The drug quality and Security Act (DQSA) was established in 2013 in response to contaminated steroid injections intended for intrathecal use that had caused a fungal meningitis outbreak.

The outbreak infected a confirmed 753 individuals and led to the deaths of 64.

 The contaminated steroid injections were manufactured by the New England Compounding Center. Title I of the DQSA, the Compounding Quality Act, amends the Federal Food, Drug, and Cosmetic Act regarding the compounding of drug products. Out of this amendment, section 503B was born.

503B outsourcing facilities can produce large batches of medication for distribution to clinics, doctor’s offices, and health care centers, with or without prescriptions, whereas 503A pharmacies produce limited amounts of anticipatory compounding and patient-specific medication. 503B facilities are subject to stricter regulations than traditional 503A compounding pharmacies. Registration with the Drug Enforcement Administration, the FDA, and state boards of pharmacy is a requirement for 503B outsourcing facilities, as well as compliance with United States Pharmacopeia (USP) general chapters <795>, <797>, and current Good Manufacturing Practices (cGMP) (21 Code of Federal Regulations, Parts 210 & 211).

503B facilities are also subject to inspection by the FDA. cGMP regulations define the minimum requirements needed during the processing, testing, packaging, and distributing of drug products.

 To comply with cGMP, facilities establish a quality system, which provides the structure to ensure the quality and safety of products.

An important aspect of a quality system is an independent quality unit that is responsible for creating procedures, investigating deviations, reviewing records, and ultimately approving and releasing, or rejecting, compounded products (see Figure).

A quality system is a checks and balances system in which the quality unit oversees all aspects of a 503B outsourcing facility, from incoming raw materials to the release
of the final product. In addition to having an independent quality unit, there are many other critical aspects to a quality system in a 503B facility, including standard operating procedures (SOPs), which provide clear, consistent instructions for performing tasks.

503B facilities are required to have SOPs for compounding drug products and executing the myriad other activities performed under the quality system. SOPs eliminate or reduce ambiguity in the facility’s processes and are a key tool in training personnel.

Releasing raw materials and supplies confirms the identity and quality of raw materials used in the drug compounding processes. Samples are taken of raw materials and tested to ensure that they meet predetermined specifications prior to use. Certificates of analysis are obtained for each lot of components and raw materials to ensure they meet quality standards and specifications. Environmental monitoring of air cleanliness standards exists in 503B facilities such that facilities are designed in a manner that minimizes the level of contaminants, thereby preventing microbiological contamination of drug products.

Regular testing of the environment is required for ensuring the cleanliness of drug compounding areas. International Organization for Standardization (ISO) 5 areas are tested minimally each production shift, whereas ISO 7 or 8 areas must be tested at least weekly to ensure that the requirements of air cleanliness are being met.

Training programs at 503B compounding facilities need to encompass training in regulations and standards, such as cGMP and USP <797>, in addition to job-specific training in aseptic technique and garbing, among others. Various methods, such as proficiency evaluations and written exams, are used to ensure that personnel are qualified to perform their job functions.

Validation is the collection and evaluation of data that establishes scientific evidence that a desired result with predetermined criteria will be achieved each time. Process validation significantly contributes to ensuring drug quality. Each step of the drug compounding process is controlled so that the finished product meets its quality attributes and specifications. Test method validation ensures that tests comply with USP standards. All product batches are thoroughly tested using validated methods prior to being released for use.

A high degree of accuracy is needed in drug compounding. Equipment used in a 503B facility must be calibrated regularly to ensure exact measurements. In addition, a preventive maintenance program keeps equipment operating optimally. Supplier qualification suppliers of goods and services are vetted and approved prior to the purchase of their products. The qualification process is a means of ensuring that the supplier can provide consistent quality components, packaging, materials, packaging, and services in compliance with regulatory requirements.

Summary 503B outsourcing facilities came about as a result of the DQSA. The establishment of section 503B allows health care centers to obtain sterile drug products produced with high levels of compliance and quality. Because 503B facilities operate on a larger scale compared with 503A traditional compounding pharmacies, they are mandated to follow cGMP regulations. 503B facilities play a key role in health care because of their bulk production, stringent quality standards, and wide distribution. They fill a gap between 503A pharmaceutical manufacturers and pharmacies, and ensure that the public has access to effective and safe medications.

, is director of research quality
and compliance at the University of Rochester Medical Center in New York.

1. Goldman TR. Regulating compounding pharmacies. HealthAffairs. May 1, 2014. Accessed October 31, 20219. http://healthaffairs.org/healthpolicybriefs/brief_pdfs/healthpolicybrief_114.pdf

2. Multistate outbreak of fungal meningitis and other infections – case count. October 30, 2015. Updated May 9, 2019. Accessed October 31, 2021. CDC. https://www.cdc.gov/hai/outbreaks/ meningitis-map-large.html

3. Drug Quality and Security Act, HR 3204, 113th Cong, 1st Sess, §102 (2013).

4. Food and Drugs. 21 CFR §210-§211 (1978).

5. Quality systems approach to pharmaceutical current good manufacturing regulations. FDA. October 2006. Updated April 16, 2020. Accessed October 31, 2021. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/ quality-systems-approach-pharmaceutical-current-good-manufacturing-practice-regulations

Articles

Facilities play key role in health care because of their bulk production, stringent quality standards and wide distribution.

503B Has Genesis in Food, Drug, and Cosmetic Act

Cellulitis develops because of pathogen entry through breaks in the skin barrier and can range from mild to severe, depending on the extent of skin layer involvement.

The condition is most common in older patients with fragile skin or patients with impaired local host defenses, such as diabetes, obesity, or venous insufficiency or lymphedema.

 In the United States, cellulitis diagnosis leads to 2.3 million emergency department visits and accounts for 10% of infectious diseases–related hospitalizations annually.

Classic cellulitis signs and symptoms of skin inflammation include erythema, swelling, tenderness, and warmth. The skin surface often resembles an orange peel (peau d’orange) because of cutaneous edema. Systemic symptoms, including fever, hypotension, leukocytosis, and tachycardia, may also occur in some patients. Most cases involve the lower extremity and are unilateral. Most cases are also nonpurulent, with purulent cases having discharge or exudate, which may require drainage. The most common pathogen is group A streptococcus (Strep- tococcus pyogenes), with Staphylococcus aureus being less likely.

 Although the majority of cases are nonculturable, results of studies have shown a steady increase in the rates of methicillin-resistant S aureus purulent cellulitis in the United States.

 The duration of treatment of cellulitis is not standardized, with guidelines from the Infectious Diseases Society of America (IDSA) recommending a 5-day course in uncomplicated cases and recent literature supporting shorter durations.

Shorter duration of treatment for a variety of infections, including cellulitis, has been a focus of recent studies aiming to reduce antibiotic consumption and decrease the emergence of antimicrobial resistance.

 In the recently published clinical guideline from the American College of Physicians (ACP), shorter durations are recommended for cellulitis, chronic obstructive pulmonary disease exacerbations, community-acquired pneumonia, and urinary tract infections. For uncomplicated nonpurulent cellulitis, the ACP guideline recommends 5 to 6 days with an agent active against streptococci species.

 Skin infection guidelines from IDSA and the National Institute for Health and Care Excellence in England recommend a duration of 5 to 7 days, highlighting an opportunity for shorter courses in some situations.

Supporting evidence for shorter durations is evident in findings from several trials. Results from a 2004 study showed no difference in clinical outcomes among mostly outpatient adults with uncomplicated cellulitis (n =87) randomized to oral levofloxacin for 5 vs 10 days.

 Clinical success at days 14 and 28 was demonstrated in both groups (98% success rate). Uncomplicated cellulitis was defined as the absence of bacteremia, animal or human bite–associated; deeper infection; diabetic foot infection with vascular insufficiency; immunocompromised status; sepsis; or severe renal dysfunction. A decade later, 2 randomized controlled trials evaluated tedizolid (6 days) and linezolid (10 days) in patients 12 years and older with acute bacterial skin and skin structure infections (ABSSSI), and approximately half the total study population of both ESTABLISH-1 and ESTABLISH-2 (NCT01170221, NCT01421511; n=1333 combined) had a diagnosis of cellulitis.

 Exclusion criteria were similar to the previous trials and included hospitalized patients, thereby providing evidence for patients with potentially more serious infections. In the subset of patients with cellulitis, there was no statistical difference in the early clinical response end point at 48 to 72 hours, a new FDA ABSSSI clinical trial outcome requirement (79%- 85% success rate across both studies).

 A posttreatment assessment at 7 to 14 days following the end of therapy demonstrated few relapses (85%-88% success rate across both studies).

Evidence continues to be scarce to inform the optimal duration of therapy in hospitalized patients with cellulitis. To address this, the controlled, multicenter, randomized DANCE trial (NCT02032654) investigated flucloxacillin intravenous (IV), with an option for oral step-down, for 6 (n=74) vs 12 (n=77) days in hospitalized patients with cellulitis or erysipelas.

 The primary outcome was clinical cure by day 14 without relapse by day 28 in the intent-to-treat population. Secondary outcomes included a 90-day relapse rate. Demographics included a mean age of 62 years, a high proportion of patients with diabetes and obesity (body mass index, ≥30 kg/m2), and higher severity of disease defined by a visual scoring system used in the 2004 study above, plus C-reactive protein and erythema measurements. Patients were included and randomized if they were improving on flucloxacillin IV and were afebrile and not bacteremic. Notable exclusion criteria were having a β-lactam allergy, a diabetic foot infection, receipt of prior antimicrobials, or other concurrent infections. Primary outcomes were similar between the 6-day and 12-day groups (50% vs 49%); however, investigators observed a higher 90-day relapse in the 6-day group than in the 12-day group (8 of 34 [24%] vs 2 of 35 [6%]). The study was interrupted early because of the inability to reach the target study sample size (n =158 per group, assuming an 85% cure rate); therefore noninferiority could not be ascertained as the study was underpowered. The authors concluded that hospitalized patients with severe cellu- litis may experience a higher-than-normal rate of recurrence, prompting the need for a longer treatment course.

Shorter courses of therapy of 5 to 6 days should be considered for patients without risk factors for complications, such as those with diabetes with vascular insufficiency, renal dysfunction, or sepsis or sepsis shock, or those who are immunocompromised. Treatment for cellulitis should primarily cover group A streptococci. Larger controlled, randomized trials are needed to optimize the duration of therapy for severe cellulitis or patients with complicating risk factors.

is senior manager of pharmacy education and training at Cleveland Clinic Abu Dhabi in the United Arab Emirates.

is an associate professor at Sullivan University College of Pharmacy and Health Sciences in Louisville, Kentucky.

Stevens DL, Bisno AL, Chambers HF, et al; Infectious Diseases Society of America. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis. 2014;59(2):e10-52. doi:10.1093/cid/ciu444

Khachatryan A, Patel D, Stephens J, Johnson K, Patel A, Talan D. Skin and skin structure infections (SSSIs) in the emergency department (ED): who gets admitted? Society for Academic Medicine. Accessed September 12, 2021. http://content.stockpr.com/duratatherapeutics/db/ Publications/2774/file/5-6e_SAEM_Poster.pdf

Christensen KLY, Holman RC, Steiner CA, Sejvar JJ, Stoll BJ, Schonberger LB. Infectious disease hospitalizations in the United States. Clin Infect Dis. 2009;49(7):1025-1035. doi:10.1086/605562

Moran GJ, Krishnadasan A, Gorwitz RJ, et al; EMERGEncy ID Net Study Group. Methicillin-resistant S aureus infections among patients in the emergency department. N Engl J Med. 2006;355(7):666-674. doi:10.1056/NEJMoa055356

Hepburn MJ, Dooley DP, Skidmore PJ, Ellis MW, Starnes WF, Hasewinkle WC. Comparison of short-course (5 days) and standard (10 days) treatment for uncomplicated cellulitis. Arch Intern Med. 2004;164(15):1669-1774. doi:10.1001/archinte.164.15.1669

Joseph WS, Culshaw D, Anuskiewicz S, De Anda C, Prokocimer P. Tedizolid and linezolid for treatment of acute bacterial skin and skin structure infections of the lower extremity versus non-lower-extremity infections: pooled analysis of two phase 3 trials. J Am Podiatr Med Assoc. 2017;107(4):264-271. doi:10.7547/15-218

Moran GJ, Fang E, Coey GR, Das AF, De Anda C, Prokocimer P. Tedizolid for 6 days versus linezolid for 10 days for acute bacterial skin and skin-structure infections (ESTABLISH-2): a randomised, double-blind, phase 3, non-inferiority trial. Lancet Infect Dis. 2014;14(8);696-705. doi:10.1016/S1473-3099(14)70737-6

Spellberg B, Rice LB. Duration of antibiotic therapy: shorter is better. Ann Intern Med. 2019;171(3):210-211. doi:10.7326/M19-1509

Lee RA, Centor RM, Humphrey LL, et al. Appropriate use of short-course antibiotics in common infections: best practice advice from the American College of Physicians. Ann Intern Med. 2021;174(6):822-827. doi:10.7326/M20-7355

Cellulitis and erysipelas: antimicrobial prescribing. National Institute for Health and Care Excellence. September 27, 2019. Accessed September 12, 2021. https://www.nice.org.uk/guidance/ ng141/resources/cellulitis-and-erysipelas-antimicrobial-prescribing-pdf-66141774778309

Cranendonk DR, Opmeer BC, van Agtmael MA, et al. Antibiotic treatment for 6 days versus 12 days in patients with severe cellulitis: a multicentre randomized, double-blind, placebo-controlled, non-inferiority trial. Clin Microbiol Infect. 2020;26(5):606-612. doi:10.1016/j.cmi.2019.09.019

Duration of therapy may be just 5 to 6 days for patients without risk factors for complications.

Long Story Short: Cellulitis Can Be Treated in Less Than a Week

Cancer in the prostate begins in the glands of the walnut-sized organ, which is found only in men. The prostate gland produces the seminal fluid that helps nourish and transport sperm. Prostate cancer is one of the most common types of cancer in the United States and the most common cancer diagnosed in men of all races, aside from nonmelanoma skin cancer.

In 2018, about 212,000 cases of prostate cancer were reported, and 31,000 of these patients died. However, when prostate cancer is discovered early and confined to the prostate gland, it is often treatable and the prognosis is positive.

Prostate cancer symptoms vary. There may be no signs or symptoms in the early stages of the disease, but more advanced stages may include blood in the semen or urine, decreased force in the urine stream, trouble urinating, and weight loss. The causes of prostate cancer are not entirely understood. It is thought, however, that the cells’ DNA changes and that they then divide more rapidly than they normally would.

Several risk factors are associated with prostate cancer occurrence. These include being Black, being older than 50 years, having a family history of prostate cancer, and being obese.

Complications from prostate cancer can include the cancer metastasizing to other parts of the body, such as the bladder, bones, and lymph nodes. Once metastasis
is advanced, the cancer can still be treated, although it becomes harder to cure. Erectile dysfunction can result either from prostate cancer itself or the treatments, such as hormone or radiation therapy and surgery. Prostate cancer can also cause incontinence, which for some patients improves over time but for others worsens. Treatment options for incontinence may include catheters, medication, and surgery.

Screening tools for prostate cancer include a digital rectal exam, magnetic resonance imaging, a prostate-specific antigen test, and an ultrasound. Treatment options include cryotherapy, heating prostate tissue, orchiectomy, and radiation therapy. The next option would be hormone therapy, which helps stops the body from making testosterone. Stopping testosterone helps stop the growth of cancer cells. Hormone therapy medications may include luteinizing hormone-releasing hormone (LHRH) or gonadotropin-releasing hormone (GnRH) agonists and antagonists, which prevent the body’s cells from receiving messages to make testosterone.

Other medications that block testosterone from reaching cancer cells include antiandrogens, which are sometimes given with LHRH agonists. LHRH drugs may include goserelin (Zoladex), histrelin (Vantas), leuprolide (Lupron), leuprolide mesylate (Camcevi), and triptorelin (Trelstar).

Androgen receptor blockers that are approved in the United States include first-generation drugs such as bicalutamide (Casodex), flutamide, and nilutamide (Nilandron), as well as second-generation ones including apalutamide (Erleada), darolutamide (Nubeqa), and enzalutamide (Xtandi).

 Chemotherapy options for prostate cancer include cabazitaxel (Jevtana), docetaxel (Taxotere), enzalut- amide (Xtandi), estramustine (Emcyt), and mitoxantrone (Novantrone).

Immunotherapy options include sipuleucel-T (Provenge), a cancer vaccine that can boost the immune system to help it attack prostate cancer cells.

 Pembrolizumab (Keytruda) is a drug that targets programmed cell death protein 1 and by blocking it boosts the immune response against prostate cancer cells. Pembrolizumab is given as an intra- venous infusion every 2 or 3 weeks. Rucaparib (Rubraca) is an inhibitor of poly (ADP-ribose) polymerase (PARP) enzymes, including PARP-1, PARP-2, and PARP-3, for the treatment of patients with deleterious BRCA mutation–associated metastatic castration-resistant prostate cancer. Similarly, olaparib (Lynparza) is another PARP inhibitor, given to patients with prostate cancer after orchiectomy. Relugolix (Orgovyx) is a GnRH receptor antagonist, indicated to treat advanced prostate cancer, and comes in 120-mg tablets.

Paying attention to prostate cancer and treating it as aggressively and early as possible is the key to surviving the disease. With the myriad medication options available, patients with prostate cancer have an increased chance of survival and having a better quality of life.

, is a vice president of pharmacy operations, population health management, and chronic health conditions in the Los Angeles, California, area.

1. Prostate cancer. Mayo Clinic. June 4, 2021. Accessed October 5, 2021. https://www.mayoc- linic.org/diseases-conditions/prostate-cancer/symptoms-causes/syc-20353087

2. Cancer statistics at a glance. CDC. June 2021. Accessed October 5, 2021. https://gis.cdc.gov/ Cancer/USCS/#/AtAGlance/

3. Hormone therapy for prostate cancer. National Cancer Institute. February 22, 2021. Accessed October 5, 2021. https://www.cancer.gov/types/prostate/ prostate-hormone-therapy-fact-sheet

4. Immunotherapy for prostate cancer. American Cancer Society. Updated August 1, 2019. Accessed October 5, 2021. https://www.cancer.org/cancer/prostate-cancer/treating/ vaccine-treatment.html

5. Rubraca. Prescribing information. Clovis Oncology Inc; 2021. Accessed October 5, 2021. https://clovisoncology.com/pdfs/RubracaUSPI.pdf

Oncology Focus

More medication options mean a greater chance for patients to survive and enjoy a better quality of life.

Prostate Cancer Requires Aggressive and Early Treatment

Medication nonadherence can cause many drug-related adverse effects (AEs), and pharmacists are in a prime position to use every patient interaction as an opportunity to address barriers, improve adherence, and increase the safe management of medications.

A common reason for nonadherence is complex medication regimens with multiple medications to treat multiple chronic disease states, posing a safety risk for patients. Complexity means patients can get confused, miss doses, or take them inappropriately. For example, in patients with diabetes and hypertension, overall adherence rates were within the range of 50% to 60%. The causes are so multifactorial that the World Health Organization (WHO) has broken down the reasons for patients not following the recommended treatment regimen into factors. These include economic and social factors, as well as those related to the health care system, the patient, the provider, and the therapy.

Briesacher et al examined adherence rates among patients with diabetes, gout, hypercholesterolemia, hypertension, hypothyroidism, osteoporosis, and seizure disorders and found that the rates varied from 36.8% to 72.3%.

 Yeaw et al evaluated adherence rates among patients on angiotensin II receptor blockers, bisphosphonates, oral antidiabetic medication, overactive bladder medication, prostaglandin analogues, and statins. After 12 months, adherence rates ranged from 35% to 72%.

The WHO said that, on average, adherence among individuals experiencing chronic disease was 50%.5 This nonadherence to prescribed therapy is estimated to generate at least 100,000 preventable deaths and $100 billion in preventable direct and indirect medical costs per year.

The Kaiser Family Foundation reported that nearly 1 in 4 Americans who takes prescription medications finds it challenging to afford them, and 29% of older adults said they did not take their medicines as prescribed because of the expense.

Pharmacists can help patients safely take their medications by addressing any barriers during each interaction with the patient. Patient-related barriers include cognitive impairment, cultural issues, denial, depression, and lack of health literacy and motivation.1 Treatment-related barriers include complexity of treatment, cost, fear of AEs, inconvenience, and time.

 Others include an asymptomatic disease being treated or an inadequate patient-practitioner relationship.

Pharmacist and team-based or coordinated care interventions have been shown to improve medication adherence rates and patient safety. Neiman et al reported that patients assigned to team-based care, including collaborative care between a cardiologist or primary care provider and a pharmacist; pharmacist-led medication reconciliation and tailoring; pharmacist-led patient education; and 2 types of voice messaging (educational and medication refill reminder calls), were significantly more adherent with their medication regimen 12 months after hospital discharge (89%) than patients not receiving team-based care (74%). Patients reported that team-based care improved their comfort in asking clarifying questions, raising concerns about their medication regimen, and collaborating to develop their treatment plan.

Countless low-tech strategies for improving adherence have been demonstrated to be helpful in studies that are typically of short duration. Such strategies include bundling medication refills together so patients can pick up all medications at the same time, clarifying medication ingestion schedules, discussing the value of medications with patients, prescribing less expensive equivalent or generic medications, telephone outreach, and verifying adherence by checking blood levels. In some disease populations, including patients with AIDS or tuberculosis, pharmacists have used email, telephone calls, and text messaging. When promoting adherence to antiretroviral therapy, birth control, and prenatal vitamins, some pharmacists have also used e-cards and text messaging.

Close to 50 companies are developing technology to help patients with medication adherence, with many addressing patient safety. Some are placing ingestible sensors in pills. Other examples include alarms to remind patients when a scheduled medication should be taken and bottles with wireless technology to track the number of pills ingested. Notably, many of these solutions to nonadherence require the transmission of data about the patient’s medication use to 1 or more third parties. These include caregivers, family members, and health care professionals, who could then mediate in real time to help ensure that the patient takes the medication.

Technology allows patients to safely manage their medications with electronic reminders, which helps them play an essential part in their self-care and increases patient safety.

In addition, technology helps practitioners, who often lack detailed information about patients’ actual behaviors. For example, specific, sound adherence data can support practitioners’ efforts to explain why a medication failed to work as expected. Often, inpatients in skilled-nursing facilities or other environments, where medication distribution is complex and time-consuming, can no longer take medication on their own. In these instances, smart technology can be used to audit and track consumption, decreasing the number of health care professionals needed to monitor adherence.

Pharmacists play an essential role in promoting the safe handling of medications and decreasing nonadherence. They can use new strategies to improve adherence and medication safety, often with minimal investment, and new technology can help pave the way.

Kleinsinger F. The unmet challenge of medication nonadherence. Perm J. 2018; 22:18-033. doi:10.7812/TPP/18-033

Chaudri NA. Adherence to long-term therapies evidence for action. Ann Saudi Med. 2004;24(3):221-222. doi:10.5144/0256-4947.2004.221

Briesacher BA, Andrade SE, Fouayzi H, Chan A. Comparison of drug adherence rates among patients with seven different medical conditions. Pharmacotherapy. 2008;28(4):437-443. doi:10.1592/phco.28.4.437

Yeaw J, Benner JS, Walt JG, Sian S, Smith DB. Comparing adherence and persistence across 6 chronic medication classes. J Manag Care Pharm. 2009;15(9):728-740. doi:10.18553/jmcp.2009.15.9.728

Sorensen TD, Pestka DL, Brummel AR, Rehrauer DJ, Ekstrand MJ. Seeing the forest through the trees: improving adherence alone will not optimize medication use. J Manag Care Spec Pharm. 2016;22(5):598-604. doi:10.18553/jmcp.2016.22.5.598

Klein D. Medication non-adherence: a common and costly problem. PAN Foundation. June 2, 2020. Accessed October 28, 2021. https://www. panfoundation.org/medication-non-adherence/

Neiman AB, Ruppar T, Ho M, et al. CDC grand rounds: improving medication adherence for chronic disease management – innovations and opportunities. MMWR Morb Mortal Wkly Rep. 2017;66(45):1248-1251. doi:10.15585/mmwr.mm6645a2

McCormick JB, Green MJ, Shapiro D. Medication nonadherence:
there’s an app for that! Mayo Clin Proc. 2018;93(10):1346-1350. doi:10.1016/j.mayocp.2018.05.029

Choudhry NK, Krumme AA, Ercole PM, et al. Effect of reminder devices on medication adherence: the REMIND randomized clinical trial. JAMA Intern Med. 2017;177(5):624-631. doi:10.1001/jamainternmed.2016.9627

Safe Handling

Addressing barriers such as cognitive impairment, cultural issues, and denial can help patients avoid adverse effects.

Help Patients Safely Handle Medications to Improve Adherence

Aspirin's mechanism of action was identified in 1971 as inhibiting irreversible cyclooxygenase and reducing prostaglandin production.

In 2007, approximately 20% of American adults took aspirin every other day for heart health. In individuals who were aged 65 years or older, nearly 50% were taking the drug, according to the Agency for Healthcare Research and Quality.

Although a low-dose aspirin regimen became commonplace as a staple of cardiovascular health and medicine because of aspirin’s preventive properties, updated findings are challenging this long-standing practice.

For many years, it was recommended that prescribers start individuals at increased risk of heart disease or stroke on low-dose daily aspirin.

 However, new data show there can be more risk than benefit for certain groups.

Draft guidelines released by the US Preventive Services Task Force (USPSTF), which consists of a panel of experts in disease prevention and evidence-based medicine, assert that there is strong evidence to support the development of serious adverse effects from taking once- daily aspirin versus the potential benefits, especially in certain populations.

The possible harm in older individuals is believed to outweigh the potential benefits of what had been considered an inexpensive method in the battle against heart disease, according to the task force.

 The risk of life-threatening internal bleeding can increase from daily aspirin use with increasing age. Thus, if an individual does not present with the risk of heart attack or stroke, this regimen is now not recommended.

In addition, the USPSTF recommends that individuals 60 years or older who do not have a history of heart attack or stroke do not initiate aspirin therapy.

 The task force also plans to revise its 2016 recommendation on the use of baby aspirin as a preventive measure for colorectal cancer, given data that raise specific questions about its potential benefit for cancer.

As a result of the proposed changes to the guidance by the USPSTF, millions of Americans will be affected. Because heart disease is the leading cause of death in the United States, these draft recommendations indicate that patients, particularly those aged 40 to 59 years, should talk to their providers about whether to take aspirin.

The decision to initiate low-dose aspirin for the primary prevention of cardiovascular disease in patients aged 40 to 59 years who have a 10% or greater 10-year cardiovascular risk should be made on a case-by-case basis, because the benefit of daily aspirin in this group is small.

Those individuals aged 40 to 59 years who have a higher risk of cardiovascular disease but do not present with a history of the disease should discuss with their providers whether they need an aspirin regimen based on their circumstances.

 is a professor of health care administration at Columbia Southern University in Orange Beach, Alabama.

1. Ittaman SV, VanWormer JJ, Rezkalla SH. The role of aspirin in the prevention of cardiovascular disease. 

. 2014;12(3-4):147-154. doi:10.3121/cmr.2013.1197

2. Miner J, Hoffhines A. The discovery of aspirin’s antithrombotic effects. 

3. Chiu A. Americans should limit use of daily aspirin meant to prevent heart attack or stroke, task force says. 

 October 12, 2021. Accessed October 27, 2021. 

https://www.washingtonpost.com/lifestyle/2021/10/12/low-dose-aspirin-heart-attack-stroke/

4. Rabin RC. Aspirin use to prevent 1st heart attack or stroke should be curtailed, US panel says. 

https://www.nytimes.com/2021/10/12/health/aspirin-heart-attack-stroke.html

5. Maddipatla M. Aspirin use to prevent first heart attacks not recommended for most older adults-US panel. Reuters

https://www.reuters.com/business/healthcare-pharmaceuticals/aspirin-use-prevent-first-heart-attacks-not-recommended-most-older-adults-us-2021-10-12/

6. Tanner L. Advice shifting on aspirin use for preventing heart attacks. 

https://www.usnews.com/news/health-news/articles/2021-10-12/advice-shifting-on-aspirin-use-for-preventing-heart-attacks

7. Aspirin use to prevent cardiovascular disease: preventive medicine. US Preventive Services Task Force. October 12, 2021. Accessed October 27, 2021. 

https://www.uspreventiveservicestaskforce.org/uspstf/draft-recommendation/aspirin-use-to-prevent-cardiovascular-disease-preventive-medication

8. Howard J. US task force proposes adults 60 and older should not start daily aspirin to prevent heart disease or stroke. CNN Health

 Updated October 13, 2021. Accessed October 27, 2021. 

https://www.cnn.com/2021/10/12/health/daily-aspirin-heart-disease-stroke-draft-recommendation-wellness/index.html

Clinical Care Focus

New guidelines suggest older individuals should not start taking the drug for heart disease or stroke prevention.

Patients Should Use Caution When Taking Aspirin

will likely bring a continued focus on COVID-19’s substantial effect on prices and utilization of services.

In its annual report, health care services company Vizient predicts a 3.1% increase in total pharmaceutical spending in 2022. Oncology drugs will account for about 25% of the increase, with continued spending on pharmacotherapy related to COVID-19.

The sustained impact of COVID-19 on health care is due to the continuing emergence of disease variants coupled with vaccine hesitancy, according to Vizient.

The company also predicts that specialty pharmaceutical pricing will grow at a rate of 4.68% in 2022, driven by the likely approval of new therapies as well as price increases for adalimumab, a specialty drug used to treat autoimmune diseases.

Further, Vizient estimates that with recent endorsements from diabetes management guidelines and organizations the cost of influential diabetes agents such as glucagon-like peptide 1 and 2 and insulin, will increase by 2.63% next year. These novel diabetes drugs are gaining diverse indications beyond the management of blood glucose, such as for the prevention of cardiovascular events and other disease complications.

The report states that “when combined with the increasing prevalence of the disease, health systems are expected to see growing use of these products in their patient populations.”

The COVID-19 pandemic brought challenges that overwhelmed the health care system and required greater flexibility in cooperation and responsibilities from all essential health care providers, including pharmacists. In 2022, there will likely be continuing evolvement and expansion of the pharmacist’s role with their recognition as critical frontline workers in the fight against COVID-19. Additionally, pharmacists are extensively involved in education and research, while remaining active members of inpatient and outpatient COVID-19 recovery clinic multidisciplinary teams and vaccination efforts. Moreover, with the increased use of telehealth during the pandemic, health systems are investing more in digital innovation. Pharmacists are taking advantage of virtual postintensive care syndrome clinics, among others, to adjust medications and to counsel and educate patients. The results of a recent study show that in the beginning of 2020, 0.1% of Medicare primary care visits were conducted using telehealth, but this number increased to 43% within 3 months because of the pandemic.

 This growth is expected to continue, and some experts recommend that organizations start aligning their virtual strategies with the evolving needs.

Meanwhile, Amazon’s entry into pharmacy services may have a large impact in 2022. Consumers are so accustomed to using Amazon to order a whole slew of merchandise and it will be interesting to see how the prescription services landscape will be affected.

In 2022, organizations will continue to take a holistic approach to infusion care covering extended sites, including home infusion. Home infusion services had previously existed in health systems but some had stopped providing the service because of increased competition and payor rates. However, the pandemic led to more patients preferring to receive infusion therapy at home, leading to a heightened interest in providing these services.

Over the past decade, more than 500 health system and hospital mergers have occurred. An advantage of this partnership is the availability of large data sets that can guide health care delivery programs, prevention efforts, and wellness with wide-ranging medication management. The pursuit of medication errors prevention and quality improvement has led to a growing interest in artificial intelligence (AI) and precision medicine. An example of AI technology gaining traction in health care is machine learning, which focuses on the development and use of computer systems that can adapt and emulate without following explicit instructions. The systems use algorithms and statistical models to analyze and draw inferences from data patterns.

AI has been hailed as a transformational force in health care. In the past few years, the AI health market has experienced explosive growth, with investments worth billions of dollars, and in 2022, huge investments will likely continue to be made on the digital front. Health care is embracing AI for a range of applications, including clinical research, drug development, and robotic surgery. In addition, AI is being adopted as a practical tool to improve medication safety and patient outcomes, monitor medication adherence, reduce drug costs, replace labor-intensive and repetitive tasks that are prone to error, and streamline prior authorizations. These applications of AI will transform medication management. Thorough digestion and utilization of health care data are crucial, once the data analyses have been completed; equally important is knowing what to do based on the findings. Increasingly, real-time data assessment, models, and predictions are being used to help detect and prevent patient deterioration and manage health care crises. As data sets require the expertise and skills of data scientists, pharmacy departments will need to recruit these scientists to support predictive modeling to drive health care delivery. In 2022, AI will continue to be a priority and will have a positive and profound effect on the delivery of health care and medication management. On a similar front, genetics will continue to play a key role in personalized medication treatment to achieve the desired therapeutic effects.

Another growing trend that will continue to garner attention is the emphasis on gender inequity and sexual harassment in the pharmacy profession. In 2020, a petition titled End Gender Inequality in Clinical Pharmacy led to a response from several major pharmacy organizations. The petition advocates for gender equality, the development of policies against such behavior, and guidance and support for members of the profession who encounter gender bias, harassment, predatory conduct, or other intimidating or threatening behaviors. These organizations stand on values such as a culture that strongly supports diversity, equality, and inclusion. Major underpinning is required to promote gender equity more effectively within the profession, but this work is critical to ensuring future sustained infrastructure. Gender inequity and sexual harassment are widespread in the medical community, the pharmacy profession, and our society. All members of the pharmacy profession should have equal opportunity and support to reach their highest potential. However, major gaps in support of the diverse membership of the pharmacy profession have highlighted a lack of awareness of harassment resulting from gender and gender inequity issues. Fostering greater diversity in the workforce cultivates innovation, decreases health disparities, and improves communication, health care access, patient satisfaction, and problem solving for complex challenges.

 The potential benefits of gender equity are vast, including economic benefits, patient satisfaction, and the cultivation of diversity, innovation, and a unified profession. Women in pharmacy have started the discussion using online platforms and professional networks, but the drivers of continued change will be through organizational leadership and advocacy as well as through awareness by individual pharmacists.

In light of the pandemic’s challenges, the new year will see a continued focus on health care delivery through continued testing, vaccination, and treatment. Other important trends will include rising health care costs and an increase in digital health care. Moreover, it is hoped that progress will be made in addressing gender equity and sexual harassment in the pharmacy profession.

Deepali Dixit, PharmD, BCPS, BCCCP, FCCM, 

is a clinical associate professor at Ernest Mario School of Pharmacy at Rutgers, The State University of New Jersey in Piscataway, and a clinical pharmacy specialist in critical care at Robert Wood Johnson University Hospital in New Brunswick, New Jersey.

1. Pharmacy market outlook. Vizient. Accessed October 1, 2021. 

https:/info.vizientinc.com/pharmacy-market-outlook

2. Martin G. Top 10 emerging trends in health care for 2021: the new normal. AHA Trustee Services. Accessed October 1, 2021.https://trustees.aha.org/top-10-emerging-trends-health-care-2021-new-normal

3. Aungst TD, Franzese C, Kim Y. Digital health implications for clinical pharmacists services: a primer on the current landscape and future concerns. 

2021;4(4):514-524. doi.org/10.1002/jac5.1382

4. Institute of Medicine (US) Committee on the Robert Wood Johnson Foundation Initiative on the Future of Nursing, at the Institute of Medicine. 

The Future of Nursing: Leading Change, Advancing Health

5. Bissell BD, Johnston JP, Smith RR, et al. Gender inequity and sexual harassment in the pharmacy profession: evidence and call to action. 

 Published online July 7, 2021. doi:10.1093/ajhp/zxab275

Trends to watch include increased spending on drugs and treatments, expansion of pharmacists' role, and ongoing interest in home infusion therapy.

COVID-19 Impact Will Continue to Dominate in 2022

my colleague Sharyl Zaccaglino, MS, director of research quality and compliance at the University of Rochester Medical Center in New York, provides a succinct overview of the requirements of section 503B on outsourcing pharmacies.

Her summary is timely given that on October 7, 2021, the FDA published revised guidance titled “Hospital and Health System Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act” in the 

 When finalized, this guidance could have a significant effect on the number of health systems and hospitals providing pharmaceuticals for the care of patients within their facilities and may lead to increased reliance on 503B outsourcing pharmacies. Immediately after the release of this revised guidance, many were happy to learn that the absurd and arbitrary “1-mile rule” was dropped. However, we should be cautious in our celebration because other limitations are being introduced with this revision that, depending on interpretation, could greatly limit pharmacy practice.

Probably the single most important issue to understand with this guidance is the FDA’s definition of a compounded drug and how that may contrast with how local boards of pharmacy and pharmacy professionals interpret the term.

In the guidance, the FDA speaks about a compounded drug as a product used for patients “whose medical needs cannot be met by an FDA-approved drug product….” They go on to say that “compounded drugs are not FDA approved…” and that “…compounded drug products should only be used when an FDA-approved product is not available to meet the needs of an individual patient.”

In other words, a health system pharmacy that prepares an FDA-approved drug in accordance with its labeling and according to United States Pharmacopeia (USP) standards for stability, sterility, and storage is not preparing a compounded drug product and those activities should be outside the scope of the guidance. This guidance is specifically concerned with the preparation of drug products that are not FDA approved by a health system or hospital pharmacy that is not registered as a 503B outsourcing pharmacy for the treatment of patient-specific needs, as documented by a patient prescription or order.

Most pharmacists in health systems and hospitals refer to the preparation of nonsterile and sterile FDA-approved drugs as “compounding.” However, the FDA is quite clear in that this guidance is specifically concerned with the extemporaneous compounding of drug products that the agency has not approved. Of course, altering an FDA-approved drug to meet unique needs, such as using tablets to prepare an oral suspension, meets the definition of compounding under this guidance. We should interpret and apply this guidance, once finalized, according to its stated intent.

The document goes on to state that the FDA has limited enforcement resources and that it will be selective in its enforcement priorities according to criteria detailed in the document. This can also be interpreted as enforcement for compliance with 503A requirements for health systems and hospitals, which will remain primarily with local boards of pharmacy. It is reasonable to anticipate that this guidance will be adopted by the state boards and maybe even before it has been finalized by the FDA.

The challenge is that state boards of pharmacy may apply very different definitions of 

than is presumably intended by this guidance.

For example, in New York State, where I practice, our board defines 

as the “combining, admixing, mixing, diluting, pooling, reconstituting, or otherwise altering of a drug or bulk drug substance to create a drug.”

This has been broadly interpreted to mean that even adding water to an FDA-approved amoxicillin suspension consistent with the approved label is “compounding.” Under this draft guidance, this product reconstituted in a hospital pharmacy would need to be discarded after 24 hours, despite the FDA-approved label indicating that the drug is stable for at least 10 days.

More importantly, it is likely that the New York State Board of Pharmacy, and probably boards of pharmacy in many other states, will interpret any preparation of an FDA-approved drug product in a clean room as “compounding” under this guidance, which is arguably not the intent.

During the comment period, we should implore the FDA to clearly define what is meant by a compounded drug and ask that the intent of this guidance be limited to that category of drug products not approved by the agency. The preparation, storage, and distribution of FDA-approved drugs compliant with regulatory guidance and standards established by the FDA, Joint Commission, and USP should not be restricted further by this guidance.

The guidance is clearly intended to compel health systems to rely on 503B registered outsourcing pharmacies for most compounding needs, based upon the assumption that FDA-regulated pharmacies will lead to higher quality and patient safety. Ironically, all the examples cited in terms of patient safety issues were from outsourced pharmacy providers, not health system or hospital pharmacy providers.

As I have written previously in this column, outsourcing pharmacies have found a loophole in the federal regulations that allows them to compound products using bulk active pharmaceutical ingredients without an approved drug application. This is essentially creating a shadow pharmaceutical industry without the safeguards intended by the Food, Drug, and Cosmetic Act, which the FDA is responsible for upholding.

 In fact, it is becoming difficult to find outsourced products that are not compounded using active pharmaceutical ingredients, despite no shortage of FDA-approved drugs. I suspect this is being driven by profit at the potential expense of patient safety. For those of us who do not wish to partake in this quasi-legal pharmaceutical industry, a broad application of this guidance by local boards of pharmacy may force our hands. The good news is that if history is any indicator, it will likely take the FDA several years to finalize the guidance.

is the chief pharmacy officer for the University of Rochester health care system in New York.

Hospital and health system compounding under section 503A of the Federal Food, Drug, and Cosmetic Act. FDA. October 2021. Accessed October 28, 2021. https://www.federalregister.gov/ documents/2021/10/07/2021-21970/hospital-and-health-system-compounding-under-section-503a-of-the-federal-food-drug-and-cosmetic-act

Regulations of the Commissioner: part 63, pharmacy and registered pharmacy technicians. New York State Department of Education, Office of the Professions. U pdated April 13, 2021. Accessed October 28, 2021. http://www.op.nysed.gov/prof/pharm/part63.htm#6314

Haas CE. API sourcing: is this really a good idea? 

Pharmacy Times®. Directions in Health-System PharmacyTM

. November 17, 2019. Accessed October 28, 2021. https:// www.pharmacytimes.com/publications/health-system-edition/2019/November2019/ api-sourcing-is-this-really-a-good-idea

Agency's interpretation may significantly affect how health systems and hospitals provide pharmaceuticals to patients.