Compounding: Difference between revisions

In the field of [[pharmacy]], '''compounding''' (performed in '''compounding pharmacies''') is preparation of a custom formulation of a medicationmedications to fit a unique needneeds of apatients patient whichthat cannot be met with commercially availablemass-produced products. This may be done, for medical reasonsexample, such as to beprovide administeredmedication byin a differentform routeeasier (ex:for tableta given patient to ingest (e.g., liquid vs. tablet), or to avoid a [[Excipient|non-active ingredient]] that thea patient is allergic to, or to provide an exact dose that isn't commerciallyotherwise available. MedicallyThis necessarykind of patient-specific compounding, according to a prescriber's specifications, is referred to as "traditional" compounding.<ref>{{cite web | url=https://www.pharmacist.com/Practice/Patient-Care-Services/Compounding/Compounding-FAQs may| alsotitle=Compounding beFAQs done}}</ref> forThe medicallynature optionalof reasons,patient need for such ascustomization can range from absolute necessity (e.g. avoiding allergy) to individual optimality (e.g. ideal dose level) to even preference of(e.g. flavor or texture, or [[dietary restriction]]s).

Compounding bulk preparations of a given formulation in advance batches, as opposed to preparation for a specific patient on demand, is known as "non-traditional" compounding. Differentand jurisdictionsis haveakin differentto rulessmall-scale regardingmanufacturing. theJurisdictions applicabilityhave ofvarying regulations whichthat apply to [[drug manufacturer]]s toand pharmacies whichthat do performadvance bulk compounding.

{{refimprovemore citations needed section|date=July 2010}}

The earliest [[chemist]]s were familiar with various natural substances and their uses. These professionalsThey compounded a variety of preparations such as medications, dyes, incense, perfumes, ceremonial compounds, preservatives and cosmetics. In the [[Islamic Golden Age|medieval Islamic world]] in particular, [[Islamic medicine|Muslim pharmacists]] and [[Alchemy and chemistry in Islam|chemists]] developed advanced methods of compounding drugs. The first [[Pharmacy|drugstores]] were opened by Muslim pharmacists in [[Baghdad]] in 754.<ref name=Hadzovic>Information taken from the abstract of {{Cite journal | issn = 0350-199X | volume = 51 | issue = 1–2 | pages = 47–50 | last = Hadzović | first = S | title = [Pharmacy and the great contribution of Arab-Islamic science to its development] (Article in Croatian) | journal = Medicinski Arhiv | year = 1997 | pmid = 9324574}}</ref><ref>{{cite journal|author=Kaf al-Ghazal, Sharif |journal=Journal of the International Society for the History of Islamic Medicine|year=2004 |volume=3|pages=3–9 [8]|url=http://www.ishim.net/islam/alrazi3.htm|title=The valuable contributions of Al-Razi (Rhazes) in the history of pharmacy during the middle ages}}</ref> The modern age of pharmacy compounding began in the 19th century with the isolation of various compounds from [[coal tar]] for the purpose of producing [[synthetic dyes]]. From this came the earliest [[antibacterial]] [[sulfa drugs]], [[phenol]]ic compounds made famous by [[Joseph Lister, 1st Baron Lister|Joseph Lister]], and [[plastic]]s.

During the 1800s, pharmacists specialized in the raising, preparation and compounding of [[crude drugs]]. Crude drugs, like [[opium]], are from natural sources and usually contain several [[chemical compounds]]. The compounding pharmacist extracted these crude drugs using solvents such as [[water]] or [[ethanol|alcohol]] to form [[extract]]s, [[concoction]]s and [[decoction]]s. PharmacistsThey eventually began isolating and identifying the [[active ingredient]]s contained withinin these crude drug concoctions. Using [[fractionation]] or [[recrystallization (chemistry)|recrystallization]], the compounding pharmacist wouldthey separateseparated an active ingredient from the crude preparation, and compoundcompounded a medication using this active ingredient.

A physician may choose to prescribe a compounded medication for a patient with an unusual health need that cannot be met with commercially manufactured products. The physician may choose to prescribe a compounded medication for reasons such as:

*Patients requiring a different formulation, such as turning a [[Pill (pharmacy)|pill]] into a liquid or transdermal gel for people who cannot swallow pills due to disability<ref>{{Cite web |title=Services Overview {{!}} Services {{!}} Bayview Pharmacy |url=https://www.bayviewrx.com/services/overview |access-date=2023-01-11 |website=www.bayviewrx.com}}</ref>

* Many types of [[bioidentical hormone replacement therapy]]<ref name = Boothby2008>{{cite journal |vauthors=Boothby LA, Doering PL |title=Bioidentical hormone therapy: a panacea that lacks supportive evidence |journal=Curr. Opin. Obstet. Gynecol. |volume=20 |issue=4 |pages=400–7 |date=August 2008 |pmid=18660693 |doi=10.1097/GCO.0b013e3283081ae9 |s2cid=22449765 }}</ref><ref name = NASEMcBHT>{{cite report |vauthors= ((National Academies of Sciences, Engineering & Medicine)) |title=Clinical Utility of Treating Patients with Compounded “Bioidentical Hormone Replacement Therapy”|date=2020 |url=https://www.nationalacademies.org/our-work/clinical-utility-of-treating-patients-with-compounded-bioidentical-hormone-replacement-therapy }}</ref>

*Patients who require multiple medications combined in various doses<ref name="urlThe Benefits of Compounding Sports Meds into a Single Dose">{{cite web |url= https://compoundingrxusa.com/blog/the-benefits-of-compounding-sports-meds-into-a-single-dose/ |title=The Benefits of Compounding Sports Meds into a Single Dose |work= compoundingrxusa.com |date=4 December 2018 |access-date=2018-12-04}}</ref>

Both sterile and non-sterile compounding are legal provided the compounding is done for therapeutic use in a particular patient, and the compounded product is supplied on or from the compounding pharmacy.<ref>{{cite web|title=Therapeutic goods regulations: Exempt goods|url=https://www.tga.gov.au/sites/default/files/dr4-appendix-08.pdf|publisher=Australian Government. Department of Health and Aging. Therapeutic Goods Administration|access-date=2017-02-21|date=December 1997}}</ref> There are additional requirements for sterile compounding. Not only must a laminar flow cabinet [laminar flow hood] be used, but the environment in which the hood is located must be strictly controlled for microbial and particulate contamination and all procedures, equipment and personnel must be validated to ensure the safe preparation of sterile products. In non-sterile compounding, a powder containment hood is required when any hazardous material (e.g. hormones) are prepared or when there is a risk of cross-contamination of the compounded product. Pharmacists preparing compounded products must comply with these requirements and others published in the Australian Pharmaceutical Formulary & Handbook.{{cncitation needed|date=August 2020}}

In the [[United States]], compounding pharmacies are licensed and regulated by states. National standards have been created by Pharmacy Compounding Accreditation Board (PCAB),<ref name="urlInternational Academy of Compounding Pharmacists: Frequently Asked Questions">{{cite web |url=http://www.iacprx.org/site/PageServer?pagename=FAQs |archive-url=https://web.archive.org/web/20060819002609/http://www.iacprx.org/site/PageServer?pagename=FAQs |archive-date=2006-08-19 |title=International Academy of Compounding Pharmacists: Frequently Asked Questions |access-date=2010-07-18}}</ref> however, obtaining accreditation is not mandatory and inspections for compliance occur only every three years.<ref>Kotz, Deborah (2012-10-11) [https://www.boston.com/dailydose/2012/10/11/how-risky-are-compounding-pharmacies/5qEMXl6fMzSl4fTtolachJ/story.html How risky are compounding pharmacies?]. Boston.com. Retrieved on 2013-05-13.</ref> The [[Food and Drug Administration]] (FDA) has authority to regulate "manufacturing" of pharmaceutical products–whichproducts—which applies when drug products are not made or modified as to be ''tailored in some way to the individual patient''–regardless—regardless of whether this is done at a factory or at a pharmacy.

Poor practices on the part of drug compounders can result in contamination of products, or products that do not meet their stated strength, purity, or quality. Unless a complaint is filed or a patient is harmed, drugs made by compounders are seldom tested.{{cn|date=August 2020}} In Texas, one of only two states that does random testing, significant problems have been found.{{cn|date=August 2020}} Random tests by the state’sstate's pharmacy board over the last several years have found that as many as one in four compounded drugs was either too weak or too strong. In Missouri, the only other state that does testing, potency varied by as much as 300 percent.<ref name=autogenerated1>Bogdanich, Walt and Tavernise, Sabrina (2012-10-22). [https://www.nytimes.com/2012/10/23/health/before-meningitis-outbreak-group-advised-how-to-avoid-fda.html U.S. Concern Over Compounders Predates Outbreak of Meningitis]. New York Times.</ref>

<ref>[https://www.usatoday.com/story/news/nation/2012/10/09/meningitis-outbreak-deaths/1622869/ Meningitis outbreak toll: 119 cases, 11 deaths]. Usatoday.com (2012-10-09). Retrieved on 2012-12-19.</ref> At that time it was also disclosed that the United States and Massachusetts state health regulators were aware in 2002 that steroid treatments from the New England Compounding Center could cause adverse patient reactions.<ref>{{cite web|last=Morgan|first=David|title=Health officials knew of problem steroids in 2002: U.S. House panel|url=https://www.reuters.com/article/2012/10/23/us-usa-health-meningitis-congress-idUSBRE89M00820121023|publisher=Reuters|date=October 22, 2012}}</ref> It was further disclosed that in 2001–02, four people died, more than a dozen were injured and hundreds exposed after they received back-pain injections tainted with a common fungus dispensed by two compounding pharmacies in California and South Carolina.<ref name = "WSJ2">Burtin, T. M.; Grimaldi, J. V. and Martin, T. W. (2012-10-14). [https://www.wsj.com/articles/SB10000872396390444657804578052972230404046 Pharmacies Fought Controls; Industry at the Focus of Meningitis Outbreak Beat Back More Federal Oversight], Wall Street Journal</ref>

In August 2013 further reports tied to the [[New England]] compounding center said that about 750 people were sickened, including 63 deaths, and that infections were linked to more than 17,600 doses of [[methylprednisolone acetate]] [[steroid]] injections used to treat back and [[joint]] pain that were shipped to 23 states. At that time, another incident was reported after at least 15 people at two [[Texas]] hospitals developed bacterial infections. All lots of medications dispensed since May 9, 2013, made by Specialty Compounding, LLC of [[Cedar Park, Texas]] were recalled. The hospitals reported affected were Corpus Christi Medical Center Bay Area and Corpus Christi Medical Center Doctors Regional. The patients had received intravenous infusions of [[calcium gluconate]], a drug used to treat [[calcium]] deficiencies and too much [[potassium]] in the blood. Implicated in these cases is the [[Rhodococcus]] bacteria, which can cause symptoms such as fever and pain.<ref>{{cite web|url=https://www.cbsnews.com/8301-204_162-57598110news/texas-compounding-pharmacy-recalls-drugs-after-15-infections/ |title=Texas compounding pharmacy recalls drugs after 15 infections |publisherwork=CBS News |date=2013-08-12 |access-date=2014-02-18}}</ref>

The FDA, among others, claims that larger compounding pharmacies act like drug manufacturers and yet circumvent FDA regulations under the banner of compounding. Drugs from compounding pharmacies can be cheaper or alleviate shortages, but can pose greater risk of contamination due in part to the lack of oversight. "Non-traditional" compounders behave like drug manufacturers in some cases by having sales teams that market non-personalized drug products or production capability to doctors, by making drugs that are essentially the same as commercially available mass-produced drug products, or by preparing large batches of a given drug product in anticipation of additional prescriptions before actually receiving them.<ref name=r1>Grady, Denise; Pollack, Andrew and Tavernise, Sabrina (2012-10-07). [https://www.nytimes.com/2012/10/07/us/scant-drug-maker-oversight-in-meningitis-outbreak.html?_r=0 Scant Oversight of Drug Maker in Fatal Meningitis Outbreak]. New York Times.</ref><ref name=WSJ1>{{cite web|title=Outbreak Spurs Calls for New Controls |url=https://www.wsj.com/articles/SB10000872396390443982904578044682649925200?mod=WSJ_hpp_LEFTTopStories|publisher=The Wall Street Journal|author1=Martin, T. W. |author2=Burton, T. M. |author3=Dooren, J. C. |date = 2012-10-09 |work=The Wall Street Journal|access-date=2012-10-09}}</ref> An FDA spokesperson stated, "The methods of these companies seem far more consistent with those of drug manufacturers than with those of retail pharmacies. Some firms make large amounts of compounded drugs that are copies or near copies of FDA-approved, commercially available drugs. Other firms sell to physicians and patients with whom they have only a remote professional relationship."<ref name="SpecialRisks">{{cite web| url= https://www.fda.gov/ForConsumers/ConsumerUpdates/ucm107836.htm |title= The Special Risks of Pharmacy Compounding | publisher= Food and Drug Administration |date= 2012-12-03 | access-date=2012-12-19 | archive-url=https://web.archive.org/web/20150107131013/http://www.fda.gov/forconsumers/consumerupdates/ucm107836.htm | archive-date=January 7, 2015}}</ref> The head of the FDA has recently requested the following authority from Congress:<ref>[http://docs.house.gov/meetings/IF/IF02/20130416/100668/HHRG-113-IF02-Wstate-HamburgM-20130416.pdf A Continuing Investigation into the Fungal Meningitis Outbreak and Whether It Could Have Been Prevented]. Statement of Margraret A. Hamburg, M.D., Commissioner of Food and Drugs, April 16, 2013.</ref>

Various ideas have been proposed to expand federal US regulation in this area, including laws making it easier to identify misuse or misnomered-use<ref>[https://web.archive.org/web/20130113034157/http://articles.baltimoresun.com/2012-11-14/health/bs-hs-meningitis-hearing-20121114_1_meningitis-outbreak-massachusetts-facility-pharmacies Pikesville man joins push for drug oversight reform after meningitis outbreak – Baltimore Sun]. Articles.baltimoresun.com (2012-11-14). Retrieved on 2013-05-13.</ref> and/or stricter enforcement of the longstanding distinction between ''compounding'' versus ''manufacturing''.<ref>Morin, Monte. (2013-04-16) [https://www.latimes.com/news/science/sciencenow/la-sci-sn-fda-chief-vows-to-get-aggressive-with-compounding-pharmacies-20130416,0,2370769.story FDA chief vows to get 'aggressive' with compounding pharmacies]. latimes.com. Retrieved on 2013-05-13.</ref><ref>[http://www.mjlr.org/2013/03/compounding-reform-reconsidering-the-draft-safe-drug-compounding-act-of-2007-in-light-of-the-ongoing-fungal-meningitis-outbreak/ Michigan Journal of Law Reform » Compounding Reform: Reconsidering the Draft Safe Drug Compounding Act of 2007 in Light of the Ongoing Fungal Meningitis Outbreak]. Mjlr.org (2013-03-17). Retrieved on 2013-05-13.</ref> Some US states have also taken initiatives to strengthen oversight of compounding pharmacies.<ref>[http://cidreview.cidmcorp.com/1864/workers-comp/proposed-legislative-reforms-addressing-compounded-drugs/ Proposed Legislative Reforms Addressing Compounded Drugs] {{webarchive|url=https://web.archive.org/web/20130512060933/http://cidreview.cidmcorp.com/1864/workers-comp/proposed-legislative-reforms-addressing-compounded-drugs/ |date=2013-05-12 }}. cidreview.cidmcorp.com</ref> A major source of opposition to new Food and Drug Administration regulation on compounding is makers of [[dietary supplement]]s.<ref>Barrett, Paul M. (2012-11-14) [https://web.archive.org/web/20121116154508/http://www.businessweek.com/articles/2012-11-14/americas-shadow-pharmacies America's Shadow Pharmacies]. Businessweek. Retrieved on 2013-05-13.</ref>

== See also ==

* [[Apothecary]] —- the ancestral practitioner of compounding, and histheir shop

* [[New England Compounding Center meningitis outbreak]]