The purpose of this chapter is to provide compounders with guidance on applying good compounding practices for the preparation of compounded formulations for dispensing and/or administration to humans or animals.It is expected that pharmacists or compounders engaged in the compounding of drugs will compound in conformance with applicable state and federal compounding laws,regulations,or guidelines.

Compounding (seePharmaceutical Compounding—Nonsterile Preparations á795ñ)—Compounding involves the preparation,mixing,assembling,packaging,and labeling of a drug or device in accordance with a licensed practitioner's prescription under an initiative based on the practitioner/patient/pharmacist/compounder relationship in the course of professional practice.Compounding includes the following:
  1. Preparation of drugs or devices in anticipation of prescription drug orders based on routine,regularly observed prescribing patterns.
  2. Reconstitution of commercial products that may require the addition of two or more ingredients as a result of a licensed practitioner's prescription drug order.
  3. Manipulation of commercial products that may require the addition of one or more ingredients as a result of a licensed practitioner's prescription drug order.
  4. Preparation of drugs or devices for the purposes of,or as an incident to,research,teaching,or chemical analysis.
Levels of Compounding—
Level 1 Nonsterile (topical)
Mixing of one or two creams
Mixing of creams with alcohol,water,etc.(as per
manufacturer's labeling instruction)
Level 2 Nonsterile (topical)
Preparation of nonsterile topical ointment,cream
Preparations with no dosage limitation
Level 3 Nonsterile (reconstituting or flavoring)
Reconstitution according to manufacturer's
labeling instruction
Addition of flavoring
Level 4 Sterile (simple injections,e.g.,reconstituted for
immediate administration)
Preparation of injections for immediate administration
Level 5 Nonsterile (dosage forms)
Preparation of solid oral dosage forms (tablets,
Preparation of liquid oral dosage forms
Preparation of suppositories,lozenges
Level 6 Sterile (ophthalmics/otics)
Preparation of ophthalmic and otic suspensions,
Level 7 Sterile (complex injections)
Preparation of injections for many patients
Preparation of injection not for immediate
Preparation of total parenteral nutritions (TPNs)
Preparation of multi-component injection
Level 8 Other sterile injections and patches
Preparation of chemotherapeutic injections or
Preparation of transdermal medications
Level 9 Sterile (radiopharmaceuticals)
Preparation of radiopharmaceuticals
Manufacturing— Manufacturing involves the production,propagation,conversion,or processing of a drug or device,either directly or indirectly,by extraction of the drug from substances of natural origin or by means of chemical or biological synthesis.Manufacturing also includes (1)any packaging or repackaging of the substance(s)or labeling or relabeling of containers for the promotion and marketing of such drugs or devices;(2)any preparation of a drug or device that is given or sold for resale by pharmacies,practitioners,or other persons;(3)the distribution of inordinate amounts of compounded preparations or the copying of commercially available drug products;and (4)the preparation of any quantity of a drug product without a licensed prescriber/patient/licensed pharmacist/compounder relationship.
Component— Acomponent is any ingredient used in the compounding of a drug product,including any that are used in its preparation,but may not appear on the labeling of such a product.(See Pharmaceutical Compounding—Nonsterile Preparations á795ñfor additional definitions.)
Pharmacy Generated Product (PGP)— Apharmacy generated product (PGP)is a product that is prepared,packaged,and labeled in a pharmacy and can be sold by the pharmacy without a prescription.PGPs are clearly different from drugs defined in section 201(g)of the Federal Food,Drug,and Cosmetic Act.
Compounder— Acompounder is a pharmacist or a physician who is engaged in the act of compounding pursuant to a precription order by a licensed prescriber.

  1. Compounders who are engaged in drug compounding or nutriceutical compounding shall be proficient in compounding and should continually expand their compounding knowledge by participating in seminars and/or studying appropriate literature.
  2. Acompounder shall be familiar with all of the details ofPharmaceutical Compounding—Nonsterile Preparations á795ñ,Pharmaceutical Compounding—Sterile Preparations á797ñ,and other applicable state or federal compounding guidelines or laws.In addition,the compounder shall be responsible for the following:
    • certifying all prescription orders;
    • approving or rejecting all components,drug product containers,closures,in-process materials,and labeling;
    • preparing and reviewing all compounding records to assure that errors have not occurred in the compounding process;
    • assuring the proper maintenance,cleanliness,and use of all equipment used in a prescription compounding practice;
    • assuring that only personnel authorized by the compounding supervisor shall be in the immediate vicinity of the drug compounding operations;
    • assuring that the drug product and components of drug products are not on the list of federally recognized drug products that have been withdrawn or removed from the market for public health reasons.
  3. The compounder shall ensure that personnel engaged in compounding wear clean clothing appropriate to the type of compounding performed,e.g.,coats,gowns,gloves,masks,shoes,aprons,or other items as needed for protection of personnel from chemical exposures and for prevention of drug contamination.
  4. The compounder shall implement procedures to prevent cross-contamination when compounding with drugs (e.g.,penicillins)that require special precaution to prevent cross-contamination.

All personnel involved in the compounding,evaluation,packaging,and dispensing of compounded preparations shall be properly trained for the type of compounding conducted.All training activities will be covered by appropriate standard operating procedures (SOPs)and documentation.
All compounders and all personnel involved in compounding must be well trained and must participate in current,relevant training programs.It is the responsibility of the pharmacist to ensure that a training program has been implemented and that it is ongoing.Standards of pharmacy practice require that all employees be adequately trained in their job functions and that all of the training is properly documented.Steps in the training procedure will include the following:
  1. All employees involved in pharmaceutical compounding shall read and become familiar with Pharmaceutical Compounding—Nonsterile Preparations á795ñ,Pharmaceutical Compounding—Sterile Preparations á797ñ,and Pharmaceutical Calculations in Prescription Compounding á1160ñ.
  2. All employees shall read and become familiar with each of the procedures related to compounding,including those involving the facility,equipment,personnel,actual compounding,evaluation,packaging,storage,and dispensing.
  3. The compounder shall meet with employees to review their work and answer any questions the employees may have concerning SOPs.
  4. The compounder shall demonstrate the procedures for the employee,and will observe and guide the employee throughout the procedure.The employee will then repeat the procedure without any assistance from,but under the supervision of,the pharmacist.
  5. When the employee has demonstrated to the compounder a verbal and functional knowledge of the procedure,then and only then,will the employee be permitted to perform the procedure without supervision.
  6. When the compounder is satisfied with the employee’s knowledge and proficiency,the compounder will sign off on the documentation records to show that both the employee and the compounder agree.
  7. The compounder shall continually monitor the work of the employee and answer any questions the employee may have concerning the SOPs.

All significant procedures performed in the compounding area will be covered by SOPs and will be documented.
Procedures should be developed for the facility,equipment,personnel,preparation,packaging,and storage of compounded preparations to ensure accountability,accuracy,quality,safety (including access to Material Safety Data Sheets)and uniformity in a compounding practice.More importantly,implementing SOPs establishes procedural consistency and also provides a reference for orientation and training of personnel.
Documentation enables a pharmacy,whenever necessary,to systematically trace,evaluate,and replicate the steps included throughout the preparation process of a compounded product.

  1. Compounding facilities shall have an adequate space that is specifically designated for compounding of prescriptions.This area may include a space for the storage of equipment and materials.
  2. Sterile compounded preparations shall be compounded in accordance with the provisions in Pharmaceutical Compounding—Sterile Preparations á797ñ,and aseptic processes shall be conducted in an area separate and distinct from the area used for the compounding of nonsterile products.
  3. The areas used for compounding shall be maintained in clean,orderly,and sanitary conditions.
  4. The areas for drug compounding shall be maintained in a good state of repair.The plumbing system shall be free of defects that could contribute to contamination of any compounded product.Adequate washing facilities shall be easily accessible to the compounding areas.Such facilities shall include,but not be limited to,hot and cold water,soap or detergent,and an air-drier or single-use towels.
  5. Potable water shall be supplied under continuous positive pressure.
  6. The area for compounding shall have adequate lighting and ventilation.
  7. The area for compounding shall be free of infestation by insects,rodents,and other vermin.Trash shall be held and disposed of in a sanitary and timely manner.
  8. Sewage and other refuse in the area of compounding shall be disposed of in a safe and sanitary manner.
  9. Bulk drugs and other chemicals or materials used in the compounding of drugs must be stored as directed by the manufacturer,or according to USPmonograph requirements,in a clean,dry area (defined temperature condition),or in a refrigerator or freezer as specified.The bulk chemicals shall be stored in a manner such that they are protected from contamination.All containers shall be properly labeled.
  10. If parenteral products are compounded,the compounder shall refer to Pharmaceutical Compounding—Sterile Preparations á797ñ,and Injections á1ñfor compounding technique applications.

  1. The equipment or utensils used for compounding of a drug product shall be of appropriate design and capacity.The equipment shall be stored in such a manner as to protect it from contamination,and shall be located in such a place as to facilitate operations for its use,maintenance,and cleaning.
  2. The equipment shall be cleaned and sanitized prior to use to prevent contamination that may affect the safety or quality of compounded preparations.
  3. The equipment shall be of suitable composition such that the surfaces that contact components are neither reactive,additive,nor absorptive and therefore will not affect or alter the purity of the compounded preparations.
  4. Automated,mechanical,electronic,and other types of equipment used in compounding shall be routinely inspected,calibrated as necessary,and checked to ensure proper performance.
  5. Immediately prior to initiation of compounding operations,the equipment shall be inspected by the compounder to determine its suitability for use.
  6. The equipment shall be cleaned appropriately using special instructions when cross-contaminating products or products requiring special precaution,e.g.,antibiotics,cytotoxins,cancer drugs,and other hazardous materials,are used with the equipment.If possible,special equipment may be dedicated for such use or if the same equipment is being used for all drug products,appropriate procedures must be in place to allow meticulous cleaning of equipment prior to use with other drugs.

  1. The compounder shall first attempt to use USP–NFdrug substances manufactured in an FDA-registered facility.
  2. The compounder shall also first attempt to use inactive components manufactured in an FDA-registered facility.
  3. If components are not obtainable from an FDA-registered facility or if the FDAand/or the providing company cannot document FDAregistration,compounders shall use their professional judgment in first receiving,storing,or using the components that meet official compendial requirements or are provided by another high quality source.
  4. If components of compendial quality are not obtainable,components of high quality such as those that are chemically pure,analytical reagent grade,American Chemical Society-certified,or Food Chemical Codex grade may be used.
  5. When a component is not obtained from an official compendial source or is not obtainable from the sources mentioned above,the component may be obtained from a source deemed acceptable and reliable in the professional judgment of the compounder.
  6. When a component is derived from ruminant animals (e.g.,bovine,caprine,ovine)the supplier shall provide written assurance that these animals were born,raised,or slaughtered in countries where bovine spongiform encephalopathy (BSE)and scrapie are known not to exist.
  7. The compounder shall not use components that are listed by FDAto be withdrawn from the market for public health reasons.
  8. Components shall be stored off the floor,handled and stored to prevent contamination,and rotated so that the oldest stock is used first.

  1. The compounder shall ensure that the containers and container closures used in packaging the compounded preparations meet the requirements under Containers á661ñand Containers—Permeation á671ñ.The compounder shall obtain written records from the supplier to show that the containers meet USPrequirements.
  2. Containers and container closures intended for compounding of sterile preparations and nonsterile preparations must be handled,sterilized (if appropriate),and stored as described inPharmaceutical Compounding—Sterile Preparations á797ñandPharmaceutical Compounding—Nonsterile Preparations á795ñ.The use of commercially available presterilized containers may be considered.
  3. The containers and closures shall be stored off the floor,handled and stored to prevent contamination,and rotated so that the oldest approved stock is used first.
  4. The containers and container closures shall be stored in such a way as to permit inspection and cleaning of the work area.
  5. The containers and container closures shall be made of clean materials that are neither reactive,additive,nor absorptive.
  6. The containers and closures shall be of suitable material so as not to alter the quality,strength,or purity of the compounded drug.
  7. The compounder shall ensure that the containers and container closures selected to dispense the finished compounded prescription,whether sterile or nonsterile or radiopharmaceutical,meet the criteria in sections (a)–(f)above.

  1. The compounder shall ensure that there are written procedures for the compounding of drug products to assure that the finished products have the identity,strength,quality,and purity that they purport to have.
  2. The compounder shall establish procedures for listing components,their amounts (weight or volume),the order of component mixing,and a description of the compounding process.
  3. The compounder shall list all equipment,utensils,and container closure systems relevant to the sterility,stability,and intended use of a drug.
  4. The written procedures described above shall be followed in execution of the compounding process.
  5. The compounder shall accurately weigh,measure,and subdivide as appropriate.
  6. The compounder shall check and recheck each procedure at each stage of the process to ensure that each weight or measure is correct as stated in the written compounding procedures.
  7. If a component is transferred from the original container to another container (e.g.,a powder is taken from the original container,weighed,placed in a container,and stored in that other container),the new container shall be identified with the component name,weight or measure,the lot or control number,the expiration or beyond-use date,and the transfer date.
  8. The compounder shall have drug compounding procedures available in either written form or electronically stored with printable documentation.
  9. The procedures shall include a description of (1)the components,their amounts,the order of component additives,and the compounding process;(2)the required equipment and utensils;and (3)the drug product container and closure system.
  10. The compounder shall have established written procedures that will describe the tests or examinations to be conducted on the product compounded (e.g.,the degree of weight variation among capsules)to assure uniformity and integrity of compounded drug products.
  11. Appropriate control procedures shall be established to monitor the output and to validate the performance of those compounding processes that may be responsible for causing variability in the final compounded preparations.Factors that may cause variability include (1)capsule weight variation;(2)adequacy of mixing to assure uniformity and homogeneity;and (3)clarity,completeness,or pHof solutions.
  12. Appropriate written procedures shall be designed to prevent microbiological contamination of compounded drug products purporting to be sterile,and these procedures shall be followed.Such procedures shall include validation of sterilization processes (seePharmaceutical Compounding—Sterile Preparations á797ñ).
  13. The compounder shall establish appropriate beyond-use dates determined either from available USP–NFmonographs,appropriate testing,or from peer-reviewed literature.
  14. The compounder shall adopt appropriate storage requirements as provided in Preservation,Packaging,Storage,and Labelingunder General Notices and Requirements.

  1. Products prepared in anticipation of a prescription prior to receiving a valid prescription should not be prepared in an inordinate amount.Aregularly used amount should be prepared on the basis of a history of prescriptions filled by the pharmacy.These products shall be labeled or documentation referenced with the following:
    1. Acomplete list of ingredients or preparation name and reference or established name or distinct common name
    2. Dosage form
    3. Strength
    4. Preparation date
    5. Name and address of compounder
    6. Inactive ingredients
    7. Batch or lot number
    8. Assigned beyond-use date,based on published data,or appropriate testing,or USP–NFstandards.
    Storage conditions for these products shall be dictated by their composition and sterility,e.g.,stored in a clean,dry place (defined temperature condition),in a refrigerator,or at controlled room temperature.
  2. The compounder shall examine the product for correct labeling after completion of the compounding process.
  3. The compounder's prescription label shall contain the following:
    1. Patient's name
    2. Prescriber's name
    3. Name and address of compounder
    4. Prescription number
    5. Established name or distinct common name (cannot use trademarked name of a manufactured product)
    6. Strength
    7. Statement of quantity
    8. Directions for use
    9. Date filled
    10. Beyond-use date/storage,etc.
    11. An appropriate designation that this is a compounded prescription
    12. Any other federal or state requirements
    NOTE—The compounder shall not use an NDCnumber assigned to another product.
  4. The compounder shall label any excess compounded products so as to reference them to the formula used,the assigned control number,and beyond-use date based on the compounder's appropriate testing,published data,or USP–NFstandards.

  1. The compounder shall maintain records,including but not limited to,the hard copy of the prescription to indicate that the prescription is compounded.
  2. The compounder shall keep adequate records of controlled drug substances (scheduled drugs)used in compounding.
  3. All records of all compounded products shall be kept for a period of time as set forth in the state laws or regulations.Such records shall be readily available for authorized inspection.

  1. Compounders may prepare compounded drug products for a prescriber's office use pursuant to federal and state requirements.
  2. An order by the prescriber indicating the formula and quantity ordered may be filled in the compounder's facility.
  3. The compounder shall compound the product for the purpose of administration by or for the prescriber.
  4. Arecord of the compounding process shall be maintained.
  5. Alabel may be generated and a number may be assigned.

  1. Compounders shall compound prescriptions for animals on the basis of prescription orders.
  2. These prescriptions shall be handled and filled as are human prescriptions.

  1. Compounders may prepare compounded drug products that can be sold without a prescription.
  2. Pharmacy generated products (PGP)shall be compounded using the same procedures as those for prescription drug products detailed in this chapter.
  3. Additional labeling sufficient for patient use will be required to meet the individual State Board of Pharmacy and federal requirements.[NOTE—PGPs are clearly different from drugs defined in section 201(g)of the Federal Food,Drug,and Cosmetic Act.]