| 213 | | Table 1. Minimum Frequency for Cleaning and Sanitizing Surfaces in |
| 214 | | Nonsterile Compounding Areas |
| |
| Site | | Minimum Frequency |
| Ceilings | | Every 3 months, after spills, and when surface contamination (e.g., splashes) is known or suspected |
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| 215 | | |
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| +Is it really necessary to clean ceilings every 3 months in a nonsterile compounding area? Possibly necessary if compounding large numbers/volumes of preparations and using a lot of powders but not necessary for others. Every 6 months should be sufficient, especially for low numbers/volumes of preparations. |
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| 216 | | 6. EQUIPMENT AND COMPONENTS |
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| 217 | | 6.1 Equipment |
| 226 | | Automated, mechanical, electronic, and other types of equipment used in |
| 227 | | the compounding or testing of compounded preparations must be inspected |
| 228 | | prior to use and verified for accuracy at the frequency recommended by the |
| 229 | | manufacturer, and at least annually. Immediately after compounding, the |
| 230 | | equipment must be cleaned to prevent cross-contamination of the next |
| 231 | | preparation. |
| |
| +Confusing. Equipment also includes hot plates, stirrers, mixers, etc�..must these be verified for accuracy? Possibly change to, "As appropriate, automated, mechanical, electronic�etc.) |
| |
| 232 | | Any weighing, measuring, or other manipulation of an active |
| 233 | | pharmaceutical ingredient (API) or added substance in powder form that |
| 234 | | could generate airborne contamination from drug particles must occur inside |
| 235 | | a containment device such as a containment ventilated enclosure (CVE) (i.e., |
| 236 | | powder containment hood). The CVE must be cleaned as described in Table |
| 237 | | 2. The CVE must be certified annually. If the CVE is not equipped with an |
| 238 | | exhaust alarm, the device should be certified every 6 months according to |
| 239 | | requirements such as the current Controlled Environment Testing |
| 240 | | Association (CETA) or American Society of Heating, Refrigerating, and Air- |
| 241 | | Conditioning Engineers (ASHRE) guidelines, or other jurisdictional standards. |
| |
| +This will be quite costly and one wonders if ALL powders, both APIs and excipients, is too broad. There are numerous powders that are safe, have higher densities, and less likely to become airborne that could be considered to be manipulated outside a CVE. Also, if only doing 1 or 2 a day, this may be cost-prohibitive with little demonstrated need. |
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| 244 | | 6.2 Components |
| 245 | | Compounding personnel must establish, maintain, and follow written SOPs |
| 246 | | for the selection and inventory control of all components, including all |
| 247 | | ingredients (i.e., APIs, inactive ingredients), containers, and closures, from |
| 248 | | receipt to use in a CNSP. |
| |
| +Does this mean an ongoing inventory requiring a lot of time without a lot of return on investment of time; also, what is involved in "�from receipt to use in a CNSP"? This appears to be unnecessary to keep track of ingredients, containers, and closures as they progress through the process from receiving, storage, usage, dispensing, etc. |
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| 252 | | COMPONENT SELECTION |
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| 266 | | All ingredients other than APIs should be obtained from an FDA-registered |
| 267 | | facility. |
| |
| +"Should" is appropriate here as excipients may or may not be available from FDA-registered facilities. |
| |
| | Outside of the US, the facility must comply with applicable laws and |
| 268 | | regulations of the regulatory jurisdiction. These ingredients should be |
| 269 | | accompanied by a valid COA that verifies that the ingredient meets an |
| 270 | | official monograph, if one exists, and any additional specifications for the |
| 271 | | ingredient. If ingredients other than APIs cannot be obtained from an FDA |
| 272 | | registered facility, the designated person must select a material that is |
| 273 | | suitable for the intended use. The designated person must establish the |
| 274 | | identity, strength, purity, and quality of the API by reasonable means. These |
| 275 | | means may include visual inspections, evaluation of the COAs, and/or |
| 276 | | verification by analytically testing a sample to determine conformance with |
| 277 | | the COA. |
| |
| +Line 276-Analytically testing excipients can be very costly. |
| |
| 278 | | Purified Water, or an equivalent quality of water, must be used to |
| 279 | | reconstitute conventionally manufactured nonsterile products when water |
| 280 | | quality is not stated in the manufacturer�s labeling (see Water for |
| 281 | | Pharmaceutical Purposes <1231>). |
| |
| +If "reconstitution of conventionally manufactured nonsterile products" is not in the definition of compounding, why is this here? It should be in the FDA-approved labeling of the product. |
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| 282 | | COMPONENT RECEIPT |
| |
| 289 | | ��If there is a compendial monograph |
| 290 | | for any ingredient received, the COA for the ingredient must be verified to |
| 291 | | ensure that the ingredient has met the acceptance criteria of all specified |
| 292 | | monograph tests for that lot and includes the test results. |
| |
| +If the provider of the ingredients is FDA registered and must provide a valid COA, then why must the pharmacy take the time to verify it to ensure that the ingredient has met the acceptance criteria of all specified monograph tests for that lot and include the test results? This should be the responsibility of the provider and the pharmacy just spot checking to confirm the COA. |
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| 309 | | COMPONENT EVALUATION BEFORE USE |
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| 323 | | COMPONENT HANDLING AND STORAGE |
| 324 | | All ingredients used to prepare CNSPs must be handled and stored in |
| 325 | | accordance with the manufacturer�s instructions or per applicable laws and |
| 326 | | regulations of the regulatory jurisdiction. The handling and storage must |
| 327 | | prevent contamination, mix-ups, and deterioration (e.g., loss of identity, |
| 328 | | strength, purity, and quality). If specific instructions are not available, |
| 329 | | ingredients must be stored in tightly closed containers under controlled |
| 330 | | temperature, humidity, and lighting conditions as detailed in this chapter. |
| 331 | | Moisture-sensitive ingredients must be stored in tight, well-closed |
| 332 | | containers. |
| |
+Many excipients only require "well-closed" containers. Does this mean they will need to be repackaged into "tight containers"? USP definitions are as follows:
- Well-Closed Container: A container-closure system that protects the contents from contamination by extraneous solids and from loss of the article under ordinary or customary conditions of handling, shipment, storage and distribution.
- Tight Container: A container-closure system that protects the contents from contamination by extraneous liquids, solids, or vapors; from loss of the article; and from efflorescence, deliquescence, or evaporation under the ordinary or customary conditions of handling, shipment, storage, and distribution, and is capable of tight reclosure.
+Humidity control is not necessarily required in USP APIs or USP Product Monographs except where it states to store in a Dry Place.
- A Dry Place is a place that does not exceed 40% average relative humidity at 20� (68� F) or the equivalent water vapor pressure at other temperatures. The determination may be made by direct measurement at the place. Determination is based on NLT 12 equally spaced measurements that encompass either a season, a year, or, where recorded data demonstrate, the storage period of the article. There may be values of up to 45% relative humidity provided that the average value does not exceed 40% relative humidity. Storage in a container validated to protect the article from moisture vapor, including storage in bulk, is considered a Dry Place.
The geographical variations in the US from coastal, gulf, desert, etc. results in pharmacies with low and some with high humidities. Once a door is opened, the humidity inside the facility changes. The reference to humidity should possibly be removed.
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| |
| 333 | | Packages of ingredients that lack a vendor�s expiration date must not be |
| 334 | | used after 1 year from the date of receipt by the compounding facility. |
| |
| +This can be quite wasteful. Not aware that the current chapter "3 years" has been a problem over the years. Recommend 3 years be maintained unless documentation shows it is a problem. |
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| 343 | | COMPONENT SPILL AND DISPOSAL |
