Rita Peters is the former editorial director of 

Pharmaceutical Technology, Pharmaceutical Technology Europe

Rita C. Peters

spoke with Anil Kane, executive director, global science and technology, pharmaceutical development services, at Thermo Fisher Scientific about the industry’s need for more capacity in the manufacture of highly potent APIs (HPAPIs) and how contract development and manufacturing companies (CDMOs) can ensure they are developing and manufacturing HPAPIs safely.

 In your presentation at CPhI North America 2019, one of the questions from the audience was about capacity challenges for HPAPIs. Can you talk a little bit about that?

 The question that came up from the talk was about capacity and having access to contained equipment, facilities, and infrastructure in the industry to support manufacturing. In my opinion, there is capacity [for development-scale and commercial-scale], but of course the infrastructure is limited, so it’s all about planning and scheduling. The contained pieces of equipment infrastructure to handle highly potent compounds is not available at many places. There are a few CDMOs that can offer a wide spectrum of contained process trains for manufacturing drug products. At Thermo Fisher, we have continued to monitor the demand for HP compounds both on the API side and the drug product side and are planning ahead to invest into contained equipment to be able to support the pharmaceutical industry.

	If clients see the need to handle a specific compound in a certain contained manner, it is good to talk early [and] plan ahead, simply because some of the newer investment and contained equipment also has a long lead time. So, even if we start discussing the need, there is a lead time for the manufacturer/vendor to make this equipment and then to qualify and bring it up and running for the actual use for manufacturing. Again, this is beyond the existing equipment infrastructure and capacity, if there is a special need. There is always the possibility to discuss in partnering on investment, co-investment, and different business models that have been successful within Thermo Fisher, and I’m sure elsewhere as well. The point being [is to plan] ahead and make sure we have the right capacity at the right time, because no customer will like to wait or has the time to wait for 6, 9, 12, or in some cases 18 months to have the infrastructure up and ready, the same with equipment, whether its small scale or commercial scale.

	For commercial scale, I would say there is always that time for planning, but for early phase, speed is of the essence to confirm proof of concept and proof of efficacy where only clinical results are key to understand the potential that a molecule has to offer.

Has Thermo had some recent expansions in this area?

 Yes, absolutely. In the oral solids area, where the risk of containment of HP products is higher, we have continued to invest in the infrastructure like contained process trains (e.g., contained encapsulators, contained tablet presses, contained roller compactors, etc.). In the past two to five years, we have continued to invest at several of our facilities across the network. We have also seen an increase in highly potent compounds on the injectables side; however, on the injectables side, the risk is rather less because it is in a liquid format and everything is sterile and contained, so the challenges are less in terms of having multiple process trains in injectables.

 Are these equipment installations new technology to handle HP or are you adapting existing?

 It’s more adapting the existing equipment to have contained solutions to prevent the exposure to personnel operators. It takes a little more time to set up this equipment because the access to such equipment is limited to the purpose they are built, but they do provide protection to the operator from a HPAPI handling perspective.

 Do you see any emerging technologies or automation to further separate the person from the process?

 Oh absolutely. Continuous manufacturing is a great solution; however, this comes into interest for the pharmaceutical industry later in the development chain or beyond clinical proof of concept. In continuous processing, everything is a closed loop. There is no operator intervention or a break in the process. There is no potential for exposure between multiple unit processes, so that is one solution. However, there are limitations. Not every product or process can be manufactured under continuous processing based on the stage of the project, the type of the project, etc. The other solution we have adopted for several years now for HPAPIs is vacuum transfer systems between unit processes. This is not new, but not very common as well because it takes time to qualify and validate such processes where you have a continuous transfer between the unit batch process equipment, and this then prevents any intervention by the operator or potential for exposure. The material characterization and properties, the process needs to be developed and validated to suit such vacuum transfers to ensure product quality, but such development work can be planned and done up front. Softgel dosage form is another drug delivery solution for HPAPIs, and we at Thermo Fisher have had success in containment of potent solids in switching from oral solid dosage forms to a softgel.

Supplement: Outsourcing Resources
	August 2019
	Pages: s9

	When referring to this article, please cite it as R. Peters “Ensuring Manufacturing of HPAPIs Under Safe Conditions," 

Pharmaceutical Technology Outsourcing Resources

Articles

Pharmaceutical Technology spoke with Anil Kane, executive director, global science and technology, pharmaceutical development services, at Thermo Fisher Scientific about the industry’s need for more capacity in the manufacture of highly potent APIs.

Ensuring Manufacturing of HPAPIs Under Safe Conditions

	The May 2019 approval of Zolgensma, a gene therapy to treat spinal muscular atrophy, by FDA’s Center for Biologics Evaluation and Research was marked by sticker shock: a $2.1-million price tag for the drug, making it the most expensive drug approved to date (1). Patient-advocates noted the curative nature of the therapy was worth the price, and the drug company offered a phased-payment approach. Proponents cited it as another example of the high costs of drugs (2).

		Meanwhile, a bipartisan effort by the Senate Health, Education, Labor and Pensions (HELP) committee has led to a contentious debate between FDA and standards-setting organization, the US Pharmacopeial Convention (USP). The committee voted 20–3 on June 26, 2019 to advance legislation designed to lower healthcare and drug costs; proposals include changes to patent policy, ending “surprises” in medical bills, increasing transparency in healthcare, and reducing roadblocks that delay generic drugs and biosimilars getting to market (3).

		For example, Section 208 of the proposed legislation changes existing regulations so drug manufacturers cannot receive new chemical entity exclusivity for making small changes to existing drugs.

		It is provisions in Section 207, how- ever-designated as promoting biological drug innovation-that are proving controversial, pitting FDA and USP in an exchange of policy statements. Ac- cording to HELP committee documents, Section207isintendedtopreventde- lays in the licensure of biosimilar and interchangeable products by excluding biological products subject to regulation under the Public Health Service

compendial standards. A similar provision to make bio- logics exempt from meeting USP standards was removed from the final 21st Century Cures Act of 2016 (4).

		“A biological product is so inherently complex and variable that the established structure of the 

monograph standards process does not serve it well, and in fact, can impede technological progress or innovation,” noted Steven Kiozlowski, director of the Office of Bio- technology Products in FDA’s Office of Pharmaceutical Quality in an interview published by FDA (5).

		Due to the inherent differences in bio- logical products, the “sameness” standard used in 

monographs for chemical- based drugs cannot apply to biologic drugs, FDA argues.

		USP, backed by patient groups and pharmacists, argues that the elimination of required standards would harm patients. In a letter to the committee, USP noted the role standards play in providing quality benchmarks; supply chain security; reliability and predict- ability for drug product development, manufacturing, and distribution; and promote transparency and accountability that leads to patient trust (6).

		“Essential to the framework that safeguards the quality and safety of medicines in the United States is the principle that public quality standards, required under the law, establish and articulate quality expectations for medicines, including biologics,” USP noted in the letter.

		FDA has no legal authority to control the price of drugs. However, the agency notes it is “committed to facilitating increased competition in the market for prescription drugs through the approval of lower-cost, generic medicines” and “makes sure that safe and effective drugs are available to improve the health of consumers” (7).

		That’s a lot of priorities to balance in today’s partisan environment.

		1. R. Stein, “At $2.1 Million, New Gene Therapy Is the Most Expensive Drug Ever,” 

, May 24, 2019.
		2. Novartis, “AveXis Announces Innovative Zolgensma Gene Therapy Access Programs for US Payers and Families,” Press Release, May 24, 2019.
		3. S. 1895, US Senate, 116th Congress, 1st Session (Washington, DC).
		4. J. Wechsler, “

FDA Challenges USP Standards for Biologics

CDER Conversation: Ensuring That Standardization Does Not Impede Biological Product Innovation

		When referring to this article, please cite it as R. Peters, “A Biologics Partisan Divide," 

FDA and USP take sides in debate on biologic drug standards. 

A Biologics Partisan Divide

	As schools in the United States close for the summer break, student grades serve as a measure of how well teachers shared knowledge, how well students understood and retained that information, and how the school, as a whole, performed this year.

	FDA recently issued a report card of the bio/pharma industry’s manufacturing quality performance, which provided insight on how well manufacturers and regulatory authorities executed their responsibilities, and lessons learned for future improvements.

	The Report on the State of Pharmaceutical Quality (1), issued in May 2019 by the Office of Pharmaceutical Quality in FDA, Center for Drug Evaluation and Research, assessed the ability of pharmaceutical manufacturers to deliver quality pharmaceutical products to the US market during fiscal year 2018. The report analyzed product recalls, quality defect reports, drug shortages, and application state (e.g., submissions, approvals, refuse-to-file, refuse-to-receive, and complete response letters) as a basis for its analysis.

	The report examined manufacturing site data by geographic region, therapeutic category, application type, and manufacturing sector. FDA issues a site inspection score-on a scale of 1 to 10 with a higher number indicating greater compliance with current good manufacturing practices-based on FDA quality inspections over the past 10 years.

	The number of sites in FDA’s site catalog-4676 at the end of FY2018-needs some clarification. Of the total sites in the catalog, 42% manufacture “no application” products, such as over-the-counter products, monograph, unapproved, or homeopathic products. The remaining 58% of sites manufacture application drug products (e.g., new drug application [NDA], abbreviated new drug applications [ANDA], biologic license application, etc.) and nearly half (46%) of these sites manufacture both NDA and ANDA products.

	The report noted “volatility” in the site catalog in the past year; the agency removed from the catalog “a large number” of sites in India, China, and South Korea in FY2018 because they did not make products for the US market and, therefore, did not have to be registered with FDA. The need to purge manufacturing sites from the list indicates “a lack of understanding of the registration and listing requirements,” FDA noted in the report.

	The data also show shifts in the types of site registrations. FDA reported a 32.8% net increase in the number of packaging and labeling sites-suggesting an increase in outsourcing of these functions. In addition, there was a 29.7% net increase in the number of “no application” sites and a net loss in the number of NDA sites.

	Less than 40% of the drugs for the US market are manufactured in the US; India (12%) and China (11%) are the two largest offshore suppliers. FDA also noted that a small number of sites manufacture a large number of listed products; the number of products manufactured at a site is a risk factor used in prioritizing the need for surveillance inspections. In the US, three sites-two of which make homeopathic products-account for 9.5% of all products listed by all US sites. The number of listed products manufactured by the top three sites in China (11.2%) and India (12%) are even higher.

	In FY2018, FDA conducted 1346 drug quality inspections, covering less than one-third of sites in its catalog; more than half of the inspections were outside the US. The average inspection score of 7.5 for FY2018 was down slightly from FY2017 (7.7). Sites in the European Union (7.9) and the US (7.7) scored higher than average; sites in China (7.0), India (7.0), and the rest of the world (7.2) were lower than average. Statistical differences were also noted in application areas, with sterile non-application products as one of the lowest performing.

	FDA noted “… some trends highlight opportunities for increased outreach to, surveillance of, and enforcement of certain markets,” indicating that for regulated drug manufacturing, school is never out.

Report on the State of Pharmaceutical Quality

	When referring to this article, please cite it as R. Peters, “Pharma Facilities Still Have a Lot to Learn,” 

FDA’s annual manufacturing report card shows more quality compliance is needed.

Pharma Facilities Still Have a Lot to Learn

	The reputation of the pharmaceutical industry has taken a number of hits in recent years, with most negativity a result of its own creation. Recent news stories have not done much to encourage optimism.

	For example, recalls of angiotensin II receptor blocker (ARB) drug products-triggered by the identification of a suspected carcinogen in the widely used blood pressure medication-continued. To help clarify the status of drugs in the class, FDA developed a list that reports the results of the agency’s testing for the presence of nitrosamine and indicates those drugs that are still to be tested (1).

	Perhaps the two most egregious issues in the eyes of patients, policymakers, and the public, however, are high drug prices and the opioid epidemic.

	The discourse about the high cost of drugs in recent years can be characterized as a low simmer, with occasional outbursts from elected officials, a lot of finger pointing, and little progress. The topic should erupt to a fever pitch in the coming months as the 2020 presidential election gains steam.

	Finger pointing has also been the response from various sectors of the healthcare and pharma industries in response to the opioid crisis. Recent media attention upped the scrutiny of business practices of companies manufacturing and distributing the drugs. For example, a recent article detailed how drug distributors had previously been cited and fined for lax monitoring of suspicious orders or circumventing guidelines (2).

	Although civil lawsuits have been filed in multiple states, the first criminal charges related to improper opioid distribution were filed in late April 2019 against executives at a New York drug distributor. The US Attorney’s office charged two executives at the Rochester Drug Cooperative with unlawfully distributing oxycodone and fentanyl and conspiring to defraud the Drug Enforcement Administration (3). Time will tell if criminal penalties will be more a deterrence than previous civil fines.

	There is some promising news in the fight to eradicate or reduce the effects of malaria, one of the world’s oldest and deadliest diseases. The World Health Organization reported 219 million cases and 435,000 deaths worldwide in 2017, with no significant progress in reducing the number of cases in 2015–2017 (4).

	World Malaria Day (April 25, 2019) was marked with the launch of a pilot program in Malawi of the first malaria vaccine for children up to two years old. The RTS,S vaccine, in development for 30 years, was demonstrated in clinical trials to prevent approximately 4 in 10 malaria cases, including 3 in 10 cases of life-threatening severe malaria, WHO reports. The pilot program will be extended to Ghana and Kenya in coming weeks (5). GlaxoSmithKline will donate up to 10 million vaccine doses for the pilot (6).

	Another recent therapy, Krintafel (tafenoquine) was approved by FDA in July 2018 as the first new treatment for 

) malaria in more than 60 years. Developed by GlaxoSmithKline in collaboration with Medicines for Malaria Venture, the drug was approved for the radical cure (prevention of relapse) of 

 malaria in patients aged 16 years and older who are receiving appropriate antimalarial therapy for acute P. vivax infection (7).

FDA’s Assessment of Currently Marketed ARB Drug Products

, accessed April 22, 2019.
	2.  D. Hakim, W. K. Rashbaum, R. C. Rabin, “The Giants at the Heart of the Opioid Crisis,” 

, April 22, 2019.
	3. US Dept. of Justice, “Manhattan U.S. Attorney and DEA Announce Charges Against Rochester Drug Co-Operative and Two Executives for Unlawfully Distributing Controlled Substances,” Press Release, April 23, 2019.
	4. WHO, 

, November 2018.
	5. WHO, “Malaria Vaccine Pilot Launched in Malawi,” Press Release, April 23, 2019.|
	6. GSK, “Fighting Malaria in the Lab and on the Ground,” 

, April 18, 2019.
	7. GSK, “US FDA Approves Krintafel (tafenoquine) for the Radical Cure of 

 Malaria,” Press Release, July 20, 2018.

	When referring to this article, please cite it as R. Peters, “Working for the Greater Good,” 

Pharma delivers a positive message with renewed efforts to eradicate malaria.

Working for the Greater Good

The threats posed by counterfeit drug products entering the healthcare system and reaching patients have been well documented. The World Health Organization estimates that 1 in 10 medical products in low- and middle-income countries is substandard or falsified (1). A report based on 2013 data identified prescription drugs as the leading type of counterfeited products worldwide, exceeding fraudulent sales of electronics, food, auto parts, toys, clothing, and shoes (2).

	Chances are, the inexpensive handbag or watch sold by a street vendor is not the authentic brand product; however, a knock-off fashion accessory will not cause the buyer physical harm. Substandard or falsified drugs can have serious health implications for patients, especially when fake drugs look like the real thing.

	Regulators routinely warn consumers against buying drugs from unknown sources and have worked to shut down fraudulent online pharmacies. The Falsified Medicines Directive introduced by the European Commission and the Drug Supply Chain Security Act in the United States set standards for product identification and traceability for finished prescription drug products. Drug companies and contract manufacturers have made significant investments in packaging, labeling, software, and electronic monitoring systems to track drug packages throughout the supply chain. Materials such as edible taggants are proposed as options to track the drug product itself.

	While these anticounterfeiting efforts are directed at the final drug product, bio/pharma companies must be vigilant for fraudulent or substandard materials at the other end of the supply chain: the raw materials used to make the drug.

	Contaminated or substandard ingredients pose serious safety threats. Two examples, one from more than a decade ago and one that is ongoing, illustrate the vulnerability of the raw materials supply chain, shortcomings in quality control processes at drug companies, good manufacturing practice failures, flaws in regulatory oversight, and the need for improved test methods.

	Following reports in 2007 and 2008 of adverse reactions, including deaths, to the commonly prescribed blood thinner heparin, an investigation revealed that the patients received contaminated doses of the drug containing over-sulfated chondroitin sulfate (OSCS), an inexpensive synthetic adulterant. Regulators suspected that the OSCS was added to offset a shortage of heparin, which was in short supply due to a disease outbreak in pigs, the animal species used to source the material.

	Regulators traced a complicated supply chain from a US-based firm to an affiliated China-based manufacturer, and the crude heparin supply chain in China. The supplier argued that existing GMPs and pharmacopeial testing standards could not detect, identify, or remove the substance (3). In response to the heparin crisis, the US and European pharmacopeias made extensive revisions to their respective heparin monographs.

	The current contaminant case, which involves recalls of generic angiotensin II receptor blocker (ARB) drug products, began in mid-2018 when a generic drug manufacturer identified N-nitrosodimethylamine (NDMA), a probable human carcinogen, in an API supplied by China-based Zhejiang Huahai Pharmaceutical Co., Ltd. (ZHP). Subsequent testing found N-nitrosodiethylamine (NDEA) in valsartan products and some irbesartan and losartan products; in March 2019, N-nitroso-N-methyl-4-aminobutyric acid (NMBA) was identified in losartan potassium products.

	The agency suspects the impurity may have been generated by chemical reactions during the API manufacturing process, or from the reuse of materials, such as solvents.

	While admitting that neither the industry or agency understood how NDMA or NDEA could form during the API manufacturing process, FDA clearly established that the responsibility for quality control is with the API manufacturer, stating: “It is the manufacturer’s responsibility to understand and assess their manufacturing process, assess any changes to that process, and based on that assessment and understanding, ensure test methods utilized can detect impurities expected to develop during the manufacturing process” (4).

	The agency reinforced that message in a warning letter to ZHP in November 2018: “Your response states that predicting NDMA formation during the valsartan manufacturing process required an extra dimension over current industry practice, and that your process development study was adequate. We disagree. We remind you that common industry practice may not always be consistent with CGMP [current good manufacturing practice] requirements and that you are responsible for the quality of drugs you produce” (5).

	“The global nature of drug supply chains and manufacturing practices has evolved dramatically in recent decades,” says Jaap Venema, chief science officer at the US Pharmacopeia (USP). “This has made it necessary for all stakeholders involved in drug manufacturing to explore emerging areas of risk and identify where medicine quality may be vulnerable to being compromised.” FDA, USP, and other stakeholders must work together to develop best practices and appropriate predictive tools for understanding and addressing these risks, he says.

	“Recent industry disruptions around recalls and adulteration drive home the importance of knowing your suppliers and understanding their sources and suppliers of materials,” says Maxine Fritz, executive vice-president, Pharma BioTech, NSF International. “It’s essential to have a process that traces raw materials to origin and verifies the integrity of the system at every point along the way.”

	The supplier must have product requirements that include the composition of the materials, as well as any product/process and/or material degradants or variability. In addition, manufacturers that rely on sole source suppliers are at the mercy of that supplier’s ability to deliver the materials as needed, says Fritz. 

	“Because of the complexity of the global excipient supply chain, it is often difficult for a pharmaceutical manufacturer to know the actual source of materials, or to have complete faith in the testing of critical quality attributes of a material, even from trusted suppliers,” says Catherine Sheehan, senior director, excipients, USP. Over time, suppliers may change production processes, organizational structures, distribution chains, or lab services. “Routine identity testing of incoming materials and periodic supplier validation may help reduce risks,” she says.  

	The global scale and variety of suppliers for pharmaceutical raw materials creates complications for vetting suppliers, says Frederic Prulliere, Raman ID products manager, Agilent Technologies. “This leaves room for low purity, adulterated, counterfeited, or even harmful products to enter the drug manufacturing supply chain. Limited governmental oversight, multiple industry suppliers, and geopolitical events can all add to the challenge of supplying raw materials in the pharmaceutical industry,” he says.

	The potential to receive counterfeit materials is greater for high value excipients, says Sheehan. “Some materials, like glycerin, have shown a high risk of economic adulteration. More than 800 deaths have been attributed to multiple glycerin adulteration events within the past century,” she reports. “Without proper testing, substandard or even poisonous substances can then enter the pharmaceutical supply chain.” 

	It is imperative that pharma companies follow 21 Code of Federal Regulations 211.84(d)(1) (2), which mandates full identity testing for all incoming lots of drug product components, Sheehan recommends. If a supplier’s certificate of analysis (CoA) is used in lieu of analysis of other attributes, that supplier’s test results should be regularly validated by the pharma company.

	While the potential for introducing adulterated materials in the pharmaceutical supply chain is real, companies with a risk-based approach to incoming raw materials inspection are unlikely to use counterfeit or adulterated products, says Prulliere. “Controlling the quality of the raw material before it enters production, qualifying and vetting suppliers, assessing and managing risks, and tolerance for these risks are the quality pillars that pharmaceutical companies should implement to deal with this potential,” he says.

	Current standards should help pharma companies identify counterfeit materials before they enter production, says Sheehan; however, not all pharma companies are applying this standard consistently and performing identity testing on each lot of incoming raw materials, including excipient raw materials. “Occasional or skip lot testing or reliance on a supplier’s CoA is inadequate,” she says, noting that FDA cited 20 different firms in 2018 for failure to adequately test incoming raw materials.

	Many, but not all, drug manufacturers are testing for substandard materials, which is concerning from a public health standard, says Fritz.

	“A certificate of analysis is a strong reassurance, but a certificate is only as good as the testing performed, the quality oversight, and the quality systems that the supplier has in place,” says Fritz.

	“A company can’t watch raw materials being produced, load them in a truck, and transport them to their factory. Using a robust supplier qualification that includes routine inspection and verification will help to lower risk and increase confidence in the quality of incoming raw materials,” says Sheehan. “However, routine material analytical testing of each incoming lot using a USP documentary standard and associated reference standard, if available, provides a final quality check and safeguard to help ensure only acceptable materials are released into production.”

	Ideally, pharma manufacturers should test for critical quality attributes, but at a minimum they must perform a full identity test for all incoming lots of components, she says.

	“Using PIC/S [Pharmaceutical Inspection Co-operation Scheme] guidance, quality control labs are only required to identify raw materials provided a supplier evaluation program is in place. If not, a full analysis is usually conducted,” says Prulliere.

	 Mid-infrared, near infrared, or Raman spectroscopy are typically effective for verifying incoming raw materials due to probing the vibrational modes of a material providing a structure specific spectrum, he says. “Spatially offset Raman spectroscopy (SORS) is gaining popularity. SORS extends the depth of penetration to eliminate container contribution to the measurement and permit analysis through non-transparent containers.”

	A third-party supplier verification service can be used to ensure suppliers are adhering to a culture of quality, follow appropriate CGMP regulations, and produce materials that pass random lot analytical testing at regular intervals, says Sheehan.  “Incorporating this verification plan within a quality standard operating procedure may help pharma manufacturers comply with FDA supplier validation requirements for using CoA data,” she says.

Substandard and Falsified Medical Products

.”
	2. P. Behner, M-L Hecht, and F. Wahl, 

Fighting Counterfeit Pharmaceuticals: New Defenses for an Underestimated-and Growing-Menace

, PriceWaterhouseCoopers (2017).
	3. D. G. Strunce, 

Statement, Scientific Protein Laboratories–Subcommittee on Oversight & Investigations Committee on Energy & Commerce US House of Representatives

Q&A on Angiotensin II Receptor Blocker (ARB) Medication Class Investigation

Zhejiang Huahai Pharmaceutical, Warning Letter

Vol. 43, No. 4
	April 2019
	Pages: 60–62

	When referring to this article, please cite it as R. Peters, “Locking Fraudulent Materials Out of the Supply Chain," 

Supplier vetting and monitoring-plus comprehensive testing-ensure quality of raw materials.

Locking Fraudulent Materials Out of the Supply Chain

	As editor of a publication for bio/pharmaceutical development, I spend a lot of time reading about the latest drug development trends; one emerging theme is patient-centric drug design.

	That topic came to mind as I experienced the trials and tribulations of dealing with a recent bout of flu-like symptoms (despite getting a flu shot).  For example, attempting to match symptoms to the hundreds of over-the-counter (OTC) medicines in the drug store aisle was a dizzying task, especially while ill. Difficult-to-open packages, blister packs that did not list expiration dates, and confusing dosing instructions contributed to my frustration. And the prescription and OTC medicines I took literally left a bad taste in my mouth.

	While my illness was routine and I soon recovered, the implications for patients with serious medical conditions who do not adhere to complex dosing regimens can be health- or life-threatening. Therapies that require multiple oral doses per day, painful injections, administration by trained medical professionals, or have adverse side effects are just a few challenges to effective dosing of drugs. Physical limitations, such as problems swallowing, also complicate delivery of the drug.

	In the cover story for this issue, formulation experts discuss the need to bring the patient’s experience to the forefront of drug formulation strategies. Development strategies should include more than just studying the biopharmaceutical and physicochemical characteristics of a drug molecule. Understanding the patient’s physical and dosing needs at early stages of development will be crucial.

	I will moderate a panel discussion on patient-centric drug design at CPhI North America in Chicago on April 30, 2019. See the CPhI North America Planning Guide in the accompanying 

	While I cannot confirm where I picked up the virus that made me sick, I stayed home for a week to contain the illness. Practical measures such as isolation of an infected person and vaccinations can help contain disease outbreaks.

	The Centers for Disease Control (CDC) (1) estimates that 31–36 million people experienced seasonal flu illnesses in the 2018–2019 flu season, prompting an estimated 16.8 million doctor visits, a half million hospitalizations, and up to 46,800 deaths. Based on CDC estimates, the 2018–2019 season was the second most severe in the number of illnesses and doctor visits, fifth in hospitalizations, and fourth in deaths, when compared with other flu seasons dating back to 2010. And, an estimated 169.1 million doses of flu vaccine were distributed in 2018–2019, an increase of almost 9% over the previous season (2).

	While measles was declared eliminated from the United States in 2000, reported cases spiked in 2019. Through mid-March, the CDC reported more than 300 confirmed cases of the disease in 15 states, up from 17 cases in 2018. The outbreak was attributed to international travelers bringing the disease to the United States as well as clusters of unvaccinated people in certain communities.

	An outbreak in Rockland County, New York prompted county officials to declare a state of emergency that barred anyone under age 18 who was not vaccinated against the measles from public places for 30 days or until they receive a vaccination (3).

	Officials told media outlets the measures were taken to get the public’s attention and encourage more vaccinations. Backlash against the emergency order illustrated that opinions about a patient’s (or parent’s) right to refuse treatment are strong and present another medical treatment challenge.

.
	3.  Rockland County, Press Release, March 26, 2019.

	When referring to this article, please cite it as R. Peters, “Designing for Patient and Public Health," 

Better drug design and patient education may promote improved personal and public health.