLOSURE SYSTEM.
Y.	QUALITY ASSURANCE:  FOR PURPOSES OF THESE REGULATIONS, QUALITY ASSURANCE IS THE SET OF ACTIVITIES USED TO ENSURE THAT THE PROCESSES USED IN THE PREPARATION OF STERILE DRUG PRODUCTS LEAD TO PRODUCTS THAT MEET PREDETERMINED STANDARDS OF QUALITY.
Z.	QUALITY CONTROL:  FOR THE PURPOSES OF THESE REGULATIONS, QUALITY CONTROL IS THE SET OF TESTING ACTIVITIES USED TO DETERMINE THAT THE INGREDIENTS, COMPONENTS AND FINAL STERILE PRODUCTS PREPARED MEET PREDETERMINED REQUIREMENTS WITH RESPECT TO IDENTITY, PURITY, NON-PYROGENICITY AND STERILITY.
AA.	REPACKAGING.  FOR THE PURPOSES OF THIS REGULATION, REPACKAGING MEANS THE SUBDIVISION OR TRANSFER OF A COMPOUNDED PRODUCT FROM ONE CONTAINER OR DEVICE TO A DIFFERENT CONTAINER OR DEVICE.
BB.	SINGLE-DOSE CONTAINER: A SINGLE-UNIT CONTAINER FOR ARTICLES OR PREPARATIONS INTENDED FOR PARENTERAL ADMINISTRATION ONLY.  IT IS INTENDED FOR SINGLE USE AND IS LABELED AS SUCH.  EXAMPLES INCLUDE PREFILLED SYRINGES, CARTRIDGES, FUSION-SEALED CONTAINERS, AND CLOSURE-SEALED CONTAINERS WHEN SO LABELED.
CC.	STERILE PHARMACEUTICAL: A DOSAGE FORM FREE FROM LIVING MICROORGANISMS.
DD.	STERILIZATION:  A VALIDATED PROCESS USED TO RENDER A PRODUCT FREE OF VIABLE ORGANISMS.
EE.	STERILIZING GRADE FILTER: A FILTER THAT WILL REMOVE ALL MICROORGANISMS FROM A FLUID STREAM, PRODUCING A STERILE EFFLUENT.  SUCH FILTERS TYPICALLY HAVE A NOMINAL POROSITY OF 0.2 MICROMETERS.
FF.	STERILIZATION BY FILTRATIONS: PASSAGE OF A FLUID OR SOLUTION THROUGH A STERILIZING GRADE FILTER TO PRODUCE A STERILE EFFLUENT.
GG.	TERMINAL STERILIZATION: THE APPLICATION OF A LETHAL PROCESS, E.G. STEAM UNDER PRESSURE OR AUTOCLAVING, TO SEALED CONTAINERS FOR THE PURPOSE OF ACHIEVING A PREDETERMINED STERILE ASSURANCE LEVEL.
HH.	TEMPERATURES:
1.	FROZEN MEANS TEMPERATURES BETWEEN TWENTY DEGREES BELOW ZERO AND TEN DEGREES BELOW ZERO CELSIUS (-20 AND -10 DEGREES C.) (FOUR BELOW ZERO AND FOURTEEN DEGREES FAHRENHEIT (-4 AND 14 DEGREES F).
2.	REFRIGERATED MEANS TEMPERATURES BETWEEN TWO AND EIGHT DEGREES CELSIUS (2 AND 8 DEGREES C.) (THIRTY-SIX AND FORTY-SIX DEGREES FAHRENHEIT (36 AND 46 DEGREES F.)).
3.	ROOM TEMPERATURES MEAN ROOM TEMPERATURES BETWEEN FIFTEEN AND THIRTY DEGREES CELSIUS (15 AND 30 DEGREES C.) (FIFTY-NINE AND EIGHTY-SIX DEGREES FAHRENHEIT (59 AND 86 DEGREES F.)).
II.	UNIDIRECTIONAL FLOW:	AN AIRFLOW MOVING IN A SINGLE DIRECTION, IN A ROBUST AND UNIFORM MANNER, AND AT SUFFICIENT SPEED TO REPRODUCIBLY SWEEP PARTICLES AWAY FROM THE CRITICAL PROCESSING OR TESTING AREA.
JJ.	VALIDATION:  DOCUMENTED EVIDENCE PROVIDING A HIGH DEGREE OF ASSURANCE THAT SPECIFIC PROCESSES WILL CONSISTENTLY PRODUCE A PRODUCT MEETING PREDETERMINED SPECIFICATIONS AND QUALITY ATTRIBUTES.
21.20.20	DEFINITIONS OF STERILE COMPOUNDED PRODUCTS BY RISK LEVEL:
A.	RISK LEVEL 1 (LOW RISK CSPS):  APPLIES TO COMPOUNDING STERILE PRODUCTS THAT EXHIBIT CHARACTERISTICS 1, 2, AND 3, STATED BELOW.  ALL RISK LEVEL 1 PRODUCTS SHALL BE COMPOUNDED WITH ASEPTIC MANIPULATIONS ENTIRELY WITHIN ISO CLASS 5 OR BETTER AIR QUALITY.  THE PRODUCTS SHALL BE PREPARED WITH STERILE EQUIPMENT, STERILE INGREDIENTS AND SOLUTIONS AND STERILE CONTACT SURFACES FOR THE FINAL PRODUCT.  RISK LEVEL 1 INCLUDES THE FOLLOWING:
1.	UNPRESERVED STERILE PRODUCTS PREPARED FOR ADMINISTRATION TO ONE (1) PATIENT OR BATCH-PREPARED PRODUCTS CONTAINING SUITABLE PRESERVATIVES PREPARED FOR ADMINISTRATION TO MORE THAN ONE (1) PATIENT.
2.	THE COMPOUNDING INVOLVES ONLY TRANSFER, MEASURING, AND MIXING MANIPULATIONS USING NO MORE THAN THREE COMMERCIALLY MANUFACTURED STERILE PRODUCTS AND ENTRIES INTO ONE CONTAINER PACKAGE OF STERILE PRODUCT TO MAKE THE CSP.
3.  	MANIPULATIONS ARE LIMITED TO ASEPTICALLY OPENING AMPULES, PENETRATING STERILE STOPPERS ON VIALS WITH STERILE NEEDLES AND SYRINGES, AND TRANSFERRING STERILE LIQUIDS IN STERILE SYRINGES TO STERILE ADMINISTRATION DEVICES, PACKAGE CONTAINERS OF OTHER STERILE PRODUCTS, AND CONTAINERS FOR STORAGE AND DISPENSING. 
B.	RISK LEVEL 2 (MEDIUM RISK CSPS):  STERILE PRODUCTS EXHIBIT CHARACTERISTIC 1., 2., OR 3, STATED BELOW.  WHEN CSPS ARE COMPOUNDED ASEPTICALLY UNDER RISK LEVEL 1 CONDITIONS, AND ONE OR MORE OF THE FOLLOWING CONDITIONS EXISTS, SUCH AS CSPS ARE AT A MEDIUM RISK LEVEL OF CONTAMINATION:
1.	MULTIPLE INDIVIDUAL OR SMALL DOSES OF STERILE PRODUCTS ARE COMBINED OR POOLED TO PREPARE A CSP THAT WILL BE ADMINISTERED EITHER TO MULTIPLE PATIENTS OR TO ONE PATIENT ON MULTIPLE OCCASIONS.
2.	THE COMPOUNDING PROCESS INCLUDES COMPLEX ASEPTIC MANIPULATIONS OTHER THAN THE SINGLE VOLUME TRANSFER.
3.	THE COMPOUNDING PROCESS REQUIRES UNUSUALLY LONG DURATION, SUCH AS THAT REQUIRED TO COMPLETE DISSOLUTION OR HOMOGENEOUS MIXING.
C.	RISK LEVEL 3 (HIGH RISK LEVEL CSPS):  CSPS COMPOUNDED UNDER ANY OF THE FOLLOWING CONDITIONS ARE EITHER CONTAMINATED OR AT HIGH RISK TO BECOME CONTAMINATED WITH INFECTIOUS MICROORGANISMS:
1.	PRODUCTS COMPOUNDED FROM NON-STERILE INGREDIENTS OR COMPOUNDED WITH NON-STERILE COMPONENTS, CONTAINERS OR EQUIPMENT BEFORE TERMINAL STERILIZATION.
2.	STERILE CONTENTS OF COMMERCIALLY MANUFACTURED PRODUCTS, CSPS THAT LACK EFFECTIVE ANTIMICROBIAL PRESERVATIVES, AND STERILE SURFACES OF DEVICES AND CONTAINERS FOR THE PREPARATION, TRANSFER, STERILIZATION, AND PACKAGING OF CSPS ARE EXPOSED TO AIR QUALITY WORSE THAN ISO CLASS 5 FOR MORE THAN 1 HOUR.
3.	BEFORE STERILIZATION, NONSTERILE PROCEDURES SUCH AS WEIGHING AND MIXING ARE CONDUCTED IN AIR QUALITY WORSE THAN ISO CLASS 7, COMPOUNDING PERSONNEL ARE IMPROPERLY GARBED AND GLOVED; OR WATER–CONTAINING PREPARATIONS ARE STORED FOR MORE THAN 6 HOURS.
4.	IT IS ASSUMED, AND NOT VERIFIED BY EXAMINATION OF LABELING AND DOCUMENTATION FROM SUPPLIERS OR BY DIRECT DETERMINATION, THAT THE CHEMICAL PURITY AND CONTENT STRENGTH OF INGREDIENTS MEET THEIR ORIGINAL OR COMPENDIAL SPECIFICATIONS IN UNOPENED OR IN OPENED PACKAGES OF BULK INGREDIENTS.
21.20.30	POLICY AND PROCEDURE MANUAL.
A.	A MANUAL, OUTLINING POLICIES AND PROCEDURES ENCOMPASSING ALL ASPECTS OF COMPOUNDING RISK LEVEL 1, 2 AND 3 PRODUCTS, SHALL BE AVAILABLE FOR INSPECTION AT THE PHARMACY.  THE MANUAL SHALL BE REVIEWED ON AN ANNUAL BASIS.  SUCH REVIEW SHALL BE SIGNED AND DATED BY THE PHARMACIST MANAGER.  IN THE EVENT THE PHARMACIST MANAGER CHANGES, THE NEW MANAGER SHALL REVIEW, SIGN, AND DATE THE MANUAL WITHIN 30 DAYS OF BECOMING PHARMACIST MANAGER.
B.	THE POLICY AND PROCEDURE MANUAL SHALL ADDRESS AT LEAST THE FOLLOWING:
1.	RESPONSIBILITY OF COMPOUNDING PERSONNEL;
2.	VERIFICATION OF COMPOUNDING ACCURACY AND STERILIZATION;
3.	PERSONNEL TRAINING AND EVALUATION IN ASEPTIC MANIPULATION SKILLS;
4.	ENVIRONMENTAL QUALITY AND CONTROL;
5.	PROCESSING;
6.	LABELING AND RECORDKEEPING;
7.	FINISHED PREPARATION RELEASE CHECK AND TESTS;
8.	STORAGE AND BEYOND-USE DATING;
9.	MAINTAINING PRODUCT QUALITY AND THE CONTROL AFTER THE CSP LEAVES THE PHARMACY;
10.	PATIENT OR CAREGIVER TRAINING;
11.	ADVERSE EVENT REPORTING AND RECALLS; AND
12.	QUALITY ASSURANCE PROGRAM.
21.20.40	PERSONNEL EDUCATION, TRAINING AND EVALUATION.
A.	RISK LEVEL 1:  ALL PHARMACY PERSONNEL PREPARING STERILE PRODUCTS MUST RECEIVE SUITABLE DIDACTIC AND EXPERIENTIAL TRAINING.
B.	RISK LEVEL 2:  IN ADDITION TO RISK LEVEL 1 REQUIREMENTS, PERSONNEL TRAINING INCLUDES ASSESSMENT OF COMPETENCY IN ALL RISK LEVEL 2 PROCEDURES VIA PROCESS SIMULATION.
C.	RISK LEVEL 3:  IN ADDITION TO RISK LEVEL 1 AND 2 REQUIREMENTS, OPERATORS HAVE SPECIFIC EDUCATION, TRAINING AND EXPERIENCE TO PREPARE RISK LEVEL 3 PRODUCTS.  THE PHARMACIST KNOWS PRINCIPLES OF GOOD COMPOUNDING PRACTICE FOR RISK LEVEL PRODUCTS, INCLUDING:
1.	ASEPTIC PROCESSING;
2.	QUALITY ASSURANCE OF ENVIRONMENTAL, COMPONENT, AND END-PRODUCT TESTING;
3.	STERILIZATION; AND
4.	SELECTION AND USE OF CONTAINERS, EQUIPMENT, AND CLOSURES.

21.20.50	PERSONNEL TRAINING AND EVALUATION IN ASEPTIC MANIPULATION SKILLS.

A.	PERSONNEL WHO PREPARE CSPS SHALL BE PROVIDED APPROPRIATE TRAINING BEFORE THEY BEGIN PREPARING CSPS.

B.	COMPOUNDING PERSONNEL SHALL PERFORM DIDACTIC REVIEW AND PASS WRITTEN AND MEDIA-FILL TESTING OF ASEPTIC MANIPULATIVE SKILLS INITIALLY; AT LEAST ANNUALLY THEREAFTER FOR RISK LEVEL I AND II PRODUCTS; AND EVERY SIX MONTHS, THEREAFTER, FOR RISK LEVEL 3 COMPOUNDING.

C.	PERSONNEL WHO FAIL WRITTEN TESTS, OR WHOSE MEDIA-FILL TEST VIALS RESULT IN GROSS MICROBIAL COLONIZATION, MUST BE IMMEDIATELY REINSTRUCTED AND RE-EVALUATED BY EXPERT COMPOUNDING PERSONNEL TO ENSURE CORRECTION OF ALL ASEPTIC PRACTICE DEFICIENCIES.

D	RESULTS OF THESE TESTS SHALL BE RETAINED AND BE AVAILABLE FOR INSPECTION AT THE OUTLET FOR AT LEAST TWO YEARS.

21.20.60	ENVIRONMENTAL QUALITY AND CONTROLS.

A.	ALL CSPS SHALL BE COMPOUNDED IN AIR QUALITY OF A CLASS 100 (ISO CLASS 5) ENVIRONMENT OR BETTER.

B.	ALL PRIMARY ENGINEERING CONTROLS SHALL BE PLACED IN A BUFFER AREA THAT IS OF AIR QUALITY CLASS 10,000 (ISO CLASS 7) OR BETTER.

C.	THE SURFACES OF THE CEILING, WALLS, FLOOR, FIXTURES, SHELVING, COUNTERS, AND CABINETS IN THE BUFFER AREA OR CLEAN ROOM SHALL BE SMOOTH, IMPERVIOUS, FREE FROM CRACKS AND CREVICES AND NON-SHEDDING.  JUNCTURES OF CEILINGS TO WALLS SHALL BE COVED OR CAULKED.  THERE SHALL BE NO SINK OR FLOOR DRAINS IN THE BUFFER AREA OR CLEAN ROOM.

D.	AN ANTEROOM SHALL BE PHYSICALLY ISOLATED FROM THE BUFFER AREA OR CLEAN ROOM.  IN THIS AREA, SUPPLIES ARE UNCARTONED AND DISINFECTED.  HAND SANITIZING AND GOWNING OCCURS IN THIS AREA.  A DEMARCATION LINE OR BARRIER IDENTIFIES THE SEPARATION OF THE BUFFER AREA FROM THE ANTEROOM AREA.  THE AIR QUALITY OF THE ANTEROOM SHALL BE CLASS 100,000 (ISO CLASS 8) OR BETTER.

21.20.70	ENVIRONMENTAL MONITORING.

A.	CLASS 100 OR BETTER CLEAN ROOMS AND/OR PRIMARY ENGINEERING CONTROLS SHALL BE CERTIFIED BY QUALIFIED OPERATORS AT LEAST EVERY SIX MONTHS AND WHENEVER THE DEVICE OR ROOM IS RELOCATED OR MAJOR SERVICE TO THE FACILITY IS PERFORMED.  CERTIFICATION RECORDS SHALL BE MAINTAINED AND BE AVAILABLE FOR INSPECTION AT THE OUTLET FOR AT LEAST TWO YEARS FROM THE CERTIFICATION DATE.  

B.	CERTIFICATION THAT EACH ISO CLASSIFIED AREA IS WITHIN ESTABLISHED GUIDELINES SHALL BE PERFORMED NO LESS THAN EVERY SIX MONTHS AND WHENEVER THE PRIMARY ENGINEERING CONTROL IS RELOCATED OR THE PHYSICAL STRUCTURE OF THE BUFFER AREA OR ANTEROOM HAS BEEN ALTERED.  THE TESTING SHALL BE PERFORMED BY QUALIFIED OPERATORS USING STATE-OF-THE-ART ELECTRONIC EQUIPMENT WITH THE FOLLOWING RESULTS:

1.	NOT MORE THAN 3,520 PARTICLES 0.5 MICROMETER SIZE AND LARGER PER CUBIC METER OF AIR FOR ANY PRIMARY ENGINEERING CONTROL (ISO CLASS 5).

2.	NOT MORE THAN 352,000 PARTICLES OF 0.5 MICROMETER SIZE AND LARGER PER CUBIC METER OF AIR (ISO CLASS 7) FOR ANY BUFFER ROOM; AND

3.	NOT MORE THAN 3,520,000 PARTICLES OF 0.5 MICROMETER SIZE AND LARGER PER CUBIC METER OF AIR (ISO CLASS 8) FOR ANY ANTEROOM/AREA.
 
 C.	CERTIFICATION RECORDS SHALL BE MAINTAINED AND BE AVAILABLE FOR INSPECTION AT THE OUTLET FOR AT LEAST TWO YEARS FROM THE CERTIFICATION DATE.

D.	TESTS SHALL BE DONE FOR AIRBORNE MICROORGANISMS BY ELECTRIC AIR SAMPLERS.  THE INSTRUCTIONS IN THE MANUFACTURER’S USER MANUAL FOR VERIFICATION AND USE OF THE ELECTRIC AIR SAMPLE THAT ACTIVELY COLLECTS VOLUMES OF AIR FOR EVALUATION MUST BE FOLLOWED.  THE SAMPLING IS PERFORMED AT LOCATIONS JUDGED BY COMPOUNDING PERSONNEL TO BE THE MOST PRONE TO CONTAMINATION.  THESE TESTS SHALL BE DONE MONTHLY FOR OUTLETS MAKING RISK LEVEL I AND II CSPS AND SHALL BE DONE WEEKLY FOR OUTLETS MAKING RISK LEVEL III CSPS.  THE OUTLET SHALL HAVE WRITTEN POLICIES TO REEVALUATE CLEANING PROCEDURES, OPERATIONAL PROCEDURES, AND AIR FILTRATION EFFICIENCY IF THE NUMBER OF COLONY FORMING UNITS INCREASES OVER THE NORMAL BASELINE LEVEL.  RECORDS OF THESE TESTS SHALL BE MAINTAINED AND BE AVAILABLE FOR INSPECTION AT THE OUTLET FOR AT LEAST TWO YEARS FROM THE TESTING DATE.

E.	GLOVE FINGERTIP SAMPLING SHALL BE CONDUCTED WEEKLY FOR AT LEAST ONE INDIVIDUAL OR 10% OF THE COMPOUNDING PERSONNEL IF COMPOUNDING RISK LEVEL 1 AND 2 CSPS AND DAILY IF COMPOUNDING RISK LEVEL 3 CSPS.  WHEN A FINGER PLATE RESULT FOR PERSONNEL MONITORING AFTER PROPER INCUBATION EXCEEDS THE ACTION LIMIT, A REVIEW OF HAND HYGIENE AND GARBING PROCEDURES AS WELL AS GLOVE AND SURFACE DISINFECTION PROCEDURES AND WORK PRACTICES SHALL OCCUR.

F.	A PRESSURE GAUGE OR VELOCITY METER SHALL BE INSTALLED TO MONITOR THE PRESSURE DIFFERENTIAL OR AIRFLOW BETWEEN THE CLEANROOM AND ANTEROOM AND THE ANTEROOM AND THE GENERAL PHARMACY AREA.  THE RESULTS SHALL BE REVIEWED AND DOCUMENTED ON A DAILY BASIS IN A WRITTEN FORMAT.  THE PRESSURE BETWEEN THE ISO CLASS 7 AND GENERAL PHARMACY AREA SHALL NOT BE LESS THAN 5 PA (0.02-INCH WATER COLUMN, W.C.).  FACILITIES USED TO COMPOUND RISK LEVEL I CSPS UTILIZING DIRECTIONAL AIRFLOW SHALL MAINTAIN A MINIMUM VELOCITY OF 0.2M/S.

21.20.80		CLEANING AND DISINFECTING THE WORKSPACES.
A.	THE CLEANING AND SANITIZING OF THE WORKSPACES SHALL BE DONE PURSUANT TO WRITTEN PROCEDURES AND SHALL BE THE RESPONSIBILITY OF TRAINED OPERATORS, USING APPROPRIATE DISINFECTING AGENTS.
B.	THE DIRECT AND CONTIGUOUS COMPOUNDING AREA (DCCA), INCLUDING ISO CLASS 5 AREAS, SHALL BE CLEANED AND DISINFECTED PRIOR TO THE BEGINNING OF EACH SHIFT.  ALL ITEMS SHALL BE REMOVED FROM THE DCCA AND ALL SURFACES SHALL BE CLEANED OF LOOSE MATERIAL AND RESIDUE FROM SPILLS PRIOR TO CLEANING.
C.	WORK SURFACES IN THE ISO CLASS 7 BUFFER AREAS AND ISO CLASS 8 ANTEROOM/AREAS ARE CLEANED AND DISINFECTED AT LEAST DAILY.  
D.	DUST AND DEBRIS SHALL BE REMOVED AS NECESSARY FROM THE STORAGE AREAS FOR COMPOUNDING INGREDIENTS AND SUPPLIES.
E.	STORAGE SHELVING SHALL BE DISINFECTED AT LEAST MONTHLY.  ALL ITEMS SHALL BE REMOVED FROM THE SHELVING PRIOR TO CLEANING.
F.	THE WALLS AND CEILINGS IN THE BUFFER AND ANTEROOM AREAS SHALL BE CLEANED AND DISINFECTED AT LEAST MONTHLY.
G.	FLOORS IN THE BUFFER AND ANTEROOM AREAS SHALL BE MOPPED DAILY WHEN NO ASEPTIC OPERATIONS ARE IN PROGRESS.
H.	ALL CLEANING TOOLS, SUCH AS WIPERS, SPONGES, AND MOPS SHALL BE NONSHEDDING AND DEDICATED TO USE IN THE BUFFER OR CLEAN AREA.  FLOOR MOPS MAY BE USED IN BOTH THE BUFFER OR CLEAN AREA AND ANTEROOM AREA, BUT ONLY IN THAT ORDER.  MOST WIPERS SHALL BE DISCARDED AFTER ONE USE.  IF CLEANING TOOLS ARE REUSED, THEIR CLEANLINESS SHALL BE MAINTAINED BY THOROUGH RINSING AND DISINFECTION AFTER USE AND BY STORING IN A CLEAN ENVIRONMENT BETWEEN USES.  TRASH SHALL BE COLLECTED IN SUITABLE PLASTIC BAGS AND REMOVED WITH MINIMAL AGITATION.
21.20.90	PERSONNEL CLEANSING AND GARBING.
A.	PRIOR TO ENTERING THE CONTROLLED (BUFFER) AREA, OPERATORS SHALL REMOVE OUTER LAB JACKETS, MAKEUP, AND JEWELRY.
B.	AFTER DONNING DEDICATED SHOES OR SHOE COVERS, HEAD AND FACIAL HAIR COVERINGS, HANDS AND ARMS SHALL BE THOROUGHLY SCRUBBED UP TO THE ELBOW.  AFTER DRYING HANDS AND ARMS, OPERATORS SHALL PROPERLY DON NONSHEDDING DISPOSABLE GOWNS THAT FIT SNUGLY AROUND THE WRISTS.  
C.	ONCE INSIDE THE CLEAN AREA, HANDS SHALL BE CLEANSED WITH AN ANTISEPTIC HAND CLEANSER.  STERILE POWDER-FREE GLOVES SHALL THEN BE DONNED.
D.	DURING PROTRACTED COMPOUNDING ACTIVITIES, PERSONNEL SHALL INTERMITTENTLY RESANITIZE THEIR GLOVES.
E.	FOR RISK LEVEL 1 AND 2 COMPOUNDING:  IF PERSONNEL LEAVE THE BUFFER AREA, THEY SHALL DON NEW HAIR COVERS, MASKS, SHOE COVERS, AND GLOVES PRIOR TO REENTRY.  GOWNS MAY BE REUSED DURING THE SAME COMPOUNDING SESSION IF HUNG IN THE ANTEROOM.
F.	FOR RISK LEVEL 3:  IF PERSONNEL LEAVE THE BUFFER AREA, THEY MUST DON NEW HAIR COVERS, MASKS, SHOE COVERS, COATS AND GLOVES PRIOR TO REENTRY.

21.21.00	PROCESSING.

A.	A WRITTEN DESCRIPTION OF SPECIFIC TRAINING AND PERFORMANCE EVALUATION PROGRAM FOR PERSONNEL INVOLVED IN THE USE OF ASEPTIC TECHNIQUES FOR THE PREPARATION OF STERILE PRODUCTS SHALL BE DEVELOPED FOR EACH OUTLET.

B.	COMPOUNDING PERSONNEL SHALL UTILIZE TECHNIQUES DESIGNED TO PRECLUDE CONTAMINATION OF DRUGS, PACKAGING, EQUIPMENT, OR SUPPLIES BY MICROORGANISMS DURING PROCESSING.

21.21.10	COMPONENTS.

A.	COMPOUNDING PERSONNEL SHALL ASCERTAIN THAT INGREDIENTS FOR CSPS ARE OF THE CORRECT IDENTITY AND APPROPRIATE QUALITY USING THE FOLLOWING INFORMATION:  VENDORS’ LABELS, LABELING, CERTIFICATES OF ANALYSIS, DIRECT CHEMICAL ANALYSIS, AND KNOWLEDGE OF COMPOUNDING FACILITY STORAGE CONDITIONS.  NO EXPIRED COMPONENTS MAY BE USED IN COMPOUNDING.  NO COMPONENT MAY BE USED WHICH WILL EXPIRE PRIOR TO THE BEYOND-USE DATE OF THE FINISHED CSP.

B.	ACTIVE INGREDIENTS USED IN A COMPOUNDED PREPARATION SHALL ONLY BE PROCURED FROM AN ENTITY OR PERSON REGISTERED BY THE COLORADO STATE BOARD OF PHARMACY AND SHALL BE A USP/NF GRADE SUBSTANCE THAT IS FDA-APPROVED.

C.	INACTIVE INGREDIENTS USED IN A COMPOUNDED PREPARATION SHALL PREFERABLY BE A USP/NF GRADE SUBSTANCE THAT IS FDA-APPROVED. 

D.	IF USP/NF GRADE SUBSTANCES ARE NOT AVAILABLE FOR INACTIVE INGREDIENTS, OR WHEN FOOD, COSMETICS, OR OTHER SUBSTANCES ARE, OR MUST BE USED, THE SUBSTANCE SHALL BE OF A CHEMICAL GRADE IN ONE OF THE FOLLOWING CATEGORIES:

1.	CHEMICALLY PURE (CP);
2.	ANALYTICAL REAGENT (AR); 
3.	AMERICAN CHEMICAL SOCIETY (ACS); OR
4.	FOOD CHEMICAL CODEX.

E.	IF AN INACTIVE INGREDIENT IS NOT FDA-APPROVED, THE PHARMACIST SHALL ESTABLISH PURITY AND STABILITY BY OBTAINING A CERTIFICATE OF ANALYSIS FROM THE SUPPLIER.

F.	A MANUFACTURED DRUG PRODUCT MAY BE A SOURCE OF ACTIVE INGREDIENT.  ONLY MANUFACTURED DRUGS FROM CONTAINERS LABELED WITH A BATCH CONTROL NUMBER AND A FUTURE EXPIRATION DATE ARE ACCEPTABLE AS A POTENTIAL SOURCE OF ACTIVE INGREDIENTS.  WHEN COMPOUNDING WITH MANUFACTURED DRUG PRODUCTS, THE COMPOUNDER MUST CONSIDER ALL INGREDIENTS PRESENT IN THE DRUG PRODUCT RELATIVE TO THE INTENDED USE OF A COMPOUNDED PREPARATION.

G.	DRUG PREPARATIONS THAT APPEAR ON THE FDA LIST OF DRUG PRODUCTS WITHDRAWN OR REMOVED FROM THE MARKET FOR SAFETY REASONS MAY NOT BE COMPOUNDED.

	H.	STERILE INGREDIENTS AND COMPONENTS

1.	A WRITTEN PROCEDURE FOR PHYSICAL INSPECTION OF INGREDIENTS AND COMPONENTS PRIOR TO COMPOUNDING SHALL BE FOLLOWED.

	I.	NONSTERILE INGREDIENTS AND COMPONENTS

1.	IF ANY NONSTERILE COMPONENTS OR INGREDIENTS, INCLUDING CONTAINERS, DEVICES, AND INGREDIENTS, ARE UTILIZED TO MAKE THE CSP, THE PRODUCT SHALL BE COMPOUNDED AT RISK LEVEL 3.  

2.	IF NON-USP OR NON-NF ACTIVE INGREDIENTS, ADDED SUBSTANCES, OR EXCIPIENTS ARE UTILIZED, A CERTIFICATE OF ANALYSIS FROM THE SUPPLIER OF THE INGREDIENT SHALL BE MAINTAINED WITH THE COMPOUNDING RECORD.

3.	WHEN NON-STERILE INGREDIENTS AND COMPONENTS ARE RECEIVED AT THE OUTLET, THEIR CONTAINER SHALL BE MARKED, IN INDELIBLE PENCIL OR INK, WITH THE DATE OF RECEIPT.  IN THE ABSENCE OF A SUPPLIER’S EXPIRATION DATE ON THE PRODUCT, THE EXPIRATION DATE OF THE INGREDIENT SHALL BE ONE-YEAR FROM THE DATE OF RECEIPT, UNLESS EITHER APPROPRIATE INSPECTION OR TESTING INDICATES THAT THE INGREDIENT HAS RETAINED ITS PURITY AND QUALITY FOR USE IN CSPS.

4.	PRIOR TO COMPOUNDING WITH NONSTERILE INGREDIENTS AND COMPONENTS, THE INGREDIENTS SHALL BE VISUALLY INSPECTED FOR EVIDENCE OF DETERIORATION, OTHER TYPES OF UNACCEPTABLE QUALITY AND WRONG IDENTIFICATION.

21.21.20	EQUIPMENT.

A.	WRITTEN PROCEDURES OUTLINING REQUIRED EQUIPMENT, CALIBRATION, ANNUAL MAINTENANCE, MONITORING FOR PROPER FUNCTION, CONTROLLED PROCEDURES FOR USE OF THE EQUIPMENT AND SPECIFIED TIME FRAMES FOR THESE ACTIVITIES SHALL BE ESTABLISHED AND FOLLOWED.  RESULTS OF EQUIPMENT CALIBRATION, ANNUAL MAINTENANCE REPORTS, AND ROUTINE MAINTENANCE SHALL BE KEPT ON FILE AT THE OUTLET AND AVAILABLE FOR INSPECTION FOR THE LIFETIME OF THE EQUIPMENT.

B.	ACCURACY ASSESSMENTS OF AUTOMATED COMPOUNDING DEVICES (ACD) SHALL BE CONDUCTED DAILY.  AT LEAST WEEKLY, THE PHARMACIST MANAGER SHALL REVIEW THESE ASSESSMENTS TO AVOID POTENTIALLY CLINICALLY SIGNIFICANT CUMULATIVE ERRORS OVER TIME.  THESE ASSESSMENTS SHALL BE DOCUMENTED AND BE MAINTAINED AND AVAILABLE FOR INSPECTION AT THE OUTLET FOR AT LEAST TWO YEARS.

21.21.30	FINISHED PREPARATION RELEASE CHECKS AND TESTS.

A.	PHYSICAL INSPECTION

1.	FINISHED CSPS SHALL BE INDIVIDUALLY INSPECTED AFTER COMPOUNDING PURSUANT TO WRITTEN PROCEDURES.  IMMEDIATELY AFTER COMPOUNDING, AND PRIOR TO DISPENSING OR DISTRIBUTION, EACH PRODUCT SHALL BE INSPECTED FOR EVIDENCE OF PARTICULATES OR OTHER FOREIGN MATTER, CONTAINER-CLOSURE INTEGRITY, PRECIPITATION, CLOUDINESS, AND ANY OTHER APPARENT VISUAL DEFECT.  DEFECTIVE PRODUCT SHALL BE SEGREGATED FROM OTHER PRODUCT AND SHALL NOT BE DISPENSED OR DISTRIBUTED.

B.	COMPOUNDING ACCURACY CHECKS

1.	WRITTEN PROCEDURES FOR DOUBLE-CHECKING COMPOUNDING ACCURACY SHALL BE FOLLOWED FOR EVERY CSP DURING PREPARATION AND IMMEDIATELY PRIOR TO RELEASE.  OUTLETS WHICH COMPOUND CSPS SHALL HAVE AT LEAST THE FOLLOWING WRITTEN PROCEDURES FOR VERIFYING THE CORRECT IDENTITY AND QUALITY OF CSPS PRIOR TO DISPENSING OR DISTRIBUTION:

a.	VERIFICATION OF LABEL FOR ACCURACY;
b.	CORRECT IDENTITIES, PURITIES, AND AMOUNTS OF INGREDIENTS HAVE BEEN USED BY COMPARING THE ORIGINAL WRITTEN ORDER TO THE WRITTEN COMPOUNDING RECORD FOR THE CSP; AND
c.	CORRECT FILL VOLUMES IN CSPS AND CORRECT QUANTITIES OF FILLED UNITS OF THE CSPS WERE OBTAINED.  

C.	STERILITY TESTING.

1.	STERILITY TESTING SHALL BE DONE ON THE FOLLOWING RISK LEVEL 3 CSPS:

a.	BATCHES LARGER THAN 25 IDENTICAL INDIVIDUAL SINGLE-DOSE PACKAGES (AMPULES, BAGS, SYRINGES, VIALS, ETC);
b.	MULTIPLE DOSE VIALS FOR ADMINISTRATION TO MULTIPLE PATIENTS;
c.	PRODUCT IS EXPOSED LONGER THAN 12 HOURS AT REFRIGERATOR TEMPERATURES PRIOR TO STERILIZATION; OR
d.	PRODUCT IS EXPOSED LONGER THAN 6 HOURS TO TEMPERATURES WARMER THAN REFRIGERATOR TEMPERATURE PRIOR TO STERILIZATION.

2.	THE STERILITY TEST SHALL BE COMPLIANT WITH USP <71>.  A METHOD NOT DESCRIBED IN THE USP MAY BE USED IF VERIFICATION RESULTS DEMONSTRATE THAT THE ALTERNATIVE IS AT LEAST AS EFFECTIVE AND RELIABLE AS THE USP METHODS.

3.	WHEN A RISK LEVEL 3 CSP IS DISPENSED OR DISTRIBUTIED BEFORE RECEIVING THE RESULTS OF THE STERILITY TEST, THERE SHALL BE A WRITTEN PROCEDURE REQUIRING DAILY OBSERVATION OF THE INCUBATING TEST SPECIMENS AND REQUIRING AN IMMEDIATE RECALL IF THERE IS ANY EVIDENCE OF MICROBIAL GROWTH.  IN ADDITION, THE PATIENT AND THE PRACTITIONER OF THE PATIENT TO WHOM A POTENTIALLY CONTAMINATED CSP WAS ADMINISTERED SHALL BE NOTIFIED OF THE POTENTIAL RISK.  POSITIVE STERILITY RESULTS SHALL PROMPT A RAPID AND SYSTEMATIC INVESTIGATION OF ASEPTIC TECHNIQUE, ENVIRONMENTAL AND OTHER STERILITY ASSURANCE CONTROLS TO IDENTIFY SOURCES OF CONTAMINATION AND CORRECT PROBLEMS IN THE METHODS OR PROCESSES.

D.	BACTERIAL ENDOTOXIN (PYROGEN) TESTING

1.	ENDOTOXIN TESTING SHALL BE DONE ON THE FOLLOWING RISK LEVEL 3 CSPS THAT ARE TO BE ADMINISTERED PARENTERALLY:

a.	BATCHES LARGER THAN 25 IDENTICAL INDIVIDUAL SINGLE-DOSE PACKAGES (AMPULES, BAGS, SYRINGES, VIALS, ETC.);
b.	MULTIPLE DOSE VIALS FOR ADMINISTRATION TO MULTIPLE PATIENTS;
c.	PRODUCT IS EXPOSED LONGER THAN 12 HOURS AT REFRIGERATOR TEMPERATURES PRIOR TO STERILIZATION; OR
d.	PRODUCT IS EXPOSED LONGER THAN 6 HOURS TO TEMPERATURES WARMER THAN REFRIGERATOR TEMPERATURE PRIOR TO STERILIZATION.

2.	THE ENDOTOXIN TEST SHALL BE COMPLAINT WITH USP <85>.  IN THE ABSENCE OF A BACTERIAL ENDOTOXINS LIMIT IN THE OFFICIAL MONOGRAPH OR OTHER CSP FORMULA SOURCE, THE CSP MUST NOT EXCEED THE AMOUNT OF USP ENDOTOXIN UNITS (EU PER HOUR PER KG OF BODY WEIGHT) SPECIFIED FOR THE ROUTE OF ADMINISTRATION.

21.21.40	STORAGE AND BEYOND-USE DATING.

A.	THE TEMPERATURE OF DRUG STORAGE AREAS OF CSPS SHALL BE MONITORED AND RECORDED DAILY, EITHER MANUALLY OR ELECTRONICALLY.   TEMPERATURE RECORDS SHALL BE MAINTAINED AND BE AVAILABLE FOR INSPECTION FOR AT LEAST TWO YEARS.

B.	FINISHED CSPS THAT ARE NOT IMMEDIATELY DISPENSED OR ADMINISTERED SHALL BE REFRIGERATED UNLESS THEIR CHEMICAL AND PHYSICAL STABILITY ARE KNOWN TO BE ADVERSELY AFFECTED BY COLD TEMPERATURES.  

C.	IN THE ABSENCE OF STERILITY TESTING COMPLIANT WITH USP <71>, THE BEYOND-USE DATE (BEFORE ADMINISTRATION) SHALL NOT EXCEED THE FOLLOWING:

1.	RISK LEVEL 1:  

ROOM TEMPERATURE:  		NO MORE THAN 48 HOURS
REFRIGERATED TEMPERATURE:	NO MORE THAN 14 DAYS
FROZEN:				NO MORE THAN 45 DAYS

2.	RISK LEVEL 2:

ROOM TEMPERATURE:		NO MORE THAN 30 HOURS
REFRIGERATED TEMPERATURE:	NO MORE THAN 9 DAYS
FROZEN:			NO MORE THAN 45 DAYS

3.	RISK LEVEL 3:  

ROOM TEMPERATURE:		NO MORE THAN 24 HOURS
REFRIGERATED TEMPERATURE:	NO MORE THAN 3 DAYS
FROZEN:			NO MORE THAN 45 DAYS

D.	FOR RISK LEVEL 3 PRODUCTS, THERE MUST BE A RELIABLE METHOD FOR ESTABLISHING ALL EXPIRATION DATES, INCLUDING LABORATORY TESTING OF PRODUCT STABILITY, PYROGENICITY, PARTICULATE CONTAMINATION AND POTENCY.    THERE MUST BE A RELIABLE METHOD FOR ESTABLISHING ALL BEYOND-USE DATING.  PRODUCTS MAINTAINING BEYOND-USE DATING OF GREATER THAN THIRTY (30) DAYS SHALL HAVE LAB TESTING OF PRODUCT STABILITY AND POTENCY.
E.	EACH OUTLET SHALL ADHERE TO MANUFACTURERS’ INSTRUCTIONS FOR HANDLING AND STORING OF ADD-VANTAGE®, MINI BAG PLUS®, ADD A VIAL®, ADD-EASE® PRODUCTS, AND ANY SIMILAR PRODUCTS.
21.21.50	FORMULATION RECORD:	FOR EACH COMPOUNDED PREPARATION, A UNIFORM, READILY RETRIEVABLE FORMULATION RECORD SHALL BE MAINTAINED AND AVAILABLE FOR INSPECTION FOR TWO YEARS FROM THE DATE LAST UTILIZED, DOCUMENTING:
A.	THE NAME, STRENGTH, DOSAGE FORM, AND ROUTE OF ADMINISTRATION OF THE COMPOUNDED PREPARATION;

B.	ALL INGREDIENTS AND THEIR QUANTITIES;

C.	THE EQUIPMENT USED TO PREPARE THE PREPARATION, WHEN APPROPRIATE, AND MIXING INSTRUCTIONS;

D.	THE BEYOND USE DATE;
E.	THE CONTAINERS USED IN DISPENSING;

F.	STORAGE REQUIREMENTS; AND

G.	PROCEDURES FOR QUALITY CONTROL
21.21.60	COMPOUNDING RECORD. FOR COMPOUNDED STERILE PRODUCT PREPARED, A RECORD SHALL BE MAINTAINED AND AVAILABLE FOR INSPECTION FOR TWO YEARS ON THE ORIGINAL ORDER, OR ON A SEPARATE, UNIFORM, READILY RETRIEVABLE RECORD DOCUMENTING THE FOLLOWING:
A.	NAME AND STRENGTH OF THE COMPOUNDED PREPARATION;

B,	FORMULATION RECORD REFERENCE FOR THE PREPARATION;

C.	SOURCES AND LOT NUMBER OF EACH INGREDIENT;

D.	MANUFACTURER’S EXPIRATION DATE OF EACH INGREDIENT, WHEN APPLICABLE;

E.	TOTAL NUMBER OF DOSAGE UNITS COMPOUNDED;

F.	NAME OF THE PERSON WHO PREPARED THE PREPARATION;

G.	NAME OF THE PHARMACIST WHO APPROVED THE PREPARATION;

H.	BATCH (LOT) NUMBER ASSIGNED, IF MULTIPLE UNITS COMPOUNDED;

I.	DATE OF PREPARATION;

J.	BEYOND USE DATE;

K.	PRESCRIPTION NUMBER(S), IF APPROPRIATE;

L.	RESULTS OF QUALITY CONTROL PROCEDURES;

M.	SAMPLE LABEL;

N.	CERTIFICATE OF ANALYSIS FOR EACH NONSTERILE COMPONENT IS SUCH COMPONENT IS NON-USP OR NON-NF; AND

O.	IF A RISK LEVEL 3 PRODUCT, THE RECORD SHALL ALSO INCLUDE COMPARISONS OF ACTUAL WITH ANTICIPATED YIELDS, STERILIZATION METHODS, AND QUARANTINE SPECIFICATIONS.
21.21.70	LABELING OF CSPS.
A.	LABELING OF CSPS DISPENSED PURSUANT TO AN ORDER SHALL INCLUDE AT LEAST THE FOLLOWING:

1.	ALL REQUIREMENTS OF CRS 12-22-123;
2.	BATCH (LOT) NUMBER, IF APPROPRIATE;
3.	BEYOND-USE DATE;
4.	IF FOR PARENTERAL ADMINISTRATION, THE FOLLOWING SHALL BE INCLUDED:
a.	NAME OF BASE SOLUTION; AND
b.	NAME AND AMOUNTS OF DRUGS ADDED.
5.	STORAGE DIRECTIONS; AND
6.	“THIS PRODUCT WAS COMPOUNDED BY THE PHARMACY.”
 
B.	LABELING OF CSPS DISTRIBUTED TO PRACTITIONERS SHALL INCLUDE AT LEAST THE FOLLOWING:

1.	NAME AND ADDRESS OF THE OUTLET;
2.	NAME AND STRENGTH OF THE DRUG(S);
3.	TOTAL QUANTITY IN PACKAGE;
4.	QUANTITY OF ACTIVE INGREDIENT IN EACH DOSAGE UNIT;
5.	BEYOND-USE DATE;
6.	BATCH (LOT) NUMBER;
7.	SPECIFIC ROUTE OF ADMINISTRATION;
8.	STORAGE DIRECTIONS;
9.	“RX ONLY”; AND
10.	“THIS PRODUCT WAS COMPOUNDED BY THE PHARMACY.”
	
C.	LABELING OF CSPS DISTRIBUTED WITHIN HOSPITALS AS FLOOR STOCK SHALL INCLUDE AT LEAST THE FOLLOWING:

1.	NAME AND ADDRESS OF THE OUTLET;
2.	NAME AND STRENGTH OF THE DRUG(S);
3.	TOTAL QUANTITY IN PACKAGE;
4.	QUANTITY OF ACTIVE INGREDIENT IN EACH DOSAGE UNIT;
5.	BEYOND-USE DATE;
6.	BATCH (LOT) NUMBER;
7.	SPECIFIC ROUTE OF ADMINISTRATION; AND
8.	STORAGE DIRECTIONS.	
21.21.80	MAINTAINING PRODUCT QUALITY AND CONTROL AFTER THE CSP LEAVES THE OUTLET.
A.	THE OUTLET SHALL HAVE WRITTEN POLICIES AND PROCEDURES THAT ARE ADHERED TO WHICH 	SHALL ENSURE THE CSP IS PACKAGED PROPERLY FOR TRANSIT, STORED PROPERLY DURING TRANSIT, AND 	STORED PROPERLY AT SITE OF ADMINISTRATION.  SUCH POLICIES AND PROCEDURES SHALL ALSO DISCUSS PATIENT OR CAREGIVER TRAINING.
21.21.90	PATIENT MONITORING, ADVERSE EVENTS REPORTING, AND PRODUCT RECALL
A.	OUTLETS WHICH COMPOUND CSPS SHALL PROVIDE PATIENTS AND OTHER RECIPIENTS OF CSPS WITH A WAY TO ADDRESS THEIR QUESTIONS AND REPORT ANY CONCERNS THAT THEY MAY HAVE WITH CSPS AND THEIR ADMINISTRATION DEVICES.
B.	THE OUTLET SHALL HAVE WRITTEN POLICIES DESCRIBING SPECIFIC INSTRUCTIONS FOR RECEIVING, ACKNOWLEDGING, AND DATING RECEIPTS; AND FOR RECORDING, OR FILING, AND EVALUATING REPORTS OF ADVERSE EVENTS AND OF THE QUALITY OF PREPARATION CLAIMED TO BE ASSOCIATED WITH CSPS.
C.	COPIES OF ADVERSE EVENT REPORTS SHALL BE SUBMITTED IN WRITING TO THE BOARD AND TO THE FOOD AND DRUG ADMINISTRATION (FDA) WITHIN THREE BUSINESS DAYS.
D.	IF A CSP IS BELIEVED TO BE DEFECTIVE IN ANY WAY, THE OUTLET SHALL IMMEDIATELY RECALL ANY PRODUCT DISPENSED OR DISTRIBUTED.  ANY PRODUCT REMAINING IN THE OUTLET SHALL BE IMMEDIATELY QUARANTINED AND SHALL NOT BE DISPENSED OR DISTRIBUTED.  THE OUTLET SHALL IMMEDIATELY NOTIFY THE BOARD AND FDA IN WRITING OF PRODUCT RECALLS.  SUCH RECALL NOTIFICATION SHALL INCLUDE AT LEAST THE FOLLOWING:

1.	PRODUCT NAME, STRENGTH, DOSAGE FORM;
2.	REASON FOR RECALL;
3.	AMOUNT OF PRODUCT MADE;
4.	DATE MADE; AND
5.	AMOUNT OF PRODUCT DISPENSED OR DISTRIBUTED.

E.	THE OUTLET SHALL CONDUCT APPROPRIATE TESTS ON THE RECALLED PRODUCT TO IDENTIFY THE REASON THE PRODUCT WAS DEFECTIVE.  RESULTS OF THESE TESTS SHALL BE SUBMITTED TO THE BOARD UPON RECEIPT.

F.	ADVERSE EVENT REPORTS AND PRODUCT RECALLS SHALL BE RETAINED AND BE AVAILABLE FOR INSPECTION AT THE OUTLET FOR AT LEAST TWO YEARS.
21.22.00	QUALITY ASSURANCE PROGRAM.
A.	OUTLETS THAT MAKE CSPS SHALL HAVE A FORMAL WRITTEN QUALITY ASSURANCE (QA) PROGRAM WHICH SHALL PROVIDE A MECHANISM FOR MONITORING, EVALUATING, CORRECTING, AND IMPROVING THE ACTIVITIES AND PROCESSES REGARDING THE COMPOUNDING OF STERILE PRODUCTS.  
B.	AT A MINIMUM, THE  WRITTEN QA PROGRAM SHALL INCLUDE THE FOLLOWING:
1.	CONSIDERATION OF ALL ASPECTS OF THE PREPARATION, DISPENSING, AND DISTRIBUTION OF PRODUCTS, INCLUDING ENVIRONMENTAL TESTING, VALIDATION RESULTS, ETC.;
2.	DESCRIBE SPECIFIC MONITORING AND EVALUATION ACTIVITIES;
3.	SPECIFICATION OF HOW RESULTS ARE TO BE REPORTED AND EVALUATED;
4.	IDENTIFICATION OF APPROPRIATE FOLLOW-UP MECHANISMS WHEN ACTION LIMITS OR THRESHOLDS ARE EXCEEDED; AND
5.	DELINEATION OF THE INDIVIDUALS RESPONSIBLE FOR EACH ASPECT OF THE QA PROGRAM.
21.22.10	CYTOTOXIC DRUG PREPARATION.
A.	CYTOTOXIC DRUGS SHALL BE COMPOUNDED IN A VERTICAL FLOW, CLASS II BIOLOGICAL SAFETY CABINET OR AN ISOLATOR.  IF USED FOR OTHER PRODUCTS, THE CABINET MUST BE THOROUGHLY CLEANED;
B.	PROTECTIVE APPAREL SHALL BE WORN BY PERSONNEL COMPOUNDING CYTOTOXIC DRUGS WHICH SHALL INCLUDE DISPOSABLE MASKS, GLOVES AND GOWNS WITH TIGHT CUFFS;
C.	APPROPRIATE SAFETY AND CONTAINMENT TECHNIQUES FOR COMPOUNDING CYTOTOXIC DRUGS SHALL BE USED IN CONJUNCTION WITH THE ASEPTIC TECHNIQUES REQUIRED FOR PREPARING STERILE PRODUCTS;
D.	APPROPRIATE DISPOSAL CONTAINERS FOR USED NEEDLES, SYRINGES, AND IF APPLICABLE, CYTOTOXIC WASTE FROM THE PREPARATION OF CHEMOTHERAPY AGENTS AND INFECTIOUS WASTE FROM PATIENTS’ HOMES.  DISPOSAL OF CYTOTOXIC WASTE SHALL COMPLY WITH ALL APPLICABLE LOCAL, STATE AND FEDERAL REQUIREMENTS;
E.	WRITTEN PROCEDURES FOR HANDLING MAJOR AND MINOR SPILLS AND GENERATED WASTE OF CYTOTOXIC AGENTS MUST BE DEVELOPED AND MUST BE INCLUDED IN THE POLICY AND PROCEDURE MANUAL; AND
F.	PREPARED DOSES OF CYTOTOXIC DRUGS MUST BE LABELED WITH PROPER PRECAUTIONS INSIDE AND OUTSIDE, AND SHIPPED IN A MANNER TO MINIMIZE THE RISK OF ACCIDENTAL RUPTURE OF THE PRIMARY CONTAINER.
21.22.20	EXEMPTION FOR STERILE COMPOUNDING OF PRODUCTS IN CLOSED OR SEALED SYSTEM.
A.	PHARMACISTS AND PHARMACIES OR OTHER OUTLETS WHERE STERILE COMPOUNDING IS PROVIDED MAY BE EXEMPT FROM THIS RULE WHEN COMPOUNDING IS RESTRICTED TO UTILIZING COMPOUNDS OR PRODUCTS THAT ARE CONTAINED ONLY IN A CLOSED OR SEALED SYSTEM AND CAN BE TRANSFERRED OR COMPOUNDED WITHIN THIS SELF-CONTAINED SYSTEM OR TOPICAL PRODUCTS THAT REQUIRE FURTHER TRANSFER OR COMBINATION IN ORDER TO ACHIEVE A FINISHED PRODUCT WITHOUT FURTHER MODIFICATION OF THE PRODUCT.